Efficacy of Tounongsan decoction on pyogenic liver abscess: network pharmacology and clinical trial validation.

OBJECTIVE: To elucidate the molecular mechanisms governing the effect of Tounongsan decoction (, TNS) on the pyogenic liver abscess. METHODS: Based on oral bioavailability and drug-likeness, the main active components of TNS were screened using the Traditional Chinese Medicine Systems Pharmacology platform. The GeneCard and UniProt databases were used to establish a database of pyogenic liver abscess targets. The interactive network map of drug-ingredients-target-disease was constructed using Cytoscape software (Version 3.7.2). A protein-protein interaction network was constructed using the STRING database, and the related protein interaction relationships were analyzed. biological process of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the core targets. Finally, a clinical trial was performed to verify the reliability of the network pharmacology. RESULTS: Forty active components of TNS decoction were obtained, and 61 potential targets and 11 proteins were identified. Pathways involved in the treatment of pyogenic liver abscess include the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT), advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), and tumor necrosis factor (TNF) signaling pathways. The results of network pharmacology analysis combined with clinical trials validated that TNS decoction could alleviate the inflammatory response of pyogenic liver abscesses by decreasing interleukin 6 (IL-6) levels. CONCLUSIONS: TNS decoction has the characteristics of being multi-system, multi-component, and multi-target. Active ingredients in TNS, such as quercetin, kaempferol, fisetin, and ß-sitosterol, have strong potential to be candidate drugs for treating pyogenic liver abscesses. The possible mechanism of TSN decoction includes regulating immune and inflammatory responses and reducing IL-6 production to control inflammatory development.

The Effect of Modified Shugan Dingji Decoction （疏肝定悸汤） on the Occurrence of Endpoint Events in Patients with Paroxysmal Atrial Fibrillation of Liver Constraint and Qi Stagnation： A Retrospective Cohort Study / 中医杂志

ObjectiveTo retrospectively analyze the effect of modified Shugan Dingji Decoction （疏肝定悸汤） on the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation. MethodsA retrospective cohort study was conducted using the electronic medical record database of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine to screen and include patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation from January 1st， 2018， to December 31th， 2021. The included patients were divided into an exposure group and a non-exposure group， each consisting of 100 cases， based on whether they received modified Shugan Dingji Decoction. General information of the patients including age， gender， body mass index， duration of illness and comorbidities， medication history， cardiac structure and function indicators such as left atrial diameter， left ventricular end-diastolic diameter， stroke volume and ejection fraction， and the occurrence of endpoint events assessed through 24-hour dynamic electrocardiography or electrocardiogram to determine the recurrence of paroxysmal atrial fibrillation were collected. Kaplan-Meier （K-M） curves and Log-Rank tests were used to conduct survival analysis on the occurrence of endpoint events in the two groups of patients. Univariate and multivariate Cox regression analyses were used to analyze the impact of various factors on entry into endpoint events. Additionally， a safety assessment was performed by comparing liver and kidney function indicators before and after treatment. ResultsIn the non-exposure group， a total of 49 cases （49.0%） experienced endpoint events， while in the exposure group， there were 26 cases （26.0%）. The Log-rank test indicated significant difference between the two groups （χ2=11.211， P=0.001）. Univariate Cox regression analysis showed that age， duration of illness， hypertension， diabetes， chronic heart failure， left atrial diameter， stroke volume， and the use of modified Shugan Dingji Decoction may be the influencing factors for the occurrence of endpoint events in patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation （P＜0.05 or P＜0.01）. Multivariate Cox regression analysis showed that the risk of endpoint events in the exposure group was significantly lower than that in the non-exposure group （P＜0.01）. Patients with a duration of illness ＞12 months had a significantly higher risk of endpoint events compared to those with a duration of illness ≤12 months （P＜0.01）. Patients without concomitant hypertension had a lower risk of endpoint events compared to those with hypertension （P＜0.05）. Patients with left atrial diameter ＞40 mm had significantly higher risk of endpoint events than those with left atrial diameter ≤40 mm （P＜0.01）. There was no statistically significant difference in liver and kidney function indicators between the two groups before and after treatment （P＞0.05）. ConclusionThe use of modified Shugan Dingji Decoction is a protective factor for patients with paroxysmal atrial fibrillation of liver constraint and qi stagnation， which can help to reduce the recurrence and progression of atrial fibrillation. Long duration of illness， concomitant hypertension， and enlarged left atrial diameter are risk factors for patients to experience endpoint events.

Honeybee symbiont Bombella apis could restore larval-to-pupal transition disrupted by antibiotic treatment.

Numerous studies have demonstrated the vital roles of gut microbes in the health, immunity, nutrient metabolism, and behavior of adult worker honeybees. However, a few studies have been conducted on gut microbiota associated with the larval stage of honeybees. In the present study, we explored the role of a gut bacterium in larval development and larval-pupal transition in the Asian honeybee, Apis cerana. First, our examination of gut microbial profiling showed that Bombella apis, a larvae-associated bacterium, was the most dominant bacterium colonized in the fifth instar larvae. Second, we demonstrated that tetracycline, an antibiotic used to treat a honeybee bacterial brood disease, could cause the complete depletion of gut bacteria. This antibiotic-induced gut microbiome depletion in turn, significantly impacted the survivorship, pupation rate and emergence rate of the treated larvae. Furthermore, our analysis of gene expression pattens revealed noteworthy changes in key genes. The expression of genes responsible for encoding storage proteins vitellogenin (vg) and major royal jelly protein 1 (mrjp1) was significantly down-regulated in the tetracycline-treated larvae. Concurrently, the expression of krüppel homolog 1(kr-h1), a pivotal gene in endocrine signaling, increased, whilethe expression of broad-complex (br-c) gene that plays a key role in the ecdysone regulation decreased. These alterations indicated a disruption in the coordination of juvenile hormone and ecdysteroid synthesis. Finally, we cultivated B. apis isolated from the fifth instar worker larval of A. cerana and fed tetracycline-treated larvae with a diet replenished by B. apis. This intervention resulted in a significant improvement in the pupation rate, emergence rate, and overall survival rate of the treated larvae. Our findings demonstrate the positive impact of B. apis on honeybee larvae development, providing new evidence of the functional capacities of gut microbes in honeybee growth and development.

Efficacy of Lushi Runzao decoction on ameliorating Sjogren's syndrome: a network pharmacology and experimental verification-based study.

OBJECTIVE: To investigate the possible mechanism underlying the effect of the Lushi Runzao decoction on Sjogren's syndrome using network pharmacology and to verify the mechanismsanimal experiments. METHODS: Available biological data on each drug in the Lushi Runzao decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the target proteins of Sjogren's syndrome were retrieved from the GeneCards database. Information regarding Sjogren's syndrome and the targets of the drugs were compared to obtain overlapping elements. This information was imported into the STRING platform to obtain a protein-protein interaction network diagram, following which a "component-target" network diagram was constructed using screened drug components and target informationCytoscape software. The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal experiments. RESULTS: The Lushi Runzao decoction ameliorated Sjogren's syndrome mainly by influencing tumor necrosis factor as well as certain cytokines and chemokines. The decoction also influenced the interleukin-17 and advanced glycosylation end products (AGE)-receptor for AGE signaling pathways. CONCLUSION: The Lushi Runzao decoction ameliorates Sjogren's syndromemultiple targets and multiple signaling pathways. Network pharmacology is useful for making a comprehensive prediction regarding the efficacy of the Lushi Runzao decoction, and this information may be helpful in clinical research.

Efficacy of Qifu Lizhong enema prescription on intestinal mucosal tight junction function modulation of ulcerative colitis rat model.

OBJECTIVE: To investigate the efficacy and mechanism of Qifu Lizhong enema prescription(, QFLZ) on intervening ulcerative colitis (UC) rat model with TCM spleen and kidney insufficiency syndrome. METHODS: Seventy-two male Sprague-Dawley rats were randomly assigned to six groups: normal model, mesalazine, and QFLZ high, medium, and low dose groups, each with 12 rats. After 3 d of adaptation feeding, all groups except the normal group were induced using rhubarb decoction in combination with trinitrobenzene sulfonic acid (TNBS)/55 % ethanol to establish a UC rat model. Following successful modeling, the normal and model groups received daily saline enema, while the Chinese medicine and Western medicine groups received daily QFLZ and Mesalazine enema for 2 weeks respectively. The disease activity index score, hematoxylin and eosin staining, immunohistochemistry, and Western blotting were used to determine the expression of claudin 1, claudin 2, zonula occludens-1 protein (ZO-1), and F-actin proteins in each rat colon tissue following treatment. RESULTS: QFLZ significantly alleviated the structural disorganization in the form of epithelial glands in the intestinal mucosa of rats with UC and retarded the progression of the disease. The intestinal mucosal epithelial cells of UC rats showed decreased expression of claudin 1, ZO-1, F-actin ( 0.05), claudin 2 appeared elevated ( 0.05), which resulted in impaired TJ. Treatment with QFLZ resulted in elevated expression of claudin 1 ( 0.05), ZO-1 ( 0.05) and F-actin ( 0.05) and decreased expression of claudin 2 ( 0.05), which allowed for repair of the intestinal mucosal TJ, which in turn served as a treatment for UC. CONCLUSIONS: The mechanism of repairing TJ function and repairing the intestinal mucosal barrier by QFLZ may be associated with up-regulation of claudin 1, ZO-1, and F-actin levels, and down-regulation of claudin 2 expression level.

