Objective:To analyze the problems and risk factors of the investigator initiated out-of-range trial, propose countermeasures and suggestions, and provide reference for improving project standardization and quality, and preventing research risks.Methods:Through literature analysis and field research, combined with personal work experience, this study sorted and analyzed the problems in the regulation of out-of-range IIT conducted in hospital, and proposed countermeasures.Results:Through analysis, it was found that the current out-of-range IIT trial in China faces 5 problems: imperfect management regulations, incomplete IIT management organizational system in medical institutions, insufficient scientificity of research protocols, insufficient ethical review, and insufficient research funds.Conclusions:Out-of-range IIT is of great significance in promoting pharmaceutical innovation. Standardized management of such projects requires the efforts of regulatory authorities, medical institutions, and ethics committees, as well as the continuous improvement of researchers' awareness and research capabilities to promote the orderly, high-quality, and rapid development of IIT. Based on the above analysis, this article proposed countermeasures and suggestions: at the national level, summarize practical experience from various regions as soon as possible, improve IIT management regulations and technical guidelines; establishing clinical research and design guidance departments in medical institutions and strengthening scientific review; the ethics committee formulates ethical review standards and processes for out-of-range IIT projects to enhance review capabilities; establish a normalized clinical research training mechanism in hospitals; expand and standardize the channels for IIT funding.

Objective:In order to strictly prevent academic misconduct, effectively improve the understanding and judgment ability of researchers on medical ethics issues involved in papers, and ensure scientific and standardized research results, strict ethical review is crucial.Methods:It mainly reviews whether the clinical research paper to be submitted has obtained an ethical approval certificate, whether the content of the paper exceeds the scope of ethical approval permission or violates research ethical standards, etc., and establishing a sound paper ethics review mechanism.Results:This paper summarizes the issues, points and considerations of ethical review before submission of clinical research papers, hoping to provide some practical methods and references for the ethical review of clinical research papers in China.Conclusions:Medical and health institutions mostly carry out biomedical research involving humans, and should pay more attention to ethical norms and requirements, educate and guide researchers to strengthen ethical awareness, and improve their attention and judgment ability to medical ethical issues in papers.

Objective:To explore the feasibility of autologous transplantation of frozen-thawed ovarian tissue to induce pubertal development in adolescent females.Methods:Before hematopoietic stem cell transplantation in patient with severe β-thalassemia, 11 pieces of ovarian tissue were frozen in the Center of Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University in 2019. The patient was diagnosed as premature ovarian failure after hematopoietic stem cell transplantation. There were no signs of puberty development and menarche. Orthotopic ovarian tissue transplantation was performed for the patient through laparoscopy, and a total of 5 pieces of ovarian tissue were transplanted on January 20, 2022. Postoperatively, we followed up the sex hormone levels, growth and development of the patients and menarche.Results:The patient developed menarche 5 months after ovarian transplantation. The levels of sex hormones showed that follicle-stimulating hormone and luteinizing hormone were significantly decreased, and estradiol levels were significantly increased, indicating that ovarian tissue transplantation was successful, and follicles had begun to recruit and develop. The patient's ultrasonography revealed a markedly enlarged uterus and a thickened endometrium. Antral follicles were detected in the left implantation site of pelvic cavity.Conclusion:Cryopreservation of ovarian tissue is recommended for fertility preservation in prepubertal children. Autologous frozen-thawed ovarian tissue transplantation can induce natural puberty development and restore the reproductive endocrine function in children with ovarian failure, delayed puberty development or even stagnation.

Objective:To explore the feasibility of autologous transplantation of frozen-thawed ovarian tissue to induce pubertal development in adolescent females.Methods:Before hematopoietic stem cell transplantation in patient with severe β-thalassemia, 11 pieces of ovarian tissue were frozen in the Center of Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University in 2019. The patient was diagnosed as premature ovarian failure after hematopoietic stem cell transplantation. There were no signs of puberty development and menarche. Orthotopic ovarian tissue transplantation was performed for the patient through laparoscopy, and a total of 5 pieces of ovarian tissue were transplanted on January 20, 2022. Postoperatively, we followed up the sex hormone levels, growth and development of the patients and menarche.Results:The patient developed menarche 5 months after ovarian transplantation. The levels of sex hormones showed that follicle-stimulating hormone and luteinizing hormone were significantly decreased, and estradiol levels were significantly increased, indicating that ovarian tissue transplantation was successful, and follicles had begun to recruit and develop. The patient's ultrasonography revealed a markedly enlarged uterus and a thickened endometrium. Antral follicles were detected in the left implantation site of pelvic cavity.Conclusion:Cryopreservation of ovarian tissue is recommended for fertility preservation in prepubertal children. Autologous frozen-thawed ovarian tissue transplantation can induce natural puberty development and restore the reproductive endocrine function in children with ovarian failure, delayed puberty development or even stagnation.

Objective:To study the different region (DFR) genotyping of 15 strains of Yersinia pestis from Inner Mongolia. Methods:Fifteen strains of Yersinia pestis isolated from Otog Banner and Darhan Muminggan Joint Banner in Meriones unguiculatus plague foci in Inner Mongolia Plateau, Zhengxiangbai Banner in Spermophilus dauricus plague foci in the Songliao Plain in 2019 were amplified by PCR, and identified DFR genotyping. Results:Two strains of Yersinia pestis in Otog Banner jointly deleted DFR loci 1, 6, 7, 13, 15, 16, 17, 18, 23, and 13 strains of Yersinia pestis in Darhan Muminggan Joint Banner and Zhengxiangbai Banner jointly deleted DFR loci 1, 6, 7, 12, 13, 15, 16, 17, 18 and 23. G17 and G20 were classified as genotyping by comparison with DFR locus distribution and genotyping results. Conclusion:The genotyping of Yersinia pestis in the natural foci of Meriones unguiculatus plague foci in Inner Mongolia Plateau and Spermophilus dauricus plague foci in the Songliao Plain is the same as that of the historical strain.

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of microRNA-146a (miR-146a) with clinical features of rheumatoid arthritis (RA). METHODS: In 126 patients with RA and 102 matched healthy controls, SNPs of miR-146a rs2910164 locus were determined with a high-resolution melting method. The association of such polymorphisms with disease activity score in 28 joints (DAS28) and clinical features of RA was assessed. RESULTS: The distribution of SNPs of miR-146a rs2910164 among RA patients did not differ from that of the control group. No significant association was found between miR-146a rs2910164 polymorphism with DAS28. However, RA patients with a GG genotype had a greater chance to develop extra-articular manifestations (P<0.01). CONCLUSION Polymorphisms of miR-146a rs2910164 locus is not an independent risk factor for RA, though its GG genotype may be associated with extra-articular manifestations of RA.
Arthritis, Rheumatoid ; genetics ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; MicroRNAs ; genetics ; Polymorphism, Single Nucleotide

Objective The aim of this study was to investigate the microbial contamination situation in infant formula powder during the processes of production.Methods A total of 880 samples were collected from Gansu Province,which included raw materials,manufacturing facilities,personnel swabs and final infant formula powder.The detection method conducted in this study were complied with the standard of the SN/T 0738-1997 and GB 4789,and the microbial species detected in this study included Enterobacteriaceae,Enterobacter sakazakii,and Bacillus cereus.Results The detection rate of Enterobacteriaceae was 28.41％ (250/880),the detection rates of Enterobacter sakazakii and Bacillus cereus were 0.46％ (4/872) and 16.94％ (31/183) respectively.The prevalence of Enterobacteriaceae (40.00％,40/100) was the highest in raw materials.Four Enterobacter sakazakii strains were isolated from the pretreatment workshop,equipment and environment surface.The prevalence of Bacillus cereus was 22.73％ (10/44) in final product.Conclusion The microbial contamination was existent widely in infant formula powder and the production procession.Rigid laws and managements should be conducted to reduce the microbial contamination in raw materials,production processes and the environment,which might improve the quality of infant formula powder.

The content of endogenous anabolic steroids is extremely low in biological matrices.Its chemical structure contains polar functional groups such as hydroxyl and carbonyl, which limits their applicability in GC-MS.The lack of ionized groups in the chemical structure leads to poor sensitivity in LC-MS, which plays a significant role in various physiological activities analysis.It is an effective way to enhance the response of mass spectrometer by modifying the chemical structure of endogenous anabolic steroids through derivatization technology.This review summarizes various derivatization reagents and corresponding derivatization processes of endogenous anabolic steroids analysis in the methods based on different testing instruments and methodologies.The advantage and disadvantage of all kinds of derivatiaztion methods and the prospect of the endogenous anabolic steroids derivatiaztion techniques are also discussed.

Background:Functional dyspepsia (FD)with anxiety and gastric hypersensitivity is still one of the therapeutic difficulties in clinic. Gastrodin (Gas)may have dual effects of modulating gastric sensitivity and anxiety. Aims:To investigate the effect of Gas on gastric sensitivity and anxiety-like behavior in FD with anxiety-like gastric hypersensitivity in rats. Methods:Forty rats were randomly divided into control group,model group,buspirone group,low-dose Gas group and high-dose Gas group. Maternal separation,acute gastric irritation and restraint stress were sequentially performed to induce FD model with anxiety-like gastric hypersensitivity. At the 8th week,rats in control group and model group were intraperitoneally injected with 0. 9% NaCl solution 2. 0 mL/ kg,rats in buspirone group were given buspirone 3. 125 mg/kg,and rats in low- and high-dose Gas groups were given 62. 5,125. 0 mg/ kg Gas,respectively. The course was 7 days. Then elevated plus maze (EPM),open field test,abdominal withdrawal reflex (AWR)and electromyography (EMG) were performed. Results:Compared with control group,EPM test showed that proportions of open arms entries and duration were significantly decreased (P < 0. 01);open field test showed that virtual central grids duration (P < 0. 05),number of virtual grids climbed and times of lifting were significantly decreased (P < 0. 01);when gastric balloon dilatation pressure was equal or greater than 40 mm Hg,AWR score,area under ROC curve (AUC)of EMG was significantly increased in model group (P < 0. 05). Compared with model group,above-mentioned indices in low- and high-dose Gas groups were significantly ameliorated (P < 0. 05). Conclusions:Gas could influence the gastric sensitivity and anxiety-like behavior of the brain-stomach axis regulated anxiety-like gastric hypersensitivity in FD rat model.

Objective To illustrate more accurately the feasibility of DNA barcode technology in species identification in different geographical areas.Methods Four plague host animals were selected from three plague natural foci in Inner Mongolia for DNA barcode comparison,GC base content,codon preference and genetic distance calculation,and a phylogenetic tree was constructed.Results Compared between different foci of A llactaga sibirica,the difference of base content was statistically significant (F =5.34,P ＜ 0.05);the variation of Meriones unguiculatus focus Allactaga sibirica base content was larger,and compared with other foci Allactaga sibirica,the difference was statistically significant (all P ＜ 0.05).Different foci between one species rarely exist in codon sites.The genetic distance of intraspecific was less than 1％,and the genetic distance of interspecific was more than 18％.Conclusions DNA barcode of each species is specific,with no interspecific species sharing,and does not change with geographical position.Molecular identification of plague host animal is effective by DNA barcode.