This article introduces an overview of management system for conflict of interest of the European Pharmacopoeia Commission (EPC) and the United States Pharmacopoeia Convention (USP). The EPC and USP have standardized the management system for conflict of interest in drug standard work in multiple management documents, such as the Guide for the Work, Code of Practice for the Work, Form for Declaration of Interests and Confidentiality Undertaking of the EPC, bylaws, Rules and Procedures of the Council of Experts, Code of Ethics, Standards of Conduct of the USP, in order to ensure the transparency and fairness of drug standard development, improve the credibility and rigor of drug standards. This article introduces the management system for conflict of interest of the EPC and USP, providing reference for the improvement of relevant management systems of the Chinese Pharmacopoeia Commission.

Objective To investigate the association between body mass index(BMI),sex hormone and single nucleotide polymorphisms(SNPs)of follicle-stimulating hormone receptor(FSHR)gene rs2268361 and rs2349415 and its correlation with the risk of polycystic ovary syndrome(PCOS).Methods Peripheral blood was collected from 213 PCOS patients and 207 healthy controls,attending the Department of Reproductive Medicine at the First Hospital of Shanxi Medical University,and 32 follicular fluids were randomly collected from each of the PCOS and control groups from March to August 2021.Calculation of BMI of the PCOS and control groups;The levels of follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),testosterone(T),progesterone(P)and prolactin(PRL)in peripheral blood of the two groups were detected by immunochemiluminescence method.Polymerase chain reaction(PCR)and high-resolution melting curve(HRM)were used to analyze the polymorphisms of rs2268361 and rs2349415 in FSHR of the two groups.Quantitative real-time PCR was used to detect the expression of FSHR gene mRNA in peripheral blood and ovarian granulosa cells.Results There was a strong positive correlation between LH and LH/FSH(r=0.88,P<0.05);The levels of BMI,E2,LH,LH/FSH and T in PCOS group were significantly higher than those in control group(P<0.05);FSH level was significantly lower than that of control group(P<0.001).HRM analysis showed the frequencies of CC,CT and TT genotypes at rs2349415 were 55.9%,34.3%and 9.8%in PCOS group and 68.6%,23.2%and 8.2%in control group,respectively.The frequencies of C and T alleles were 73.0%and 27.0%in PCOS group and 80.2%and 19.8%in control group,respectively.There were significant differences in genotype frequencies and allele frequencies between the two groups(P<0.05);The expression level of FSHR mRNA was higher in ovarian granulosa cells in PCOS group than in control group(P=0.004),the expression level of FSHR mRNA in rs2349415 TT genotype was higher than that in CC(P=0.002)and CT(P=0.035)genotype.Conclusion High levels of BMI, LH, E2 and T allele of rs2349415 increased the risk of PCOS.

Objective To analyze the correlation between the ELL2 gene 1119 T>C polymorphism and the susceptibility to pleomorphic adenoma of the salivary gland.Methods The pedigree of the pleomorphic adenoma family of salivary gland was drawn.The exons of ELL2 gene in 5 members of salivary pleomorphic adenoma family were sequenced.A case-control study was conducted.One hundred and twelve patients with pleomorphic adenoma of the salivary gland who visited the Department of Oral and Maxillofacial Surgery of Shanxi Bethune Hospital from January 2016 to July 2020 were taken as case group,and 176 healthy examinees from January 2019 to January 2020 were taken as control group with age and sex as matching conditions.The 1119 T>C polymorphism of ELL2 genes in the two groups were detected with high resolution melting(HRM)curve.Chi-square test was adopted to analyze the correlation between gene polymorphism and the occurrence of pleomorphic adenoma of the salivary gland,stratified analysis was performed to evaluate the synergistic effect of smoking and genotype,and real time quantitative reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression level of ELL2 in individuals with different genotypes.Results The 1119 T>C polymorphism site existed in the exon 8 of ELL2 gene in a family with pleomorphic adenoma of salivary gland.The results of case-control study showed that the genotype frequency of homozygous CC was significantly higher in patients with pleomorphic adenoma of salivary gland than that in the controls(24.1%vs.11.9%,P=0.002).Homozygous CC was associated with increased risk for developing pleomorphic adenoma of salivary gland(OR=3.059,95%CI 1.494-6.263)in this cohort.Stratification analysis showed that smoking and 1119C allele cooperated to increase the risk of pleomorphic adenoma of salivary gland(OR=3.200,95%CI 1.460-7.014).The expression level of ELL2 mRNA in CC genotype was significantly higher than that in individuals with CT or TT genotype(P<0.05).Conclusion The genetic variation of ELL2 may play an important role in the occurrence of pleomorphic adenoma of salivary gland,and smoking combined with the 1119C allele increased the risk of this disease.

