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

Excessive ionizing radiation can disrupt the molecular structures of organisms,leading to health issues such as acute radiation syndrome and cancer,posing serious threats to human health.The development of radioprotective drugs holds significant importance for mitigating ionizing radiation damage and safeguarding public health,yet its research process faces multidimensional ethical challenges.This paper systematically explores the ethical issues involved in the full lifecycle of radioprotective drug development,focusing on the ethical particularities of animal experimentation,ethical dilemmas in human trials,data privacy and security risks,as well as challenges in managing conflicts of interest.Targeted solutions are proposed,including strengthening ethical review mechanisms,promoting interdisciplinary collaboration,constructing data security management systems,and establishing conflict-of-interest mediation mechanisms.These comprehensive measures aim to build a scientifically rigorous ethical framework for radioprotective drug research,fostering sustainable development in this field.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.

AIM To investigate the effects of Rutong Ruanjian Tablets on angiogenesis in cancer tissues of rats with preneoplastic breast cancer(PBC).METHODS 60 female SD rats were randomly divided into a blank group of 10 rats and a model group of 50 rats for the establishment of the PBC models of Liver-Qi Stagnation and Blood Stasis Pattern with 9 weeks of oral administration of 7,12-dimethylbenz[a]anthracene(DMBA)and cervical ligation.After successful modeling,the rats were randomly divided into the model group,the tamoxifen group(3.2 mg/kg),the Rutong Ruanjian Tablets group(128 mg/kg),the 3,5-difluorobenzoyl group(DAPT,5 mg/kg),and the Rutong Ruanjian Tablets(128 mg/kg via gavage)+DAPT(5 mg/kg intraperitoneal injection)group,for 1 month corresponding drug administration,with 10 rats in each group.Then the rats had their cancer progression and syndrome scores observed;their angiogenesis evaluated by assessment of microvascular density(MVD);their vascular endothelial growth factor(VEGF)expression assessed by immunohistochemistry;and their mRNA and protein expressions of proteins related to the DLL4/Notch1/Hes1 pathway measured using RT-qPCR,immunohistochemistry and Western blot.RESULTS During carcinogenesis of rats induced by DMBA,there was gradual disappearance of E-cadherin expression and consistency of HE staining result with the PBC progression confirming the success of the modeling.Compared with the blank group,the model group showed increased MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).Compared with the model group,the Rutong Ruanjian Tablets group exhibited reduced MVD values,mRNA expression of Notch1 and Hes1,and protein expressions of VEGF,DLL4,Notch1 and Hes1(P＜0.05,P＜0.01).The Rutong Ruanjian Tablets+DAPT group showed reduced mRNA expression of Notch1 and Hes1,and protein expressions of DLL4,Notch1 and Hes1 compared to the Rutong Ruanjian Tablets group(P＜0.05,P＜0.01).CONCLUSION Rutong Ruanjian Tablets can inhibit angiogenesis and attenuate cancer progression in PBC rats of Liver-Qi Stagnation and Blood Stasis Pattern,and the mechanism may lie in the downregulation of DLL4/Notch1/Hes1 signaling pathway related proteins.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To investigate the effects of Huayu Xiaopi Decoction on the proliferation and migration of AGS cells;To explore its mechanism in treating precancerous lesions of gastric cancer.Methods AGS cells were divided into blank group,inhibitor group and Huayu Xiaopi Decoction high-,medium-and low-dosage groups.The blank group was cultured with 15%control serum,the inhibitor group was cultured with 10 μmol/L HIF-1α inhibitor,and the Huayu Xiaopi Decoction high-,medium-and low-dosage groups were cultured with 12%,6%and 3%drug containing serum,respectively.CCK-8 method was used to detect cell survival rate,cell migration ability was detected by scratch test,immunofluorescence was used to detect the expressions of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase(MMP)-2 and MMP-9 in AGS cells,the expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 mRNA and HIF-1α,COX-2,VEGF,VEGFR2 proteins in AGS cells were detected by RT-PCR and Western blot.Results Compared with the blank group,the cell survival rate and migration rate were significantly decreased in the inhibitor group and each dosage of Huayu Xiaopi Decoction groups(P<0.05),the expressions of PCNA,MMP-2 and MMP-9 significantly decreased in the inhibitor group and Huayu Xiaopi Decoction high-and medium-dosage groups(P<0.05),the mRNA expressions of HIF-1α,COX-2,VEGF,VEGFR2,MMP-2,MMP-9 and the protein expression of HIF-1α,COX-2,VEGF,VEGFR2 were significantly decreased(P<0.05).Conclusion Huayu Xiaopi Decoction can inhibit the proliferation and migration of AGS cells,and its mechanism is related to the regulation of the expression of key molecules in HIF-1α/VEGF signaling pathway.

Sepsis is a life-threatening organ dysfunction disease caused by a dysregulated host response to infection.It has com-plex pathophysiological changes,and in severe cases,it can rap-idly develop into septic shock and multiple organ dysfunction or multiple organ failure.At present,the pathological mechanism of sepsis and its induced organ dysfunction is complex and the in-fluencing factors are numerous.So far,there is still a lack of specific and effective treatment strategies.RNA modify-N6-methyladenosine(m6 A)is one of the most common post-tran-scriptional modifications on eukaryotic RNAs.It is involved in the regulation of the occurrence and development of a variety of inflammatory diseases,including sepsis,and even multiple organ dysfunction induced by sepsis by affecting the metabolism of RNAs.It includes cardiac dysfunction,acute lung injury(ALI)and acute kidney injury(AKI).Therefore,this article will dis-cuss the effect of m6A modification on the function of immune cells,and its important role in sepsis and its induced multiple or-gan dysfunction diseases by regulating inflammatory signals,py-roptosis,mitochondrial damage and ferroptosis.This will provide new therapeutic targets and strategies for the clinical prevention and treatment of sepsis and its induced multiple organ dysfunc-tion diseases.

Objective:To conduct a bibliometric analysis of research on auricular acupoint therapy (AAT) published between 2014 and 2024 in the China National Knowledge Infrastructure (CNKI) , in order to identify research hotspots and explore future research trends.Methods:CiteSpace, VOSviewer, and CNKI's bibliometric visualization platform were used to analyze publications from multiple perspectives, including annual publication trends, institutional distribution, author collaboration networks, keyword co-occurrence, and journal sources.Results:From 2014 to 2024, research on auricular acupoint therapy underwent a transition from rapid growth to steady development. The research focus shifted from traditional Chinese medicine theories to integration with modern neuroscience and technology. Domestic research was primarily concentrated in universities and institutes of traditional Chinese medicine, with collaboration mainly occurring at the regional level. Randomized controlled trials (RCTs) became the predominant study design, although issues related to methodological rigor persist. Keyword analysis showed a shift in research hotspots from traditional conditions like headache and insomnia to contemporary health concerns such as depression, anxiety, and hyperlipidemia.Conclusions:Auricular acupoint therapy is increasingly incorporating modern scientific and technological approaches. Research methodologies are becoming more standardized, and areas of application are continuously expanding. Future studies should focus on enhancing interdisciplinary collaboration, improving research design quality, and deepening international cooperation to promote the broader adoption and development of AAT within the global healthcare system.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.