Efficacy of Urate-Lowering Therapy in Patients With Chronic Kidney Disease: A Network Meta-Analysis of Randomized Controlled Trials.

PURPOSE: The goal of this study was to systematically review the efficacy and safety of urate-lowering therapy in patients with chronic kidney disease (CKD). METHODS: PubMed, the Cochrane Central Registration of Controlled Trials, and EMBASE databases and several websites were electronically searched to collect randomized clinical trials on the efficacy of urate-lowering therapy in CKD from inception to December 31, 2020. The key primary end points were uric acid or estimated glomerular filtration rate (eGFR) levels; the safety end points were death, renal event, cardiovascular event, and gastrointestinal event. A Bayesian network meta-analysis was conducted with the use of ADDIS and R software. FINDINGS: A total of 17 randomized clinical trials involving 2059 patients were included. The results of network meta-analysis showed that urate-lowering therapy could reduce urate levels in patients with CKD. Febuxostat was the most effective treatment in lowering urate levels according to the rank probability. Urate-lowering therapy has the tendency to delay the decline of eGFR, but the difference was not statistically significant. Ranking probability showed that benzbromarone, febuxostat, and allopurinol ranked higher than placebo in reducing the decline of eGFR. There were no statistically significant differences between groups in the incidence of all adverse effects. IMPLICATIONS: All urate-lowering therapies could reduce the urate level in patients with CKD, but the benefit of such therapy in renal disease is still unclear. PROSPERO identifier: CRD42020222601.

Chinese Herbal Medicine Suyin Detoxification Granule Inhibits Pyroptosis and Epithelial-Mesenchymal Transition by Downregulating MAVS/NLRP3 to Alleviate Renal Injury.

PURPOSE: Proteinuria is an independent risk factor of chronic kidney disease (CKD). Albumin-induced tubulointerstitial inflammation and epithelial-mesenchymal transition (EMT) via the activation of NLRP3 inflammasome is a potential therapeutic target for CKD. Suyin Detoxification Granule (SDG) improves proteinuria and postpones renal failure. However, the underlying mechanism is still unknown. METHODS: Firstly, the rat model of renal failure was established using intragastric administration of adenine. Renal function, proteinuria, inflammatory indicators in serum, and renal pathology were assessed, and renal immunohistochemical staining of NLRP3 inflammasomes was performed after intervention with low and high concentrations of SDG. Secondly, the model of renal tubular epithelial HK-2 cells was established using albumin in vitro, and the cell viability, EMT phenotype, and the expression of proteins in the NLRP3 inflammasome signaling pathway were measured after the freeze-dried powder of Suyin Detoxification Prescription (SDP) and CY-09, which is a selective and direct NLRP3 inhibitor, were co-incubated with albumin. ATP, SOD, mitochondrial membrane potential, and ROS were further measured in vitro, and changes in the mitochondrial function after SDP intervention were observed. The mitochondrial antiviral signaling protein (MAVS) was knocked down using siRNA, and the interaction between MAVS and NLRP3 was verified using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. RESULTS: SDG improved renal function and proteinuria, alleviated renal fibrosis, and reduced serum inflammation and the expression of the components of the NLRP3 inflammasome in the kidney. In vitro, SDP and CY-09 enhanced cell viability after injury with albumin and inhibited pyroptosis induced by the NLRP3 inflammatory signaling pathway and expression of proteins involved in EMT. It was further found that SDP alleviated the mitochondrial dysfunction caused by albumin. The knockdown of MAVS reduced the expression of NLRP3 pathway proteins and their mRNA levels and also weakened the co-localization of NLRP3, thus, reducing cell pyroptosis. CONCLUSION: SDP protected renal tubular epithelial cells from cell pyroptosis and EMT by regulating the albumin-induced mitochondrial dysfunction/ MAVS/ NLRP3-ASC-caspase-1 inflammasome signaling pathway.

Changes in clinical trials of endocrine disorder and metabolism and nutrition disorder drugs in mainland China over 2010-2019.

