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.

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 investigate the correlation between preoperative N-terminal pro-B-type natriuretic peptidogen(NT-proBNP)levels and early postoperative outcomes in elderly and critically ill pa-tients with hip fractures.Methods A total of 593 elderly and critically ill patients with hip fractures from January 2018 to April 2021 were selected,including 189 males and 404 females,aged≥65 years,BMI 12.0-35.5 kg/m2,ASA physical status Ⅱ-Ⅳ.General preoperative information,intraoperative and post-operative discharge outcomes of patients were retrospectively obtained by the electrical clinical medical record system or telephone follow-up.The receiver operator characteristic(ROC)curve of preoperative plas-ma NT-proBNP and postoperative 30-day death was plotted,and the corresponding optimal cut-off value was 1 765.0 pg/ml.According to NT-proBNP values,the patients were divided into two groups:low-ratio group(NT-proBNP≤1 765.0 pg/ml,group L,n = 463)and high-ratio group(NT-proBNP＞1 765.0 pg/ml,group H,n = 130).The correlation between different plasma concentrations of NT-proBNP before surgery and ICU length of stay,total length of stay,postoperative complications,and 30-day mortality rate were an-alyzed using univariate and multivariate logistic regression analysis.Results Compared with group L,age,preoperative comorbidities with coronary heart disease,arrhythmia,chronic heart failure,lung disease,and chronic kidney disease,as well as mortality within 30 days after surgery were significantly increased in group H(P＜0.05).The multivariate logistic regression analysis showed that high preoperative plasma NT-proBNP concentration was positive correlation with postoperative ICU length of stay(OR = 1.215,95%CI 1.073-1.375,P = 0.020)and 30-day mortality rate(OR = 32.696,95%CI 7.158-149.338,P＜0.001).Conclusion High preoperative plasma NT-proBNP concentration is positive correlation with postoperative ICU hospitalization timeand 30-day mortality.

Objective:To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR).Methods:This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded.Results:None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0–300.0) minutes, 240.0 (225.0–270.0) minutes and 270.0 (240.0–356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7–12.7; OR=2.6, 95%CI: 1.0–6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0–12.0) days, 10.0 (8.0–17.0) days and 11.5 (9.0–19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5–8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ 2=4.133, P=0.023). Conclusions:In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Objective To investigate the changes and clinical significance of peripheral blood mucosal-associated invariant T(MAIT)cells in children with influenza.Methods Children with influenza who received treatment in the outpatient and inpatient departments of a children's hospital from January to May 2023 were selected and divided into the common type group and the severe type group.Healthy children who underwent physical examination in this hospital during the same period were selected as the healthy control group.Within 24 hours after admission,children's venous blood was drawn for testing;ratios of MAIT cells(CD3+CD161+TCRVα7.2+cells)and MAIT cells expressing PD-1,CD69,perforin,and CD107 α were tested by flow cytometry,respectively.Differences among all the groups were compared.Results Compared with the control group,the proportion of peripheral blood MAIT cells in children with common and severe influenza gradually decreased,while the proportion of CD69-ex-pressing and perforin-positive MAIT cells increased gradually.Differences were statistically significant(all P＜0.05).There was no statistically significant difference in the proportion of MAIT cells expressing CD107(P＞0.05).The proportion of PD-1 positive MAIT cells increased(P＜0.05),but there was no statistically significant difference be-tween the common type and severe type groups(P＞0.05).Conclusion The decrease of peripheral blood MAIT cells accompanied with immune activation plays a role in the pathogenesis of influenza.

Objective:To study the influence of neoadjuvant chemoradiotherapy on peritoneal wound recovery after abdominoperineal resection (APR).Methods:This was a retrospective cohort study of data of 219 patients who had been pathologically diagnosed with low rectal cancer and undergone APR in the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology between January 2018 and December 2021. Of these patients, 158 had undergone surgery without any pre-surgical treatment (surgery group), 35 had undergone surgery after neoadjuvant chemotherapy (neoadjuvant chemotherapy group), and 26 had undergone surgery after neoadjuvant chemoradiotherapy (neoadjuvant chemoradiotherapy group). The primary outcome was perineal wound complications occurring within 30 days. The status of wound healing was classified into the following three levels: Level A: abnormal wound seepage that improved after wound discharge; Level B: wound infection and dehiscence; and Level C: Level B plus fever. The patients' general condition, tumor status, perianal wound healing level, and intra- and post-operative recovery were recorded.Results:None of the study patients had any complications during surgery. The duration of surgery was 240.0 (180.0–300.0) minutes, 240.0 (225.0–270.0) minutes and 270.0 (240.0–356.2) minutes in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=6.508, P=0.039). The rates of perineal wound complications were 34.6% (9/26) and (22.9%, 8/35)in the neoadjuvant chemoradiotherapy group and the neoadjuvant chemotherapy group, being significantly higher than that in the surgery group (10.1%, 16/158). After adjusting for patient age and sex using a logistic regression model, the risk of complications was still higher in the neoadjuvant chemoradiotherapy than in the surgery group (OR=4.6, 95%CI: 1.7–12.7; OR=2.6, 95%CI: 1.0–6.8), these differences being statistically significant (both P<0.05). The duration of hospital stay was 9.5 (7.0–12.0) days, 10.0 (8.0–17.0) days and 11.5 (9.0–19.5) days for patients in the surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy groups, respectively ( H=0.569, P=0.752). However, after adjusting for patient age and sex by using a generalized linear model, hospital stay was longer in the neoadjuvant chemoradiotherapy than in the surgery group (β [95% CI]: 4.4 [0.5–8.4], P=0.028). After surgery, 155 of 219 patients required further adjuvant chemotherapy. A higher proportion of patients with than without wound complications did not attend for follow-up (32.2% [10/31] vs. 16.1% [20/124]); this difference is statistically significant (χ 2=4.133, P=0.023). Conclusions:In patients with low rectal cancer, neoadjuvant radiotherapy may be associated with an increased risk of perineal wound infection and non-healing.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Amyloidosis ; Biopsy ; Humans ; Liver Cirrhosis/diagnosis*