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 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 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 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.

Currently, transcatheter intervention has emerged as a first-line treatment for coarctation of the aortic. Due to the radiation exposure associated with catheter interventional therapy, there are numerous restrictions, which harms both patients and medical personnel and is dependent on sizable radiation apparatus. Here, we report for the first time a case of echo-guiding percutaneous aortic stent implantation for a 27 years female patient of reproductive age. After discharge, the patient's aortic coarctation pressure decreased to 18 mm Hg, and the surgical results were satisfactory.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Objective:To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women.Methods:A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m 2≤BMI<24.0 kg/m 2, n=91), the overweight group(24.0 kg/m 2≤BMI<28.0 kg/m 2, n=115), and the obese group(BMI≥28.0 kg/m 2, n=87). The measurement results were analyzed. Results:In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group( P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group( P<0.001, P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI( P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI( P<0.05). Conclusion:The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

Long-term burden of illness and associated medication usage make osteoporosis(OP) a common complication of respiratory diseases. The pathogenic risk factors and treatment strategies for respiratory diseases related OP are similar to primary OP. However, due to differences in the pathogenesis of each disease, there are distinctions in the characteristics of bone loss and treatment approaches. Therefore, targeted diagnostic and therapeutic plans need to be formulated. This article provides a comprehensive review of secondary OP caused by common respiratory diseases in terms of epidemiological characteristics, related risk factors or possible mechanisms, changes in bone metabolic indexes or characteristics of bone damage, and progress in diagnosis and treatment. The aim of this review is to offer insights into the prevention and treatment of secondary OP related to respiratory diseases and promote the development of a multidisciplinary collaborative approach.

Objective To evaluate the safety and mid- to long-term efficacy of surgical correction of isolated partial anomalous pulmonary venous connection (IPAPVC). Methods We retrospectively collected consecutive patients who were diagnosed with IPAPVC and underwent surgical correction at Fuwai Hospital of Chinese Academy of Medical Sciences and Fuwai Yunnan Cardiovascular Hospital from June 2009 to May 2019, summarized the basic preoperative and intraoperative data of patients, analyzed the postoperative and mid- to long-term follow-up results. Results A total of 54 patients were enrolled, including 29 males and 25 females, with an average age of 16.20±2.40 years, ranging from 1 month to 62 years. There were 28 (51.9%) patients with varying degrees of arrhythmia, 22 (40.7%) patients with cardiac insufficiency, and 39 (72.2%) patients with pulmonary hypertension. According to Bordy's typing, 14 (25.9%) patients were classified as type A, 23 (42.6%) type B, 4 (7.4%) type C, 5 (9.3%) type D and 8 (14.8%) mixed type. Transthoracic echocardiography was performed in the whole group of patients and the accuracy of staging diagnosis was 66.7% (36/54), and cardiac CT angiography (CTA) was performed in 37 patients and the accuracy of staging diagnosis was 94.6% (35/37). All surgical procedures were assisted with cardiopulmonary bypass, aortic cross-clamping time was 0-219 (67.02±5.23) min, cardiopulmonary bypass time was 40-261 (105.09±5.23) min, and there was no serious intraoperative complication. Postoperative tracheal intubation time was 0-230 (13.33±4.20) h, intensive care unit stay was 0-13 (1.89±0.28) days, postoperative hospital stay was 5-18 (7.20±0.38) days, and follow-up time was 16-140 (62.58±5.12) months. There were 2 (3.7%) all-cause postoperative deaths, including 1 in-hospital death and 1 death during the follow-up, and there was no intraoperative death. Among the survivors, there were 3 patients with surgery-related complications: 1 patient had atrial septal defect with the second surgical treatment, 1 early obstruction of the superior vena cava and 1 arrhythmia. Two patients had complications of IPAPVC (atrial fibrillation, collateral circulation) prior to surgery and underwent the second surgery with a poor prognosis, and 1 patient had preoperative cardiac insufficiency and atrial fibrillation, whose symptoms persisted for a long time during the follow-up. Conclusion IPAPVC accounts for a lower percentage of partial anomalous pulmonary venous connection, transthoracic echocardiography combined with CTA improves diagnostic accuracy, and IPAPVC should be treated with elective surgery after diagnosis. The surgical approach should be individualized with imaging features such as disease staging, number of drains and drainage location. Surgical treatment of IPAPVC is safe and effective, and regular follow-up is warranted.