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

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

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.

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.

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: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 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: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.

Objective To explore differentially expressed proteins in the serum exosomes of acute myeloid leukemia(AML)patients and healthy controls by using the proteomics method,and provide new biomarker for the diagnosis and treatment of AML.Methods A total of 76 AML patients diagnosed and treated in the First People's Hospital of Honghe State from November 2022 to June 2024 were selected as the experimental group,and 60 healthy physical examination participants were selected as the control group.Tandem Mass Tag(TMT)labeled proteomics was used to identify the differences in protein expression in serum exosomes between the experimental and control groups,and the identified differentially expressed proteins were subjected to bioinformatics analysis.Western-Blot was used to verify the differentially expressed proteins.Results Comparedwith healthy controls,146 aberrantly expressed proteinswere detected in serum exosomes of AML patients,of which 89 were up-regulated and 57 were down-regulated.Among them,Alpha-1-antichymotrypsin(α1-ACT),Angiogenin(ANG),Vitronectin(VIT),Clusterin(Clu),Fibronectin(FN),Keratin type I cytoskeletal-18(KRT18),and actinin alpha4(ACTN4)showed changed significantly.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis indicated that differentially expresseproteins were involved in biological processes such as neutrophil immunity,neutrophil degranulation,neutrophil activation immune response,and protein activation cascade,significantly enriched in 25 biological pathways including complement and coagulation cascades,extracellular matrix(ECM)-receptor interaction,and hypoxia-inducible factor-1(HIF-1)signaling pathways.Western-blot validation results showed that compared with the control group,the expression levels of ANG,Clu and FN in the serum exosomes of AML patients were significantly increased,while the expression level of ACTN4 was significantly decreased,with statistically significant differences(t=-11.854～18.569,all P<0.05).The expression levels of ANG and FN were correlated with white blood cell count(F=8.888,7.818,all P<0.05)and cytogenetics(F=8.619,7.983,P<0.05).The expression level of Clu protein was correlated with white blood cell count(F=2.571,P<0.05),but not significantly associated with cytogenetics(F=1.886,P>0.05).ANG,FN and Clu showed no significant correlation with FAB classification(F=0.175,0.434,0.042,all P>0.05).Conclusion The expression of exosomal proteins in the serum of AML patients compared to healthy individuals are significant differences,which may serve as serological markers for the diagnosis and treatment of AML.