Traditional Chinese Medicine in Treatment of Ulcerative Colitis Based on NLRP3 Inflammasome： A Review / 中国实验方剂学杂志

Ulcerative colitis （UC） is a common inflammatory bowel disease （IBD） in clinical practice， characterized by symptoms such as abdominal pain， diarrhea， and bloody mucus in the stool. It is difficult to cure and has a high recurrence rate. The pathogenesis of UC is related to abnormal immune response， oxidative stress in intestinal tissues， and inflammatory reactions. As reported， the abnormal activation of the NOD-like receptor pyrin domain-containing protein 3 （NLRP3） inflammasome is involved in the pathological process of UC. This activation triggers pathological mechanisms such as oxidative stress， pyroptosis， and inflammation in intestinal epithelial cells. Therefore， blocking the abnormal activation of NLRP3 is beneficial for alleviating UC. Currently， western medicine treatment for UC mainly includes salicylic acid derivatives， corticosteroids， and biologics， but the overall efficacy is unsatisfactory. Traditional Chinese medicine （TCM） treatment of this disease has the advantages of significant efficacy and low recurrence rate. In recent years， great advances have been made in the basic research of using TCM methods to treat UC. Studies have found that TCM intervention targeting the NLRP3 inflammasome can significantly promote intestinal mucosal healing and treat UC， and the mechanism of action involves multiple targets， levels， and pathways. This article summarized the experimental research on the impact of TCM targeting the NLRP3 inflammasome on UC in recent years， and found that NLRP3 interacted with factors such as Caspase-1 and nuclear factor-κB （NF-κB）， thereby promoting the release of pro-inflammatory factors and cell pyroptosis in intestinal epithelial cells. This activation triggered oxidative stress， inflammatory reactions， and other pathological mechanisms. TCM acted on the NLRP3 inflammasome and its upstream and downstream factors to block the pathological process of UC， inhibit the pathological damage to the intestinal mucosa， and thereby alleviate colonic ulcers. The findings of this study provide a theoretical basis for the prevention and treatment of UC and further drug development.

Active Components in Chinese Medicinal Herbs Regulate Osteogenic Signaling Pathway in Treatment of Steroid-induced Osteonecrosis of Femoral Head： A Review / 中国实验方剂学杂志

As a threat to human health， steroid-induced osteonecrosis of femur head is a common refractory orthopedic disease mainly caused by glucocorticoids， with poor prognosis and unclear pathogenesis. Osteogenesis-associated signaling pathways play an important role in bone formation. Glucocorticoid-induced abnormal activation and transport of these signaling pathways lead to abnormal differentiation of bone marrow mesenchymal stem cells， dysfunction of bone metabolism， and osteogenesis disorders， which may be the main reasons for the occurrence and development of steroid-induced osteonecrosis of femur head. Bone formation and remodeling need the participation of bone marrow mesenchymal stem cells， which are stem cells characterized by continuous self-renewal and differentiation. The key to strengthening bone remodeling is to improve the osteogenic differentiation capacity， which is the key point to inhibit bone resorption and prevent bone marrow mesenchymal stem cells from differentiating into osteoclasts. Traditional Chinese medicine （TCM） has been used in the treatment of osteonecrosis in ancient times. It is recorded in the Treasury of Words on Materia Medica （《本草汇编》） that "The deficiency in the lower energizer cannot be tonified without Eucommiae Cortexz.The soreness in lower legs cannot be alleviated without Eucommiae Cortex...The pain in the waist and knee cannot be relieved without Eucommiae Cortex...Tonifying liver and invigorating kidney， Eucommiae Cortex is an essential medicine." This indicates that ancient physicians have already begun to use the liver-tonifying， kidney-invigorating， and sinew-bone-strengthening effects of Eucommiae Cortex for the treatment of osteonecrosis. As the national support for the development of TCM strengthens， increasing studies have been conducted on the TCM prevention and treatment of steroid-induced osteonecrosis of femur head. Studies have suggested that Chinese medicinal herbs can exert a positive effect on the differentiation of bone marrow mesenchymal stem cells by affecting targeted signaling molecules， and promote osteogenesis and bone defect repair， thus combating the occurrence and development of steroid-induced osteonecrosis of femur head. The regulation of osteogenic signaling pathway by Chinese medicines to prevent steroid-induced osteonecrosis of femoral head has become a hot research topic. This article reviews the studies about the prevention and treatment of steroid-induced osteonecrosis of femur head with the active components in Chinese medicinal herbs by regulating osteogenic signaling pathways. We then explore the mechanism of the active components in promoting the differentiation of bone marrow mesenchymal stem cells into osteoblasts and inhibiting their differentiation into osteoclasts to facilitate bone formation， aiming to provide a reference for the further study of treating steroid-induced osteonecrosis of femoral head with Chinese medicinal herbs.

