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 compare the effecacy of colistin sulphate with cefoperazone and sulbactam in the treatment of pan-resistant Acinetobacter baumannii with the combination therapy of tigecycline with cefoperazone and baubactam. Methods By retrospective analysis, 216 ICU patients with pneumonia diagnosed with Acinetobacter baumannii from January 1，2019 to July 31，2021 were propensity matching divided into a test group （71） and a control group （145） by 1∶2. The test group was treated with colistin sulfate combined with cefoperazone and sulbactam, the control group was treated with tigecycline combined with cefoperazone and sulbactam. According to the changes of clinical symptoms and indicators before and after treatment in the two groups, the clinical response rate, bacterial clearance rate and 28 d mortality rate of the two groups were observed. Results The early clinical response and bacterial clearance of the test group were higher than that of the control group （P<0.05）; At the end of treatment, the clinical response rate and 28 d mortality were not statistically significant. Conclusion Colistin sulfate combined with cefoperazone and sulbactam was comparable to its efficacy and was superior to tigecycline combined with cefoperazone and sulbactam group in early assessment of clinical efficacy and bacterial clearance.

With the accelerating trend of population aging, the number of elderly patients with lung cancer continues to rise, and the disease burden is becoming increasingly heavy. The clinical management of these patients faces severe challenges due to their decreased physiological reserve, complex comorbidities, and significant individual heterogeneity. Consequently, under traditional diagnosis and treatment models, doctors often struggle to identify the individualized risks of elderly patients in a timely and comprehensive manner, which can easily lead to decision biases such as undertreatment or overtreatment. In view of this, this study advocates for the establishment of an umbrella decision-making model specifically tailored for elderly lung cancer patients. Grounded in a multidisciplinary team (MDT) platform, this model deeply integrates oncological indicators with the comprehensive geriatric assessment (CGA) system. By holistically considering multidimensional variables including tumor burden, organ function, frailty index, cognitive status, and social support, the model establishes an operational mechanism characterized by "single entry, precise stratification, and targeted selection". Accordingly, patients can be scientifically triaged into distinct intervention tiers, such as active surveillance, minimally invasive surgery, drug therapy, radiotherapy, and best supportive care, thereby achieving real-time alignment between treatment intensity and patient fitness. This article elaborates on the construction logic and key operational procedures of this novel decision-making framework, aiming to guide clinical practice beyond the limitations of a tumor-centric perspective toward a holistic, dynamic, whole-course management strategy. This transition seeks to ensure optimal quality of life and clinical net benefit for elderly patients alongside survival prolongation.

Objective To explore the differences in coronary-based and lesion-based fat attenuation index(FAI)in patients with coronary artery disease(CAD)across different risk stratifications,and to compare the diagnostic efficiency of coronary-based and lesion-based FAI in stable CAD patients with myocardial ischemia.Methods The patients with CAD,who underwent preoperative coronary CT angiography(CCTA)and invasive coronary angiography(ICA)with coronary fractional flow reserve(FFR)measurement between Apr 2019 and Oct 2022 in Zhongshan Hospital,Fudan University,were retrospectively collected.There were 57 cases of acute coronary syndrome(ACS)patients and 206 cases of stable CAD patients included following inclusion criteria.The coronary-based and lesion-based FAI were measured,and the differences in these indices were recorded and analyzed among ACS patients,ischemic and non-ischemic groups of stable CAD patients(FFR=0.8 as the threshold).ROC curves were utilized to assess the diagnostic efficiency of coronary-based and lesion-based FAI for myocardial ischemia in stable CAD patients.Results The coronary-based FAI and lesion-based FAI in ACS patients were significantly higher than those in stable CAD patients[coronary-based FAI:(-72.40±6.83)HU vs.(-76.82±9.01)HU,P<0.001;lesion-based FAI:(-65.65±4.79)HU vs.(-77.48±8.64)HU,P<0.001].Among stable CAD patients,the lesion-based FAI in the ischemic group was significantly higher than that in the non-ischemic group[(-69.28±5.65)HU vs.(-80.10±7.75)HU,P<0.001].The diagnostic efficiency of lesion-based FAI for predicting myocardial ischemia in stable CAD patients was superior to coronary-based FAI(AUC:0.892 vs.0.525,Z=9.803,P<0.001).Conclusion Coronary-based and lesion-based FAI tended to be higher in ACS patients than in stable CAD patients,suggesting a potential for stratifying CAD patients with different risks.Lesion-based FAI showed some promise in evaluating myocardial ischemia among stable CAD patients.

