Abstract：ObjectiveTo compare the therapeutic efficacies of Wujiwan at two different compatibilities （No.1 and No.2） on irritable bowel syndrome （IBS） based on neuro-endocrine-immune network， and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine （TCM）.MethodThe chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty （PTCA） in suckling rats. The animals were randomly divided into a control group， a model group， a dicetel group （0.01 g·kg-1）， low- （0.335 g·kg-1）， medium- （0.67 g·kg-1）， and high-dose （1.34 g·kg-1） No. 1 Wujiwan groups， and low- （0.385 g·kg-1）， medium- （0.77 g·kg-1）， and high-dose （1.54 g·kg-1） No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells （MC） in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine （5-HT）， substance P （SP）， somatostatin （SS）， and vasoactive intestinal peptide （VIP） in the blood/colon tissue were detected by enzyme-linked immunosorbent assay （ELISA） and immunohistochemistry （IHC） assay.ResultThere was no significant difference in body weight among different groups. Compared with the control group， the model group exhibited decreased thresholds of abdominal elevation and bow back elevation （P<0.01）， increased density of MCs in the colon tissue （P<0.05）， up-regulated levels of 5-HT， SP， and SS in the blood and colon tissue （P<0.05， P<0.01）， and elevated VIP level in the colon tissue （P<0.05）. Compared with the model group， Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation （P<0.01）， diminish the count of MC in the colon tissue （P<0.05）， and reduce the levels of 5-HT， SP， SS， and VIP （P<0.05）. As demonstrated by the comparison of No. 1 and No. 2 Wujiwan， No. 1 was superior to No. 2 in reducing the concentrations of 5-HT， SP， and SS in the blood， especially in 5-HT （P<0.01）. No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan， No. 2 significantly reduced SP expression， and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups （P<0.05）.ConclusionWujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect， No. 1 was superior to No. 2， while in terms of local effect， No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics， while No. 2 had an advantageous effect on intestinal sensation over No. 1.
Abstract：Taohong Siwutang， originating from Fuke Bingjian by CHAI Dehua in the Qing Dynasty， has been included in the first batch of the 100 classical prescriptions published by the National Administration of Traditional Chinese Medicine（TCM）. Taohong Siwutang is composed of six Chinese medicinals， namely the wine-washed Angelicae Sinensis Radix， wine-washed Rehmanniae Recens Radix， wine-washed Carthami Flos， wine-processed Paeoniae Alba Radix， Persicae Semen undergoing peel-off process in hot water， and Chuanxiong Rhizoma， possessing the effects of nourishing blood， promoting blood circulation， and removing blood stasis， and it is mainly applicable to patients with blood deficiency and stasis syndrome. The textual research on the key information of classical prescriptions and the summarization of their ancient and modern applications are conducive to learning about the research status and confirming the subsequent research direction， thus better guiding the preparation of substance benchmarks and the in-depth exploration of preparations. By exploring the sources and historic evolution of Taohong Siwutang and each Chinese medicinal， this paper uncovered the prescription composition， origin of each Chinese medicinal， processing method， and prescription dose. The review of its clinical applications showed that the application scope in modern times has been extended and expanded in contrast to that recorded in ancient books. As revealed by the clinical application literature， it has been mainly employed for treating gynecological diseases such as dysmenorrhea and irregular menstruation， orthopedic diseases like fracture， dermatological diseases such as chloasma， and internal diseases such as coronary heart disease， all of which were differentiated into the blood deficiency and stasis syndrome. It could be seen that Taohong Siwutang had great clinical application value. This review of the ancient and modern literature concerned with Taohong Siwutang and the analysis and determination of its key information are expected to provide a reference for the rational clinical application and further research of Taohong Siwutang.
Abstract：ObjectiveTo study the protective effect of essential oil from Alpiniae Zerumbet Fructus （EOAZF） against high glucose （HG）-induced injury of human umbilical vein endothelial cells （HUVECs） in vitro， so as to provide experimental evidence for the treatment of diabetes-induced cardiovascular diseases with EOAZF.MethodThe cells were divided into the normal group， model group （25 mmol·L-1 glucose）， positive control group （100 mg·L-1 vitamin C）， and the low- （0.25 μg·L-1）， medium- （1 μg·L-1）， and high-dose （4 μg·L-1） EOAZF groups. The HUVECs were damaged by HG. The secretion amounts of malondialdehyde （MDA）， nitric oxide （NO）， and endothelin-1 （ET-1） in HUVECs of different groups were measured to assess the protective effect of EOAZF against HG-induced injury. The effects of EOAZF on the apoptosis and reactive oxygen species （ROS） generation of HUVECs damaged by HG were detected by Annexin V-fluorescein isothiocyanate/propidium iodide （Annexin V-FITC/PI） staining and dichloro-dihydro-fluorescein diacetate （DCFH-DA） assay. The protein and mRNA expression levels of thioredoxin interacting protein （TXNIP） and thioredoxin 1 （Trx-1） were determined by Western blot and Real-time polymerase chain reaction （Real-time PCR）， followed by the measurement of total intracellular Trx-1 activity with insulin disulfide reduction method.ResultThe comparison with the control group revealed that the proliferation of HUVECs in the model group was significantly inhibited and their shape was damaged. Compared with the model group， EOAZF protected HUVECs against HG-induced injury in a concentration-dependent manner. The secretion amounts of MDA and ET-1 （P<0.05） in the model group were increased in contrast to those in the control group， while the NO level was decreased （P<0.01）. Compared with the model group， EOAZF at all the three concentrations， especially at 4 μg·L-1， obviously reduced the secretion of MDA and ET-1 （P<0.05）， but elevated NO after HG induction （P<0.05）. The cell apoptosis assay and ROS detection results demonstrated that the apoptosis and ROS level in the model group were higher than those in the control group （P<0.01）. Compared with the model group， EOAZF at 4 μg·L-1 significantly lowered the ROS level and apoptosis （P<0.05） of HUVECs damaged by HG. The Western blot assay and Trx-1 activity detection uncovered that the protein and mRNA expression levels of TXNIP in the model group were significantly up-regulated as compared with those in the control group （P<0.05）， whereas the Trx-1 activity was decreased （P<0.01）. Compared with the model group， EOAZF at 4 μg·L-1 significantly down-regulated the mRNA and protein （P<0.05） expression levels of TXNIP and enhanced the total Trx-1 activity （P<0.05） in HUVECs， thus suppressing the oxidative stress.ConclusionEOAZF exerts the protective effects against HG-induced injury in HUVECs by improving the endothelial function and reducing intracellular ROS and apoptosis. Its efficacy in anti-oxidative stress may be related to the down-regulation of mRNA and protein expression levels of TXNIP and the enhancement of Trx-1 activity.
Keywords：essential oil from Alpiniae Zerumbet Fructus;high glucose;human umbilical vein endothelial cells （HUVECs）;thioredoxin interacting protein （TXNIP） signaling pathway
Abstract：ObjectiveTo investigate the possible mechanism of Wenjing Tongluo decoction （WTD） in alleviating articular cartilage defect in knee osteoarthritis （KOA） and delaying joint degeneration.MethodThe KOA model was established by anterior cruciate ligament transection （ACLT）. Mice were classified into sham-operated group， model group， WTD high-dose and low-dose groups， and positive control group. Four weeks after modeling， WTD groups and the positive control group were given WTD （80， 20 g·kg-1） and glucosamine sulfate capsules （0.29 g·kg-1）， respectively， and the sham-operated group and model group received normal saline of the equivalent volume. After continuous intervention for 4 weeks， hemoxylin-eosin （HE） staining was used to observe the morphological changes of cartilage and Mankin scoring system was employed to score the knee cartilage. Western blot was combined with Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） to detect the protein and mRNA levels of vascular endothelial growth factor α （VEGFA）， vascular endothelial growth factor receptor 2 （VEGFR2）， extracellular signal-related kinase 1/2 （ERK1/2） and a disintegrin and metalloproteinase with thrombospondin motifs 4 （ADAMTS4）.ResultThe Mankin score in the model group increased as compared with that in the sham-operated group （P<0.01）. Compared with the model group， administration groups demonstrated alleviated articular cartilage defect and low Mankin score （P<0.01）， but there was no statistical significance in Mankin score between the WTD groups and positive control group. The protein and mRNA levels of VEGFA， VEGFR2， ERK1/2， and ADAMTS4 in the model group were significantly higher than those in the sham-operated group （P<0.01）. The protein expression of VEGFA and ERK1/2 was inhibited in each administration group as compared with that in the model group （P<0.01）， and the inhibition in the positive control group was stronger than that in the WTD low-dose group （P<0.05） but weaker than that in the WTD high-dose group （P<0.01）. Glucosamine Sulfate capsules suppressed the expression of VEGFR2 and ADAMTS4 to the extent the same with low-dose WTD but weaker than the high-dose WTD （P<0.05）.ConclusionWTD can relieve the articular cartilage injury in KOA mice， and the mechanism may be related to VEGF/VEGFR2/ERK1/2 signaling pathway.
Abstract：ObjectiveTo observe the difference in drying dampness between Scutellariae Radix and Atractylodis Rhizoma in model rats with spleen-stomach dampness-heat syndrome and clarify their property-efficacy relationship.MethodSixty-four healthy male SD rats were randomized into the blank group， model group， high-， medium-， and low-dose Scutellariae Radix groups， as well as high-， medium-， and low-dose Atractylodis Rhizoma groups. The rats were exposed to high-fat and high-sugar diet and external dampness-heat environment for 20 days for inducing the spleen-stomach dampness-heat syndrome. The macroscopic manifestations of rats were observed and the morphological changes in stomach and colon were detected under a light microscope after hematoxylin-eosin （HE） staining， followed by the calculation of pathological scores. The serum tumor necrosis factor-α （TNF-α）， interleukin-4 （IL-4）， and interferon-γ （IFN-γ） levels were determined by enzyme-linked immunosorbent assay （ELISA）. The protein and mRNA expression levels of aquaporin-4 （AQP4） in the gastric tissue were measured by Western blot and Real-time polymerase chain reaction （Real-time PCR）， respectively.ResultRats in the model group presented with the manifestations of dampness-heat syndrome. The inflammatory reaction in stomach and colon was obvious， and the pathological score was significantly increased （P<0.01）. The serum IFN-γ， IL-4， and TNF-α levels were elevated （P<0.05）， and so were the AQP4 protein and mRNA expression levels in the gastric tissue except that there was no statistical difference. The clinical symptoms of rats in the medication groups were alleviated. Scutellariae Radix significantly relieved the gastric and colonic inflammation in model rats. Atractylodis Rhizoma inhibited the colonic inflammation in model rats to a certain extent， but it had no obvious effect on gastric inflammation. The pathological score of each Scutellariae Radix group was decreased. In terms of the pathological score of gastric tissue， only the high-dose Scutellariae Radix produced a significant difference （P<0.01）， and the pathological scores of the three Atractylodis Rhizoma groups were not significantly different from that in the model group. As for the pathological score of colonic tissue， all the medication groups except for the low-dose Atractylodis Rhizoma group exhibited a significant difference in comparison with that of the model group （P<0.01）. Scutellariae Radix and Atractylodis Rhizoma at each dose reduced not only the serum IFN-γ， IL-4， and TNF-α levels （P<0.05， P<0.01）， but also the AQP4 protein expression in gastric tissue of model rats （P<0.01）. The AQP4 mRNA expression in the gastric tissue of model rats declined in the high- and low-dose Scutellariae Radix groups， while that in the medium-dose Scutellariae Radix group and each Atractylodis Rhizoma group rose without statistical difference.ConclusionScutellariae Radix and Atractylodis Rhizoma display a certain property-efficacy relationship in drying dampness of rats with spleen-stomach dampness-heat syndrome. Specifically， the efficacy of drying dampness is related to their cold/heat property， and the resulting outcome of bitter-cold Scutellariae Radix is better than that of bitter-warm Atractylodis Rhizoma.
Abstract：ObjectiveTo investigate the effects of oxymatrine（OM） on proliferation，migration， and invasion of non-small cell lung cancer（NSCLC） A549 and H1299 cells and to explore the possible mechanism.MethodA549 and H1299 cells were treated by OM of different concentrations（0， 1.0，2.0，4.0，8.0，16.0， 32.0， and 64.0 mmol·L-1） and the cell viability was detected by cell counting kit-8 （CCK-8） assay. Transwell invasion and wound healing assays were applied to determine the effect of OM of different concentrations （8.0，16.0， and 32.0 mmol·L-1） on the invasion and migration of A549 and H1299 cells. Western blot was adopted to detect the changes in the expression of proteins related to the Notch signaling pathway after the treatment by OM of different concentrations （8.0，16.0， and 32.0 mmol·L-1）.ResultCompared with the control，OM could inhibit the proliferation （P<0.05，P<0.01） and hinder the cell invasion and migration of A549 and H1299 cells （P<0.01） in a dose-dependent manner. The results of Western blot showed that OM（32.0 mmol·L-1） could effectively counteract the expression levels of Notch1 intracellular domain（NICD），transcriptional complex proteins ［TNF-alpha converting enzyme（TACE） and recombining binding protein suppressor of hairless（RBPSUH）］， and Hes family hairy and enhancer of split 1（Hes1） in A549 and H1299 cells.ConclusionOM was capable of inhibiting the proliferation，migration， and invasion of A549 and H1299 cells and also hindering the expression of proteins related to Notch signaling pathway.
Abstract：ObjectiveTo investigate the effects of total glucosides of paeony （TGPs） on intestinal motility， barrier function， and gut microbiota in non-obese diabetic （NOD） mice with Sjogren's syndrome （SS）.MethodThirty NOD mice were randomly assigned into the model group （deionized water）， prebiotic fructo-oligosaccharide （FOS） group （700 mg∙kg-1）， and the low- （160 mg∙kg-1）， medium- （320 mg∙kg-1）， and high-dose （640 mg∙kg-1） TGP groups， with six mice in each group. Moreover， the BALB/c mice were employed as the normal control and administered with deionized water. The food and water intakes， number of discharged fecal particles， and fecal moisture content were observed to evaluate the effect of TGPs on intestinal motility in SS mice. The levels of D-lactate （D-Lac） content， diamine oxidase （DAO）， and junction-associated protein zonula occludens-1 （ZO-1） in mouse serum were detected by enzyme linked immunosorbent assay （ELISA）. The fecal samples collected at different time points were determined by spread plate method and gas chromatography for uncovering the intestinal microbial communities and the content of short-chain fatty acids.ResultCompared with the normal group， the model group exhibited decreased food and water intakes （P<0.01）， weakened intestinal propulsion （P<0.01）， elevated D-Lac and DAO （P<0.05，P<0.01）， lowered ZO-1 and SCFAs （P<0.05，P<0.01）， and reduced number of intestinal bacteria （P<0.01）. The comparison with the model group revealed that TGPs significantly increased the number of discharged fecal particles and fecal moisture content （P<0.05，P<0.01）， enhanced intestinal propulsion （P<0.05， P<0.01）， decreased serum D-Lac and DAO levels （P<0.05，P<0.01）， and up-regulated ZO-1 expression （P<0.01）. Apart from increasing the proportions of Bifidobacterium and Lactobacillus and decreasing the proportion of Enterobacter in intestinal flora （P<0.05，P<0.01）， TGPs also accelerated the production of acetic acid and butyric acid （P<0.05，P<0.01）.ConclusionTGPs attenuate SS-mediated constipation and restore the impaired intestinal barrier function in mice by increasing fecal moisture content， boosting intestinal motility， regulating intestinal microbial communities， elevating acetic acid and butyric acid levels， and up-regulating tight junction protein expression.
