Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective To analyze the research hotspots and frontier trends of transcranial magnetic stimulation(TMS)in the field of rehabilitation in the last decade.Methods The literatures of TMS in the field of rehabilitation from January,2014 to September,2024 were searched in the database of Web of Science core collection,and the visual analysis was carried out by using CiteSpace 6.4.R1 software.Results A total of 1 065 articles were included,showing an increasing trend in annual publication volume.China was the leading country in publication volume,Harvard University was the institution with the largest number of pub-lished articles,and Simone Rossi was the most frequently cited author.Keywords with high co-occurrence fre-quency included stroke,noninvasive brain stimulation,plasticity,cortical excitability,θ burst stimulation and up-per limb.Brain-computer interface was the bursting keyword in the past two years.Conclusion In the past decade,the research interest in TMS in the field of rehabilitation has been on the rise.It focused on the application of multimodal combined therapies,including TMS,to improve the upper limb function and aphasia of stroke patients and to explore the plasticity of brain nerves.Future research should focus on the deep integration of TMS and brain-computer interface technology to realize the individualization and accuracy of TMS treatment.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

Objective:To construct an evidence-based practice program for dietary management of patients with non-dialysis chronic kidney disease (CKD) based on best evidence and to evaluate the effectiveness of its application.Methods:The best evidence for dietary management of non-dialysis CKD patients was summarized. From September to October 2022, following the evidence clinical transformation model of the Fudan University Centre for Evidence-based Nursing, the best evidence was screened and evidence-based practice program were developed, taking into account patients' wishes, expert opinions, and clinical contexts. From November 2022 through March 2023, baseline reviews, analysis of barriers and facilitators were implemented. Between April 2023 and April 2024, evidence-based practice was carried out in the Department of Nephrology of the Second Affiliated Hospital of Guangzhou Medical University to compare the implementation rate of review indicators at the system, practitioner, and patient levels, and practitioners' knowledge before and after the application of evidence.Results:A total of 14 review indicators were developed. The implementation rate of the 12 review indicators and the practitioners' knowledge of the CKD diet were elevated after the evidence-based practice ( P<0.05) . Conclusions:Evidence-based practice program for dietary management of patients with non-dialysis CKD has a positive effect on improving practitioners' knowledge of non-dialysis CKD diets, implementation rate of dietary management behaviors, and patients' dietary behaviors.

Objective To analyze the research hotspots and frontier trends of transcranial magnetic stimulation(TMS)in the field of rehabilitation in the last decade.Methods The literatures of TMS in the field of rehabilitation from January,2014 to September,2024 were searched in the database of Web of Science core collection,and the visual analysis was carried out by using CiteSpace 6.4.R1 software.Results A total of 1 065 articles were included,showing an increasing trend in annual publication volume.China was the leading country in publication volume,Harvard University was the institution with the largest number of pub-lished articles,and Simone Rossi was the most frequently cited author.Keywords with high co-occurrence fre-quency included stroke,noninvasive brain stimulation,plasticity,cortical excitability,θ burst stimulation and up-per limb.Brain-computer interface was the bursting keyword in the past two years.Conclusion In the past decade,the research interest in TMS in the field of rehabilitation has been on the rise.It focused on the application of multimodal combined therapies,including TMS,to improve the upper limb function and aphasia of stroke patients and to explore the plasticity of brain nerves.Future research should focus on the deep integration of TMS and brain-computer interface technology to realize the individualization and accuracy of TMS treatment.

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism.MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

Objective:To summarize the evidence of diet management in patients with chronic kidney disease (CKD) in stage 3-5 D, so as to provide a reference for clinical nursing.Methods:After establishing evidence-based nursing questions, according to the "6S evidence model", the evidence on diet management of patients with CKD in stage 3-5 D was searched by computer, including computer decision support system evidence, guidelines, best evidence summary and systematic review. The search time limit was from the establishment of the database to September 2020. The guideline quality assessment was independently completed by two research nurses and a doctor of nephrology. The quality assessment of non-guideline article was independently completed by two research nurses, and an evidence-based instructor participated in decision-making. The evidence was extracted, evaluated and graded using the Joanna Briggs Institute (JBI) 2014 version of the intervention research evidence pre-grading system.Results:A total of 19 articles that met the requirements were included, including 5 guidelines, 8 systematic reviews, 4 randomized controlled trials, 1 clinical decision, and 1 national standard. A total of 22 pieces of the best evidence on diet management of patients with CKD in stage 3-5 D were summarized from three aspects, namely, diet/nutrition assessment, diet management, teamwork and education.Conclusions:The best evidence of diet management in patients with CKD in stage 3-5 D provides a certain reference for clinical practice, so as to improve the quality of diet management in patients with CKD and the clinical outcomes of patients.

Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.

Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.