Shengma Gegentang is one of the classic formulas in the Catalogue of Ancient Classic Prescriptions （Second Batch）. This study reviewed ancient and modern literature and used literature tracing and bibliometric methods to analyze the historical evolution， efficacy， indications， dosage decoctions， and modern clinical disease spectrum of Shengma Gegentang. The results indicated that the earliest record of Shengma Gegentang can be found in the Taiping Huimin Heji Jufang of the Song dynasty， but its origin can be traced back to the Shaoyao Siwu Jiejitang in the Beiji Qianjin Yaofang of the Tang dynasty. The composition dosage of Shengma Gegentang is 413 g of Cimicifugae Rhizoma， 619.5 g of Puerariae Lobatae Radix， 413 g of Paeoniae Radix Alba， and 413 g of Glycyrrhizae Radix et Rhizoma， which are ground into coarse powder. Each dose is 12.39 g， and the amount of water added is 300 mL. 100 mL of solution is decocted and taken at the right time. The four drugs in the formula play the role of relieving exterior syndrome， penetrating pathogenic factors， and detoxicating together. Its indications are widely involved in internal medicine， pediatrics， surgery， ophthalmology and otorhinolaryngology， obstetrics and gynecology， sexually transmitted diseases， and other diseases， such as measles， sores， acne， spots， surgical gangrene， red eyes， toothache， chancre， and fetal poison. The epidemic diseases treated by Shengma Gegentang are complicated， including rash， pox， macula， numbness， summer diarrhea， dysentery， sha disease， febrile symptoms， spring warmth， winter warmth， and cold pestilence. At the same time， it is a plague prevention formula. Although Shengma Gegentang has a wide range of indications， it cannot be separated from the pathogenic mechanism of evil Qi blocking the muscle surface and heat in the lungs and stomach. The modern clinical disease spectrum of Shengma Gegentang involves the ophthalmology and otorhinolaryngology system， nervous system， pediatric-related diseases and syndromes， skin system， hepatobiliary system， and digestive system. It plays a key role in the treatment of epidemic diseases such as measles， chronic hepatitis B， dysentery， and tetanus.

OBJECTIVE To construct an evaluation index system for the core competencies of ethics committee members of drug clinical trial institution， providing a basis for optimizing the training system for committee members， improving the quality of ethical review， and fully safeguarding the safety and rights of subjects. METHODS Using methods such as literature research and expert consultation， a preliminary core competency evaluation index system was constructed. The Delphi method was employed to revise and validate it， ultimately forming an evaluation index system for the core competencies of ethics committee members. Based on this system， a questionnaire survey was conducted among 90 ethics committee members from 29 drug clinical trial institutions nationwide， comparing their importance rating and self-assessment scores of the core competency indexes. RESULTS The evaluation system constructed included 4 primary indicators （ethics and professional knowledge， ethics review ability， communication and expression ability， moral integrity and work style） and 39 secondary indicators （familiarity with the content of clinical trial-related laws and regulations， ability to complete project ethics review and identify ethical defects in research protocols within a short period of time， ability to judge the scientific value of clinical research， etc.）. The results of questionnaire survey showed that the interviewed ethics committee members had significant capability gaps in dimensions such as regulatory knowledge， ethical norms， review efficiency， risk judgment， and problem analysis. The differences between the importance rating scores of corresponding secondary indicators and the self-assessment scores were all no less than 0.38. CONCLUSIONS This study has developed a quantifiable and stratified core competency assessment tool for ethics committee members. It can provide a scientific framework for committee member training， qualification certification， and standardized management of ethics committees.

BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.

ObjectiveTo explore the possible mechanism of Pingwei Capsules （平胃胶囊） for chronic atrophic gastritis from rapidly accelerated fibrosarcoma / mitogen-activated protein kinase /extracellular-signal-regulated kinase （Raf/MEK/ERK） pathway that influences the activation of fibrosarcoma protein/mitogen. MethodsFifteen SD rats were randomly divided into 5 rats in the blank group and 10 rats in Pingwei Capsules group. The rats in the blank group were given 1 ml/100 g of saline by gavage， and the rats in Pingwei Capsules group were given 0.63 g/（kg·d） of Pingwei Capsule suspension by gavage， and serum was collected for 3 consecutive days. N-methyl-N'-nitro-N-nitrosoguanidine （MNNG） was used to induce human gastric mucosal epithelial cells GES-1 to establish a precancerous lesion cell model. The successful cells were divided into control group （10% fetal bovine serum）， blank serum group （10% fetal bovine serum plus 10% blank serum）， and medication-containing serum group （serum with medication of Pingwei Capsule）， and the volume fraction and time of intervention of Pingwei Capsule-containing serum were screened by CCK-8 assay. Human gastric mucosal epithelial cells GES-1 were divided into normal group， model group， blank serum group， medication-containing serum group， U0126 group， and combined group， with 6 replicate wells in each group. After successful modelling of the cells in all groups except the blank group， an equal volume of fetal bovine serum was added to the normal and model groups， an equal volume of blank serum was added to the blank serum group， a screening volume fraction of Pingwei Capsule-containing serum was added to Pingwei Capsule group， a 10 μmol/L mitogen-activated extracellular signal regulated kinase 1 （MEK1） inhibitor U0126 was administered in the U0126 group， an equal dose of Pingwei Capsule-containing serum plus 10 μmol/L of U0126 was administered to the combined group. After the selected incubation time， the level of interleukin 6 （IL-6） was detected in the cells by ELISA， the expression of IL-6 and MEK1 was detected by immunofluorescence， and the expression of IL-6， Raf， MEK1， and ERK mRNA was detected by RT-qPCR， and the expression of IL-6， Raf， MEK1， and ERK mRNA in the cells was detected by Western blot. ResultsThe 5.35% volume fraction， 48 h intervention of Pingwei Capsule-containing serum was selected for subsequent experiments. Compared with the normal group， the IL-6 content in cell supernatants and the expression of IL-6， Raf， MEK1， ERK mRNA and ERK1/2 proteins in cells increased in the model group and blank serum group （P＜0.01）. Compared with the model group， all of the above indexes were improved in medication-containing serum group， U0126 group， and combined group （P＜0.05 or P＜0.01）. Compared with medication-containing serum group， the expression of IL-6， MEK1 expression， the expression of IL-6， Raf， MEK1 and ERK mRNA， and the expression of IL-6， Raf， MEK1 and ERK1/2 proteins reduced in the cells of combined group （P＜0.05 or P＜0.01）. Compared with the U0126 group， IL-6 expression reduced and IL-6， MEK1 and ERK1/2 protein expression reduced in cells of combined group （P＜0.05 or P＜0.01）. ConclusionThe Pingwei Capsule-containing serum may play a role in the treatment of chronic atrophic gastritis by improving the inflammation-cancer transformation of GES-1 cells through inhibiting the Raf/MEK/ERK pathway.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective To investigate the safety and effectiveness of transumbilical repair for hernia of linea alba within 3 cm above the umbilicus.Methods Clinical data of 26 patients who underwent transumbilical approach hernia repair in our hospital from June 2016 to July 2022 were retrospectively analyzed.Color ultrasound examination showed that the distance from the lower edge of the hernia to the upper edge of the umbilicus was≤3 cm.The hernia repair was performed through the fascial space via the upper edge approach of the umbilical ring.There were 7 boys and 19 girls.The age was 7 months to 11 years old(median,3 years old).The distance from the lower edge of the hernia sac to the upper edge of the umbilicus was(1.46±0.66)cm,and the diameter of the hernia of linea alba was(1.16±0.57)cm.Results The surgery was completed smoothly.The operation time was(39.1±26.3)min.No complication was noted.All the patients were discharged one day after surgery.The follow-ups lasted for 1 year and 2 months to 7 years and 3 months(median,5 years and 1 month).No wound infection,bleeding or other complications occurred.No recurrence of hernia or formation of skin granulomas happened.Conclusion Transumbilical approach repair for hernia of linea alba within 3 cm above the umbilicus is safe and effective,with good cosmetic results.

