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: 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

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.

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

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 clinical efficacy of a novel reduction device in the treatment of A3N0/1 thoracolumbar fracture using navigation-assisted techniques.Methods:A retrospective analysis was conducted on 45 patients (29 males, 16 females; mean age 40.67±16.11 years, range 24-57) with thoracolumbar fractures who underwent fracture reduction and pedicle screw fixation via the Wiltse approach at Zhengzhou Orthopaedic Hospital between January 2022 and January 2023. Injury levels included: T 10 in 2 cases, T 11 in 5 cases, T 12 in 13 cases, L 1 in 20 cases, L 2 in 3 cases, L 3 in 2 cases. All patients underwent fracture reduction via the Wiltse approach using the spinal fracture reduction instrument for vertebral body reduction. Among them, 20 patients received O-arm navigation-assisted internal fixation and vertebral reduction (O-arm group), while 25 received C-arm fluoroscopy-guided internal fixation and vertebral reduction (C-arm group). Operative time, intraoperative blood loss, vertebral reduction time using the instrument, first-time screw placement success rate, screw placement accuracy, and complications were compared. Mid-vertebral body height ratio (MVBHr), local Cobb angle of the fractured vertebra, visual analogue scale (VAS) score, and Oswestry disability index (ODI) were compared preoperatively, at 1 week postoperatively, 3 months postoperatively, and final follow-up. Results:All surgeries were successfully completed in both groups. Operative time was significantly shorter in the O-arm group (106.8±14.4 min) than in the C-arm group (119.1±16.4 min, P<0.05). All patients were followed up for a mean duration of 15.9±3.9 months (range 12-20 months). Vertebral reduction time was significantly shorter in the O-arm group (11.0±2.2 min) than in the C-arm group (20.4±5.7 min, P<0.05). The first-time screw placement success rate was significantly higher in the O-arm group (100%) than in the C-arm group (95.3%, P<0.05). Screw placement accuracy (Grade I) was significantly higher in the O-arm group (117 screws, 97.5%) than in the C-arm group (136 screws, 90.7%, P<0.05). No cases of wrong-level surgery, infection, or spinal cord/nerve injury occurred. Both groups showed significant improvements in MVBHr, Cobb angle, VAS, and ODI at all postoperative time points compared to preoperative values ( P<0.05). At final follow-up, the O-arm group demonstrated significantly better outcomes than the C-arm group in MVBHr (90.6%±4.5% vs. 86.4%±6.9%, P<0.05), Cobb angle (7.6°±1.8° vs. 10.1°±3.2°, P<0.05), VAS (1.3±0.4 vs. 1.7±0.6, P<0.05), and ODI (4.6%±1.9% vs. 7.7%±2.0%, P<0.01). Conclusion:O-arm navigation-assisted intrasegmental push reduction for A3N0/1 type thoracolumbar fractures demonstrates advantages including faster and more accurate screw placement, precise reduction with improved outcomes, and significant postoperative pain relief.

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 quality of clinical trials is critical to ensuring the safety and rights of participants, and ensuring the reliability of trial data. It directly affects the scientific validity of research conclusions and the effectiveness of regulatory decisions. This study aimed to establish an efficient quality management system to enhance the overall quality of clinical trials. Our hospital had established a dedicated quality control team, and developed a quality management module which was integrated to the clinical trial management system. Since February 2021, the hospital had fully digitized the electronic management of quality control processes, and achieved closed-loop management throughout the entire clinical trial by using this system. Key measures of the system included formulating tailored quality control plans, optimizing the design of quality control checklists, and refining quality control feedback mechanisms to improve management efficiency. In 2024, the annual quality control workload had reached 807 activities, with a completion rate of 93% and a timeliness rate of 91%. These outcomes demonstrate that the system could effectively improve the management quality and efficiency of pharmaceutical and medical devices clinical trials. The system could provide insights and practical references for the standardized implementation and quality assurance of clinical trials.

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 explore the role and possible mechanism of ACOT11 in renal fibrosis model mice.Methods:A mouse model of renal fibrosis was established by unilateral ureteral obstruction(UUO)(Sham group and UUO7 group),and the expression of ACOT11 in the kidneys of UUO induced fibrosis mouse models was detected by protein immunoblotting and real-time fluorescence quantitative PCR(qRT-PCR).Subsequently,immunohistochemistry,Masson staining,H&E staining,PAS staining,and other experimental methods were used to detect the expression levels of fibrosis biomarkers fibronectin,α-SMA,and COL-1 in the kidneys of control and experimental group mice.In addition,by constructing ACOT11 gene knockout model mice and using the gene knockout model mice to construct a renal fibrosis model,the expression levels of fibrosis biomarkers such as fibronectin,α-SMA,COL-1,as well as fibrosis mechanism pathway related indicators TGF-β and Smad2 in the kidneys of each group of mice were further detected.Results:The results of WB and qRT-PCR experiments showed that the expression of ACOT11 in the kidney tissue of UUO model mice was significantly reduced compared to the Sham group.After knocking out the ACOT11 gene,H&E staining,PAS staining,and Masson staining showed that pathological inflammatory reactions such as abnormal glomerular and tubular structures,inflammatory cell infiltration and interstitial fibrous tissue proliferation in mice were significantly aggravated compared to the control group,and the expression of fibrosis markers Fibronectin,α-SMA,and COL-1 was significantly higher than that of the control group.Conclusion:ACOT11 plays a protective role in mice with unilateral ureteral obstruction model.After ACOT11 gene knockout,the fibrosis biomarkers of the mouse kidney increases and the degree of fibrosis worsens.