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 predictive value of endothelial activation and stress index (EASIX) for the prognosis of patients with mantle cell lymphoma (MCL). METHODS: A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023, had therapeutic indications and received standard treatment. RESULTS: A total of 66 patients were included and divided into high EASIX group and low EASIX group, according to a cutoff value of 0.97 determined by the receiver operating characteristic (ROC) curve. Multivariate Cox regression analysis showed that prealbumin <0.2 g/L, high EASIX, and ECOG PS score ≥2 were independent risk factors influencing overall survival (OS) in MCL patients. The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months, and the median progression-free survival was 8.8 and 26.0 months, respectively. The proportions of patients with ECOG PS score ≥2 and prealbumin <0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group. CONCLUSION At the time of initial diagnosis, EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL. Furthermore, patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.
Humans ; Lymphoma, Mantle-Cell/pathology* ; Prognosis ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; ROC Curve

Sigma-1 receptor (σ ₁R) has become a focus point of drug discovery for central nervous system (CNS) diseases. A series of novel 1-phenylethan-1-one O-(2-aminoethyl) oxime derivatives were synthesized. In vitro biological evaluation led to the identification of 1a, 14a, 15d and 16d as the most high-affinity (K _i < 4 nmol/L) and selective σ ₁R agonists. Among these, 15d, the most metabolically stable derivative exhibited high selectivity for σ ₁R in relation to σ ₂R and 52 other human targets. In addition to low CYP450 inhibition and induction, 15d also exhibited high brain permeability and excellent oral bioavailability. Importantly, 15d demonstrated effective antipsychotic potency, particularly for alleviating negative symptoms and improving cognitive impairment in experimental animal models, both of which are major challenges for schizophrenia treatment. Moreover, 15d produced no significant extrapyramidal symptoms, exhibiting superior pharmacological profiles in relation to current antipsychotic drugs. Mechanistically, 15d inhibited GSK3β and enhanced prefrontal BDNF expression and excitatory synaptic transmission in pyramidal neurons. Collectively, these in vivo proof-of-concept findings provide substantial experimental evidence to demonstrate that modulating σ ₁R represents a potential new therapeutic approach for schizophrenia. The novel chemical entity along with its favorable drug-like and pharmacological profile of 15d renders it a promising candidate for treating schizophrenia.

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

OBJECTIVE: This study aimed to evaluate the relationships of white blood cell (WBC) count, platelet (PLT) count, and PLT-to-WBC ratio (PWR) with muscle mass in Chinese older adults. METHODS: This cross-sectional analysis involved 4,033 Chinese older adults aged ≥ 65 years from the Healthy Ageing and Biomarkers Cohort Study. Muscle mass and total skeletal muscle mass index (TSMI) were measured by bioelectric impedance analysis. WBC, PLT, and PWR were measured using standard methods. Multivariate linear regression was used to examine the associations of WBC count, PLT count, and PWR with TSMI. RESULTS: High WBC count, PLT count, and PWR were associated with low TSMI, with coefficients of -0.0091 (95% confidence interval [ CI]: -0.0142 to -0.0041), -0.0119 (95% CI: -0.0170 to -0.0068), and -0.0051 (95% CI: -0.0102 to -0.0001). The associations between the three inflammatory indices and TSMI were linear. Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged < 80 years than in their counterparts. CONCLUSION Elevated WBC count, PLT count, and PWR correlated with muscle mass loss. This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
Humans ; Aged ; Male ; Female ; China ; Leukocyte Count ; Cross-Sectional Studies ; Platelet Count ; Aged, 80 and over ; Muscle, Skeletal/anatomy & histology* ; Independent Living ; Blood Platelets ; Leukocytes ; Sarcopenia

Objective To explore the effect of Polysaccharides of Panax notoginseng(PPN)on anti-exercise fatigue in mice.Methods One hundred male KM mice were randomly divided into negative control group,positive control group and experimental-L,-M,-H groups,with 20 cases per group.Experimental-L,-M,-H groups was given 100,200,400 mg·kg-1 PPN,respectively;positive control group was given 200 mg·kg-1 vitamin C;negative control group was given 0.1 mL·10 g-1 0.9％NaCl.Five groups were gavaged once a day for 28 days.After the last administration,the loaded swimming time was measured;after 90 minutes of the unloaded swimming test,the mice were allowed to rest for 30 minutes,the levels of lactic acid(LD),blood urea nitrogen(BUN),glycogen,and malondialdehyde(MDA)were measured,the safety of PPN with organ indices and histopathology.Results LD levels in negative control group,positive control group and experimental-L,-M,-Hgroupswere(4.76±0.84),(2.86±0.34),(3.00±0.69),(2.35±0.65)and(1.39±0.48)mg·kg-1;BUN contents were(13.65±1.25),(12.55±0.91),(12.12±1.24),(11.06±1.30)and(9.85±1.05)mmol·L-1;liver glycogen contents were(3.24±0.56),(11.11±2.16),(5.61±1.41),(6.60±1.49)and(12.05±2.25)mg·g-1;MDA levels were(2.36±0.21),(1.23±0.41),(1.93±0.23),(1.73±0.21)and(1.04±0.18)mg prot·mL-1.Compared with negative control group,the differences of above indexes in the positive control group and experimental-L,-M,-H groups were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion PPN can increase exercise endurance in mice and has an anti-fatigue effect.This study provides a theoretical basis for the application of PPN in the field of anti-fatigue research.