Keywords：total glucosides of paeony;Sjogren's syndrome （SS）;constipation;intestinal barrier function;short-chain fatty acids
Abstract：ObjectiveTo evaluate the safety and effectiveness of Tiandan Tongluo capsule in the treatment of cerebral infarction （CI） in convalescence （stoke involving meridians and collaterals due to wind-phlegm-static blood obstructing vessels）， with Naoshuantong capsule as a control.MethodA total of 352 convalescent patients with CI differentiated into stoke involving meridians and collaterals due to wind-phlegm-static blood obstructing vessels in traditional Chinese medicine （TCM） were included in this multi-center， randomized， double-blind， single-simulated， Naoshuantong capsule-controlled clinical trial， which lasted from 28 December， 2016 to 12 April， 2019. After being randomized into an experimental group and a control group at a ratio of 3∶1， patients in the experimental group were provided with oral Tiandan Tongluo capsule， five capsules per time， three times per day， whereas those in the control group received both Naoshuantong capsule simulator， two capsules per time， three times per day， and Naoshuantong capsule， three capsules per time， three times per day， for 12 successive weeks. The patients were followed up until 180 days after onset. The Barthel activities of daily living （ADL） index （BI） score was used as the primary outcome， and the secondary outcomes included neurological deficit score ［assessed with National Institutes of Health Stroke Scale （NIHSS）］， modified Rankin scale （mRS）， TCM syndrome score， and proportion of patients with new vascular events. The changes in laboratory indexes and the incidence of adverse reactions during treatment were observed.ResultAmong the 389 cases enrolled， 30 dropped out， with the drop-out rate being 7.71%. There were 374 cases included in the full analysis set and 377 in the safety set. The comparison with the control group revealed that the total BI score and the percentage of BI score ≥ 75 in the experimental group were increased， but the difference was not statistically significant. The percentage of mRS score ≤ 2 within 180 days after onset in the experimental group obviously elevated in contrast to that of the control group （P<0.05）. As demonstrated by TCM syndrome score analysis， the markedly effective rate in the experimental group was significantly higher than that in the control group （P<0.05）. During the trial， the incidence rates of new vascular events in the experimental group and the control group were 0.00% and 1.09% （one case）， respectively， exhibiting no statistically significant difference between the two groups.ConclusionTiandan Tongluo capsule and Naoshuantong capsule both produce definite therapeutic effects in the treatment of CI in convalescence （stoke involving meridians and collaterals due to wind-phlegm-static blood obstructing vessels）. Compared with Naoshuantong capsule， Tiandan Tongluo capsule better alleviates neurological deficit， promotes neural functional recovery， and improves TCM syndrome score， without inducing severe adverse reactions.
Keywords：Tiandan Tongluo capsule;cerebral infarction （CI） in convalescence;stoke involving meridians and collaterals;syndrome of wind-phlegm-static blood obstructing vessels;stroke
Abstract：ObjectiveTo observe the effect of modified Dihuangyin on vascular dementia due to kidney empty phlegm and blood stasis syndrome，and its effect on phosphoinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway ［PI3K，microtuble-associated protein 1 light chain 3（LC3）Ⅱ/LC3Ⅰ，Akt，phosphorylatedprotein kinase B（p-Akt）］ in peripheral blood.MethodTotally 100 cases were randomly divided into control group （50 cases） and observation group （50 cases），and were given donepezil，modified Dihuangyin combined with donepezil for 30 d，respectively. The main efficacy indicators ［mini-mental state examination （MMSE），clinical dementia rating （CDR），activity of daily living scale （ADL），traditional Chinese medcine（TCM） syndrome］ were compared in two groups. The cerebral blood flow dynamics ［middle cerebral artery （MCA），basilar artery （BA），anterior cerebral artery （ACA），posterior cerebral artery （PCA）］ speed，serum inflammatory factors ［tumor necrosis factor-α （TNF-α），interleukin-6 （IL-6），transforming growth factor-β （TGF-β），C-reactive protein （CRP）］，oxidative stress indicators ［malondialdehyde （MDA），superoxide dismutase （SOD），glutathione peroxidase （GSH-Px） ，homocysteine （Hcy）］，peripheral blood PI3K/Akt signaling pathway （PI3K，LC3Ⅱ/LC3Ⅰ，Akt，p-Akt） were tested. The efficacy and adverse reactions of the two groups were compared.ResultThe total effective rate was 95.9% in observation group was higher than that 72.3% in control group （χ2=5.673，P<0.05）. Compared with the control group after treatment，the MMSE，ADL，SOD，GSH-Px，TGF-β，PI3K，Akt and p-Akt in the observation group were increased （P<0.05），CDR，MCA，BA，ACA and PCA were increased （P<0.05），and the TCM syndromes，MDA，Hcy，TNF-α，IL-6，CRP，LC3Ⅱ/LC3Ⅰ were decreased （P<0.05）. There was no significant difference incidence of adverse reactions between two groups.ConclusionModified Dihuangyin can significantly improve the clinical symptoms of patients with vascular dementia due to kidney empty phlegm and blood stasis syndrome，and the mechanism of action may be related to PI3K/Akt signaling pathway in peripheral blood.
Keywords：modified Dihuangyin;vascular dementia;kidney empty phlegm and blood stasis syndrome;phosphoinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway
Abstract：ObjectiveTo observe the clinical effect of modified Zengyetang in treating slow transit constipation （STC） due to Qi-Yin deficiency and its effect on gastrointestinal function.MethodOne hundred and thirty eligible patients were randomly divided into a control group （n=65， 6 cases dropped out or were lost to follow-up and 59 completed the trial） and a treatment group （n=65， 3 cases dropped out or were lost to follow-up and 62 completed the trial）. Patients in the control group received oral mosapride citrate dispersible tablets， 5 mg per time， three times per day， while those in the treatment group were treated with modified Zengye Tang， one bag per day， for four successive weeks. The main symptom constipation， the Patient Assessment of Constipation Symptoms （PAC-SYM）， and traditional Chinese medicine （TCM） syndrome scores， colonic transit， as well as motilin （MTL）， vasoactive intestinal peptide （VIP）， and substance P （SP） levels before and after treatment were recorded， together with the frequency of spontaneous complete bowel movements （SCBMs） per week and STC recurrence during treatment.ResultThe clinical efficacy （95.16%） of the treatment group was higher than that （81.36%） of the control group （χ2=5.631 4， P<0.05）， whereas the recurrence rate （30.65%） of the treatment group was significantly lower than that （57.63%） of the control group （χ2=8.941 1， P<0.01）. After treatment， the main symptom constipation， three sub-scale and total PAC-SYM， and TCM syndrome scores in the treatment group were obviously decreased as compared with those in the control group （P<0.01）. The proportions of residual markers at 24， 48， and 72 h in the treatment group declined in contrast to those in the control group （P<0.01）. The frequency of SCBMs per week in the 2nd， 3rd， and 4th weeks of the treatment group was higher than that in the control group （P<0.01）. Compared with the control group after treatment， the treatment group exhibited significantly elevated MTL and SP but lowered VIP （P<0.01）.ConclusionModified Zengyetang relieves the clinical symptoms， regulates gastrointestinal hormone secretion， increases the frequency of SCBMs， enhances colonic transit， and decreases the recurrence of patients with STC due to Qi-Yin deficiency.
