OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Objective To analyze and compare the disease burden of high BMI in Kunshan City in different periods, and to provide a scientific basis for the prevention and control of overweight and obesity in Kunshan City. Methods Using the global burden of disease research method, the number of deaths attributable to high BMI and attributable YLL in Kunshan City were calculated using the survey data of chronic diseases and their risk factors and the data of the death registration system in Kunshan City. Results In 2023, R5.46% of deaths in Kunshan City were attributed to high BMI, with 345 attributable deaths, and attributable mortality rate and standardized attributable mortality rate were 39.16/100 000 and 33.82/100 000, Rrespectively. Attributable YLL rate and standardized attributable YLL rate were 692.35/100 000 and 604.46/100 000, respectively. High BMI caused a loss of 0.52 years of life expectancy per capita. Compared with 2012, PAF, standardized attributable mortality rate, standardized attributable YLL rate and life expectancy loss per capita of high BMI in 2023 increased by 121.95%, 100.71%, 57.05%, and 100%, respectively. Among different genders, PAF increased by 91.05% for males and 161.97% for females from 2012 to 2023. Among different diseases, cardiovascular and cerebrovascular diseases and cancers had the highest attributable disease burden, while diabetes, chronic kidney disease and Alzheimer's disease all had a significant increase. Conclusion The burden of disease attributable to high BMI has risen dramatically in Kunshan City, and the adverse health effects of overweight and obesity need to be reduced through scientific weight loss and comprehensive practical measures.

Objective To analyze the burden of disease of malignant tumors in Kunshan City from 2006 to 2021. Methods The global burden of disease research methodology was applied. The indicators of cancer incidence, mortality, and disability-adjusted life years (DALYs) in Kunshan were calculated using the data from the Tumor Registry System and Death Registry System in Kunshan. The changes in cancer were compared. Results In 2021, the number of incidences and deaths and the DALYs of cancer were 4724 cases, 1618 cases, and 20887.90 person-years, respectively. The incidence, mortality, and DALYs rates were 427.42/100000, 146.39/100000, and 18.90‰. Compared with those in 2006, the incidence rate increased by 53.40%, and the mortality and DALYs rates decreased by 24.23% and 25.73%, respectively. The DALYs rate of cancer was higher for males than for females at 22.12‰ and 15.91‰ in 2021, respectively. The DALYs rate increased with age, and it started to increase sharply after 45 years of age. The top 10 cancers in 2021 in terms of DALYs were lung cancer, stomach cancer, colorectal cancer, liver cancer, pancreatic cancer, breast cancer, leukemia, esophageal cancer, brain and nervous system cancer, and gallbladder and biliary tract cancer, accounting for 83.83% of all cancers. The proportion of years lived with disability (YLD) in DALYs increased continuously (27% in 2021), with females increasing faster than males. Conclusion The disease burden of cancer in Kunshan City remains high, and the incidence of cancer must be reduced by developing comprehensive measures and continuously strengthening the capacity of early screening and treatment of cancer.

Objective:To investigate the impact of tumor origin (ventral pancreatic origin and dorsal pancreatic origin) on prognosis in patients with pancreatic head cancer.Methods:A retrospective analysis was performed on the clinical data of 150 patients with pancreatic head cancer who received surgical treatment at the First Affiliated Hospital of the Naval Medical University from October 2014 to December 2017. Among these patients, 92 were male and 58 were female, aged (61.2±8.8) years. The 150 patients were divided into two groups based on tumor origin: the ventral pancreatic cancer group ( n=72) and the dorsal pancreatic cancer group ( n=78). A comparative analysis of clinical, pathological, and imaging charac-teristics was conducted between the two groups. Univariate and multivariable Cox proportional hazards models were used to analyze the association between pancreatic head cancer origin and overall survival (OS). Results:Patients with pancreatic head carcinoma arising from the ventral and dorsal pancreas accounted for 48%(72/150) and 52%(78/150) of the study cohort, respectively. Pancreatic head carcinoma arising from the dorsal pancreas were more likely to show pathological features of pancreatic parenchymal atrophy [73.1%(57/78) vs. 47.2%(34/72), χ2=10.49, P=0.001] and pancreatitis [44.9%(35/78) vs. 29.2%(21/72), χ2=3.95, P=0.047]. In contrast, patients with pancreatic head carcinoma arising from the ventral pancreas was more frequently associated with contact with the superior mesenteric artery [25.0%(18/72) vs. 1.3%(1/78), χ2=19.04, P<0.001], perineural invasion [100%(72/72) vs. 88.5%(69/78), χ2=8.84, P=0.003], and positive surgical margins [15.3%(11/72) vs. 2.6%(2/78), χ2=7.65, P=0.006], with all differences statistically significant. The ventral pancreatic cancer group demonstrated cumulative survival rates of 33.2% and 0 at 1-year and 2-year postoperative intervals, respectively, while the dorsal pancreatic cancer group exhibited rates of 56.7% and 24.8% at the corresponding timepoints. Comparison of Kaplan-Meier survival curves between the two groups showed a statistically significant difference ( χ2=6.00, P=0.014). Multivariable Cox proportional hazards analysis identified dorsal pancreatic origin pancreatic head cancer as an independent predictor of increased mortality risk compared to ventral origin tumors ( HR=2.75, 95% CI: 1.52-4.98, P=0.001). Conclusion:The embryonic origin of pancreatic head cancer determines its clinical, pathological, and imaging heterogeneity, and pancreatic head cancer arising from the ventral pancreas demonstrates significantly worse prognostic outcomes compared to dorsal pancreatic origin.

