OBJECTIVE To investigate the effect and potential mechanism of astilbin （AST） on renal injury in chronic renal failure （CRF） rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group， AST low-dose group （AST-L group）， AST high-dose group （AST-H group）， high-dose of AST+Notch pathway activator （Jagged-1/FC chimerin， referred to as “JFC”） group （AST-H+ JFC group）， and control group （CK group） for open surgery without resection was set up， with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST， respectively； the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC， and the rats in the CK group and Model group were given an equal volume of normal saline， once a day， for 4 weeks. After the last administration， the serum levels of blood urea nitrogen （BUN）， serum creatinine （SCr）， and the level of 24 h urinary protein （UP） in urine， as well as the serum levels of lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate （ATP） and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β （TGF- β）， hypoxia-inducible factor-1α （HIF-1α）， α-smooth muscle actin （α-SMA）， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group， the renal tissue of rats in the Model group was obviously damaged， renal tissue fibrosis was severe； the serum BUN and SCr levels， urine UP level， serum 4 LDH， TNF-α and IL-6 levels， as well as the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were significantly increased， while the serum IL-10 level， ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased （P＜0.05）. Compared with Model group， the renal tissue damage and fibrosis in the AST groups were reduced， the serum BUN and SCr levels， urine UP level， serum LDH， TNF-α and IL-6 levels， and the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 were significantly decreased， while the serum IL-10 level， ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased； the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group（P＜0.05）. JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats （P＜0.05）. CONCLUSIONS AST can reduce inflammation in CRF rats， alleviate renal tissue damage and fibrosis， and improve renal mitochondrial capacity metabolism， possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.

The concept of holism is the core idea of traditional Chinese medicine （TCM）. Various organs and tissues coordinate with each other to maintain the body's life activities， with a close and mutual influence between the spleen， stomach， and the central nervous system （brain）. The gut-brain axis plays an important bridging role between the digestive system and the central nervous system， achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence， coordination， and integration between different organs and systems； multimodality， on the other hand， utilizes multiple sensory modalities， such as vision， hearing， and touch， to convey information. By combining TCM theory with the gut-brain axis theory， a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders， precancerous gastrointestinal diseases， Alzheimer's disease， Parkinson's syndrome， type 2 diabetes， and depression.

Female ; Humans ; Breast Neoplasms ; Testosterone ; Prolactin ; Estradiol ; Testosterone Congeners ; China

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

ObjectiveTo evaluate the effect of antihypertensive and lipid-regulating Chinese patent medicine combined with conventional Western medicine in the treatment of hypertension with dyslipidemia. To carry out the evidence synthesis of clinical research and provide evidence-based evidence support for clinical decision-making. MethodThe databases including China National Knowledge Infrastructure （CNKI），Wanfang Data Knowledge Service Platform （WF），VIP，SinoMed，Embase，PubMed，Web of Science （WOS），and the Cochrane Library were searched for randomized controlled trials （RCT） of all listed Chinese patent medicines in the treatment of hypertension with dyslipidemia from the establishment of the databases to April 15，2023. The literature was screened and extracted，and the risk of bias tool 2.0 （RoB2） was used to assess the quality and risk of bias of the methodology. Revman 5.4.1 software was used to analyze the outcome indicators. Grading of Recommendations Assessment，Development and Evaluation （GRADE） was applied to assess the quality of evidence formed by clinical research data. The inclusion and recommendation of Chinese patent medicines in the National Drug Catalogue for Basic Medical Insurance，Work-related Injury Insurance and Maternity Insurance （2022） and domestic guidelines and consensus were searched to form a bubble chart. ResultA total of 15 studies were included. The evaluation of the methodological quality of each study showed that the risk of bias stemmed from the lack of blinding and allocation concealment，and low sample size. The comprehensive analysis of clinical studies showed that Dengzhan Shengmai capsules combined with rosuvastatin and amlodipine besylate，Yindan Xinnaotong capsules combined with simvastatin and levamlodipine tablets，Xiaoshuan Tongluo capsules combined with nifedipine controlled release tablets and pravastatin sodium tablets，Xinshubao capsules combined with atorvastatin calcium tablets and irbesartan，Wenyading capsules combined with enalapril，and Jiangzhining tablets combined with conventional Western medicines were all superior to conventional Western medicines used in the control group in improving systolic blood pressure （SBP），diastolic blood pressure （DBP），cholesterol （TC），triglyceride （TG），low density lipoprotein cholesterol （LDL-C），and high density lipoprotein cholesterol （HDL-C）. There was no significant difference in the incidence of adverse reactions between the two groups. The GRADE evaluation of the main outcome indicators showed that the evidence quality of SBP and incidence of adverse reactions was graded as B，that of DBP as C，and that of total TC，TG，LDL-C，and HDL-C as D. The evaluation of Chinese patent medicines covered by medical insurance and recommended by guidelines and consensus showed that Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules belonged to class B drugs of medical insurance，and were recommended for 7，6 and 3 times in the guidelines and consensus，respectively. ConclusionCompared with simple medicine treatment，Chinese patent medicine combined with conventional Western medicine has more advantages in improving blood pressure and blood lipid，and shows higher safety. Among them，Yindan Xinnaotong soft capsules，Dengzhan Shengmai capsules and Xiaoshuan Tongluo capsules have stronger clinical applicability and economy. All the trials included in this article adhered to the principle of randomization and reported the outcome measures. However，the quality of evidence in related clinical studies was low. In terms of trial design，large-sample，multi-center，blinded randomized controlled trials based on the consolidated standards of reporting trials （CONSORT） statement are still needed for comprehensive trial designs and reporting，to further improve the GRADE quality evaluation and guideline formulation under the guidance of evidence-based medicine，so as to provide higher quality evidence-based research evidence for clinical decision-making.

