Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Objective:To investigate the role and mechanism of TrxR1 in reprogramming tumor-associated macrophage in breast cancer,providing novel insights and theoretical foundations for clinical breast cancer treatment.Methods:TISIDB database was used to analyze the relationship between TXNRD1(encoding TrxR1)and tumor immunity.Mouse breast cancer 4T1 cells conditioned medium was collected and co-cultured with bone marrow-derived macrophage(BMDM)cells for 48 h to detect the expression of macrophage immunosuppression-related factors.TrxR1 secretion by tumor cells was measured using ELISA kits.TXNRD1 knockdown efficiency was verified via Western blot.Fluorescence quantitative PCR(qPCR)and flow cytometry were used to detect the expression levels of macrophage immunosuppressive factors after TXNRD1 knockdown in tumor cells.JASPAR database was used to analyze the potential regulatory factors,and Western blot was used to verify the expression of pathway-related proteins.Results:Database analysis found that TXNRD1 expression positively correlated with survival risk indices across multiple cancers,with the strongest association observed in breast cancer.Further analysis found that elevated TXNRD1 expression correlated with reduced infiltration of M1 macrophages and natural killer(NK)cells,but increased M2 macrophage infiltration.qPCR and flow cytometry demonstrated that tumor-conditioned medium enhanced macrophage immunosuppression,whereas medium from TXNRD1-knockdown tumor cells suppressed this effect.And TrxR1-neutralizing antibodies could also reversed this effect.JASPAR database analysis identified STAT3 and STAT6 as potential transcriptional regulators,and Western blot confirmed that TXNRD1-knockdown tumor cells conditioned medium inhibited STAT6 pathway activation in macrophages.Conclusion:In the tumor microenvironment,breast tumor-derived TrxR1 promotes macrophage immunosuppression,potentially through activation of the STAT6 signaling pathway.

Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Pancreatic β-cell dysfunction is a critical factor in the pathogenesis of type 2 diabetes mellitus(T2DM).Recent studies have identified iron overload as a significant risk factor for T2DM, wherein excess iron contributes to β-cell dysfunction through multiple pathways, including oxidative stress, mitochondrial dysfunction, and a reduction in the number of pancreatic β-cells.These mechanisms adversely affect insulin synthesis, secretion, and release.This review aims to summarize the recent advancements in understanding the relationship between iron overload and pancreatic β-cell dysfunction.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Objective To explore the risk factors for postoperative atrial fibrillation (POAF) after off-pump coronary artery bypass grafting (OPCAB) alone. Methods A retrospective analysis was conducted on the clinical data of patients who underwent OPCAB in the Department of Cardiac Surgery Ward No.1 of Zhengzhou Seventh People’s Hospital from January 2020 to January 2024. Patients were categorized into a POAF group and a non-POAF group based on the occurrence of POAF. The clinical data of both groups were analyzed. Parameters underwent univariate analysis, and variables with P≤0.05 in univariate analysis were further analyzed through binary multivariate logistic regression to identify independent risk factors. Results A total of 496 patients were included. There were 312 males and 184 females, with age ranging from 50 to 78 years. There were 148 patients in the POAF group and 348 patients in the non-POAF group. The incidence of POAF after isolated OPCAB surgery was 29.8%. Results of univariate analysis showed that there were statistical differences in the incidence of diabetes (P=0.012), >75% stenosis of the left circumflex artery (LCX) (P=0.036), shock (P<0.001), graded left ventricular diastolic function (P<0.001), left ventricular ejection fraction (P<0.001), age (P<0.001), preoperative resting heart rate (P<0.001), left atrial diameter (P<0.001), E/A ratio (P<0.001), postoperative K+ concentration (P<0.001), and postoperative Mg2+ concentration (P<0.001). Binary multivariate logistic regression analysis revealed that age (OR=1.436, 95%CI 1.094 to 1.884, P=0.009), diabetes (OR=2.032, 95%CI 1.006 to 4.145, P=0.043), preoperative resting heart rate (OR=1.008, 95%CI 1.001 to 1.015, P=0.018), left atrial diameter (OR=4.409, 95%CI 1.711 to 11.359, P=0.002), and E/A ratio (OR=1.713, 95%CI 1.115 to 2.633, P=0.014) were independent risk factors for POAF after isolated OPCAB. The occurrence of POAF significantly prolonged mechanical ventilation time and ICU stay (both P＜0.001). Conclusion Age, diabetes, left atrial diameter, E/A ratio, and preoperative resting heart rate are potential independent risk factors for POAF following OPCAB surgery. Additionally, the occurrence of POAF can lead to prolonged mechanical ventilation and extended stay in the intensive care unit.