Objective To observe the inhibitory effect of Guiqi Yiyuan ointment on tumor growth in mice with Lewis lung cancer,and to explore the molecular mechanism of Guiqi Yiyuan ointment combined with cisplatin through phosphoinositide 3-kinase/protein kinase B/mammalian rapamycin target protein(PI3K/Akt/mTOR)signal pathway.Methods Sixty C57BL/6 mice were randomly divided into 6 groups with 10 mice in each group.Except for the blank group(0.9％NaCl),Lewis lung cancer-bearing mice were randomly divided into model group(0.9％NaCl),control group(0.9％NaCl,cisplatin 5 mg·kg-1)and low,medium,high dose experimental groups(Guiqi Yiyuan ointment 1.6,3.3,6.6 g·kg-1,cisplatin 5 mg·kg-1).Flow cytometry was used to detect bone marrow-derived suppressor cells(MDSCs);the expression of related proteins in tumor tissues was detected by Western blot.Results The tumor inhibition rates in control group and low,medium,high dose experimental groups were(39.87±4.45)％,(45.74±14.97)％,(57.78±4.70)％and(69.82±11.05)％.The proportion of MDSCs in bone marrow of in blank group,model group,control group and low,medium,high dose experimental groups were(36.13±1.08)％,(68.63±2.94)％,(58.93±2.02)％,(58.00±1.50)％,(50.93±5.06)％and(43.07±2.41)％.The protein expressions of p-PI3K/PI3K in model group,control group and low,medium and high experimental groups were 0.97±0.03,0.77±0.02,0.72±0.01,0.68±0.03 and 0.53±0.02;PTEN were 0.21±0.07,0.65±0.07,0.74±0.06,0.99±0.13,1.11±0.13;p-Akt/Akt were 1.01±0.02,0.82±0.02,0.77±0.00,0.72±0.03 and 0.52±0.04;p-mTOR/mTOR were 1.01±0.01,0.76±0.05,0.69±0.07,0.59±0.06 and 0.47±0.06.There were significant differences between low,medium,high experimental groups and control group(all P＜0.05).Conclusion Guiqi Yiyuan ointment combined with cisplatin can significantly improve the quality of life and inhibit tumor growth in mice.The mechanism may be the inhibition of PI3K/Akt/mTOR signal pathway and the enhancement of tumor cell apoptosis and autophagy.

Objective To observe the effects of traditional Chinese medicine compound Platycodon grandiflorum Bai powder on the growth of subcutaneously implanted tumor and the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cysteinyl aspartate specific proteinase(caspase)-3 and caspase-9 in subcutaneously implanted tumor of Lewis lung cancer mice.Methods The model of transplanted tumor of Lewis lung cancer in mice was established.Seventy SPF male C57BL/6 mice were randomly divided into blank group,model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combined group.Blank group and model group were given 0.9％NaCl 0.2 mL by gavage;control group was given 0.9％NaCl by gavage and 25 mg·kg-1cisplatin intraperitoneally;high,medium,low dose experimental groups were given 193,96,48 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,respectively;combined group was given 96 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,and 25 mg·kg-1 cisplatin intraperitoneally,once every other day.The myelogenous suppressor cells(MDSCs)of mouse bone marrow were detected by flow cytometry,and the expressions of Bel-2,Bax,caspase-3 and caspase-9 in tumor cells were detected by immunofluorescence.Results The percentage of MDSCs in bone marrow of mice in blank group,model group,low dose experimental,medium,high dose experimental group,control group and combination group were(32.50±2.76)％,(63.13±3.14)％,(48.43±2.23)％,(42.53±1.28)％,(32.93±3.56)％,(51.30±4.25)％and(19.90±6.21)％,respectively.The fluorescence intensities of Bax in model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combination group were 10.42±0.68,12.40±1.23,15.14±0.65,22.95±1.76,27.18±1.62 and 31.61±1.28;Bel-2 were 36.85±0.80,33.92±4.20,28.88±1.01,20.04±2.21,15.69±2.36 and 6.05±0.73;caspase-3 were 5.28±0.44,7.63±0.55,9.66±0.85,14.73±1.18,17.95±1.29 and 22.92±1.95;caspase-9 were 9.48±0.90,11.57±0.72,13.45±0.93,15.73±1.44,19.20±0.96 and 23.21±1.51.There were significant differences between medium,high dose experimental groups and model group(all P＜0.05),and there were significant differences between combined group and control group(all P＜0.05).Conclusion Platycodon grandiflorum Bai powder can up-regulating the expression of Bax,caspase-3 and caspase-9,down-regulating the expression of Bel-2,inhibiting MDSCs,promoting tumor cell apoptosis and inhibiting tumor growth.

This article elaborates on the complex cross-talk and close relationship between muscles and bones involved in this disease,as well as its pathogenesis.It also summarizes that the difficulty of its treatment lies in the need to simultaneously consider both muscles and bones.And elaborated on the key role of the Hedgehog signaling pathway in embryonic development,tissue morphology establishment,and human tissue regeneration and repair.Investigated the remodeling effect of the Hedgehog signaling pathway on skeletal muscle from three aspects:Proliferation and differentiation of muscle stem cells,precursor cell and muscle fiber generation,inhibition of inflammation,and regulation of immunity;this article elucidates the role of the Hedgehog signaling pathway in bone reconstruction from two aspects.

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 This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.