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

BackgroundSchizophrenia， as a common chronic mental disorder， although second-generation antipsychotic drugs have shown significant efficacy in alleviating positive symptoms， the widespread cognitive dysfunction among patients remains a challenge in clinical treatment. Traditional Chinese medicine has unique advantages in the treatment of mental disorders. However， the current clinical research on the combination of Wendan Decoction and antipsychotic drugs for schizophrenia varies in quality， and there is a lack of systematic reviews evaluating its effects on cognitive improvement and safety. ObjectiveTo systematically evaluate the effects of modified Wendan Decoction combined with antipsychotic drugs on schizophrenia symptoms and cognitive improvement， providing evidence-based support for the clinical application of Wendan Decoction. MethodsLiterature searches were conducted in China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP Information， China Biomedical Literature Service System， China Clinical Trial Registry， PubMed， Web of Science， the Cochrane Library， and Embase to collect randomized controlled trials （RCTs） of modified Wendan Decoction combined with antipsychotic drugs for the treatment of schizophrenia. The search period was from the establishment of the databases to March 19， 2026. The quality of the included literature was evaluated using the Cochrane 6.3. Meta-analysis was performed using RevMan 5.3 software. ResultsA total of 11 studies were included， involving 1 130 patients with schizophrenia. Among them， 566 cases were in the study group （receiving modified Wendan Decoction combined with antipsychotic drugs）， and 564 cases were in the control group （receiving antipsychotic drugs only）. Meta-analysis showed that the effective rate of improvement in psychotic symptoms in the study group was higher than that in the control group （RR=1.21，95% CI： 1.15–1.27， P<0.01）. In terms of psychotic symptoms， the Positive and Negative Symptom Scale （PANSS） positive symptom score （MD=-3.69， 95% CI： -5.87–-1.51， P<0.01） and PANSS total score （MD=-9.20， 95% CI： -11.80–-6.59， P<0.01） of the study group were lower than those of the control group. In cognitive function assessments， the Mini-Mental State Examination （MMSE） score （MD=2.51， 95% CI： 1.33–3.68， P<0.01） and the Loewenstein Occupational Therapy Cognitive Assessment （LOTCA） score （MD=11.85， 95% CI： 2.55–21.15， P=0.010） of the study group were higher than those of the control group， and the Wisconsin Card Sorting Test （WCST） score was lower than that of the control group （MD=-9.34， 95% CI： -12.57–-6.11， P<0.01）. The levels of brain-derived neurotrophic factor （BDNF） （SMD=1.34， 95% CI： 0.63–2.05， P<0.01） and nerve growth factor （NGF） （MD=6.94， 95% CI： 4.00–9.89， P<0.01） of the study group were higher than those of the control group. In terms of safety， there was no statistically significant difference in the incidence of adverse reactions between the two groups （RR=0.60， 95% CI： 0.31–1.18， P=0.14）. ConclusionThe modified Wendan Decoction combined with antipsychotic drugs may be more effective than antipsychotic drugs alone in improving positive symptoms and cognitive function in patients with schizophrenia， and it also exerts a favorable neurotrophic regulatory effect. ［Funded by Postgraduate Education Reform and Quality Improvement Project of Henan Province （number， YJS2023AL060）； Key Scientific Research Projects of Higher Education Institutions in Henan Province （number， 24B320018， 25B310004）］

