BACKGROUND: Stress cardiomyopathy (SCM) currently has a high incidence in older adults, and the theories regarding its causes include "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system in the pathogenesis of SCM remains unknown. We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. METHODS: An SCM model was created using male Sprague-Dawley (SD) rats, immobilized for 6 h every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography examinations were performed to verify the changes in cardiac structure and function in rats with SCM. RNA sequencing was used to explore the changes in the hypothalamus during SCM. In addition, brain and heart tissues were collected to detect microglial activation and sympathetic activity. RESULTS: The main findings were as follows: (1) immobilization stress successfully induced SCM in SD rats; (2) microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickening, increases in the number of microglial branches, and microglia enriched in the PVN; (3) in SCM, the microglia in the PVN exhibited increased central and peripheral cardiac sympathetic activity and increased the expression of neuroinflammatory factors; and (4) it is possible that inhibiting microglial activation could suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats. CONCLUSIONS SCM was induced in SD rats by immobilization stress, acting through the activation of the hypothalamic microglia. The activated microglia were specifically enriched in the PVN, increasing the activity of the central and peripheral sympathetic nervous systems by regulating the expression of neuro-inflammatory factors, mediating dysfunction of the left ventricle, and increasing the susceptibility to ventricular arrhythmias.

COVID-19 Nucleic Acid Testing/methods* ; Clinical Laboratory Techniques ; Containment of Biohazards ; Disinfection ; Environmental Monitoring ; Humans ; Nucleic Acids/isolation & purification* ; SARS-CoV-2/isolation & purification* ; Specimen Handling

Objective To compare the efficacy and safety of tacrolimus with those of cyclosporine in treating idiopathic membranous nephropathy (IMN) via network meta-analysis. Methods Databases including PubMed,Embase,CENTRAL (Cochrane),Wanfang Database,CNKI,and VIP citation database were searched for relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Package Meta 4.5.0 and Gemtc 0.8.1 in R 3.3.1 were used to analyze the included studies. Results In this network meta-analysis,the complete remission rate (RR=0.98,95% CI:0.70-1.40)and the total remission rate (RR=1.00,95% CI:0.90-1.20)of idiopathic membranous nephropathy did not differ significantly between IMN patients treated with cyclosporine A or tacrolimusand,nor did the incidences of hepatic dysfunction(RR=1.40,95% CI:0.52-4.00),infection(RR=0.75,95% CI:0.18-3.10),or gastrointestinal syndrome(RR=2.1,95% CI:0.36-28.00). Conclusion Cyclosporine A seems to have similar effectiveness and safety to tacrolimus in treating IMN.

Objective The aims of this study were to assess incidences and characteristics of arterial thromboembolic events (ATEs) and venous thromboembolic events (VTEs) in Chinese patients with idiopathic membranous nephropathy (IMN), and to identify the predisposing risk factors of them.Methods A total of 766 consecutive Chinese patients with IMN were enrolled in this retrospective cohort study. The cumulative incidences of newly diagnosed ATEs and VTEs were calculated using Kaplan-Meier methods. Univariable risk prediction model analysis followed by multivariable survival analysis was used to evaluate the potential risk factors of ATE and VTE.Results At 0.5, 1, 2, 3, and 5 years after biopsy diagnosis of IMN, the cumulative incidence of newly diagnosed ATEs were 4.3%, 5.7%, 6.3%, 7.1%, and 8.0%, and of newly diagnosed VTEs were 5.9%, 6.8%, 6.9%, 7.0%, and 7.2%, respectively. In 78 ATEs events (71 patients), cardiovascular diseases, thrombotic ischemic stroke (IS) and peripheral artery disease accounted for 50%, 45% and 5% respectively; in 60 VTEs events(53 patients), the deep vein thrombosis, renal vein thrombosis and pulmonary embolism accounted for 60%, 13% and 27% respectively. At the time of event, 42.1% patients with ATEs and 81.5% patients with VTEs were at nephrotic syndrome(NS) status (χ =18.1, P<0.001). Severe proteinuria, aging, smoking, hypertension and prior ATE history were associated with ATEs. Aging was demonstrated as the independent risk factor for ATEs (P=0.001), and hypoalbuminemia was the dominant independent risk factor for VTEs (P=0.03). Conclusions Patients with IMN have increased incidences of ATEs and VTEs, and most of events occurred within the first 6 months of the disease. IS was very common in ATEs in our cohort. Severe proteinuria and classic risk factors for atherosclerosis were associated with onset of ATEs. Hypoalbuminemia independently predicted VTEs. Risks of both ATEs and VTEs were particularly high in the status of NS, particularly VTEs.

