Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. RESULTS: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31-1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p = 0.042). CONCLUSION: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591.

Triglyceride-lowering therapy for the prevention of cardiovascular events, stroke, and mortality in patients with diabetes: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Triglyceride (TG)-lowering therapy is efficient for the prevention of cardiovascular disease (CVD) in the general population; however, for diabetic individuals, it is more controversial. The purpose of this study was to pool the results from randomized controlled trials (RCTs) to clarify whether the lowering of TG is beneficial for the prevention of CVD events, stroke, and mortality in subjects with diabetes. METHODS: MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials were searched to identify the relevant literature. We included randomized controlled trials (RCTs) to assess the association of triglyceride-lowering therapy with the prevention of CVD events, stroke, and mortality in diabetic patients. RESULTS: Overall, 19 studies were included in this meta-analysis. Compared with the control groups, TG lowering was associated with a decreased risk of CVD events (RR = 0.91, 95% CI 0.87-0.95, p = 0.000) and CVD mortality (RR = 0.93, 95% CI 0.86-1.00, p = 0.047). There was no significant correlation between TG-lowering therapy and the incidence of stroke and all-cause mortality (RR = 0.93, 95% CI 0.86-1.02, p = 0.129 and RR = 0.97, 95% CI 0.93-1.01, p = 0.107, respectively). Subgroup analysis showed that the decreased CVD risk resulting from TG-lowering therapy was independent of age, sex, region, duration of follow-up, degree of TG reduction and glycemic control. CONCLUSIONS: TG-lowering therapy is associated with a reduction in CVD events and cardiovascular-specific mortality, but not in stroke and all-cause mortality. Future large, multicenter RCTs will further confirm these conclusions.

The Efficacy of SARS-CoV-2 Vaccination in the Elderly: A Systemic Review and Meta-analysis.

BACKGROUND: Given the reduced immune response to vaccines in older populations, this study aimed to evaluate the efficacy of COVID-19 vaccinations and its impact on breakthrough infection, hospital admission, and mortality in the elderly. METHODS: We carried out a systemic review and meta-analysis where MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials were queried to identify relevant literature. We included randomized controlled trials (RCTs), non-randomized trials, prospective, observational cohort, and case-control studies assessing breakthrough infection, hospital admission, and mortality after coronavirus 2 (SARS-CoV-2) vaccination in the elderly (≥ 60 years old). RESULTS: Overall, 26 studies were included in this meta-analysis. Compared with the unvaccinated group, the vaccinated group showed a decreased risk of SARS-CoV-2 infection after 28-34 (relative risk [RR] = 0.42, 95% confidence interval [CI] 0.37-0.49) and 35-60 days (RR = 0.49, 95% CI 0.37-0.62). There was a step-wise increase in efficacy with additional doses with the two-dose group experiencing decreased risk of breakthrough infection (RR = 0.37, 95% CI 0.32-0.42), hospital admissions (RR = 0.25, 95% CI 0.14-0.45), disease severity (RR = 0.38, 95% CI 0.20-0.70), and mortality (RR = 0.21, 95% CI 0.14-0.32) compared with those receiving one or no doses. Similarly three-dose and four-dose vaccine groups also showed a decreased risk of breakthrough infection (3-dose: RR = 0.14, 95% CI 0.10-0.20; 4-dose RR = 0.46, 95% CI 0.4-0.53), hospital admissions (3-dose: RR = 0.11, 95% CI 0.07-0.17; 4-dose: RR = 0.42, 95% CI 0.32-0.55), and all-cause mortality (3-dose: RR = 0.10, 95% CI 0.02-0.48; 4-dose: RR = 0.48, 95% CI 0.28-0.84) Subgroup analysis found that protection against mortality for vaccinated vs. unvaccinated groups was similar by age (60-79 years: RR = 0.59; 95% CI, 0.47-0.74; ≥ 80 years: RR = 0.76; 95% CI, 0.59-0.98) and gender (female: RR = 0.66; 95% CI, 0.50-0.87, male: (RR = 0.58; 95% CI, 0.44-0.76), and comorbid cardiovascular disease (CVD) (RR = 0.69; 95% CI, 0.52-0.92) or diabetes (DM) (RR = 0.59; 95% CI, 0.39-0.89. CONCLUSIONS: Our pooled results showed that SARS-CoV-2 vaccines administered to the elderly is effective in preventing prevent breakthrough infection, hospitalization, severity, and death. What's more, increasing number of vaccine doses is becoming increasingly effective.

Association of remnant cholesterol with risk of cardiovascular disease events, stroke, and mortality: A systemic review and meta-analysis.

BACKGROUND AND AIMS: Lipid disorders are associated with the risk of cardiovascular diseases (CVDs). Remnant cholesterol (RC), a non-traditional previously neglected risk factor for CVD, has received much attention in recent years. The aim of this study is to evaluate the association of RC with the risks of CVD, stroke, and mortality. METHODS: MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials were searched. We included randomized controlled trials (RCTs), non-RCTs, and observational cohort studies assessing the association of RC with the risks of cardiovascular (CV) events, coronary heart disease (CHD), stroke, and mortality. RESULTS: Overall, 31 studies were included in this meta-analysis. Compared with low RC, elevated RC was associated with an increased risk of CVD, CHD, stroke, CVD mortality, and all-cause mortality (RR = 1.53, 95% CI 1.41-1.66; RR = 1.41, 95% CI 1.19-1.67; RR = 1.43, 95% CI 1.24-1.66; RR = 1.83, 95% CI 1.53-2.19; and RR = 1.39, 95% CI 1.27-1.50; respectively). A subgroup analysis demonstrated that each 1.0 mmol/L increase in RC was associated with an increased risk of CVD events and CHD. The association of RC with an increased CVD risk was not dependent on the presence or absence of diabetes, a fasted or non-fasted state, total cholesterol, or triglyceride or ApoB stratification. CONCLUSIONS: Elevated RC is associated with an increased risk of CVD, stroke, and mortality. In addition to the traditional cardiovascular risk factors, such as total cholesterol and LDL-C, clinicians should also pay attention to RC in clinics.

Experience of double plasma purification in 603 patients from a single center in Shanghai, China.

INTRODUCTION: To summarize the clinical experiences with double plasma purification (DPP). METHOD: Using Plasauto iQ automatic blood purification system, model KM-9000 for DPP. RESULTS: A total of 603 patients with different entity undergoing 811 purification procedures were included in this study. The most common purification modes were dual filtration plasma plasmapheresis (DFPP). Hyperlipidemia was the lead entity, 423 patients with hyperlipidemia performed DFPP, and two cases of severe acute pancreatitis caused by extremely high triglyceride levels completely recovered after two consecutive DFPP treatments. DFPP combined with immunosuppressants tended to decrease independent HD and reduced HD frequency in 53 patients with antineutrophil cytoplasmic antibody-associated vasculitis. Two patients developed hypotensive or hypoglycemia episodes, respectively, during purification procedures. CONCLUSION: DPP is rapid for the treatment of patients with severe hyperlipidemia and acute pancreatitis caused by severely high triglyceride levels. For those who are intolerant to statins，DPP provides another treatment choice. DPP process is safe.

Clinical characteristics and short-term mortality of 102 hospitalized hemodialysis patients infected with SARS-CoV-2 omicron BA.2.2.1 variant in Shanghai, China.

Background: The aim of this study was to analyze clinical features and short-term mortality in hemodialysis (HD) patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron BA.2.2.1 variant. Methods: In a retrospective single-center case series, 102 consecutive hospitalized HD patients infected with the coronavirus omicron variant were assessed at Pudong Hospital in Shanghai, China, from April 6 to April 18, 2022; the final date of follow-up was May 16, 2022. Clinical, laboratory, chest CT, and treatment data were collected and analyzed. The association between these factors and all-cause mortality was studied using univariate and multivariate analyses. The relationship between lymphocyte count and short-term mortality was based on receiver operating characteristic (ROC) curve analysis. Kaplan-Meier analysis was used to assess overall survival. Results: In total, 102 patients were included in this study. The patients were divided into two groups: HD patients with pneumonia (N = 46) and without pneumonia (N = 56). Of the 102 patients, 12 (11.8%) died. Multivariate regression analysis revealed that all-cause mortality was correlated with lymphocyte counts and type B natriuretic peptide (BNP), C-reactive protein (CRP), and D-dimer levels (P < 0.05). The cut-off value of lymphocyte counts was 0.61 × 109/L for all-cause mortality. The overall survival rate was significantly different between HD patients with and without pneumonia (P < 0.05). Conclusions: Lymphocyte counts are important for the prediction of short-term mortality in HD patients with SARS-CoV-2 infection. HD patients with lung involvement have poorer survival rates than those without lung involvement.

Statin use and the risk of CVD events, stroke, and all-cause mortality in patients with diabetes: A systematic review and meta-analysis.

AIMS: Considering the lack of evidence on statin use and the risk of cardiovascular disease (CVD) in patients with diabetes in primary and secondary prevention, this study aimed to evaluate the effect of statin use in individuals with diabetes for primary and secondary prevention. DATA SYNTHESIS: The MEDLINE, Web of Science, Embase, ClinicalTrials.gov, and Cochrane Central Register for Controlled Trials databases were searched. We included studies that assessed the effect of statin use in individuals with diabetes for at least 1 year. The outcomes included CVD, all-cause mortality, and stroke. A total of 24 studies including 2,152,137 patients with diabetes were included in the meta-analysis. Compared with statin non-users, patients who received statins showed a lower risk of CVD events (primary prevention: risk ratio [RR] = 0.80, 95% confidence interval [CI] 0.69-0.94, P = 0.006; secondary prevention: RR = 0.75, 95% CI 0.65-0.87, P < 0.0001). No association was observed between statin and non-statin users and the risk of all-cause mortality. The pooled results also revealed that statin use reduced the risk of ischemic stroke in patients with diabetes (primary prevention: RR = 0.83, 95% CI 0.70-0.97, P = 0.020; secondary prevention: RR = 0.74, 95% CI 0.63-0.85, P < 0.0001). CONCLUSIONS: Statin use significantly reduced the risk of CVD events and stroke, but not all-cause mortality, in individuals with diabetes undergoing both primary and secondary prevention. More data are required to verify the effects of statins in patients with diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021281132.

Association of the Coexistence of Somnipathy and Diabetes With the Risks of Cardiovascular Disease Events, Stroke, and All-Cause Mortality: A Systematic Review and Meta-analysis.

Background Somnipathy and diabetes are independently associated with an increased risk of cardiovascular disease (CVD). However, whether a combination of both conditions is associated with a higher risk of CVD events remains uncertain. Therefore, the aim of this meta-analysis was to clarify this association. Methods and Results We searched MEDLINE, Web of Science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Controlled Trials. We included randomized controlled trials, nonrandomized trials, and prospective observational cohort studies that assessed the combined effect of diabetes and comorbid somnipathy on CVD risk and mortality for at least 1 year. Outcomes included CVD, coronary heart disease, stroke, and all-cause mortality. Twelve studies involving 582 267 participants were included in the meta-analysis. Patients with somnipathy and comorbid diabetes exhibited increased risks of CVD, coronary heart disease, stroke, and all-cause mortality (risk ratio [RR], 1.27 [95% CI, 1.12-1.45], P<0.0001; RR, 1.40 [95% CI, 1.21-1.62], P<0.0001; RR, 1.28 [95% CI, 1.08-1.52], P=0.004, and RR, 1.56 [95% CI, 1.26-1.94], P<0.0001, respectively). Conclusions The coexistence of somnipathy and diabetes is associated with higher risks of CVD, coronary heart disease, stroke, and mortality than somnipathy or diabetes alone. Resolving sleep problems in patients with diabetes may reduce the risks of CVD, stroke, and mortality. Registration Information https://www.crd.york.ac.uk/prospero/. Identifier: PROSPERO CRD42021274566.

Polyphenol and Anthocyanin Composition and Activity of Highland Barley with Different Colors.

In this research, the composition of free phenols, bound phenols, and anthocyanins and their in vitro antioxidant activity and in vitro α-glucosidase inhibiting activity were observed in different barley colors. The outcomes revealed that the contents of total phenols (570.78 mg/100 gDW), total flavonoids (47.08 mg/100 gDW), and anthocyanins (48.07 mg/100 g) were the highest in purple barley. Furthermore, the structure, composition, and concentration of phenolics differed depending on the colors of barley. The types and contents of bound total phenolic acids and flavonoids were greater than those of free total phenolic acids and flavonoids. The main phenolic acids in blue barley were cinnamic acid polyphenols, whereas in black, yellow, and purple barley, benzoic acid polyphenols were the main phenolic acids, and the main types of flavonoids in black and blue barley were chalcones and flavanones, respectively, whereas flavonol was the main type of flavonoid in yellow and purple barley. Moreover, cornflower pigment-3-glucoside was the major anthocyanin in blue, yellow, and purple barley, whereas the main anthocyanin in black barley was delphinidin-3-glucoside. The dark color of barley indicated richness in the anthocyanins. In addition, the free polyphenol fractions had stronger DPPH and ABTS radical scavenging capacity as compared to the bound ones. In vitro α-glucosidase-inhibiting activity was greater in bound polyphenols than in free polyphenols, with differences between different varieties of barley. Purple barley phenolic fractions had the greatest ABTS radical scavenging and iron ion reduction capacities, as well as the highest α-glucosidase-inhibiting activity. The strongest DPPH radical scavenging capacity was found in yellow barley, while the strongest in vitro α-glucosidase-inhibiting activity was found in anthocyanins isolated from black barley. Furthermore, in different colors of barley, there was a strong association between the concentration of specific phenolic compounds and antioxidant and α-glucosidase-inhibiting activities. The outcomes of this study revealed that all colored barley seeds tested were high in phenolic compounds, and had a good antioxidant impact and α-glucosidase-inhibiting activity. As a result, colored barley can serve as an antioxidant and hypoglycemic food. Polyphenols extracted from purple barley and anthocyanins extracted from black barley stand out among them.

[The Expression and Function of NK Cells in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the expression characteristics of antigens and functional markers of natural killer (NK) cells in patients with acute myeloid leukemia (AML). METHODS: Multi-parameter flow cytometry was used to detect NK cell surface markers and their functional indicators in 56 newly diagnosed AML patients and 24 healthy controls, including activating receptors NKG2D, NKP46, DNAM-1, and killing indicators granzyme B, perforin. RESULTS: Referring to the WHO hematopoiesis and lymph tissue tumor classification criteria, 56 cases were roughly divided into three types: AML M1, M2, and M4/M5. However, there was no differences about NK cells among the three types, so it was no longer subdivided. NK cells were divided into two groups: CD3-CD56hiCD16- (CD56hiNK) and CD3-CD56dimCD16+ (CD56dimNK). Compared with CD56dimNK cell population, except for NKP46, the positive expression levels of NKG2D and other receptors of CD56hiNK cells in AML patients decreased (P<0.001). Compared with healthy controls, the proportion of CD56hiNK cells in AML patients increased, while the number and proportion of NK cells and proportion of CD56dimNK cells significantly decreased (P<0.05). The proportion of perforin in CD56hiNK cells significantly increased (P<0.05). The expression of DNAM-1 in CD56hiNK cells, NKG2D, DNAM-1, and perforin in CD56dimNK cells decreased significantly (P<0.05). There was no statistically significant difference in expression of other functional indexes in AML patients compared with corresponding indexes of healthy controls. In addition, the proportion of CD56hiNK cells was positively correlated with the expression of CD34+ in AML (r=0.303). CONCLUSION: Compared with CD56dimNK, the ratio of CD56hiNK and the expression of functional markers in AML patients are lower. Compared with healthy controls, the number and expression ratio of NK cells in AML patients decrease and the expression of functional markers is abnormal, indicating that its function is impaired.

Plasma Purification Treatment Relieves the Damage of Hyperlipidemia to PBMCs.

Background: Hyperlipidemia {hypercholesterolemia [cholesterol >5.18 mmol/L) or hypertriglyceridemia [triglycerides >2.3 mmol/L], mixed hyperlipidemia [cholesterol >5.18 mmol/L and triglycerides >2.3 mmol/L], and high low-density lipoproteinemia [low-density lipoprotein (LDL) >3.4 mmol/L]} is a strong risk factor for arteriosclerosis and cardiovascular disease (CVD). Therapy with lipid-lowering drugs often results in many side effects. Our study aimed to investigate the potential effects of non-drug therapy with double-filtration plasmapheresis (DFPP) on lipid metabolism-, endoplasmic reticulum (ER) stress-, and apoptosis-related proteins in peripheral blood mononuclear cells (PBMCs) before and after lipid clearance in patients with hyperlipidemia. Methods: Thirty-five hyperlipidemia patients were selected. Proteins related to lipid metabolism [CD36, proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL receptor], ER stress [glucose-regulated protein 78 (Grp78), C/EBP homologous protein (CHOP), activating transcription factor 4 (ATF4), and eukaryotic initiation factor 2α (EIF2α)], and apoptosis [B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (BAX), and cysteinyl aspartate specific proteinase-3 (Caspase-3)] were assayed by Western blot, reactive oxygen species (ROS) were measured by flow cytometry (FCM), and ELISA detected serum inflammatory [interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α)] factors. Results: Compared with their pre-DFPP values, the values of most lipid metabolic parameters, such as cholesterol, triglycerides, LDL, lipoprotein a [Lp(a)], and small dense LDL (sdLDL) cholesterol, were reduced after DFPP. DFPP was associated with the downregulation of proteins related to lipid metabolism, ER stress, and apoptosis, resulting in decreased ROS and serum inflammatory factor release. Conclusion: DFPP has lipid-lowering activity and can also regulate lipid metabolism-, ER stress-, and apoptosis-related proteins in PBMCs and reduce the levels of inflammatory factors in patients with hyperlipidemia (ClinicalTrials.gov number: NCT03491956).

The Effectiveness of Music Therapy on Hand Function in Patients With Stroke: A Systematic Review of Randomized Controlled Trials.

Objective: This study aims to evaluate the efficacy of music-supported therapy for stroke patients' hand function. Methods: The databases used included Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, PubMed, Embase, Music Index, and Google Scholar. Studies published between January 2010 and August 2020 were included. The searching key terms included "music-supported therapy," "music therapy," "hand function," "hand dysfunction," "stroke," "ischemic," and "hemorrhagic." Randomized controlled trials or controlled trials involving adults who have hand function problems caused by stroke are included in this study. The methodological quality and risk of bias of the included studies were rated by two independent assessors under the guidance of Cochrane collaboration's risk of bias tool. Results: Twelve studies that met the inclusion criteria were included in this study. Totally, the data included 598 stroke patients (345 male, 253 female) with recruited time from 1.7 months to 3 years, and the mean age of the participants were 61.09 years old. Based on the Cochrane risk of bias tool, study quality ranged from three to seven out of seven points. Compared with the control group, outcomes including hand strength, range of joint motion, dexterity of hands, arm function, and quality of life were significantly superior with music-supported therapy. Five studies reported improved dexterity of hands, and one study reported the improvement of range of motion and strength of patients' hands, which supported the therapy has positive effects on patients' hand function and improving their quality of life after the therapy. The therapy ranged over a period of 4-8 weeks, with an average duration of 30 min/session and an average of three times per week. Conclusion: Based on the results, music-supported therapy could be a useful treatment for improving hand function and activities of daily living in patients with stroke, especially for patients within 6 months after stroke. However, the low certainty of evidence downgrades our confidence to practice in hospital. More and more randomized controlled trials and larger sample sizes are required for a deeper review.

Identification of differentially expressed genes in diabetic kidney disease by RNA-Seq analysis of venous blood platelets.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. However, because of shared complications between DKD and chronic kidney disease (CKD), the description and characterization of DKD remain ambiguous in the clinic, hindering the diagnosis and treatment of early-stage DKD patients. Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of DKD, early-stage DKD is rarely accompanied by a high estimated glomerular filtration rate, and thus there is a need for new sensitive biomarkers. Transcriptome profiling of kidney tissue has been reported previously, although RNA sequencing (RNA-Seq) analysis of the venous blood platelets in DKD patients has not yet been described. In the present study, we performed RNA-Seq analysis of venous blood platelets from three patients with CKD, five patients with DKD and 10 healthy controls, and compared the results with a CKD-related microarray dataset. In total, 2097 genes with differential transcript levels were identified in platelets of DKD patients and healthy controls, and 462 genes with differential transcript levels were identified in platelets of DKD patients and CKD patients. Through Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, we selected 11 pathways, from which nine potential biomarkers (IL-1B, CD-38, CSF1R, PPARG, NR1H3, DDO, HDC, DPYS and CAD) were identified. Furthermore, by comparing the RNA-Seq results with the GSE30566 dataset, we found that the biomarker KCND3 was the only up-regulated gene in DKD patients. These biomarkers may have potential application for the therapy and diagnosis of DKD, as well aid in determining the mechanisms underlying DKD.

Febuxostat Use and Risks of Cardiovascular Disease Events, Cardiac Death, and All-cause Mortality: Metaanalysis of Randomized Controlled Trials.

OBJECTIVE: To assess whether febuxostat use increases the risk of developing cardiovascular (CV) events, cardiac death, and all-cause mortalities. METHODS: The relevant literature was searched in several databases including MEDLINE (PubMed, January 1, 1966-February 29, 2020), Web of Science, EMBASE (January 1, 1974-February 29, 2020), ClinicalTrials. gov, and Cochrane Central Register of Controlled Trials. Manual searches for references cited in the original studies and relevant review articles were also performed. All studies included in this metaanalysis were published in English. RESULTS: In the end, 20 studies that met our inclusion criteria were included in our metaanalysis. Use of febuxostat was found not to be associated with an increased risk of all-cause mortality (RR 0.87, 95% CI 0.57-1.32, P = 0.51). Also, there was no association between febuxostat use and mortalities arising from CV diseases (CVD; RR 0.84, 95% CI 0.49-1.45, P = 0.53). The RR also revealed that febuxostat use was not associated with CVD events (RR 0.98, 95% CI 0.83-1.16, P = 0.83). Further, the likelihood of occurrence of CVD events was found not to be dependent on febuxostat dose (RR 1.04, 95% CI 0.84-1.30, P = 0.72). CONCLUSION: Febuxostat use is not associated with increased risks of all-cause mortality, death from CVD, or CVD events. Accordingly, it is a safe drug for the treatment of gout.

Pyruvate-Enriched Oral Rehydration Solution Improves Glucometabolic Disorders in the Kidneys of Diabetic db/db Mice.

