Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid–induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Glycosylation constitutes a critical, highly intricate, and diverse co- and post-translational modification characterized by the covalent attachment of sugar moieties to proteins, lipids, or small RNAs. Complex glycans are ubiquitously present across nearly all living organisms. Despite their prevalence, our comprehension of glycan diversity remains limited, likely due to the inherent challenges associated with elucidating their structural complexity. Among post-translational modifications, protein glycosylation is notably prevalent, involving the enzymatic transfer of oligosaccharides to specific amino acid residues by glycosyltransferases. This modification plays a pivotal role in modulating protein function, including participation in various biological and biochemical recognition processes. G protein-coupled receptors (GPCRs), encoded by approximately one thousand genes, share a conserved architecture comprising seven transmembrane helices interconnected by three intracellular and three extracellular loops. Representing the largest family of human membrane proteins, GPCRs regulate a vast array of physiological and pathological processes, thereby constituting the most extensive class of therapeutic targets. In mammalian systems, the majority of GPCRs undergo glycosylation predominantly at their extracellular N-terminus or extracellular loops, primarily through N-linked and O-linked glycosylation. These covalent carbohydrate modifications exert profound effects on multiple facets of GPCR biology, including endoplasmic reticulum folding and quality control, membrane trafficking and surface expression, receptor internalization and recycling or degradation, ligand binding and signal transduction, biased signaling, and receptor dimerization. Notably, glycosylation can exert both positive and negative regulatory influences on these processes. Dysregulation of GPCR glycosylation has been implicated in a range of pathological conditions, such as cancer, diabetes, and neurological disorders, underscoring its physiological and pathological significance. Aberrant glycosylation patterns may lead to dysfunctional receptor signaling, thereby contributing to disease progression. Consequently, elucidating the precise roles of glycosylation in GPCR function not only enhances fundamental understanding of receptor biology but also facilitates the development of novel therapeutic strategies targeting glycosylation pathways or specific GPCR glycoforms. Although the functional consequences of glycosylation have been investigated for several decades, delineating their exact structural underpinnings has remained challenging due to the intrinsic flexibility and heterogeneity of carbohydrate structures. Recent advances in structural biology, particularly single-particle cryo-electron microscopy (cryo-EM) and X-ray crystallography, have catalyzed a paradigm shift in our understanding of GPCR glycosylation. The integration of these sophisticated structural techniques with biochemical approaches has redefined glycosylation as a complex structural element integral to receptor function. These developments provide a molecular framework for comprehending how glycans influence receptor pharmacology and open new avenues for the rational design of glyco-engineered biologics and allosteric modulators targeting specific extracellular motifs. This mini-review concentrates on glycosylation within the GPCR superfamily, summarizing the impact of glycosylation modifications on receptor function and regulatory mechanisms, recent progress in the structural biology of GPCR glycosylation, and prospective directions for future research in this field.

Objective: Some regions in China have lowered the minimum interval for whole blood donation to 3 months through local regulations: Hainan, effective from March 1, 2012, allows men to donate at intervals of≥3 months and women at intervals of≥4 months; Shenzhen, effective from November 1, 1995, allows whole blood donation at intervals of≥3 months. The aim of this study was to evaluate the impact of shortening the whole blood donation interval on blood donation adverse reactions and donation behavior, thereby providing scientific evidence for policy evaluation and revision of relevant regulations. Methods: This was a multicenter, retrospective cohort study based on blood donation registry data from Shenzhen and Hainan. Data were obtained from the blood information management systems of Hainan Province (1991-2025) and Shenzhen City (2018-2024). Eligible participants were donors aged 18-65 years who had donated whole blood at least twice and met health eligibility criteria. The exposure was defined as a shorter donation interval (whole-blood interval≥3 months and<6 months) and was treated as a time-varying variable. The primary outcome was blood donation adverse reactions. Negative binomial regression with person-years as an offset was used to estimate incidence rate ratios for adverse reactions. Marginal standardization was used to estimate the adjusted incidence rate difference, and donor-level bootstrap resampling was used to estimate the 95% confidence interval of the adjusted incidence rate difference. Non-inferiority was assessed by comparing the upper limit of the 95% confidence interval with the prespecified non-inferiority margin of Δ=0.00 070 per person-year. In addition, Andersen-Gill models were used to analyze adverse reaction-free probability for recurrent