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.

Objective To investigate the cIinicopathological features and immunohistochemical expression of gastric hyperplastic polyps(GHPs)with dysplasia/adenocarcinoma.Methods A retrospective analysis of 24 cases(44 polyps)that were diagnosed as GHPs with dysplasia/adenocarcinoma in our hospital from January 2020 to December 2024 was reviewed,and clinical,histomorphological,immunophenotypic and follow-up data were analyzed.Results There were 20 female and 4 male cases,with a mean age of(65.5±7.9)(range 56～76)years.Among 44 polyps,3 occurred in the antrum of the stomach,1 in the gastric horn,and 40 in the fundus/body.Among the polyps,32 cases were diagnosed as high-grade dysplasia,4 cases as low-grade dysplasia,4 cases as coexistence of low-grade+high-grade dysplasia,2 cases as mucinous adenocarcinoma,1 cases as poorly differentiated adenocarcinoma,and 1 cases as signet-ring cell carcinoma.The histological manifestations of 23 cases of background mucosa were autoimmune metaplastic atrophic gastritis(AMAG).the P53 of 8 polyps showed a mutant expression pattern.Through MUC5/MUC6/MUC2/CD10 joint examination,33 cases showed gastric type(25 cases of which were foveal epithelium type),4 cases were intestinal type,5 cases were mixed gastrointestinal type,and 2 cases were non-gastrointestinal type.Conclusion The neoplastic transformation of GHPs is closely related to AMAG.It is necessary for clinicians and pathologists to strengthen their evaluation of background mucosa,to achieve early detection,early diagnosis and early treatment.

Objective:To preliminarily investigate the role of methylation in the epigenetic regulation of the pathogenesis of non-syndromic orofacial clefts (NSOC), and to address the gaps in previous explorations of susceptibility genes associated with NSOC.Methods:We conducted an association analysis of single nucleotide polymorphisms (SNPs) and genes related to methylation using data from a large-scale genome-wide association study involving Han Chinese patients with non-syndromic orofacial clefts and healthy controls.Results:A significant association was found between NSOC and the DNA methylation gene TET1, as well as the histone methylation gene NSD1. Specifically, the minor allele G of rs3733875 significantly increased the risk of non-syndromic cleft lip with or without palate (NSCLP) ( P=1.18×10 -4, OR=1.292), while the minor allele C of rs10998379 elevated the risk of non-syndromic cleft palate only (NSCPO) ( P=7.29×10 -5, OR=1.268); conversely, the minor allele T of rs4558056 was identified as a protective factor for NSCL/P ( P=1.17×10 -4, OR=0.792). Conclusions:This study revealed that the DNA methylation gene TET1 and the histone methylation gene NSD1 are associated with NSOC. The pathogenesis of NSOC involves interactions among multiple factors, including genetic, environmental, and epigenetic determinants, among which methylation modifications represent a crucial component.

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.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective:To explore the application of full-thickness advancement flap of upper abdominal wall in breast-conserving surgery for lower quadrant breast cancer.Methods:This is a retrospective case series study. The clinic data of 25 lower quadrant breast cancer patients who underwent a breast-conserving surgery with advancement flap of full-thickness of upper abdominal wall at the Breast Center, Beijing Tongren Hospital, Capital Medical University, from June 2022 to September 2023 were analyzed retrospectively. All patients were female, aged (47.6±5.8) years (range: 38 to 57 years). Tumor staging included stageⅠ in 8 cases, stageⅡA in 13 cases, stageⅡB in 4 cases. The subcutaneous fat thickness of the upper abdominal walls and the volume of wide local excision of the tumor were measured and recorded. The operation time of repairing the breast, the duration of retention of postoperative drainage tubes, postoperative complications, and cosmetic results were recorded.Results:The subcutaneous fat thickness in the upper abdominal walls was (1.7±0.2) cm (range: 1.3 to 2.2 cm), the excision volume of breast-conserving surgery was (70.8±13.6) mm 3 (range: 49 to 97 mm 3), the operation time of repairing the breast was (55.4±5.1) minutes (range: 45 to 65 minutes) and the retention time of the drainage tube was (7.4±0.8) days (range: 6 to 9 days). Cosmetic results: excellent in 12 cases (48.0%), good in 9 cases (36.0%) and fair in 4 cases (16.0%). There was 1 case of postoperative seroma in the donor area, which healed after repositioning the negative pressure drain. Conclusion:In breast-conserving surgery for lower quadrant breast cancer, using a full-thickness abdominal wall advancement flap to repair breast defects is a simple and effective tumor reconstructive technique, yielding good results in achieving postoperative symmetry of the lower quadrant of the breast.

Objective:To investigate the feasibility and therapeutic efficacy of robot-assisted radical resection for hilar cholangiocarcinoma.Methods:This is a retrospective case series study. The clinical data of 29 patients who underwent robot-assisted radical resection for hilar cholangiocarcinoma at the Department of Minimally Invasive Hepatic Surgery,the First Affiliated Hospital of Harbin Medical University from July 2021 to February 2025 were retrospectively collected. There were 16 males and 13 females, aged ( M(IQR)) 68.0 (10.0) years (range:36 to 78 years), and body mass index (24.0±2.9) kg/m 2 (range:17.5 to 29.1 kg/m 2). Bismuth-Corlette classification: 12 cases type Ⅰ, 4 cases type Ⅱ, 6 cases type Ⅲb, and 7 cases type Ⅳ. Preoperative CA19-9 was 161.7(320.9) U/ml (range:7.1 to 1 000.0 U/ml), and carcinoembryonic antigen was 2.8(2.1)μg/L (range:0.3 to 203.1 μg/L). Preoperative total bilirubin was 134.2 (348.9) μmol/L (range:10.4 to 557.9 μmol/L), direct bilirubin was 90.8 (264.1) μmol/L (range:2.5 to 418.7 μmol/L), ALT was 136.4 (134.8) U/L (range:13.0 to 569.9 U/L), AST was 122.2 (119.9) U/L (range:16.0 to 384.0 U/L), and albumin was (34.5±6.3) g/L (range:21.7 to 41.3 g/L). Comparison of quantitative data at different time points using paired t-test or Mann-Whitney U test. Cox univariate analysis was performed for the relevant variables, and Cox multivariate regression analysis was used to screen the independent prognostic factors of patients after robot-assisted radical resection for hilar cholangiocarcinoma. Results:All the 29 patients successfully underwent robot-assisted radical resection of hilar cholangiocarcinoma, and the R0 resection rate was 93.1% (27/29) without conversion to laparotomy. The operation time was 295.0 (87.5) minutes (range:195 to 590 minutes), the intraoperative blood loss was 100.0 (150.0) ml (range:20 to 1 000 ml), the intraoperative blood transfusion rate was 20.1% (6/29), the number of lymph nodes dissected was 10.0 (7.0) pieces (range: 6 to 18 pieces), the first postoperative deflatus time was 3.0 (1.0) days (range:2 to 4 days), The oral feeding time was 5.0 (1.0) days (range: 4 to 7 days), the drainage tube removal time was 8.0 (2.0) days (range: 6 to 26 days), and the postoperative hospital stay time was 10.0 (6.0) days (range:7 to 27 days). The incidence of complications above grade Ⅱ of the Clavien-Dindo complication grading system was 24.1% (7/29), including 3 cases of gastrointestinal bleeding with recurrent high fever, 1 case of delayed gastric emptying, 1 case of bile leakage, and 5 cases of hypoalbuminemia. The total bilirubin was 42.8 (66.8) μmol/L (range:6.8 to 195.9 μmol/L), direct bilirubin was 28.1 (38.5) μmol/L (range:4.3 to 88.6 μmol/L), ALT was 55.8 (56.0) U/L (range:9.9 to 207.1 U/L), AST was 33.9 (17.9) U/L (range:10.6 to 122.7 U/L), and albumin was (32.1±3.8) g/L (range:22.8 to 37.7 g/L), the levels of transaminase and bilirubin in the postoperative liver function indexes were significantly improved compared with those before operation, and the differences were statistically significant (all P<0.05). The mortality rate of patients without perioperative death was 3.4% (1/29) at 90 days after surgery. The results of Cox multivariate regression analysis showed that R0 resection was an independent prognostic factor for survival at 1 year after surgery ( P<0.05). The follow-up time was 15.0 (12.0) months (range:6 to 30 months), 1 of the 29 patients died of intra-abdominal infection 1 week after discharge, and the remaining 28 patients were completely followed up, of which 20 patients had no recurrence and metastasis during the follow-up period, and the tumor-free survival was 15.0 (12.0) months (range:6 to 30 months), the tumor-free survival rate was 65.5% (19/29), the overall survival rate was 68.9% (20/29), and 8 patients with postoperative recurrence and metastasis. One patient with liver metastasis survived after reoperation, and one patient underwent postoperative chemoradiotherapy and died due to recurrence. There were 8 deaths during the follow-up, of which 7 died due to tumor recurrence and metastasis, and 1 died due to previous underlying diseases. Conclusion:Robot-assisted radical resection for hilar cholangiocarcinoma is feasible and effective.

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.

Aim To explore the mechanisms of PM2.5 exposure exacerbating bleomycin(BLM)-induced idio-pathic pulmonary fibrosis(IFP)by regulating ferropto-sis via nuclear factor 2 related factor 2(Nrf2)/solute carrier family 7 member 11(SLC7A11)/glutathione peroxidase(GPX)4 axis.Methods Forty C57BL/6J mice were randomized into the control,BLM,PM2.5,BLM+PM2.5 and sulforaphane(SFN,Nrf2 agonist)groups,with eight mice in each group.PM2.5 expo-sures were conducted to the BLM-induced IPF mice for two weeks.The lung function was measured,and the content of hydroxyproline(HYP)in lung tissue and the pathomorphology of lungs were observed.Reactive oxygen species(ROS),malondialdehyde(MDA),ferrous ion(Fe2+)and glutathione(GSH)of the lung tissue were measured by ELISA.The mRNA and pro-teins levels of Nrf2,SLC7A11,GPX4,collagen typeⅠ(COL-1),α-smooth muscle actin(α-SMA)were measured by quantitative polymerase chain reaction(qPCR)and Western blot.Results Compared with the control group,the lung function of mice was signif-icantly reduced(P＜0.01)in the BLM and PM2.5 groups,while lung tissue showed the characteristic pathological changes of pulmonary fibrosis such as a large number of inflammatory cell infiltration,alveolar wall fracture,thickening,collagen deposition,and sig-nificantly increased HYP,Fe2+,ROS,MDA(P＜0.05,P＜0.01),genes and proteins of COL-1,α-SMA(P＜0.01);and decreased GSH,Nrf2,SLC7A11,GPX4 genes and proteins(P＜0.05,P＜0.01).The above-mentioned lesions were markedly aggravated in the BLM+PM2.5 group compared with the BLM(P＜0.05)and PM2.5 groups(P＜0.01),and were also improved in the SFN group(P＜0.05,P＜0.01).Conclusions PM2.5 exposures can exac-erbate IPF-induced IPF in mice,and the regulating of Nrf2/SLC7 A1 1/GPX4 axis and ferroptosis might be in-volved in the related mechanisms.