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:Varicocele(VC)induces male infertility by mediating changes in the testicular microenvironment,in which testicular hypoxia and high-pressure are important pathological conditions.This study aims to compare the mouse spermatogenesis(GC-2spd)cells and Sertoli(TM4)cells of mouse testis after hypoxic modeling and hypoxic and high-pressure combined modeling,and to explore the feasibility of establishing a hypoxic and high-pressure combined cell model.Methods:On the basis of cell hypoxia induced by CoCl2,the complex model of testicular cell hypoxia and high pressure was constructed by changing the osmotic pressure of GC-2 and TM4 cell medium with a high concentration of NaCl solution.After selecting the intervention concentration of CoCl2 by MTT test and detecting the expression level of HIF-1α for the determination of the optimal osmotic pressure conditions of the cell model,the cells were divided into normal group,hypoxia model group and composite model group.And the levels of OS,programmed cell death,inflammatory factors,and the expression levels of pyroptosis-related proteins were compared between the normal group and the groups with different modeling methods.Results:The optimal intervention concentration of CoCl2 in GC-2 and TM4 cells was 150 and 250μmol/L,respectively,and the expression of HIF-1α was the highest in both cells under osmotic pressure of 500 mOsmol/kg(P＜0.05).Compared with the normal group,the SOD levels of GC-2 and TM4 cells decreased(all P＜0.05),CAT level decreased(all P＜0.05),and MDA level increased(all P＜0.01),and the OS level of GC-2 and TM4 cells was more obvious than that of the hy-poxia model group(all P＜0.05).Compared with the normal group,apoptosis occurred in GC-2 and TM4 cells after composite model-ing(all P＜0.05).Compared with the normal group,the mRNA expressions of IL-1β,IL-18,TNF-α and COX-2 in GC-2 and TM4 cells significantly increased(P＜0.01)and higher than those in hypoxia model group(P＜0.05)and induced pyroptosis(P＜0.01).The expression level of GSDMD increased(P＜0.05).Conclusion:The cell model with hypoxia and high pressure com-bined modeling can not only induce oxidative stress and apoptosis of cells better than that with hypoxia alone,but also further cause in-flammatory response damage and pyroptosis,which simulates the changes of testis microenvironment mediated by hypoxia and high pressure combined conditions in VC.This cell model can be used for studying the pathogenesis of VC-associated male infertility,evalu-ating drug efficacy,and exploring pharmacological mechanisms.

Objective To search,evaluate and synthesise the best available evidence on prevention strategies for unplanned extubation of nasogastric tube in adult inpatients and to offer a reference in management of safety and efficiency.Methods Literature on prevention strategies for unplanned extubation of nasogastric tube in adult inpatients was retrieved across BMJ Best Practice,UpToDate,JBI Center for Evidence Based Healthcare International Collaboration Library,Medlive,US National Guidelines Database,International Guidelines Collaboration Group,Scottish InterAcademy Guidelines Network,Ontario Registered Nurses Association of Canada,UK National Institute for Clinical Optimization,New Zealand Guidelines Research Group,PubMed,EMbase,Cochrane Library,Web of Science,EBSCO,CINAHL,CNKI,CBM Database,Wanfang Data and VIP Database,from the inception of databases to August 2024.Retrieved literature included guidelines,clinical decisions,recommended practices,evidence summaries,expert consensus and systematic reviews.Two researchers evaluated the literature methodologically and then summarised evidence from the included data.Results Fifteen publications(2 guidelines,1 clinical decision,3 recommended practices,7 evidences and 2 systematic reviews)were included.A total of 30 pieces of evidence were extracted and they were grouped into 7 themes:risk assessment,selection of nasogastric tube,depth of intubation,tube fixation,tube position,tube management and patient education.Conclusion Clinicians should integrate the best evidences into clinical practice and assess risk factors for unplanned extubation of nasogastric tube in adult inpatients.Personalised early intervention plans should be made to reduce or avoid the unplanned extubation.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

This study was aimed at determining the molecular characteristics of Yersinia pestis in the natural plague foci around Qinghai Lake through single nucleotide polymorphism technology,to lay a foundation for molecular epidemiological and source-tracing analysis of Y.pestis in this area.Using the whole genome sequencing technology,we obtained the whole genome sequences of 84 representative Y.pestis strains.Using the sequences of Y.pestis and Yersinia pseudotuberculosis IP32953 from the NCBI database as references,we compared and analyzed the 2 298 SNP loci of these strains.From 1957 to 2020,84 representative strains of Y.pestis from the natural plague foci around Qinghai Lake were divided into two clades:1.IN2 and 3.ANT1.The 1.IN2 clade was the characteristic population of Y.pestis throughout all epidemic years in this area.Additionally,analysis of the SNP distribution and hosts in the region indicated that the 1.IN2 clade was located in five counties except Wulan,whereas the 3.ANT1 clade was isolated from Himalayan marmot and dog in two counties.In conclusion,the population structure of SNP of Y.pestis in the natural plague foci around Qinghai Lake is relatively simple,and SNP analysis of Y.pestis provided a scientific basis for tracing plague epidemic sources and formulating plague prevention and control measures in this area.

Objective To design a Five-Elements Music Software based on Traditional Chinese Medicine's(TCM)theory of five elements music therapy and music emotion classification.The software is intended to provide appropriate music selections tailored to the negative emotional states of cancer patients and evaluate its effectiveness in psychological rehabilitation.Methods ①Music screening and classification:Qualitative analysis was used by six experts in TCM,psychology,nursing,and musicology to screen five elements music and classify corresponding emotional categories.②Software design and development:Based on screening and classification of music materials,design and develop a"Five Elements Music Software Based on Emotion Classification".③Software application evaluation:Recruit 50 cancer patients from the"Beijing Anti Cancer Paradise"as participants to have a trial listening experience with music software,and fill out a satisfaction questionnaire to evaluate its application effect.Results This study established a music database containing 150 pieces of five-elements musical tunes and completed the classification of emotional categories.Among the included subjects,80%of the recruited objects were satisfied with the experience of the five elements music software,of which the application experience of female patients was significantly better than that of male patients,and breast cancer patients were better than other cancer patients,with a statistically significant difference(P<0.05).The five elements music Software in clinic showed comparing with other two groups after four weeks,there was a significant difference for HAMD when comparing five elements music software group and the other two groups(P<0.05).Conclusion The five-element music software designed based on emotion classification effectively meets the psychological rehabilitation needs of cancer patients.It provides appropriate music selections and convenient listening method to regulate cancer-related negative emotions,extending psychological rehabilitation from the hospital to the home.

Objective:To explore the predictive value of the geriatric nutritional risk index (GNRI) for anesthesia related adverse reaction (ARAR) in elderly patients undergoing radical resection of colorectal cancer.Methods:The clinical data of 178 elderly patients undergoing radical resection of colorectal cancer from March 2020 to October 2023 in Mianyang Central Hospital were retrospectively analyzed. Among them, 48 cases had ARAR (ARAR group), and 130 cases did not experience ARAR (control group). The gender, age, body mass index, smoking history, alcoholism history, hypertension, diabetes, hyperlipidemia, tumor location, TNM stage, pathological type, preoperative intestinal obstruction, preoperative chemotherapy, operation mode, operation time, intraoperative bleeding, American Society of Anesthesiologists (ASA) grade, number of lymph node dissection and GNRI were recorded. The prognostic analysis indexes were recorded, including length of hospital stay, unplanned ICU transfer and in-hospital death. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of GNRI for ARAR in elderly patients undergoing radical resection of colorectal cancer. Multifactor Logistic regression analysis was used to analyze the independent risk factors of ARAR in elderly patients undergoing radical resection of colorectal cancer.Results:The age, ASA grade Ⅱ proportion and preoperative chemotherapy proportion in ARAR group were significantly higher than those in control group: (75.35 ± 6.43) years vs. (70.12 ± 5.94) years, 41.67% (20/48) vs. 22.31% (29/130) and 20.83% (10/48) vs. 4.62% (6/130), the GNRI was significantly lower than that in control group: 96.73 ± 6.23 vs. 106.21 ± 6.95, and there were statistical differences ( P<0.01 or <0.05); there were no statistical differences in other indexes between the two groups ( P>0.05). ROC curve analysis result showed that the area under the curve of GNRI for predicting ARAR in elderly patients undergoing radical resection of colorectal cancer was 0.832 (95% CI 0.770 to 0.894, P<0.01), with an optimal cutoff value of 100.5, sensitivity of 70.80%, and specificity of 75.00%. Multifactor Logistic regression analysis result showed that GNRI<98, age ≥80 years, preoperative chemotherapy and ASA grade Ⅱ were independent risk factors for ARAR in elderly patients undergoing radical resection of colorectal cancer ( OR = 2.372, 2.144, 2.708 and 3.280; 95% CI 1.108 to 5.069, 1.072 to 4.382, 1.180 to 6.136 and 1.072 to 9.882; P<0.01 or <0.05). The length of hospital stay and unplanned ICU transfer rate in ARAR group were significantly higher than those in control group: (14.58 ± 3.82) d vs. (11.94 ± 3.66) d and 22.92% (11/48) vs. 10.77% (14/130), and there were statistical differences ( P<0.01 and <0.05); there was no statistical difference in in-hospital mortality between the two groups ( P>0.05). Conclusions:The GNRI is a predictive index of ARAR in elderly patients undergoing radical resection of colorectal cancer. For patients with nutritional risk, preoperative nutritional support should be strengthened to reduce the occurrence of ARAR.

Objective:To investigate the expression of long noncoding RNA (lncRNA) BMPR1B-AS1 in ovarian cancer and its impact on prognosis, so as to evaluate its value as a potential biomarker.Methods:The TCGA, GEPIA, and UALCAN databases were used to retrospectively analyze the expression differences of BMPR1B-AS1 in gynecological tumors, and prognostic analysis was performed in combination with clinical data. The expression level of BMPR1B-AS1 in ovarian cancer tissues and cell lines was verified by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-qPCR), and univariate and multivariate Cox regression models were used to analyze its relationship with the prognosis of ovarian cancer.Results:Database analysis showed that the expression of BMPR1B-AS1 in ovarian cancer and endometrial cancer was higher than that in the non-tumor group (all P<0.05), and high expression of BMPR1B-AS1 in ovarian cancer was associated with better prognosis ( P<0.05). Experimental verification showed that the expression of BMPR1B-AS1 in ovarian cancer tissues was significantly higher than that in benign ovarian tissues, and the expression of BMPR1B-AS1 in ovarian cancer cell lines was higher than that in normal human ovarian epithelial cells ( P<0.05). Cox regression analysis indicated that high expression of BMPR1B-AS1 was an independent protective factor for the prognosis of ovarian cancer ( P<0.05). Conclusions:The expression of BMPR1B-AS1 in ovarian cancer and endometrial cancer is higher than that in non-tumor groups, and it is an independent protective factor for good prognosis in ovarian cancer patients. It may serve as a new biomarker, providing new ideas for the diagnosis and treatment of ovarian cancer.