Abstract：ObjectiveTo evaluate the clinical efficacy of Qingkailing injection in the treatment of children with sepsis and heat syndrome， and investigate its anti-inflammatory， anticoagulant and protective effects.MethodEighty patients were randomly divided into control group and observation group with forty cases in each group according to the number table. Both groups received comprehensive treatment measures such as fluid resuscitation， anti-infection， anti-inflammatory， anticoagulation， vasoactive drugs， and protection of vital organ functions. While patients in observation group additionally took Qingkailing injection， 5-10 mL each time， intravenous drip after dilution， 1 time/day. Treatment course was five days in both groups. Before and after treatment， the scores of quick sequential organ failure assessment （qSOFA）， pediatric critical illness score （PCIS） and acute physiology and chronic health evalution Ⅱ （APACHEⅡ） were graded； procalcitonin （PCT）， serum amyloid A protein （SAA） before and after treatment， heparin-binding protein （HBP）， tumor necrosis factor-α （TNF-α）， high-sensitivity C-reactive protein （hs-CRP）， interleukin-6 （IL-6）， IL-10， N-terminal brain sodium Peptide precursor （NT-proBNP）， high-sensitivity cardiac troponin T （hs-cTnT） level， cardiac troponin I （cTnI）， creatine kinase isoenzyme （CK-MB）， D-dimer （D-D ）， fibrinogen （FIB） and antithrombin Ⅲ （AT-Ⅲ） levels were detected.ResultThe APACHEⅡ and qSOFA scores in the observation group were lower than those in the control group （P<0.05）， while the PCIS score was higher than that in the control group （P<0.05）. The levels of PCT， SAA，HBP，TNF-α， hs-CRP and IL-6 in the observation group were lower than those in the control group （P<0.01）， while the IL-10 level was higher than that in the control group （P<0.01）. The levels of NT-proBNP， hs-cTnT， cTnI， CK-MB， D-D and FIB in the observation group were lower than those in the control group （P<0.01）， while the AT-Ⅲ activity was higher than that in the control group （P<0.01）.ConclusionQingkailing injection as the adjuvant therapy in children with sepsis and fever syndrome， can play the role of anti-inflammatory， anticoagulant， reducing infection and myocardial damage， thereby reducing the severity of the disease and improving the prognosis.
Keywords：sepsis;children;toxic heat syndrome;Qingkailing injection;inflammatory factors;biochemical markers of infection;myocardial injury;blood coagulation function
Abstract：ObjectiveTo observe the clinical efficacy and mechanism of Shugan Bushen Huoxue decoction in the treatment of perimenopausal perio syndrome （PPS） with kidney deficiency， liver depression and blood stasis syndrome.MethodOne hundred and twelve patients were randomly divided into control group and observation group according to random number table. Both groups took Remifemin orally， 1 tablet/time， by swallowing in the morning and evening. The patients in control group additionally took Fuke Yangrong capsules， 4 capsules/time， 3 times/day. The patients in observation group additionally took Shugan Bushen Huoxue decoction， 1 dose/day. The course of treatment was 12 weeks in both groups. Before and after treatment， scores were graded for modified Kupperman index （KI）， traditional Chinese medicine （TCM） syndromes， menopausal quality of life scale （MENQOL）， self-rating depression scale （SDS） and self-rating anxiety scale （SAS）. Follicle stimulating hormone （FSH），luteinizing hormone （LH），serum estrogen （E2）， 5-hydroxytryptamine （5-HT）， dopamine （DA）， norepinephrine （NE）， 5-hydroxyindole acetic acid （5-HIAA）， endothelin （ET）， and nitric oxide （NO） levels were detected before and after therapy.ResultIn the observation group， scores of KI， TCM syndrome， SDS and SAS were lower than those in the control group （P<0.01）. All dimensions of MENQOL scores in the observation group were lower than those in the control group （P<0.01）. FSH and LH levels in the observation group were lower than those in the control group， and the E2 level was higher than that of the control group （P<0.01）. The levels of 5-HT， 5-HIAA， DA and NE in the observation group were higher than those in the control group （P<0.01）. The ET level in the observation group was lower than that in the control group， and the NO level was higher than that of the control group （P<0.01）. In observation group，the clinical efficacy was superior to that in control group （Z=2.073，P<0.05）， and the efficacy of TCM syndromes was also superior to that in control group （Z=2.086，P<0.05）.ConclusionShugan Bushen Huoxue decoction in the treatment of PPS in patients with kidney deficiency and liver depression and blood stasis can significantly reduce clinical symptoms， depression and anxiety， regulate the sex hormones， vasomotor factors and monoamine neurotransmitters levels， and improve the quality of life， with obvious clinical efficacy and high safety， so it is worthy of clinical use.
Abstract：ObjectiveTo investigate the inhibitory effects and mechanism of Reyanning mixture （RYN） combined with linezolid （LNZ） against methicillin-resistant Staphylococcus aureus （MRSA） and its biofilm.MethodThe minimum inhibitory concentrations （MICs） of RYN and LNZ against MRSA were determined by microdilution assay. The microplate method was used to detect the changes in viable count before and after MRSA administration at four time points （0， 6， 12， 24 h） in the process of biofilm growth. The morphological changes of MRSA after 24 h were observed by scanning electron microscope. Metabonomic technique was applied to analyze the changes in terminal metabolites of endogenous small molecules from MRSA treated by the two drugs at four time points.ResultThe MICs of RYN and LNZ were 1/2 of the stock solution concentration and 4 mg·L-1， respectively. The inhibitory effect of LNZ （2 mg·L-1） against viable bacteria at 0 h was better than that of 1/16 RYN. At 6， 12， 24 h， 1/16 RYN was superior to LNZ in inhibiting MRSA. The inhibitory effects of RYN combined with LNZ were better than those of RYN or LNZ alone at the four time points. RYN combined with LNZ caused more severe damages to the morphological structure of MRSA biofilm at 24 h than RYN or LNZ alone. Cyclic adenosine monophosphate （cAMP）， adenosine diphosphate （ADP）-D-ribose and 2-methylbutanoyl-coenzyme A （2M-CoA）， as the metabolites related to biofilm formation， were immune to LNZ， but 2M-CoA and ADP-D-ribose were influenced by RYN at 12 h and 24 h. The combined use of RYN and LNZ interfered with the three metabolites at 24 h. L-tryptophan， phenylpyruvic acid， cytidine and sebacic acid were the pharmacometabolic markers of LNZ， and the related biological pathways were phenylalanine， tyrosine and tryptophan biosynthesis and phenylalanine metabolism. Four metabolites such as L-histidine， uric acid， and L-lysine were the pharmacometabolic markers of RYN， with phenylalanine metabolism and aminoacyl-transfer ribonucleic acid （tRNA） biosynthesis confirmed as the related biological pathways. Nine metabolites such as L-tryptophan， L-lysine， and sphingosine-1-phosphate were responsible for the efficacy of RYN combined with LNZ. The related biological pathways involved aminoacyl-tRNA biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， novobiocin biosynthesis， and tyrosine metabolism.ConclusionRYN combined with LNZ better exerts the inhibitory effects against MRSA at each time point of its biofilm formation， which is attributed to cAMP metabolism. The synergistic effect resulted from aminoacyl-tRNA biosynthesis and phenylalanine， tyrosine and tryptophan biosynthesis. RYN combined with LNZ can serve as a potentially effective solution to MRSA infection.
