Exploration of potential active ingredients and mechanism of action of Xihuang pill-medicated serum against glioma based on HPLC-Q-TOF-MS/MS, network pharmacology and experimental verification / 药学学报

Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC50 of 30.96 μmol·L-1, and KBA (30 μmol·L-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Activation of Nrf2/HO-1/NQO1 Signaling Pathway by Shenqi Tangluo Pill Improves Oxidative Stress Injury of Skeletal Muscle of Type 2 Diabetes Mellitus Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Shenqi Tangluo pill （SQTLP） on oxidative stress injury of skeletal muscle of type 2 diabetes mellitus （T2DM） mice based on nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） pathway. MethodA total of 60 7-week-old male db/db mice ［specific pathogen-free （SPF） grade］ were selected and fed for one week for adaption. They were divided into the model control group， SQTLP low-， medium- and high-dose （19， 38， and 76 g·kg-1） groups and metformin group （0.26 g·kg-1） by gavage. Each group consisted of 12 mice. Twelve male db/m mice of the same age were selected as the blank group. The intervention was implemented continuously for 8 weeks. Fasting blood glucose （FBG） was detected. Fasting serum insulin （FINS） levels were detected by enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment-insulin resistance （HOMA-IR） index and the homeostasis model assessment-insulin sensitivity index （HOMA-ISI） were calculated. Oral glucose tolerance test （OGTT） and insulin tolerance test （ITT） were conducted. The activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） and the contents of malondialdehyde （MDA） and reduced nicotinamide adenine dinucleotide phosphate （NADPH） in skeletal muscle tissues were detected by biochemical kits. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in skeletal muscle tissues. The levels of reactive oxygen species （ROS） and 4-hydroxynonenal （4-HNE） in skeletal muscle tissue were detected by immunofluorescence （IF）. The expression levels of Nrf2， HO-1， NQO1 and glutamate-cysteine ligase catalytic subunit （GCLC） proteins in skeletal muscle tissues were detected by Western blot. ResultCompared with those in the blank group， FBG， FINS and HOMA-IR in the model group were significantly increased （P<0.05）， while HOMA-ISI was decreased （P<0.05）. The results of OGTT and ITT showed that blood glucose was significantly increased at all time points （P<0.05）， and glucose tolerance and insulin tolerance were significantly impaired. SOD and GSH-Px activities in skeletal muscle tissues were significantly decreased （P<0.05）， and MDA and NADPH contents were significantly increased （P<0.05）. In skeletal muscle tissues， the arrangement of muscle fibers was loose， the nucleus was disordered， and inflammatory cells were infiltrated. The expression levels of ROS and 4-HNE in skeletal muscle tissues were significantly increased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly decreased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the metformin group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that blood glucose in the metformin group was significantly decreased at all time points （P<0.05）. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue of the metformin group. The expressions of ROS and 4-HNE in skeletal muscle tissues were decreased （P<0.05）. The protein expression levels of Nrf2， HO-1， NQO1 and GCLC in skeletal muscle tissues were significantly increased （P<0.05）. Compared with those in the model group， FBG， FINS and HOMA-IR in the SQTLP medium- and high-dose groups were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the glucose tolerance and insulin tolerance of mice were improved in each dose group of SQTLP. The GSH-Px activity in the SQTLP low-dose group was significantly increased （P<0.05）， and the NADPH content was decreased （P<0.05）. The activities of SOD and GSH-Px in the SQTLP medium- and high-dose groups were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. The skeletal muscle tissue injury of mice in each dose group of SQTLP was ameliorated to different degrees. In the SQTLP medium- and high-dose groups， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05）. Compared with those in the SQTLP low-dose group， FBG and HOMA-IR in the SQTLP high-dose group were significantly decreased （P<0.05）， while HOMA-ISI was increased （P<0.05）. The results of OGTT and ITT showed that the SQTLP high-dose group significantly improved the glucose tolerance and insulin tolerance of mice. The activities of SOD and GSH-Px in skeletal muscle tissues were significantly increased （P<0.05）， while the contents of MDA and NADPH were significantly decreased （P<0.05）. No obvious abnormality was found in the skeletal muscle tissue， the expressions of ROS and 4-HNE were decreased （P<0.05）， and the protein expression levels of Nrf2， HO-1， NQO1 and GCLC were significantly increased （P<0.05） in the skeletal muscle tissue of the SQTLP high-dose group. ConclusionSQTLP can significantly improve IR in T2DM mice， and the mechanism is related to SQTLP activating the Nrf2/HO-1/NQO1 signaling pathway， promoting the expression of antioxidant enzymes， and thus improving the oxidative stress injury in the skeletal muscle.

Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury / 中国药房

OBJECTIVE To explore the mechanism of Zadi-5 pill in improving myocardial ischemia-reperfusion injury （MIRI）. METHODS The targets and pathways of potential effects of Zadi-5 pill improving MIRI were screened based on the network pharmacology. Seventy-two rats were randomly divided into model group， sham operation group， Danshen group [Compound danshen dripping pills 80 mg/（kg·d）] and Zadi-5 pill high-dose， medium-dose and low-dose groups [1.6， 0.8， 0.4 g/（kg·d）]， with 12 rats in each group. The rats in each group were given corresponding drugs intragastrically， once a day， for 14 consecutive days. After the last administration， MIRI model was established by ligating the anterior descending branch of left coronary artery in rats， while rats in the sham operation group were threaded without ligation. The contents of creatine kinase （CK）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）， cardiac troponin T （CTn-T）， apoptotic rate of cardiomyocyte， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax） and caspase-3 in myocardial tissue were detected in each group after modeling； the morphological changes of myocardial tissue were observed. RESULTS A total of 177 active ingredients and 220 targets of Zadi-5 pill were obtained， including 51 targets involved in improving myocardial ischemia； the core target of Zadi-5 pill improving MIRI was AKT1， including PI3K-Akt， endoplasmic reticulum and hypoxia-inducible factor-1. Compared with model group， the contents of CK， LDH， AST and CTn-T， the apoptotic rate of cardiomyocyte as well as the protein expressions of caspase-3 and Bax were significantly decreased in Danshen group and Zadi-5 pill high-dose group （P＜0.05 or P＜0.01）， while the protein expressions of PI3K， Akt and Bcl-2 in myocardial tissue were significantly increased （P＜0.05 or P＜0.01）， respectively； the myocardial histopathological changes were significantly improved. The above indicators were improved to varying degrees in Zadi-5 pill low-dose and medium-dose groups， too. CONCLUSIONS Zadi-5 pill may inhibit apoptosis by activating the PI3K-Akt signaling pathway， thus playing a role in improving MIRI.

Exploring the mechanism of Xihuang Pill's anti-hyperplasia of mammary glands effect based on UPLC-Q-orbitrap-MS technology / 药学学报

Based on UPLC-Q-orbitrap-MS and biological network analysis tools, the mechanism of Xihuang Pill in improving hyperplasia of mammary glands was systematically analyzed. The rat model of hyperplasia of mammary glands was established by intramuscular injection of estradiol benzoate and progesterone. LC-MS tissue metabolomics was used to explore the key metabolites and metabolic pathways of Xihuang Pill in improving hyperplasia of mammary glands in rat. The network analysis of the key metabolites regulated by Xihuang Pill was carried out by integrating biological network analysis tools, focusing on the key metabolic pathways, and exploring the potential targets of Xihuang Pill to improve hyperplasia of mammary glands. Compared with the control group, there were significant differences in the content of 49 differential metabolites in the tissues of the model group (P < 0.05). Xihuang Pills could significantly call back 17 metabolites such as L-alanine, threonine, indole-3-carboxylic aldehyde, lysine, arginine, alanylleucine, glycyltyrosine, γ-glutamyl leucine, vitamin B3, serine leucine, threonine leucine, isoleucine glutamic acid, γ-glutamyl tyrosine, decanoyl-L-carnitine, uric acid, leucylleucine, S-adenosyl-methionine. Further network analysis and literature research on the key metabolites regulated by Xihuang Pills showed that the AGE-RAGE signaling pathway may be one of the important pathways for Xihuang Pills to improve hyperplasia of mammary glands. STAT3, MAPK1, EGFR, CASP3, CASP8, PRKCA and JUN in the AGE-RAGE signaling pathway may be potential targets for Xihuang Pills to improve hyperplasia of mammary glands. The animal experiment operations involved in this paper follow the provisions of the Animal Ethics Committee of Gansu University of Traditional Chinese Medicine and pass the ethical review of animal experiments (approval number: 2022-705).

