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 investigate the expression of serum microRNA(miR)-16a and mir-15b in patients with early-onset neonatal sepsis(EONS)and its value in clinical diagnosis and prognosis evaluation.Methods 114 children diagnosed with EONS admitted to the Department of Neonatology,Baoding Hospital of Beijing Children's Hospital Affiliated to Capital Medical University from October 2020 to October 2023 were selected as the EONS group,and 114 healthy newborns in the hospital during the same period were selected as the control group.Follow up was conducted on all EONS patients for a period of 6 months,including 34 cases in the poor prognosis group and 80 cases in the good prognosis group.The relative expression levels of miR-16a and miR-15b were measured within 6h of admission using real-time fluorescence quamtitative PCR(qRT-PCR).ROC curve was applied to analyze the diagnostic and prognostic value of serum miR-16a and miR-15b for EONS.Multivariate Logistic regression was applied to analyze the factors that affected the poor prognosis of EONS.Results Compared with the reference group,the birth weight of children in the EONS group(3.44±0.35kg/m2 vs 3.89±0.40kg/m2)was obviously reduced,and there was a obvious difference(35/114,1/114)in pathological jaundice between the two groups,and the differences were statistically significant(t=9.040,χ2=35.922,all P＜0.05).Compared with the reference group,the serum levels of miR-16a and miR-15b in the EONS group were obviously increased,and the differences was statistically significant(t=7.699,8.606,all P＜0.05).The area under the curve(AUC)of the ROC curve for the combined diagnosis of EONS by serum miR-16a and miR-15b was higher than that of miR-16a and miR-15b alone,and the differences were statistically significant(Z=2.619,2.157,all P<0.05).Compared with the good prognosis group,the poor prognosis group had a obvious decrease in body weight at birth,and a obvious increase in serum levels of miR-16a and miR-15b,and the differences were statistically significant(t=5.434,6.308,all P＜0.05).The AUC of serum miR-16a and miR-15b combined for prognostic evaluation was higher than that of miR-16a and miR-15b evaluated separately,and the differences were statistically significant(Z=2.364,2.073,all P＜0.05).Birth weight,miR-16a,miR-15b expression level was a prognostic factor of EONS(Wald χ2=33.459,16.146,49.797,all P<0.05).Conclusion MiR-16a and miR-15b are highly expressed in the serum of children with EONS,and they have certain diagnostic and prognostic value for EONS.

Objective:To summarize the risk factors for and outcomes of financial toxicity in heart failure patients, to identify populations at risk for financial toxicity and the consequent health impacts, so as to provide evidence for subsequent intervention study.Methods:Relevant studies on economic toxicity factors and outcomes of patients with heart failure were searched from China National Knowledge Infrastructure, China Biomedical Literature Database, VIP database, Wanfang Database, PubMed, Embase, CINAHL, Web of Science and Scopus. The search period was from establish to August 23, 2024. The included literatures were screened and summarized.Results:A total of 5 955 articles were retrieved, including 9 studies from 6 countries. The risk factors included socioeconomic, demographic, disease and treatment, psychological and cognitive factors. The outcomes caused by economic toxicity include physical changes, psychological changes, behavioral responses and clinical outcomes.Conclusions:The influencing factors of economic toxicity in patients with heart failure are complex, and there are many adverse outcomes. Therefore, it is necessary to develop specific assessment tools and construct intervention strategies based on multiple levels and perspectives, in order to reduce economic toxicity and adverse effects in patients with heart failure.

Objective To analyze the clinical characteristics and prognosis of Pseudomonas aeruginosa peritoneal dialysis-associated peritonitis(PaeP).Methods Peritoneal dialysis-associated peritonitis(PDAP)patients who were followed up in the nephrology outpatient department of a hospital from January 2019 to December 2020 were analyzed retrospectively.According to bacterial culture results,patients were divided into the PaeP group and non-PaeP group.Clinical characteristics of PaeP patients and antimicrobial susceptibility testing results of Pseudomonas aeruginosa were analyzed,clinical manifestations,laboratory test results,and prognosis of two groups of patients were compared.Results A total of 124 peritoneal dialysis patients were included in analysis,164 cases of peritoni-tis occurred,16 cases were in the PaeP group and 148 in the non-PaeP group.11 patients developed 16 episodes of Pseudomonas aeruginosa infection,accounting for 8.9％of PDAP patients.Among them,4 patients had peritoneal dialysis catheter exit-site infection,with 5 recurrence cases,1 case cured,1 case died,and 9 cases were extubated.Among the extubated patients,1 withdrew dialysis,3 were recovered to peritoneal dialysis after hemodialysis,5 changed to permanently hemodialysis,with a technical failure rate of 54.5％.Compared with the non-PaeP group,patients in the PaeP group had a shorter dialysis time(13.83±4.92 vs 38.53±35.77 months).During the infection period,C-reactive protein levels were higher(96.61±6.17 vs 45.87±44.65 mg/L),while albumin levels were lower(25.62±4.42 vs 29.46±8.25 g/L).At the onset of infection,the proportion of polymorphonuclear cells in perito-neal dialysis fluid was relatively higher.On the 5th day of treatment,the negative conversion rate of white blood cell count in peritoneal dialysis fluid was relatively low.Differences were all statistically significant(all P＜0.05).The cure rate of patients in the PaeP group was lower than that in the non-PaeP group,the technical failure rate was higher than that in the non-PaeP group,both with statistically significant differences(both P＜0.05).There was no statistically significant difference in the mortality between two groups of patients(P＞0.05).Conclusion PaeP patients have severe clinical manifestations,poor clinical treatment prognosis,high recurrence and extubation rates.For patients with repeated episodes,resetting and replacing the tunnel after extubation is an effective means to re-duce technical failures.

