Identification of terpene synthase gene family in Gynostemma pentaphyllum and expression pattern analysis under abiotic stresses / 中国中药杂志

The present study aimed to investigate the composition of the terpene synthase(TPS) gene family in Gynostemma pentaphyllum and its role in abiotic stresses. The G. pentaphyllum TPS gene family was identified and analyzed at the genome-wide level using bioinformatics analysis, and the expression patterns of these family members were analyzed in different tissues of G. pentaphyllum as well as under various abiotic stresses. The results showed that there were 24 TPS gene family members in G. pentaphyllum with protein lengths ranging from 294 to 842 aa. All of them were localized in the cytoplasm or chloroplasts and unevenly distributed on the 11 chromosomes of G. pentaphyllum. The results of the phylogenetic tree showed that the G. pentaphyllum TPS gene family members could be divided into five subfamilies. As revealed by the analysis of promoter cis-acting elements, TPS gene family members in G. pentaphyllum were predicted to respond to a variety of abiotic stresses such as salt, low temperature, and dark stress. The analysis of gene expression patterns in different tissues of G. pentaphyllum revealed that nine TPS genes were tissue-specific in expression. The qPCR results showed that GpTPS16, GpTPS17, and GpTPS21 responded to a variety of abiotic stresses. This study is expected to provide references in guiding the further exploration of the biological functions of G. pentaphyllum TPS genes under abiotic stresses.

Clinical Efficacy of Dingkundan in Treatment of Ovulatory Disorder Infertility Based on Real-world / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Dingkundan in the treatment of ovulation disorder infertility based on the real world and provide reliable evidence-based medical support for clinical practice. MethodClinical diagnosis and treatment data of patients with ovulation disorder infertility in the real world were collected through the Medroad Cloud system. Patients were grouped according to their real-world treatments， and the total effective rate， ovulation rate per cycle， number of days of follicle development， gonadotropin （Gn） dosage， levels of mature follicle-related hormones， endometrial thickness and classification， pregnancy rate per cycle， clinical pregnancy rate， ectopic pregnancy rate， and early pregnancy loss rate were observed. ResultA total of 207 patients were included， and the most common traditional Chinese medicine （TCM） syndrome in the entire population was liver depression and kidney deficiency. The patients were divided into a Chinese medicine group （Dingkundan， 60 cases）， a western medicine group （ovulation induction， 51 cases）， and a combination group （Dingkundan + ovulation induction， 96 cases）. The combination group（98.96%，95/96） had the highest total effective rate， which was statistically significant when compared with the Chinese medicine group（88.33%，53/60） （χ2=8.328， P<0.05）. The mature follicle estradiol （E2） and luteinizing hormone （LH） levels were the highest in the combination group， and there were statistically significant differences when compared with the western medicine group （P<0.01）. The endometrial thickness was higher in the Chinese medicine group and the combination group than in the western medicine group （P<0.01）. The proportion of type A endometrium was highest in the combination group（85.90%，201/234）， and there was a statistically significant difference when compared with the western medicine group（73.81%，93/126） （χ2=7.993， P<0.01）. The clinical pregnancy rate was 60.42%（58/96） in the combination group， which was higher than 36.67%（22/60） in the Chinese medicine group （χ2=8.336， P<0.01） and 39.22%（20/51） in the western medicine group （χ2=6.011， P<0.05）. Compared with the western medicine group， the combination group showed a favorable trend in total effective rate， ovulation rate per cycle， number of days of follicle development， Gn dosage， pregnancy rate per cycle， ectopic pregnancy rate， and early pregnancy loss rate， but the differences were not statistically significant. ConclusionIn real-world clinical practice， the combination of Dingkundan with ovulation induction can increase endometrial thickness， improve the proportion of type A endometrium， enhance egg quality， and increase the clinical pregnancy rate in patients with ovulation disorder infertility. This approach deserves further clinical research and application.