Analysis of 111 cases of aristolochic acids nephropathy / 药学实践杂志

Objective To analyze the clinical characteristics and regularity of aristolochic acid nephropathy (AAN) induced by drugs containing aristolochic acid. Methods The clinical data of 111 patients with AAN induced by aristolochic acid were reviewed. The clinical features, medication and treatment of AAN were analyzed. Results Among 111 patients, there were more females than males (2.58∶1), 101 cases (90.99%) were over 50 years old； the mean age was (63.70±11.67) years old;the average duration of medication was (8.08±6.94) years. The drugs involved were Guanxinsuhe pill and Longdanxiegan pill in 106 cases (95.50%). Serum creatinine increased in 108 cases, urea nitrogen increased in 106 cases and hemoglobin decreased in 103 cases, most of which were hypogravity urine, mild to moderate proteinuria and occult blood. Ultrasonic examination revealed that the kidneys were damaged to varying degrees. Pathological biopsy of kidney showed renal tubular damage. Most patients had an insidious onset and varying degrees of progression, which were not proportional to the age and the duration of taking the medicine. In clinical, the renal function was progressively damaged, most of which were irreversible and with a poor prognosis. Conclusion Patients with renal impairment differed greatly individually, and the renal damage was not paralleled with the medication duration and dose of drugs containing aristolochic acid.AAN progressed rapidly, and the disease still progressed even after stopping taking drugs containing aristolochic acid. Strengthening pharmacovigilance, implementing early diagnosis and effective intervention could help to reduce the occurrence of AAN and attenuate its development.

Clinical Study of Modified Shenqi Pill （肾气丸） Plus Tongdu Tiaoshen Acupuncture （通督调神针刺） for Neurogenic Bladder After Spinal Cord Injury of Kidney-Yang Deficiency Syndrome / 中医杂志

ObjectiveTo observe the clinical efficacy of modified Shenqi Pill （肾气丸） plus Tongdu Tiaoshen Acupuncture （通督调神针刺） in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment， i.e. oral methylcobalamin tablets （0.5 mg each time， 3 times a day） and paraplegic conventional acupuncture （once a day， 6 consecutive days a week）. The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment； and the treatment group was given modified Shenqi Pill orally （1 dose a day， 150 ml each time， taken warmly in morning and evening） and Tongdu Tiaoshen Acupuncture （once a day， 6 consecutive days per week） in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency， 24 h urine leakage frequency， 24 h single urine volume， bladder residual urine volume， international lower urinary tract symptom （LUTS） score， traditional Chinese medicine （TCM） syndrome score were compared between the two groups， and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination， the number of 24 h urine leakage， bladder residual urine volume， LUTS score， and the TCM syndrome scores decreased after treatment in both groups， and the 24 h single urine volume increased （P＜0.01）； and much more improvement was found of each index in the treatment group than in the control group （P＜0.05 or P＜0.01）. The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% （17/20） respectively， which were statistically significantly higher than 45.00% （the total clinical effectiveness， 9/20） and 60.00% （TCM syndrome effectiveness， 12/20） in the control group （P＜0.01）. ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome， having better effectiveness than simple bladder function rehabilitation training， and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.

Efficacy of Tiaogan Huaxian Pills in Prevention and Treatment of Hepatic Fibrosis in Hepatitis B and Its Effect on Diffusion-weighted Imaging / 中国实验方剂学杂志

ObjectiveTo investigate the preventive and therapeutic effects of Tiaogan Huaxian pills combined with entecavir on hepatic fibrosis in chronic hepatitis B with liver Qi stagnation， spleen deficiency， and blood stasis syndrome and its effect on diffusion-weighted imaging （DWI）. MethodClinical data of 117 patients with liver disease who visited the Department of Hepatology at the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2021 to April 2022 were retrospectively analyzed. According to different treatment plans， they were divided into a control group （59 cases） and a treatment group （58 cases）. Both groups of patients received entecavir-based etiology treatment， and the treatment group added Tiaogan Huaxian pills on the basis of basic treatment. Both groups were treated for 24 weeks. Before and after treatment， the two groups were compared in terms of alanine aminotransferase （ALT）， advanced surgical technologies （AST）， total bilirubin （TBil）， hepatitis B virus （HBV）-DNA conversion rate， liver stiffness measurement （LSM）， four items of liver fibrosis （hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， and laminin）， the fibrosis index based on four factors （FIB-4）， the aspartate aminotransferase to platelet ratio index （APRI）， the apparent diffusion coefficient （ADC） value in magnetic resonance imaging （MRI）， and traditional Chinese medicine symptom scores， so as to analyze the efficacy of the two groups. ResultBefore treatment， there was no significant difference in ALT， AST， TBil， LSM， four items of liver fibrosis， FIB-4， APRI， HBV-DNA conversion rate， ADC value， and traditional Chinese medicine symptom scores between the two groups. After treatment， both groups of patients showed significant reductions in ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， and APRI （P<0.05） and a significant increase in ADC value （P<0.05） and HBV-DNA conversion rate （P<0.01）. The traditional Chinese medicine symptom score of the treatment group decreased significantly （P<0.05）. Compared with the control group after treatment， the effective rate of clinical traditional Chinese medicine in the treatment group was 91.38% （53/58）， which was significantly higher than that of the control group （54.23%， 32/59） （Z=-4.325， P<0.01）. In the treatment group， ALT， AST， TBil， LSM， hyaluronidase， type Ⅲ pro-collagen， type Ⅳ collagen， laminin， FIB-4， APRI， and traditional Chinese medicine symptom scores all decreased significantly （P<0.05）， and the increase in ADC values was more significant （P<0.05）， while the difference in HBV-DNA conversion rate was not statistically significant. There were no serious adverse reactions or events in either group. ConclusionTiaogan Huaxian pills combined with entecavir have significant clinical efficacy in the treatment of hepatic fibrosis in chronic hepatitis B， which can reduce liver inflammation activity， delay hepatic fibrosis progression， and reduce traditional Chinese medicine symptom scores. It is worthy of clinical promotion and application.

Recomendaciones de terapia Antihipertensiva: la importancia de las combinaciones Avalado por la Sociedad Centroamericana y del Caribe de Cardiología / Antihypertensive therapy recommendations: the importance of combinations Endorsed by the Central American and Caribbean Society of Cardiology

RESUMEN El presente trabajo es el resultado de una iniciativa para analizar, resumir y mostrar la evidencia científica más reciente sobre el tema de la hipertensión y la implementación de las mejores terapéuticas disponibles. Este documento fue creado con la colaboración conjunta de médicos especialistas para dar una perspectiva local a la gestión basada en la mejor evi- dencia científica y en el contexto de la región de Centroamérica y el Caribe. Este artículo cuenta con el respaldo científico y académico de la Sociedad Centroamericana y del Caribe de Cardiología y es el primero de su tipo en abordar el problema y tema de la hipertensión. Se desarrolló a partir de una revisión detallada de la evidencia científica utilizando los principales buscadores médicos, seleccionando los estudios pivotales y poblacionales con mayor nivel de evidencia disponible. La in- tención es brindar información sencilla, con recomendaciones fáciles de implementar en el manejo diario de los pacientes con hipertensión arterial. Este documento contó con el apoyo logístico del Laboratorio Servier, tanto con los autores como en su edición; sin embargo, la información clínica presentada no estuvo condicionada por el laboratorio. Este material es responsabilidad de los autores.

ABSTRACT Antihypertensive therapy recommendations: the importance of combinations Endorsed by the Central American and Caribbean Society of Cardiology The present work is the result of an initiative to analyze, summarize, and show the latest scientific evidence on the subject of hypertension and the implementation of the best available therapeutics. This document was created with the joint collaboration of medical specialists to give a local perspective to the management based on the best scientific evidence and in the context of the Central American and Caribbean region. This paper has the scientific and academic support of the Central American and Caribbean Society of Cardiology and is the first of its kind to address the problem and topic of hypertension. It was developed from a detailed review of the scientific evidence using the main medical search engines, selecting the pivotal and population-based studies with the highest level of evidence available. The intention is to provide simple information, with easy-to-implement recommendations to implement in the daily management of patients with arterial hypertension. This document had the logistic support of Servier Laboratory, both with the authors as well as its editing; however, the clinical information presented was not conditioned by the laboratory. This material is the responsibility of the authors.

Do antihypertensive drugs combinations in single-pill combination improve cardiovascular outcomes? / ¿Las combinaciones de medicamentos antihipertensivos en un solo comprimido mejoran los resultados cardiovasculares?

Abstract Recommendations and guidelines propose to com bine antihypertensive drugs to improve BP control, highlighting the advantages of single-pill combinations (SPCs) to improve treatment adherence. It is speculated that, compared with free-dose combinations (Free-DCs), SPC should achieve a reduction in cardiovascular (CV) events and mortality through better adherence and BP control. However, there is little information in this regard. For this reason, the objective of this review was to provide a descriptive analysis the differences in CV outcomes between SPCs antihypertensive drugs treat ments vs. Free-DCs treatments. Ten studies were found and none had a randomized controlled design. Medi cation adherence was higher with SPCs, but outcomes were not adjusted for the adherence/persistence. When groups were compared according to similar adherence degrees, the statistical significance in favor of SPCs disappeared. Thus, randomized controlled studies are necessary to evaluate if SPCs have any effect beyond the improvement of the adherence to hypertensive treatment.

Resumen Las recomendaciones y las guías proponen combinar fármacos antihipertensivos para mejorar el control de la presión arterial, destacando las ventajas de las combi naciones en un solo comprimido para mejorar la adhe rencia al tratamiento. Se especula que, en comparación con las combinaciones en varios comprimidos, deberían lograr una reducción de los eventos cardiovasculares y de la mortalidad a través de una mejor adherencia y con trol de la presión. Sin embargo, hay poca información al respecto. Por esta razón, el objetivo de esta revisión fue proporcionar un análisis descriptivo de las diferencias en los resultados cardiovasculares y la mortalidad entre los tratamientos con combinaciones de antihipertensi vos en un solo comprimido vs. combinaciones de los mismos grupos de fármacos en varios comprimidos. Se encontraron diez estudios, pero ninguno tenía un dise ño controlado aleatorio. La adherencia a la medicación fue mayor con las combinaciones en un comprimido, pero los resultados no se ajustaron por la adherencia/ persistencia. Cuando se compararon los grupos según grados de adherencia similares, la significación estadís tica a favor de las combinaciones en un comprimido se perdió. Por lo tanto, son necesarios estudios controlados aleatorios para evaluar si las combinaciones de antihi pertensivos en un comprimido tienen algún efecto más allá de la mejora de la adherencia al tratamiento.

Meta-analysis on Xixian Tongshuan Capsules/Pills combined with western medicine in treating cerebral infarction / 国际中医中药杂志

Objective:To systematically evaluate the clinical efficacy and safety of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction.Methods:All RCTs about Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction were retrieved from CNKI, Wanfang Database, VIP database, PubMed and CBM. The search period was from the database establishment to December 31, 2021. Two researchers independently extracted the basic literature data and evaluated the methodological quality, then used RevMan5.4 software for meta-analysis.Results:Totally 9 articles were included, involving a total of 988 patients, including 505 cases in the observation group and 483 cases in the control group. Meta-analysis showed that the total effective rate of Xixian Tongshuan Capsules/Pills combined with Western medicine in treating cerebral infarction was higher than that of conventional Western medicine [ RR=1.20, 95% CI (1.13, 1.27), P<0.05]. At the same time, the effect of NIHSS score, Barthel score and FIB were better than those of conventional Western medicine [respectively: MD=-3.21, 95% CI (-4.45, -1.97), P<0.05; MD=11.83, 95% CI (10.66, 13.00), P<0.05; MD=-0.95, 95% CI (-1.36, -0.54), P<0.05]. After treatment with Xixian Tongshuan Capsules/Pills combined with Western medicine, the adverse reactions mainly included dizziness, nausea, indigestion, rash, facial blushing, etc. There was no statistically significant difference in safety between the two groups [ RR=1.50, 95% CI (0.75, 3.01), P>0.05]. Conclusions:Under the treatment of conventional Western medicine, the addition of Xixian Tongshuan Capsules/Pills can improve the clinical efficacy of cerebral infarction treatment, effectively improve the symptoms of neurological impairment, improve the ability of daily life, and promote the prognosis and recovery, and without increasing the incidence of adverse reactions. However, large sample and high quality studies are still needed to support the conclusion.

Zisheng Pill Formula （资生丸方） in Treating Malignant Tumor Targeted Therapy-induced Diarrhea with Spleen-stomach Weakness Syndrome：A Randomized-controlled Trial / 中医杂志

ObjectiveTo evaluate the clinical efficacy and safety of Zisheng Pill Formula （资生丸方， ZPF） in the treatment of malignant tumor targeted drugs-related diarrhea with spleen-stomach weakness syndrome. MethodsThis was an randomized controlled study， involving 34 cases in the treatment group and 33 cases in the control group. The treatment group was given ZPF decoction， one dose daily by twice， 200 ml each time， while the control group was given montmorillonite powder， three times per day， 3 g each time， with the first dose doubled， both groups for two weeks. The diarrhea frequency， stool characteristics， common terminology criteria for adverse events （CTCAE） for diarrhea， traditional Chinese medicine （TCM） syndrome score， the European organization for research on treatment of cancer （EORTC） quality of life questionnaire （EORTC QOL-C30） score， levels of serum intestinal functional indicators including diamine oxidase （DAO）， D-lactic acid （D-LA）， endotoxin （ET） levels were evaluated before and after treatment， and the safety was assessed. ResultsThere were 33 cases in the treatment group and 32 cases in the control group in terms of the per-protocol set （PPS）. The total effective rate of diarrhea of the treatment group and control group was 84.85% and 37.50%， respectively， and the total effective rate of TCM syndromes was 93.94% and 34.38%， with statistically significant differences between the groups （P＜0.01）. After treatment， the frequency of diarrhea and CTCAE grade decreased in both groups， with improved stool characteristics， increased overall health score， and decreased DAO， D-LA and ET levels； in the treatment group， the frequency of diarrhea， the TCM symptom scores in terms of stool characteristics， fear of cold and cold limbs， fatigue， numbness， nausea and vomiting， abdominal distension and abdominal pain were reduced， while the physical function score increased； in the control group， the frequency of diarrhea， stool characteristics and abdominal pain score decreased （P＜0.05 or P＜0.01）. The results favored the treatment group than the control group in all the outcomes except for the nausea and vomiting score， abdominal pain score， overall health score， physical function score， and ET level （P＜0.05 or P＜0.01）. During the treatment， one case of gastrointestinal infection and one case of constipation occurred in the treatment group， while one case of tumor progression in the control group. ConclusionZPF can effectively improve the clinical symptoms， increase quality of life， decrease serum DAO， D-LA and ET levels， and is safe when treating malignant tumor targeted drug-related diarrhea with spleen-stomach weakness syndrome. The possible mechanism may be related to the repair of intestinal mucosa barrier function.