Developing process and term analysis of WFAS standard: General Requirements for the Risk Control in the Safe Use of Acupuncture / 中国针灸

In order to promote the application of WFAS standard, General Requirements for the Risk Control in the Safe Use of Acupuncture and the safe practice of acupuncture technology worldwide, the paper introduces the developing process and main contents of this standard, explains the developing purpose, scope, ideas, methods and basis, and analyzes the definition of the relevant terms. Through strictly complied with the development procedure of standard, the terms related to acupuncture risk in this standard are defined. The connotations of 5 special terms are clarified, i.e. "acupuncture risks" "adverse events of acupuncture" "adverse reactions of acupuncture" "acupuncture accidents" and "acupuncture negligence". The range, rank, control flow and source of risk, as well as the control measures are determined. The standard extracts the underlying common problems and basic requirement of the safe practice of acupuncture so as to lay a framework for the development of the relevant technical standards of acupuncture.

Mechanism of Zhibai Dihuang decotion in treating postmenopausal osteoporosis / 药学学报

In this study, the ovarian surgery (ovariectomy, OVX) was used to establish the osteoporosis mice model of primary menstruation, in order to evaluate the protective effects and mechanisms of Zhibai Dihuang decotion on postmenopausal osteoporosis (PMOP). The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Jinan University (number: 20210315-03), in compliance with the Institutional Animal Care Guidelines. C57BL/6 mice were divided into five groups, including Sham group, OVX group, low (32 g·kg-1·day-1) and high dose (64 g·kg-1·day-1) of Zhibai Dihuang decotion groups, positive drug group (alendronate, 9.9 mg·kg-1·q3d). After modeling, mice were given medication intervention for 8 weeks, and then femoral and tibial tissues were taken to detect indicators such as bone microstructure, bone resorption, and oxidative stress. The experimental results showed that after Zhibai Dihuang decotion administration, the bone microstructure damage caused by OVX surgery was alleviated, and the relevant parameters bone mineral density (BMD), bone volume/total volume (BV/TV), trabecular number (Tb. N) and connectivity density (Conn. D) both significantly increased. At the same time, the number of TRAP positive osteoclasts decreased significantly, and the levels of proteins and genes related to osteoclast differentiation decreased, indicating that Zhibai Dihuang decoction could inhibit the increased activity of osteoclast caused by OVX. Afterwards, network pharmacology was used to construct the active compound action target network of Zhibai Dihuang decotion, and it was found that the target genes of its active ingredients were closely related to the oxidative stress pathway. Finally, the detection results of oxidative stress levels in bone tissues showed that after treatment with Zhibai Dihuang decotion, the levels of oxidative stress products 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) in bone tissues of mice significantly decreased, while the levels of antioxidant stress substance L-glutathione (GSH) increased. These above results indicated that Zhibai Dihuang decotion can regulate the level of oxidative stress in the body and inhibit osteoclast activity, which played a therapeutic role in PMOP, as well as provided theoretical basis for the prevention and treatment of PMOP with traditional Chinese medicine.

Progress of epidermal growth factor receptor-tyrosine kinase inhibitors in treatment of operable non-small cell lung cancer / 肿瘤研究与临床

Patients with operable non-small cell lung cancer (NSCLC) receiving neoadjuvant or adjuvant chemotherapy have a very limited improvement in 5-year survival rate. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) have made a breakthrough in the treatment of EGFR-mutant advanced NSCLC, which shed light for the exploration of perioperative targeted therapy in NSCLC patients. Significant progress has been made in the research of targeted therapy of the first and third generation EGFR-TKI in perioperative patients. The availability of novel potent and less toxic targeted therapy has brought new treatments for the operable NSCLC. This article reviews the progress and existing problems of adjuvant and neoadjuvant targeted therapy in NSCLC harboring EGFR mutation.

Systematic Review on Safety of Chinese Medicines Combined with Tripterygium wilfordii Preparations in Treatment of Rheumatoid Arthritis and Exploration on Underlying Network Regulatory Mechanisms of Enhancing Efficacy and Reducing Toxicity / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Chinese medicines combined with Tripterygium wilfordii polyglycoside tablets/Tripterygium wilfordii tablets （TWPT/TWT） in the treatment of rheumatoid arthritis （RA）， and to explore the network regulatory mechanisms of enhancing efficacy and reducing toxicity of commonly used combination regimes. MethodThe literature involving the adverse reactions of TWPT/TWT in treating RA was searched and collected from three Chinese databases （CNKI， Wanfang Data， VIP） and three English databases （PubMed， Cochrane Library， Embase） from the inception of the databases to July 2021. All studies were assessed by the Cochrane risk of bias tool， and the data were extracted and analyzed by Stata 15.0. Furthermore， Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine 2.0 （TCMIP v2.0，http：//www.tcmip.cn/） was used to construct a "drug target-symptom gene of efficacy and toxicity" interaction network， to explore the underlying network regulatory mechanisms of enhancing efficacy and reducing toxicity of common T. wilfordii preparation combinations. ResultA total of 2 132 articles on Chinese medicines combined with TWPT/TWT in the treatment of RA were retrieved， and 18 of them were finally included. The systematic review showed that the adverse reactions of TWPT/TWT against RA mainly occurred in the digestive system， blood system， and reproductive system， of which digestive system had the highest incidence of damages. However， the combination with Chinese medicines effectively alleviated the adverse reactions caused by TWPT/TWT ［RR （95% CI）=0.45 （0.30， 0.66）， P<0.01］. In addition， the subgroup analysis indicated that the age of RA patients， course of disease， combination regimen， medication dosage and duration of treatment all affected the occurrence of adverse reactions of TWPT/TWT. It was found in clinical studies that total glucosides of paeony （TGP） and TWPT/TWT was most widely combined， and the effect of TGP in reducing TWPT/TWT-induced hepatotoxicity was also more significant than that of other Chinese medicines. Moreover， taking this combination regime as an example， this paper explored the "efficacy-toxicity" association mechanisms of TGP-TWPT/TWT against RA. The "drug target-symptom gene of efficacy and toxicity" interaction network revealed that the core network targets of TGP-TWPT/TWT enhanced efficacy and reduced toxicity mainly through regulating immunity-inflammation-related pathways， metabolic pathways and cell signal transduction. Especially， interleukin-4 （IL-4） and interleukin-13 （IL-13）， which were involved in the "immunity-inflammation" module， were the common targets of TGP-TWPT/TWT to enhance efficacy and reduce toxicity. The endogenous sterols， bile acids and bile salts， insulin secretion and other metabolic pathways in the "body metabolism" module were closely associated with the mechanisms of TWPT/TWT inducing hepatotoxicity and TGP reducing hepatotoxicity. While cell function regulation pathways， such as stem cell factor （SCF）/tyrosine kinase receptor （KIT） signaling pathway and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）signaling pathway were involved in both anti-RA effects and hepatotoxicity of TWPT/TWT. ConclusionClinical application of suitable Chinese medicines combined with TWPT/TWT in the treatment of RA can effectively improve the rheumatism and reduce the adverse reactions of TWPT/TWT， and TGP-TWPT/TWT has the most significant toxicity-reducing effect. Further biological network-based investigation indicates that the toxicity-reducing mechanism of TGP-TWPT/TWT may be related to the regulation of interleukin signaling pathway and bile acid metabolism pathway， and the synergistic efficacy-enhancing effect of the combination may be achieved by acting on interleukin signaling pathway and cell function regulation pathway.

Exploration on "Efficacy-toxicity" Association Mechanisms of Tripterygium wilfordii Polyglycoside Tablets Against Rheumatoid Arthritis Based on Multi-omics Integrated Regulatory Network / 中国实验方剂学杂志

