Characterization of the gut microbiota in frail elderly patients.

BACKGROUND: The change in the composition of gut microbiota has been reported in the elderly and in the frail individuals; however, studies on gut microbiota in frail elderly are limited. AIMS: This study aimed to investigate the gut microbiota of the frail elderly. METHODS: From September 2017 to February 2018, 27 elderly patients hospitalized in the Department of Geriatrics of our hospital were enrolled and divided into the frailty group (n = 15) and the control group (n = 12) based on the cutoff of 0.25 for the frailty index. The fecal samples were collected for 16S rRNA-amplicon sequencing to analyze the composition and richness of gut microbiota. Operational taxonomic unit (OTU) clustering was performed using Usearch software. Intra-sample diversity (alpha-diversity) analysis and inter-sample diversity (beta-diversity) analyses were performed. The community richness was compared between the two groups at family and genus levels. RESULTS: There were 1903 and 1880 OTUs identified in the control and frailty groups, respectively, with 1282 OTUs overlap between the two groups. The alpha diversity of microbiota community was similar between the two groups, whereas the frailty group had larger beta diversity than the control group. The top-10 taxonomy categories and abundances of gut microbiota between the two groups were similar. As for the gut microbiota composition, 4 families and 17 genera were significantly different between the two groups (p < 0.05). CONCLUSION: These results suggested that frailty can affect gut microbiota diversity and compositions in late elderly hospitalized patients.

Clinicopathological and prognostic value of PD-L1 in urothelial carcinoma: a meta-analysis.

Objective: Our objective was to conduct a meta-analysis to investigate the clinicopathological features and prognostic value of programmed cell death ligand 1 (PD-L1) expression in patients with urothelial carcinoma (UC). Materials and methods: Twenty-seven studies with 4,032 patients were included in the meta-analysis. Pooled ORs and 95% CIs were used to examine the associations between clinical factors and PD-L1 expression. HRs and 95% CIs were extracted from eligible studies. Heterogeneity was evaluated using the chi-squared-based Q test and I2 statistic. Results: Expression of PD-L1 on tumor cells (TCs) was associated with muscle-invasive disease (OR=3.67, 95% CI: 2.53-5.33), and inversely associated with the history of intravesical bacilli Calmette-Guerin therapy (OR=0.39, 95% CI: 0.18-0.82) in bladder cancer patients. PD-L1 expression on TCs was associated with worse overall survival (HR=2.06, 95% CI: 1.38-3.06) in patients with organ-confined bladder cancer. PD-L1 expression in patients with UC was significantly related to better objective response rate after PD-1/PD-L1 antibody treatment. Conclusions: Expression of PD-L1 on TCs was associated with muscle-invasive disease in patients with bladder cancer. Patients with PD-L1-positive UC had a significantly better response to PD-1/PD-L1 targeted treatment.

Bone-derived Nestin-positive mesenchymal stem cells improve cardiac function via recruiting cardiac endothelial cells after myocardial infarction.

BACKGROUND: Bone-derived mesenchymal stem cell (BMSC) transplantation has been reported to be effective for the treatment of ischemic heart disease, but whether BMSCs are the optimal cell type remains under debate. Increasing numbers of studies have shown that Nestin, an intermediate filament protein, is a potential marker for MSCs, which raises the question of whether Nestin+ cells in BMSCs may play a more crucial role in myocardial repair. METHODS: Nestin+ cells were isolated using flow cytometry by gating for CD45- Ter119- CD31- cells from the compact bone of Nestin-GFP transgenic mice, expressing GFP driven by the Nestin promoter. Colony-forming and proliferative curve assays were conducted to determine the proliferative capacity of these cells, while qRT-PCR was used to analyze the mRNA levels of relative chemokines and growth factors. Cardiac endothelial cell (CEC) recruitment was assessed via a transwell assay. Moreover, permanent ligation of the left anterior descending (LAD) coronary artery was performed to establish an acute myocardial infarction (AMI) mouse model. After cell transplantation, conventional echocardiography was conducted 1 and 4 weeks post-MI, and hearts were harvested for hematoxylin-and-eosin (HE) staining and immunofluorescence staining 1 week post-MI. Further evaluation of paracrine factor levels and administration of a neutralizing antibody (TIMP-1, TIMP-2, and CXCL12) or a CXCR4 antagonist (AMD3100) in MI hearts were performed to elucidate the mechanism involved in the chemotactic effect of Nestin+ BMSCs in vivo. RESULTS: Compared with Nestin- BMSCs, a greater proliferative capacity of Nestin+ BMSCs was observed, which further exhibited moderately high expression of chemokines instead of growth factors. More CEC recruitment in the Nestin+ BMSC-cocultured group was observed in vitro, while this effect was obviously abolished after treatment with neutralizing antibodies against TIMP-1, TIMP-2, or CXCL12, and more importantly, blocking the CXCL12/CXCR4 axis with a AMD3100 significantly reduced the chemotactic effect of Nestin+ BMSCs. After transplantation into mice exposed to myocardial infarction (MI), Nestin+ BMSC-treated mice showed significantly improved survival and left ventricular function compared with Nestin- BMSC-treated mice. Moreover, endogenous CECs were markedly increased, and chemokine levels were significantly higher, in the infarcted border zone with Nestin+ BMSC treatment. Meanwhile, neutralization of each TIMP-1, TIMP-2, or CXCL12 in vivo could reduce the left ventricular function at 1 and 4 weeks post-MI; importantly, the combined use of these three neutralizing antibodies could make a higher significance on cardiac function. Finally, blocking the CXCL12/CXCR4 axis with AMD3100 significantly reduced the left ventricular function and greatly inhibited Nestin+ BMSC-induced CEC chemotaxis in vivo. CONCLUSIONS: These results suggest that Nestin+ BMSC transplantation can improve cardiac function in an AMI model by recruiting resident CECs to the infarcted border region via the CXCL12/CXCR4 chemokine pathway. And we demonstrated that Nestin+BMSC-secreted TIMP-1/2 enhances CXCL12(SDF1α)/CXCR4 axis-driven migration of endogenous Sca-1+ endothelial cells in ischemic heart post-AMI. Taken together, our results show that Nestin is a useful marker for the identification of functional BMSCs and indicate that Nestin+ BMSCs could be a better therapeutic candidate for cardiac repair.

Study of Acute Kidney Injury on 309 Hypertensive Inpatients with ACEI/ARB - Diuretic Treatment.

BACKGROUND: The present study investigated risk factors for acute kidney injury (AKI) in patients found to be hypertensive during hospitalization who were prescribed angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor antagonists (ARB) + diuretic combinations, in order to determine which type of diuretic or combination of diuretics used in ACE/ARB-treated patients leads to a higher risk of acute kidney injury. METHOD: Data on basic information, medical history, diagnostic information and medications prescribed were obtained from the patients' medical records. Retrospective analysis of potential risk factors and ACEI/ARB + diuretic use with AKI was performed. RESULTS: Multivariate analysis showed initial risk factors for AKI to be chronic kidney disease and poor cardiac function. In univariate analysis, patients whose baseline serum creatinine was between 115 and 265 µmol/L also had a higher risk of AKI. The combination of furosemide and spironolactone produced only approximately a third of the risk of AKI as the combination of hydrochlorothiazide and spironolactone. CONCLUSIONS: Chronic kidney disease and poor cardiac function are major risk factors for AKI in hypertensive inpatients using ACEI/ARB + diuretic therapy. The combination of thiazide diuretic and aldosterone antagonist had a higher risk of AKI than other single diuretics or diuretic combinations.