Objective To investigate the value of combined detection of serum interleukin-25(IL-25),interleukin-33(IL-33),C-C motif chemokine ligand 2(CCL-2)and C-C motif chemokine ligand 17(CCL-17)in children with bronchial asthma.Methods A total of 91 children diagnosed with bronchial asthma were enrolled into asthma group,and 46 healthy children undergoing routine physical examinations during the same period were included in control group.General clinical data,airway inflammatory markers[fractional exhaled nitric oxide(FeNO)and immunoglobulin E(IgE)]and pulmonary function parameters[forced vital capacity(FVC),forced expiratory volume in one second(FEV1),peak expiratory flow(PEF),minute resting ventilation(VE)and specific airway resistance(Raw)]were comparedbetween the two groups.The levels of serum IL-25,IL-33,CCL-2 and CCL-17 were compared between the two groups.According to the severity of asthma,the patients were further divided into severe asthma subgroup(n=31)and non-severe asthma subgroup(n=60).Spearman correlation analysis was performed to evaluate the association between serum levels of IL-25,IL-33,CCL-2 as well as CCL-17 and the severity of asthma.Multivariate logistic regression analysis was used to identify independent risk factors for severe exacerbation in children with bronchial asthma.The predictive value of serum IL-25,IL-33,CCL-2 and CCL-17 for severe at-tacks of bronchial asthma was analyzed by using the receiver operating characteristic(ROC)curve.Results The levels of FeNO,IgE,IL-25,IL-33,CCL-2 CCL-17 and VE in the asthma group were significantly higher than those in the healthy group,while the levels of FVC,FEV1,PEF and Raw were significantly lower than those in the healthy group(P＜0.05).The levels of FeNO,IgE,IL-25,IL-33,CCL-2,CCL-17 and VE in the severe group were significantly higher than those in the non-severe group,while the levels of FVC,FEV1,PEF and Raw were significantly lower than those in the non-severe group(P＜0.05).The levels of serum IL-25,IL-33,CCL-2 and CCL-17 in children of the asthma group were positively correlated with the severity of asthma(r=0.382,0.416,0.475,0.501,P＜0.05).The levels of serum IL-25,IL-33,CCL-2 and CCL-17 were in-dependent influencing factors for severe asthma.The area under the receiver operating characteristic curve for the combined detection of IL-25,IL-33,CCL-2 and CCL-17 was greater than that obtained from each individual biomarker.Conclusion The combined prediction of serum IL-25,IL-33,CCL-2 and CCL-17 has relatively high value in predicting the development of severe asthma in chil-dren with bronchial asthma.

AIM:To investigate the median effec-tive dose of ciprofol combined with sufentanil to in-hibit tracheal intubation reaction in patients under-going intracranial aneurysm embolization.METH-ODS:Forty-five patients who underwent emboliza-tion for intracranial aneurysms were divided into two groups according to age:non-elderly group(aged 18-64 years)and elderly group(aged＞65 years).Patients in the two groups were first given intravenous ciprofol,of which the initial dose of cip-rofol was 0.4 mg/kg and sufentanil 0.3 μg/kg and rocuronium 0.6 mg/kg were respectively injected according to BIS value and modified observer's as-sessment of alertness and sedation(MOAA/S)score.Then,endotracheal intubation was defined as 3 minutes after the induction of the study drug.Dixon sequential method was adopted,and the dose of ciprofol for the next patient was deter-mined according to whether the tracheal intuba-tion reaction was positive(Positive reaction of tra-cheal intubation was defined as the patient's kino-motor reaction such as coughing during tracheal in-tubation or the increase of MAP or HR within 2 minutes after intubation was greater than 20％of the basic value).When the tracheal intubation indi-cated a positive response,the next patient was raised by one gradient,otherwise,it was lowered by one gradient until the study ended at 7 crosses.The common dose ratio of adjacent patients was 1∶1.1.The Probit probability method was used to cal-culate the 50％effective dose(ED50),95％effective dose(ED95)and the corresponding 95％confidence interval(CI)of ciprofol.Perioperative adverse reac-tions were recorded in both groups.RESULTS:In the non-elderly group,the ED50 of ciprofol inhibit-ing positive tracheal intubation reaction was 0.472 mg/kg(95％CI 0.419-0.565 mg/kg),and the ED95 was 0.567 mg/kg(95％CI 0.513-1.293 mg/kg).In the elderly group,the ED50 of ciprofol inhibiting tra-cheal intubation reaction was 0.409 mg/kg(95％CI 0.383-0.434 mg/kg)and the ED95 was 0.452 mg/kg(95％CI 0.430-0.591 mg/kg).CONCLUSION:The ED50 of ciprofol combined with sufentanil inhibiting positive tracheal intubation reaction was 0.472 mg/kg in non-elderly patients and 0.409 mg/kg in elder-ly patients.

Objective:To evaluate the progress and trends in perioperative management of postoperative delirium(POD)in the elderly over the past decade,providing insights for future research in China.Methods:Literature related to perioperative management of POD in elderly patients was retrieved from the Web of Science database published from Jan 1,2014,to Dec 31,2023.Articles and reviews were selected,and CiteSpace 6.3.1 software was used for duplicate removal and comprehensive analysis.Results:A total of 655 relevant publications were included,showing an overall increasing trend in annual output.China contributed 147 publications(22.44%,147/655),while the United States produced 134 publications(20.46%,134/655).Research hotspots focused on"hip fracture","neurocognitive disorders","Alzheimer's disease",and"oxidative stress".Conclusions:Research on the prevention and treatment of POD in elderly patients is growing globally.Although China has produced a substantial number of publications,its academic influence remains relatively limited.While clinical studies have elucidated strategies for POD prevention and treatment,further research is needed to validate intervention efficacy and explore underlying mechanisms.

AIM:To investigate the median effec-tive dose of ciprofol combined with sufentanil to in-hibit tracheal intubation reaction in patients under-going intracranial aneurysm embolization.METH-ODS:Forty-five patients who underwent emboliza-tion for intracranial aneurysms were divided into two groups according to age:non-elderly group(aged 18-64 years)and elderly group(aged＞65 years).Patients in the two groups were first given intravenous ciprofol,of which the initial dose of cip-rofol was 0.4 mg/kg and sufentanil 0.3 μg/kg and rocuronium 0.6 mg/kg were respectively injected according to BIS value and modified observer's as-sessment of alertness and sedation(MOAA/S)score.Then,endotracheal intubation was defined as 3 minutes after the induction of the study drug.Dixon sequential method was adopted,and the dose of ciprofol for the next patient was deter-mined according to whether the tracheal intuba-tion reaction was positive(Positive reaction of tra-cheal intubation was defined as the patient's kino-motor reaction such as coughing during tracheal in-tubation or the increase of MAP or HR within 2 minutes after intubation was greater than 20％of the basic value).When the tracheal intubation indi-cated a positive response,the next patient was raised by one gradient,otherwise,it was lowered by one gradient until the study ended at 7 crosses.The common dose ratio of adjacent patients was 1∶1.1.The Probit probability method was used to cal-culate the 50％effective dose(ED50),95％effective dose(ED95)and the corresponding 95％confidence interval(CI)of ciprofol.Perioperative adverse reac-tions were recorded in both groups.RESULTS:In the non-elderly group,the ED50 of ciprofol inhibit-ing positive tracheal intubation reaction was 0.472 mg/kg(95％CI 0.419-0.565 mg/kg),and the ED95 was 0.567 mg/kg(95％CI 0.513-1.293 mg/kg).In the elderly group,the ED50 of ciprofol inhibiting tra-cheal intubation reaction was 0.409 mg/kg(95％CI 0.383-0.434 mg/kg)and the ED95 was 0.452 mg/kg(95％CI 0.430-0.591 mg/kg).CONCLUSION:The ED50 of ciprofol combined with sufentanil inhibiting positive tracheal intubation reaction was 0.472 mg/kg in non-elderly patients and 0.409 mg/kg in elder-ly patients.

Objective:To evaluate the progress and trends in perioperative management of postoperative delirium(POD)in the elderly over the past decade,providing insights for future research in China.Methods:Literature related to perioperative management of POD in elderly patients was retrieved from the Web of Science database published from Jan 1,2014,to Dec 31,2023.Articles and reviews were selected,and CiteSpace 6.3.1 software was used for duplicate removal and comprehensive analysis.Results:A total of 655 relevant publications were included,showing an overall increasing trend in annual output.China contributed 147 publications(22.44%,147/655),while the United States produced 134 publications(20.46%,134/655).Research hotspots focused on"hip fracture","neurocognitive disorders","Alzheimer's disease",and"oxidative stress".Conclusions:Research on the prevention and treatment of POD in elderly patients is growing globally.Although China has produced a substantial number of publications,its academic influence remains relatively limited.While clinical studies have elucidated strategies for POD prevention and treatment,further research is needed to validate intervention efficacy and explore underlying mechanisms.