ObjectiveTo evaluate the quality of research and evidence related to antihypertensive Chinese patent medicines combined with western medicines for the treatment of hypertension， synthesize and update the evidence， form expert consensus， and provide evidence for clinical decision-making. MethodThe databases of China National Knowledge Infrastructure （CNKI）， WanFang Data Knowledge Service Platform （WanFang）， Vip Chinese Science and Technology Journal Database （VIP）， Chinese Biomedical Literature Service System （Sinomed）， National Library of Medicine （PubMed）， Cochrane Library， Web of Science， and US Clinical Trials Registry were searched for randomized controlled trials of antihypertensive Chinese medicine combined with western medicine for the treatment of hypertension from database construction to July 31， 2022. The quality of the literature was evaluated using the bias risk assessment tool in Cochrane Handbook 6.3. Evidence synthesis of main outcome indicators was performed using R software. The Grading of Recommendations Assessment， Development， and Evaluation profiler （GRADEprofiler） 3.6 was employed to evaluate the quality of evidence. Expert consensus was formed based on the Delphi method after two rounds of voting. Result64 pieces of literature were included， and the results of literature quality evaluation and risk of bias showed that 70.31% （45/64） of the studies indicated some risks， and 29.69% （19/64） indicated high risks. Compared with conventional western medicines， the combination of Chinese patent medicines with western medicines can significantly lower systolic pressure （SBP） and diastolic pressure （DBP）， increase the effective rate of antihypertensive， reduce the incidence of adverse reactions， endothelin-1， and traditional Chinese medicine syndrome scores. Egger's test showed that Songling Xuemaikang capsules reduced SBP and DBP. Tianma Gouteng granules reduced SBP and DBP and increased the effective rate of antihypertensive， and Xinmaitong capsules reduced SBP and increased the effective rate of antihypertensive， without significant publication bias. Songling Xuemaikang capsules increased the effective rate of antihypertensive， and Xinmaitong capsules decreased DBP， with significant publication bias. The results of the GRADE evidence quality evaluation showed that most evidence was at grades B and C. Finally， four strong recommendations and 14 weak recommendations were formed. ConclusionCompared with conventional western medicines for the treatment of hypertension， antihypertensive Chinese patent medicines combined with western medicines have advantages in reducing blood pressure and improving drug use safety， but they are mostly weak recommendations in terms of efficacy， and more high-quality evidence is needed.

ObjectiveTo systematically collect， analyze， and evaluate the randomized controlled trials （RCT） of Chinese patent medicine combined with western medicine in the treatment of hypertension， map the evidence， and provide reference for the future clinical research and formulation of guidelines and policies. MethodThe relevant articles were retrieved from China Biology Medicine disc， China National Knowledge Infrastructure （CNKI）， VIP， Wanfang Data， PubMed， Embase， and Cochrane Library with the time interval from inception to December 31， 2022. The RCT of Chinese patent medicines combined with western medicine in the treatment of hypertension were included. The research characteristics and methodological quality were analyzed and evaluated. ResultA total of 330 RCTs of treating hypertension with Chinese patent medicines combined with Western medicine were included in this study， all of which were published in Chinese. These RCTs involved 88 Chinese patent medicines and 37 788 patients， and 46% of RCT had the sample size ≥100 patients. Eighty-seven percent of RCT showed the study period within 3 months. All the interventions in the RCTs were Chinese patent medicine + western medicine vs western medicine. Among the evaluation indicators， blood pressure， response rate， TCM syndrome score， endothelial cell function， and safety were mainly concerned. In terms of methodological quality， most articles did not mention the generation of random sequences， allocation concealment， or blinding method. The blinding evaluation of outcomes showed low risks of bias， and there was insufficient information to judge whether there was selective bias or other bias. ConclusionThere were many Chinese patent medicines used in combination with western medicine in the treatment of hypertension， and they were mainly taken orally. The existing RCT had problems such as small sample size， unclear clinical value positioning， imperfect design failing to reflect the value of Chinese patent medicines， unreasonable measurement indicators， and non-standard measurement methods. Future research should solve the above problems， improve the research quality， value， and authenticity， and enhance the reliability and extension of evidence.

Objective To investigate the clinical characteristics of stasis-toxin pathogenesis in patients with non-small cell lung cancer(NSCLC)of blood stasis and qi stagnation type,and to explore the interventional mechanism of adjuvant therapy with Bufei Huayu Decoction.Methods Seventy-eight patients with NSCLC of blood stasis and qi stagnation type admitted to the Department of Respiratory Medicine of Liu'an Hospital of Traditional Chinese Medicine from January 2021 to September 2022 were selected as the NSCLC group,and 71 volunteers who underwent physical examination during the same period served as the healthy control group.The clinical characteristics of stasis-toxin pathogenesis in the NSCLC group were observed,and the differences in the indicators of coagulation function were compared between NSCLC group and the healthy control group.According to the therapy,the NSCLC patients were divided into Bufei Huayu Decoction group(40 cases)and conventional treatment group(38 cases).The conventional treatment group was treated with conventional chemotherapy,while Bufei Huayu Decoction group was treated with Bufei Huayu Decoction together with conventional chemotherapy.Three weeks constituted one course of treatment,and the treatment lasted for 2 courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,coagulation function,immune function,serum nitric oxide(NO),vascular endothelial growth factor(VEGF)level in Bufei Huayu Decoction group and conventional treatment group were observed before and after treatment.Moreover,the clinical efficacy of the two groups and the occurrence of adverse reactions were compared during the treatment period.Results(1)NSCLC patients were classified into the clinical stages Ⅲ and Ⅳ and the pathological types of squamous carcinoma and adenocarcinoma,had the high proportion of KPS scores lower than 70,and were scored with high TCM syndrome scores,suggesting that the illness condition of patients with NSCLC was serious.Compared with the healthy control group,plasminogen time(PT)and thrombin time(TT)in NSCLC patients were significantly shortened,and levels of fibrinogen(FIB)and D-dimer(D-D)were significantly increased,and the differences were statistically significant(P＜0.01).(2)After 6 weeks of treatment,the total effective rate and total stability rate of Bufei Huayu Decoction group were 32.50%(13/40)and 85.00%(34/40),which were significantly superior to those of the conventional treatment group[versus 13.16%(5/38)and 60.53%(23/38)],and the differences were statistically significant(P＜0.05).(3)After 3 weeks of treatment,obvious improvement was presented in the scores of all the TCM symptoms of fatigue,chest distress and shortness of breath,stabbing pain in the chest,and blood stasis in the vessels and collaterals of Bufei Huayu Decoction group and in the scores of the fatigue,chest distress and shortness of breath of the conventional treatment group when compared with those before treatment(P＜0.05).After 6 weeks of treatment,all of the TCM syndrome scores of the two groups were improved compared with those before treatment and after three weeks of treatment(P＜0.05).The intergroup comparison showed that except for the scores of chest distress and shortness of breath after 3 weeks of treatment,the effect on improving all of the TCM syndrome scores in Bufei Huayu Decoction group was significantly superior to that in the conventional treatment group after 3 and 6 weeks of treatment(P＜0.05 or P＜0.01).(4)After 6 weeks of treatment,the levels of coagulation function indicators of PT,TT,FIB and D-D in the Bufei Huayu Decoction group were significantly improved compared with those before treatment(P＜0.05),while only FIB and D-D in the conventional treatment group were improved compared with those before treatment(P＜0.05).The intergroup comparison showed that Bufei Huayu Decoction group had stronger effect on improving the levels of PT,FIB and D-D than the conventional treatment group(P＜0.05).(5)After 6 weeks of treatment,the serum NO and VEGF levels in both groups were significantly lower than those before treatment(P＜0.05),and the effect on lowering serum NO and VEGF levels of the Bufei Huayu Decoction group was significantly superior to that of the conventional treatment group(P＜0.01).(6)After 6 weeks of treatment,the immune function parameters of CD3+,CD4+ levels and CD4+/CD8+ ratio in the Bufei Huayu Decoction group were increased(P＜0.05)and CD8+level was decreased(P＜0.05)as compared with those before treatment,whereas CD3+,CD4+ levels and CD4+/CD8+ ratio in the conventional treatment group were decreased(P＜0.05)and CD8+ level was increased(P＜0.05).The intergroup comparison showed that the effect of Bufei Huayu Decoction group on the increase of CD3+,CD4+ levels and CD4+/CD8+ ratio and the effect on the decrease of CD8+ level were significantly superior to those of the conventional treatment group(P＜0.01).(7)In terms of the quality of life,the KPS scores of patients in the two groups after 6 weeks of treatment were significantly higher than those before treatment(P＜0.05),and the effect of Bufei Huayu Decoction group on the increase of KPS scores was significantly superior to that of the conventional treatment group(P＜0.01).(8)During the course of treatment,the incidence of adverse reactions such as gastrointestinal reactions and alopecia in the two groups was not statistically significant(P＞0.05),while the incidence of hepatic and renal impairment,bone marrow suppression,and toxicity of oral mucosa in Bufei Huayu Decoction group was significantly lower than that of the conventional treatment group(P＜0.05 or P＜0.01),suggesting that Bufei Huayu Decoction group reduced the adverse reactions induced by chemotherapy to a certain extent.Conclusion Patients with NSCLC of blood stasis and qi stagnation type generally have advanced disease progression and high blood coagulation,which is consistent with the stasis-toxin pathogenesis in TCM.The use of Bufei Huayu Decoction against the stasis-toxin pathogenesis can significantly improve patients'TCM syndrome scores and coagulation function,down-regulate the levels of serum NO and VEGF,and improve the immune function,which brings about the enhancement of clinical efficacy and quality of life,and the reduction of adverse reactions caused by chemotherapy,with a high safety.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

