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Online FirstList of IssuesDocument Types
Inhibitory Effect and Mechanisms of Yupingfeng San on HMGB1-induced Angiogenesis in Liver Cancer via Modulating RAGE/MEK/ERK Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the inhibitory effects and mechanisms of Yupingfeng San （YPFS） on high-mobility group box protein 1 （HMGB1）-induced angiogenesis in liver cancer.MethodsAn orthotopic liver cancer model was established in 30 C57BL/6 mice. The mice were randomly divided into a model group， YPFS low-， medium-， and high-dose groups （20， 30， 40 g·kg-1， respectively）， a positive control group （sorafenib， 10 mg·kg-1）， and a normal control group. After 14 days of medication， tumor and adjacent tissues were harvested. Tumor inhibition rates were calculated based on tumor weight. Microvascular density was determined via immunohistochemistry. HMGB1 and vascular endothelial growth factor （VEGF） expression levels were determined using immunofluorescence. An HMGB1-induced human umbilical vein endothelial cell （HUVEC） proliferation model was established， and cell proliferation was evaluated by a methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay. HUVECs were randomly divided into a blank group， a model group （HMGB1 800 μg·L-1）， along with YPFS low-， medium-， and high-dose groups （HMGB1 800 μg·L-1 + YPFS 10， 30， 50 g·L-1， respectively）. HUVEC migration ability was evaluated via a scratch assay and a Trans well chamber assay. Tube formation ability was detected by a tube formation assay. Microvascular sprouting ability was evaluated by an aortic ring assay. Furthermore， RAGE/MEK1/2/ERK1/2 pathway-related protein expression in HUVECs was measured using Western blot （WB）.ResultsCompared with the model group， all three doses of YPFS significantly reduced tumor weight in mice with orthotopic liver cancer （P<0.01）， with inhibition rates of 31.49% ± 8.27%， 49.60% ± 3.77%， and 56.81% ± 9.70%， respectively. Also， YPFS significantly decreased microvascular density in tumor and adjacent tissues （P<0.05）， as well as VEGF and HMGB1 expression levels （P<0.01）. Compared with the blank group， HMGB1 promoted HUVEC proliferation， migration， tube formation， and microvascular sprouting in aortic rings （P<0.05）. After YPFS administration， the HMGB1-induced proliferation rate， migration rate， number of tube formations， and microvascular sprouting in aortic rings were significantly reduced compared with the model group （P<0.01）. Additionally， YPFS downregulated receptor for advanced glycation end products （RAGE）， mitogen-activated protein kinase kinase 1/2 （MEK1/2）， phosphorylated MEK1/2 （p-MEK1/2）， extracellular signal-regulated kinase 1/2 （ERK1/2）， and phosphorylated ERK1/2 （p-ERK1/2） protein expression in HMGB1-induced HUVECs （P<0.01）.ConclusionYPFS exerts anti-angiogenic effects against HMGB1 induction by suppressing the RAGE/MEK/ERK signaling pathway， thereby inhibiting liver cancer tumor growth.Keywords：Yupingfeng San;angiogenesis;high-mobility group box protein 1 （HMGB1）;liver cancer;receptor for advanced glycation end-products （RAGE）/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway26|7|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02Qige San Regulates miR-133a/PI3K/Akt Signaling Pathway-mediated Tumor Angiogenesis to Treat Esophageal Cancer AI Introduction
Abstract：ObjectiveTo observe the mechanism through which Qige San inhibits tumor angiogenesis in esophageal cancer （EC） by regulating the microRNA-133a （miR-133a）/phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway.MethodsCell experiments were conducted by transfecting miR-133a mimics through liposomes and utilizing PI3K/Akt signaling pathway inhibitors. The effects of 60 mg·L-1 and 100 mg·L-1 Qige San on inflammatory factor secretion in the supernatant of EC9706 cells （esophageal cancer cells） were observed. EC9706 cell supernatants were then extracted and used as conditioned media to treat human umbilical vein endothelial cells （HUVECs）. The effects of the conditioned media on the proliferation， migration， tube formation， and apoptosis of HUVECs were examined. Animal experiments involved establishing a subcutaneous tumor model in nude mice with EC9706 cells. After grouping and administration， tumor volumes were measured regularly. At the end of the experiment， tumors were harvested， and histopathological changes were observed under a microscope after hematoxylin-eosin （HE） staining. Real-time polymerase chain reaction （Real-time PCR） was adopted to measure miR-133a expression in the tumor tissue of each group， while Western blotting was employed to analyze the expression of key signaling molecules， such as phosphorylated Akt （p-Akt）， as well as endothelial cell markers， cluster of differentiation 31 （CD31） and cluster of differentiation 34 （CD34）， in the tumor tissue.ResultsCell experiments showed that compared with the blank group， the supernatant of EC9706 cells promoted tube formation of HUVECs （P<0.05）. Both low and high doses of Qige San inhibited tube formation of HUVECs （P<0.05）. All doses of Qige San， PI3K/Akt inhibitor， and the combination reduced the content of interleukin-6 （IL-6） （P<0.05）， while high-dose Qige San， inhibitor， and combination all reduced the content of interleukin-8 （IL-8） （P<0.05）. Compared with the EC9706 blank supernatant group， Qige San-conditioned medium inhibited the proliferation of HUVECs （P<0.05）. Qige San， the inhibitor， and the combination all inhibited the migration and tube formation （P<0.05） and increased the late apoptosis and total apoptosis rates of HUVECs （P<0.05）. In addition， the low-dose combination induced early apoptosis of EC9706 cells （P<0.05）. Compared with the blank supernatant group， the miR-133a mimic combined with Qige San synergistically reduced IL-6/IL-8 （P<0.05）， and enhanced the inhibition on proliferation， migration， and tube formation of HUVECs （P<0.05）. Animal experimental results showed that compared with the model group， both Qige San and cisplatin inhibited the growth of xenograft tumors in nude mice （P<0.05）， promoted tumor cell necrosis， and reduced capillary formation. High-dose Qige San upregulated miR-133a expression （P<0.05）. Moreover， compared with the model group， cisplatin， Qige San， and the combination all downregulated the expression of p-Akt， CD31， and CD34 （P<0.05）.ConclusionQige San upregulates miR-133a expression， inhibit PI3K/Akt signaling pathway activity， and improve the tumor inflammatory microenvironment to suppress the growth and tumor angiogenesis of HUVECs， thereby inhibiting esophageal cancer.Keywords：Qige San;esophageal cancer;miR-133a/ phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway;endothelial cells;angiogenesis23|6|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02- Abstract：ObjectiveTo investigate the intervention effect of modified Xiangsha Liujunzitang （M-XSLJZ） on insulin resistance-regulated fatty acid synthesis via Lon protease 1 （Lonp1） in the liver of spleen-deficiency hyperlipidemia rats.MethodsA total of 70 male SD rats were randomly allocated into seven groups （n=10）： blank control group， high-fat diet （HFD） group， spleen-deficiency hyperlipidemia （PX-HFD） model group， low-， medium-， and high-dose Modified Xiangsha Liujunzitang （JW-L， JW-M， JW-H）， and rosuvastatin group. The spleen-deficiency model was induced in the PX-HFD， JW-L， JW-M， JW-H， and rosuvastatin groups by irregular diet combined with exhaustive swimming. Except for the control group， all groups were fed an HFD for 10 weeks to establish a hyperlipidemia rat model. Following modeling， the rats in the JW-L， JW-M， and JW-H groups received the decoction by gavage at 3.51， 7.02， 14.04 g·kg-1， respectively， while the rosuvastatin group received 9×10-4 g·kg-1. After 8 weeks of administration， samples were collected. D-xylose excretion rate was quantified using the phloroglucinol method. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured by an automatic biochemical analyzer. Hepatic TG content was quantified by the glycerol phosphate oxidase-peroxidase anti-peroxidase （GPO-PAP） method. Serum insulin （INS）， fasting blood glucose （FBG）， hepatic reactive oxygen species （ROS） levels， and mitochondrial complex Ⅰ activity were assessed by enzyme-linked immunosorbent assay （ELISA）. The mRNA levels of Lonp1， and acetyl-CoA carboxylase 1 （ACC1） were determined by real-time quantitative PCR （Real-time PCR）. Protein expression levels of Lonp1， c-Jun N-terminal kinase （JNK）， phosphorylated （p）-JNK， insulin receptor substrate 1 （IRS1）， p-IRS1， and ACC1 in liver tissues were analyzed by Western blot.ResultsCompared with the control group， the HFD group showed a significant increase in body weight （P<0.01）. The PX-HFD group showed a significant decrease in D-xylose excretion rate （P<0.01）. Both the HFD and PX-HFD groups exhibited significantly elevated serum levels of TC， TG， HDL-C， LDL-C， FBG， INS， and HOMA-IR （P<0.01）， along with increased orange-red lipid droplets， prominent fatty vacuoles， and significantly elevated hepatic TG level （P<0.01）. Mitochondrial complex Ⅰ activity significantly decreased （P<0.05）， while ROS level， Lonp1 mRNA and protein expression， and ACC1 mRNA and protein expression significantly increased （P<0.05， P<0.01）. The p-IRS1/IRS1 protein expression ratio significantly decreased （P<0.01）， whereas the p-JNK/JNK protein expression ratio significantly increased （P<0.01）. Compared with the HFD group， the PX-HFD group showed significantly reduced D-xylose excretion rate and serum HDL-C level （P<0.01）， significantly decreased hepatic TG level （P<0.05）， and significantly increased HOMA‑IR index （P<0.01）. Hepatic Lonp1 mRNA and protein expression significantly decreased （P<0.05， P<0.01）， p‑IRS1/IRS1 protein expression ratio was significantly decreased （P<0.01）， while ACC1 mRNA and protein expression and p‑JNK/JNK protein expression ratio were significantly increased （P<0.01）. Compared with the PX-HFD group， all treatment groups showed significantly reduced serum TC， TG， LDL-C levels， and HOMA-IR index （P<0.05， P<0.01）， with ameliorated orange‑red lipid droplet deposition and significantly reduced hepatic TG and ROS levels （P<0.05， P<0.01）. The JW-M， JW-H， and rosuvastatin groups exhibited significantly decreased body weight （P<0.05， P<0.01）， significantly increased D‑xylose excretion rate （P<0.01）， significantly decreased HDL‑C level （P<0.05， P<0.01）， significantly increased mitochondrial complex I activity， Lonp1 mRNA and protein expression， and p-IRS1/IRS1 protein expression ratio （P<0.05， P<0.01）， as well as significantly decreased p-JNK/JNK protein expression ratio （P<0.01）.ConclusionM-XSLJZ may exert its lipid‑lowering effect by regulating Lonp1 expression in rat liver， thereby improving insulin resistance and subsequently inhibiting hepatic lipid synthesis.Keywords：hyperlipidemia;Lon protease 1 （Lonp1）;insulin resistance;lipid metabolism;modified Xiangsha Liujunzitang21|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo investigate the mechanism by which Sini San （SNS） treats liver fibrosis through regulating the polarization of intrahepatic Kupffer cells.MethodsSixty SPF-grade male Balb/c mice were randomized into blank control， model， silymarin （0.2 g·kg-1）， and low-， medium-， and high-dose （2.93， 5.85， 11.70 g·kg-1， respectively） SNS groups. A mouse model of liver fibrosis was induced by intraperitoneal injection of CCl4. After 5 weeks of administration， the body mass， liver pathological changes ［Hematoxylin and Eosin （HE）， Masson， and Sirius red staining］， serum biochemical indicators ［alkaline phosphatase （ALP）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT）］， liver fibrosis markers ［procollagen type Ⅲ （PCⅢ）， laminin （LN）， and hyaluronic acid （HA）］， inflammatory cytokines ［interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10）］， and fibrosis-related proteins ［α-smooth muscle actin （α-SMA）， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ）］ were assessed. A co-culture system of THP-1 cells （M1 macrophages） and human hepatic stellate cells （LX-2） was established. The cell experiment was designed with blank control （LX-2 alone）， model （LX-2 + M1 macrophages）， and low-， medium-， and high-dose SNS （co-culture with 5%， 10%， or 20% SNS-containing serum， respectively） groups. Cell viability， inflammatory cytokines， and macrophage phenotype were examined. Human primary hepatic Kupffer cells were allocated into blank control， M1 （LPS 100 μg·L-1+IFN-γ 20 μg·L-1）， M2 （IL-4 20 μg·L-1+IL-13 20 μg·L-1）， M1+M2， M1+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M1 conditions for 24 h）， M2+SNS （supplemented with 10% SNS-containing serum for 2 h after culture under M2 conditions for 24 h）， and M1+M2+SNS groups （supplemented with 10% SNS-containing serum for 2 h after culture under M1+M2 conditions for 24 h）， and the expression of nuclear factor-κB （NF-κB） p65 and signal transducer and activator of transcription 3 （STAT3） at protein and mRNA levels was determined.ResultsCompared with the blank group， the model group exhibited increased serum levels of ALT， AST， ALP， PCⅢ， LN， HA， IL-6， and TNF-α， upregulated protein and mRNA levels of α-SMA， Col Ⅰ， and Col Ⅲ in the liver tissue （P<0.05， P<0.01）， and decreased IL-10 level and STAT3 mRNA level （P<0.05， P<0.01）， accompanied by marked collagen deposition and inflammatory infiltration in the liver. Compared with the model group， all doses of Sini San reversed these alterations （P<0.05， P<0.01）， with the high-dose group showing the most pronounced effects. Cell experiments demonstrated that， compared with the blank control group， the model group had elevated levels of pro-inflammatory cytokines （IL-1β， IL-6， and TNF-α） and upregulated protein and mRNA levels of M1 markers ［cluster of differentiation 86 （CD86， inducible nitric oxide synthase （iNOS）， and monocyte chemoattractant protein-1 （MCP-1）］ （P<0.01）， along with declined level of IL-10 and downregulated expression of M2 markers ［（CD163， CD206， and arginase-1 （Arg-1）］ （P<0.05，P<0.01）. Compared with the model group， treatment with Sini San-containing serum at various concentrations lowered the levels of pro-inflammatory cytokines and expression of M1 markers （P<0.05， P<0.01）， while increasing the IL-10 level and M2 marker expression （P<0.05， P<0.01）. Additionally， Sini San downregulated the mRNA level of NF-κB and upregulated the mRNA level of STAT （P<0.05， P<0.01）. In the experiment with human primary Kupffer cells， compared with the blank group， the M1 group showed increased NF-κB p65 expression （P<0.01） and decreased STAT3 expression （P<0.05）， whereas the M2 group exhibited increased STAT3 expression （P<0.01）. Compared with the respective model groups， Sini San-containing serum reversed the M1-induced overexpression of NF-κB p65 （P<0.05， P<0.01） and further enhanced the M2-induced STAT3 expression （P<0.05， P<0.01）.ConclusionSini San can inhibit the NF-κB p65/STAT3 signaling pathway and repolarize intrahepatic Kupffer cells from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype to attenuate inflammation and suppress hepatic stellate cell activation and collagen deposition， thereby exerting anti-fibrotic effect.Keywords：Sini San;liver fibrosis;macrophage polarization;Kupffer cells;nuclear factor-κB （NF-κB） signaling pathway34|14|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo investigate the mechanism by which Haizao Yuhu Tang regulates the nuclear receptor subfamily 4 group A member 1 （NR4A1）signaling pathway to modulate CD8-positive T lymphocyte （CD8+T） cell exhaustion-mediated immune escape in transgenic mice with papillary thyroid carcinoma （PTC）.MethodsSixty C57BL/6J mice carrying the conditional BRAFV600E point mutation were randomly assigned to five groups （n=12）： Model， low-dose （7.28 g·kg-1·d-1） Haizao Yuhu Tang， medium-dose （14.56 g·kg-1·d-1） Haizao Yuhu Tang， high-dose （29.12 g·kg-1·d-1） Haizao Yuhu Tang， and vemurafenib （PLX4032， 0.02 g·kg-1·d-1）. In addition， 12 BRAFV600E-negative mice were selected as the control group. All the groups received continuous intervention for 8 weeks. After treatment， the thyroid tumor weight and volume of mice in each group were measured. Hematoxylin and eosin （HE） staining was performed to observe the morphological characteristics of thyroid tumors. Enzyme-linked immunosorbent assay （ELISA） was adopted to quantify the serum levels of interferon-γ （IFN-γ）， interleukin-2 （IL-2）， tumor necrosis factor-α （TNF-α）， C-X-C motif chemokine ligand 9 （CXCL9）， and C-X-C motif chemokine ligand 10 （CXCL10）. Flow cytometry was employed to determine the proportion of cytotoxic CD8+T cells in the tumor tissue. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of molecules related to the NR4A1 signaling pathway.ResultsCompared with the control group， the model group showed significantly increased thyroid tumor volume and weight （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups and the vemurafenib group exhibited varying degrees of reduction in thyroid tumor volume and weight （P<0.05， P<0.01）， with the medium-dose Haizao Yuhu Tang group and the vemurafenib group showing the most pronounced therapeutic effects （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups and the vemurafenib group showed increased serum levels of IFN-γ， IL-2， TNF-α， CXCL9， and CXCL10， decreased mRNA and protein levels of NR4A1， Programmed cell death-1 （PD-1）， and Programmed cell death-ligand 1 （PD-L1）， and enhanced cytotoxic activity of CD8+T cells （P<0.05， P<0.01） Among these groups， the medium-dose Haizao Yuhu Tang group exhibited the optimal therapeutic effects. In addition， compared with that in the model group， T-cell factor-1 （TCF-1） expression was increased in the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups （P<0.01）， whereas no significant change in TCF-1 expression was observed in the vemurafenib group.ConclusionHaizao Yuhu Tang may restore the cytotoxic function of CD8+T cells by inhibiting the NR4A1 signaling pathway， thereby suppressing immune evasion in PTC and delaying PTC growth.Keywords：Haizao Yuhu Tang;papillary thyroid carcinoma;CD8-positive T lymphocyte （CD8+T） cell exhaustion;immune escape3|0|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo explore the mechanism of Huashi Baidu granules in treating influenza A （H1N1） virus infection based on the gut-lung axis.MethodsBALB/c mice were randomly assigned into a blank control group， a model control group， a positive control （oseltamivir phosphate capsules， 19.5 mg·kg-1） group， and a Huashi Baidu granules （17.81 g·kg-1） group. Mice in other groups except the blank control group were instilled nasally by H1N1 viral fluid for the modeling of influenza viral pneumonia and treated with corresponding drugs once daily by gavage for 5 consecutive days. The mouse lung index was calculated， and pathological changes in the lung and colon tissue were observed. Western blot was employed to quantify the expression levels of nucleotide-binding oligomeric domain-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific proteinase -1 （Caspase-1）， apoptosis-associated Speck-like protein containing a CARD （ASC）， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β， and colonic tight junction protein 1 （CLDN1）， and Occludin in the lung and colon tissue. Non-targeted metabolomics was employed to analyze the metabolic profiles of the lung tissue and intestinal contents. The 16S rRNA sequencing was performed to analyze the gut microbiota structure in intestinal contents. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the 5-hydroxytryptamine （5-HT） levels in the serum， lung tissue， and colon tissue.ResultsCompared with the blank control group， the model control group showed elevated lung index， marked inflammatory cell infiltration and alveolar structural destruction in the lung tissue， obvious inflammatory cell infiltration and mucosal epithelial damage in the colon tissue， upregulated protein levels of NLRP3 inflammasome pathway proteins NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in the lung and colon tissue （P<0.05， P<0.01）， downregulated protein levels of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Compared with the model control group， Huashi Baidu Granules reduced the lung index （P<0.01）， alleviated pathological damage in the lungs and colon， inhibited the expression of NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in lung and colon tissue （P<0.05， P<0.01）， and upregulated the expression of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Metabolomics analysis showed that Huashi Baidu Granules downregulated the 5-HT pathway and arachidonic acid metabolism pathway in the lung and colon tissue， while upregulating nucleotide metabolism and TCA cycle. Compared with the blank control group， the model control group exhibited elevated levels of 5-HT in the serum， lung tissue， and colon tissue （P<0.01）. The intervention with Huashi Baidu Granules lowered the levels of 5-HT in the serum （P<0.05） and the lung and colon tissue （P<0.01）. Huashi Baidu Granules increased the diversity of gut microbiota， enriched beneficial bacteria such as Blautia， and inhibited pathogenic bacteria such as Desulfovibrio.ConclusionHuashi Baidu Granules significantly alleviate lung inflammation and pathological damage in mice infected with influenza A （H1N1） virus， reshape the intestinal microecology， and repair the intestinal barrier. It may exert cross-organ regulation by inhibiting the cascade of "gutogenic 5-HT release-circulatory transport-pulmonary 5-HT receptor activation-NLRP3 inflammasome assembly." It exerts therapeutic effects on influenza viral pneumonia through the gut-lung axis. This study provides a modern biological interpretation for the TCM theories of interior-exterior relationship between the lung and large intestine and simultaneous treatment of the lung and intestine.Keywords：Huashi Baidu Granules;influenza A virus;H1N1;gut-lung axis;NLRP3 inflammasome;gut microbiota40|14|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo observe the effects of astragaloside Ⅳ （AS-Ⅳ） and tanshinone ⅡA （Tan ⅡA） in antagonizing adverse cardiac remodeling after myocardial infarction （MI） and to explore the mechanism by which they regulate myocardial copper homeostasis to improve the mitochondrial function.MethodsA total of 70 C57BL/6J mice were randomly assigned into a sham-operation group and a modeling group. The MI model was established by ligation of the left anterior descending coronary artery in mice. Successfully modeled mice were assigned into model （MI）， AS-Ⅳ （2 mg·kg-1·d-1）， Tan ⅡA （15 mg·kg-1·d-1）， and AS-Ⅳ+Tan ⅡA （2 mg·kg-1·d-1 AS-Ⅳ+15 mg·kg-1·d-1 Tan ⅡA） groups. In the sham operation group， the left anterior descending artery was passed with a suture but not ligated. After 4 weeks of drug intervention， the cardiac function was assessed by echocardiography. Wheat germ agglutinin （WGA） staining and Masson staining were adopted to evaluate myocardial hypertrophy and fibrosis， respectively. Cardiac copper content was measured by colorimetry. The protein levels of copper transporter 1 （CTR1）， ATPase copper transporting alpha （ATP7A）， ATPase copper transporting beta （ATP7B）， copper metabolism domain containing 1 （COMMD1）， cytochrome C oxidase copper chaperone COX17 （COX17）， and cytochrome C oxidase subunit Ⅳ isoform 1 （COXⅣ） were determined by Western blot. In the cell experiments， a cardiomyocyte oxygen-glucose deprivation （OGD） model was established， and cells were allocated into normal， OGD， AS-Ⅳ （51 µmol·L-1）， Tan ⅡA （1.7 µmol·L-1）， and AS-Ⅳ+Tan ⅡA （51 µmol·L-1 AS-Ⅳ+1.7 µmol·L-1 Tan ⅡA） groups. Intracellular copper content was measured by colorimetry， and reactive oxygen species （ROS） production was detected through the ROS fluorescent probe. Mitochondrial morphology and function were assessed by Mito-Tracker Red and JC-1 probes， respectively. ATP content was