Objective To investigate the metabolic characteristics of patients with early-onset type 2 diabetes mellitus(T2DM)and to develop a risk prediction model for microvascular complications.Methods A retrospective study was conducted on 980 T2DM patients admitted for treatment between April 2020 and April 2024.Based on age at diagnosis,the patients were divided into two groups,an early-onset T2DM group(age at diagnosis<40 years,n=265)and a late-onset T2DM group(age at diagnosis≥40 years,n=715).Differences in metabolic indicators between the two groups were compared.Patients in the early-onset group were further divided into a complication subgroup(n=142)and a non-complication subgroup(n=123)based on the presence or absence of microvascular complications.Data on baseline characteristics,metabolic parameters,and laboratory indicators were collected and compared between the two groups.Multivariate logistic regression analysis was used to identify independent risk factors for microvascular complications,and a nomogram prediction model was constructed.The model's discriminative performance was assessed using receiver operating characteristic(ROC)curves,and its calibration was evaluated using calibration curves and the Hosmer-Lemeshow test.Decision curve analysis(DCA)was also performed to assess the model's clinical utility.Results Compared with the late-onset group,patients in the early-onset group exhibited more pronounced metabolic abnormalities,including higher body mass index(BMI),proportion of family history of diabetes mellitus,glycated hemoglobin(HbA1c)levels,total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),triglyceride-glucose index(TyG),and lactate dehydrogenase(LDH)levels(all P<0.05),along with a shorter disease duration and lower levels of high-density lipoprotein cholesterol(HDL-C)(P<0.05).According to a multivariate analysis,systolic blood pressure(SBP),total bilirubin(TBIL),HDL-C,LDL-C,TyG,and LDH were identified as independent risk factors for microvascular complications in patients with early-onset T2DM.A predictive model based on these factors was established as the follows,Log(P)=-19.915+0.017×SBP-0.136×TBIL-1.241×HDL-C+0.684×LDL-C+0.769×TyG+0.050×LDH.The area under the ROC curve(AUC)was 0.864(95%CI,0.820-0.907),and the Hosmer-Lemeshow test indicated good model fit(χ2=10.286,P=0.246).The slope of the DCA curve was also close to 1.Conclusion The nomogram prediction model based on SBP,TBIL,HDL-C,LDL-C,TyG,and LDH demonstrates good predictive performance for microvascular complications and can provide a reference for clinical risk stratification and individualized intervention.

Alzheimer disease(AD)is a progressive neurodegenerative disorder characterized by cognitive dysfunction and declining learning and memory abilities,significantly impacting daily lives and behavioral capacities of the patients.The mitogen-activated protein kinase(MAPK)signaling pathway,primarily composed of extracellular signal-regulated kinase,p38 MAPK,and c-Jun N-terminal kinase.Mounting evidence suggests that the MAPK signaling path-way is intimately linked to the pathogenesis of AD,providing crucial insights into the disease's progression.In recent years,traditional Chinese medicine(TCM)has demonstrated promising potential in treating AD,with its advantages of personalized therapy and multi-target regulation garnering increasing research attention.This study aims to review the ex-perimental research landscape of TCM interventions targeting the MAPK signaling pathway for the prevention and treat-ment of AD over the past five years.The findings reveal that effective compounds and herbal formulas in TCM,such as isorhamnetin,nobiletin,parthenolide,Glehnia littoralis,Ishige okamurae,shikonin,artemisinin,kaempferol,myrice-tin,and Tripterygium glycosides,can alleviate AD symptoms by modulating the MAPK signaling pathway.These interven-tions mitigate Aβ-induced neuronal damage,reduce Tau protein hyperphosphorylation,and suppress neuroinflammatory responses.The objective of this review is to provide a scientific and theoretical reference for the clinical prevention and treatment of AD and to inform the development of novel therapeutic agents.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.