Knockdown of PIK3R6 impedes the onset and advancement of clear cell renal cell carcinoma.

In this research, we investigated the role of PIK3R6, a regulatory subunit of PI3Kγ, known for its tumor-promoting properties, in clear cell renal cell carcinoma (CCRCC). Utilizing the UALCAN website, we found PIK3R6 upregulated in CCRCC, correlating with lower survival rates. We compared PIK3R6 expression in CCRCC tumor tissues and adjacent normal tissues using immunohistochemistry. Post RNA interference-induced knockdown of PIK3R6 in 786-O and ACHN cell lines, we performed CCK-8, colony formation, Edu staining, flow cytometry, wound healing, and transwell assays. Results showed that PIK3R6 silencing reduced cell proliferation, migration, and invasion, and induced G0/G1 phase arrest and apoptosis. Molecular analysis revealed decreased CDK4, Cyclin D1, N-cadherin, Vimentin, Bcl-2, p-PI3K and p-AKT, with increased cleaved caspase-3, Bax, and E-cadherin levels in CCRCC cells. Moreover, inhibiting PIK3R6 hindered tumor growth. These findings suggest a significant role for PIK3R6 in CCRCC cell proliferation and metastasis, presenting it as a potential therapeutic target.

Anxiety, depression, and related factors in hemodialysis patients during the lockdown period of COVID- 19 in China: a multicenter study.

The outbreak of coronavirus disease 2019 (COVID-19) made a huge impact on hemodialysis (HD) patients. The aim of the study was to survey the anxiety, depression and related factors of HD patients during the lockdown and to explore the factors that affect their anxiety and depression. From February 1 to 15, 2020, an online survey was conducted in HD patients; the survey collected information on demographic data, epidemic perception, travel status and Zung's Self-rating Anxiety Scale (SAS) and Zung's Self-rating Depression Scale (SDS). The original SAS and SDS data from 96 HD patients gathered between May and August 2018 were retained as data for the control group. A total of 506 HD patients were recruited, and the prevalence of anxiety and depression was 22.33% and 45.45%, respectively. They had significantly higher SAS and SDS scores than the HD patients before the epidemic (p < 0.01; p < 0.05). It was found that self-threat perception, trouble related to transportation and skipping dialysis sessions were factors related to anxiety in HD patients during the lockdown (p ˂ 0.05). Education level, trouble related to transportation and the awareness of the seriousness of the epidemic were factors related to depression (p ˂ 0.05). During the COVID-19 lockdown period, HD patients reported higher levels of psychological distress than HD patients before the pandemic. Psychological support and transport policies should be provided to them.

Epidemiology of hospitalizations due to pesticide intoxication-associated acute kidney injury in China.

BACKGROUND: There is a paucity of epidemiological data regarding pesticide intoxication-associated acute kidney injury (AKI). Therefore, the aim of this study was to identify the epidemiological features, risk factors, and adverse outcomes of AKI in this population. METHODS: The data used in this multi-center, hospitalized population-based, retrospective study were retrieved from electronic medical records. AKI was defined as an acute increase in serum creatinine according to the criteria of Kidney Disease: Improving Global Outcomes. The Charlson Comorbidity Index was used to evaluate the burden of in-hospital mortality. RESULTS: Of 3,371 adult patients in 11 hospitals, 398 (11.8%) were diagnosed with AKI (grade 1, 218 [6.5%]; grade 2, 89 [2.6%]; grade 3, 91 [2.7%]). Herbicide intoxication was associated with the highest incidence of AKI (53.5%) and higher grades of AKI. After multivariable adjustment, pesticide categories and moderate or severe renal disease were independently associated with AKI. As compared with the referred category, insecticide and herbicide intoxications were associated with a 1.3-fold (95% CI 1.688-3.245) and 3.8-fold (95% CI 3.537-6.586) greater risk of AKI. Regardless of the pesticide category, AKI was independently associated with in-hospital mortality, with odds ratios of 3.433 (95% CI 1.436-8.203) for insecticides, 2.153 (95% CI 1.377-3.367) for herbicides, and 4.524 (95% CI 1.230-16.632) for unclassified or other pesticides. CONCLUSION: AKI is common in pesticide intoxication and associated with an increased in-hospital mortality. Herbicides pose the greatest risks of AKI and death.

Efficacy of medium cut-off dialyzers and comparison with high-flux dialyzers in patients on maintenance hemodialysis: A systematic review and meta-analysis.

