Hepatitis B virus(HBV)infection is the main risk factor for the development and progres-sion of hepatocellular carcinoma(HCC).Through re-peated inflammatory stimulation,liver cells regen-eration,fibrosis,and scar formation,it may eventu-ally progress to HCC.Antiviral treatment reduces the incidence of HBV-related HCC and the risk of postoperative recurrence by reducing HBV DNA lev-el,thereby improving prognosis.Many recent stud-ies have found that different kinds of nucleos(t)ide analogues(NAs)may have differential improve-ments in the prevention of HBV-related HCC occur-rence and postoperative recurrence.This article re-views the differential improvement of different cat-egories of NAs in HBV-related HCC and the possible mechanisms.

Objective:To analyze the application efficacy of employing high-density porous polyethylene （Su-por） in combination with temporoparietal fascial flaps via a minimally invasive scalp incision in auricular reconstruction. Methods:This study carried out a retrospective analysis of 50 patients （50 ears in total） who underwentprimary auricular reconstruction with a Su-por scaffold in our hospital from June 2022 to January 2024. All patients underwent primary auricular reconstruction using a minimally invasive scalp incision with high-density porous polyethylene （Su-por） and temporoparietal fascial flaps. The postoperative treatment effects and complications were statistically analyzed. Results:The reconstructed ears of all patients survived. After 6 months of follow-up, the scar hyperplasia of the scalp minimally invasive incision was not obvious in any patient, and no significant hair loss was observed. The reconstructed auricle of 48 patients had a realistic shape and strong three-dimensional sense. With the extension of follow-up time, the three-dimensional structure of the auricle became clearer, and patient satisfaction increased. Among the remaining two patients, one case of flap necrosis survived after skin grafting and dressing changes. One patient had scar hyperplasia at the incision of the reconstructed ear due to a scar-prone constitution, and the shape of the auricle was not ideal, but the scar hyperplasia at the scalp incision was not obvious. Conclusion:One-stage ear reconstruction with high-density porous polyethylene （Su-por） combined with superficial temporal fascia flap through a minimally invasive scalp incision can better show the fine structure of the reconstructed ear. The minimally invasive scalp incision can effectively reduce the occurrence of scar hyperplasia and postoperative alopecia at the scalp incision.
Humans ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Surgical Flaps ; Tissue Scaffolds ; Polyethylene ; Ear Auricle/surgery* ; Male ; Scalp/surgery* ; Female ; Skin Transplantation ; Fascia/transplantation* ; Porosity ; Adult ; Middle Aged

Objective:To investigate the impact of Waardenburg syndrome（WS） -associated Sox10 p.S100Rfs*9 mutation on inner ear function and its mechanism in noise-induced hearing impairment. Methods:A mice model carrying the Sox10 p.S100Rfs*9 mutation was established using CRISPR-Cas9 gene editing technology. Auditory phenotypes were assessed under baseline conditions and after noise exposure（96 dB SPL, 2 hours）. Auditory brainstem response（ABR） tests were performed to evaluate hearing function, combined with immunofluorescence staining of cochlear basilar membrane whole-mounts to observe hair cells and ribbon synapses. Transcriptome sequencing was conducted to analyze molecular mechanisms. Results:Sox10 p.S100Rfs*9 heterozygous mice exhibited normal hearing thresholds with characteristic ventral pigmentation abnormalities under baseline conditions. Following noise exposure, mutant mice showed significantly higher ABR thresholds at 24 000 Hz compared to wild-type controls（[60.00±6.12]vs[48.13±4.28]dB SPL, P<0.000 1）, and a significant reduction in ribbon synapses（CtBP2-positive puncta） in the basal turn（[55.0±2.3]vs[64.8±3.3]per inner hair cell, P=0.006 6）, while hair cell morphology and number remained intact. Transcriptome analysis revealed altered expression of genes involved in immune regulation, membrane structures, ion channels, and neuroactive ligand-receptor interactions. Conclusion:The Sox10 p.S100Rfs*9 mutation does not alter baseline hearing function but significantly increases inner ear susceptibility to noise damage, primarily manifested as enhanced ribbon synapse vulnerability, especially in high-frequency regions. This gene-environment interaction reveals that Sox10 haploinsufficiency may compromise noise tolerance by affecting synaptic stability and inner ear protective mechanisms. These findings provide new perspectives on the phenotypic heterogeneity in WS patients and theoretical basis for individualized noise protection strategies for patients carrying SOX10 mutations.
Animals ; SOXE Transcription Factors/genetics* ; Waardenburg Syndrome/physiopathology* ; Mice ; Hearing Loss, Noise-Induced/genetics* ; Evoked Potentials, Auditory, Brain Stem ; Mutation ; Noise ; Disease Models, Animal ; Ear, Inner/physiopathology*

