Congenital disorders of glycosylation(CDG)are a group of rare inherited metabolic diseases due to defects in the glycosylation of glycoproteins and/or glycolipids.Most of them are autosomal recessive and have multisystemic manifestations, which is characterized by dysmorphic facial features, developmental delay, growth failure, hypotonia, neurological abnormalities, hypoglycemia and multisystem disfunctions.Isoelectrofocusing(IEF)analysis of transferrin(Tf)and mass spectrometry(MS)technology can diagnose some subtypes of CDG, while many currently rely on genomic sequencing technology for diagnosis.A few subtypes can be clinically relieved or even cured by treatment, but most have no effective treatment.Development of molecular, biochemical and facial recognition techniques may deepen our understanding of this disease.

Objective The concentration of cytokines in the amniotic fluid ( AF) may reflect the immune state of maternal-fetal interface .This study aimed to investigate the level of inflammation -related cytokines in the mid-trimester AF of normal pregnant women. Methods This study included 263 pregnant women undergoing mid-trimester genetic amniocentesis , and all of them had normal pregnancy outcomes .Using MILLIPLEX MAP and Luminex, we measured the concentrations of interleukin IL-10, IL-1β, IL-6, monocyte chemotactic MCP-1, and tumor necrosis factor TNF-αin the AF collected from the women at 18-22 +6 weeks′gesta-tion.We analyzed the correlation of their concentrations with maternal age , gestational age , and fetal gender by rank sum test . Results The median concentrations of IL-10, IL-1β, IL-6, MCP-1, and TNF-αin AF at mid-trimester were 7.91, 0.97, 78.15, 1 135.57, and 8.47 pg/mL, respectively.The levels of IL-10 and IL-1βwere higher in the pregnancies with male fetuses than in those with female fetuses (8.54 and 1.18 pg/mL vs 7.72 and 0.85 pg/mL, P=0.043 and 0.008).Maternal age or gestational week at the mid-trimester exhibited no influence on the concentrations of the 5 cytokines. Conclusion The levels of IL-10, IL-1β, IL-6, MCP-1 and TNF-αremain stable in AF at mid-trimester and the former 2 are higher in pregnancies with male fetuses .

Objective Through investigating the clinicians’ scientific research level and weakness,we can carry out targeted clinical research training systematically,and then strengthen their utilization of clinical resources and data,and finally promote the transformation of scientific research resuits.Methods Filling and submitting the online questionnaires through WeChat,a popular chatting tool in China,physicians from 13 affiliated hospitals of a university in Shanghai have joined this research.Results 507 valid questionnaires have been received online:In terms of clinical research capacity,there seemed to be more barriers in the following issues:comprehension of the types and applications to design a clinical trial,formulation of the details including PICO elements(Patient-Intervention-Comparison-Outcome),methodological application including the category and principle of randomization,the category and principle of blind method and how to control the confounding elements and probable bias,and statistical problems in scientific research including discrimination of the different definition between FAS(Full Analysis Set) based on the principle of ITT(Intention-To-Treat) and PPS(Per-Protocol Set),how to write a standardized SAP(Statistical Analysis Plan) and how to calculate the sample size of a trial),and various management of clinical trials including data management,follow-up management,adverse event management and so on,and writing a protocol and a CRF (Case Report Form) in a standard and professional way.As for the needs for training,the top three topics were how to design a clinical research in a standardized style,how to practice the methodology and how to utilize the statistical skills into clinical trials.Conclusions Standardized design and writing of clinical trial protocols according to the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items:Recommendations for Interventional Trials),and the application of epidemiological and statistical methods are still short boards that most clinicians need to improve urgently,also are what they most concerned about at the same time.So it is necessary for physicians to receive systematic clinical research training to enhance their scientific research capacity.

Objective To improve clinical research capability and quality,this study aims to explore the methodological support system of Investigator Initiated Trials (IITs).Methods By comparing the clinical research supporting system between commercial and academic organization at home and abroad,this study summarized their characteristics and make systematic analysis combined with IITs.Results Compared with international level,there is an urgent need to improve of domestic,professional support for clinical research.Academic clinical research supporting academic system could better satisfy the requirement of IITs in China.Taking Shanghai Jiao Tong University School of Medicine as an example,this paper introduces the a collaborative construction model,namely Multiple-center Academic Clinical Research Organization (MACRO),based on two levels of clinical research institutes in university and affiliated hospitals.At universities level,we focused on development of clinical research,top-level study design,clinical research methodology,clinical research professionals and standardized clinical research platform.At hospitals level,project process management can be emphasized,and which will be the main implementation content to build an applied clinical research technology center in MACRO.Conclusions With the construction of MACRO,the functional module paradigms of academic clinical research centers in university can be effectively linked to affiliated hospitals.This will be conducive for establishing collaborative support system,which is centered on academic research and complementary functions with multiple centers,improving full-time technical team and further enhancing the scientific validity and research quality of IITs.

Objective:Investigator Initiated Trials (IIT) play a key role in promoting comprehensively the development and homogeneity of clinical diagnosis and treatment, thus, this article aims to explore a set of recommendations for the construction and management of clinical research institutes that support IIT.Methods:Through the combination of literature review and institutional construction practice cases, based on the experience of domestic and foreign universities and well-functioning medical institutions in building clinical research centers, as well as summarizing the construction cases of the clinical research institute of Shanghai Jiao Tong University School of Medicine, to discuss the construction and management plan of such centers.Results:Propose recommendations for the construction and management standards of clinical research centers that support IIT, covering the principles of center construction, basic settings, organizational structure, functional departments, basic platforms, staffing, document management and institutional evaluation.Conclusions:We hope this study can provide reference to universities and medical institutions for the construction of the clinical research institute.

By comparing the training status of clinical research methods between United States and China, this article introduces comprehensive training system in the United States in and after the university, and discusses the problems in clinical research methodology training in China. These issues include that when medical students at school do not receive the training of professional clinical research courses, and after they go to the work, they also lack professional and accurate clinical research methodology training, which make it difficult for doctors to independently conduct clinical research. Therefore, it is recommended that Chinese medical schools should systematically establish clinical research methodology courses for undergraduates and graduate students to cultivate the clinical research capabilities of medical students. Secondly, according to the clinical research levels of doctors, different training models are proposed in the study. The existing social resources should be scientifically guided. We hope our work would provide some references for the improvement of clinical research methodology in China, to promote clinicians to be independently responsible for conducting clinical research, and improve the national medical level.

Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic syndrome associated with abnormal activation of RAS-mitogen-activated protein kinase(RAS-MAPK)signal transduction pathway.Causative genes are BRAF, MAP2K1, MAP2K2 and KRAS.CFCS is an autosomal dominant disorder characterized by dysmorphic craniofacial features, congenital heart disease, dermatologic abnormalities, gastrointestinal dysfunction, failure to thrive, neurocognitive delay and epilepsy, whose phenotype overlaps with many other RASopathies.Final diagnosis of CFCS can be reached by classical presentation and genetic testing.Early diagnosis helps to evaluate risk of severe complications of specific genotype and improve prognosis of CFCS patients.At present, there is no effective treatment of CFCS although inhibitors of MEK may improve partial phenotype of CFCS animal models.Once diagnosed with CFCS, the patients need multidisciplinary assessment and treatment.

Effective supervision of the clinical research management department can guarantee and improve the quality of the investigator initiated trials(IIT). The authors analyzed relevant clinical research regulations and literature and summarized the current situation of risk-based IIT project process quality management. On such basis, they determined the risk-based IIT project process quality management method in combination with the previous research of the research group.From 2021 to 2022, this method was used to implement process quality management for 353 IIT projects in Shanghai′s tertiary hospitals. More than 3 000 risk points were identified through centralized supervision, and then on-site supervision was carried out to correct the problems found. As proven by the results, the method could find existing problems in time and define the risk level of the project, and also formulate an individualized risk supervision plan accordingly, so as to effectively ensure the data reliability and scientific results. It is suggested that the clinical research management department implement risk based management for the whole process of IIT projects, increase funding and staffing, and implement hierarchical management for the projects by research types, so as to promote the sustainable development of IITs.

Objective To determine the incidence and prevalence of transient ischemic attack (TIA) and to evaluate its epidemiological situation in Hunan province.Methods Seven monitoring points were randomly selected from the province,a total of 8 311 subjects aged≥50 years were then chosen by stratified sampling.The cases counted in prevalence was defined as patients diagnosed before 24:00 o'clock August 31st,2013,and the new diagnosis for incident counting was defined as those diagnosed between 00:00 September 1st,2012 and 24:00 August 31st,2013.Results Among all 8 311 screened subjects,the number of TIA patients was 24 (288.8 per 100 000 people),the incidence of TIA was 7 (85.2 per 100 000 people).Standardized prevalence and incidence were 283.2 and 82.4 per 100 000 respectively using 2010 China census population.Among them,the standardized incidence rate of female was higher than that of male (114.8 per 100 000 person-years vs.48.8 per 100 000 person-years),and the prevalence rate of males was higher than that of female (288.2 per 100 000 people vs.273.2 per 100 000 people).Hypertension is the most important risk factor for TIA (55.2％).Conclusion The incidence and prevalence of TIA in Hunan province are higher than the national average.Hypertension is the main risk factor.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Adolescent ; Humans ; Male ; China ; Computational Biology ; Genomics ; Genotype ; Mutation