Medium cut-off (MCO) dialyzers were designed to provide better clearance of uremic toxins. We conducted a meta-analysis comparing MCO with high-flux (HF) dialyzers for the effect on uremic toxins in maintenance hemodialysis (HD) patients. Five databases were systematically searched for relevant studies and nine studies were identified finally. Reduction ratio (RR) of urea, urea, creatinine, ß2-macroglobulin (ß2-MG), kappa free light chain (κFLC), and lambda FLC (λFLC) levels were not significantly different between MCO and HF dialyzers. But RR of ß2-MG, κFLC, and λFLC were greater for MCO than HF dialyzers. MCO dialyzers could better reduce tumor necrosis factor-α (TNF-α) levels. Subgroup analysis stratified by study design indicated that in randomized controlled trial (RCT) studies, albumin levels was lower in MCO than HF dialyzers group, but the two dialyzers treatments were equivalent in non-RCT subgroup. Compared with HF dialyzers, MCO dialyzers provided higher middle-molecules uremic toxins clearance and obviously reduced TNF-α levels.

The diagnostic value of circulating microRNAs as biomarkers for coronary artery disease: A meta­analysis.

OBJECTIVE: In recent years, research on microRNAs (miRNAs) associated with coronary artery disease (CAD) has attracted considerable attention. However, findings of these studies on the validity of circulating miRNAs in CAD diagnosis are controversial. A meta-analysis was therefore conducted to determine the potential value of miRNAs as biomarkers in CAD diagnosis. METHODS: Relevant documents on miRNAs expression levels in the diagnosis of CAD were searched and collected from Pubmed, Embase, and Web of Science. They were collected from the time of inception of the database till January 31, 2020. A meta-analysis was conducted using Stata14.0 software. Forest maps were studied and a comprehensive evaluation of the diagnostic value of the expression levels of mRNAs in CAD was conducted using statistical indicators such as the summary receiver operating characteristic curve. RESULTS: Overall, 14 studies were included, with 38 data sets, involving 29 miRNAs with 846 cases and 898 controls. The meta-analysis revealed that the average sensitivity and specificity of miRNAs for CAD diagnosis were 0.80 (0.75-0.84) and 0.78 (0.75-0.81), respectively. The positive likelihood, negative likelihood, and diagnostic odds ratios were 3.7 (3.1-4.4), 0.26 (0.21-0.33), and 14 (10-21), respectively, and the area under the curve was 0.85 (0.82-0.88). Subgroup analysis revealed that the accuracy in the Asian population was higher than that in the non-Asian population. Multiple miRNAs may be more diagnostically accurate than single miRNAs. MiRNAs in whole blood were more accurate than those in plasma, serum, and peripheral blood mononuclear cells. The diagnostic performance of the quantitative real-time polymerase chain reaction group was better than that of the qPCR group. CONCLUSION: According to our study, miRNAs may be a new, non-invasive diagnostic tool for the diagnosis of CAD. As a screening tool in clinical practice, it has potential diagnostic value and is worthy of clinical promotion. Considering the number and quality of the studies included in this meta-analysis, the above conclusion requires more quality research to verify it.

Feasibility of coding-based Charlson comorbidity index for hospitalized patients in China, a representative developing country.

BACKGROUND: The Charlson Comorbidity Index (CCI) can be automatically calculated from the International Classification of Disease (ICD) code. However, the feasibility of this transformation has not been acknowledged, particularly in hospitals without a qualified ICD coding system. Here, we investigated the utility of coding-based CCI in China. METHODS: A multi-center, population-based, retrospective observational study was conducted, using a dataset incorporating 2,464,395 adult subjects from 15 hospitals. CCI was calculated using both ICD-10-based and diagnosis-based method, according to the transformation rule reported previously and to the literal description from discharge diagnosis, respectively. A κ coefficient of variation was used as a measure of agreement between the above two methods for each hospital. The discriminative abilities of the two methods were compared using the receiver-of-operating characteristic curve (ROC) for prediction of in-hospital mortality. RESULTS: Total agreement between the ICD-based and diagnosis-based CCI for each index ranged from 86.1 to 100%, with κ coefficients from 0.210 [95% confidence interval (CI) 0.208-0.212] to 0.932 (95% CI 0.924-0.940). None of the 19 indices of CCI had a κ coefficient > 0.75 in all the hospitals included for study. The area under the curve of ROC for in-hospital mortality of all 15 hospitals was significantly lower for ICD-based than diagnosis-based CCI [0.735 (0.732, 0.739) vs 0.760 (0.757, 0.764)], indicative of more limited discriminative ability of the ICD-based calculation. CONCLUSIONS: CCI calculated using ICD-10 coding did not agree with diagnosis-based CCI. ICD-based CCI displayed diminished discrimination performance in terms of in-hospital mortality, indicating that this method is not promising for CCI scoring in China under the present circumstances.