Objective By observing and measuring the relevant data of the buccal branch of the facial nerve,the parotid duct and the facial artery,the positional relationship among the three was analyzed to avoid accidental injury to the buccal branch of the facial nerve and the parotid duct when ligaturing the facial artery during the operation.Methods Forty adult head and neck specimens were dissected to observe the relationship between the buccal branch of the facial nerve and the parotid duct,the course and positional relationship of the facial artery,and the relationship between the buccal branch of the facial nerve and the peripheral vascular network.The relevant diameters were measured with a vernier caliper.Results The buccal branch of the facial nerve was divided into the superior buccal branch and the inferior buccal branch,and there was no direct anastomosis or connecting fiber between the buccal branch of the facial nerve and the parotid duct.The superior buccal branch was relatively thick,and it has a relatively constant position,which was parallel to the parotid duct.The position of the inferior buccal branch was not constant and it ran on or slightly above the plane of angulus oris.The superior buccal branch was located(10.76±5.54)mm from the parotid duct,while the inferior buccal branch was positioned(6.84±4.06)mm away from the parotid duct.The course of the main trunk of the facial artery was relatively fixed.Moreover,if the branch of the facial artery was missing,other branches of the facial artery would extend to replace the missing branch artery.The main trunk of the facial artery had a diameter of(2.34±0.83)mm,and its branches formed anastomoses with the buccal branch of the maxillary artery,creating a vascular network in the parotid and buccal regions.There was a vascular network around the buccal branch of the facial nerve,which was mostly small branches of the facial artery and the superficial temporal artery.Conclusion The buccal branch of the facial nerve exhibits a consistent anatomic relationship with the parotid duct and the facial artery.During the ligation of the facial artery,the parotid duct can serve as a landmark to accurately locate the buccal branch of the facial nerve,thereby significantly reducing the risk of inadvertent injury to the buccal branch of the facial nerve and the parotid duct.

Objective To explore the association between psychological resilience and internet addiction among senior primary school students,so as to provide a scientific basis for formulating strategies for preventing internet addiction and enhancing psychological resilience in this group.Methods A stratified cluster sampling method was employed.In May 2021,a total of 1 618 fourth-and fifth-grade students from 5 primary schools in Jiading District,Shanghai were surveyed on psychological resilience and internet addiction through questionnaires.Independent sample t-tests,chi-square tests,and Logistic regression models were used for data analysis.Results Among the 1 618 students,the prevalence rate of internet addiction was 8.8%(142 students).The total score of psychological resilience(t=6.215,P<0.001)and the scores of three dimensions,namely family support(t=3.509,P<0.001),goal focus(t=6.965,P<0.001),and positive perception(t=5.887,P<0.001),of those reported with internet addiction were all significantly lower than those without internet addiction.Multivariate logistic regression analysis showed that compared with individuals with low psychological resilience,those with moderate(aOR=0.395,95%CI:0.267-0.584,P<0.001)and high psychological resilience(aOR=0.167,95%CI:0.077-0.365,P<0.001)had a lower probability of internet addiction.The three sub-dimensions of psychological resilience,namely goal focus,positive perception and family support,also showed a statistically significant negative association with internet addiction in these students.Conclusion Nearly one-tenth senior primary school students in Jiading District self-reported internet addiction.Higher levels of psychological resilience were associated with a lower probability of internet addiction among senior primary school students.Focusing on enhancing the goal focus,positive perception and family support dimensions in psychological resilience may be of great significance for preventing internet addiction among senior primary school students.

Objective:To analyze the association between standardized management of clinical research, initiated by investigators and guided by clinical research management policies in healthcare institutions, and changes in the research behavior of graduate students.Methods:Theses related to cardiovascular health published by graduate students in the Sichuan-Chongqing region of China between January 2019 and June 2024 were retrieved from the China National Knowledge Infrastructure database. Multilevel models were used to analyze changes in ethical compliance awareness, research methodology standardization, and academic collaboration of graduate students before and after policy implementation. Using Shapiro Wilk test and percentage representation.Results:Among the 712 theses included in this study, the proportion of studies with ethical review reports increased from 44.50% to 55.32% following the implementation of standardized management [odds ratio ( OR)=1.80, P=0.017]. Standardized management significantly improved the quality scores of cross-sectional studies and randomized controlled trials ( P<0.001), as well as significantly increased the frequencies of multi-center collaboration ( OR=2.84, P=0.001) and intra-provincial collaboration ( OR=2.80, P=0.001). Conclusions:Standardized clinical research management shows significant association with positive changes in the research behavior of graduate students. Further optimization of management measures is recommended to comprehensively enhance the clinical research capabilities of graduate students.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.