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 factors influencing global longitudinal strain(GLS)measured by cardiac magnetic resonance(CMR)in patients with acute ST-segment elevation myocardial infarction(STEMI).Methods Clinical data of 315 hospitalized patients diagnosed with acute STEMI who underwent percutaneous coronary intervention(PCI)at the First Medical Center of Chinese PLA General Hospital from June 2016 to September 2021 were retrospectively collected.After analyzing CMR images of all patients,GLS and other strain parameters were obtained,and then the patients were divided into two groups according to the median GLS.In order to balance gender and age differences,1:1 propensity score matching was performed,and 206 patients were eventually included:GLS>-11.3%group(indicating severe GLS impairment,n=103)and GLS≤-11.3%group(n=103).Baseline characteristics,laboratory indicators,coronary angiographic parameters,electrocardiogram(ECG)features,and CMR parameters were compared between the two groups.Variables showing significant differences were analyzed for their correlation with GLS.Multivariate logistic regression and multiple stepwise linear regression analyses were performed to identify factors associated with GLS impairment.Results Compared with GLS≤-11.3%group,GLS>-11.3%group had significantly higher peak levels of creatine kinase-MB(CK-MB)and troponin T(TnT)(P<0.001).A higher proportion of patients in GLS>-11.3%group had the left anterior descending artery(LAD)as the culprit vessel,while a lower proportion had the right coronary artery(RCA)as the culprit vessel(P<0.001).Additionally,GLS>-11.3%group had longer QRS duration(P<0.001)and a higher incidence of pathological Q waves(P=0.001).Regarding CMR parameters,GLS>-11.3%group exhibited larger global circumferential strain(GCS),infarct size(IS),and left ventricular end-systolic volume(LVESV),as well as lower global radial strain(GRS)and left ventricular ejection fraction(LVEF)(P<0.001).Multivariate logistic regression indicated that peak TnT(OR=1.092,P=0.001),LAD culprit vessel(OR=3.744,P<0.001),and QRS duration(OR=1.026,P<0.001)were significantly associated with severely impaired GLS.Multiple stepwise linear regression analysis showed that the logarithmic value of peak TnT,LAD as the culprit vessel,and the square root of QRS duration were linearly correlated with GLS values(adjusted R2=0.301,P<0.001),and these independent variables explained 30.1%of the variation in GLS.Conclusion Elevated peak TnT,prolonged QRS duration,and LAD as the culprit vessel are significantly associated with severe GLS impairment in STEMI patients,indicating more severe myocardial infarction and worse left ventricular function.

Objective To investigate the effect of Anlotinib on proliferation and apoptosis in non-small cell lung cancer(NSCLC)cells and its molecular mechanism.Methods Non-small cell lung cancer cell lines A549 and H1299 were incubated with Anlotinib,miR-16-5p agonist and/or PD-1 overexpression vector respectively.CCK-8 assay and EDU assay were applied to detect the proliferation.Flow cytometry was performed to detect the cell apop-tosis.The relative expression of miR-16-5 p in A549 and H1299 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).The relative protein expression of PD-1 in A549 and H1299 was detected by Western blot assay.The interaction between miR-16-5p and PD-1 was determined by dual luciferase reporter assay.Finally,A549 cell xenograft model was established to assess the effect of Anlotinib on tumor growth in vivo.Results Anlotinib significantly increased miR-16-5p expression and decreased PD-1 expression in A549 cells and H1299 cells,inhibited cell proliferation and promoted apoptosis in a dose-dependent manner(P＜0.05).The highly-expressed miR-16-5p inhibited proliferation and promoted cell apoptosis(P＜0.05).Also,miR-16-5p targeted at PD-1 and negatively regulated PD-1 expression.Knockdown of PD-1 inhibited proliferation and pro-moted cell apoptosis(P＜0.05).PD-1 over-expression reversed the Anlotinib-mediated pro-proliferation and anti-apoptosis of miR-16-5p in A549 cells and H1299 cells(P＜0.05).Anlotinib significantly reduced tumor growth in vivo(P＜0.05).Conclusions Anlotinib may inhibit cell proliferation,anti-apoptosis,and reduce tumor growth for NSCLC,which is involved in miR-16-5p/PD-1 axis.

Objective To investigate the changes of serum cardiac-specific troponin I (cTnI) level in patients after lung transplantation. Methods Clinical data of patients undergoing lung transplantation in our hospital from December 2016 to December 2022 were retrospectively analyzed. The relationship between postoperative serum cTnI level and clinical characteristics were explored. Results Finally 20 patients were collected, including 15 males and 5 females with an average age of (51.65±12.79) years. The serum cTnI level was significantly increased after lung transplantation. The serum cTnI reached the highest level on the first day after transplantation, and significantly decreased from the third day after transplantation. The serum cTnI levels in patients with obstructive pulmonary disease and bilateral lung transplantation were significantly higher than those in patients with restrictive pulmonary disease and unilateral lung transplantation on the day after surgery and on the first day after transplantation. Conclusion Transient myocardial injury can occur after lung transplantation, which is characterized by an abnormal increase in serum cTnI level.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.