High hemoglobin is associated with increased in-hospital death in patients with chronic obstructive pulmonary disease and chronic kidney disease: a retrospective multicenter population-based study.

BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity of chronic obstructive pulmonary disease (COPD). Although high hemoglobin (Hb) is detrimental to CKD patients, its relationship with poor outcomes in the COPD population has not been reported. This study aimed to investigate the relationship between high Hb and in-hospital mortality and to explore reference Hb intervals in patients with COPD and CKD. METHODS: This retrospective study was multicenter population-based. A total of 47,209 patients who presented with COPD between January 2012 and December 2016 were included. The average Hb level during hospitalization was used as the Hb level. CKD and advanced CKD were defined as estimated glomerular filtration rates < 60 and < 30 ml/min/1.73 m2, respectively. The association between Hb level (measured in 1 g/dL intervals) and in-hospital mortality was analyzed in different multivariable logistic regression models by CKD stratification. RESULTS: The Hb level was decreased in the CKD subgroup. In the non-CKD group, a higher Hb level was not associated with an increased risk of in-hospital death. However, the Hb level and mortality showed a U-shaped relationship in the CKD group. After adjusting for age and Charlson Comorbidity Index, multivariable regression analysis showed that an Hb level > 17 g/dL was associated with an increased risk of death in the CKD group with an odds ratio (OR) of 2.085 (95% CI, 1.019-4.264). Hb > 14 g/dL was related to an increased risk of death in advanced CKD patients (OR, 4.579 (95% CI, 1.243-16.866)). CONCLUSIONS: High Hb is associated with an increased risk of in-hospital death in COPD patients with CKD, especially among those with advanced CKD. In this group of patients, attention should be paid to those with high Hb levels.

miR-200bc/429 cluster alleviates inflammation in IgA nephropathy by targeting TWEAK/Fn14.

Immunoglobulin A nephropathy (IgAN) is one of the most common glomerular diseases worldwide. Various studies have identified a host of microRNAs (miRNAs) abnormally expressed in IgAN and might affect the pathogenesis and progression of IgAN. However, miR-200bc/429 cluster in the pathopoiesis of IgAN remains poorly understood. For this study, we found that miR-200bc/429 cluster is downregulated in IgAN tissues and IgAN podocytes and HK2 cells compared with their matched controls respectively. In addition, overexpression of miR-200bc/429 cluster in IgAN podocytes and HK2 cells could attenuate the release of inflammatory cytokines MCP-1, IL-6 and RANTES. Moreover, the 3' untranslated region (UTR) of TNF-like weak inducer of apoptosis (TWEAK) was identified to be a direct target of miR-200bc/429 cluster. Furthermore, our results showed that miR-200bc/429 cluster can inhibit TWEAK mediated NF-κB pathway activation in IgAN. Overall, our findings revealed that miR-200bc/429 cluster alleviates inflammation in IgAN through TWEAK/Fn14 system and might serve as a biomarker as well as a promising therapeutic target for IgAN.

Insect tea extract attenuates CCl4-induced hepatic damage through its antioxidant capacities in ICR mice.

The Insect tea extract (ITE) contained many polyphenols, the aim of the present study was to determine the preventive effects of ITE on CCl4-induced hepatic damage in mice. ITE treated mice could reduce hepatic injury compared to the control mice. The 200 mg/kg ITE increased TC, ALB, SOD, CAT, GSH-Px serum levels, and decreased ALT, AST, ALP, TG, BUN, NO, MDA levels compared to the control group. By histological observation, ITE reduced injury to hepatic cells, and these effects were close to that seen with the drug silymarin. The antioxidant related mRNA and protein expressions of Mn SOD, Gu/Zn SOD, CAT, and GSH-Px increased with ITE treatment in hepatic damage mice. ITE treated mice also showed higher IκB-α mRNA and protein expression, and lower NF-κB-p65, iNOS, COX-2 expressions than those of control mice. These results proved ITE has a prophylactic effect in protecting against hepatic injury through the antioxidant capacities.