measured by colorimetry， and the protein levels of CTR1， ATP7A， ATP7B， COMMD1， COX17， and COXⅣ were determined by Western blot. COMMD1 levels were examined by immunofluorescence staining.ResultsCompared with the sham operation group， the model group showed decreased left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） （P<0.01）， increased cardiomyocyte hypertrophy and collagen blue staining （P<0.01）， a declined copper ion level in the cardiac tissue （P<0.01）， upregulated protein levels of ATP7A， ATP7B， and COMMD1 （P<0.01）， downregulated protein levels of COX17 and COXⅣ （P<0.01）， and no significant change in CTR1 protein level. Compared with the model group， the AS-Ⅳ， Tan ⅡA， and AS-Ⅳ+Tan ⅡA groups exhibited increased LVEF and LVFS （P<0.01）， reduced cardiomyocyte hypertrophy and collagen blue staining （P<0.01）， elevated copper ion levels in the cardiac tissue （P<0.01）， and recovered protein expression （P<0.01）. The cell experimental results showed that compared with the control group， the model group exhibited decreases in intracellular copper ion level， mitochondrial membrane potential， and ATP content （P<0.01）， an increase in ROS level （P<0.01）， upregulation in the protein levels of CTR1， ATP7A， ATP7B， and COMMD1 （P<0.01）， and downregulation in the protein levels of COX17 and COXⅣ （P<0.01）. Compared with the model group， the AS-Ⅳ， Tan ⅡA， and AS-Ⅳ+Tan ⅡA groups showed increased intracellular copper ion levels， mitochondrial membrane potential， and ATP content （P<0.01）， decreased ROS levels （P<0.01）， and recovered protein expression （P<0.01）.ConclusionThe combination of AS-Ⅳ and Tan ⅡA can alleviate myocardial fibrosis and hypertrophy after MI by restoring myocardial copper homeostasis and subsequently improving the mitochondrial function.Keywords：myocardial infarction;cardiac remodeling;copper homeostasis;mitochondrial respiratory chain;astragaloside Ⅳ;tanshinone ⅡA40|15|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules （SSNX） in regulating the nuclear factor-κB （NF-κB） and mitogen-activated protein kinase （MAPK） pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury （MIRI） in rats.MethodsThe 45 healthy male Sprague-Dawley （SD） rats were divided into sham operation group， model group， and SSNX capsules group （90 mg·kg-1）. The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography， and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin （HE） staining， immunohistochemistry， and TdT-mediated dUTP nick end labeling （TUNEL）. The expression levels of cardiac inflammatory cytokines， including interleukin-1α （IL-1α）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Core differentially expressed genes （DEGs） and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to verify the mRNA expression of Toll-like receptor 2 （TLR2）， chemokine （C-X-C motif） ligand 1 （CXCL1） and prostaglandin-endoperoxide synthase 2 （PTGS2）， as well as the protein expression of Caspase-3， cleaved Caspase-3， p-NF-κB/NF-κB， phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2/ERK1/2） and p-p38 MAPK/p38 MAPK.ResultsCompared with the sham operation group， the ejection fraction （EF）， fractional shortening （FS）， stroke volume （SV） and cardiac output （CO） of the model group were significantly decreased （P<0.01）， the peak time of myocardial perfusion was prolonged （P<0.01）， hypoxia-inducible factor （HIF）-1α and α-smooth muscle actin （SMA） expression increased （P<0.01）， the concentrations of inflammatory factors IL-1α， IL-6， TNF-α， TLR2， CXCL1 and PTGS2 increased （P<0.01）， and the expression of cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased （P<0.01）. SSNX could improve cardiac function （P<0.05， P<0.01）， and significantly shorten the peak time of myocardial perfusion （P<0.01）. Moreover， it could also down-regulate HIF-1α and a-SMA expression （P<0.05， P<0.01）， and reduce the concentrations of IL-1α， IL-6， TNF-α （P<0.01）， and the mRNA expression of TLR2， CXCL1 and PTGS2 （P<0.01）. Additionally， SSNX inhibited the apoptosis rate （P<0.01） and significantly reduced the expression of Cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins （P<0.01）.ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways， thereby effectively preventing and alleviating myocardial reperfusion injury.Keywords：Shuangshen Ningxin capsules;myocardial ischemia-reperfusion injury （MIRI）;cardiac inflammation;nuclear factor-κB （NF-κB） signaling pathway;mitogen-activated protein kinase （MAPK） signaling pathway36|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
Yifei Zhuji Formula Reverses Epithelial-mesenchymal Transition of Non-small Cell Lung Cancer by Regulating PI3K/Akt/mTOR Signaling Pathway AI Introduction
Abstract：ObjectiveTo investigate the effects of Yifei Zhuji formula （YFZJF） on epithelial-mesenchymal transition （EMT） in non-small cell lung cancer （NSCLC） through regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway.MethodsThe Lewis lung carcinoma mouse model and human lung adenocarcinoma PC-9 cell model were used in this study. In the animal experiments， 60 C57BL/6 mice were randomized into a blank group and a Lewis lung carcinoma modeling group. The modeled mice were further randomized into model， low-， medium-， and high-dose （7.475， 14.95， 29.9 g·kg-1·d-1， respectively） YFZJF， and cisplatin groups， with 10 mice in each group. Mice in YFZJF groups were administrated with YFZJF at different doses by gavage， and those in the cisplatin group received intraperitoneal injection of cisplatin at 6 mg·kg-1. Mice in the blank group and model group were administrated with equal volumes of normal saline by gavage every day. All the groups were treated for 14 consecutive days， and samples were collected for analysis after completion of treatment. Changes in body mass， tumor volume， and tumor mass were measured. Hematoxylin-eosin （HE） staining was performed to observe pathological changes in the lung tissue. Immunohistochemistry， Real-time PCR， and Western blot were employed to determine the expression of proliferating cell nuclear antigen （Ki-67）， PI3K/Akt/mTOR signaling pathway-related molecules， and EMT-related molecules in the tumor tissue. In the cell experiments， human lung adenocarcinoma PC-9 cells were allocated into control， YFZJF-containing serum， and cisplatin groups， which were treated with 20% blank rat serum， 20% YFZJF-containing rat serum， and 5.4 μmol·L-1 cisplatin for 48 h， respectively. The cell counting kit-8 （CCK-8） assay was adopted to detect cell proliferation and determine drug concentration. Cell scratch assay and Transwell assay were employed to evaluate cell migration and invasion. Immunofluorescence staining and Real-time PCR were used to analyze changes in expression of EMT markers.ResultsCompared with those in the model group， the tumor volume and tumor mass were reduced in the high-dose YFZJF group （P<0.01）. Immunohistochemical results showed that compared with the model group， the medium- and high-dose YFZJF groups exhibited reduced Ki-67 expression in the tumor tissue （P<0.01）. HE staining results showed that YFZJF alleviated the pathological injury of the lung tissue to different degrees. Real-time PCR results in the tumor tissue showed that compared with the model group， the high-dose YFZJF group displayed downregulated mRNA levels of protein kinase B1 （Akt1） and N-cadherin （P<0.05）， phosphatidylinositol 3-kinase p85 regulatory subunit （p85） （P<0.01）， mTOR （P<0.01）， and Vimentin （P<0.01）， and an upregulated mRNA level of E-cadherin （P<0.01）. Western blot results showed that compared with the model group， the high-dose YFZJF group exhibited downregulated protein levels of phosphorylated （p）-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， Vimentin， and N-cadherin （P<0.01）， and an upregulated protein level of E-cadherin （P<0.01） in the tumor tissue. The cell experiment results showed that compared with the blank serum group， YFZJF-containing serum inhibited the proliferation， migration， and invasion of PC-9 cells （P<0.05， P<0.01）. Immunofluorescence results showed that compared with the control group， YFZJF-containing serum downregulated the protein levels of N-cadherin and Vimentin and upregulated the protein level of E-cadherin （P<0.01）. Real-time PCR results showed that compared with the control group， YFZJF-containing serum upregulated the mRNA level of E-cadherin （P<0.05） and downregulated the mRNA levels of N-cadherin， Vimentin， P85， Akt1， and mTOR （P<0.05， P<0.01）.ConclusionYFZJF can significantly inhibit the progression of non-small cell lung cancer and reduce the migration and invasion of tumor cells by inhibiting the abnormal activation of PI3K/Akt/mTOR signaling pathway and reversing EMT.Keywords：Yifei Zhuji Formula;non-small cell lung cancer;phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway;epithelial-mesenchymal transition48|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02Gantou Fumu Decoction Inhibits Hepatic Stellate Cell Activation by Regulating Nrf2/ARE Signaling Pathway AI Introduction
Abstract：ObjectiveTo explore the mechanism through which Gantou Fumu decoction （GDFMT）-containing serum inhibits the activation of hepatic stellate cells.MethodsSerum pharmacology techniques were employed to prepare GDFMT-containing serum samples. Rat hepatic stellate cells （HSCT6） were randomly allocated into three groups： Control， penicillamine （90 mg·kg-1）， and GDFMT （6.8 g·kg-1）. Cell viability was assessed by the cell counting kti-8 （CCK-8） assay， intracellular ROS levels were determined by flow cytometry using the DCFH‑DA fluorescent probe and while extracellular collagen Ⅰ （ColⅠ） levels were quantified via enzyme linked immunosorbent assay （ELISA）. Intracellular α-smooth muscle actin （α-SMA） expression was visualized through immunofluorescence staining. Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to evaluate alterations in the expression of nuclear factor-erythroid 2-related factor 2 （Nrf2）， glutamate cysteine ligase， catalytic （GCLC）， glutamate-cysteine ligase， modifier subunit （GCLM）， Kelch-like ECH-associated protein 1 （Keap1）， NAD（P）H：Quinone oxidoreductase 1 （NQO1）， and heme oxygenase-1 （HO-1）. Genetic knockdown of Nrf2 was achieved through small interfering （siRNA） transfection to validate pathway specificity.ResultsCCK-8 data indicated that under the selected experimental conditions， culturing HSCT6 cells with 10% （volume fraction） GDFMT-containing serum for 48 h demonstrated equivalent effect in inhibiting HSCT6 cell proliferation compared with culturing HSCT6 cells with 10% （volume fraction） penicillamine-containing serum for 36 h， with no statistically significant difference between the two groups. After treatment of HSCT6 cells with siRNA-mediated Nrf2 gene transfection technique， the inhibitory effect of GDFMT on the activation process of HSCT6 cells was significantly weakened. After HSCT6 cells were cultured with GDFMT-containing serum for 48 h， the flow cytometry with a fluorescence probe showed that the content of reactive oxygen species （ROS） in the cells was significantly reduced. After the expression level of the Nrf2 gene in HSCT6 cells was knocked down by siRNA transfection， the content of ROS increased （P<0.01）， indicating that GDFMT significantly reduced the ROS level in activated HSCT6 cells， and this effect strictly depended on the integrity of the Nrf2 pathway. Quantitative analysis by ELISA showed that the synthesis of ColⅠ in the HSCT6 cell culture system treated with GDFMT-containing serum for 48 h was lower than that in the control group （P<0.01）. After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection， the ColⅠ concentration in the culture supernatant increased （P<0.01）. The results of α-SMA detection by IF method showed that compared with the normal group， GDFMT-containing serum reduced the expression of α-SMA （P<0.01） and the protein level of α-SMA in HSCT6 cells was increased （P<0.01） after siRNA-mediated Nrf2 silencing， suggesting that Nrf2 signaling pathway may be involved in regulating the phenotypic transformation process of the cells. Real-time PCR and Western blot results showed that GDFMT-containing serum reduced the protein level of α-SMA （P<0.01） and enhanced the gene and protein levels of Nrf2 in the nucleus and GCLC， HO-1， Keap1， GCLM， and NQO1 in the cytoplasm of HSCT6 cells （P<0.05， P<0.01）. After the Nrf2 gene level of HSCT6 cells was knocked down by siRNA transfection， the protein level of α-SMA was increased （P<0.01）， and the levels of GCLC， GCLM， Keap1， NQO1， and HO-1 were decreased （P<0.05， P<0.01）. These results indicated that GDFMT-containing serum successfully triggered the Nrf2 signaling pathway of HSCT6 cells.ConclusionThe anti-hepatic fibrosis effect of 10%GDFMT was equivalent to that of penicillamine. In addition， GDFMT can inhibit HSC activation and reduce oxidative stress damage by activating the Nrf2/antioxidant response element （ARE） pathway， as manifested by the up-regulated expression of Nrf2 and downstream antioxidant genes （GCLC， GCLM， HO-1， Keap1， and NQO1） and reduced secretion of ROS， α-SMA， and ColⅠ.Keywords：Gantou Fumu decoction （GDFMT）;hepatolenticular degeneration;nuclear factor-erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） signaling pathway;hepatic fibrosis;hepatic stellate cell33|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02- Abstract：ObjectivePremenstrual syndrome （PMS） is a cyclical psychosomatic disorder associated with neuroendocrine dysfunction and dysregulation of monoamine neurotransmitters. Yiqi Weixue prescription （YQWX）， with both medicinal and edible value， shows the potential in alleviating PMS， yet its multi-target synergistic mechanism remains unclear. This study aims to explore the multi-target synergistic mechanism of YQWX in alleviating premenstrual syndrome through transcriptomics.MethodsThe rat model of PMS was established by progesterone injection combined with restraint stress. A total of 49 female Wistar rats were randomized into a normal group， a solvent group， a model group， low-， medium-， and high-dose （359， 718， 1 436 mg·kg-1， respectively） YQWX groups， and a positive control （Kuntai capsules， 540 mg·kg-1） group. After two weeks of intervention， behavioral changes were assessed by open field， forced swimming， and sucrose preference tests. Serum levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE）， and brain-derived neurotrophic factor （BDNF）， as well as serum levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β）， were measured by enzyme-linked immunosorbent assay （ELISA）. Hippocampal RNA was extracted for transcriptomic sequencing， followed by screening of differentially expressed genes （DEGs）， and then Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses were performed. The expression of key genes was validated by quantitative Real‑time polymerase chain reaction （Real-time PCR）， ELISA， and immunohistochemical （IHC） staining.ResultsCompared with the solvent group， the model group showed decreases in total movement distance， active time， rearing frequency， central zone duration， and grid line crossings in the open field test （P<0.01）， increases in peripheral zone duration and immobility time in the forced swimming test （P<0.01）， a reduced sucrose preference rate （P<0.01）， declined serum levels of 5-HT， NE， and BDNF （P<0.01）， and elevated serum levels of IL-6 and IL-1β （P<0.01）. Compared with the model group， the medium and high-dose YQWX groups exhibited significant improvements in the above behavioral parameters （P<0.05， P<0.01）. The medium-dose YQWX group showed restoration of 5-HT and BDNF levels （P<0.05）， and the high-dose YQWX group showed restoration of NE levels （P<0.01）. All YQWX groups reduced serum IL-6 and IL-1β levels （P<0.01）. Transcriptome sequencing identified 513 DEGs in the model group compared with the solvent group and 512 DEGs in the YQWX group compared with the model group. Enrichment analyses pointed out key pathways related to platelet activation， complement， coagulation cascade， inflammation， and neuroendocrine regulation. Experimental validation demonstrated that YQWX upregulated the mRNA and protein levels of F9 in the liver tissue （P<0.01）. Medium- and high-dose YQWX upregulated the mRNA level of PLCD3 in the hippocampus and uterus （P<0.05， P<0.01）， as well as protein levels of CAMK2G and SNCAIP in the hippocampus （P<0.01）.ConclusionYQWX synergistically alleviates behavioral and neurobiochemical abnormalities in PMS rats by regulating key genes， providing a molecular basis for its traditional effects of replenishing Qi， nourishing blood， and harmonizing the liver and spleen.Keywords：premenstrual syndrome;Yiqi Weixue prescription;transcriptional regulation;coagulation;inflammation;neuroendocrine25|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo investigate the mechanism by which Bushao Tiaozhi capsules （BSTZ） ameliorate hyperlipidemia based on untargeted metabolomics and targeted bile acid quantification.MethodsA rat model of hyperlipidemia was established with a high-fat diet. The rats were randomized into five groups： normal control， model， atorvastatin calcium （1.8 mg·kg-1）， and low-dose （2.88 g·kg-1） and high-dose （5.76 g·kg-1） BSTZ groups. All treatments were administered for four consecutive weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by biochemical assays. Hepatic histopathological changes were evaluated via hematoxylin-eosin （HE） staining， and lipid droplet deposition was assessed by oil red O staining. Integrated untargeted metabolomics and targeted bile acid quantification were employed to investigate BSTZ-induced alterations in hepatic metabolic profile and bile acid profile. Additionally， correlation analyses were conducted between differential bile acids and lipid parameters to identify key bile acids.ResultsCompared with the normal control group， the model group exhibited elevated serum TC， TG， and LDL-C levels （P<0.01） and a reduced HDL-C level （P<0.01）， along with marked hepatic steatosis and extensive lipid droplet deposition. Compared with the model group， all BSTZ treatment groups showed decreased TC， TG， and LDL-C levels （P<0.01） and increased HDL-C levels （P<0.01）， accompanied by notably alleviated hepatic steatosis and lipid deposition. Untargeted metabolomics and targeted bile acid quantification revealed that BSTZ significantly remodeled the hepatic bile acid profile， characterized by elevated levels of secondary bile acids （DCA， HDCA， TDCA， and TLCA） and reduced levels of primary bile acids （CDCA and TCDCA）. Correlation analyses further demonstrated strong associations between differential bile acids and lipid parameters： elevated secondary bile acids were negatively correlated with serum TC， TG， and LDL-C levels， whereas primary bile acids were positively correlated with these parameters.ConclusionBSTZ can ameliorate dyslipidemia and hepatic lipid accumulation in hyperlipidemic rats by regulating hepatic bile acid homeostasis， which provides metabolic clues for subsequent mechanism validation.Keywords：Bushao Tiaozhi capsules;hyperlipidemia;targeted bile acid metabolomics;untargeted metabolomics44|16|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo identify the direct target proteins for the anti-obesity effect of resveratrol （Res） via chemical proteomic analysis and systematically explore the molecular mechanisms by which Res inhibits lipid accumulation in adipocytes from mitochondrial function regulation， adipocyte browning， and inflammation inhibition， thus providing new targets and experimental evidence for the prevention and treatment of obesity and related metabolic diseases.MethodsThe cell counting kit-8 （CCK-8） assay was adopted to detect the safe and effective doses （7.5， 15， 30 μmol·L-1） of Res for treating 3T3-L1 cells based on the cell survival rate. After being induced to differentiate into mature adipocytes， the cells were assigned into the blank ［treated with dimethyl sulfoxide （DMSO）］ group and the Res （7.5， 15， 30 μmol·L-1） groups and treated for 48 h. Oil red O staining and total triglyceride （TG） content were assessed to measure lipid accumulation in adipocytes. Target protein identification of Res was conducted through IAA-P-based chemical proteomics combined with high-resolution mass spectrometry. Target proteins of Res were validated by cellular thermal shift assay （CETSA） combined with Western blot analysis. Furthermore， the expression of browning markers peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） and mitochondrial uncoupling protein 1 （UCP1）， as well as the target proteins NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8） and high-mobility group protein B1 （HMGB1） were determined by Western blot. The ATP assay kit was used to measure the ATP concentration. Mitochondrial biogenesis was characterized with MitoTracker Green， on the basis of which the regulatory effect of Res on mitochondrial function was analyzed. The level of the inflammatory cytokine tumor necrosis factor-α （TNF-α） was measured by enzyme-linked immunosorbent assay （ELISA）， on the basis of which the anti-inflammatory effect of Res on adipocytes was evaluated.ResultsCompared with the control group， Res demonstrated safety and efficacy within the range of 7.5-30 μmol·L-1， without significantly affecting cell viability. Compared with the control group， different concentrations of Res reduced lipid accumulation in 3T3-L1 adipocytes （P<0.01）， promoted the expression of NDUFS8 （P<0.01）， increased the ATP concentration and the protein levels of UCP1 and PGC-1α， elevated the level of TNF-α （P<0.05， P<0.01）.ConclusionNDUFS8 and HMGB1were identified as the target proteins of Res in mitigating obesity. Res promotes mitochondrial biogenesis to induce the browning of 3T3-L1 adipocytes via targeting NDUFS8 and it inhibits the TNF-α-mediated inflammatory signaling via targeting HMGB1， thus inhibiting lipid accumulation and ameliorating obesity.Keywords：chemical proteomics;resveratrol （Res）;lipid accumulation;NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）;high-mobility group protein B1 （HMGB1）34|17|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo explore the anti-eczema efficacy and mechanism of Mongolian medicine Cymbaria dahurica n-butanol extract.MethodsThe compounds of C. dahurica n-butanol extract were obtained by ultra-performance liquid chromatography-quadrupole-electrostatic field orbital trap high resolution mass spectrometry （UPLC-Q-Exactive MS） analysis and literature mining. GEO chip analysis and network pharmacology were employed to predict potential targets and pathways for the anti-eczema effect. Seventy-five mice were randomized into a normal group （10 mice） and a modeling group （65 mice）. The model was induced by 1% dinitrochlorobenzene （DNCB） for 3 days. The modeled mice were grouped as follows： Positive drug （hydrocortisone butyrate cream， 250 mg·kg-1·d-1） and low-， medium-， and high-dose （95.94， 191.88， and 383.76 mg·kg-1·d-1， respectively） C. dahurica n-butanol extract， with 13 mice in each group. From day 5 of the experiment， 0.5% DNCB was applied， once every other day， until day 22. At the same time， drugs were applied daily from day 5. The appearance damage of back skin of mice in each group was analyzed. The pathological changes of the back skin of mice in each group were observed by hematoxylin-eosin （HE） staining and toluidine blue （TB） staining. The levels of inflammatory factors ［histamine （HIS）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TFN-α）］， thymic stromal lymphopoietin （TSLP）， and immunoglobulin E （IgE） in the serum were determined by enzyme-linked immunosorbent assay （ELISA）. Metabolomics analysis was performed for the mouse skin. The HaCaT cell model of eczema was induced with TNF-α/interferon-γ （IFN-γ）. The secretion levels of IL-6， IL-8， thymus and activation-regulated chemokine （TARC/CCL17）， macrophage-derived chemokine （MDC）， and TSLP in the cell supernatant from each group were measured by ELISA， while the protein levels of phosphorylated （p）-Janus kinase 2 （JAK2）， JAK2， p-signal transducer and activator of transcription 3 （STAT3）， and STAT3 were assessed by Western blot.ResultsThrough UPLC-Q-Exactive MS and literature review， a total of 125 compounds of C. dahurica n-butanol extract were obtained. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis showed that the anti-eczema mechanism of C. dahurica n-butanol extract may be related to the Janus kinase/signal transducer and activator of transcription （JAK/STAT） pathway. The results of animal experiments showed that compared with the normal group， the modeling group exhibited redness， swelling， exudation， erosion， and scab formation on the back skin surface， and thickened dermis and epidermis with inflammatory cell infiltration. Compared with the modeling group， the positive drug and C. dahurica n-butanol alleviated the skin lesions （including redness， swelling， exudation， roughness， and keratosis and scab formation on the back）， reduced the thickness of dermis and epidermis， mitigated inflammatory cell infiltration， and restored the skin tissue structure. Compared with the normal group， the modeling group showed elevated levels of HIS， IL-4， IL-6， IL-8， TNF-α， TSLP， and IgE （P<0.05， P<0.01）， which were reversed in the positive drug group and C. dahurica n-butanol extract groups （P<0.05， P<0.01）. The results of metabolomics analysis showed that 12 differential metabolites might be the key substances for mitigating metabolic disorders of the skin and were closely related to the JAK/STAT signaling pathway. The cell experiement showed that compared with the normal group， the model group exhibited upregulated expression levels of IL-6， IL-8， MDC， TARC， TSLP， p-JAK2， p-STAT3， p-JAK2/JAK2， and p-STAT3/STAT3 in HaCaT cells （P<0.05， P<0.01）. Compared with the model group， C. dahurica n-butanol extract and dexamethasone downregulated the expression levles of these molecules （P<0.05， P<0.01）.ConclusionC. dahurica n-butanol extract may play an anti-eczema role by inhibiting the JAK2/STAT3 signaling pathway， reducing the inflammatory response， and correcting the metabolic disorder.Keywords：multi-technology cross-fusion;Mongolian medicine;Cymbaria dahurica n-butanol extract;eczema;mechanism28|12|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：Anal stenosis can be categorized into congenital and acquired types based on etiology. Congenital anal stenosis falls under the spectrum of congenital anorectal malformations， being resulted from abnormal embryonic development. Acquired stenosis is not an independent disease but rather a secondary manifestation of various anorectal conditions or injuries， with primary etiologies being primary tumors and local scar formation in the anorectum. Currently， the diagnosis and treatment for anal stenosis both domestically and internationally face challenges of inconsistent standards and significant variability in management strategies. In particular， there is a lack of systematic guidance on the standard application of diagnosis and treatment models with integrated traditional Chinese and Western medicine. Focusing on cicatricial anal stenosis， this guideline was developed by the project team through a comprehensive process including expert interviews， clinical investigation， evidence retrieval and screening， evidence evaluation， formulation of recommendations， guideline drafting， self-assessment and solicitation of feedback， and professional society review. It is based on the best available evidence-based medical data and fully incorporates expert clinical experience. The guideline aims to standardize the clinical diagnosis and treatment process for cicatricial anal stenosis with integrated traditional Chinese and Western medicine， providing clinicians with standardized management strategies and methods. This document covers the etiology， pathology， diagnostic classification， integrated traditional Chinese and Western medicine treatment， and preventive care. By incorporating the characteristics of syndrome differentiation and treatment in traditional Chinese medicine， it establishes personalized， stepped treatment protocols， thereby benefiting more patients with anal stenosis and improving their quality of life and prognosis.Keywords：anal stenosis;traditional Chinese medicine;integrated traditional Chinese and western medicine;guideline for diagnosis and treatment21|14|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo investigate the efficacy of Poge Jiuxin decoction （PGJXD） on fluid resuscitation in septic shock patients and its effects on vascular endothelial function based on clinical randomized controlled trials （RCTs） and network pharmacology， and to reveal its molecular mechanisms and signaling pathways through network pharmacology.MethodsSeventy-two septic shock patients were enrolled and randomly assigned to either the treatment group or the control group （36 cases each） through a random number table. Both groups received conventional Western medical treatment for sepsis. Additionally， the treatment group received PGJXD （100 mL， twice daily） for 3 consecutive days. The two groups were compared in terms of the Sequential Organ Failure Assessment （SOFA） score， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score， vascular endothelial function indicators ［endothelium-derived relaxing factor （EDRF）， nitric oxide （NO）， and 6-keto-prostaglandin F1α （6-keto-PGF1α）］， inflammation indicators ［tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， nuclear factor kappa-B （NF-κB）， and procalcitonin （PCT）］， perfusion indicators ［mean arterial pressure （MAP）， lactate （Lac）， and 72-hour lactate clearance rate （Lcr）］， fluid resuscitation target achievement time， vasopressor use duration， length of hospital stay， and 28-day mortality. Databases including TCMSP， HIT 2.0， and Uniprot were searched for active components of PGJXD and their targets. Gene targets for septic shock were obtained from GeneCards， OMIM， and DrugBank databases. Venny software was used to identify common targets between PGJXD and septic shock. Cytoscape software and the STRING database were utilized to construct a "drug-component-target-disease" network and a protein-protein interaction （PPI） network. Gene Ontology （GO） functional enrichment analysis， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis， and molecular docking were performed to explore the molecular mechanisms and signaling pathways of PGJXD in treating septic shock.ResultsFive patients withdrew from the treatment group and seven from the control group. After treatment， both groups showed decreases （P<0.01） in APACHE Ⅱ score， SOFA score， EDRF， 6-keto-PGF1α， TNF-α， IL-6， NF-κB， PCT， MAP， and Lac， and increases in NO （P<0.01）. The treatment group exhibited more significant decreases （P<0.05， P<0.01） in APACHE Ⅱ score， SOFA score， 6-keto-PGF1α， TNF-α， IL-6， NF-κB， MAP， Lac， Lcr， fluid resuscitation target achievement time， and vasopressor use duration than the control group. Differences in EDRF， NO， PCT， length of hospital stay， and 28-day mortality were not statistically significant. No significant adverse reactions were observed in either group during treatment. Network pharmacology identified 189 components and 257 potential targets of PGJXD， and 136 common targets shared by PGJXD and septic shock. GO enrichment analysis primarily involved positive regulation of cell migration， response to peptide， response to inorganic substance， etc. KEGG enrichment analysis mainly implicated signaling pathways such as NF-κB， VEGF， and Relaxin.ConclusionPGJXD can significantly ameliorate the condition of septic shock patients and enhance the efficacy of fluid resuscitation. Its key mechanism may involve protecting vascular endothelial cells by regulating the TNF-α/NF-κB signaling pathway and reducing the inflammatory response.Keywords：septic shock;Poge Jiuxin decoction;network pharmacology;vascular endothelial cell function;nuclear factor-κB （NF-κB） signaling pathway49|12|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
Effect of Qihuang Jianpi Zishen Granules for Treat-to-target on Renal Podocyte Injury Markers in Patients with Systemic Lupus Erythematosus AI Introduction
Abstract：ObjectiveTo investigate the clinical efficacy of Qihuang Jianpi Zishen granules in the treatment of systemic lupus erythematosus （SLE），observe their effects on renal podocyte injury，and decipher related mechanisms.MethodsSixty-two SLE patients with renal damage who met the inclusion criteria and treated in the First Affiliated Hospital of Anhui University of Chinese Medicine between November 2022 and July 2024 were selected. They were randomly allocated into a control group and an observation group （31 patients in each group）. The control group was treated with oral hydroxychloroquine sulfate，prednisone acetate，and mycophenolate mofetil. The observation group received Qihuang Jianpi Zishen granules orally in addition to the regimen in the control group. After 12 weeks of continuous treatment，the SLE Responder Index-4 （SRI-4） response rate was evaluated for both groups. Comparisons were made between the two groups before and after treatment regarding disease activity scores，traditional Chinese medicine （TCM） symptom scores，kidney-related indicators ［serum creatinine （SCr），cystatin C （Cys C），24-hour urine protein quantitation （24 h Pro），urine protein/creatinine ratio （UPCR），and urine albumin/creatinine ratio （UACR）］，immune and inflammatory markers ［anti-double-stranded DNA antibody，interferon-γ （IFN-γ），and monocyte chemoattractant protein-1 （MCP-1）］，urinary podocyte injury markers （Nephrin，Podocin，and WT-1），and mRNA levels of apoptosis-related factors （Bax，Bcl-2，and Caspase-3） in peripheral blood mononuclear cells. Adverse reactions were recorded.ResultsAfter 12 weeks of treatment，the SRI-4 response rate in the observation group was 48.38%（15/31），which was higher than that in the control group 36.66%（11/30）. Within-group comparisons showed that after treatment，both groups exhibited decreases in TCM symptom scores，kidney-related indicators （UACR，UPCR，24 h Pro，SCr，and CysC），inflammatory markers （IFN-γ and MCP-1），podocyte injury markers （Nephrin，Podocin，and WT-1），and the mRNA levels of Bax and Caspase-3 （P<0.05，P<0.01） and an increase in the mRNA level of Bcl-2 （P<0.01）. After treatment，the observation group showed lower disease activity score，TCM symptom scores，levels of UACR，UPCR，24 h Pro，SCr，IFN-γ，MCP-1，and podocyte injury markers （Nephrin，Podocin，WT-1），and mRNA level of Bax （P<0.05，P<0.01） and higher mRNA level of Bcl-2 （P<0.05） than the control group. No serious adverse reactions occurred during the treatment period.ConclusionQihuang Jianpi Zishen granules can effectively reduce the disease activity，TCM symptoms，proteinuria，podocyte injury，and renal damage in patients with SLE by regulating the immune-inflammatory state，mitigating podocyte injury，and inhibiting cell apoptosis.Keywords：Qihuang Jianpi Zishen granules;systemic lupus erythematosus;podocytes;podocyte injury markers;apoptosis29|12|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02Interpretation and Enlightenment of Expert Consensus on Clinical Application of Yifei Zhike Capsules AI Introduction
Abstract：ObjectiveTo interpret the main contents of the Expert Consensus on Clinical Application of Yifei Zhike Capsules （hereinafter referred to as the Consensus）， analyze its evidence basis， and explore future research directions， thus providing a reference for rational drug use in clinical practice.MethodsThe core contents of the Consensus are summarized. Focusing on clinical issues， this paper summarizes the recommendations and consensus suggestions in the Consensus and explains them from aspects such as indications， key advantages， usage and dosage， combined medication， contraindications， precautions， and safety.ResultsThe Consensus clearly states that Yifei Zhike capsules can be used for acute or chronic bronchitis， pulmonary tuberculosis and other respiratory system diseases. It for the first time proposes that the applicable TCM syndrome of Yifei Zhike capsules is Qi-Yin deficiency together with combined phlegm and stasis. For different diseases， the Consensus provides specific usage instructions， dosage， and treatment course recommendations， supplementing the contents not covered in the drug instructions. In terms of combined medication， the Consensus emphasizes the principle of using this drug in combination with standardized chemotherapy regimens or conventional Western medicines and the applicability for the treatment of pulmonary tuberculosis and moderate to severe acute or chronic bronchitis. In terms of safety， the Consensus proposes methods for identifying common adverse reactions， drug contraindications， and precautions based on a review of the existing data and preliminarily builds a risk management framework. However， the evidence on which the Consensus is based are mostly early studies， with small sample sizes， which result in the low evidence grades （mainly C and D） of some recommendations.ConclusionThe Consensus provides specific guidance for the clinical use of Yifei Zhike capsules. However， due to the limited quality of the existing research evidence， more high-quality clinical studies are needed in the future to further verify its efficacy， safety， and explore its broader application prospects.Keywords：Yifei Zhike capsules;Miao medicine;expert consensus;clinical application;interpretation41|14|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02Quality Appraisal of Clinical Practice Guidelines and Expert Consensus Statements for Knee Osteoarthritis Based on AGREE Ⅱ （2019—2025） AI Introduction
Abstract：ObjectiveTo evaluate the quality of clinical practice guidelines and expert consensus statements on knee osteoarthritis （KOA） based on the Appraisal of Guidelines for Research & Evaluation Ⅱ （AGREE Ⅱ）， thus providing a new perspective for clinical selection as well as guideline development and updating.MethodsA systematic search was conducted for KOA-related guidelines and consensus statements published from November 1， 2019 to December 31， 2025. The databases and platforms searched included CNKI， VIP， Wanfang Data， PubMed， Web of Science， the National Institute for Health and Care Excellence （NICE）， SinoMed， Yimaitong， and relevant official websites. Two researchers independently screened the literature， and four researchers used AGREE Ⅱ to score the included documents and completed the quality appraisal after reaching a unified understanding. Subgroup analyses were further performed according to developing organization， document type， medical approach， funding status， and region of development， and longitudinal comparisons were conducted by year of publication.ResultsA total of 23 guidelines and consensus statements were included. The standardized scores of the six AGREE Ⅱ domains， from the highest to the lowest， were clarity of presentation ［（70.36±8.13）%］， scope and purpose ［（67.46 ± 11.44）%］， editorial independence ［（64.50±20.01）%］， rigor of development ［（62.24±15.26）%］， stakeholder involvement ［（55.73±10.29）%］， and applicability ［（53.89±13.17）%］. In terms of overall recommendation， 6 documents were rated as grade A and 17 as grade B. Stratified analyses showed that professional organizations scored higher than comprehensive organizations. The overall scores of traditional Chinese medicine/integrative medicine and Western medicine guidelines （or consensus statements） were similar. Guidelines scored higher than consensus statements. The overall scores were similar between documents with reported funding and those without reported funding. International guidelines scored higher than domestic guidelines. Longitudinal comparisons showed that the largest number of documents was published in 2021. The overall scores were higher in 2021—2022， and some domain scores declined in 2023—2024. Overall， the quality of recent guidelines and consensus statements for KOA showed slight fluctuations， without a clear linear trend.ConclusionThe included guidelines and consensus statements for KOA can generally serve as references for clinical practice. However， the quality across domains remains uneven， and stakeholder involvement and applicability are still weak domains. Future guideline development and updating should further improve methodological standardization and transparency in reporting.Keywords：knee osteoarthritis;clinical practice guideline;expert consensus;Appraisal of Guidelines for Research & Evaluation Ⅱ （AGREE Ⅱ）;quality appraisal38|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02- Abstract：ObjectiveTo screen and identify uridine diphosphate （UDP）-rhamnose synthase （RHM） genes from Ornithogalum saundersiae and verify their UDP-rhamnose （UDP-Rha） biosynthetic functions， thereby providing reliable candidate genes for the efficient biosynthesis of neohesperidin and other rhamnoside natural products.MethodsBased on previously reported plant RHM sequences， two candidate RHM genes， OsRHM1 and OsRHM2， were identified from O. saundersiae through transcriptome screening and sequence alignment. The two genes were cloned and subjected to bioinformatics analysis and multiple sequence alignment. An in vitro RHM-Cm1，2RhaT cascade reaction was established， and the ability of OsRHM1 and OsRHM2 to catalyze the conversion of UDP-glucose （UDP-Glc） to UDP-Rha was evaluated based on neohesperidin production. Real-time fluorescence quantitative polymerase chain reaction PCR （Real-time PCR） was performed to analyze the relative expression levels of the two genes in roots， bulbs， and leaves.ResultsThe open reading frame （ORF） of OsRHM1 was 2 076 bp and encoded 692 amino acids， with a predicted protein molecular mass of 77.97 kDa and a theoretical isoelectric point of 7.25. The ORF of OsRHM2 was 2 019 bp and encoded 673 amino acids， with a predicted protein molecular mass of 75.82 kDa and a theoretical isoelectric point of 7.24. Multiple sequence alignment showed that OsRHM1 and OsRHM2 contained the typical conserved motifs GxxGxxG/A and YxxxK of the plant RHM family and shared high amino acid sequence identity with previously reported RHMs. The in vitro cascade reaction demonstrated that both OsRHM1 and OsRHM2 were capable of catalyzing the conversion of UDP-Glc to UDP-Rha. The neohesperidin production in the OsRHM2 cascade reaction system was approximately 2.58-fold that in the OsRHM1 system. Real-time PCR analysis showed that the relative expression levels of OsRHM1 and OsRHM2 were higher in roots than in bulbs and leaves.ConclusionOsRHM2 exhibited a relatively high capacity for UDP-Rha supply and may serve as a candidate enzyme resource for the subsequent biosynthesis of rhamnoside natural products and the construction of UDP-Rha supply systems.Keywords：Ornithogalum saundersiae;rhamnose synthase;UDP-rhamnose;cascade reaction;functional identification15|9|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveIn response to the policy promoting the "three-combination" evidence framework for the regulatory review of traditional Chinese medicine （TCM）， this study aimed to evaluate the efficacy evidence of commonly used Chinese patent medicines for ulcerative colitis （UC） by applying the Integrated Evidence Chain-Based Effectiveness Evaluation of Traditional Chinese Medicine （iEC-Eff） method and the Grading of Recommendations， Assessment， Development and Evaluation （GRADE） system in parallel， compare their grading results and assessment characteristics， and explore the applicability of the iEC-Eff method.MethodsUC-related guidelines and consensus statements were systematically retrieved， and commonly used Chinese patent medicines were selected using a modified formula based on Zipf's law. Evidence from clinical experience， experimental research， and clinical trials was retrieved separately. The iEC-Eff method and GRADE system were applied in parallel to assess evidence quality. The two methods were compared in terms of evidence sources， grading criteria， and grade assignments. The historical origins， composition， and related pharmacological studies of the medicines were also examined.ResultsSix guidelines and seven consensus statements were included， and five commonly used Chinese patent medicines were identified. Under the GRADE system， the evidence for Xilei powder， Kangfuxin liquid， Shenling Baizhu preparations， and Hudi Enteric-Coated Capsules was rated as grade C， indicating low-certainty evidence. Bupi Yichang Wan was not graded due to the lack of high-quality randomized controlled trials （RCTs）. Under the iEC-Eff method， Xilei powder （AAB）， Kangfuxin liquid （AAB）， and Shenling Baizhu preparations （A⁺A⁺⁺B） were classified as having high-level evidence， while Hudi Enteric-Coated Capsules （CC⁺A⁺） was classified as having moderate-level evidence. Bupi Yichang Wan remained ungraded because of an incomplete evidence chain. The two methods yielded different grading results and showed some complementarity in evidence sources and assessment dimensions.ConclusionThe parallel application of the iEC-Eff method and GRADE system may help present the available evidence for Chinese patent medicines in the treatment of UC from two perspectives： integration of evidence from multiple sources and assessment of evidence certainty. This approach may provide a reference for efficacy evidence evaluation and clinical use of Chinese patent medicines. The iEC-Eff method shows potential for the separate appraisal and integrated grading of evidence from clinical experience， experimental research， and clinical trials. However， its evaluation criteria and applicability require further validation and refinement.Keywords：Chinese patent medicines;ulcerative colitis;Grading of recommendations， assessment， development， and evaluation （GRADE） system;integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine （iEC-Eff） method;evidence-based medicine38|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：ObjectiveTo improve the quality of artificial cultivation of the source plant of Fritillariae Cirrhosae Bulbus （FCB）， an XGBoost regression model was constructed based on the Group-Lasso method to screen the characteristic variables. The key factors affecting the quality formation of the source plant were then analyzed.MethodsFirstly， with the total alkaloid content （TAC） of FCB as the dependent variable， explanatory characteristic variables were screened from the influencing factors of TAC in the literature studying FCB quality from 2010 to 2024 based on the Group-Lasso regression algorithm. The screening results were verified by ten-fold cross-validation. Secondly， the present study established an XGBoost regression model to analyze the influencing factors of the quality formation of the source plant， and calculated the importance score of the explanatory characteristic variables.ResultsGroup-Lasso regression removed 2 numerical independent variables and retained the remaining 5 categorical variables and 6 numerical variables； cross-validation also showed that the number of screening variables is 11， with the corresponding optimal λ parameter value of 0.000 515 225 1. The results of XGBoost regression model confirmed the geographical origin as the most critical factor affecting the quality formation of source plants， followed by growth status and soil type， and then by mean temperature of the warmest month， original plant type， mean annual temperature， and altitude. Climate type， precipitation， frost-free period and relative humidity of the geographical origin exerted little effect.ConclusionThe prediction tools of Group-Lasso and XGBoost regression analysis models were preliminarily established for the quality formation of FCB. These models overcame the multicollinearity among numerical independent variables， and explored the geographical distribution of TAC and its key driving factors. The suitable cultivation areas can be selected or wild-tending bases established based on these key factors， thereby effectively avoiding blind introduction and cultivation. Finally， the present study provided a reference for the development and utilization of FCB， a theoretical basis for the market expansion and quality regulation， and a direction for the sustainable development and protection of new and efficient FCB resources.Keywords：Fritillariae Cirrhosae Bulbus;total alkaloids;Group-Lasso;variable screening;XGBoost17|13|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
Exploring Clinical Application of Phlegm-resolving and Detoxifying Prescriptions Based on Lung Cancer Treatment AI Introduction
Abstract：Lung cancer is the leading cause of cancer-related deaths worldwide. While modern medical therapies such as surgery， chemotherapy， and radiotherapy have achieved progress， they often come with severe side effects and drug resistance. Traditional Chinese medicine （TCM）， characterized by its multi-component， multi-target， and holistic regulatory properties， plays a significant role in the adjunctive treatment of lung cancer. It offers unique advantages in alleviating clinical symptoms， enhancing patients' quality of life， prolonging survival， and enhancing efficacy while reducing toxicity， serving as an important therapeutic modality for lung cancer. The theory of cancer-toxin pathogenesis proposes that phlegm-toxin is a key pathogenic factor in lung cancer， with phlegm-toxin mutual entanglement being the core pathogenesis of lung cancer. The pathogenic characteristics-viscosity， dispersion， and damage to the healthy Qi-of phlegm-toxin are closely related to the accumulation of acidic metabolic products， tumor invasion and metastasis， and immune suppression during the course of lung cancer. Phlegm resolving and toxin clearing are the core therapeutic methods for lung cancer. Such prescriptions possess dual functions of resolving phlegm and dissipating mass， as well as inhibiting tumor and detoxifying. They exert antitumor effects through multiple pathways， including regulating metabolic reprogramming of glucose and lipids， improving the acidic microenvironment of tumors， and inhibiting inflammatory signaling pathways. This paper systematically reviews the current clinical application status and mechanisms of phlegm-resolving and detoxifying Chinese herbal medicines. By integrating the theory of cancer-toxin pathogenesis with modern pharmacological research findings， this paper explores their application in lung cancer treatment and establishes a clinical application system for phlegm-resolving and detoxifying therapies in lung cancer based on phlegm-toxin pathogenesis. This system integrates ancient and modern experiences with contemporary mechanisms， aiming to provide theoretical foundations and practical references for integrated traditional and Western medicine diagnosis， treatment， and drug development for lung cancer and other conditions.Keywords：lung cancer;phlegm toxin;phlegm-resolving and detoxifying Chinese herbal medicine;efficacy mechanism;theory of cancer-toxin pathogenesis28|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02- Abstract：This article explores the pathogenesis ， evolution and the prevention-treatment strategies of hypertension-related coronary microvascular dysfunction （H-CMD） from the collateral disease theory. Long-term hypertension may lead to coronary microvascular vasomotor imbalance， endothelial injury， vascular remodeling， microthrombosis， reduced perfusion reserve， and microvascular rarefaction， suggesting a progressive pathological process from functional disturbance to structural injury， collateral obstruction， and insufficient repair. Collateral disease theory emphasizes the network-like distribution， gradual branching， and permeating and nourishing functions of collaterals， as well as the concept that prolonged disease enters the collaterals， providing a reference for understanding coronary microcirculatory dysfunction and malnourishment of heart collaterals. Accordingly， the traditional Chinese medicine （TCM） pathogenesis of H-CMD can be summarized into four interconnected stages： Collateral Qi stagnation， scorching injury of collateral vessels， phlegm-stasis obstruction of collaterals， and collateral deficiency with malnourishment. Collateral Qi stagnation is the initiating stage， mainly corresponding to abnormal coronary microvascular vasomotor regulation and endothelial dysfunction. Scorching injury of collateral vessels represents the developmental stage and is closely associated with inflammation， oxidative stress， and endothelial barrier injury after Qi stagnation transforms into fire. Phlegm-stasis obstruction of collaterals represents the prolonged stage and may aggravate vascular wall thickening， luminal stenosis， microthrombosis， and insufficient microcirculatory perfusion. Collateral deficiency with malnourishment is the late-stage outcome， reflecting deficiency of healthy Qi， collateral damage， Qi-blood malnourishment， and weakened repair capacity， mainly manifested as microvascular rarefaction， occlusion， and microcirculatory homeostatic imbalance. Therapeutically， stage-based syndrome differentiation and the combined strategy of dredging and nourishing collaterals should be emphasized. Specifically， promoting Qi movement， resolving stagnation， soothing the liver， and harmonizing collaterals should be adopted in the early stage. Clearing heat， pacifying the liver， calming and protecting collaterals should be adopted in the developmental stage. Resolving phlegm， activating blood， and dredging collaterals should be implemented in the prolonged stage. Supplementing Qi， nourishing blood， tonifying the kidney， regulating balance， strengthening healthy Qi， and nourishing collaterals should be carried out in the late stage. Related formulas and medicinals may act by regulating the nitric oxide/endothelin-1（NO/ET-1） balance， inhibiting inflammation and oxidative stress， improving microcirculatory perfusion， and promoting angiogenesis and endothelial repair. Collateral disease theory may provide a theoretical basis for understanding the dynamic pathogenesis of H-CMD and for stage-based TCM intervention.Keywords：hypertension;coronary microvascular dysfunction;collateral disease theory;pathogenesis evolution;prevention-treatment strategies37|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
Pathogenesis and Treatment of Combined Phlegm and Stasis in Lung Cancer Based on Abnormal Iron Metabolism AI Introduction
Abstract：Abnormal iron metabolism constitutes a pivotal pathological mechanism in lung cancer progression. It induces cellular dysfunction， triggers inflammatory responses， promotes ferroptosis tolerance， and facilitates the formation of tumor immune microenvironments. These processes align with traditional Chinese Medicine （TCM） pathogenesis of combined phlegm and stasis， collectively driving malignant progression. The occurrence of iron overload and ferroptosis resistance in lung cancer represents critical components of abnormal iron metabolism， which may induce lipid deposition and hypercoagulable states—mechanisms closely associated with phlegm and stasis in TCM. Both abnormal iron metabolism and combined phlegm and stasis originate from dysfunction of the lung， spleen， and kidney. Their pathological manifestations share similarities： obstructing Qi and blood circulation and accumulating pathological products， and synergistically exacerbating disease progression through tumor growth and metastasis. This study elucidates the interconnections between combined phlegm and stasis， abnormal iron metabolism， and lung cancer， highlighting their pathophysiological correlations. Regarding clinical therapeutic strategies， this paper proposes three approaches： ① invigorating the spleen to resolve phlegm and alleviate iron overload for tumor suppression； ②activating blood to induce ferroptosis and inhibit tumor invasion； ③modulating iron metabolism through phlegm-resolving and stasis-eliminating therapies to reverse drug resistance. These strategies enrich the theoretical framework of phlegm-stasis regulation in lung cancer management. Integrating modern medical research with TCM pathogenesis theories， this study reveals the intrinsic link between abnormal iron metabolism and combined phlegm and stasis in lung cancer， offering new perspectives for understanding tumor development and metastasis. By establishing iron metabolism as a bridge， this study provides innovative insights into the pathogenesis of combined phlegm and stasis in lung cancer.Keywords：abnormal iron metabolism;lung cancer;combined phlegm and stasis;iron overload;ferroptosis26|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02- Abstract：The collateral disease theory stands as one of the most instructive frameworks for elucidating the pathology of Mycoplasma pneumoniae pneumonia （MPP）. Its characteristic pathological features—toxin damaging collaterals， dysfunction of Qi collaterals， and protracted illness involving collaterals—closely align with the manifestations of cytokine storms， immune dysregulation， and chronic damage induced by M. pneumoniae （MP）. Drug-resistant MP further exacerbates these manifestations and poses challenges in clinical treatment， making it essential to clarify the intrinsic relationship between the collateral disease theory and MPP. However， existing studies still lack relevant elaboration， resulting in a gap in guidance by traditional Chinese medicine （TCM） theory in clinical practice. Considering the instructive， scientific， and necessary role of the collateral disease theory in MPP， this paper thoroughly elucidates the pathological manifestations of MPP and the core evolutionary characteristics of collateral damage， and further provides a scientific interpretation from the perspective of collateral disease on the clinical efficacy and mechanism of TCM treatment of MPP over the past five years. This review aims to reveal the intrinsic relationship between the collateral disease theory and MPP， enrich the scientific connotation of TCM theory， and bridge the gap in TCM theoretical guidance， thereby providing scientific research clues for TCM treatment of MPP.Keywords：Mycoplasma pneumoniae pneumonia （MPP）;traditional Chinese medicine （TCM）;clinical efficacy;mechanism;research progress40|11|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：Heart failure （HF） is the end-stage of various cardiovascular diseases， with high morbidity and mortality. The existing “new quadruple” standard treatment can hardly reverse the core pathological process of myocardial remodeling， and long-term medication may pose risks of drug resistance and adverse reactions. Therefore， new therapeutic targets and strategies are urgently needed. Metabolic reprogramming is the upstream core mechanism regulating phenotypic polarization and functional activation of macrophages， which drives the occurrence and development of HF through the core axis of metabolic reprogramming-immune imbalance-ventricular remodeling and has become a cutting-edge potential target for the prevention and treatment of HF. Traditional Chinese medicine （TCM） has a long history in the prevention and treatment of HF. A large number of studies in recent years have confirmed that different therapeutic methods of TCM can correct the polarization imbalance， restore the homeostasis of myocardial immune microenvironment， inhibit myocardial injury， and delay the pathological process of HF by targeting and regulating the metabolic reprogramming of glucose， lipids， mitochondria， and amino acids in macrophages. This paper systematically expounds the core pathological mechanism of metabolic reprogramming of macrophages in HF， sorts out the research progress of TCM in preventing and