Applying an ArcCHECK detector to the dose verification for ultra-long target volumes of cervical cancer / 中华放射医学与防护杂志

Objective:To explore the feasibility of applying an ArcCHECK detector to the dose verification for ultra-long target volumes of cervical cancer.Methods:This study retrospectively selected patients suffering from cervical cancer with ultra-long target volumes (lengths: ≥ 26 cm; 50 cases; the ultra-long target volume group) and conventional target volumes (lengths: < 26 cm; 50 cases; the conventional target volume group). Subsequently, this study designed treatment plans using the Volumetric Modulated Arc Therapy (VMAT) technique and then collected and verified doses using an ArcCHECK detector. The dose detection for the conventional target volume group was performed at the central point of the detector (marked by iso and Short-0 cm). Then, the detector was moved for 5 cm along the bed exit direction (marked by iso 1), followed by the dose verification of the ultra-long target volume group (marked by Long-5 cm) and conventional target volume group (marked by Short-5 cm). The geometric parameters (the length and volume of a target volume), mechanical parameters (machine hop count and the duration of irradiation), and gamma pass rates (GPRs) under different detection conditions of each group were analyzed.Results:The target lengths, target volumes, machine hop counts, and irradiation durations of the ultra-long target group were higher than those of the conventional target group ( t = 2.61-18.56, P < 0.05). For the conventional target group, the GPRs at iso 1 were significantly lower than those at iso ( t = 2.14-8.17, P < 0.05). Meanwhile, the GPRs at iso 1 of the ultra-long target volume group were significantly lower than those of the conventional target volume group ( t = -4.70 to -2.73, P < 0.01). The GPRs of each group met clinical requirements for criteria of both 3%/3 mm and 3%/2 mm. Conclusions:The deviation of the positioning center and the length of the target volume serve as primary factors affecting the dose verification result of cervical cancer. For ultra-long target volumes, dose verification can be performed by moving the positioning center, thus ensuring treatment accuracy for cervical cancer patients.

Clinical application of bipolar tweezers-clamp for hepatic parenchymal transection / 中华外科杂志

Objective: To investigate the clinical value of the bipolar tweezers-clamp for the hepatic parenchymal transection in the resection of hepatocellular carcinoma. Methods: From January 2020 to January 2021,63 patients with the hepatocellular carcinoma for hepatectomy at Department of Hepatopancreatobiliary Surgery,Yuebei People's Hospital Affiliated to Shantou University Medical College were analyzed retrospectively.According to the different instruments used in the hepatic parenchymal transection,the patients were divided into bipolar tweezers-clamp group and ultrasonic scalpel group.There were 32 patients in bipolar tweezers-clamp group,with age of (55.5±10.5)years(range:37 to 78 years),including 22 males and 10 females,tumor size was (6.0±3.4)cm(range:2.4 to 13.4 cm). There were 6 patients with portal vein tumor thrombus and 5 patients with portal hypertension. There were 31 patients in ultrasonic scalpel group,with aged(57.8±10.1)years(range:37 to 79 years),including 27males and 4 females,tumor size was(7.9±5.1)cm(range: 2.4 to 21.3 cm),3 patients with portal vein tumor thrombus and 2 patients with portal hypertension. The preoperative baseline data,operation time,blood loss,postoperative liver function and the complications were compared between two groups using t test,χ2 test and Fisher exact probabilityrespectively. Results: The operation was successfully completed in both groups.Compared with the ultrasonic scalpel group,the operation time was significantly shorter((219.3±76.4)minutes vs.(294.0±100.8)minutes,t=-3.322,P=0.002),the blood loss was less((250(475)ml vs. 500(1 050)ml,t=-2.307,P=0.026),the concentrate red blood cells transfusion volume was less(0.92(0.88)U vs. 2.32(4.00)U,Z=-1.987,P=0.047) in the bipolar tweezers-clamp group.The postoperative serum ALB level was higher in the bipolar tweezers-clamp group than that in the ultrasonic scalpel group((33.5±6.1)g/L vs. (29.5±4.2)g/L,t=3.226,P=0.020) on postoperative day 1;((35.7±4.5)g/L vs.(30.1±3.2)g/L,t=5.575,P<0.01) on postoperative day 3;((33.2±3.7)g/L vs. (31.0±4.4)g/L,t=3.020,P=0.004) on postoperative day 7. There was no significant difference in serum ALT,TBIL and PT level between the two groups(all P>0.05).No postoperative bile leakage occurred in both groups.The postoperative complications occurred in 8 cases(25.0%)in the bipolar tweezers-clamp group,including liver failure in one,and in 11 cases(35.5%)in the ultrasonic scalpel group,including liver failure in two(P>0.05). Conclusion: The bipolar tweezers-clamp is a safe and reliable method for the hepatic parenchymal transaction,which is quick and less bleeding during the hepatic resection.

Interpretation and reflection of Traditional Chinese Medicine registration evidence system in Canada / 国际中医中药杂志

Traditional Chinese Medicine (TCM) products could be registered as natural health products (NHPs) in Canada. Its registration process could be mainly divided into simple-application, traditional-application and non-traditional application. By analyzingi the TCM registration evidence system and its safety, effectiveness and quality required by different registration categories in Canada, we found that "simple-application" procesure needs to submit evidence based on the parameters of a component in the monograph. As for "traditional application", TCM products need to be used at least 50 years with, traditional material or Pharmacopoeia can be used as evidence; As for non-traditional application, TCM products need to provide evidence according to the disease risk level, and most of them need to provide scientific experiment evidence. Therefore, from the experience of TCM registration evidence system in Canada, the registration of TCM products should pay attention to improve the its classification method, refining its evidence requirements and data types, promoting the formulation of monograph of TCM, realizing the scientific evaluation and rapid review of classic famous prescriptions, and promoting the inheritance and innovative development of TCM in China.

Introduction and analysis of the registration process of Traditional Chinese Medicine as a natural health product in Canada / 国际中医中药杂志

At present, the registration process of Traditional Chinese Medicine (TCM) in Canada is refering to the requirements of Natural Health Products (NHPs). In terms of registration material, both NHPs and TCM include plants, animals and minerals with medicinal components, but the fundamental difference between them is that TCM is guided by the basic theory of TCM. As for the registration classification of TCM in Canada, first of all, judge whether the product to be applied for is NHPs; Secondly, we should clarify the types and ways of registration, mainly including simple application, traditional application and non-traditional application, and provide application forms, label texts, summary reports, evidence, animal tissue forms, finished product specifications and other materials according to different requirements. At present, the successful registration experience of TCM products in Canada mainly mainly includes applying for superior varieties, selecting appropriate application channels, communicating with local health management units and providing sufficient scientific evidence and good clinical application records. The regulations on the registration of NHPs in Canada have not fully considered the particularity of TCM and the registration of TCM products is still facing some difficulties. In the future, we can learn from the registration process and requirements of the Health Canada, promote the interconnection and mutual recognition of the Pharmacopoeia of the People's Republic of China and the NNHPD monographs in Canada, reduce the obstacles to the local application for registration of TCM, and promote the further improvement of the international standards of TCM.

Analysis of Traditional Chinese Medicine regulation in Canada / 国际中医中药杂志

This paper analyzes the laws, regulations and concre measures of Traditional Chinese Medicine (TCM) in Canada, so as to provide reference for TCM products to enter Canada, and for the establishment of TCM regulation system and the improvement of its detailed rules in China. The regulation of TCM in Canadian, on the one hand, supervision is to provide guidance for the protection of consumers' rights and interests, including the guidance of rational drug use and rational purchase for consumers; on the other hand, it is to supervise enterprises, including the safety, effectiveness and quality certification of TCM products, labeling and packaging requirements, as well as the site certification of product manufacturing, packaging, labeling and import. The Ministry of health of Canada takes evidence as the core of evaluation, and ensures the safe and effective use of TCM products in Canada through product and site licensing evaluation. In the supervision of TCM, relevant departments in China should further strengthen the protection of consumers' drug rights and interests, strengthen the construction of TCM registration evidence system, and pay attention to the risk management of drug production quality.

Analysis on the registration of Chinese patent medicines in Canada and its referantial significance to the international registration of Traditional Chinese Medicines / 国际中医中药杂志

By searching for the Canadian Licensed Natural Health Products Database, (LNHPD), this paper analyzed the characteristics and current status of 92 Chinese patent medicines successfully registered and listed in Canada, and found that the enterprises of successfully registered enterprises are mainly located in areas with better development condition of Traditional Chinese Medicine (TCM) such as Beijing, Guangdong and Tianjin; The successfully registered Chinese patent medicines include 64 kinds of single medicine or medicine with single active ingredient (69.6%) and 28 kinds of compound medicine (30.4%), the forms of the dosage are mainly tablets and capsules, which have the characteristics of accuracy in dosage and stable physicochemical properties. There are also granules, solutions, powders and other dosage forms, which can be preserved for a long time and have low requirements on technic and environment. These Chinese patent medicines are mainly used to treat respiratory and circulatory system diseases, some are used to treat urogenital and digestive system diseases, and few are used to treat difficuilt diseases like tumors, diabetes. There are some other health care products. It is suggested to strengthen the connection between domestic standards of TCM registration and international standards, and promote the scientific and technological capacity of relevant enterprises, and encourage enterprises to strengthen international registration of advantageous products, so as to accelerate the speed of international development of TCM in China.

Analysis of simplified registration of traditional herbal medicinal products in European Union / 国际中医中药杂志

Europe occupies an important position in the world herbal medicine market. The registration of Traditional Chinese Medicine (TCM) in EU is of great significance to the internationalization of TCM. The European Medicines Agency (EMA) has designed a relatively complete management system and regulatory guidelines for the registration and supervision of herbal medicinal products. The promulgation of the DIRECTIVE 2004/24/EC (2004 / 24 / EC) indicates that TCM could enter the EU market through simplified registration. Based on the registration conditions, registration authority and document guideines of Traditional Herbal Medicinal Products (THMPs) in EU, this paper analyzes the application requirements of simple registration of traditional herbal products in EU, and provides suggestions for the simplified registration of TCM in EU according to the registration requirements of medicinal history, quality requirements and application data format.

Bushen Huatan recipe for treatment of polycystic ovary syndrome: therapeutic mechanism based on network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To explore the pharmacological mechanism of Bushen Huatan (BSHT) recipe in the treatment of polycystic ovary syndrome (PCOS).@*METHODS@#The active ingredients in the component drugs of the recipe were screened through TCMSP, and their potential targets were predicted by PubChem and Swiss target prediction. Genecards and OMIM were used to screen the therapeutic targets in the treatment of PCOS. The drug targets and disease targets were corrected using Uniprot, and the intersection targets were obtained. The protein-protein interaction (PPI) network was constructed using STRING, and the intersection targets were analyzed with CytoNCA to screen the core targets. DAVID was used for GO enrichment analysis and KEGG pathway enrichment analysis, and the core components and core targets were verified using AutoDock. Animal experiment was performed to verify the results using a female C57BL/6J mouse model of PCOS, treated daily with 1 mg/kg BSHT recipe granule for 35 days, and the ovarian expressions of the core targets and pathways were detected using Western blotting.@*RESULTS@#We identified a total of 125 potential active ingredients from the 14 component drugs in the recipe, 990 drug targets, 4759 PCOS targets and 434 intersection targets. The core active ingredients of the recipe included β -Sitosterol, kaempferol, and quercetin, whose core targets included PIK3CA, PIK3R1, APP, AKT1, and MAPK1. GO enrichment analysis highlighted such processes as drug reaction, negative regulation of apoptosis, and positive regulation of transcription from RNA polymerase Ⅱ promoter. The enriched KEGG pathways included primarily the cancer pathway and PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had strong binding ability with the core targets. In the animal experiment, BSHT recipe was shown to improve the symptoms, down-regulate the expressions of PI3K and Akt proteins and up-regulate MAPK1 expression in the ovary of mice with PCOS.@*CONCLUSION@#The therapeutic mechanism of BSHT recipe for PCOS involves multiple active ingredients, multiple therapeutic targets and multiple pathways.

Four-stitch cholangiojejunostomy / 中华肝胆外科杂志

Objective:To evaluate the clinical application efficacy of four-stitch cholangiojejunostomy.Methods:Of 38 patients who received four-needle biliary and enterointestinal anastomosis in the Department of Hepatobiliary Surgery, Yuebei People's Hospital Affiliated to Shantou University Medical College from November 2016 to April 2020 were included, and the diseases, surgical methods and postoperative complications of four-needle biliary and enterointestinal anastomosis were analyzed.Results:There were 26 males and 12 females with an average of 57.3(44-77) years. Among 38 patients, there were 12 hilar cholangiocarcinoma patients, 10 pancreatic head cancer, 9 duodenal papillary cancer, 4 intrahepatic and extrahepatic bile duct stones, 1 pancreatic cystic adenoma, 1 gastric cancer invading pancreatic head and 1 gallbladder carcinoma. The procedure included pancreatoduodenectomy in 20, radical resection of hilar cholangiocarcinoma in 12, hepatectomy with biliary-enteric anastomosis in 4, radical resection of gastric cancer combined with pancreaticoduodenectomy in 1, radical resection of gallbladder carcinoma in 1. One, two and three ductal openings were anastomosed in 27, 7 and 4 patients, respectively. 10 patients have bile duct diameter <6 mm. Postoperative anastomotic leakage occurred in 1, and all patients were received followed-up visit for 2 months to 4 years without anastomotic stenosis.Conclusion:Four-stitch cholangiojejunostomy is simple, safe, effective, and convenient for small biliary ductal surgeries.

Dosimetric effects study of set-up error in postoperative intensity modulated radiotherapy of rectal cancer / 中国辐射卫生

Objective To measure set-up errors in intensity modulated radiotherapy of postoperative rectal cancer (IMRTPRC), and analyze the effects of target volumes and normal tissues by set-up errors in IMRTPRC. Methods electrical field device was used to measure the set-up errors of 30 patients in IMRTPRC; we randomly selected 6 patients, and simulated their radiotherapy set-up errors in TPS. Then were counted the dose distribution and analyze relative dosimetrical parameters of target volumes, normal tissues and got the set-up errors effecting on dosimetry. Statistical analysis was performed using an SPSS statistical package(Version 19.0). Results The set-up errors on X, Y and Z direction are (−0.82 ± 2.67) mm, (0.42 ± 2.91) mm and (0.47 ± 1.64) mm respectively. In regard to set-up errors of L5, R7, G8, T5, B6 and A4, most of statistical properties of PTV’s D98%, D95%, D50%, D2%, Hi and Ci are smaller than 0.05, so the differences have statistical values; In L5-Hi, G8-D2%, T5-D50% and B6-D2%, so these differences have not statistical value (P>0.05). In L5, R7, G8, T5, B6 and A4, about half of the statistical properties of normal tissue like bowl, bladder and femur heads, are smaller than 0.05 and have statistical value, and the rest of them are negative. Conclusion The dose of PTV is decreased due toset-up error. Uniformity and conformity is also gone bad. So the dosimetry quantity of PTV can not get reach to the initial design level. However, the dose of normal tissues like bowl, bladder and femur heads, are increased unexpectedly.

Analysis of Inhibitory Mechanism of Reyanning Mixture Combined with Linezolid Against MRSA and Its Biofilm Based on Metabonomics / 中国实验方剂学杂志

Objective:To investigate the inhibitory effects and mechanism of Reyanning mixture （RYN） combined with linezolid （LNZ） against methicillin-resistant <italic>Staphylococcus aureus</italic> （MRSA） and its biofilm. Method:The minimum inhibitory concentrations （MICs） of RYN and LNZ against MRSA were determined by microdilution assay. The microplate method was used to detect the changes in viable count before and after MRSA administration at four time points （0， 6， 12， 24 h） in the process of biofilm growth. The morphological changes of MRSA after 24 h were observed by scanning electron microscope. Metabonomic technique was applied to analyze the changes in terminal metabolites of endogenous small molecules from MRSA treated by the two drugs at four time points. Result:The MICs of RYN and LNZ were 1/2 of the stock solution concentration and 4 mg·L^-1， respectively. The inhibitory effect of LNZ （2 mg·L^-1） against viable bacteria at 0 h was better than that of 1/16 RYN. At 6， 12， 24 h， 1/16 RYN was superior to LNZ in inhibiting MRSA. The inhibitory effects of RYN combined with LNZ were better than those of RYN or LNZ alone at the four time points. RYN combined with LNZ caused more severe damages to the morphological structure of MRSA biofilm at 24 h than RYN or LNZ alone. Cyclic adenosine monophosphate （cAMP）， adenosine diphosphate （ADP）-<italic>D</italic>-ribose and 2-methylbutanoyl-coenzyme A （2M-CoA）， as the metabolites related to biofilm formation， were immune to LNZ， but 2M-CoA and ADP-<italic>D</italic>-ribose were influenced by RYN at 12 h and 24 h. The combined use of RYN and LNZ interfered with the three metabolites at 24 h. <italic>L</italic>-tryptophan， phenylpyruvic acid， cytidine and sebacic acid were the pharmacometabolic markers of LNZ， and the related biological pathways were phenylalanine， tyrosine and tryptophan biosynthesis and phenylalanine metabolism. Four metabolites such as<italic> L</italic>-histidine， uric acid， and <italic>L</italic>-lysine were the pharmacometabolic markers of RYN， with phenylalanine metabolism and aminoacyl-transfer ribonucleic acid （tRNA） biosynthesis confirmed as the related biological pathways. Nine metabolites such as <italic>L</italic>-tryptophan，<italic> L</italic>-lysine， and sphingosine-1-phosphate were responsible for the efficacy of RYN combined with LNZ. The related biological pathways involved aminoacyl-tRNA biosynthesis， phenylalanine， tyrosine and tryptophan biosynthesis， novobiocin biosynthesis， and tyrosine metabolism. Conclusion:RYN combined with LNZ better exerts the inhibitory effects against MRSA at each time point of its biofilm formation， which is attributed to cAMP metabolism. The synergistic effect resulted from aminoacyl-tRNA biosynthesis and phenylalanine， tyrosine and tryptophan biosynthesis. RYN combined with LNZ can serve as a potentially effective solution to MRSA infection.