Diabetes is prevalent worldwide, but ideally intensive therapeutic strategy in clinical diabetes and diabetic nephropathy (DN) is still lack. Pyruvate is protective from glucometabolic disturbances and kidney dysfunction in various pathogenic insults. Present studies focused on oral pyruvate effects on diabetes status and DN with 0.35% pyruvate in pyruvate-enriched oral rehydration solution (Pyr-ORS) and 1% pyruvate as drinking water for 8 weeks, using the model of diabetic db/db mice. Both Pyr-ORS and 1% pyruvate showed comparable therapeutic effectiveness with controls of body weight and blood sugar, increases of blood insulin levels, and improvement of renal function and pathological changes. Aberrant key enzyme activities in glucometabolic pathways, AR, PK, and PDK/PDH, were also restored; indexes of oxidative stress and inflammation, NAD+/NADH ratio, and AGEs in the kidneys were mostly significantly preserved after pyruvate treatments. We concluded that oral pyruvate delayed DN progression in db/db mice and the modified Pyr-ORS formula might be an ideal novel therapeutic drink in clinical prevention and treatment of type 2 diabetes and DN.

EGCG Attenuates Renal Damage via Reversing Klotho Hypermethylation in Diabetic db/db Mice and HK-2 Cells.

To explore whether epigallocatechin-3-gallate (EGCG) improves renal damage in diabetic db/db mice and high-glucose- (HG-) induced injury in HK-2 cells by regulating the level of Klotho gene promoter methylation. Western blotting was used to detect the protein expression levels of DNA methyltransferase 1 (DNMT1), DNMT3a, DNMT3b, transforming growth factor-ß1 (TGF-ß1), α-smooth muscle actin (α-SMA), and Klotho. The methylation level of the Klotho gene promoter was detected by pyrosequencing. Chromatin immunoprecipitation was used to detect the binding of the Klotho gene promoter to DNMT1 and DNMT3a. The expression of oxidative stress markers (reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)) and inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α)) in kidney homogenates was also measured using ELISA. Klotho and DNMT3b protein expression was upregulated, while DNMT1, DNMT3a, TGF-ß1, and α-SMA protein expression was downregulated after EGCG treatment. EGCG treatment also reduced the methylation level of the Klotho gene promoter as well as the binding of DNMT3a to the Klotho gene promoter. In addition, EGCG treatment significantly decreased the levels of ROS, MDA, 8-OHdG, IL-1ß, IL-6, and TNF-α and increased the levels of CAT and SOD. Under HG conditions, EGCG regulated Klotho gene promoter methylation via DNMT3a and decreased the methylation level of the Klotho gene promoter, thereby upregulating the expression of the Klotho protein to exert its protective effect.

Pyruvate alleviates high glucose-induced endoplasmic reticulum stress and apoptosis in HK-2 cells.

Endoplasmic reticulum (ER) stress plays a critical role in the development of diabetic nephropathy (DN). We previously demonstrated that pyruvate (Pyr)-enriched oral rehydration solution improved glucometabolic disorders and ameliorated DN outcome in db/db mice. Here, we investigated the effects of Pyr on high glucose-induced ER stress and apoptosis in HK-2 cells. Our results suggest that high glucose can induce reactive oxygen species production, apoptosis and ER stress in HK-2 cells, and that Pyr treatment can ameliorate these effects and restore the expression of key proteins involved in ER stress. Thus, Pyr may have potential for the development of novel strategies for the prevention and treatment of clinical DN.

Suicide in Chinese Graduate Students: A Review From 2000 to 2019.

Suicide is an important public problem in China. The characteristics of Chinese graduate students' suicides and the reasons they occur have never been reported systematically. We conducted a systematic search of public reports on local media and medical websites in this review to gain a basic understanding of these questions. A total of 150 cases of graduate students' suicides were reported from 2000 to 2019. Among the 150 students, 65.8% were male, nearly half between 26 and 30 years old, most (83.3%) never married, and 43.4% of graduation students committed suicide in graduation year and postponed years. The top three suicide methods were jumping, hanging, and drowning. Graduation pressure, depression, and academic pressure were the three leading suicidal causes. There is an urgent need for the Chinese government and universities to pay more attention to prevent suicides among graduate students.