To explore the correlation between MTHFR C677T gene polymorphism and hypertension, hyperhomocysteinemia(Hcy), and hyperlipidemia in the Tibetan population of Tibet.

Investigator-initiated clinical trials （IIT） are an important part of scientific and technological activities involving human study participants. Among them， high-quality IIT can be used to support the marketing and registration application of drugs， medical devices， and other products when conditions permit. Currently， there is a huge gap between IIT and industry-initiated clinical trials. The use of unlisted products in IIT has problems， such as lack of regulatory support， insufficient research funding support， the need to improve the ability of clinical research management departments， the weakness of professional clinical research teams， and the difficulty of ethics review to match the demands. The challenges could be addressed by improving regulations and conducting pilot trials on a small scale， guaranteeing adequate research funding， strengthening the construction of clinical research management systems， building professional clinical research teams， ensuring the quality of ethical reviews and strict follow-up reviews， shifting from ethical reviews to a system for protecting research participants， and reinforcing training for researchers. Ethics committees should strictly review key points， such as the risk-benefit ratio， informed consent， research funding， compensation for damages， qualifications and equipment of research team members， and management of conflict of interest.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

Alzheimer's disease(AD)is the leading cause of dementia,and no effective treatment has been devel-oped for it thus far.Recently,the use of natural compounds in the treatment of neurodegenerative diseases has garnered significant attention owing to their minimal adverse reactions.Accordingly,the potential therapeutic effect of pterostilbene(PTS)on AD has been demonstrated in multiple in vivo and in vitro experiments.In this study,we systematically reviewed and summarized the results of these studies investigating the use of PTS for treating AD.Analysis of the literature revealed that PTS may play a role in AD treatment through various mechanisms,including anti-oxidative damage,anti-neuroinflammation,anti-apoptosis,cholinesterase activity inhibition,attenuation of β-amyloid deposi-tion,and tau protein hyperphosphorylation.Moreover,PTS interferes with the progression of AD by regulating the activities of peroxisome proliferator-activated receptor alpha(PPAR-α),monoamine oxi-dase B(MAO-B),silent information regulator sirtuin 1(SIRT1),and phosphodiesterase 4A(PDE4A).Furthermore,to further elucidate the potential therapeutic mechanisms of PTS in AD,we employed network pharmacology and molecular docking technology to perform molecular docking of related proteins,and the obtained binding energies ranged from-2.83 to-5.14 kj/mol,indicating that these proteins exhibit good binding ability with PTS.Network pharmacology analysis revealed multiple po-tential mechanisms of action for PTS in AD.In summary,by systematically collating and summarizing the relevant studies on the role of PTS in treatment of AD,it is anticipated that this will serve as a reference for the precise targeted prevention and treatment of AD,either using PTS or other developed drug interventions.

OBJECTIVE: To investigate the clinical phenotype and genetic etiology of a patient with tall stature and primary amenorrhea presenting with 47,XYY Disorder of sex development (DSD). METHODS: A female patient presenting with "tall stature and primary amenorrhea" at Nanjing Drum Tower Hospital in July 2024 was selected as the study subject. A retrospective study design was employed to collect the patient's clinical data. Peripheral venous blood sample was collected. Following the extraction of genomic DNA, genetic testing was performed including chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), multiplex PCR for the AZF regions and sex-determining genes Y (SRY), and whole-exome sequencing (WES). Candidate variants were validated by Sanger sequencing and classified for pathogenicity based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital (Ethics No.: 2022-451-01). RESULTS: The patient had a height of 188 cm and a body weight of 50 kg, in addition with infantile uterus, absent ovaries, and primary amenorrhea. G-banded karyotyping analysis of peripheral blood sample revealed 47,XYY. CNV-seq indicated Seq[GRCh37]Yp11.32q12×2. No deletion was detected in the AZF regions of Y chromosome, and SRY was positive. WES identified a heterozygous c.86C>A (p.Thr29Lys) variant of the NR5A1 gene, leading to substitution of threonine with lysine at position 29 of the encoded protein. Sanger sequencing confirmed the presence of the variant. According to the ACMG guidelines, this variant was classified as variant of uncertain significance (VUS) with supporting evidence (PS3_Moderate+PM5+PP3+PM2_Supporting+PS4_Supporting). Reviewing the nearly 60 years of previously reported cases, all 7 documented 47,XYY DSD patients were assigned a female social gender and presented with abnormal gonadal and external genitalia development. Among them, 5 cases underwent SRY testing, all of which were positive. Only 1 case underwent whole-exome sequencing (WES), but no pathogenic or likely pathogenic variants were identified. CONCLUSION This DSD patient presented with the clinical features of tall stature and primary amenorrhea. The NR5A1 gene variant c.86C>A (p.Thr29Lys) probably underlay the Disorder of sex development in this patient. Above finding has enriched the spectrum of pathogenic variants of the NR5A1 gene.
Humans ; Female ; Steroidogenic Factor 1/genetics* ; DNA Copy Number Variations/genetics* ; XYY Karyotype/genetics* ; Karyotyping ; Retrospective Studies ; Phenotype ; Sex Chromosome Disorders of Sex Development/genetics* ; Sex Chromosome Disorders