Abstract：ObjectiveTo investigate the relationship between the single nucleotide polymorphism（SNP）of function genes and effective components of Salvia miltiorrhiza and the molecular mechanism of specific quality formation of S. miltiorrhiza.MethodThe fingerprints of components in S. miltiorrhiza from eight different habitats and varieties were obtained by high-performance liquid chromatography （HPLC）. The full-length cDNA of three functional genes acetyl-CoA C-acetyltransferase（SmAACT），4-diphosphocytidyl-2-C-methyl-D-erythritol kinase（SmCMK） and isopentenyl diphosphate isomerase（SmIPPI） in tanshinone metabolic pathway were amplified by polymerase chain reaction（PCR），cloned， and sequenced，followed by bioinformatics analysis.ResultThe full-length cDNA sequences of three functional genes SmAACT，SmCMK， and SmIPPI in tanshinone metabolic pathway were obtained from 23 strains of S. miltiorrhiza from eight different habitats and varieties. As revealed by the analysis of SNP and amino acid polymorphisms of three functional genes，18，16， and 14 SNP sites were found respectively. HPLC results showed the samples from Beijing，Hubei，Shandong （No. SDB），Shanxi，Henan， and Shandong （No. SDZ） were clustered into one branch，and those from Hebei and Inner Mongolia were clustered into another branch， which suggested that the variation trend of S. miltiorrhiza components had little correlation with geographical distance，but the variety was a critical factor for the quality.ConclusionThere was an obvious genetic differentiation trend in S. miltiorrhiza from different habitats，and different origin-specific genotypes were formed. The molecular mechanism of the formation of the specific quality of S. miltiorrhiza from different habitats was discussed，which laid a foundation for the stability and effectiveness of clinical medication，and guided the breeding of excellent varieties of S. miltiorrhiza.
Abstract：ObjectiveTo establish a new fast and accurate method for identifying the authenticity and specifications of Fritillariae Cirrhosae Bulbus based on electronic nose technology， and to discuss the feasibility of this technology in the identification of decoction pieces.MethodFritillariae Cirrhosae Bulbus was used as the research object， 80 batches of samples to be tested were collected， and the olfactory sensory data of the electronic nose were taken as independent variables （X）， the results of the method contained in the 2020 edition of Chinese Pharmacopoeia were taken as the focus， and the traditional empirical identification results were used as benchmarking information （Y）. Four chemometric methods， including discriminant analysis （DA）， least square support vector machine （LS-SVM）， principal component analysis-DA （PCA-DA） and partial least squares-DA （PLS-DA）， were used to establish the identification model ［Y=F（X）］ of authenticity and commodity specifications of Fritillariae Cirrhosae Bulbus， respectively. Wherein， the identification accuracy and time-consuming was taken as indicators to discuss the results.ResultAfter cross-verification by leave-one-out method， the correct rates of the above four models were 93.75%， 91.25%， 95.00% and 95.00%， respectively， and the PCA-DA and PLS-DA identification models were the best in terms of authenticity identification. In specification identification， the correct rates of these four models were 86.67%， 88.00%， 89.33% and 68.00%， respectively， and the PCA-DA identification model was the best. The electronic nose had a high accuracy in the identification of authenticity and specification model， and the time consuming was relatively short.ConclusionElectronic nose technology can identify Fritillariae Cirrhosae Bulbus accurately and quickly， and has significant advantages in terms of timeliness and correct judgment rate.
Abstract：ObjectiveTo investigate bonding ability between 4-sulfonylcalix ［6］ arene （SCA6） and 15 alkaloids （matrine， allomatrine， dauricine， daurisoline， quinidine， quinine， crotaline， vincristine， gelsemine， koumine， tetrandrine， aloperine， oxymatrine， sophocarpine and sinomenine）， and to evaluate viability in vitro of HepG2 and H9c2 cells with 12 alkaloids/SCA6 bonding systems （except allomatrine， oxymatrine， sinomenine）.MethodFluorescence competitive titration was used to determine the binding constants of alkaloids and SCA6， the inhibitory effect of alkaloid/SCA6 complex on proliferation of HepG2 and H9c2 cells was investigated by cell counting kit-8 （CCK-8）.ResultAll the 15 alkaloids had good bonding with SCA6 at the ratio of 1∶1 （the binding constants >1×105 mol·L-1， R2>0.98）， the aloperine （quinolizidine alkaloids） and SCA6 had the biggest binding constant （20.55×106 mol·L-1）. In addition to gelsemine， crotaline， matrine and sophocarpine， 8 alkaloids （including aloperine， tetrandrine， dauricine， daurisoline， quinidine， quinine， vincristine and koumine） exhibited significant anti-tumor effects on HepG2 cells. Except for daurisoline， the anti-proliferation effect of the other 11 alkaloids before and after binding with SCA6 had no difference in HepG2 cells. In addition to gelsemine， crotaline， matrine and sophocarpine， the anti-proliferation effect of the other 8 alkaloids before and after binding with SCA6 had no difference in H9c2 cells.ConclusionSCA6 shows intense binding ability with bisbenzylisoquinoline， quinolizidine and indole alkaloids. It can improve the solubility of alkaloids without affecting their anti-tumor activity， which provides a reference for subsequent related applications of SCA6 as a drug delivery carrier.
Keywords：traditional Chinese medicine;alkaloids;supramolecular compounds;sulfonated calixarene;anti-tumor;HepG2 cells;H9c2 cells
Abstract：ObjectiveTo compare the adsorption and desorption properties of different anion exchange resins for total ginsenosides， clarify their adsorption/desorption mechanism， and establish a simple protocol for the purification of total ginsenosides.MethodThe adsorption and desorption properties of five different resins （D301， D315， D312， D330， D201） on total ginsenosides were evaluated with specific adsorption capacity， specific desorption capacity， desorption rate and recovery rate as indices. The adsorption kinetics and thermodynamics of the selected resin and D101 macroporous resin were investigated by pseudo-first-order and pseudo-second-order kinetic models， as well as Langmuir and Freundlich isothermal adsorption models， and the differences of adsorption mechanism between anion exchange resin and conventional macroporous resin were elucidated. The dynamic adsorption and desorption experiments were used to determine the optimum chromatographic parameters for anion exchange resin. After verifying the purification process of total ginsenosides， nine individual ginsenosides were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry （LC-MS）.ResultD301 anion exchange resin was obviously superior to the other four kinds of anion exchange resin， the optimum parameters were set as follows：pH 8 of loading solution， loading volume of 2 BV， loading speed of 4 BV·h-1， eluted with 3 BV of water and 20% ethanol for the impurities， eluted with 8 BV of 80% ethanol with elution speed of 4 BV·h-1. After purified by D301 resin， the enrichment coefficients of 9 monomer ginsenosides were simultaneously increased to different degrees， the overall enrichment coefficient was up to 5.3， the recovery rate for the total amount of these ginsenosides was calculated to be 80.9%， and the purity of total ginsenosides in Ginseng Radix et Rhizoma extract increased from 17.07% to 91.19%.ConclusionD301 anion exchange resin is suitable for rapid and practical purification of total ginsenosides， hence allowing for the enrichment of high-purity total ginsenosides from Ginseng Radix et Rhizoma via one-dimensional column chromatography.
Abstract：ObjectiveHigh performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS） was used to identify the main chemical constituents of Daishenning.MethodCosmosil 5 C18-AR-Ⅱ column （4.6 mm×250 mm， 5 μm） was employed for chromatographic separation with mobile phase of acetonitrile （A）-0.5% formic acid aqueous solution （B） for gradient elution （0-10 min， 5%A； 10-20 min， 5%-20%A； 20-30 min， 20%A； 30-55 min， 20%-35%A； 55-65 min， 35%-55%A； 65-75 min， 55%-100%A； 75-80 min， 100%A； 80-85 min， 100%-5%A； 85-90 min， 5%A）， the flow rate was 1 mL·min-1， column temperature was 40 ℃， and injection volume was 10 μL. Electrospray ionization （ESI）， positive and negative ion detection modes and mass scanning range of m/z 100-2 000 were selected for mass spectrometry. The main chemical constituents in Daishenning were identified by MassHunter B.06.00 software in combination with PubChem， MassBank， ChemicalBook and other databases， and reference information.ResultA total of 96 components were identified from Daishenning， including 32 flavonoids， 19 organic acids， 6 glycosides， 6 terpenoids， 5 phenylpropanoids， 8 phenols， 14 other components and 6 unknown components.ConclusionThe established method can simultaneously analyze different types of compounds in Daishenning， it is helpful for further research on the extraction and separation of main chemical components and quality control of this preparation. In addition， through the rapid identification of the chemical constituents in Daishenning， it is speculated that the main effective substances of Daishenning may be flavonoids and organic acids.
Keywords：medicine of Dai nationality;ethnic medicine;Daishenning;high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （HPLC-Q-TOF-MS/MS）;chemical constituents;flavonoids;organic acids
Abstract：ObjectiveTo explore the macroscopic medication rule of Chinese medicine for the treatment of primary liver cancer and provide references for clinical medication.MethodThe databases of CNKI，VIP， and Wanfang Data were searched for research articles published from September 1959 to June 2019 with the terms of "Chinese medicine" and "liver cancer". A database was established based on the collected Chinese medicinal prescriptions for the treatment of primary liver cancer. The frequency，clustering， and association rules were analyzed by Excel， etc.ResultIn this study，106 effective articles were included，and after the modified prescriptions were removed， 92 effective prescriptions were screened out，involving 281 Chinese herbal medicines used for 1 181 times in total. The top 5 high-frequency drugs were Poria （deficiency-tonifying），Astragali Radix （heat-clearing），Bupleuri Radix （blood-activating and stasis-resolving），Paeoniae Radix Alba （urination-promoting and dampness-draining）， and Codonopsis Radix （Qi-regulating）. The analysis of drug flavor with a frequency higher than 10 showed that most of the drugs were sweet，bitter， and pungent in flavor，cold，warm， and plain in nature，and acted on spleen and liver meridians. Four combinations and 10 herbal pairs were obtained by the cluster analysis of high-frequency drugs and association analysis， respectively. The high-frequency drugs and potential herbal pairs were classified targeting the specific clinical syndromes in different stages of liver cancer.ConclusionReplenishing Qi， invigorating spleen，clearing heat， removing toxin，activating blood， and resolving stasis were the basic principles for the treatment of primary liver cancer. The combination of those drugs was the main therapeutic strategy. In addition，the resulting 10 potential herbal pairs from high-frequency drugs and cluster analysis could inspire the clinical treatment of primary liver cancer in different clinical stages with various clinical syndromes， which was of reference value for the clinical medication.
Keywords：primary liver cancer;traditional Chinese medicine （TCM） clinical practice;medication law;high-frequency drugs;cluster analysis;clinical syndromes
Abstract：To systematically evaluate the effect of traditional Chinese medicine（TCM） on the expression of inflammatory factors in peripheral blood of patients with coronary heart disease complicated with anxiety and depression，and explore its efficacy and safety in treatment of anxiety and depression. In this study，CNKI，VIP database，WanFang database，PubMed and Cochrane Library were searched to collect randomized controlled trials（RCTs） of TCM in the treatment of coronary heart disease complicated with anxiety and depression，and 2 researchers independently screened the literatures and extracted the data. The quality of the included literatures was evaluated with Cochrance bias risk evaluation tool and Meta analysis was conducted by Cochrane Revman 5.3 software. A total of 21 research articles were included，with a total sample size of 2 342 cases，1 175 cases in the treatment group and 1 167 cases in the control group. Meta analysis results showed that the treatment group reduced the hypersensitive C-reactive protein（hs-CRP）［standard mean difference（SMD）=-1.61，95% confidence interval（CI）（-2.14，-1.09），P<0.01］，interleukin（IL）-8［mean difference（MD）=-5.03，95% CI（-8.37，-1.70），P=0.003］，IL-17［MD=-33.27，95% CI（-40.15，-26.39），P<0.01］，tumor necrosis factor（TNF）-α［SMD=-1.18，95% CI（-1.98，-0.38），P<0.01］，and homocysteine（Hcy）［MD=-3.45，95% CI（-4.85，-2.04），P<0.01］. The treatment group was better than the control group in terms of relieving anxiety and depression，i.e. scores of Hamilton anxiety scale（HAMA） ［SMD=-1.97，95% CI（-2.48，-1.46），P<0.01］，Hamilton depression scale（HAMD） ［SMD=-1.94，95% CI（-2.50，-1.38），P<0.01］，and self-rating depression scale（SDS）［SMD=-0.72，95% CI（-0.90，-0.54），P<0.01］，so in terms of ，with statistically significant difference. 4 articles mentioned that no obvious adverse reactions occurred，4 articles mentioned that the treatment group had drowsiness，dry mouth and bitter mouth，gastrointestinal reactions，but the incidence rates were significantly lower than those of the control group. The other 13 articles did not mention the occurrence of adverse reactions.
Keywords：coronary heart disease with anxiety and depression;Chinese medicine;inflammation factors;Meta-analysis
Abstract：ObjectiveTo explore the potential molecular mechanism of Nelumbinis Plumula alkaloids （NAPs） in the prevention and treatment of non-small cell lung cancer （NSCLC） based on network pharmacology and cell experiment.MethodThe main active components of NAPs were obtained by searching Traditional Chinese Medicine System Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and their main targets were predicted and analyzed by employing Swiss Target Prediction. The main target genes of NSCLC were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DrugBank databases. The resulting common targets were imported into STRING platform for constructing the protein-protein interaction （PPI） network， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis based on Database for Annotation， Visualization， and Integrated Discovery （DAVID）. The NAPs-common target -pathway network was constructed by Cytoscape 3.7.1. After NSCLC cell line A549 was treated with isoliensinine， the cell morphology was observed under an inverted fluorescence microscope. The effect of isoliensinine on A549 vitality was detected by cell counting kit-8 （CCK-8） assay and the target protein changes were verified by Western blot.ResultThe main active components for NAPs against NSCLC were lysicamine， liensinine， and isoliensinine. The phosphatidylinositol-3-kinase-protein kinase B （PI3K-AKT）， RAS-related protein 1 （Rap1）， epidermal growth factor family of receptor tyrosine kinases （ErbBs）， and hypoxia inducible factor-1 （HIF-1） pathways were mainly involved for binding adenosine triphosphate （ATP） and regulating protein kinase activity. The main targets included protein kinase B-1 （AKT1）， alpha catalytic subunit of phosphoinositol-3-kinase （PIK3CA）， cyclin-dependent kinase 2 （CDK2）， mitogen-activated protein kinase-1 （MAPK1）， epidermal growth factor receptor （EGFR）， adenosine triphosphate-binding cassette B1 （ABCB1）， mammalian target of rapamycin （mTOR）， tyrosine kinase （Src）， Janus kinase 1 （JAK1）， and G1-phase-specific gene cyclin-D1 （CCND1）. The in vitro cell experiment also revealed that isoliensinine down-regulated the expression of phosphorylated AKT （p-AKT） and phosphorylated mTOR （p-mTOR） in a concentration- and time-dependent manner and inhibited the growth of A549 cells.ConclusionNAPs exert the preventive and therapeutic effects against NSCLC through multiple components， multiple targets， and multiple pathways， especially the PI3K-AKT pathway.
Keywords：Nelumbinis Plumula alkaloids （NAPs）;network pharmacology;non-small cell lung cancer （NSCLC）;phosphatidylinositol-3-kinase/protein kinase B （PI3K/AKT） pathway
Abstract：In recent years， the incidence of neurological diseases has been increasing year by year. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of neurological disorders， identify the breakthrough point of integrating TCM with western medicine， and further standardize the clinical diagnosis and treatment of TCM， the China Association of Chinese Medicine organized neurologists in TCM and western medicine to carry out in-depth discussion on the neurological diseases responding specifically to TCM and integrated TCM and western medicine， such as stroke， headache， vertigo， multiple sclerosis， and epilepsy， aiming to formulate a well-recognized and integrated treatment protocol for TCM and western medicine and improve the efficacy of neurological disorders. Furthermore， the treatment suggestions of the corresponding diseases in TCM and western medicine were proposed to provide references for clinical practice and scientific research.
Keywords：neurology;diseases responding specifically to traditional Chinese medicine （TCM）;expert consensus
Abstract：With the publication of Registration and Classification of Traditional Chinese Medicine （TCM） and Application Data Requirements， the related management and technical documents of TCM with the same name and prescription need to be further studied and formulated. In this paper， the management mode and technical evaluation of TCM with the same name and prescription are discussed to provide reference for the formulation of management and technical documents of TCM with the same name and prescription. The issues to be discussed include which management mode to adopt， how to select the control drugs with the same name and prescription， whether the indication risk level should be divided， whether the indication should be limited to medium and low risk， and how to carry out the technical evaluation of similarity/consistency. From the perspective of technical document research and formulation， this paper mainly focuses on the technical level. However， there are still other theoretical possibilities in the management mode and technical evaluation of TCM with the same name and prescription. Therefore， this paper， as a preliminary summary of the management and technical evaluation of TCM with the same name and prescription， needs more scholars and industry experts to pay attention to and participate in this work.
Keywords：traditional Chinese medicine;medicine with the same name and prescription;management mode;control drugs with the same name and prescription;technical evaluation of similarity/consistency
Abstract：Notoginsenosides， the saponins extracted from Panax notoginseng， have many pharmacological effects， such as anti-inflammation， anti-oxidation， anti-tumor， nervous system and cardiovascular system protection， microcirculation improvement and calcium overload inhibition. At present， notoginsenosides are widely used clinically for treating many diseases with good efficacy， especially for nervous system diseases such as stroke， stroke sequelae and Alzheimer's disease. In recent years， the mechanism underlying their neuroprotective effect has been continuously explored. To advance the applied research on notoginsenosides in the prevention and treatment of central nervous system diseases， this paper， combined with the latest reports， summarizes their neuroprotective effect and mechanisms in terms of regulating voltage-gated ion channels， protecting nerve cells and neurovascular unit， inhibiting oxidative stress and inflammatory reaction， promoting angiogenesis and reducing excitatory neurotoxicity. Although the protective mechanism of notoginsenosides for the nervous system mainly involves the above several aspects， some of them still remain to be fully elucidated， which necessitates the further exploration of neuroprotective effect of notoginsenosides with molecular biology， metabolomics， proteomics and other technologies.
Keywords：notoginsenosides;neuroprotective effect;mechanism of action;research progress
Abstract：Perimenopausal anovulatory dysfunctional uterine bleeding （ADUB） is a severe acute disease that is difficult to be dealt with in gynecology， accounting for about 70% of abnormal uterine bleeding. The significant differences in bleeding patterns make it particularly challenging to treat. The main manifestations of perimenopausal ADUB are prolonged menstrual period， inexhaustible menstrual bleeding， or heavy inter-menstrual vaginal bleeding， which allow it to be classified into the category of metrorrhagia and metrostaxis in traditional Chinese medicine （TCM）. After conducting in-depth research on this disease， physicians of the past dynasties have figured out its etiology and pathogenesis and accumulated rich experience in its differentiation and treatment， thus forming a relatively systematic theoretical system. The existing literature mainly focuses on four types of its pathogenesis， namely blood heat， blood stasis， spleen deficiency， and kidney deficiency， and there are few discussions on liver. However， patients with metrorrhagia and metrostaxis due to liver dysfunction are commonly seen in clinical practice. The theory of liver being innate basis of women explores the special physiological and pathological characteristics of women and emphasizes the important role of liver in the treatment of this disease based on its characteristic functions and meridian circulation. Considering the close relationship of liver Qi and blood with spleen， kidney， and thoroughfare and conception vessels， this paper discussed the TCM treatment of perimenopausal ADUB from the following four aspects： soothing liver Qi and nourishing liver blood， liver and kidney sharing the same source， simultaneous regulation of liver and spleen， and liver meridian circulation， so as to broaden the clinical treatment options. Perimenopause is a unique physiological period when women tend to suffer from Qi stagnation and blood deficiency. Liver， characterized by Yin in property and Yang in function， governs the free flow of Qi， induces ovulation， stores blood， and regulates blood volume. Therefore， the liver should be emphasized in the treatment of perimenopausal ADUB， which contributes to correcting the hormone disorder caused by abnormal ovulation， stopping bleeding， and alleviating perimenopausal symptoms. This paper has provided a new direction for the clinical treatment of perimenopausal ADUB .
Keywords：perimenopause;abnormal uterine bleeding;liver being innate basis of women;metrorrhagia and metrostaxis
Abstract：Wulingsan， a classic prescription first recorded in the Treatise on Cold Damage （Shang Han Lun） by ZHANG Zhong-jing for patients with water retention syndrome due to the disturbance of Qi transformation in bladder， has often been modified by ancient and modern doctors for the treatment of renal diseases. It produced satisfactory outcomes without inducing adverse reactions. The databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data Knowledge Service Platform， and PubMed were searched for articles concerning the clinical application and pharmacological mechanism of Wulingsan in the treatment of renal diseases published by domestic and foreign scholars in recent years. The summary of the included articles revealed that Wulingsan has been widely employed for the treatment of renal edema， diabetic nephropathy， acute and chronic glomerulonephritis， nephrotic syndrome， renal insufficiency， abnormal urination， etc.， and the resulting outcomes were satisfactory. Wulingsan alone or in combination with western medicine yielded better clinical outcomes than the western medicine alone. In the exploration of its pharmacological mechanism， there existed some individual reports by Korean scholars， while Chinese scholars tended to work as a team. After years of research， each team has found that Wulingsan was superior to Wulingsan decoction in excreting water， which might be related to the absence of massive low-polarity and volatile components in the decoction that were responsible for regulating the expression of aquaporins （AQP） in kidney of saline-loaded rats. Wulingsan regulates the endocrine state of rats with kidney yang deficiency， inhibits the reabsorption of water， increases the activity of Na+-K+-ATPase， and reduces the expression of AQP 1， AQP 2， AQP 3， and AQP 4. Besides， it bi-directionally regulates the human water metabolism， which is achieved via the dual-directional regulation of purinergic P2X3 receptor expression on bladder detrusor. The efficacy of Wulingsan in treating chronic renal failure is attributed to its protection against the damaged renal tissue，structure and fanction. Hence， this paper summarized the research progress of Wulingsan in the treatment of renal diseases in recent years， aiming to provide a reference for the clinical and basic exploration of Wulingsan against renal diseases in the future.
Abstract：Prostatic carcinoma （PCa） is one of the most common male malignancies， accounting for 10% of all male cancers， and has become a global health problem. At present， it is mainly tackled with radical prostatectomy and endocrine therapy. However， most patients will develop drug resistance， allowing the progression of PCa into castration-resistant prostate cancer （CRPC）. Guided by the principles of holism and treatment based on syndrome differentiation， traditional Chinese medicine （TCM） alleviates cancer pain， regulates immune balance， and improves the quality of life of patients via multiple targets， multiple pathways， and multiple mechanisms without inducing obvious side effects， thus better exerting the preventive and therapeutic effects against PCa. This paper retrieved relevant articles concerning PCa intervention with TCM published in recent five years from PubMed and China National Knowledge Infrastructure （CNKI）， and summarized the molecular mechanism of PCa， its etiology and pathogenesis in TCM， and TCM interventions. The findings showed that the active ingredients of Chinese medicinals， single Chinese medicinals and Chinese medicinal compounds inhibited PCa by interfering with not only the classical pathways of PCa such as androgen receptor（AR）， Wnt/β-catenin， PI3K/Akt/mTOR， and NF-κB but also other pathways like ERS/UPR， RIPK， CIP2A/PP2A/ERK， EGFR， etc. The intervention of active ingredients from Chinese medicinals in PCa has been explored extensively， but there are fewer studies on single Chinese medicinals and Chinese medicinal compounds that can better reflect the unique advantages of TCM. Further research is needed to provide an important theoretical and experimental basis for the development of novel anti-PCa Chinese medicinal products and their clinical application.
Abstract：Perilla frutescens is a traditional medicinal and edible plant widely distributed in China and enjoys an extensive usage. P. frutescens contains multiple essential oils， which are composed of monoterpenes， sesquiterpenes， and their oxygen-containing derivatives. Compared with other parts of P. frutescens， Perillae Folium produce more oils， with volatile oils as the main constituents. There are many active substances in the volatile oils from Perillae Folium， mainly including perillaldehyde， perillaketone， perillaalcohol， D-limonene， β-caryophylene， etc. Such factors as germplasm， growth environment， extraction method， cultivation time， and harvest period all can trigger changes in volatile oil constituents and content from Perillae Folium. The volatile oils from Perillae Folium have diverse pharmacological effects like anti-oxidation， anti-bacteria， anti-inflammation， vasodilation， anti-tumor， and anti-depression， implying its high clinical application value. However， the chemical constituents in volatile oils from Perillae Folium are complex and unstable and their pharmacological activities are affected by many factors， so the safety and effectiveness of clinical medication fail to be guaranteed， which may has impeded the rational and effective use of these volatile oils. Many scholars in China and abroad have conducted a lot of research on the volatile oils from Perillae Folium， but there is currently no systematic and comprehensive research report on the chemical constituents of volatile oils from Perillae Folium and their pharmacological effects. This paper reviewed the relevant domestic and foreign literature， analyzed the development status of volatile oils from Perillae Folium， and summarized their extraction process， chemical constituents， and pharmacological actions， aiming to provide a reference for their further development， clinical application， and risk assessment.
Keywords：volatile oils from Perillae Folium;extraction process;chemical constituents;pharmacological activities;research advances
Abstract：In recent years， the role of quantitative pharmacological models in applicable population of drugs and dose optimization has been widely recognized. In order to improve the efficiency of clinical development and optimize clinical rational drug use， quantitative pharmacological models are being gradually introduced into the research of traditional Chinese medicine （TCM）. There are various types of quantitative pharmacological models， among which the following three models are commonly used：①Population pharmacokinetic （PPK） model， which is mainly used to explore the pharmacokinetic characteristics in different populations.②Pharmacokinetic-pharmacodynamic （PK-PD） model， which is used to reveal the internal relationship among dose， time and efficacy. ③PPK-PD model， which integrates both the characteristics of PPK model and PK-PD model. The paper summarizes the application of the above three models in TCM， and extracts the main ideas and methods of TCM model research， in order to provide reference for clinical research and rational use of TCM.
Keywords：quantitative pharmacology;population pharmacokinetic （PPK） model;pharmacokinetic-pharmacodynamic （PK-PD） model;PPK-PD model;traditional Chinese medicine
Abstract：The homology of medicine and food has long been recognized in China， and the medicinal and edible resources are often employed to prevent and treat diseases or maintain health in traditional Chinese medicine （TCM）. Due to the unique geographical and climatic conditions， the Xinjiang Uygur Autonomous Region （hereinafter referred to as Xinjiang） is blessed with abundant medicinal and edible resources， like Rosae Rugosae Flos， Punica granatum， and Amygdalus communis， which have been widely used by local ethnic communities as medicine in light of the remarkable pharmacological activities， guaranteeing their health condition to some extent. This paper collected the relevant articles from China National Knowledge Infrastructure （CNKI） database through the keyword and full-text search with the medicinal and edible resource Rosae Rugosae Flos as the search term， and the subsequent analysis revealed that the medicinal and edible resources in Xinjiang has a wide range of applications in food， medicine， and ecological protection. This paper further explored their research value， status， and prospects， so as to provide some references for the rational， effective， and sustainable development and utilization of these medicinal and edible resources in Xinjiang， thus better achieving "poverty alleviation" and "rural revitalization"， popularizing TCM culture， and building a healthy China.
Keywords：Xinjiang Uygur Autonomous Region （Xinjiang）;homology of medicine and food;research status;development
Abstract：This paper collated the western medicine and traditional Chinese medicine （TCM） diagnostic criteria of pulmonary fibrosis （PF） based on its clinical characteristics and relevant literature reports and summarized the inductive agents， methods， objects， and mechanisms for replicating the PF animal models as well as their respective advantages and disadvantages. By analyzing the consistency of symptoms among successfully modeled animal models with the clinical characteristics in TCM and western medicine， we found that the intratracheal injection of bleomycin was the most frequently employed method for modeling， and the resulting outcomes were very similar to clinical characteristics in TCM and Western Medicine. Besides， considering the time-saving process， high stability， good repeatability， and low cost， such method was suitable for the rapid screening of drugs. The second preferred method was intraperitoneal injection of paraquat， which exhibited the advantages of high degree of consistency with clinical characteristics of PF caused by paraquat poisoning， low cost， high success rate， and easy operation， which allowed it to be suitable for exploring the mechanism of paraquat poisoning and developing the antidotes. The existing PF animal models shared a fairly high degree of consistency in symptoms with patients diagnosed as having PF in western medicine. However， the criteria for TCM syndrome differentiation remained unclear， and the animal models failed to reflect TCM pathogenesis. It is necessary to establish more accurate TCM diagnostic criteria that focus on syndrome differentiation and reveal TCM etiology and pathogenesis and carry out more experiments concerning TCM syndromes of PF in the future， so as to better treat PF with integrated TCM and Western Medicine.
Keywords：pulmonary fibrosis （PF）;animal models;combination of disease with syndrome