High Resolution Computed Tomography (HRCT) Imaging Findings of Oval Window Atresia with Surgical Correlation

INTRODUCTION@#Isolated oval window atresia (OWA) is a rare cause of congenital conductive middle ear deafness and may be overlooked owing to the normal appearance of the external ear. This anomaly has been previously described, although the published numbers with both imaging and surgical findings are few. Our aim is to correlate the imaging features of OWA with intraoperative findings.@*MATERIALS AND METHODS@#This is a single-centre retrospective evaluation of patients who were diagnosed with OWA and who received surgery from January 1999 to July 2006. No new case was diagnosed after 2006 to the time of preparation of this manuscript. High resolution computed tomography (HRCT) imaging of the temporal bones of the patients were retrospectively evaluated by 2 head and neck radiologists. Images were evaluated for the absence of the oval window, ossicular chain abnormalities, position of the facial nerve canal, and other malformations. Imaging findings were then correlated with surgical findings.@*RESULTS@#A total of 9 ears in 7 patients (two of whom with bilateral lesions) had surgery for OWA. All patients had concomitant findings of absent stapes footplate with normal, deformed or absent stapes superstructure and an inferiorly displaced facial nerve canal. HRCT was sensitive in identifying OWA and associated ossicular chain and facial nerve abnormalities, which were documented surgically.@*CONCLUSION@#OWA is a rare entity that can be diagnosed with certainty on HRCT, best visualised on coronal plane. Imaging findings of associated middle ear abnormalities, position of the facial nerve canal, which is invariably mal-positioned, and associated deformity of the incus are important for presurgical planning and consent.

Pancreatic and duodenal homeobox-1 in pancreatic ductal adenocarcinoma and diabetes mellitus / 中华医学杂志(英文版)

Diabetes mellitus and pancreatic ductal adenocarcinoma are two common diseases worldwidely which are both derived from different components of pancreas. The pancreatic and duodenal homeobox-1 (PDX1) is an essential transcription factor for the early development of pancreas that is required for the differentiation of all pancreatic cell lineages. Current evidence suggests an important role of PDX1 in both the origin and progression of pancreatic diseases. In this review, we discussed recent studies of PDX1 in diabetes mellitus and pancreatic cancer, and the therapeutic strategies derived from this transcription factor.

Effects of Dingkun Dan combined with Western medicine on endometrial β-catenin, VEGF and MMP-9 mRNA expression in rats with multiple lesions / 中国中药杂志

The aim of this paper was to investigate the effect of Dingkun Dan on endometrial receptivity in rats with multiple lesions. Forty SD female rats with regular sexual cycle were randomly divided into 5 groups, control group, model group, progynova group, Dingkun Dan group and combination group. The thin endometrium model of kidney-yang deficiency was established in all the other rats except normal control group. The rats in normal control group were free to drink and eat; the rats in the model group were administered with distilled water; the rats in the progynova group were treated with progynova; rats in Dingkun Dan group were treated with Dingkun Dan, and the rats in combination group were treated with Dingkun Dan and progynova. After 15 days, serum levels of OPN, VEGF and MMP-9 were measured by ELISA. HE staining, immunohistochemistry and RT-PCR were used to analyze endome-trial morphology, endometrial thickness and the treatment mechanism of Dingkun Dan. As compared with the control group, the serum levels of OPN, VEGF and MMP-9 in the model group were significantly increased(P<0.01). As compared with the model group, the serum levels of OPN and MMP-9 were decreased in Dingkun Dan group(P<0.05, P<0.01). As compared with the control group, endometrial stromal cells were fewer, the endometrium glands and blood vessels were sparse, and the endometrium was thinner significantly in the model group(P<0.01). As compared with the model group, there were more endometrial glands, rich intimal vessels, and dense stromal cells in various treatment groups, and the endometrium were thickened significantly in the treatment groups(P<0.01). As compared with the control group, the expression area of CK19 in the model group was decreased significantly(P<0.01). As compared with the model group, the expression area of CK19 in each treatment group was increased significantly(P<0.05). As compared with the control group, endometrial β-catenin and MMP-9 mRNA expression levels were increased significantly in the model group(P<0.05), while VEGF mRNA expression was decreased(P<0.05). As compared with the model group, MMP-9 mRNA expression was decreased significantly in the progynova group and the combination group(P<0.05). Dingkun Dan combined with progynova can improve endometrial receptivity by up-regulating expression of β-catenin, VEGF mRNA and down-regulating the expression of MMP-9 mRNA in the injury rats.

Research Strategy of Mechanism of Efficacy Enhancing and Toxicity Reducing of Antibiotics Combined with Chinese Medicine for Infectious Diseases / 中国实验方剂学杂志

The decreased efficacy and severe side effects of antibiotics, as well the increase of multidrug resistant pathogens are seriously threatening human health. It has become an urgent task for the whole world to actively respond to threats and establish effective prevention and control plans. Traditional Chinese medicine (TCM) has a long history with exact curative effect in the treatment of infectious diseases. It not only inhibits pathogens and eliminates endotoxin, but also has therapeutic effect on inflammation, immune abnormality and overall disorder caused by infection. Antibiotics mainly inhibit the pathogen itself, while the combination of TCM and antibiotics is complementary with each other and is considered as a feasible solution to the challenges. Some clinical observations have shown that TCM has potentiality of enhancing antibiotics efficiency and reducing toxicity. Exploring its mechanism is the necessary measure to optimize and popularize treatment regimen. Firstly, multi-level and multi-dimensional systematic pharmacology network analysis methods are used to predict the mechanism of TCM combined with antibiotics in the treatment of infectious diseases, so as to provide the evidence for further empirical research and selection of test indicators. Then by following the principle of corresponding drug use in specific TCM syndromes, the antibiotics and TCM are individually and jointly applied to treat patients with specific syndrome conditions of infectious diseases. Besides routine and comprehensive evaluation of synergistic and attenuated effect of the combined drug use, multi-omics technique is also used to find the subtle effects of these two drugs at a molecular level. The sensitive and stable clinical biomarkers of synergism and attenuation of combined drug use are determined by using biomolecular network analysis technology. Finally, taking these biomarkers as clues, the biotransformation process and regulation mechanism of the biomarkers are traced back in animal models of infectious diseases and cell level, and all of these are clinically verified. As a result, the mechanism of efficacy enhancing and toxicity reducing of combined drug use can be revealed, providing basis for the promotion and application of such combined drug use.

Intervention of Modified Yupingfeng San Combined with Aspirin on D-dimer， PagT Levels of RSA with Seronegative APS / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of aspirin combined with modified Yupingfeng San on patients with recurrent spontaneous abortion and Seronegative antiphospholipid syndrome. Method:From December 2016 to March 2018, 109 cases of recurrent spontaneous abortion patients with seronegative antiphospholipid syndrome in Affiliated Hospital of Nanjing University of Chinese Medicine were selected as the study objects. According to the random number table, they were divided into three groups:blank group, control group and study group. The blank group was treated with folic acid tablets, 1 pill/time, qd, as placebo, the control group was treated with folic acid tablets, 1 pill/time, qd, Danshen pills, 4 pills/time, tid, and aspirin, 1 pill/time, tid, and the study group was treated with folic acid tablets, 1 pill/time, qd, aspirin, 1 pill/time, tid, and modified Yupingfeng San, 150 mL/time, bid. These patients were all asked for pregnancy preparation for 1 year and treated with aspirin, 1 pill/time, tid, and progesterone pills, 1 pill/time, tid, since the beginning of pregnancy until 13 weeks or abortion. The pregnancy rate, miscarriage rate, coagulation index before and after treatment, traditional Chinese medicine (TCM) symptom score as well as months of abortion were all observed and compared. Result:The coagulation index and TCM symptom score of the study group were significantly lower than those before treatment (PPPPPConclusion:The data proved that the combination of anti-coagulation medicine with either single herb or herbal compound can improve the curative effect of the patients, and traditional Chinese herbal compound can regulate the immune system, reduce the thrombosis and improve the symptoms of TCM, which made the curative efficacy more prominent. However, more samples were needed for further research. Because the time of fetal protection may not change the outcome of pregnancy, the therapy should be maintained at least until the end of the early pregnancy.

ExperimentalStudyonDetectionofDeadandLive Mycobacterium Tuberculosis by FlowCytometry / 中山大学学报(医学科学版)

@#：【Objective】To provide basic experimental basis for quantitative detection and analysis of antibiotic susceptibilityandheteroresistancein Mycobacterium tuberculosis byflowcytometry，weinvestigatedtheperformanceof propidiumiodide（PI）and6-carboxyfluoresceindiacetae（6-cFDA）inidentifyingdeadorlivingMycobacterium tubercu⁃ losis.【Methods】PIand6-cFDAwereusedtostain10strainsofpureculturedliving Mycobacterium tuberculosis suspen⁃ sion with turbidity of 1 McClell and the corresponding suspension with turbidity of 1 McClell heated at 85℃ for 30 minutes，respectively.Themeanfluorescenceintensity（MFI）wasmeasuredbyflowcytometry.TheMFIboundaryvalue fordistinguishingdeadandlivingMycobacterium tuberculosisweredeterminedaccordingtoreceiveroperatingcharacteristic （ROC）curves.Thesameexperimentswerecarriedoutwithother10strainsofliving Mycobacterium tuberculosis suspen⁃sionand10dead Mycobacterium tuberculosis suspension，andtheMFIthresholdwasusedtodeterminetheviabilityof bacteria.【Results】（1）IntheexperimentofdeterminingMFIboundaryvalue，theMFIof10strainsofdeadbacteria suspensionstainedwithPIwasnon-normaldistribution，themedianvaluewas2459，andtheMFIof10strainsofliving bacteriasuspensionstainedwithPIwasnormaldistribution，themeanvaluewas426±180.TheMFIboundaryvalueof deadbacteriastainedwithPIwas1329.TheMFIof10strainsofdeadbacteriaand10strainsoflivingbacteriasuspen⁃ sionstainedwith6-cFDAwasnormaldistribution，andthemeanvaluewas49±4and7144±4511，respectively.The MFIthresholdof6-cFDAstainingforlivingbacteriawas1021.（2）TheMFIthresholdsforidentifyingdeadbacteriaby PIstainingandtheMFIthresholdsforidentifyinglivingbacteriaby6-cFDAstainingwereusedtodetect10otherliving bacterialsuspensionsand10deadbacterialsuspensions.Theaccuracy，sensitivity，specificity，Yondeindex，positive predictivevalueandnegativepredictivevaluewere95%and100%，1.00and1.00，0.90and1.00，0.90and1.00，0.91 and1.00，1.00and1.00，respectively.【Conclusions】PIstainingcandetectdeadMycobacterium tuberculosisand6-cFDA stainingcandetectliving Mycobacterium tuberculosis.Identificationof Mycobacterium tuberculosis activitybasedonPIand 6-cFDAstainingwillhavebroadapplicationprospects.

Up-regulation of P2X7 Receptors Contributes to Spinal Microglial Activation and the Development of Pain Induced by BmK-I / 神经科学通报·英文版

Previous work has demonstrated that the sensitization of spinal neurons and microglia is important in the development of pain behaviors induced by BmK I, a Na channel activator and a major peptide component of the venom of the scorpion Buthus martensi Karsch (BmK). We found that the expression of P2X7 receptors (P2X7Rs) was up-regulated in the ipsilateral spinal dorsal horn after BmK I injection in rats. P2X7R was selectively localized in microglia but not astrocytes or neurons. Similarly, interleukin 1β (IL-1β) was selectively up-regulated in microglia in the spinal dorsal horn after BmK I injection. Intrathecal injection of P2X7R antagonists largely reduced BmK I-induced spontaneous and evoked pain behaviors, and the up-regulation of P2X7R and IL-1β in the spinal cord. These data suggested that the up-regulation of P2X7Rs mediates microglial activation in the spinal dorsal horn, and therefore contributes to the development of BmK I-induced pain.