The kidney is a vital organ for maintaining metabolic balance within the body and facilitating excretion. Its complex tissue structure comprises diverse cell types, including glomerular, tubular, interstitial and immune cells. The highly differentiated nature of these cells presents challenges for investigating kidney disease mechanisms. In recent years, the rapid advancement of single‑cell omics technologies has provided novel perspectives for renal research. These techniques have revealed the diversity and heterogeneity of renal cells, enabling precise identification of multiple immune cell types within the kidney. These findings further elucidate the dynamic changes in renal immune cells during disease progression and their interactions with other renal cells, laying a foundation for in‑depth analysis of renal disease pathogenesis. The present review aims to summarize the current applications of single‑cell omics technologies in renal ageing and kidney diseases, providing crucial insights for deciphering disease mechanisms and identifying therapeutic targets.

The effect of a high-fat diet (HFD) on mood is a widely debated topic, with the underlying mechanisms being poorly understood. This study explores the anxiolytic effects of a four-week HFD in C57BL/6 mice. Five-week-old mice were exposed to either an HFD (60% calories from fat) or standard chow diet (CD) for four weeks, followed by cannula implantation, virus infusion, behavioral tests, and biochemical assays. Results revealed that four weeks of an HFD induced anxiolytic-like behaviors and increased the protein levels of mature brain-derived neurotrophic factor (mBDNF) and phosphorylated tyrosine kinase receptor B (p-TrkB) in the medial prefrontal cortex (mPFC). Administration of a BDNF-neutralizing antibody to the mPFC reversed HFD-induced anxiolytic-like behaviors. Elevated BDNF levels were observed in both neurons and astrocytes in the mPFC of HFD mice. Additionally, these mice exhibited a higher number of dendritic spines in the mPFC, as well as upregulation of postsynaptic density protein 95 (PSD95). Furthermore, mRNA levels of the N6-methyladenosine (m6A) demethylase, fat mass and obesity-associated protein (FTO), and the hydrolase matrix metalloproteinase-9 (MMP9), also increased in the mPFC. These findings suggest that an HFD may induce FTO and MMP9, which could potentially regulate BDNF processing, contributing to anxiolytic-like behaviors. This study proposes potential molecular mechanisms that may underlie HFD-induced anxiolytic behaviors.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

Background: T cell exhaustion, a state where T cells lose their effector functions, is a major obstacle to tumor immune response. However, subsets of co-expressed molecular markers haven’t been evaluated systematically in the prognosis of solid tumor patients yet. We aim to investigate the relationship between co-expressed markers of exhausted T cells and the prognosis of different histologic subtypes of solid tumors. Methods: Observational cohorts were selected based on their relevance to T cell exhaustion and co-expressed inhibitory receptors, and quality assessment criteria were applied. A systematic search of PubMed, Web of Science, and EMBASE database was conducted on May 2023, identifying observational cohorts which report T cell exhaustion and composite inhibitory receptors of solid tumor patients. The outcome included overall survival (OS), recurrence-free survival (RFS), progression free survival (PFS). The study protocol is prospectively registered on PROSPERO (registration number CRD42022382916). Results: Forty-four eligible cohorts comprising 10,701 patients were identified, and all 16 studies utilized immunohistochemical techniques to report the presence of co-expressed exhaustion markers. The co-expression of exhaustion markers was found to be significantly associated with a poor prognosis of solid tumor patients, with HR values of 0.60 (95% CI: 0.54-0.67) for OS, 0.53 (95% CI: 0.40-0.70) for PFS, and 0.50 (95% CI: 0.38-0.67) for RFS. The results of the subgroup analysis indicated that the type of tumor histology, and co-expressed biomarkers have prognostic value respectively in HNSCC (HR=0.42, 95% CI: 0.31–0.59), ccRcc (HR=0.59, 95% CI: 0.47–0.73), gastrointestinal cancer (HR=0.56, 95% CI: 0.33–0.95), while no correlation was found in HCC and ovarian cancer group. Interpretation: Our findings provide evidence that different patterns of co-expressed T cell exhaustion markers are associated with poor prognosis in patients with solid tumors and suggest that assessing co-expressed T cell exhaustion markers could potentially guide therapeutic strategies.Funding: None.Declaration of Interest: Dr. Ma Xuelei has nothing to disclose. Dr. Xin Wu has nothing to disclose. Dr. Ming Chen has nothing to disclose. Dr. Yutong Wang has nothing to disclose. Dr. Liu Haoyang has nothing to disclose.

Factor XI (FXI) deficiency is a rare bleeding disorder of unpredictable severity that correlates poorly with FXI coagulation activity and that poses great challenges for perioperative hemostatic management and the dialysis methods potentially available to new end-stage renal disease (ESRD) patients. We describe an individual with both ESRD and severe FXI deficiency, who successfully underwent peritoneal dialysis (PD) after emergency abdominal surgery. In the traditional concept, recent abdominal surgery is a contraindication to PD, especially for patients with bleeding risk. However, this case report highlights that PD can still be an possible option for patients with FXI deficiency who have just undergone abdominal surgery; laparoscopic PD catheter placement offers a chance to establish PD access in patients traditionally viewed as noncandidates for this method. Careful perioperative management and fresh frozen plasma transfusion ensure successful surgery. This case should be of help to clinicians and patients considering PD in similar situations.

癌症治疗相关心脏毒性临床关注的是心血管并发症,传统抗肿瘤药物(如蒽环类药物)和靶向治疗药物(如曲妥珠单抗)均可引起心脏毒性,使病人被迫减少或停止治疗恶性肿瘤所需的药物,病人病死率增加,心脏毒性中癌症治疗相关心功能障碍(CTRCD)常见.尽管早期采用神经激素阻断剂可预防或减轻心脏毒性引起的心功能下降,但同时可导致不可逆顽固性心力衰竭和病死率明显增加.沙库巴曲缬沙坦降低心力衰竭住院率和病死率已得到证实,近年来应用于CTRCD已取得较好疗效,且相较于神经激素阻断剂有明显的优势.综述沙库巴曲缬沙坦改善CTRCD的相关临床研究进展.

Background Human dental pulp stem cells (hDPSCs) are critical for pulp generation. hDPSCs proliferate faster under hypoxia, but the mechanism by which long noncoding RNA (lncRNA) regulates this process is not fully understood. Methods Novel lncRNAs were obtained by reanalysis of transcriptome datasets from RNA-Seq under hypoxia compared with normoxia, and a differential expression analysis of target genes was performed. Bioinformatics analyses, including gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and gene set enrichment analysis, were used to understand the function of key novel lncRNAs. hDPSCs were isolated from dental pulp tissue. EdU and scratch wound healing assays were used to detect the proliferation and migration of hDPSCs. qRT-PCR was used to detect changes in the RNA expression of selected genes. RNA fluorescence in situ hybridization, small interfering RNA, qRT-PCR and Western blot analysis were used to explore the function of key novel lncRNAs. Results We identified 496 novel lncRNAs in hDPSCs under hypoxia, including 45 differentially expressed novel lncRNAs. Of these, we focused on a key novel lncRNA, which we designated HRL-SC (hypoxia-responsive lncRNA in stem cells). Functional annotation revealed that HRL-SC was associated with hypoxic conditions and the PI3K/AKT signaling pathway. HRL-SC was mainly located in the cytoplasm of hDPSCs and had stable high expression under hypoxia. Knockdown of HRL-SC inhibited the proliferation and migration of hDPSCs and the expression levels of PI3K/AKT-related marker proteins. Furthermore, the AKT activator SC79 partially offset the inhibitory effect caused by the knockdown, indicating that HRL-SC promoted hDPSCs through the PI3K/AKT signaling pathway. Conclusions Hypoxia-responsive lncRNA HRL-SC promotes the proliferation and migration of hDPSCs through the PI3K/AKT signaling pathway, and this understanding may facilitate the regenerative application of hDPSCs.

Purpose: To explore the potential impact of traditional Chinese herb FuZhengHuaYuJiangZhuTongLuo recipe (FZHY) on renal interstitial fibrosis ( RIF) in chronic kidney disease (CKD) at cellular and molecular levels. Methods: Unilateral ureteral obstruction ( UUO) rats were established as the RIF model in vivo. The rats were given intragastric administration with FZHY once a day for consecutive 7, 14 and 21 days, respectively. The renal function parameters and inflammation indicators in kidney tissues were measured using enzyme- linked immunosorbent assay, the CD4(+)/CD8(+) T cells in peripheral blood was detected using flow cytometry, the renal fibrosis degree was estimated using Masson's staining, and the fibrosis-related genes' expression was detected using quantitative polymerase chain reaction, western blotting, and immunohistochemistry analyses. Results: FZHY prescription reduced the serum creatinine and blood urea nitrogen, decreased the levels of c-reactive protein, interleukin-1, interleukin- 6 and tumor necrosis factor- alpha in kidney tissues, and increased the ratio of CD4(+)/CD8(+) T cells in peripheral blood. FZHY prescription suppressed the renal tissue fibrosis and reduced the levels of laminin, fibronectin, collagen I and collagen III. Conclusion: FZHY prescription suppressed the renal fibrosis and improved the condition of "Healthy Qi Deficiency and Evil Qi Excess" in rats with UUO, which may provide an effective method for CKD treatment.

Background: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are novel, hypoglycemic drugs exhibiting cardiovascular protective activities. If SGLT2 inhibitors can be successfully used as antihypertensive drugs, they can be administered to patients with both hypertension and type 2 diabetes, thus diminishing the risk of polypharmacy-related complications. Aim: The aim of this review was to evaluate the hypotensive efficacy of SGLT2 inhibitors in patients with hypertension and pre-hypertension. Data Sources and Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials comparing SGLT2 inhibitors and a placebo in patients with essential hypertension and pre-hypertension. Our main outcome was the mean change in office blood pressure (BP) and body weight. We assessed the pooled data using a fixed-effects model. Results: After screening 968 articles, nine trials were eligible ( n = 2450 participants). Compared to the mean changes in systolic and diastolic BP in patients who were given a placebo, those in patients who used SGLT2 inhibitors were −5.04 mmHg and −1.67 mmHg, respectively. An intensive dose of SGLT2 inhibitors resulted in a stronger BP-lowering effect than the regular dose. Compared to that in the placebo group, the mean change in mean body weight was −1.74 kg in the SGLT2 inhibitor group. There was no significant difference between the two groups regarding the risk of overall adverse events. The pooled effect estimates remained similar across all residual studies and their subgroups in the leave-one-out sensitivity analysis. Conclusion: SGLT2 inhibitors had a statistically significant BP-lowering effect on hypertension and pre-hypertension, which was further enhanced with increased drug dosage. SGLT2 inhibitors have the potential to be used as antihypertensive agents in patients with hypertension complicated by type 2 diabetes.

Review question / Objective: The aim of this systematic review and meta-analysis was to assess the effects of TCM on renal function, modulation of gut microbiota, and changes of intestinal function in patients CKD.

综述阵发性心房颤动的临床概况及复律、消融、抗凝等治疗策略及目前存在的问题,以期使阵发性心房颤动的临床防治更加科学合理.

高血压前期是在正常血压与高血压之间的一个中间区域,其在高血压防治中是一个至关重要的阶段.高血压前期在各个地区均有较高的患病率,而多项研究结果证明高血压前期患者心血管疾病风险较正常血压患者高.目前对高血压前期的干预主要以非药物治疗为主,药物治疗为辅,但近年来高血压前期药物治疗越来越受到重视.现围绕高血压前期的流行病学、并发症风险和治疗措施等方面进行讨论.

血脂异常,尤其是低密度脂蛋白胆固醇的升高,是冠状动脉粥样硬化性心脏病的主要危险因素之一.他汀类降脂药物因其多种副作用,不能完全满足临床的需要.前蛋白转化酶枯草溶菌素9抑制剂,通过抑制前蛋白转化酶枯草溶菌素9与低密度脂蛋白胆固醇受体的结合,降低血液中低密度脂蛋白胆固醇水平,从而有效地降低冠状动脉粥样硬化性心脏病事件的发生率,改善临床预后.

Review question / Objective: The aim of t h i s m e t a -a n a l y s i s o f r a n d o m i z e d controlled trials is to evaluate the efficacy of SGLT2 inhibitors on lowering blood pressure in patients with hypertension and pre-hypertension.Condition being studied: Recently, a new class of drugs, the sodium glucose cotransporter (SGLT)-2 inhibitors, has been used to treat patients with type 2 diabetes.Some trials show that SGLT-2 inhibitors may confer cardiovascular protection, including a reduction in blood pressure ( B P ) .P r e -h y p e r t e n s i o n a n d e a r l y INPLASY 1 International Platform of Registered Systematic Review and Meta-analysis Protocols INPLASY PROTOCOLEffect of Sodium-glucose cotransport-2 inhibitors on lowering blood pressure in patients with hypertension and pre-hypertension: A meta-analysis Ren, B 1 ; Chen, M 2 .To cite:

心力衰竭(心衰)是所有心脏疾病的严重表现或晚期阶段,目前心衰的发病机制和治疗的研究已有显著进展,预后得到改善,但仍不容乐观.贫血和铁缺乏是心衰常见的合并症,无论共存或独立,都与心衰预后不良有关.积极纠正贫血和铁缺乏有助于改善心衰患者症状和提高生活质量.红细胞生成刺激剂常用于心衰患者贫血的纠正,但并未改善预后,且增加不良事件风险.口服补铁方便易得,静脉补铁能改善心衰症状和运动能力,但两者的长期疗效和安全性需进一步研究.

本共识建立了成人动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)高危人群规范应用心脑宁胶囊以提升疗效的关键流程,概述了心脑宁胶囊的中医配伍理论、药学和药理研究特性,界定了心脑宁胶囊的精确适用人群、干预时机、病证疗效特点及优选应用方案,归纳了心脑宁胶囊的不良反应、使用禁忌、注意事项及非临床安全性等相关证据.本共识适合ASCVD相关专业领域的执业医师、执业中医医师和执业中西医结合医师使用.

Vascular remodeling induced by long-term hyperglycaemia is the main pathological process in diabetic vascular complications. Thus, vascular remodeling may be a potential therapeutic target in diabetes mellitus (DM) with macrovascular disease. The present study aimed to investigate the effect of RING finger protein 10 (RNF10) on vascular remodeling under conditions of chronic hyperglycaemia stimulation. We found that overexpression of RNF10 clearly decreased intimal thickness and attenuated vascular remodeling in DM. TUNEL staining showed that apoptosis was clearly inhibited, an effect that may be mediated by decreases in Bcl-2 protein expression. Quantitative analysis demonstrated that overexpression of RNF10 could suppress inflammation by reducing the levels of TNF-alpha, and MCP-1 mRNA and NF-kappa B protein. Meanwhile, overexpression of RNF10 prevented vascular smooth muscle cell (VSMC) hyperproliferation through the downregulation of cyclin D1 and CDK4 proteins. Notably, short hairpin RNF10 (shRNF10) greatly aggravated the pathological responses of diabetic vascular remodeling. These outcomes revealed that the differential expression of RNF10 had a completely opposite effect on vascular damage under hyperglycaemia, further displaying the core function of RNF10 in regulating vascular remodeling induced by diabetes. Consequently, RNF10 could be a novel target for the treatment of diabetic vascular complications.

1 血管紧张素受体拮抗剂(angiotensin receptor blocker,ARB)的作用机制 肾素血管紧张素醛固酮系统(renin-angiotensinaldosterone system,RAAS)的激活贯穿于整个心血管事件链中,其中RAAS的经典途径起着至关重要的作用.血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)是RAAS最重要的生物活性物质,也是一种前炎症因子,主要通过血管紧张素Ⅱ1型受体(type 1 angiotensin receptors,AT1 R)及血管紧张素2型受体(type 2 angiotensin receptors,AT2R)发挥活性作用.其中ATlR介导了绝大多数AngⅡ的生理作用,最主要为强烈的血管收缩作用,同时AngⅡ还能刺激肾上腺皮质分泌醛固酮,从而增加水钠潴留、增加钾的排泄[1].