Objective To investigate the impacts of long non coding RNA(LncRNA)-PH domain containing 5 antisense RNA 1(FGD5-AS1)on the proliferation,migration,and invasion of colorectal cancer(CRC)cells by regulating the miR-299-5p/recombinant lysine specific demethylase 4B(KDM4B)axis.Methods The expressions of LncRNA FGD5-AS1,miR-299-5p,and KDM4B were detected by qRT-PCR in the surgically resected CRC tissues and adjacent tissues of 34 CRC patients CRC cells HCT116 were separated into si-NC group,si-FGD5-AS1 group,si-FGD5-AS1+inhibitor NC group,and si-FGD5-AS1+miR-299-5p inhibitor group.The levels of mRNA in each group were detected.CCK8,scratch assay,and Transwell assay were ap[plied to detect the proliferation,migration,and invasion of HCT116 cells in each group.Western blot was applied to detect the expression of proteins.Dual luciferase reporter gene assay verified the interaction mechanism between LncRNA FGD5-AS1 and miR-299-5p,and between miR-299-5p and KDM4B.Results LncRNA FGD5-AS1 and KDM4B were highly expressed in CRC tissue,while miR-299-5p was low expressed in CRC tissue(P＜0.05).The expression of LncRNA FGD5-AS1 mRNA,KDM4B mRNA,OD450,scratch healing rate,invasion number,PCNA,MMP-2,MMP-9,KDM4B in the si-FGD5-AS1 group were lower than those in the si-NC group,the expression of miR-299-5p mRNA was higher than that in the si-NC group(P＜0.05).Compared with the si-FGD5-AS1 group and si-FGD5-AS1+inhibitor NC group,the expression of miR-299-5p in the si-FGD5-AS1+miR-299-5p inhibitor group decreased(P＜0.05),the KDM4B mRNA,OD450,scratch healing rate,number of invasions,and expression of PCNA,MMP-2,MMP-9,KDM4B increased(P＜0.05).LncRNA FGD5-AS1 targeted negative regulation of miR-299-5p,while miR-299-5p targeted negative regulation of KDM4B.Conclusion Knocking down LncRNA FGD5-AS1 may inhibit the proliferation,migration,and invasion of CRC cells,and its mechanism may be achieved by regulating the miR-299-5p/KDM4B signaling axis.

Objective:To integrate implicit templates with deep learning techniques, a novel neural network, the tooth-deformable deep implicit network (T-DDIN), was constructed to achieve high-precision shape completion of tooth defects in a personalized manner.Methods:A total of 550 intraoral scan models were collected from patients treated at the Department of Orthodontics and Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University (500 for training and 50 for testing), between March 2022 and March 2024. T-DDIN reconstructed defective tooth morphology using an implicit template and a latent encoding prediction network. During model evaluation, Class Ⅱ cavity defects and occlusal wear defects were simulated in the test set. Morphological restoration was performed using both traditional computer aided design (CAD) methods and the T-DDIN deep learning approach. The two methods were compared based on three-dimensional deviation, occlusal adjustment volumes, cusp angle deviation, and restoration time.Results:The T-DDIN group demonstrated significantly lower three-dimensional deviation for Class Ⅱ cavity defects and occlusal wear restoration [(0.14±0.05) and (0.16±0.09) mm], occlusal adjustment volumes [(0.44±0.03) and (0.49±0.03) mm 3], and difference value of the tooth cusp angles (5.69°±1.90° and 6.04°±0.53°) compared to the traditional CAD group (both P<0.001). No significant differences were observed within the T-DDIN group between the two defect types in terms of three-dimensional deviation ( P=0.098) or occlusal adjustment volume ( P=0.154) or difference value of the tooth cusp angles ( P=0.196). However, in the traditional CAD group, three-dimensional deviation, occlusal adjustment volume and difference value of the tooth cusp angles was significantly higher in occlusal wear restorations than in Class Ⅱ cavity defects restorations ( P<0.001). The T-DDIN group, which involved Class Ⅱ cavity defects and occlusal wear, demonstrated significantly less recovery time of morphology (37.2±7.7) and (39.4±6.2) s compared to the traditional CAD group ( P<0.001). Conclusions:T-DDIN demonstrated superior stability and accuracy in morphological reconstruction for various types of dental defects while significantly reducing restoration time.