Effects of Weichang'an Pill on contraction of isolated ileum smooth muscles in rats / 中国药理学通报

Aim To investigate the impact and mechanism of Weichang'an Pill(WCA),its ethanol extract(EE),water extract(WE),and active ingredients on the contraction of isolated rat ileum smooth muscles induced by acetylcholine(ACh). Methods In vitro tissue bath experiment,WCA,EE,WE,or their active ingredients were added under the action of ACh,and then the contraction tension of isolated ileum smooth muscle from rats was recorded. The binding affinity ofthe active ingredients to the muscarinic acetylcholine M3 receptor was explored by molecular docking. Results WCA,EE,and WE were able to considerably inhibit the excitatory contraction of the ileal smooth muscles induced by ACh. Costunolide,dehydrocostus lactone,santalol,muscone,emodin,chrysophanol,physcion,crotonoside,magnolol,and honokiol were also significantly effective against ACh-induced ileal smooth muscle contraction. Conclusions WCA,EE,WE,and their active ingredients may help to promote intestinal smooth muscle relaxation by blocking the binding of the M3 receptor on the membrane of ileal smooth muscle with ACh.

Clinical observation of Gushen antai pill combined with heparin sodium in the treatment of anticardiolipin antibody-positive recurrent abortion / 中国药房

OBJECTIVE To investigate the clinical efficacy of Gushen antai pills combined with heparin sodium in the treatment of antiphospholipin antibody （ACA）-positive recurrent abortion. METHODS A total of 203 ACA-positive recurrent abortion patients were randomly divided into control group （n＝101） and combination treatment group （n＝102）. Control group was additionally treated with heparin sodium on basis of basic treatment， and combination treatment group was additionally treated with Gushen antai pills on the basis of control group. Serum samples were collected from patients， the levels of interleukin 6 （IL- 6）， tumor necrosis factor α （TNF-α）， cyclooxygenase 2 （COX-2）， β-human chorionic gonadotropin （β-HCG） and ACA were detected by enzyme-linked immunosorbent assay. The antibody-negative conversion rate was calculated， the clinical efficacy of the patient was observed， and the occurrence of adverse drug reactions was recorded. RESULTS After treatment， the pregnancy success rate and antibody-negative conversion rate of combination treatment group were significantly higher than those in the control group （P＜0.05）， and the abortion rate was significantly lower than that in the control group （P＜0.05）. Compared with before treatment， serum levels of IL-6， TNF-α and ACA in 2 groups were decreased significantly （P＜0.05）， while the levels of COX-2 and β-HCG were increased significantly （P＜0.05）； the changes of above indexes in combination treatment group were more significant（P＜0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups（P＞0.05）. CONCLUSIONS Gushen antai pills can maintain high expression of β-HCG， reduce the level of ACA and improve immune microenvironment in patients with ACA-positive recurrent abortion by increasing the serum level of COX-2 and decreasing the serum level of IL-6， so as to increase the success rate of pregnancy.