Objective To investigate the efficacy and safety of rituximab (RTX) in the treatment of idiopathic membranous nephropathy (IMN) with nephrotic syndrome with a systematic review and meta-analysis. Methods PubMed, Embase, Cochrane Library and Clinical Trials (December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission (CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated. Result Seven studies involved 120 patients (73% were men) were included in our systematic review and meta-analysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric (four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44 (36.7%) had immunosuppressive treatment]. In 12- and 24-month, 56% (95%CI, 0.47-0.65) and 68% (95%CI, 0.41-0.87) patients could reach remission, while 15% (95%CI, 0.09-0.23) and 20% (95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions. Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.

Objective To investigate whether glomerular density (GD) could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min per 1.73 m, or for patients with time-average proteinuria < 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a > 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm(AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%) determined by ROC curve. The low GD group (GD < 1.99 per mm) experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m(six patients in lower GD group, while one patient in the other group). For patients with time-average proteinuria < 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline (4.5±16.7 ml/min per 1.73 mvs. -8.1±21.4 ml/min per 1.73 m, P = 0.038); two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 mof body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Objective:Vacuolar ATPase (V-ATPase) was found within the membranes and internal organelles of a vast array of eukaryotic cells,and was related to various kinds of highly metastatic tumors.LASS2/TMSG1 gene was a novel tumor metastasis suppressor gene cloned from human prostate cancer cell line PC-3M in 1999 by our laboratory.It was found out that protein encoded by LASS2/TMSG1 could interact with the c subunit of V-ATPase (ATP6V0C).In this study,To use RNA interference to suppress the expression of ATP6V0C and try to further investigate the molecular mechanism of ATP6V0C in tumor metastasis and its relationship with LASS2/TMSG1 gene.Methods and Results:The expression level of ATP6V0C mRNA and protein in high metastatic potential prostate cancer cell lines (PC-3M-1E8 and PC-3M) was significantly higher than that in low metastatic potential prostate cancer cell lines (PC-3M-2B4 and PC-3),the expression level in PC-3M-1E8 being the highest.Follow-up tests selected PC-3M-1E8 cells for gene silencing.The expression and secretion of MMP-2 and the expression of MMP-9 in ATP6V0C siRNA transfected PC-3M-1E8 cells displayed no obvious change,but the activity of secreted MMP-9 was abated noticeably compared with the controls (P ＜ 0.05).Extracellular hydrogen ion concentration and V-ATPase activity in interference group were both reduced significantly compared with the controls (P ＜ 0.05).The migration and invasion capacity of ATP6V0C siRNA interfered cells in vitro were diminished significantly compared with the controls (P ＜ 0.05).Furthermore,a dramatic reduction of LASS2/TMSG1 mRNA and protein level after transfection of siRNA in PC-3M-1 E8 cells was discovered (P ＜ 0.05).Confocal immunofluorescence showed a vast co-localization of ATP6V0C protein and LASS2/TMSG1 protein in plasma and membrane.The co-localization signals of control group were much stronger than those of interference group.Conclusion:Specific siRNA silencing of ATP6V0C gene inhibits the invasion of human prostate cancer cells in vitro by mechanism of inhibiting V-ATPase activity and then reducing the extracellular hydrogen ion concentration,inhibiting MMP-9 activation and affecting ECM degradation and reconstruction.Meanwhile,ATP6V0C and LASS2/TMSG1 have interaction and it is likely that ATP6V0C functions as a feedback regulator of LASS2/TMSG1.

Objective To evaluate the advantage of homemade negative pressure device combined with nano-silver dressing for promoting the healing of infected incision in rats,and explore its clinical curative effect.Methods In-fected incision model rats were randomly divided into conventional treatment group,and simple pressure suction group,pressure suction combined with silver ion dressing group.The healing time and healing area of rats in each group after treatment were evaluated,immunohistochemical and fluorescent quantitative analysis of inflammatory factors in incisional wound tissue were performed.Three methods were applied to patients with surgical site infec-tion(SSI),granulation coverage time,granulation recovery time,and incision healing time of three groups of pa-tients were compared.Results Immunohistochemistry and its IOD value,the relative mRNA expression levels of TNF-α,IL-2,and IL-8 in rat wound tissue treated with pressure suction combined with silver ion dressing were all inferior to conventional treatment group and simple negative pressure suction group,difference was statistically sig-nificant (P < 0.05);in clinical application,wound healing time,postoperative C-reactive protein level,and pain as-sessment scores in patients treated with pressure suction combined with silver ion dressing were all superior to con-ventional treatment group and simple negative pressure suction group,difference were all statistically significant (all P < 0.05).Conclusion Compared with conventional treatment method,pressure suction with silver ions dressing treatment can more effectively control SSI,reduce local inflammation of incision,and promote incision healing.

AIM:To study the growth-inhibiting and proapoptotic effects of Pim-1 kinase inhibitor SMI-4a on human acute myeloid leukemia cell line U937.METHODS:The effect of SMI-4a on U937 cell viability was measured by CCK-8 assay.The apoptotic rate was assessed by flow cytometry with Annexin V-PI staining and by fluorescence microscopy with Hoechst 33342 staining.Methylcellulose was used to assess colony formation ability of the cells.The expression of β-catenin in the cell cytosol and nucleus was detected by Western blot,and the expression of apoptosis-related proteins in the U937 cells was also examined.Intracellular distribution of β-catenin was detected by the method of immunofluorescence.RESULTS:SMI-4a inhibited the viability of U937 cells.Annexin V-PI staining showed that SMI-4a induced apoptosis in dose-and time-dependent manners.Hoechst 33342 staining also verified the apoptosis.SMI-4a significantly inhibited the colony formation capacity of the U937 cells.The results of Western blot demonstrated that SMI-4a upregulated the expression of PARP and Bax,downregulated the expression of Bcl-2 and change the distribution of β-catenin in intracellular compartment.Immunofluorescence observation found that SMI-4a decreased the expression level of β-catenin in the U937 cells.CONCLUSION:SMI-4a induces U937 cell apoptosis through regulating the expression of apoptosis-related genes.

Alzheimer's disease (AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta (Aβ) peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides (200, 400 and 800 mg/kg, p.o.) for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase (SOD), glutathione (GSH), acetylcholine esterase (AChE), and the content of malondialdehyde (MDA) as well as the level of nitric oxide (NO) in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides (400 or 800 mg/kg). All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.
Acetylcholinesterase ; metabolism ; Alzheimer Disease ; drug therapy ; etiology ; Amyloid beta-Peptides ; toxicity ; Animals ; Female ; Glutathione ; metabolism ; Hippocampus ; drug effects ; metabolism ; Interleukins ; metabolism ; Juglans ; chemistry ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; Memory Disorders ; drug therapy ; etiology ; Mice ; NF-kappa B ; metabolism ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Peptide Fragments ; toxicity ; Peptides ; pharmacology ; therapeutic use ; Plant Extracts ; pharmacology ; therapeutic use ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism