Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Objective:To evaluate the diagnostic value of the vesical imaging-reporting and data system（VI-RADS）for determining muscle invasion in variant histology urothelial carcinoma（VUC）of the bladder.Methods:A retrospective analysis was performed on the pathological and imaging data of 518 bladder cancer patients admitted to Jiangsu Province Hospital between January 2013 and January 2023. Patients were stratified into pure urothelial carcinoma（PUC）group（ n = 457）and variant urothelial carcinoma（VUC）group（ n = 61）based on the presence of histological variants. In the PUC group，there were 390 males（85.3%）and 67 females（14.7%），with a mean age of（66.9 ± 11.2）years. Tumor characteristics included maximum diameter ≥ 30 mm in 149（32.6%），< 30 mm in 308（67.4%），multiple tumors in 147（32.2%），solitary in 310（67.8%），pedunculated morphology in 143（31.3%）and non-pedunculated in 314（68.7%）. Histological grading identified high-grade tumors in 319 patients（69.8%）and low-grade tumors in 138（30.2%）. Pathological stage distribution included 191 of T a（41.8%），127 of T 1（27.8%），76 of T 2（16.6%），47 of T 3（10.3%），and 16 of T 4（3.5%）patients. The VUC group included 61 patients，comprising 51 males（83.6%）and 10 females（16.4%），with a mean age of（65.8 ± 11.4）years. Tumor characteristics were maximum diameter ≥ 30 mm in 38（62.3%），< 30 mm in 23（37.7%），multiple tumors in 16（26.2%），solitary in 45（73.8%），pedunculated morphology in 11（18.0%）and non-pedunculated in 50（82.0%）. Histological grading identified high-grade tumors in 59 patients（96.7%）and low-grade tumors in 2（3.3%）. Pathological stage distribution included 3 of T a（4.9%），15 of T 1（24.6%），15 of T 2（24.6%），20 of T 3（32.8%），and 8 of T 4（13.1%）patients. No statistically significant differences were found between the two groups in gender，age，or tumor multiplicity（ P > 0.05）. Statistically significant differences were found in pathological grade，pathological stage，maximum tumor diameter，and pedunculated morphology（ P < 0.05）. Furthermore，an external validation cohort of 278 bladder cancer patients treated between February 2023 and February 2024 from multiple centers（Jiangsu Provincial People’s Hospital，The First Affiliated Hospital of Zhengzhou University，Union Hospital Tongji Medical College Huazhong University of Science and Technology，Jiangsu Provincial Hospital of Traditional Chinese Medicine，Suzhou Municipal Hospital，Huaian First People’s Hospital，Yixing People’s Hospital）was retrospectively analyzed to externally validate the performance of VI-RADS scoring in predicting muscle invasion of VUC. This cohort included a PUC subgroup of 241 patients，comprising 196 males（81.3%）and 45 females（18.7%），with a mean age of（68.0 ± 10.7）years. Tumor characteristics were maximum diameter ≥ 30 mm in 85（35.3%），< 30 mm in 156（64.7%），multiple tumors in 65（27.0%），solitary in 176（73.0%），pedunculated morphology in 76（31.5%）and non-pedunculated in 165（68.5%）. Histological grading identified high-grade tumors in 175 patients（72.6%）and low-grade tumors in 66（27.4%）. Pathological staging comprised 107 patients of T a（44.4%），78 of T 1（32.4%），22 of T 2（9.1%），22 of T 3（9.1%），and 12 of T 4（5.0%）. The VUC subgroup consisted of 37 patients，comprising 29 males（78.4%）and 8 females（21.6%），with a mean age of（70.5 ± 9.5）years. Tumor characteristics were maximum diameter ≥ 30 mm in 23（62.2%），< 30 mm in 14（37.8%），multiple tumors in 9（24.3%），solitary in 28（75.7%），pedunculated morphology in 7（18.9%）and non-pedunculated in 30（81.1%）. Histological grading identified high-grade tumors in 36 patients（97.3%）and low-grade tumors in 1（2.7%）. Pathological staging comprised 1 patient of T a（2.7%），9 of T 1（24.3%），7 of T 2（18.9%），19 of T 3（51.4%），and 1 of T 4（2.7%）. In this validation cohort，no significant differences were found in gender，age，tumor multiplicity，or pedunculated morphology between the PUC and VUC subgroups（ P > 0.05）. Significant differences were observed in pathological grade，pathological stage，and maximum tumor diameter（ P < 0.05）. Three radiologists independently reviewed and scored the multiparametric MRI（mp-MRI）in a blinded manner. Inter-reader agreement was assessed using the weighted kappa statistic. Differences in variables between the two groups were compared using t-tests，chi-square tests，or Fisher’s exact test. The diagnostic performance of VI-RADS for muscle invasion in VUC and PUC was comprehensively evaluated using receiver operating characteristic（ROC）curves，the area under the curve（AUC），and cut-off values determined by the Youden’s index. The DeLong test was used to assess whether the diagnostic performance of VI-RADS differed between VUC and PUC. Results:In the retrospective single-center cohort，the AUC of VI-RADS for assessing muscle invasion was 0.895（95% CI 0.864?0.922）in the PUC group，with a cut-off value of > 3，and the AUC was 0.896（95% CI 0.791-0.960）in the VUC group，with a cut-off value of > 3. The difference between the two groups was not statistically significant（ P = 0.986）. Using a VI-RADS score > 3 as the cut-off value，the accuracy，sensitivity，specificity，positive predictive value（PPV），and negative predictive value（NPV）for diagnosing muscle invasion status in the PUC group were 85.8%（392/457），70.5%（98/139），92.5%（294/318），80.3%（98/122），and 87.8%（294/335），respectively. The corresponding values for the VUC group were 82.0%（50/61），76.7%（33/43），94.4%（17/18），97.1%（33/34），and 63.0%（17/27）.In the retrospective multicenter cohort，the AUC of VI-RADS for assessing muscle invasion was 0.891（95% CI 0.845?0.927）in the PUC group，with a cut-off value of > 2，and the AUC was 0.898（95% CI 0.754?0.973）in the VUC group，with a cut-off value of > 3. The difference between the two groups was not statistically significant（ P = 0.897）. Using a VI-RADS score > 3 as the cut-off value，the accuracy，sensitivity，specificity，PPV，and NPV for diagnosing muscle invasion status in the PUC group were 85.9%（207/241），58.9%（33/56），94.1%（174/185），75.0%（33/44），and 88.3%（174/197），respectively. The corresponding values for the VUC group were 81.1%（30/37），77.8%（21/27），90.0%（9/10），95.5%（21/22），and 60.0%（9/15）.In the single-center cohort，the Kappa values for inter-reader agreement in assessing muscle invasion status using VI-RADS were 0.881（ P < 0.01）for the PUC group and 0.941（ P < 0.01）for the VUC group among the three readers. In the multicenter cohort，the Kappa values were 0.858（ P < 0.01）for the PUC group and 0.838（ P < 0.01）for the VUC group. Conclusions:VI-RADS demonstrates similarly high diagnostic performance for assessing muscle invasion in both PUC and VUC，which is applicable for diagnosing muscle invasion status in VUC，and shows good inter-reader agreement.

The development of polysaccharide conjugate vaccines, which convert polysaccharide antigens into T-cell-dependent immunogens through covalent conjugation with protein carriers, represents a critical strategy for enhancing immune protection in infants and young children. Globally licensed conjugate vaccines currently employ carrier proteins including Tetanus Toxoid, Diphtheria Toxoid, and Cross-Reacting Material 197. Recent advances have focused on three key areas: novel carrier protein discovery, optimized conjugation strategies, and evaluation of immune interference during co-administration of multivalent formulations. These efforts aim to achieve broader serotype coverage, prolonged protective efficacy, and simplified immunization schedules. This review synthesizes recent progress in carrier protein development, encompassing vaccine design principles, manufacturing processes, safety profiles, and epidemiological effectiveness. Furthermore, it critically examines current selection criteria for carrier proteins, their clinical applications, and persistent challenges, providing strategic insights to inform future conjugate vaccine development and immunization policy optimization in China.

Soy is a vital source of plant carbohydrates.However,it poses significant allergenic risks,particularly to young children and animals.Among the various proteins in soy,β-conglycinin,which con-stitutes approximately 30％of total soy carbohydrates,is a primary allergen.Undigested β-conglycinin can lead to intestinal damage by inhibiting cell growth,disrupting the cytoskeleton,and inducing apopto-sis.It can also enter the lymphatic and circulatory systems,triggering allergic reactions.Conventional ELISA methods for detecting β-conglycinin rely on polyclonal or monoclonal antibodies,which are limited by their large molecular weight,difficulty in accessing the protein core,and sensitivity to acidic and bas-ic conditions.To address these limitations,this study aimed to develop nanobodies(Nbs)against β-con-glycinin.Nbs,derived from the variable regions of heavy-chain antibodies found in camelids,have a mo-lecular weight approximately one-tenth that of conventional antibodies.They offer advantages such as small size,stable structure,high specificity,and strong affinity.A female alpacas was immunized five times using β-conglycinin,which showed a heavy chain antibody potency of 1∶16 000 by ELISA.Pe-ripheral blood lymphocytes were subsequently isolated and total RNA was extracted.The variable region of the heavy-chain antibody was amplified via PCR,and recombinant plasmids were constructed and transformed into the E.coli competency strain ER2738.The resulting library contained about 3.5×108 CFU/mL,which increased to 1.15×1012 PFU/mL after phage rescue,with a 100％Nbs gene insertion rate,indicating high diversity.Its Nbs phage output was significantly enriched by four rounds of solid-phase elution with an enrichment rate of 155.9.Four rounds of solid-phase panning yielded 35 positive clones,all of which shared the same amino acid sequence upon sequencing.The selected Nb was ex-pressed in a prokaryotic system,and its binding ability to β-conglycinin was confirmed using Western blotting and ELISA.The results demonstrated excellent specificity and affinity.This research lays the groundwork for developing a rapid and efficient detection method for β-conglycinin using Nbs,potentially enhancing food safety and allergen management.

Aim To investigate the impact of G pro-tein-coupled estrogen receptor 1(GPER1),also known as GPR30 playing a significant role in the nerv-ous system,on neuronal damage and cognitive dysfunc-tion following epileptic seizures.Methods The pro-tein expression levels of GPER1 and the DNA damage marker γ-H2AX in epileptic rats were assessed using Western blot.The hippocampal neuronal damage and apoptosis in pilocarpine-induced epilepsy models were evaluated using Nissl and TUNEL staining techniques,compared with GPER1 knockdown(GPER1-KD)rats with wild-type(WT)controls.The behavioral activi-ties,including memory and spatial learning,were mo-nitored during the chronic phase of epilepsy using the IntelliCage system.Results Compared to the control group,GPER1 protein expression in the cerebral cortex and hippocampus significantly increased 24 hours post-epilepsy onset.In the GPER1-KD+EP group,hipp-ocampal neuronal damage was more severe,with a sig-nificant increase in apoptotic neurons compared to the WT+EP group.The IntelliCage data revealed that during free exploration,nose contact,position learn-ing,and reverse position learning stages in the GPER1-KD+EP group exhibited fewer visits and a higher error rate than in the WT+EP group.Conclu-sions Deficiency in GPER1 impairs memory and spa-tial learning abilities following epilepsy,potentially due to exacerbated neuronal injury,apoptosis,and inflam-mation.GPER1 represents a promising therapeutic tar-get for mitigating post-epileptic nerve damage and cog-nitive impairment.

Objective To evaluate the efficacy and safety of high-power,short-duration radiofrequency catheter ablation for the treatment of persistent atrial fibrillation.Methods This retrospective study included 392 patients diagnosed with persistent atrial fibrillation who underwent catheter radiofrequency ablation at Suzhou Kowloon Hospital,Shanghai Jiao Tong University School of Medicine,from January 2019 to December 2023.Of these,256 patients were treated with high-power,short-duration ablation,and 136 patients with low-power,long-duration ablation.The following parameters were compared:radiofrequency ablation time,total procedure time,single-circle pulmonary vein isolation rate,immediate procedural success rate,number of ablation points,and perioperative complications(including pericardial tamponade,pseudoaneurysm,arteriovenous fistula,stroke,etc.).Follow-up assessments were conducted at 3,6,and 12 months post-surgery to evaluate the 12-month sinus rhythm maintenance rate.Results The ablation time in the high-power group was significantly shorter than that in the low-power group[(14.6±2.3)min vs.(30.3±4.2)min,P＜0.001],as was the total procedure time[(113.8±24.8)min vs.(128.5±26.7)min,P=0.001].There were no significant differences between the two groups in terms of pulmonary vein isolation rate(97.7％vs.94.9％,P=0.823),number of ablation points[(71.2±8.0)vs.(74.3±14.3),P=0.168],or perioperative complications(3.1％vs.4.4％,P=0.571).Regarding the maintenance rate of sinus rhythm at 12 months post-operation,the high-power group showed a higher rate than the low-power group,but no statistically significant difference was observed(82.8％vs.79.4％,P=0.399).Conclusions High-power,short-duration radiofrequency catheter ablation can improve procedural efficiency in the treatment of persistent atrial fibrillation.Its efficacy and safety are similar to those of the low-power,long-duration technique.

Objective To specify the occurrence status,distribution characteristics and risk factors of neglected perforations in surgical gloves used during spinal surgery.Methods A total of 932 surgical gloves used during spinal surgery in our hospital from October 2022 to September 2024 were selected.The occurrence and distribution location of neglected perforations were counted.Univariate and binary Logistic regression analyses were respectively conducted on the factors that might lead to neglected perforations of gloves.Results Among the 932 surgical gloves used in spinal surgery selected in this study,a total of 122 gloves(13.09％)with neglected perforations were detected,of which the proportions of neglected perforations at the index finger of the left and right hands in the gloves were the highest,accounting for 37.50％and 37.93％respectively.The results of univariate and binary Logistic regression analyses showed that grade Ⅲ or Ⅳ surgery,open surgery,combined bone grafting operation,operation time≥120 minutes,use of rotating equipment,and gloves worn by instrument nurses were risk factors for neglected perforations(P<0.05,OR>1.0),while wearing double-layer gloves was a protective factor to avoid the occurrence of neglected perforations(P<0.05,OR<1.0).Conclusion The incidence of neglected perforations in surgical gloves used during spinal surgery is relatively high,especially in the area of the glove index finger.For high-risk spinal surgeries(grade Ⅲ or Ⅳ surgery,open surgeries,combined bone grafting procedures)and requiring rotating equipment,health care workers,especially instrumental nurses,are advised to wear double-layer gloves;furthermore,a 120-minute glove change regime is recommended,in order to reduce the incidence of neglected perforation.

OBJECTIVE: The study aim was to investigate the effects of exposure to multiple environmental organic pollutants on cardiopulmonary health with a focus on the potential mediating role of oxidative stress. METHODS: A repeated-measures randomized crossover study involving healthy college students in Beijing was conducted. Biological samples, including morning urine and venous blood, were collected to measure concentrations of 29 typical organic pollutants, including hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), bisphenol A and its substitutes, phthalates and their metabolites, parabens, and five biomarkers of oxidative stress. Health assessments included blood pressure measurements and lung function indicators. RESULTS: Urinary concentrations of 2-hydroxyphenanthrene (2-OH-PHE) ( β = 4.35% [95% confidence interval ( CI): 0.85%, 7.97%]), 3-hydroxyphenanthrene ( β = 3.44% [95% CI: 0.19%, 6.79%]), and 4-hydroxyphenanthrene (4-OH-PHE) ( β = 5.78% [95% CI: 1.27%, 10.5%]) were significantly and positively associated with systolic blood pressure. Exposures to 1-hydroxypyrene (1-OH-PYR) ( β = 3.05% [95% CI: -4.66%, -1.41%]), 2-OH-PHE ( β = 2.68% [95% CI: -4%, -1.34%]), and 4-OH-PHE ( β = 3% [95% CI: -4.68%, -1.29%]) were negatively associated with the ratio of forced expiratory volume in the first second to forced vital capacity. These findings highlight the adverse effects of exposure to multiple pollutants on cardiopulmonary health. Biomarkers of oxidative stress, including 8-hydroxy-2'-deoxyguanosine and extracellular superoxide dismutase, mediated the effects of multiple OH-PAHs on blood pressure and lung function. CONCLUSION Exposure to multiple organic pollutants can adversely affect cardiopulmonary health. Oxidative stress is a key mediator of the effects of OH-PAHs on blood pressure and lung function.
Humans ; Oxidative Stress/drug effects* ; Male ; Cross-Over Studies ; Female ; Young Adult ; Environmental Pollutants/toxicity* ; Environmental Exposure/adverse effects* ; Biomarkers/blood* ; Adult ; Blood Pressure/drug effects* ; Polycyclic Aromatic Hydrocarbons/urine* ; Beijing

Traditional Chinese medicine(TCM) resources are the essential material foundation for the development of TCM. The national survey of TCM resources serves as a periodic summary of these resources, ensuring the continuity, prosperity, and development of TCM in China. Since 1949, four national surveys of TCM resources have been conducted. The fourth survey incorporated an investigation into traditional knowledge related to TCM resources, including the traditional medicinal knowledge of Chinese ethnic minorities, with the goal of systematically exploring, preserving, and inheriting this knowledge. This manuscript provides an overview of the basic findings from the first three national surveys of TCM resources, while also clarifying the concepts, categories, forms, carriers, and acquisition pathways of traditional knowledge related to TCM resources. A preliminary summary of the findings from traditional knowledge investigations reported in current literature is also presented. Based on the fourth survey, this manuscript emphasizes the urgency of developing public medical knowledge through empirically-based investigations, the excavation, and compilation of traditional knowledge. It also outlines the potential for conducting "precise" investigations based on first-hand data obtained from the survey, as well as facilitating the discovery and evaluation of new medicines using traditional knowledge related to ethnic minority medicinal practices. This manuscript is expected to provide valuable insights for promoting the health and industrial development of ethnic minority populations in the post-"survey" phase.
Humans ; Medicine, Chinese Traditional ; China/ethnology* ; Minority Groups ; Ethnicity ; Drugs, Chinese Herbal/therapeutic use* ; Health Knowledge, Attitudes, Practice/ethnology* ; Surveys and Questionnaires