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

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 compare the efficacy and safety of cold-endoscopic mucosal resection (C-EMR) and hot-endoscopic mucosal resection (H-EMR) for the treatment of colorectal polyps sized 10-20mm.Methods:Patients who underwent colonoscopy at the Gastrointestinal Endoscopy Center of the Eighth Affiliated Hospital, Sun Yat-sen University from January 2022 to January 2023 were selected as the research subjects. Patients meeting the inclusion criteria with at least one 10-20 mm, Paris type Ⅰs, type Ⅱa polyp were selected. They were divided into C-EMR group (no high-frequency current treatment) and H-EMR group (high-frequency electrical polyp removal) based on the random number table method. The main outcome measures were the complete resection rate of polyps, the incidence of postoperative complications (bleeding, perforation and infection), and the recurrence rate of polyps in the two groups. Secondary outcomes were the procedure time and cost-effectiveness.Results:A total of 209 eligible polyps were found in 209 patients, 105 in the C-EMR group (105 patients) and 104 in the H-EMR group (104 patients). There was no significant difference in the complete removal rate of polyps [91.4% (96/105) VS 95.2% (99/104), χ2=1.184, P=0.276], the recurrence rate of polyps [2.9% (3/105) VS 1.9% (2/104), χ2=0.195, P=0.683] or the incidence of complications [5.7% (6/105) VS 1.9% (2/104), χ2=2.040, P=0.280] between the C-EMR group and the H-EMR group. Compared with H-EMR group, the operation time of C-EMR group was shorter (5.26±2.41 min VS 9.34±5.63 min, t=-8.478, P<0.001), and the number of titanium clips used was fewer (2.55±0.94 VS 3.94±1.14, t=-9.623, P<0.001), and the differences between the two groups were statistically significant. The cost of polypectomy was lower in the C-EMR group than that in the H-EMR group (2 720±452 yuan VS 3 031±293 yuan), but the difference was not stastistically significant（ t=-5.896， P=0.651）. Conclusion:C-EMR demonstrates non-inferior efficacy and safety in treating 10-20 mm colorectal polyps compared with H-EMR. Widespread adoption of C-EMR may lead to reduced healthcare costs and expenditures.

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.

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: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 effect and safety of tirofiban bridging combined with aspirin for anti-platelet therapy in patients with acute cerebral infarction (ACI) beyond the thrombolytic time window.Methods:Sixty patients with ACI treated in Beijing Royal Hospital from January 2021 to September 2022 were retrospectively analyzed. Among them, 30 cases were treated with tirofiban bridging aspirin as the observation group, while 30 cases were treated with aspirin alone as the control group. The total effective rate of clinical treatment, the degree of neurological deficit, the degree of disease outcome and the incidence of adverse reactions were compared between the two groups. The degree of neurological deficit was evaluated using the National Institutes of Health stroke scale (NIHSS), and the degree of disease outcome was evaluated using the modified Rankin scale (mRS).Results:The overall effective rate in the observation group was significantly higher than that in the control group: 93.3% (28/30) vs. 66.7% (20/30), with a statistically significant difference ( χ2 = 10.97, P<0.01). Before treatment, there was no statistically significant difference in NIHSS score between the two groups ( P>0.05). However, after treatment, the NIHSS score in the observation group was significantly lower than that in the control group: (2.83 ± 1.87) scores vs. (4.93 ± 3.05) scores, indicating a significant difference ( t = -3.21, P = 0.002). No significant difference was observed in mRS score between the two groups before treatment( P>0.05). After treatment, the observation group showed significantly lower mRS score compared to the control group: 2.00 (1.00, 2.00) scores vs. 3.00 (2.00, 4.00) scores ( P = 0.006). There was no statistical difference in the incidence of adverse reactions between the observation group and control groups ( P>0.05). Conclusions:Tirofiban bridging aspirin has stronger inhibitory effect on platelet activity than simple application of aspirin for ACI patients with ultra-thrombolytic window, which can rapidly improve the degree of neurological impairment and daily living ability of patients, and the incidence of adverse reactions has not increased significantly.

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.

Objective To investigate the expression changes of serum circRNA membrane bound O-acyltransferase 2(circRNA MBOAT2)and circRNA recombinant actinin 4(circRNA ACTN4)in patients with cholangiocarcinoma and their relationship with prognosis.Methods 96 patients with cholangiocarcinoma treated at the First Hospital of Handan City from January 2020 to January 2022 in Department of Hepatobiliary Surgery were regarded as as the cholangiocarcinoma group.Additionally,85 patients with intraductal stones and 90 healthy volunteers were collected as the stone group and control group,respectively.Quantitative real-time reverse transcription PCR(qRT-PCR)was applied to detect the expression levels of circRNA MBOAT2 and circRNA ACTN4.χ2 test was applied to analyze the relationship between circRNA MBOAT2 and circRNA ACTN4 and clinical pathological features.Pearson was applied to analyze the correlation between circRNA MBOAT2 and circRNA ACTN4 in patients with cholangiocarcinoma.ROC was applied to analyze the diagnostic value of circRNA MBOAT2 and circRNA ACTN4 in the occurrence of cholangiocarcinoma.COX was applied to analyze the influencing factors of poor prognosis in patients with cholangiocarcinoma.Kaplan-Meier method was applied for survival analysis.Results circRNA MBOAT2(1.24±0.38)and circRNA ACTN4(1.27±0.42)in cholangiocarcinoma group were higher than those in stone group(1.02±0.31,1.05±0.34)and control group(0.83±0.24,0.78±0.21),and the stone group was higher than that in control group,with statistically significance(t=5.016～14.025,all P<0.05).There was a positive correlation between circRNA MBOAT2 and circRNA ACTN4 in patients with cholangiocarcinoma group(r=0.428,P<0.05).Combined diagnosis of MBOAT2 and ACTN4 was better than single diagnosis of cholangiocarcinoma(Z=4.063,4.004,all P<0.05);circRNA MBOAT2 and circRNA ACTN4 were correlated with clinical staging and lymph node status(t=5.091～5.984,all P<0.05).Positive lymph node status and elevated levels of circRNA MBOAT2 and circRNA ACTN4 were independent risk factors for mortality(HR=1.527,1.582,1.727,all P<0.05).The cumulative survival rate of patients with high expression of circRNA MBOAT2(23.40%vs 46.94%)and circRNA ACTN4(24.00%vs 47.83%)was lower than that of patients with low expression(χ2=5.809,5.946,all P<0.05).Conclusion The serum levels of circRNA MBOAT2 and circRNA ACTN4 increase with the progression of the disease,and the combination of the two has certain value in diagnosing the occurrence of cholangiocarcinoma.