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

The size of nanodrugs plays a crucial role in shaping their chemical and physical characteristics, consequently influencing their therapeutic and diagnostic interactions within biological systems. The optimal size of nanomedicines, whether small or large, offers distinct advantages in disease treatment, creating a dilemma in the selection process. Addressing this challenge, size-transformable nanodrugs have surfaced as a promising solution, as they can be tailored to entail the benefits associated with both small and large nanoparticles. In this review, various strategies are summarized for constructing size-transformable nanosystems with a focus on nanotherapeutic applications in the field of biomedicine. Particularly we highlight recent research developments in cancer therapy. This review aims to inspire researchers to further develop various toolboxes for fabricating size-transformable nanomedicines for improved intervention against diverse human diseases.

Hepatitis B virus(HBV)infection is the main risk factor for the development and progres-sion of hepatocellular carcinoma(HCC).Through re-peated inflammatory stimulation,liver cells regen-eration,fibrosis,and scar formation,it may eventu-ally progress to HCC.Antiviral treatment reduces the incidence of HBV-related HCC and the risk of postoperative recurrence by reducing HBV DNA lev-el,thereby improving prognosis.Many recent stud-ies have found that different kinds of nucleos(t)ide analogues(NAs)may have differential improve-ments in the prevention of HBV-related HCC occur-rence and postoperative recurrence.This article re-views the differential improvement of different cat-egories of NAs in HBV-related HCC and the possible mechanisms.

Objective: To investigate the effectiveness and safety of brexpiprazole as an adjunctive treatment to antidepressant therapy (ADT) in Asian adults with major depressive disorder (MDD) and inadequate response in a real-life clinical setting in Singapore. Methods: This was a prospective, observational 3-month study of patients with MDD who had brexpiprazole added to their existing ADT. The study was conducted at two sites in Singapore between September 2020 and October 2021.The co-primary endpoints were Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S).Other endpoints included Clinical Global Impression-Improvement (CGI-I), Sheehan Disability Scale (SDS), Generalized Anxiety Disorder 7-item scale (GAD-7), and safety. Results: Twenty patients were enrolled and 16 completed the study. There were improvements in PHQ-9, CGI-S, SDS, and GAD-7 scores from baseline at Week 12, with a mean difference of −4.8, −1.3, −8.5, and −6.2, respectively.The CGI-I score improved from baseline with a mean score of 2.3 at Week 12. One third achieved response and 25% achieved remission based on PHQ-9 scores at Week 12. Similar results were obtained using CGI-S scores (38% for both). The incidences of adverse events (AEs) and treatment-related AEs were 55% (11/20) and 50% (10/20), respectively. There were no deaths or severe AEs. Two patients withdrew brexpiprazole during the study. Conclusion The observed effects and safety of adjunctive brexpiprazole in Asian adults with MDD in the real-world setting in Singapore were consistent with those from clinical trials.

Hepatitis E virus(HEV)infection is an infectious disease that can lead to acute or chronic hepatitis E and poten-tially liver failure.HEV can invade multiple organ systems outside the liver,thus leading to pathological damage and diverse clinical manifestations.Neurological disorders are the most common extrahepatic diseases associated with HEV infection.The rare associated extrahepatic diseases include renal disorders,hematological disorders,acute pancreatitis,endocrine system dis-eases,and male infertility.Hence,HEV infection should be considered as a systemic disease rather than solely a liver disease.Many reports have described nervous system diseases caused by HEV infection.This article reviews the rare extrahepatic disea-ses and pathogenic mechanisms of hepatitis E,to enhance comprehensive,in-depth understanding of HEV infection,and to provide a reference for early identification and intervention.