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

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective: To investigate the coexistence of comorbidity of myopia, overweight/obesity and depressive symptoms among middle school students in Quzhou and its associated factors, so as to provide evidence for integrated prevention and control of common multiple health issues in students. Methods: From September to November 2023, a total of 5 867 middle school students from 6 counties (cities and districts) in Quzhou City were selected by stratified random cluster sampling. Physical and visual examinations were conducted, and the Center for Epidemiological Studies - Depression Scale (CES-D) along with a questionnaire on health status and influencing factors were completed. Multivariate Logistic regression was used to analyze the related factors of coexistence of myopia, overweight/obesity, and depressive symptoms among middle school students, and a nomogram model was constructed based on the results. Results: A total of 161 middle school students in Quzhou City were identified as having comorbid myopia, overweight/ obesity and depressive symptoms, with a detection rate of 2.74%. The results of multivariate Logistic regression analysis showed that the coexistence of myopia, overweight/obesity and depressive symptoms increased among middle school students with older age ( OR =1.11), a greater number unhealthy dietary behaviors (1,2,≥3; OR =2.40, 2.70, 4.63), insufficient sleep( OR =1.78) and alcohol consumption ( OR =2.11)(all P <0.05). Compared with no homework after class, those whose homework duration after class was 1 to < 2 hour had a lower risk of comorbidity of myopia, overweight/obesity and depressive symptoms ( OR =0.53, P <0.05). The results of the nomogram model showed that the AUC (95% CI ) was 0.71 (0.67-0.74). Conclusions The coexistence of myopia, overweight/obesity and depressive symptoms among middle school students in Quzhou City is related to age, sleeping, alcohol consumption, poor dietary behavior and the duration of after school homework. The nomogram model can assist in the early screening and intervention of multiple health issues among students.

Objective To compare the effects of different exercise acclimatization(EA)durations on liver injury and inflammatory response in mice with exertional heatstroke(EHS).Methods A total of 168 male C57BL/6 mice were randomly assigned to four groups using a random number table:no exercise acclimation group(EA0W,n=54),1-week exercise acclimation group(EA1W,n=54),2-week exercise acclimation group(EA2W,n=54),and blank control group(n=6).The blank control group did not undergo acclimatization training or EHS modeling.The EA1W and EA2W groups underwent daily 2-hour exercise training at a speed of 10 m/min in an environment maintained at(26.0±0.5)℃for 1 and 2 weeks,respectively,followed by a 2-day rest after training completion.EHS modeling was performed in mice of EA0W,EA1W,and EA2W groups through running at 10 m/min under controlled environmental conditions(39.5℃ambient temperature,65%relative humidity).The modeling endpoint was defined as loss of consciousness accompanied by a core body temperature≥42.7℃.All modeling procedures were systematically documented.Following modeling,18 mice from EA0W,EA1W,and EA2W groups underwent 24-hour survival analysis.Blood samples from the abdominal aorta and liver tissues were collected at 6,12 and 24 hours post-modeling(6 mice per time point for each group).Plasma levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase(CK)were quantified.Interleukin(IL)-1β and IL-6 concentrations were determined using enzyme-linked immunosorbent assay(ELISA).Liver tissue specimens underwent hematoxylin-eosin(HE)staining and pathological scoring.Results The EHS model was successfully established in all EA groups.When all mice in EA0W group developed EHS(65 min after the modeling initiation),the incidence rates in EA1W and EA2W groups were 50.0%and 22.2%,respectively,with a statistically significant difference between EA0W group and the latter two groups(P<0.05).When all mice in the three groups developed EHS,the time to EHS onset was significantly longer in both EA1W and EA2W groups compared to EA0W group,with EA2W group showing a longer onset time than EA1W group(P<0.05).Survival analysis revealed a significantly higher 24-hour survival rate in EA2W group(61.1%)compared to EA0W group(33.3%)(P<0.05),while no significant difference was observed between EA1W group and the other two groups(P>0.05).The levels of IL-1β,IL-6,and CK were highest at 6 h post-modeling in all EA groups(P<0.05),and liver injury was most severe at 12 h post-modeling(P<0.05).Compared to EA0W group,the levels of ALT,AST,and IL-1β,as well as liver pathology scores,were significantly lower at 12 h post-modeling in both EA1W and EA2W groups(P<0.05),with EA2W group showing significantly lower ALT and AST levels,as well as liver pathology scores than EA1W group(P<0.05).At 6 h post-modeling,CK levels were significantly higher in EA1W and EA2W groups compared to EA0W group(P<0.05),with EA2W group exhibiting higher CK levels than in EA1W group(P<0.05).Conclusions Exercise acclimation helps reduce the incidence of EHS.Following EHS onset,the survival rate of exercise-acclimated mice is higher than that non-acclimated mice,with a significantly higher survival rate in mice acclimated for 2 weeks compared to non-acclimated mice.However,no significant difference in survival rate is observed between mice acclimated for 1 week and non-acclimated mice.Additionally,exercise acclimation for 2 weeks is more effective in reducing liver injury and inflammatory responses compared to 1-week acclimation.

Objective By using intravoxel incoherent motion(IVIM)double exponential model liver multi-b value diffusion-weighted imaging(DWI)scanning technique to analyze the lesion's IVIM parameters before and after interventional treatment of hepatocellular carcinoma(HCC)with conventional transcatheter arterial chemoembolization(TACE)combined with CalliSpheres drug-loaded microspheres(DEB-TACE),based on which to quantitatively evaluate the efficacy of interventional therapy for HCC.Methods A total of 40 HCC patients,who were admitted to the Department of Interventional Therapy of Anqing Municipal Hospital of China from June 2022 to November 2023 to receive DEB-T ACE,were enrolled in this study.Routine MR examination,DWI and IVIM-DWI scan were performed before and at 1,3 and 6 months after treatment,and a total of 40 interest lesions were selected.The ADC value,perfusion fraction(f),pure diffusion coefficient(D),and perfusion-related diffusion coefficient(D*)of each lesion were analyzed.The receiver operating characteristic(ROC)curve was drawn to analyze the prognosis assessment value of IVIM-DWI parameters.Results After DEB-TACE treatment,the ADC value and D value were increased,and the f value was decreased when compared with their preoperative values,the differences were statistically significant(all P＜0.01).The ADC value and D value in the patients of effective group were remarkably higher than those in the patients of ineffective group,the differences were statistically significant(both P＜0.01);the f value in the patients of effective group was slightly lower than that in the patients of ineffective group,and the difference was statistically significant(P＜0.05).The areas under ROC curve of ADC value,D value and f value for evaluating efficacy were 0.762,0.877,and 0.708 respectively.The area under the curve for the joint assessment of the three parameters was 0.928,with the highest efficacy.Conclusion IVIM-DWI can quantitatively determine the microperfusion and activity of HCC lesions before and after interventional DEB-TACE treatment,and it can also evaluate the curative efficacy of interventional therapy for HCC as well as the outcome of HCC lesions.

BackgroundIn schizophrenia， a subset of patients may progress to treatment-resistant schizophrenia owing to inadequate response to standard antipsychotic therapies， resulting in profound impairments in cognitive and social functioning alongside a cumulative burden of adverse drug reactions during the prolonged treatment. Currently， evidence supporting the use of blonanserin for treatment-resistant schizophrenia remains limited. ObjectiveTo investigate the efficacy and safety of blonanserin in the treatment of treatment-resistant schizophrenia， so as to provide references for clinical management of this condition. MethodsA total of 43 inpatients fulfilling the International Classification of Diseases， tenth edition （ICD-10） diagnostic criteria for treatment-resistant schizophrenia were consecutively recruited from Taiyuan Psychiatric Hospital from September 2024 to January 2025. Subjects were assigned to either the study group （n=21） or the control group （n=22） using the random number table method. The study group received blonanserin at a daily dosage ranging from 8 to 24 mg， while the control group was administered amisulpride at a daily dosage from 400 to 1 200 mg. At baseline and at the end of the 4^th and 8^th week of treatment， the Positive and Negative Symptom Scale （PANSS） and the Personal and Social Performance scale （PSP） were used to access patients' psychotic symptoms and social functioning， respectively. Cognitive function was evaluated using the Hopkins Verbal Learning Test （HVLT）， the Stroop Color-Word Test （SCWT）， the Trail Making Test （TMT）， the Digit Span Test （DST）， and the Digit Symbol Substitution Test （DSST）. During the treatment process， treatment-related adverse reactions were recorded between two groups. ResultsSignificant time effects were found in PANSS total scores， as well as its positive symptom， negative symptom， and general psychopathological subscale scores （F=186.505， 149.318， 135.671， 416.744， P<0.01）. The group-by-time interaction effect was significant in PANSS total scores and general psychopathological subscale scores （F=3.483， 4.318， P<0.05）. At the end of the 8^th week， the study group exhibited lower general psychopathological subscale scores and the PANSS total scores compared to the control group， with statistically significant differences （t=-2.106， -2.429， P<0.05）. Significant group effects were detected in HVLT scores， Stroop word scores and Stroop color scores （F=6.720， 7.921， 11.383， P<0.05 or 0.01）. The group-by-time interaction effect for Stroop word scores， Stroop interference scores， TMT scores and DSST scores were statistically significant （F=3.571， 4.095， 3.463， 37.000， P<0.05 or 0.01）. At the end of the 8^th week， the DSST score of the study group was higher than that of the control group （t=2.074， P<0.05）. For PSP scores， significant time effect， group effect and group-by-time interaction effect were all observed （F=433.710， 4.463， 10.491， P<0.05 or 0.01）. At the end of the 8^th week， the study group reported higher PSP score compared to the control group， with a statistically significant difference （t=3.451， P<0.05）. No significant difference in the incidence of adverse reactions was exhibited between the two groups （P>0.05）. ConclusionBlonanserin demonstrates efficacy comparable to amisulpride in ameliorating positive and negative symptoms in patients with treatment-resistant schizophrenia. Notably， blonanserin exhibits a superior efficacy to amisulpride in improving general psychopathological symptoms， cognitive and social functioning， while both agents show comparable safety profiles. （www.chictr.org.cn number： ChiCTR2400094222）

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective To investigate the value of MRI of the sternal end of clavicle in bone age assessment in Chinese population,especially its applicability in the determination of criminal responsible age.Methods A total of 431 patients aged from 10.00 to 29.99 years with neck or chest MRI were retrospectively collected.According to the Schmeling grading method,the epiphyseal development of the clavicle MRI was divided into five grades.The consistency of methods was evaluated.The correlation and general descriptive analysis between MRI grades and age was analyzed.The sex difference was analyzed.Curve fitting was used to establish a nonlinear model between age and grades.Results The grades of clavicle MRI showed a significant age-related trend(Figure 2),and the correlation was 0.861(0.887 in males and 0.840 in females).Except for grade 1,there was no significant difference between males and females in other grades.The minimum age of male grade 3 was greater than 14 years old,and the minimum age of female grade 3 was greater than 16 years old.The minimum age in grade 4 and grade 5 was over 18 years old in both sexes.The best curve fitting model was cubic model for both sexes(R2=0.805 for men and 0.722 for women).Conclusion Clavicle MRI can be used for the assessment of bone age in Chinese population.Complete epiphyseal plate closure can be used as a reliable indicator for the determination of age at 18 years old,and it is expected to achieve radiation-free forensic bone age assessment.

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals