ObjectiveThe Golgi apparatus serves as a central hub in the eukaryotic secretory pathway, responsible for the processing, sorting, and trafficking of proteins and lipids. In mammalian cells, the Golgi typically forms a perinuclear ribbon-like structure composed of laterally connected cisternae stacks.The maintenance of Golgi ribbon structure depends on the balance of membrane flux across multiple intracellular trafficking pathways, yet the specific contributions of distinct trafficking branches to Golgi macroscopic morphology remain elusive. In mammalian cells, the Golgi ribbon is typically organized as a perinuclear, laterally connected structure composed of stacked cisternae, and its integrity is highly dynamic and sensitive to perturbations in membrane trafficking. This study aims to elucidate the role of coat protein complex I (COPI)-mediated retrograde transport in maintaining the Golgi ribbon and to dissect the functional relationship between the transmembrane cargo receptors LEPROT/LEPROTL1 (LEPROTs) and the COPI adaptor GOLPH3. MethodsUsing siRNA interference and gene-deficient cell lines, we selectively perturbed COPI- or adaptor protein complex 1 (AP-1)-mediated trafficking pathways in HeLa cells. To quantitatively evaluate Golgi morphology, we employed a “Golgi Angle”-based measurement to assess its circumferential distribution around the nucleus. The spatial distribution of the Golgi ribbon was quantitatively analyzed using confocal microscopy, while Golgi ultrastructure and vesicle density were examined via transmission electron microscopy. Additionally, the subcellular distribution of COPI components was assessed by immunofluorescence co-localization. ResultsSelective inhibition of COPI retrograde transport significantly induced the circumferential extension of the Golgi ribbon around the nucleus, whereas blocking AP-1-mediated anterograde transport resulted in Golgi compaction, indicating opposing roles. These results suggest that different trafficking branches downstream of ARF1 exert distinct and even antagonistic effects on Golgi morphology. LEPROTs-deficient cells exhibited a Golgi extension phenotype highly consistent with COPI impairment. Furthermore, knockdown of GOLPH3 in a LEPROTs double-knockout background produced a significant additive effect on Golgi extension, suggesting that LEPROTs and GOLPH3 play non-redundant roles in regulating COPI-related trafficking processes. Mechanistically, loss of either LEPROTs or GOLPH3 led to the aberrant accumulation of COPI components at endoplasmic reticulum exit sites, accompanied by a reduction in COPI-like vesicles around the Golgi. This redistribution indicates a defect in COPI recycling between the ER-Golgi interface and the Golgi apparatus. Ultrastructural analysis revealed that Golgi cisternae in defective cells became shorter and thicker while maintaining a stable number of stacks. In parallel, the density of Golgi-associated vesicles was markedly decreased, further supporting an impairment in COPI vesicle formation or budding processes. ConclusionThis study demonstrates that active COPI retrograde transport is a critical factor in restricting the over-connection of the Golgi ribbon and maintaining its compactness. Rather than causing fragmentation, partial disruption of COPI function leads to a distinct morphological outcome characterized by Golgi ribbon extension at the light microscopy level and cisternal remodeling at the ultrastructural level. LEPROTs and GOLPH3 cooperatively promote the recycling and vesiculation of COPI components, thereby imposing a structural constraint on the Golgi periphery. Our findings support a model in which multiple adaptor proteins act in parallel to sustain efficient COPI cycling, thereby maintaining Golgi structural homeostasis. These findings provide new cell biological evidence for the membrane trafficking basis of Golgi morphological homeostasis.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Protrusive facial deformities, characterized by the forward displacement of the teeth and/or jaws beyond the normal range, affect a considerable portion of the population. The manifestations and morphological mechanisms of protrusive facial deformities are complex and diverse, requiring orthodontists to possess a high level of theoretical knowledge and practical experience in the relevant orthodontic field. To further optimize the correction of protrusive facial deformities, this consensus proposes that the morphological mechanisms and diagnosis of protrusive facial deformities should be analyzed and judged from multiple dimensions and factors to accurately formulate treatment plans. It emphasizes the use of orthodontic strategies, including jaw growth modification, tooth extraction or non-extraction for anterior teeth retraction, and maxillofacial vertical control. These strategies aim to reduce anterior teeth and lip protrusion, increase chin prominence, harmonize nasolabial and chin-lip relationships, and improve the facial profile of patients with protrusive facial deformities. For severe skeletal protrusive facial deformities, orthodontic-orthognathic combined treatment may be suggested. This consensus summarizes the theoretical knowledge and clinical experience of numerous renowned oral experts nationwide, offering reference strategies for the correction of protrusive facial deformities.
Humans ; Orthodontics, Corrective/methods* ; Consensus ; Malocclusion/therapy* ; Patient Care Planning ; Cephalometry

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

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Objective This study aimed to examine whether body mass index(BMI)was causally associated with blood transfusion reactions.Methods A two-sample Mendelian randomization(MR)analysis using the inverse variance weighted(IVW),MR-Egger regression,weighted median method(WME),weighted model method(WM),simple model method(SM)and simple median method(SM)was performed.Public genome-wide association study(GWAS)analysis was used as the data source,with summary statistical data sets of BMI(n=126 003;GWAS ID:ebi-a-GCST90095042)as the exposure variable and summary statistical data sets of transfusion reactions(n=199 451;GWAS ID:finn-b-ST19)as the outcome variable.The causal association between BMI and transfusion reactions was analyzed.Results 42 single nucleotide polymorphisms associated with transfusion reactions were identified by MR analysis.The IVW showed evidence to support the causal relationship between BMI and transfusion reactions(OR=0.29,95%CI=0.10～0.85).Nonetheless,the effect value β of the MR-Egger regression approach contrasts with that of IVW.The outcomes of the heterogeneity analysis,pleiotropy analysis,and sensitivity analysis indicated that P>0.05.Conclusion The results of MR analysis supported the possibility of a causal relationship between BMI and blood transfusion reactions,that is,the reduction of BMI will increase the risk of blood transfusion reactions.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.