Effects of modified Zhujing Pill on mitochondrial dynamics related protein in mice with form deprivation myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effects of modified Zhujing Pill on the mitochondrion structure and dynamin-related protein of retinal pigment epithelial cells(RPEs)in mice with form deprivation myopia.METHODS: 3-week-old C57BL/6J mice were randomly divided into control group, model group and Chinese medicine group, with 10 mice in each group. Myopia model of the right eye of mice was established by means of form deprivation in model and Chinese medicine groups. After 4wk, the Chinese medicine group were given intragastric administration of modified Zhujing Pill suspension 0.546g/(kg·d)(0.2mL/d)for 4wk, and same amount of saline was given to mice in other groups at the same time of modeling. The axial length and diopter of the right eye of the mouse were measured before and after the experiment by A-ultrasound and a strip retinoscope respectively. At the end of the experiment, the mitochondrial ultrastructure of RPEs was observed by transmission electron microscope. Western blot, and real-time fluorescent quantitative PCR(q-PCR)were used to detect quantitative and gene expression of mitofusin 1(MFN1), optic atrophy 1(OPA1), and dynamin-related protein 1(DRP1)in retinal tissues respectively.RESULTS: At the beginning of the experiment, there was no statistically significant difference in axial length and diopter of the right eye of the mouse in control, model and Chinese medicine groups(P&#x003E;0.05). At the end of the experiment, compared with the control group, the mice in the model group and the Chinese medicine group had lower diopter and continuously prolonged axial length(all P&#x003C;0.05), while the mice in the Chinese medicine group had significantly shorter axial length and higher diopter than the model group(all P&#x003C;0.05). Western blot and q-PCR results showed that the relative expression of MFN1 and OPA1 decreased and DRP1 increased in both the model group and the Chinese medicine group compared with the control group(all P&#x003C;0.05), and the relative expression of MFN1 and OPA1 increased in the Chinese medicine group compared with the model group(all P&#x003C;0.05). The electron microscopic results showed that the mitochondria in the right retina of the mice were only mildly swollen in the Chinese medicine group, while the mitochondria in the model group were obviously swollen and disordered and empty.CONCLUSION: Modified Zhujing Pill could protect the retinal mitochondria by regulating the key proteins of mitochondrial dynamics(MFN1, OPA1, and DRP1), and it has a protective effect on the retina of axial myopic mice.

The effect and mechanism of Xihuang pill inhibits the formation of vasculogenic mimicry in human glioblastoma cells by down-regulating HIF-1α/VEGFA/VEGFR2 signaling pathway / 药学学报

Our studies were aimed to explore the effect and mechanism of the inhibition of the formation of vasculogenic mimicry (VM) in human glioblastoma cells by Xihuang pill (XHP) medicated serum through regulating the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway. The medicated serum of XHP was prepared by gavage for 7 days to male SD rats (approval number of animal experiment ethics: 202105A051). The hypoxia model of U251 cells was established using 200 μmol·L-1 of CoCl2. After treatment with XHP-medicated serum, cell viability and proliferation of U251 cells were detected by CCK-8 and cell cloning experiment. Cell apoptosis and cell cycle of U251 cells were determined by flow cytometry. Cell migration and invasion were evaluated by wound healing and Transwell invasion assay. The formation of VM was assessed by three-dimensional cell culture of U251 cells. The protein expression levels of HIF-1α, VEGFA, VEGFR2, phosphorylated-VEGFR2 (p-VEGFR2), vascular endothelial-cadherin (VE-cadherin), Eph receptor tyrosine kinases A2 (EphA2), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 14 (MMP14) and laminin γ2 in U251 cells were detected by Western blot. The results showed that 10% XHP-medicated serum had little effect on the cell viability, proliferation, apoptosis and cell cycle of U251 cells under hypoxia. Compared with the model group, 10% XHP-medicated serum at 1.0, 1.5 and 2.0 h significantly decreased the migration rate (P < 0.01) and the number of invading U251 cells (P < 0.01). 10% XHP-medicated serum at 2.0 h significantly suppressed the formation of VM tubular structures in U251 cells under the condition of hypoxia (P < 0.01). Western blot experiment showed that 10% XHP-medicated serum significantly down-regulated the expression of HIF-1α, VEGFA, phospho-VEGFR2, VE-cadherin, EphA2 and MMP14 proteins (P < 0.05). In conclusion, XHP could inhibit the formation of VM in human glioblastoma U251 cells to suppress the angiogenesis by down-regulating the HIF-1α/VEGFA/VEGFR2 signaling pathway.

Mechanism of Shexiang Baoxin pill in the treatment of atherosclerosis based on network pharmacology / 药学实践杂志

Objective To study the mechanism of Shexiang Baoxin pill in the treatment of atherosclerosis, and to provide a theoretical basis for long-term clinical application. Methods The chemical components and targets of Shexiang Baoxin pill were collected and screened by TCMSP, TCMID, ETCM and BATMAN databases. The targets related to atherosclerosis were collected and screened by DisGeNet, OMIM, TCMSP, DrugBank and DisGeNet. Drug-compound target network and protein-protein interaction network were constructed. Go and KEGG enrichment analysis of Shexiang Baoxin pill in the treatment of atherosclerosis were carried out on MetaScape platform. Results 114 potential therapeutic components of Shexiang Baoxin pill on atherosclerosis were selected, corresponding to 175 targets. The results of network analysis showed that the main active components of Shexiang Baoxin pill were chenodeoxycholic acid, ursodeoxycholic acid, cinnamaldehyde and ginsenoside Rb1. The results of pathway enrichment showed that the anti-atherosclerotic mechanism of Shexiang Baoxin pill was related to the regulation of immunity, inflammation, and metabolism. Conclusion The active components of Shexiang Baoxin pill could act on ALB, INS, AKT1, ACTB, TNF, IL-6 and other targets, regulating multiple pathways to achieve the therapeutic effect on atherosclerosis.

Shire Biqing Pill in Treatment of Rheumatoid Arthritis with Damp-heat Obstruction Syndrome and Its Effect on OPG/RANKL/RANK Signaling Pathway and TNF-α / 中国实验方剂学杂志

ObjectiveTo study the clinical efficacy of Shire Biqing pill in the treatment of rheumatoid arthritis （damp-heat obstruction syndrome） and its effect on the expression of serum osteoprotegerin （OPG）， nuclear factor-κB receptor activating factor ligand （RANKL）， and tumor necrosis factor-α （TNF-α）， and to explore its mechanism from the perspective of bone destruction. MethodPatients with rheumatoid arthritis （damp-heat obstruction syndrome） were randomly divided into two groups， with 36 patients in each group. The control group was treated with methotrexate tablets and celecoxib capsule， while the treatment group was treated with Shire Biqing pill based on the control group. The treatment period was 3 months. The pain visual analogue scale （VAS） score， joint tenderness number， joint swelling number， disease activity score （DAS28-ESR）， traditional Chinese medicine （TCM） symptom quantitative score， and related adverse reactions were recorded before and after treatment， and the peripheral serum OPG， RANKL， TNF-α， erythrocyte sedimentation rate （ESR）， and Creactive protein （CRP） were detected. ResultAfter treatment， the total effective rate was 88.57% （31/35） in the treatment group and 79.41% （27/34） in the control group. The total effective rate of the treatment group was higher than that of the control group （Z=-2.089， P<0.05）. The pain VAS score， joint tenderness number， joint swelling number， and DAS28-ESR of the two groups were significantly lower than those before treatment （P<0.05）， and the pain VAS score， joint tenderness number， joint swelling number， and DAS28-ESR of the treatment group were significantly better than those of the control group after treatment （P<0.05）. Compared with that before treatment， the TCM symptom quantitative score in the two groups decreased significantly （P<0.05）， and the decrease was more obvious in the treatment group than in the control group （P<0.05）. Compared with those before treatment， the levels of RANKL， TNF-α， ESR， and CRP in the two groups decreased and the level of OPG increased （P<0.05）， and the changes in the treatment group were more obvious that in the control group （P<0.05）. There were no serious adverse events or serious adverse reactions during this clinical trial. ConclusionShire Biqing pill can effectively improve the clinical symptoms of rheumatoid arthritis （damp-heat obstruction syndrome） with good safety. Shire Biqing pill effectively regulate the OPG/RANKL/RANK system and reduce the pro-inflammatory factor TNF-α， which may be its mechanism in the intervention in rheumatoid arthritis bone destruction.

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE-/-LDLR-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Therapeutic Efficacy of Shexiang Baoxin Pill Combined with Exercise in Patients with Heart Failure with Preserved Ejection Fraction: A Single-Center, Double-Blind, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evaluate the therapeutic efficacy of Shexiang Baoxin Pill combined with exercise in heart failure patients with preserved ejection fraction (HFpEF).@*METHODS@#Sixty patients with HFpEF were randomly divided into group A (n=20), receiving Shexiang Baoxin Pill combined with home-based exercise training based on conventional drugs for 12 weeks; group B (n=20), receiving conventional drugs combined with home-based exercise training for 12 weeks; and group C (n=20), receiving conventional drug treatment only. Peak oxygen uptake (peakVO2), anaerobic threshold (AT), 6-min walking test (6MWT), Pittsburgh Sleep Quality Index (PSQI), and SF-36 questionnaire (SF-36) results before and after treatment were compared among groups.@*RESULTS@#After the 12-week intervention, patients in group C showed significant declines in peakVO2, AT, 6MWT, PSQI, and SF-36 compared with pre-treatment (P<0.01), while groups A and B both showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 results compared with pre-treatment (P<0.01). Compared with group C, patients in groups A and B showed significant improvements in peakVO2, AT, 6MWT, PSQI, and SF-36 (P<0.01). In addition, patients in group A showed more significant improvements in physical function, role-physical, vitality, and mental health scores on the SF-36 questionnaire, and PSQI scores than those in group B (P<0.01).@*CONCLUSIONS@#Exercise training improved exercise tolerance, sleep quality and quality of life (QoL) in patients with HFpEF. Notably, Shexiang Baoxin Pill played an active role in sleep quality and QoL of patients with HFpEF. (The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2100054322)).

Clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome / 中华肝脏病杂志

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.