Objective:To investigate the effect of anatomical unit resection on the overall survival rate of patients with T4 stage posterior buccal carcinoma.Methods:We conducted a retrospective study on 79 patients with T4 stage posterior buccal squamous cell carcinoma underwent radical surgery for buccal mucosa cancer and reconstruction with free anterolateral thigh flap in the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital, Central South University from March 2014 to December 2019. The 74 patients were males and the 5 patients were females, aged from 28 to 72 years old. The 40 patients in control group underwent traditional extended resection (1.5-2.0 cm safe margin), and 39 patients in the experimental group underwent anatomical unit resection. The clinicopathological parameters of patients were collected and followed up regularly. The overall survival rate was assessed by Log-rank and Cox proportional risk regression model. Multivariate analysis was performed by linear regression model.Results:There were significant differences between experimental group and control group in overall survival rates (61.53% vs 27.50%, χ2=6.624, P=0.010) and local disease control rates (74.36% vs 27.50%, χ2=17.350, P<0.001). Multiple linear regression analysis showed that local disease control rate was significantly correlated with anatomical unit resection ( t=3.880, P<0.001) and lymph node metastasis ( t=2.619, P=0.011), and also Cox proportional hazards regression model analysis identified that overall survival rate was significantly correlated with anatomical unit resection ( Z=2.421, P=0.016) and lymph node metastasis ( Z=2.793, P=0.005). Conclusion:For posterior buccal carcinoma with multiple anatomical units involved, anatomical unit resection can significantly reduce local recurrence and improve overall survival rate of patients.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective To explore the effectiveness of transperineal tension-free repair of rectal seromuscular layer in the treatment of acquired rectovestibular fistula.Methods Clinical data of 97 girls with acquired rectovestibular fistula from May 2016 to November 2023 were enrolled.The surgical age ranged from 6 months to 11 years old(median,3 years old).The fistula was disconnected and resected via the perineal approach.The anterior wall of the rectum was fully disconnected.Then the fistula was repaired with horizontal continuous tension-free suture of rectal plasmomuscular layer with 5-0 PDS sutures.After continuous suture reinforcement,the perineal muscle layer and skin were longitudinally continuously sutured.The internal fistula opening was exposured with an anal dilator or small hook,and the mucosal layer was continuously sutured with 5-0 PDS sutures.Postoperatively,the anal tube and urinary tube were retained for 5-7 d and antibiotics was administered for treatment.Results The mean operation time was(60.5±9.0)min,the mean fistula diameter was(5.2±2.1)mm,and the mean hospital stay was(7.4±1.9)d.The follow-ups time was 4.5 months to 8.5 years(median,4.25 years).Primary healing was achieved in 92 cases(94.8％),with satisfactory perineal appearance,smooth stool passage,and regular defecation.Fistula recurred within 5-10 d after operation in 5 cases(5.2％),2 of which healed after 3 weeks of sitz baths by using 3％boric acid or Kangfuxin solution,2 of which healed after second operation,and 1 of which experienced recurrence after secondary fistula repair.Conclusion Transperineal tension-free rectal seromuscular layer repair is a simple,safe,and effective surgical method for the treatment of acquired rectovestibular fistula in girls.

OBJECTIVE To optimize the molding process of Shuangye pipa granules based on the concept of quality by design （QbD） and analyze its physical fingerprint. METHODS The dry extract of Shuangye pipa granules was used as the main drug. The retention rate of total flavonoid， moisture absorption rate， dissolution rate， angle of repose and molding rate of the granules were selected as evaluation indexes. The single-factor test combined with the entropy weight method and Box-Behnken response surface design was used to optimize the molding process， and validation test was conducted. The physical fingerprints of 10 batches of Shuangye pipa granules prepared by the optimal process were comprehensively analyzed by eight secondary physical indexes （relative homogeneity， moisture， moisture absorption rate， Hausner ratio， angle of repose， bulk density， tap density and porosity）. RESULTS The optimal molding process of Shuangye pipa granules was as follows： soluble starch-maltodextrin-mannitol was 1∶1∶1 （m/m/m）， 95% ethanol was as wetting agent and the amount of it was 37%， the drug-assisted ratio was 1∶0.8 （m/m）， the drying temperature was 59 ℃， drying time was 28 min. The results of 3 validation tests showed that the average comprehensive score was 0.879 6， the RSD of which with prediction value （0.881 9 score） was 1.97%. The similarity between the physical fingerprints of 10 batches of Shuangye pipa granules and the control physical fingerprint was higher than 0.99. CONCLUSIONS The optimized molding process of Shuangye pipa granules is stable and feasible， and the physical property of Shuangye pipa granules is stable and controllable.