Objective To investigate the epidemiological characteristics of Mycoplasma pneumoniae(MP)infection among pediatric inpatients with respiratory tract infections(RTIs)at Children's Hospital of Hebei Province,providing evidence for clinical diagnosis and treatment.Methods A retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024.Nasopharyngeal aspirates or deep sputum samples were collected,and polymerase chain reaction(PCR)was used to detect nucleic acids of 13 respiratory pathogens,including MP and adenovirus.The epidemiological trends across different years,seasons,genders,and age groups were analyzed.Results Among the 79 546 enrolled cases(male:47 437,59.6%;female:32 109,40.4%),the MP-positive rate was 17.7%(14 106/79 546),peaking in 2023(28.8%)and reaching the lowest in 2021(7.0%).Except for the period from July 2020 to March 2021 with exceptionally low MP positivity,epidemic peaks consistently occurred between August and February or March of the following year.Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring(P<0.001).Female children exhibited a higher MP-positive rate(20.1%,6444/32 109)than males(16.2%,7662/47 437)(P<0.001).The MP-positive rate increased with age:infancy(3.2%,849/26 741),toddlerhood(9.3%,1935/20 763),preschool(21.2%,3918/18 448),and school-age(54.5%,7404/13 594)(P<0.001).Co-infections with other respiratory pathogens were observed in 37.3%(5264/14 106)of MP-positive cases,with human rhinovirus(HRV)being the most frequent co-pathogen(43.3%,2279/5264 of mixed infections).Conclusion MP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province.Infections occur year-round but predominantly in autumn,with higher susceptibility in females and school-age children.Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.

The efficacy of root canal therapy, as a core intervention for endodontic and periapical diseases, is highly dependent on the effectiveness of antimicrobial drugs. Although traditional drugs such as calcium hydroxide, chlorhexidine, and antibiotic pastes commonly used in the clinic play a role in preventing and controlling infections, they have obvious limitations. These drugs influence the mechanical properties of dentin, insufficiently solubilize necrotic tissues, and are susceptible to bacterial resistance, which makes achieving the desired effectiveness and safety difficult. Traditional macromolecular root canal drugs also face the challenge of the complexity of the root canal system. With the rapid development of material science in recent years, new antimicrobial agents have emerged. Metallic nanomaterials such as silver nanoparticles and zinc oxide nanoparticles are widely used in the medical field due to their unique physicochemical properties and superior antimicrobial properties. Chitosan nanoparticles have superior biosafety, calcium hydroxide nanoparticles compensate for the limitations of traditional calcium hydroxide formulations, and quaternary ammonium polyethyleneimine nanoparticles can confer antimicrobial properties to existing oral materials. Novel antimicrobial nanoparticles using nano-delivery systems, such as mesoporous calcium silicate and mesoporous silica, carry antimicrobial molecules with significant advantages in terms of anti-biofilm, biosafety, and promotion of tissue repair. Further, these agents reduce drug resistance, which improves prospects for application compared to traditional root canal disinfection drugs. The breakthrough of nanotechnology provides a novel direction for the innovation of root canal treatment drugs. Therefore, this paper reviews the research progress of nano-antimicrobial materials in root canal therapy.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Metastatic lung cancer continues to cause a high number of deaths due to high malignancy and poor prognosis, and the efficacy of typical chemotherapy or immunotherapy is less than ideal due to the low pulmonary accumulation and targeting of therapeutics. Here, a submicron-sized biomimetic liposome was formulated for the lung-targeted co-delivery of bacterial superantigen and paclitaxel. Recombinant staphylococcal enterotoxin C2 (rSEC2), a bacterial superantigen, was expressed with the Escherichia coli system and showed potent immunostimulatory activities to mediate tumor cell death. The submicron-sized (∼800 nm) biomimetic liposomes, namely 4T1 cell membrane-hybrid rSEC2 paclitaxel liposomes (TSPLs), exhibited high lung-accumulation efficiency and tumor homologous effect due to the suitable particle size and membrane hybridization of cancer cell membranes with phospholipids. Intravenous TSPLs remarkably inhibited metastatic lung cancer with limited systemic immune responses. TSPLs reversed the immunosuppressive state and increased the proportion of local CD4⁺ and CD8⁺ T cells in the lung; moreover, paclitaxel increased tumor cell apoptosis and reduced tumor burden. In summary, the high lung cancer targeting was achieved by particle size control and cell membrane hybridization, and the highly efficient anticancer effect was achieved by the co-delivery of superantigens and chemotherapeutic drugs.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent