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: 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.

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.

Objective To establish a mouse model of H1N1 influenza wind-heat syndrome by combining climate intervention with influenza virus nasal drops.Methods Seventy-two BALB/c mice were divided randomly into nine groups:a Control group,wind-heat(FR)groups(FR-3Day,FR-5Day),and Model groups(1LD-3Day,2LD-3Day,3LD-3Day,1LD-5Day,2LD-5Day,2LD-5Day,3LD-5Day)(n=8 mice per group).Mice in the Control group were housed in a normal environment,while mice in the FR and Model groups were kept in wind-heat conditions for 7 d.Mice in the Model groups received nasal PR8 influenza virus infection on the 8th day,and mice in the Control and FR heat groups received equal amounts of physiological saline nasal drops.After virus challenge,each group was housed in a normal environment and samples were taken on days 3 and 5.The appearance of the mice was observed and recorded and the lung index,routine blood parameters,lung tissue pathology,serum interleukin(IL)-6 levels,and virus titers were detected in each group based on their behavioral status,stools,and body temperature.Results After 7 d of wind-heat intervention,mice in the FR groups showed no significant abnormalities in terms of appearance,stools,body temperature,routine blood parameters,or lung tissue pathology compared with the Control group.The appearance,lung index,red blood cell count,hemoglobin,hematocrit,pathological result,and body temperature in the Model groups worsened progressively with increasing time and toxin dosage,while the neutrophil percentage,lymphocyte percentage,virus titer,and serum IL-6 levels peaked on day 3 after viral attack,for the same viral dose,and then decreased slightly on day 5.Conclusions PR8 nasal drops and 7 d of wind-heat climate intervention can be used to establish a mouse model of influenza wind-heat syndrome.

Objective:To investigate the feasibility of deep learning reconstruction (DLR) algorithm combined with a dual-low protocol (low radiation dose and low contrast medium dose) for thoracoabdominal aortic CT angiography (CTA).Methods:This cross-sectional study prospectively enrolled 56 patients suspected of aortic diseases who underwent aortic CTA at China-Japan Friendship Hospital from June 2023 to June 2024. All patients were randomly divided into two groups: Group A (28 cases) underwent CTA with a tube voltage of 100 kVp, automatic tube current modulation (noise index=10), and a contrast agent dose of 80 ml (flow rate 5 ml/s), with images reconstructed using the three-dimensional adaptive iterative dose reduction algorithm (AIDR). Group B (28 cases) underwent CTA with a tube voltage of 80 kVp, automatic tube current modulation (noise index=25), and a contrast agent dose of 40 ml (flow rate 3.5 ml/s), with images reconstructed using either the deep learning reconstruction algorithm-Advanced intelligent Clear-IQ Engine (AiCE subgroup) or the AIDR (AIDR subgroup). Two physicians evaluated the image quality of the three groups subjectively and objectively. Objective evaluation metrics included CT values, image noise (SD), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) at the ascending aorta, carina-level descending aorta, celiac trunk-origin abdominal aorta, and common iliac bifurcation abdominal aorta carina. Subjective evaluation metrics included image quality and noise scores. Comparisons among the three datasets (Group A, AiCE subgroup, AIDR subgroup) were performed using one-way ANOVA or the Kruskal-Wallis test, with appropriate post-hoc tests for pairwise comparisons.Results:No significant differences were observed in CT values of the ascending aorta, descending aorta, and abdominal aorta between Group A and the AiCE subgroup or the AIDR subgroup ( P0.05). However, significant overall differences were found in SD, SNR, and CNR values for the ascending aorta, descending aorta, and abdominal aorta ( P0.05). Pairwise comparisons revealed that, except for no significant differences in SD, SNR, and CNR values of the ascending and descending aorta between Group A and the AiCE subgroup, and no significant difference in SNR values of the ascending and abdominal aorta between Group A and the AIDR subgroup ( P0.05), all other intergroup comparisons showed statistically significant differences ( P0.05). Significant overall differences were also observed in image quality and noise scores between Group A and the AiCE and AIDR subgroups ( P0.05). Except for no significant differences in image quality and noise scores between Group A and the AiCE subgroup ( P0.05), all other pairwise comparisons showed statistically significant differences ( P0.05). Conclusions:The application of deep learning reconstruction algorithm combined with a dual-low protocol in thoracoabdominal aortic CTA can reduce radiation dose and contrast agent dose while maintaining diagnostic image quality, demonstrating significant clinical value for widespread adoption.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

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.