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

ObjectiveTo investigate the incidence and influencing factors of posttraumatic stress disorder （PTSD） three months after a traffic accident， and to explore the role of social support and coping strategies. MethodsA total of 117 individuals exposed to trauma following road traffic accidents were recruited. General demographic and clinical information was collected within one week， and the hamilton anxiety rating scale （HAMA）， the hamilton depression rating scale-24 （HAMD-24）， the social support rating scale （SSRS）， and the simplified coping style questionnaire （SCSQ） were administered. A 3-month follow-up was subsequently conducted， during which PTSD symptoms were assessed using the post-traumatic stress disorder checklist for DSM-5 （PCL-5）. Participants were divided into a PTSD group and a non-PTSD group according to whether PTSD occurred. Between-group comparisons were performed using the Mann-Whitney U non-parametric test or the χ² test， as appropriate. Spearman correlation analysis was used to examine the associations between general characteristics and PCL-5 scores. Binary Logistic regression was applied to identify factors influencing PTSD， and receiver operating characteristic （ROC） curve analysis was conducted to evaluate the diagnostic value of the SCSQ and SSRS. ResultsDuring the 3-month follow-up of the 117 trauma-exposed individuals， 17 cases developed PTSD， with a higher proportion of females （70.59%）. Between-group comparisons showed that， compared with the PTSD group， the non-PTSD group had higher scores for positive coping， objective support， and subjective support （P<0.05）， and lower scores for negative coping， HAMA， HAMD， and PCL-5 （P<0.05）. Correlation analysis indicated that female gender， negative coping， and higher HAMA and HAMD scores were associated with greater PTSD severity. Logistic regression analysis demonstrated that educational level （OR=1.715， 95% CI： 1.020-2.883， P=0.042） and negative coping （OR=1.590， 95% CI： 1.003-2.522， P=0.048） were risk factors for PTSD， whereas objective support （OR=0.646， 95% CI： 0.451-0.925， P=0.017） was a protective factor. The ROC analysis showed that the total SCSQ score and its negative and positive coping dimensions， the total SSRS score and its subjective and objective support dimensions， as well as their combined use， all demonstrated good discriminative ability in distinguishing between the PTSD and non-PTSD groups. ConclusionThe results suggest that individuals who are female， with higher HAMA and HAMD scores after a motor vehicle accident， and those with lower social support and negative coping strategies， should be given particular attention. Early interventions for these individuals may reduce the incidence of PTSD.

ObjectiveTo explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. MethodsSixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1×10⁷/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg·d), that for H_NaB was 0.5 g/(kg·d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF‑α, IL-6, IL-1β, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-κB signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results(1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in α diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-IκBα, and p-NF‑κB p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF‑α concentration in H_NaB and TNF-α concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). ConclusionOral administration of NaB can improve gut microbiota α diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-κB signaling in skeletal muscle.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Type 2 inflammation（T2 inflammation）is an immune response mediated by Th2 cells，eosinophils，type 2 innate lymphocytes，and other cells. Its pathological characteristics are manifested by the abnormally high expression of type 2 cytokines such as IL-4，IL-5，and IL-13，and it widely involves allergic diseases including asthma，allergic rhinitis，and atopic dermatitis. Ginsenosides are the core active ingredients of ginseng and the key substances for ginseng to exert its pharmacological effects. It has anti-inflammatory and immunomodulatory effects. This article reviews the mechanism of action，experimental research progress，and clinical application prospects of ginsenosides in T2 inflammation，explores the therapeutic potential and clinical challenges of ginsenosides，and proposes future research directions.

Objective The purpose of this study is to explore the implementation strategies of the"two-in-one"medical and care integration model in People's Hospital of Nanhai Economic Development Zone,focusing on resource integration,talent shortage,service quality,funding support,and information construction.Methods Through field research,data analysis,and literature review,the study investigates the"two-in-one"model of the hospital managing a government-run nursing home,and an-alyzes its specific practices and effects in resource integration,talent development,and information construction.Results Through vertical management,resource integration,and information construction,the hospital significantly improved the service quality of the nursing home.Conclusion The model of the hospital managing a nursing home has achieved a transformation from passive response to external pressure to active stimulation of internal growth,providing a reference for the promotion of medical and care integration services at the village level and offering a new solution to solve the development dilemma of hospitals.

AIM:To evaluate the pharmacokinet-ics(PK)and pharmacodynamics(PD)of two recom-binant human insulin injection by euglycemic clamp technology in healthy male subjects after a single subcutaneous injection.METHODS:We con-ducted a randomized,open-label,single dose,two period,crossover study.A total of 24 healthy male subjects were enrolled and randomized to receive single subcutaneous doses(0.2 U/kg)of the investi-gational products every period.The PK and PD characteristics were assessed by euglycemic clamp up to 14 hours after dosing.RESULTS:Euglycemic clamp technique was successfully established.C-peptide levels detected at each time point before and after administration indicated that endoge-nous insulin secretion was inhibited in the two groups after administration.The geometric mean ratio of Cmax and AUC0-tand 90％confidence interval(CI)of test preparation and reference preparation under fasting condition were in the range of 80.00％-125.00％.CONCLUSION:The human insulin produced by KP Biotech demonstrated similarity to the reference preparation Humulin? in PK and PD characteristics in healthy Chinese subjects.

Objective:To explore changes in brain activity in patients with post-traumatic stress disorder(PTSD).Methods:A total of 40 participants involved in car accidents were included,and functional magnetic reso-nance imaging(fMRI)scans were collected within one week.Anxiety,depression,and personality assessments were conducted with the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),and Eysenck Person-ality Scale for Adult(EPQ).After two months,a second fMRI scan was conducted,and a PTSD diagnosis was made.Participants were divided into a trauma-exposed group(n=23)and a PTSD group(n=17)based on wheth-er they developed PTSD.Changes in brain functional activity between the trauma-exposed group and the PTSD group were compared using the percentage of amplitude fluctuation(perAF)method.Results:Compared to the trauma-exposed group,the PTSD group showed a decreased perAF value in the left hippocampus at 1 week,and de-creased perAF values in the right mid-cingulate gyrus and left postcentral gyrus at 2 months(P＜0.05).When comparing the PTSD group at different times,the perAF values in the left middle temporal gyrus and left medial su-perior frontal gyrus decreased at 2 months(P＜0.05).Correlation analysis revealed that PCL-5 scores were posi-tively correlated with EPQ Psychoticism(r=0.32,P=0.041),HAMA(r=0.35,P＜0.05),and HAMD(r=0.34,P＜0.05).Regression analysis found that higher scores of EPQ psychoticism(OR=11.79)and HAMA(OR=1.62)were risk factors for post-accident PTSD,while higher scores of EPQ extraversion(OR=0.32)were pro-tective factors.Conclusion:It suggests that patients with post-traumatic stress disorder may show decreased activity in the right middle cingulate cortex,left postcentral gyrus,left middle temporal gyrus,and left medial superior fron-tal gyrus within two months after the traumatic event.

Objective The clinical characteristics of 21 cases of nocardiosis were reviewed and antimicrobial resistance of Nocardia strains was analyzed in order to improve the accuracy of clinical diagnosis and treatment of nocardiosis.Methods Clinical data of patients diagnosed with nocardiosis in Zhoukou Central Hospital from 2019-2023 and the corresponding results of antimicrobial susceptibility testing were retrospectively analyzed to summarize the clinical characteristics and outcomes of patients.Results Overall,the 21 cases of nocardiosis included 9 males and 12 females,aged 2-91 years.Underlying disease was reported in 15 patients.Most common type of nocardiosis was pulmonary nocardiosis in 15 cases,followed by skin and soft tissue infection,pleurisy,lymphadenitis,and disseminated nocardiosis.Laboratory tests showed increased levels of WBC,neutrophils percentage,erythrocyte sedimentation rate,C-reactive protein,and procalcitonin.The 21 strains of Nocardia included 4 strains of Nocardia cyriacigeorgica,2 strains each of Nocardia brasiliensis,Nocardia abscessus,Nocardia asiatica,Nocardia otitidiscaviarum and Nocardia beijingensis,and 1 strain each of Nocardia puris,Nocardia asteroides,Nocardia farcinica,Nocardia pneumoniae,Nocardia amamiensis,and 2 strains of unclassified Nocardia.All of the Nocardia strains(100％)were susceptible to linezolid,amikacin,and trimethoprim-sulfamethoxazole,followed by various levels of susceptibility to cefotaxime,moxifloxacin,imipenem and ceftriaxone,and lower susceptibility rate to cefepime,minocycline,ciprofloxacin and clarithromycin.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Of the 21 patients,two were referred to other hospitals,another two died,two patients received unknown treatment,and the remaining 15 patients were improved after antibiotic treatment,including sulfonamides combined with other antibiotics in 11 cases,other antibiotics in 4 cases.Conclusions Immunocompromised patients or those with underlying diseases are more susceptible to nocardiosis.The clinical features are complex and diverse.Antimicrobial susceptibility of Nocardia strains varied with different Nocardia species.Accurate identification and antimicrobial susceptibility test are essential for prescribing effective antibiotic treatment.