events. Secondary outcomes were donation behavior, including annual repeat donation rate, annual donation frequency, mean donation interval, and annual whole-blood donation volume. These were analyzed using logistic regression, negative binomial regression, and linear regression models, respectively, with adjustment for age, sex, region, and donation site. This study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (Approval No.2025011) and registered in the Chinese Clinical Trial Registry (ChiCTR2500114968). Results: A total of 375 075 repeat whole-blood donors were included, contributing 1 292 748 whole-blood donations. Among them, 119 993 had ever donated at a shorter interval and 255 082 had never done so. Over 1 281 842 person-years of follow-up in the dynamic cohort, 2 100 blood donation adverse reactions were recorded. The incidence rates of adverse reactions were 1.76 and 1.58 per 1 000 person-years in the ever-short interval and never-short interval groups, respectively. After adjustment for age, sex, province, and donation site, the ever-short interval group had a slightly higher adverse reaction rate than the never-short interval group (IRR=1.28, 95%CI: 1.15-1.41, P<0.001). Marginal standardization showed that the adjusted incidence rates were 1.73 and 2.21 per 1 000 person-years in the never-short interval and ever-short interval groups, respectively. The adjusted incidence rate difference was 0.000 48 per person-year, with a bootstrap 95%CI of 0.000 26-0.000 69 per person-year; the upper limit of the 95%CI was below the prespecified non-inferiority margin. Andersen-Gill recurrent-event analysis showed that the ever-short interval group had a higher probability of remaining adverse reaction-free. Analysis of donation behavior showed that among donors followed for at least 365 days, the ever-short interval group had a higher annual repeat donation rate than the never-short interval group (74.2% vs 18.3%; adjusted OR=12.5, 95%CI: 12.3-12.7, P<0.001). They also had a higher annual whole-blood donation rate (adjusted RR=1.98, 95%CI: 1.97-1.98, P<0.001), a shorter mean whole-blood donation interval (β=-239 days, 95%CI: -242 to -237 days, P<0.001), and a higher annual whole-blood donation volume (adjusted RR=2.14, 95%CI: 2.13-2.15, P<0.001). Conclusion: Based on real-world data from repeat whole-blood donors in Shenzhen and Hainan, lowering the minimum whole blood donation interval to 3 months did not show an absolute increase in blood donation adverse reactions exceeding the prespecified margin within the scope of this outcome. Shorter whole-blood donation interval behavior was also associated with greater repeat-donation activity, higher annual donation frequency, and higher annual whole-blood donation volume. Given the observational nature of this study and the lack of long-term donor health indicators such as iron status and longitudinal hemoglobin changes, the long-term safety of setting the minimum whole blood donation interval at 3 months requires further evaluation.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective:Investigation of the relationship between variant angina pectoris syncope and coronary artery spastic targeted location, arrhythmias, and coronary artery stenostic lesion.Methods:This study combined retrospective and prospective registry approaches. Data were sourced from the case database of Henan province "Multicenter Clinical Observation Study of Variant Angina Pectoris". A total of 507 patients with variant angina pectoris who had complete records from June 1980 to December 2022 were consecutively enrolled. Select patients among them who experienced syncope, and analyze the target vessel sites of coronary artery spasm, arrhythmias during variant angina pectoris attacks, and the degree of stenosis in coronary artery lesions.Results:Among 507 variant angina pectoris patients, 88 experienced syncope. Age was (53.9±9.7) years and 66 patients (75.0%) were male. Forty patients (45.5%, 40/88) were aged 50-59 years. The incidence of syncope in variant angina pectoris caused by left anterior descending artery (LAD) spasm, right coronary artery (RCA) spasm, and multivessel coronary artery spasm was 7.4% (15/202), 22.7% (42/185), and 23.6% (25/106), respectively. The latter two were significantly higher than those in the LAD group ( P all<0.05). Among 77 patients with variant angina pectoris syncope, definitive electrocardiogram recordings were available during syncope episodes. All patients exhibited arrhythmias during syncope: 34 cases involved tachyarrhythmias and 43 cases involved bradyarrhythmias. The incidence of rapid arrhythmias in patients with LAD, RCA, and multi-vessel spasm syncope was 72.7% (8/11), 24.3% (9/37), and 54.2% (13/24), respectively, with P<0.05 for the first two. Bradyarrhythmias occurred in 27.3% (3/11) of LAD, 75.7% (28/37) of RCA, and 45.8% (11/24) of multivessel coronary artery spasm syncope cases, with the first two showing P<0.05. Coronary angiography analysis of 56 syncope patients revealed target vessel locations and stenosis severity: 12 patients had LAD lesions and 41 had RCA lesions, stenosis ≥50% occurred in 66.7% (8/12) and 43.9% (18/41) of these lesions, respectively ( P>0.05). Conclusions:Variant angina pectoris syncope predominantly affects middle-aged males. Bradyarrhythmias triggered by RCA spasm are a common cause, while the incidence of syncope shows no significant correlation with the degree of coronary artery stenostic lesion, whether in the LAD or the RCA.

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.