Objective To investigate the attention characteristics of patients with stable schizophrenia.Methods Fifty-five stable schizophrenic patients and 55 healthy subjects were included in the study.The attention network test paradigm(ANT paradigm)was used to measure the attention of participants.The observed indexes included reaction time under four cues and three stimulus types and converted reaction time(alerting network,orienting network,and executive control network).Results Under different cue prompts and stimulus conditions,the reaction time of patients with stable-phase schizophrenia was higher than that of the control group(P<0.001).The alerting network[25.43(11.71,42.53)ms vs.39.32(27.46,51.98)ms,P=0.020]and executive control network[96.17(36.32,160.13)ms vs.44.43(18.52,89.73)ms,P<0.001]in the patient group were significantly lower than those in the control group,while there was no significant difference in the orienting network compared to the control group(P=0.136).Conclusion Patients with stable schizophrenia show significant impairment in the efficiency of the alerting and executive control networks,while the orienting network is not significantly impaired.

As a major global public health concern,cancer has witnessed a continues rise in both incidence and mortality rates.It pose not only a severe threat to human health but also a heavy burden on socioeconomic systems.Despite remarkable advancements in oncology research,critical challenges such as tumor heterogeneity,drug resistance,and limitations in early screening and diagnostic technologies remain to be addressed.Against this backdrop,artificial intelligence(AI),with its unique advantages in big data analysis,pattern recognition,and predictive modeling,has opened new avenues for cancer research.By integrating multi-modal data,including omics,imaging,and clinical information,AI not only accelerates investigations into fundamental tumor mechanisms but also demonstrates immense potential in areas such as early screening,biomarker discovery,and personalized treatment.These advancements have fostered a deeper integration of precision medicine and oncology.This review provides a comprehensive overview of the most recent progresses in the application of AI in cancer diagnosis and treatment research,with a focus on its practical value across diverse data types and clinical scenarios,as well as future directions for its development.