treating HF by intervening this target， analyzes the regulatory rules， summarizes the limitations of existing research， and puts forward future directions. This review aims to provide a systematic theoretical reference and new research ideas for TCM clinical diagnosis and treatment and new drug development of HF.Keywords：heart failure;macrophages;metabolic reprogramming;metabolism-immune regulatory axis;traditional Chinese medicine;signaling pathway52|13|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：Lipid metabolism reprogramming is a metabolic hallmark of hepatocellular carcinoma （HCC） initiation and progression. It encompasses aberrant activation of de novo lipogenesis （DNL）， remodeling of the membrane phospholipid polyunsaturated fatty acid （PUFA）/monounsaturated fatty acid （MUFA） ratio， upregulation of the mevalonate （MVA） pathway， and compensatory activation of subcellular antioxidant networks. Together with liver-specific dysregulation of iron homeostasis， these alterations shape a dual metabolic landscape in which ferroptosis susceptibility and resistance coexist， thereby driving malignant progression and therapeutic tolerance. In traditional Chinese medicine （TCM）， the core pathogenesis of HCC is conceptualized as the interplay of dampness， heat， stasis， toxin， and deficiency， which is intrinsically consistent at the biological level with the aforementioned lipid accumulation， redox imbalance， and disordered iron metabolism. According to the three therapeutic principles of clearing heat， detoxifying， and resolving dampness， activating blood to dispel stasis and counteract toxins， and reinforcing healthy Qi to consolidate the root， this review systematically delineates the molecular mechanisms by which the active components of traditional Chinese medicine modulate the lipid-ferroptosis network. Active components including berberine， tanshinone ⅡA， and ginsenosides cooperatively induce ferroptosis in HCC by disrupting the cystine/glutamate antiporter-glutathione-glutathione peroxidase 4 （System Xc-/GSH/GPX4） antioxidant axis， upregulating long-chain acyl-CoA synthetase 4 （ACSL4） to promote PUFA-containing membrane lipid peroxidation， perturbing nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 （NRF2/KEAP1） and protein kinase R-like endoplasmic reticulum kinase/activating transcription factor 4 （PERK/ATF4） signaling pathways， and disrupting ferritin homeostasis. On this basis， the review evaluates the translational prospects of these components in reversing tyrosine kinase inhibitor （TKI） resistance， sensitizing immune checkpoint inhibitor therapy， and enabling nanocarrier-mediated delivery， with the aim of providing a pharmacological basis for the development of TCM candidate agents targeting the lipid-ferroptosis axis and for the optimization of therapeutic strategies integrating Chinese and Western medicine.Keywords：lipid metabolism reprogramming;hepatocellular carcinoma;ferroptosis;active components of traditional Chinese medicine;mechanism45|16|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
Traditional Chinese Medicine Treats Diabetic Nephropathy by Regulating PPARγ Signaling Pathway： A Review AI Introduction
Abstract：Diabetic nephropathy （DN） is one of the most common and serious microvascular complications of diabetes mellitus and represents a major cause of chronic kidney disease progression and end-stage kidney disease， thereby constituting a major public health problem that adversely affects the prognosis and quality of life of patients with diabetes mellitus. The pathogenesis and progression of DN are complex and involve multiple pathological processes， including insulin resistance， inflammation， oxidative stress， lipid deposition， podocyte injury， and renal fibrosis. Although current clinical therapies can delay the progression of DN to some extent， their effectiveness remains limited by marked interindividual variability in therapeutic response and the difficulty of fully reversing renal injury. Therefore， further elucidation of the key molecular mechanisms underlying DN and the exploration of effective therapeutic strategies are of considerable importance. In recent years， with advances in the understanding of DN pathogenesis， peroxisome proliferator-activated receptor γ （PPARγ）， an important nuclear receptor transcription factor involved in the regulation of insulin resistance， inflammation， oxidative stress， and fibrotic processes， has attracted increasing attention for its role in the development and progression of DN. Traditional Chinese medicine （TCM）， characterized by multi-component， multi-target， and multi-pathway synergistic regulation， may ameliorate pathological processes including metabolic abnormalities， inflammation， oxidative stress， lipid deposition， and renal fibrosis in DN by targeting PPARγ and its associated signaling networks. This review systematically summarizes the mechanisms by which PPARγ and its related signaling pathways regulate DN and reviews recent advances in TCM interventions targeting the PPARγ signaling pathway in DN. Such TCM interventions encompass single herbs such as Coptidis Rhizoma， active constituents such as quercetin， astragaloside Ⅳ， and trigonelline， extracts of herbs such as Plantaginis Herba and Dendrobii Nobilis Caulis， and formulas such as Huangkui capsules， Shenshuaining granules， and Mudan granules. This review aims to provide a theoretical basis for the prevention and treatment of DN with TCM.Keywords：diabetic nephropathy;PPARγ signaling pathway;traditional Chinese medicine （TCM）;TCM active constituents;TCM formulas34|13|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02- Abstract：Diabetic nephropathy belongs to diabetic microvascular aseptic inflammation， which is the main cause of end-stage renal disease and can cause damage to the structure of glomeruli and tubulointerstitium. Pyroptosis is a potent pro-inflammatory model of programmed cell death mediated by gasdermin （GSDM） protein family， which is characterized by nuclear shrinkage， chromatin DNA fragmentation， plasma membrane rupture， cell swelling and deformation. Related studies have found that pyroptosis is closely related to the occurrence and development of diabetic nephropathy. Inhibition of pyroptosis to a certain extent can reduce diabetic renal injury， so the pathway of pyroptosis involved in the pathogenesis of diabetic nephropathy is the current research focus. The characteristics of multi-components， multi-targets and multi-pathways of traditional Chinese medicine have significant advantages in the treatment of diabetic nephropathy. Some components of traditional Chinese medicine， single traditional Chinese medicine and compound prescription of traditional Chinese medicine can improve diabetic renal injury by inhibiting pyroptosis pathway and related targets. Based on the molecular mechanism of pyroptosis， this paper clarifies the mechanism of pyroptosis in diabetic nephropathy by expounding the relationship between pyroptosis and its pathway targets and diabetic nephropathy. This paper summarizes the research status of traditional Chinese medicine in the treatment of diabetic nephropathy by interfering with related pyroptosis pathways in recent years， so as to provide perspectives and ideas for the prevention， early diagnosis， drug development and molecular treatment of diabetic nephropathy in the future.Keywords：diabetic nephropathy;pyroptosis;signal pathway;traditional Chinese medicine;mechanism26|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：Cuproptosis is a newly identified form of cell death triggered by copper ion dyshomeostasis， particularly characterized by the accumulation of copper in metabolic enzymes within the mitochondria. In recent years， this mechanism has garnered significant attention in the research on neurodegenerative diseases. As investigations into the pathogeneses of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease have advanced， the role of cuproptosis in these diseases has gradually been elucidated， establishing it as a breakthrough point for understanding disease progression. The current research primarily focuses on the associations between cuproptosis-related genes and neuronal damage， aiming to unravel the regulatory networks involved in the onset and development of these diseases. However， numerous questions remain regarding the specific regulatory mechanisms of cuproptosis and its relationship with the pathological changes in neurodegenerative diseases. Against this backdrop， this article systematically reviews the research progress in the molecular regulatory networks governing cuproptosis and roles of cuproptosis in various neurodegenerative diseases， with a particular emphasis on the intrinsic link between copper dyshomeostasis， neuroinflammation， and mitochondrial metabolism. Furthermore， integrating theories of traditional Chinese medicine （TCM） with advancements in modern pharmacological research， this article explores the potential value of TCM in regulating copper metabolism and intervening in cuproptosis signaling pathways. This review aims to offer new perspectives for understanding the pathogeneses of neurodegenerative diseases and lay a theoretical foundation for developing novel prevention and treatment strategies based on the modulation of cuproptosis with TCM.Keywords：cuproptosis;neurodegenerative diseases;mitochondria;Alzheimer's disease;Parkinson's disease35|10|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
- Abstract：The herb pair Hedysari Radix-Angelicae Sinensis Radix is a classic combination embodying the theory of replenishing Qi and tonifying blood in traditional Chinese medicine. The two herbs are often used together to achieve the effects of replenishing Qi， tonifying blood， activating blood， and unblocking collaterals. Clinically， this herb pair is widely applied in the treatment of blood deficiency syndrome and hematopoietic dysfunction disorders such as myelosuppression induced by radiotherapy and chemotherapy. Modern research indicates that Hedysari Radix-Angelicae Sinensis Radix and their active components can synergistically promote hematopoiesis through multiple targets and pathways. At the cellular level， the active components directly activate hematopoietic stem cells （HSCs） and hematopoietic progenitor cells （HPCs）， promoting their proliferation and differentiation， while simultaneously stimulating the production and release of peripheral blood cells. Regarding molecular regulation， this herb pair can regulate the expression of various hematopoietic-related cytokines， such as stem cell factor and erythropoietin. Additionally， it modulates key signaling pathways， including phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） and Wnt/β-catenin， providing signal support for the hematopoietic process. Furthermore， Hedysari Radix-Angelicae Sinensis Radix can improve the hematopoietic microenvironment， protect bone marrow stromal cells， and eliminate free radicals through antioxidant effects， thereby reducing damage to hematopoietic cells. Furthermore， this herb pair regulates apoptosis-related proteins to inhibit excessive apoptosis of hematopoietic cells and increase their survival rate. Its material basis primarily includes active components such as Hedysarum polybotrys polysacchcrides and flavonoids， as well as Angelica sinensis polysaccharides and ferulic acid， which synergistically contribute to its hematopoietic-promoting effects. By elaborating on the active components and mechanisms of Hedysari Radix-Angelicae Sinensis Radix in promoting hematopoiesis， this paper aims to elucidate the molecular mechanisms underlying their hematopoietic effects and provide a reference for further research and clinical application.Keywords：Hedysari Radix;Angelicae Sinensis Radix;chemical components;hematopoietic mechanism;hematopoietic stem cells52|22|0<HTML><H-PDF> <L-PDF> <XML>Updated：2026-11-02