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P＜0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P＜0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P＜0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.

Aim To investigate the effect of long-chain non-coding RNA(lncRNA)GS1-124K5.4 targeting regulation of PRDX6 on proliferation,migration and in-vasion of lung squamous carcinoma(LUSC)cells and the underlying mechanism.Methods The expression level of lncRNA GS1-124K5.4 in lung cancer tissues and adjacent tissues of 60 patients with LUSC were de-termined by fluorescence in situ hybridization.The ex-pression level of lncRNA GS1-124K5.4 in human nor-mal lung cells and LUSC cells were determined by qRT-PCR.Two kinds of LUSC cells(NCI-H 1703,SK-MES-1)with highest expression level of lncRNA GS1-124K5.4 were selected for subsequent experi-ments.The distribution of lncRNA GS1-124K5.4 in cells was studied by fluorescence in situ hybridization and prokaryotic separation.The effect of knockdown of lncRNA GS1-124K5.4 on proliferation of NCI-H1703 and SK-MES-1 cells was studied by CCK-8 experiment and cell clone formation experiment;the effect of knockdown of lncRNA GS1-124K5.4 on migration of NCI-H1703 and SK-MES-1 cells was studied by cell scratch experiment and Transwell cell migration experi-ment;and the effect of knockdown of lncRNA GS1-124K5.4 on invasion of NCI-H1703 and SK-MES-1 cells was studied by Transwell invasion experiment.The protein to be bound by lncRNA GS1-124K5.4 was detected by RNA pull-down combined with mass spec-trometry and immune-precipitation.The effect of knockdown of lncRNA GS1-124K5.4 targeting PRDX6 on proliferation,migration and invasion of NCI-H1703 and SK-MES-1 cells was studied.Results(1)The fluorescence intensity of lncRNA GS1-124K5.4 in lung squamous cell carcinoma increased compared with that in adjacent tissues(P＜0.05),and the expression of lncRNA GS1-124K5.4 was related with lymph node metastasis and clinical stage(P＜0.05).(2)The ex-pression level of lncRNA GS1-124K5.4 in NCI-H1703,NCI-H520 and SK-MES-1 cells significantly increased(P＜0.05).(3)The result of fluorescence in situ hybridization experiment and nucleoplasm sepa-ration experiment showed that lncRNA GS1-124K5.4 was mainly distributed in cell nucleus.(4)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of lncRNA GS1-124K5.4 significantly decreased(P＜0.05).(5)PRDX6 protein to be bound to LncRNA GS1-124K5.4 was determined by RNA pull-down combined with mass spectrometry and immunoprecipitation.(6)The prolif-eration,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNA GS1-124K5.4 significantly increased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with knockdown of PRDX6 significantly decreased(P＜0.05);the proliferation,migration and invasion ability of NCI-H1703 and SK-MES-1 cells with overexpression of lncRNAGS1-124K5.4 and knockdown of PRDX6 showed no signifi-cant change(P＞0.05).Conclusions LncRNA GS1-124K5.4 is highly expressed in lung squamous cell carcinoma,and it may promote the proliferation,migration and invasion of lung squamous carcinoma cells by targeting the expression of PRDX6 protein.

Objective:This study aims to construct a machine learning model to predict depression symptoms in the elderly and analyze the key influencing factors of depression in the elderly using the shapley additive interpretation (SHAP) method.Methods:Based on entries from the 2018 China Health and Retirement Longitudinal Study database, a sample of 5 954 elderly individuals was selected. Feature selection using Support Vector Machine Recursive Feature Elimination, Extreme Gradient Boosting (XGBoost) - Recursive Feature Elimination (RFE), and the Lasso algorithm, which was combined with five classifiers-logistic regression, decision trees, random forests, support vector machines, and XGBoost-to explore the classification effectiveness for depressive symptoms in the elderly. Finally, the SHAP method was used to interpret the analysis of the model with the highest receiver operating characteristic curve areas under the curve (AUC).Results:The accuracy of 15 prediction models ranged from 0.702 to 0.743, with AUC between 0.730 and 0.795. Sensitivity was reported at 0.546 to 0.588, while specificity ranges from 0.783 to 0.865. The model XGBoost-RFE-XGBoost presented the highest AUC. Based on SHAP values, the top four factors influencing depressive symptoms in older adults were life satisfaction, duration of nighttime sleep, disability status, and self-rated health.Conclusion:This study developed a highly efficient and interpretable risk prediction model for depressive symptoms in older adults, which could help identify high-risk older adults and give personalized interventions.

