Lipid metabolism reprogramming is critical for the initiation and progression of hepatocellular carcinoma (HCC). However, how the dysregulation of lipid metabolism contributes to HCC development remains largely unknown. Here, we report that the m6A reader YTHDC1-mediated epigenetic regulation of the long noncoding RNA NEAT1 activates stearoyl-CoA desaturase (SCD)-associated lipid metabolic processes during HCC progression. Mechanistically, histone lactylation in HCC induces increased expression of YTHDC1, increasing the stability of m6A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression.

Background Mesenchymal stem cells (MSCs) are widely used in a variety of tissue regeneration and clinical trials due to their multiple differentiation potency. However, it remains challenging to maintain their replicative capability during in vitro passaging while preventing their premature cellular senescence. Forkhead Box P1 (FOXP1), a FOX family transcription factor, has been revealed to regulate MSC cell fate commitment and self-renewal capacity in our previous study. Methods Mass spectra analysis was performed to identify acetylation sites in FOXP1 protein. Single and double knockout mice of FOXP1 and HDAC7 were generated and analyzed with bone marrow MSCs properties. Gene engineering in human embryonic stem cell (hESC)-derived MSCs was obtained to evaluate the impact of FOXP1 key modification on MSC self-renewal potency. Results FOXP1 is deacetylated and potentiated by histone deacetylase 7 (HDAC7) in MSCs. FOXP1 and HDAC7 cooperatively sustain bone marrow MSC self-renewal potency while attenuating their cellular senescence. A mutation within human FOXP1 at acetylation site (T176G) homologous to murine FOXP1 T172G profoundly augmented MSC expansion capacity during early passages. Conclusion These findings reveal a heretofore unanticipated mechanism by which deacetylation of FOXP1 potentiates self-renewal of MSC and protects them from cellular senescence. Acetylation of FOXP1 residue T172 as a critical modification underlying MSC proliferative capacity. We suggest that in vivo gene editing of FOXP1 may provide a novel avenue for manipulating MSC capability during large-scale expansion in clinical trials.

Chromium (Cr) is the seventh most abundant chemical element in the Earth’s crust, and Cr(III) and Cr(VI) are common stable valence states of Cr. Several Cr-containing substances, such as FeOCr 2 O 3 and stainless-steel products, exist in nature and in life. However, Cr(VI) is toxic to soil, microorganisms, and plants and poses a serious threat to human health through direct and indirect exposure. By collecting published journal literature, we found that Cr(VI) can cause acute and chronic toxicity in organisms and has carcinogenic effects, and the mechanisms causing these toxicity include endoplasmic reticulum stress, autophagy and apoptosis. However, the relationship between these mechanisms remains unclear. Many methods have been researched to purify chromium, but each of these methods has its own advantages and disadvantages. Therefore, this review summarizes the hazards of chromium and the mechanisms of chromium toxicity after entering cells and provides a number of methods for chromium contamination management, providing a direction for the next step in chromium toxicology and contamination decontamination research.

糖尿病肾病(diabetic nephropathy,DN)是糖尿病(diabetes mellitus,DM)慢性微血管并发症之一,也是导致终末期肾病(end-stage renal disease,ESRD)的主要原因.我国DM相关慢性肾脏病(chronic kidney disease,CKD)患病率己超过肾小球肾炎(glomerulonephritis,GN)相关CKD,DN己成为危害我国居民健康的一大社会问题.DN治疗方案主要为生活方式改变和药物治疗,但目前临床常用药物仅能减轻症状,延缓疾病进展,需新型药物以改善DN患者总体结局.内皮素受体拮抗剂(endothelin receptor antagonist,ERA)是一类近年被应用于DN治疗的新型药物,效果良好.现对ERA在DN治疗中的临床研究进展作一综述,旨在为临床提供参考.

盐皮质激素受体(mineralocorticoid receptor,MR)的过度激活会导致慢性肾脏疾病(chronic kidney disease,CKD)进展.新型MR拮抗剂——非奈利酮(finerenone)具有非甾体结构,能够以独特的机制与MR结合,抑制参与基因表达的转录辅因子的募集,可有效延缓糖尿病肾病(diabetic nephropathy,DN)进展.现综述非奈利酮治疗DN的作用机制、循证证据、不良反应、与钠-葡萄糖耦联转运体-2抑制剂的联合应用及未来前景等,旨在为DN临床治疗提供新的策略.

钠-葡萄糖耦联转运体2抑制剂(sodium-glucose linked transporter 2 inhibitor,SGLT-2i)是一种新型口服降糖药物,通过促进肾小管尿糖、尿钠排泄,发挥降糖、降血压、降尿酸、减轻体质量以及减少心肾不良事件等多重作用.SGLT-2i是近年来糖尿病(diabetes mellitus,DM)治疗领域的热点之一,可有效延缓DM肾病(diabetic nephropathy,DN)进展.现将综述SGLT-2i治疗DN的作用机制、临床获益、安全性及指南更新等,旨在为临床治疗工作提供新策略.

糖尿病( diabetes mellitus,DM)是一个重大的全球性健康问题,糖尿病肾病( diabetic nephropathy,DN)是其最常见的微血管并发症之一,也是导致终末期肾病( end-stage renal disease,ESRD)的主要原因,近一半的糖尿病肾病患者后期需要透析治疗[1～3].因此,良好的控制血糖对预防DN发生,延缓疾病进展有着重要意义.近年来,肠促胰素这一新型的降糖药物被成功应用于2型DM治疗,并发现具有葡萄糖非依赖性的肾脏保护潜能,包括胰高血糖素样肽1受体激动剂(glucagon-like peptide-1 receptor agonist,GLP-1RA)、二肽基肽酶4抑制剂(dipeptidyl peptidase 4,DPP-4i).但GLP-1 R激动剂和DPP4 抑制剂对肾脏潜在获益的研究进展及其机制,仍未引起肾脏科医生的足够重视.因此,本文将就近年来肠促胰素在DM患者中的肾脏保护大型临床研究作一系统整理和阐述,尤其关注肠促胰素对DN的获益.

Secreted protein acidic and rich in cysteine (SPARC) may play a notable role in aqueous humor outflow through the trabecular meshwork (TM). SPARC is a potential therapeutic target in glaucoma, and the mechanism by which it regulates intraocular pressure remains unclear. The present study aimed to observe the effects of SPARC in human TM cells (HTMCs) in vitro. SPARC was downregulated by recombinant lentiviral vectors in HTMCs, and the subsequent levels of F-actin expression, zonula occludens-1 (ZO-1) expression and cellular phagocytosis were observed and calculated. It was revealed that after 48 h of culture, the expression levels of SPARC, F-actin and ZO-1 were significantly decreased in the lentivirus group compared with those in the blank control and empty vector control groups. The downregulation of SPARC promoted phagocytosis in HTMCs after 24 or 48 h of culture. This indicated that the downregulation of SPARC decreased the expression levels of the cytoskeleton-associated proteins F-actin and ZO-1, promoted phagocytosis in HTMCs and may affect the outflow of aqueous humor via the TM pathway.

Objective:To investigate the cognition and application of palliative care in ESRD among clinical medicine students and to provide some reference for the reform of medical education in medical curriculums.Methods:From December in 2018, self-designed questionnaires were sent out to 200 medical undergraduate selected randomly from the grade 2014 and 2015 of Shanghai Jiao Tong University School of Medicine. Questionnaire stars were used to investigate the awareness of medical students on palliative care and its application in the treatment of end-stage renal disease, and the current situation of palliative medical education of medical students during undergraduate education.Results:59.6%(102/171) students failed to understand the difference between palliative care and palliative care; while 42.1%(72/171) of students had insufficient understanding of palliative care for ESRD patients. 81.3%(139/171) of students had never learned palliative care program in class and 83.5%(116/139) of them prefer to get knowledge of palliative care from clinical practice rather than in class. We also found students experienced clinical practice had deeper understanding on palliative care than those without clinical practice[(4.53±0.55)vs(4.34±0.69), t=2.08]. Conclusions:Cognition and application of palliative care in ESRD among medical students still needs to be improved. Effective access is urged to obtain the knowledge of palliative care for medical students.

肾脏是新型冠状病毒肺炎(COVID-19)可累及的主要器官之一.COVID-19造成的急性肾损伤(AKI)以肾小管损伤为主,尿常规检查的异常主要为蛋白尿,患者也可出现肾小球滤过功能受损导致的血肌酐、尿素氮水平升高.目前推测肾损伤的发生机制包括病毒直接攻击肾脏,免疫介导的肾脏损伤,以及其他因素(如继发真菌和细菌感染、腹泻、呕吐、使用抗生素等).需注意对COVID-19患者AKI的早期筛查、早期诊断和积极治疗,可行血液净化疗法.

β-Adrenergic receptor (β-AR) signaling is a pathway controlling adaptive thermogenesis in brown or beige adipocytes. Here we investigate the biological roles of the transcription factor Foxp1 in brown/beige adipocyte differentiation and thermogenesis. Adipose-specific deletion of Foxp1 leads to an increase of brown adipose activity and browning program of white adipose tissues. The Foxp1 -deficient mice show an augmented energy expenditure and are protected from diet-induced obesity and insulin resistance. Consistently, overexpression of Foxp1 in adipocytes impairs adaptive thermogenesis and promotes diet-induced obesity. A robust change in abundance of the β3-adrenergic receptor (β3-AR) is observed in brown/beige adipocytes from both lines of mice. Molecularly, Foxp1 directly represses β3-AR transcription and regulates its desensitization behavior. Taken together, our findings reveal Foxp1 as a master transcriptional repressor of brown/beige adipocyte differentiation and thermogenesis, and provide an important clue for its targeting and treatment of obesity.

Fundamental human traits, such as language and bipedalism, are associated with a range of anatomical adaptations in craniofacial shaping and skeletal remodeling. However, it is unclear how such morphological features arose during hominin evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare disorder involving speech apraxia and language impairments. Analysis of its evolutionary history suggests that this gene may have contributed to the emergence of proficient spoken language. In the present study, through analyses of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup vocalizations in a similar way to that of global Foxp2 mutants, which may be due to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate that Foxp2 helps to regulate strength and length of hind limbs and maintenance of joint cartilage and intervertebral discs, which are all anatomical features that are susceptible to adaptations for bipedal locomotion. In light of the known roles of Foxp2 in brain circuits that are important for motor skills and spoken language, we suggest that this gene may have been well placed to contribute to coevolution of neural and anatomical adaptations related to speech and bipedal locomotion.

Objective:To investigate the leading causes of death and related factors in maintenance hemodialysis( MHD) pa-tients. Methods:We retrospectively analyzed the MHD patients treated in Shanghai Jiaotong University Affiliated Sixth People Hospi-tal and Shanghai Jiaotong University Affiliated Sixth People Hospital South Campus in the period of Jan. 2008 to Dec. 2013. Elimina-ted the patients treated less than three month. There were 380 patients total, 96 patients died. Analysis the causes of death of patients and affected factors. Results:In the 96 death cases, 62 cases were males and 34 cases were females. The main causes of mortality were cardiovascular and cerebrovascular diseases(48,50%), infectious diseases(18,18. 75%),malignancies(16,16. 67%). 48 ca-ses were older than 60. Diabetic nephropathy was frequently found in elderly group. Cardiovascular mortality in patients with high blood phosphorus( >1. 45 mmol/L)was significantly higher than normal blood phosphorus(≤1. 45 mmol/L). There was statistical significance. That means higher blood phosphorus accompanied higher risk of death on cardiovascular. Logistic regression analysis showed that albumin, urea nitrogen, serum creatinine maybe the risk fators of MHD patients. Compared with the non-cardiovascular and cerebrovascular diseases, die of cardiovascular and cerebrovascular diseases, it’ s dialysis age was shorter,and serum creatinine, HB, albumin, triglyceride, and cholesterol were higher. Conclusion:In maintenance hemodialysis patients, the main cause of death was cardiovascular and cerebrovascular disease, the second was infection and tumor. Diabetes was the important factor affecting the prognosis. Control blood phosphorus levels maybe reduce the mortality.

柠檬酸又名枸橼酸( citric acid) ,是一种生理性的酸. 柠檬酸碳酸氢盐透析液是一种新型透析浓缩液,即传统碳酸氢盐透析液中用于调节透析液pH、防止其中钙镁沉积的醋酸被柠檬酸全部或大部分替代,不含或仅含极微量的醋酸. 现就此新型透析液在血液净化中的研究进展做一综述.

Background: The reticulon 1 gene (RTN1) encodes reticulons, endoplasmic reticulum stress proteins recently implicated in kidney disease progression. Methods:RTN1 single nucleotide polymorphisms (SNPs) were tested for association with type 2 diabetes (T2D)-associated end-stage kidney disease (ESKD) in African Americans (AAs) and European Americans (EAs), and AAs with non-diabetic ESKD. RTN1 SNPs that were associated with T2D-ESKD in AA cases compared to non-nephropathy controls were identified from a discovery genome-wide association study (n = 1,797), then tested for replication in 1,847 additional AA T2D-ESKD cases and controls. Results: Three intronic RTN1 variants were nominally associated with T2D-ESKD in both discovery and replication analyses: rs1952034, rs12431381 and rs12434215 (additive models); combined T2D-ESKD (discovery + replication) p values were 0.015-3.0 × 10-4 (ORs 0.67-0.77; minor alleles protective). In addition, rs12434215 was weakly associated with T2D-ESKD in 557 EA T2D-ESKD cases contrasted with 753 EA non-nephropathy controls (p = 0.019; OR 0.69, dominant model). Nominal association extended to non-diabetic causes of ESKD in 1,459 additional AA cases (rs12431381 and rs12434215 p values 0.014-0.015; OR 0.77). An all-cause ESKD association analysis contrasted the 3,594 AA ESKD cases with 1,489 AA non-nephropathy controls and detected association with rs12434215 (p = 6.7 × 10-4, OR 0.73) and rs12431381 (p = 7.5 × 10-4, OR 0.75) in dominant models. Of the 3 SNPs, only rs12434215 was weakly associated with T2D per se when contrasting T2D non-nephropathy cases with non-diabetic controls (additive model p = 0.032 AAs; p = 0.048 EAs). Conclusions: These results suggest evidence of genetic association between common variants in RTN1 and ESKD in AAs and EAs.

Objective:To investigate mechanism by which miR-26b regulates high glucose-induced mesangial cells(MCs) hypertrophy,providing a novel clue for the insight into diabetic nephropathy(DN) at early stage.Methods:Applying bioinformatics to predict the candidates of miRNAs potentially targeting glycogen synthase kinase-3β(GSK3β).To verify the expressions of all of miRNAs candidates in renal cortex of db / db mice and perform pearson relavant analysis between miRNAs and GSK3βrespectively as well.The selected miRNA and GSK3β were detected in MCs exposure to high glucose condition by using real time PCR.Furthermore,GSK3β,hypertrophic gene α-SMA and Collagen IV were detected in MCs cultured in high glucose 72 hours after transfection of selected miRNA inhibitor by real-time PCR and western blot.Results:A total of 9 miRNAs candidates potentially targeting GSK3βwere screened by bioinformatics,which were miR-199a-5p,miR-128,miR-23b,miR-23a,miR 29a,miR-29c,29b,miR-26b,miR-26a.Among these candidates,miR-128,miR-23b,miR-26b,miR-29a upregulated remarkably in renal cortex in db / db mice compare with db / m controls(P < 0.05).One of these four miRNAs,namely miR-26b showing significantly negative relevance with GSK3βby person analysis(r =-0.470 29).The similar results were found in high glucose-induced MCs.The levels of GSK3β were restored partly by transfection of miR-26b inhibitor,meanwhile α-SMA and Collagen IV ameliorated accordingly in cultured MCs in high glucose conditions.Conclusion:Taken together,miR-26b might involve in the regulation of high glucose-induced MCs hypertrophy via targeting GSK3β.The current study provides a novel insight into the pathogenesis of DN at early stage.

<正>急性胰腺炎(acute pancreatitis,AP)是临床上较常见的疾病,其发展过程中可致全身多器官损害而产生全身炎症反应综合征(systemic inflammatory response syndrome,SIRS),病死率高达50%。急性肾衰竭是重症急性胰腺炎(severe acute pancreatitis,SAP)最严重的并发症之一,病死率高达71.2%。因此,在SAP的综合抢救中,早期预防和保护肾功能,防止

Objective To investigate the effectiveness of APACHE II scores、MODS scores、SOFA scores and AKI classification for predicting prognosis in the acute kidney injury patients who treated with continuous renal replacement therapy(CRRT). Methods We retrospectively analyzed the AKI patients in ICU of Shanghai Sixth People's Hospital affiliated to Shanghai Jiaotong University treated with CRRT in the period of Jan. 2006 to Dec. 2010. The APACHE II scores、MODS scores、SOFA scores were evaluated upon ICU admission and at the commencement of CRRT. Result A total of 117 AKI patients who treated with CRRT were enrolled. Seventy-two patients died. The overall mortality in hospital rate was 61.5%. Without renal replacement therapy as a criterion,25 patients would have been classified as AKI 3 classified as AKI 2 or AKI 1. Area under ROC (AUROC) curves for predicting death by APACHE IICRRT、MODSCRRT、SOFACRRT scores were 0.901、0.851、0.885 (P<0.001),higher than the AUROC of AKICRRT 0.617 (P=0.034). Conclusion APACHE II、MODS、SOFA Scoring Systems are useful for evaluating the prognosis of AKI patients who treated with CRRT. AKI classification may have less predictive power.