Objective:To analyze the changes in the number of patients, incidence, mortality rate, disability-adjusted life year (DALY), years lived with disability (YLD), and years of life lost due to premature mortality (YLL) globally and in China from 1990 to 2021, and to predict future trends in the number of patients and DALY of inflammatory bowel disease (IBD) globally and in China.Methods:Descriptive epidemiology was applied. Data on globally and Chinese IBD burden indicators, including prevalence, incidence, mortality, DALY, YLL, and YLD were collected from the Global Burden of Disease (GBD) 2021 Database from 1990 to 2021, and the trends in the changes and distributions of age and gender were analyzed. The age-standardized rate was standardization based on the world standard population age structure estimated by GBD. Auto-regressive integrated moving average model was used to predict the number of IBD patients and DALY globally and in China from 2022 to 2030.Results:In 1990 and 2021, the global number of IBD patients was 2.170 2 and 3.830 1 million, respectively, while in China which was 62 100 and 168 100, respectively. The global crude incidence rate and age-standardized incidence rate were 3.74/100 000, 4.22/100 000, 4.75/100 000, and 4.45/100 000, respectively. The crude incidence rate and age-standardized incidence rate in China were 0.71/100 000, 0.74/100 000 and 1.75/100 000, 1.40/100 000, respectively. In 1990 and 2021, the global crude mortality rate and age-standardized mortality rate of IBD were 0.40/100 000, 0.60/100 000 and 0.54/100 000, 0.52/100 000, respectively; the crude mortality rate and age-standardized mortality rate in China were 0.37/100 000, 0.75/100 000 and 0.40/100 000, 0.33/100 000, respectively. Compared with those in 1990, the global crude DALY, YLD and YLL of IBD all increased in 2021, which were 1 510.8 thousand person-years vs. 948.9 thousand person-years, 579.2 thousand person-years vs. 330.9 thousand person-years, 931.6 thousand person-years vs. 618.0 thousand person-years; the age-standardized DALY, YLD and YLL all decreased, which were 18.07/100 000 vs. 21.54/100 000, 6.79/100 000 vs. 7.27/100 000, 11.27/100 000 vs. 14.27/100 000, respectively. Compared with those in 1990, the crude YLD and the age-standardized YLD in China both increased (26.9 thousand person-years vs. 10.1 thousand person-years, 1.47/100 000 vs. 0.91/100 000), while the crude DALY, the age-standardized DALY, crude YLL and the age-standardized YLL all decreased (136.9 thousand person-years vs. 162.2 thousand person-years, 7.68/100 000 vs. 18.38/100 000, 110 thousand person-years vs. 152 thousand person-years, 6.21/100 000 vs. 17.47/100 000).From 1990 to 2021, male and female age-standardized incidence and prevalence of IBD were all in upward trend. The difference in the incidence of IBD between males and females was relatively small, and the global age-standardized incidence of IBD in males were slightly higher than those in females, while in China the rates are similar between the two genders. The global and Chinese age-standardized prevalence in females were slightly higher than those in males. From 1990 to 2021, the estimated annual percentage change (EAPC) of age-standardized IBD incidence in global and China were 0.24 (95% confidence interval (95% CI): 0.16 to 0.31) and 1.55 (95% CI: 1.25 to 1.86), respectively; the EAPC of age-standardized DALY in global and China were -0.50 (95% CI: -0.58 to -0.41) and -2.71 (95% CI: -2.99 to -2.43), respectively. The age distribution of disease onset shifted towards middle-aged and old population. It was predicted that by 2030, the annual number of new IBD cases in global would increase to 410 100, while in China, it would decrease to 21 184. Furthermore, the global DALY of IBD would increase to 1 670 527 person-year, and in China which would be 140 563 person-year. Conclusions:From 1990 to 2021, the global and Chinese number of patients and the incidence of IBD both sustained increase. The age of IBD onset towards older population. The incidence trend of IBD was aging, with significant gender bias. The global community and China continue to face many severe challenges in IBD.

Objective:As the " Administrative Measures for Conducting investigator-initiated Clinical Research in Medical and Health Institutions" promulgated, to explore the key points and difficulties in the management of Investigator-Initiated Trials(IIT) in healthcare institutions, and provide basis for promoting the standardization and high-quality management of IIT.Methods:On the basis of policy text research , through literature investigation and working practice, this paper analyzes new requirements of the Management Measures for clinical trials management and puts forward implementation suggestions.Results:The Administrative Measures put forward new requirements for the implementation and management of clinical trials from the aspects of scientific review and ethical review, and carried out intervention research beyond the scope, clinical research management committee responsibilities. Medical and carried institutions need to strengthen the management of the whole process of clinical trials implementation.Conclusions:Medical and health institutions can strengthen clinical trials management by building the organizational structure of clinical trials whole-process management, hierarchical risk management, taking scientific review as the starting point, opening up all aspects of project management, focusing on process management, and strengthening quality control and quality assurance.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.