Objective The application effect of bedside ultrasound combined with joint movement protractor on the accurate monitoring and management of joint range of motion in extremely low birth weight infants was evaluated to reduce the incidence of secondary ectopic PICC in extremely low birth weight infants.Methods Convenience sampling was used to select 128 extremely low birth weight infants admitted to the neonatal intensive care unit of a tertiary hospital in Zhengzhou,Henan Province from February to September 2024.Among them,infants enrolled between June and September 2024 were assigned to an experimental group,while those enrolled between February and May 2024 were assigned to a control group,with 64 cases in each group.Whereas the experimental group,based on the control group,combined bedside ultrasound with a joint goniometer for precise monitoring and management of limb movement range in children with upper limb catheterization;the control group received routine prevention and management of PICC secondary displacement.After intervention,the incidence of PICC secondary displacement,the rate of PICC secondary displacement removal,the incidence of complications related to PICC secondary displacement,and the average length of stay of the infants were compared between the 2 groups.Results Ultimately,60 cases were included in each of the 2 groups.The incidence of secondary ectopic PICC in the post-intervention experimental group was 8.33％,lower of 23.33％in the control group;the extubation rate of secondary ectopic PICC was 3.33％,lower of 16.67％in the control group;the incidence of complications related to secondary ectopic PICC was 13.33％,lower of 51.67％in the control group;the average hospitalization day was 50(48,55)d,shorter of 61(55,65)d in the control group.The difference between the 2 groups was statistically significant(P＜0.05).Conclusion The combination of bedside ultrasound and joint movement protractor was used to accurately monitor and manage the range of motion of limbs in children with upper limb catheterization,which effectively guaranteed the safe position of the catheter tip and reduced the incidence of secondary ectopic complications related to PICC.It can be further promoted and applied in clinical practice.

Objective:To systematically evaluate the fairness of traditional Chinese medicine (TCM) healthcare resource allocation at the prefecture-level in China using the healthcare resource agglomeration degree (HRAD) method, so as to provide empirical evidence for optimizing resource distribution.Methods:Data on TCM healthcare resources (including the number of TCM institutions, public TCM hospitals, TCM hospital beds, and TCM healthcare technicians) were collected from 333 prefecture-level regions in 2023. The HRAD method was employed to assess fairness in geographic allocation (HRAD i) and population-based allocation (HRAD i/PAD i). A multi-indicator comprehensive evaluation was conducted using the entropy weight method to determine weighting coefficients. Results:Significant disparities were observed in the geographic agglomeration of TCM resources (HRAD i) in China. Resource-rich regions (HRAD i>5) were primarily concentrated in eastern and some central-western provinces, while resource-scarce regions (HRAD i<1) were mainly distributed in western, northeastern, and parts of central and eastern provinces. Analysis of population-based fairness (HRAD i/PAD i) revealed that most prefecture-level cities nationwide had ratios<1, with only 8 provinces having more cities with ratios>1 than<1. The comprehensive evaluation showed that top-ranked cities in the east (e.g., Hangzhou, Dongying, Shenzhen), central region (e.g., Taiyuan, Zhengzhou), and west (e.g., Hainan Prefecture, Alxa League) were predominantly core cities or sparsely populated areas. Conclusions:China′s prefecture-level TCM healthcare resource allocation exhibits significant geographic and population-based inequities, with excessive concentration in provincial capitals and developed cities. Urgent strategies are needed to optimize resource allocation, enhance fairness and accessibility, including promoting the decentralization of high-quality resources, strengthening regional collaborative support, enhancing talent attraction in underdeveloped areas, and leveraging information technology to improve efficiency.