ObjectiveTo explore the "efficacy-toxicity" association mechanisms of Tripterygium wilfordii polyglycoside tablets （TWPT） by establishing and analyzing an interaction network associated with the clinical efficacy of TWPT in the treatment of rheumatoid arthritis （RA） and TWPT-induced liver injury. MethodOn the basis of the TWPT efficacy-related gene expression profile and TWPT-induced liver injury-related protein expression profile which were both obtained from our clinical cohorts， the "efficacy-toxicity" association network of TWPT was constructed， and the key network targets were identified by calculating the topological values of the nodes， including the degree， closeness and betweenness. After that， the biological functions and pathways of the key network targets were investigated by enrichment analysis. ResultA total of 119 differentially expressed genes （58 up-regulated and 61 down-regulated） between RA patients with TWPT well and weak response were identified as TWPT efficacy-related genes by clinical transcriptomics， and 49 differentially expressed proteins （36 up-regulated and 13 down-regulated） were demonstrated to be TWPT-induced liver injury-related proteins by clinical proteomics. In addition， the clinical symptom enrichment analysis indicated that the TWPT efficacy-related genes were significantly associated with various clinical symptoms of arthralgia in traditional Chinese medicine and clinical phenotypes of modern medicine， and most of the TWPT-induced liver injury-related proteins were involved in digestive system abnormalities. Therefore， the aforementioned multi-omics data represented the main clinical symptoms of TWPT treating RA and inducing liver injury. Mechanically， the "efficacy-toxicity" association network revealed that both TWPT efficacy-related genes and TWPT-induced liver injury-related core proteins were involved in the "immune-inflammatory" imbalance， especially playing an important role in neutrophil degranulation， complement cascade reaction， and immune-inflammatory response mediated by protein post-translational modification. Notably， the above genes and proteins were also enriched in various signaling pathways related to cell proliferation and cell cycle regulation， such as RAS and mitogen-activated protein kinase （MAPK） signaling pathway， and in several liver functional processes， such as glycogen metabolism and redox reaction. ConclusionThis study systematically explained the "efficacy-toxicity" association characteristics and molecular mechanisms of TWPT by applying a research strategy integrating clinical phenomics， transcriptomics and proteomics， laying a good data foundation for exploring the "efficacy enhancing and toxicity-reducing" mechanisms of TWPT.

Research progress on vesicles from Chinese medicinal herbs / 浙江大学学报·医学版

Vesicles derived from Chinese medicinal herbs (VCMH) are nano-vesicular entities released by the cells of Chinese medicinal herbs. VCMHs have various biological effects and targeting characteristics, and their component chemicals and functional activities are closely related to the parent plant. VCMH differs from animal-derived vesicles in three ways: stability, specificity, and safety. There are a number of extraction and isolation techniques for VCMH, each with their own benefits and drawbacks, and there is no unified standard. When two or more approaches are used, high quantities of intact vesicles can be obtained more quickly and efficiently. The obtained VCMHs were systematically examined and evaluated. Firstly, they are generally saucer-shaped, cup-shaped or sphere, with particle size of 10-300 nm. Secondly, they contain lipids, proteins, nucleic acids and other active substances, and these components are an important part for intercellular information transfer. Finally, they mostly have good biocompatibility and low toxicity, with anti-inflammatory, antioxidant, anti-tumor and anti-fibrotic effects. As a new drug carrier, VCMHs have outstanding active targeting capabilities, and the capsule form can effectively preserve the drugs, considerably enhancing drug delivery efficiency and stability in vitro and in vivo. The modification of its vesicular structure by suitable physical or chemical means can further create more stable and precise drug carriers. This article reviews the extraction and purification techniques, activity evaluation and application of VCMH to provide information for further research and application of new active substances and targeted drug carriers.

A gradient-based discriminant analysis method for process quality control of carbonized TCM via Fourier transform near infrared spectroscopy: A case study on carbonized Typhae Pollen.

Carbonized traditional Chinese medicine (TCM) is a kind of distinctive traditional drug which has been widely used in various bleeding syndromes for over two thousand years, and most of them are still in clinical use. Although they share similar processing method: stir-frying, there are no specific quality standards and few quality control researches carried out on carbonized TCM up until now. Carbonized Typhae Pollen (CTP) is a typical carbonized TCM with efficacy of eliminating blood stasis and stanching bleeding. In this study, a novel process quality control model coupled with near infrared spectroscopy was established, called Gradient-based Discriminant Analysis method (GDA). Compared with conventional modeling methods (Convolutional Neural Network, Linear Discriminant Analysis, Standard Normal Variate-LDA), GDA model applied in fiber optic probe acquisition mode exhibited highest test accuracy (0.961), satisfactory correct identification (internal validation, 100%; external validation, 97.1%) and excellent model stability. This method provided a perfect guideline for process quality control of Carbonized TCM as well as ensured their clinical efficacy.

Realgar (α-As4S4) Treats Myelodysplastic Syndromes through Reducing DNA Hypermethylation / 中国结合医学杂志

DNA hypermethylation is an epigenetic modification that plays a critical role in the oncogenesis of myelodysplastic syndromes (MDS). Aberrant DNA methylation represses the transcription of promotors of tumor suppressor genes, inducing gene silencing. Realgar (α-As4S4) is a traditional medicine used for the treatment of various diseases in the ancient time. Realgar was reported to have efficacy for acute promyelocytic leukemia (APL). It has been demonstrated that realgar could efficiently reduce DNA hypermethylation of MDS. This review discusses the mechanisms of realgar on inhibiting DNA hypermethylation of MDS, as well as the species and metabolisms of arsenic in vivo.

Efficacy of Qizi Yusi Pill on Pregnancy Outcomes in Women of Advanced Reproductive Age: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To evalvate efficacy of Qizi Yusi Pills (QYP), a Chinese medicine compound preparation, on in vitro fertilization-embryo transfer (IVF-ET) in women of advanced reproductive age.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled trial was conducted from June 2018 to October 2019. A total of 124 patients were randomly allocated to either the QYP group or the placebo group using a stratified block randomization design, with 62 patients in each group. All patients completed controlled ovarian stimulation using a standard gonadotropin-releasing hormone agonist (GnRH-a) long protocol. As the QYP group, QYP was administered while the control group received placebo. QYP and placebo were administered for a total of 24 to 30 days from the day of GnRH-a pituitary downregulation to transvaginal oocyte retrieval. Both medications were taken orally at doses of 10 g three times each day. The primary outcome was cumulative pregnancy rate, and the secondary outcomes were periodic medication, follicular status, serum hormone and endometrial receptivity. Follow-up continued until 4 weeks after delivery. Maternal and neonatal complications, such as gestational diabetes, were also observed.@*RESULTS@#Overall, 119 patients completed the study, 60 in the QYP group and 59 in the placebo group. Per protocol (PP) analysis revealed that 6-month cumulative pregnancy rate in the QYP group was significantly higher than that in the placebo group [43.33% (26/60) vs. 25.42% (15/59), P=0.040). Additionally, more oocytes were retrieved from the QYP group than those from the placebo group (8.95 ± 3.12 vs. 7.85 ± 1.91, P=0.022). Moreover, the endometrial thickness of HCG day in the QYP group was significantly higher than that in the placebo group (11.78 ± 2.27 mm vs. 10.68 ± 2.07 mm, P=0.012). Maternal and neonatal complications between the two groups were not significantly different (P>0.05). Intention-to-treat analysis was in line with PP results.@*CONCLUSIONS@#QYP can enhance ovarian reserve capacity and ovarian response, and possibly promote endometrial receptivity. QYP effectively improves cumulative pregnancy rates in older patients (⩾35 years) undergoing IVF-ET. (Registration No. ChiCTR1800014427).

Problems in randomized controlled trial on acupuncture and moxibustion for migraine in the development of international standard of Guideline for Clinical Practice of Acupuncture and Moxibustion: Migraine / 中国针灸

Regarding the development of international standard of Guideline for Clinical Practice of Acupuncture and Moxibustion: Migraine, the existing problems of the design and methodology of randomized controlled trial (RCT) on acupuncture and moxibustion for migraine were summarized in views of participant, intervention, control, outcome and study design. Four directions need to be further explored, (1) research of adolescent migraine, special subtype of migraine and migraine in a special population; (2) research of the immediate analgesic effect of acupuncture and moxibuation at the attack stage of migraine and the therapeutic effect of migraine at each stage; (3) research on safety and health economics; (4) clinical trial registration of acupuncture and moxibustion. In study, the target population should be further determined and specialized, the diagnosis criteria of western medicine and traditional Chinese medicine be generalized and concentrated, the staging and type division of disease be accurate, the intervention procedure be integrated, the control design be rationalized, the outcomes be validated, and the description of randomization and blinding be clarified.

WU Xu's experience of sequential therapy for peripheral facial paralysis / 中国针灸

The paper introduces professor WU Xu 's experience of sequential therapy for peripheral facial paralysis. The sequential therapy refers to a staging treatment, but not rigidly adheres to it. With this therapy, the acupuncture- moxibustion regimen is modified flexibly in line with the specific symptoms of illness. At the acute phase of peripheral facial paralysis, warm acupuncture at Wangu (GB 12) is predominated and electroacupuncture is not recommended at the acupoints on the face. At the recovery phase, warm acupuncture at Zusanli (ST 36) is the main therapy and electroacupuncture is applied to the acupoints on the face appropriately. Besides, for the intractable case, the tapping technique with plum-blossom needle or skin needle should be combined and exerted in the local affected region. At the sequelae phase, in order to shorten the duration of illness, depending on the different types of facial paralysis, i.e. stiffness type, spasmodic type and flaccid type, the corresponding needling techniques are provided, i.e. bloodletting and moxibustion, strong stimulation with contralateral acupuncture and the technique for promoting the governor vessel and warming up yang.

Mechanism of Tibetan medicine Pterocephalus hookeri extract in treatment of rheumatoid arthritis based on serum metabonomics / 中国中药杂志

Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF/MS) was used to investigate the effect of Pterocephalus hookeri on serum metabolism of adjuvant arthritis(AA) model rats induced by complete Freund's adjuvant. After the AA model was properly induced, the serum of rats was collected 30 days after treatment. UPLC-Q-TOF-MS chromatograms were collected and analyzed by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The results revealed that compared with the control group, the model group showed increased content of 12 biomarkers in the serum(P<0.05) and reduced content of the other nine biomarkers(P<0.05). P. hookeri extract could recover the above-mentioned 19 biomarkers to a certain range. Pathway enrichment showed that these markers mainly involved eight metabolic pathways, including valine, leucine, and isoleucine degradation, arachidonic acid metabolism, arginine and proline metabolism, glycerol phospholipid metabolism, primary bile acid biosynthesis, bile acid biosynthesis, tryptophan metabolism, and unsaturated fatty acid biosynthesis. The findings of this study demonstrate that P. hookeri extract can regulate metabolic disorders and promote the regression of metabolic phenotype to the normal level to exert the therapeutic effect on AA rats. This study is expected to provide a certain scientific basis for the biological research on the treatment of rheumatoid arthritis by P. hookeri.

Effects of electroacupuncture pretreatment on M1 polarization of alveolar macrophages in rats with acute lung injury / 针灸推拿医学（英文版）

Objective: To observe the effects of electroacupuncture (EA) pretreatment on M1 polarization of alveolar macrophages (AMs) in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to explore the potential protective mechanism of EA.Methods: Forty Sprague-Dawley rats were randomly divided into a normal group, a model group, and three groups of EA pretreatment [including a Chize (LU5) group, a Zusanli (ST36) group and a Chize (LU5) plus Zusanli (ST36) group], with eight rats in each group. The model rats of ALI were established by instilling LPS [2 mg/(kg·bw)] into the trachea of rats for 3 h. The rats in each EA pretreatment group were pretreated with EA for 30 min per day at the corresponding bilateral acupoints 6 d before instilling LPS. Three hours after modeling, the pulmonary function of the rats was tested, and the lung tissue was taken to calculate the ratio of lung wet weight to dry weight (W/D). The pathological lung changes and the injury score were observed by hematoxylin-eosin staining. The contents of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and myeloperoxidase (MPO) in rat's bronchoalveolar lavage fluid (BALF) were detected by enzyme-linked immunosorbent assay. The mRNA and protein expression levels of M1 macrophage markers clusters of differentiation 86 (CD86), inducible nitric oxide synthase (iNOS), and its signaling pathway factor Toll-like receptor (TLR) 4, and nuclear factor-κB (NF-κB) p65 in the alveoli were detected by fluorescence quantitative polymerase chain reaction and Western blot, respectively. Results: After being induced by LPS, the pulmonary function of the model rats showed that the forced expiratory volume in 0.1 s (FEV0.1), forced expiratory volume in 0.3 s (FEV0.3), and their respective ratios of FEV to forced vital capacity (FVC) (including FEV0.1/FVC and FEV0.3/FVC) were significantly decreased (P<0.01), while the W/D of lung tissue was increased (P<0.01). The score of lung injury was significantly higher (P<0.01). The contents of TNF-α, IL-1β, and MPO in the BALF and the mRNA and protein expression levels of CD86, iNOS, TLR4, and NF-κB p65 in the lung tissue were significantly increased (P<0.01). After EA pretreatment, the FEV0.1, FEV0.3, FEV0.1/FVC, and FEV0.3/FVC were significantly increased, the lung injury score decreased significantly, and the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-κB p65 mRNAs and proteins in the alveoli decreased significantly (P<0.05 or P<0.01). Compared with the other two single acupoint groups, the contents of TNF-α, IL-1β, and MPO in the BALF and the expression levels of CD86, iNOS, TLR4, and NF-κB p65 mRNAs in the alveoli in the Chize (LU5) plus Zusanli (ST36) group were significantly lower (P<0.01). Conclusion: EA pretreatment at Chize (LU5) and Zusanli (ST36) can inhibit inflammation and reduce pulmonary injury in ALI rats induced by LPS. The effect of the combination of Chize (LU5) and Zusanli (ST36) is better than that of using these two acupoints separately, and its mechanism may be related to the inhibition of AMs' M1 polarization by down-regulation TLR4/NF-κB signaling pathway.