With the improvements in relevant policies, laws, and regulations regarding drug clinical trials in China, the quantity and quality of drug clinical trials have gradually improved, and the development prospects of drug clinical trials for endocrine disorders and metabolism and nutrition disorders are promising. Based on information from the clinical trials from the online drug clinical trial registration platform of the National Medical Products Administration, we aimed to review and evaluate the development of clinical trials of drugs for endocrine disorders and metabolism and nutrition disorders in mainland China from 2010 to 2019, as well as the trends over time. A total of 861 trials were carried out on 254 types of drugs for endocrine disorders and metabolism and nutrition disorders, among which 531 (61.67%) involved endocrine disorders, and 330 (38.33%) addressed metabolism and nutrition disorders. The annual number of clinical trials has been increasing gradually, with a significant increase in 2017. Among them, the proportion of clinical trials with Chinese epidemiological characteristics was relatively large (Wu, Annual Report on Development Health Management and Health Industry in China, 2018). The largest number of trials were for diabetes drugs (55.63%), followed by trials of drugs for hyperlipidemia (19.4%) and those for hyperuricemia (7.9%). It was found that the geographical area of the leading units also showed obvious unevenness according to the analysis of the test unit data. Based on the statistics and evaluation of the data, comprehensive information is provided to support the cooperation of global pharmaceutical R&D companies and research units in China and the development of international multicenter clinical trials in China. This work additionally provides clinical trial units with a self-evaluation of scientific research competitiveness and hospital development strategies. At the same time, it provides a reference with basic data for sponsors and stakeholders in these trials to determine their development strategy goals.

The Efficacy of Tai Chi and Qigong Exercises on Blood Pressure and Blood Levels of Nitric Oxide and Endothelin-1 in Patients with Essential Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Tai Chi and Qigong are the two similar traditional Chinese wellness exercises. A strong body of published clinical randomized controlled trials (RCTs) has investigated the health benefits of Tai Chi and Qigong exercises (TCQE) in patients with essential hypertension (EH). This is the first meta-analysis to evaluate the efficacy of TCQE on blood pressure (BP) and blood levels of nitric oxide (NO) and endothelin-1 (ET-1) in EH patients and explore the potential antihypertensive mechanism of TCQE. METHODS: We conducted a literature retrieval for Chinese and English studies in seven databases from their respective inceptions until January 14, 2020. All RCTs examining clinical efficacy of TCQE for EH patients were considered. The major therapeutic outcomes of TCQE were changes in the blood levels of NO, ET-1, and BP in EH patients. Methodological quality of the included RCTs was detected via The Cochrane Risk of Bias tool. We evaluated the data reported and performed the meta-analysis by Review Manager 5.3 software. RESULTS: 9 RCTs involving 516 EH patients were included. The intervention duration lasted from 1.5 months to 6 months. The results of comprehensive analysis showed that compared with control interventions, experimental interventions were more effective in reducing the systolic blood pressure and the diastolic blood pressure and contributed higher blood levels of NO and lower blood levels of ET-1. CONCLUSIONS: TCQE could be an effective complementary and alternative therapy for EH. The lower BP in EH patients who practice TCQE may have some connection with exercise-related increased blood NO levels and decreased blood ET-1 levels. However, further research is needed to make clear the efficacy of TCQE in management of EH and the mechanism of lowering BP in TCQE.

[Effects of electroacupuncture on urinary bladder function after radical hysterectomy].

OBJECTIVE: To observe the effect of electroacupuncture on recovery of urinary bladder function after radical hysterectomy. METHODS: One hundred and ten cases were randomly divided into an electroacupuncture (EA) group and a control group, 55 cases in each group. In the control group, the urinary tube was placed and kept with routine method and the urinary bladder was rinsed, and from the eighth day the abdomen was radiated with TDP, 30 min each day, for 5 days. In the EA group, on the basis of treatment in the control group EA was given at Sanyinjiao (SP 6), Zusanli (ST 36), Waiguan (TE 5), Shuidao (ST 28), Guilai (ST 29), etc. from the eighth day to twelfth day after operation. The recovery time of urinary bladder function after radical hysterectomy, urine dynamic indexes and hospitalization days were compared between the two groups. RESULTS: The cases of the bladder function recovery, retention of urine, urinary incontinence were 51(51/55), 4(4/55), 0 on the 14 th day after operation and 53(53/55), 2(2/55), 0 on the 28 th day in the EA group, and 27(27/55), 25(25/55), 3(3/55) on the 14 th day and 43(43/55), 11(11/55), 1(1/55) on the 28th day in the control group, respectively, with a very significant difference between the two groups (P < 0.01); the EA group in residual urine volume, bladder volume, mean urinary flowing rate was better than the control group on the 14 th day after operation (P < 0.01 or P < 0.05); the hospitalization days after operation was (21.1 +/- 3.3) days in the EA group and (25.5 +/- 3.5) days in the control group, the former being shorter than the later (P < 0.01). CONCLUSION: EA can promote recovery of bladder function, shorten the keeping time of urinary tube after radical hysterectomy, which is benefit to decreasing incidence rate of urinary system infection and shortening hospitalization days.