ObjectiveTo construct a cough model induced by chemical stimuli by whole-body plethysmography （WBP） for counting coughs based on cough waveforms， and use this model to explore the antitussive effect of GK-A. MethodDifferent chemical stimuli were used to induce coughs in mice or guinea pigs. Respiratory waveforms were monitored by WBP， and the recognizable and typical cough waveforms were selected for cough counting. Guinea pigs were induced to cough with different concentrations of citric acid or capsaicin， and cough waveforms were used to optimize the stimulation conditions. The optimized guinea pig model of cough was validated with dextromethorphan， and the optimized guinea pig model of capsaicin-induced cough was used to evaluate the antitussive effect of GK-A. ResultWBP could count the coughs induced by capsaicin and citric acid in guinea pigs by recognizable and typical respiratory waveforms. The optimized stimulation conditions were capsaicin concentration of 100 µmol·L^-1 and nebulization for 2 min. The validation results showed that compared with the model group， the dextromethorphan group of guinea pigs had reduced coughs （P<0.05） and prolonged cough latency （P<0.01）. GK-A prolonged the cough latency （P<0.05） and reduced coughs （P<0.05） in the mouse model of ammonia-induced cough. In the guinea pig model of capsaicin-induced cough， GK-A prolonged cough latency （P<0.05）， reduced coughs （P<0.05）， and decreased substance P （SP） content in the guinea pig serum （P<0.05， P<0.01）. ConclusionA guinea pig model of capsaicin-induced cough was successfully established based on cough waveform counting， which provided an objective and accurate cough counting method. GK-A has antitussive effects， possibly by inhibiting the neuropeptide SP.