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Introduction: Sodium zirconium cyclosilicate (SZC) is a nonabsorbed cation-exchanger approved in China for the treatment of hyperkalemia [HK; serum potassium (sK+) levels >5.0 mmol/L]. This is the first real-world study aimed to assess the effectiveness, safety, and treatment patterns of SZC in Chinese patients with HK. Here we present the results of the first interim analysis.Methods: This multicenter, prospective, cohort study included patients aged ≥18 years with documented HK within 1-year before study enrollment day. These patients were followed up for 6 months from the enrollment day after initiating SZC treatment. The treatment was categorized into correction phase (FAS-P1) and maintenance phase (FAS-P2 new and ongoing users). Subgroup analysis was performed in patients on hemodialysis (FAS-H). The primary objective was evaluation of safety profile of SZC; secondary objectives included assessment of treatment patterns of SZC and its effectiveness.Results: Of 421 screened patients, 193, 354, and 162 patients were enrolled in the FAS-P1, FAS-P2, and FAS-H groups, respectively. sK+ levels were reduced significantly from 5.9 mmol/L to 5.0 mmol/L after the correction phase. For the maintenance phase, the mean sK+ levels were maintained at 5.2 mmol/L and 5.0 mmol/L in the FAS-P2 new and ongoing user, respectively, and 5.3 mmol/L in the FAS-H subgroup. A considerable proportion of patients showed normokalemia after 48 h of SZC treatment (FAS-P1:51.3%) which was maintained up to 6 months in the maintenance phase (FAS-P2:44%). SZC was well-tolerated.Conclusion: SZC was effective and safe for the treatment of HK in real-world clinical practice in China.

Background: Uveal melanoma (UVM) is a primary intraocular malignancy that poses a significant threat to patients’ visual function and life. The basement membrane (BM) is critical for establishing and maintaining cell polarity, adult function, embryonic and organ morphogenesis, and many other biological processes. Some basement membrane protein genes have been proven to be prognostic biomarkers for various cancers. This research aimed to develop a novel risk assessment system based on BMRGs that would serve as a theoretical foundation for tailored and accurate treatment.Methods: We used gene expression profiles and clinical data from the TCGA-UVM cohort of 80 UVM patients as a training set. 56 UVM patients from the combined cohort of GSE84976 and GSE22138 were employed as an external validation dataset. Prognostic characteristics of basement membrane protein-related genes (BMRGs) were characterized by Lasso, stepwise multifactorial Cox. Multivariate analysis revealed BMRGs to be independent predictors of UVM. The TISCH database probes the crosstalk of BMEGs in the tumor microenvironment at the single-cell level. Finally, we investigated the function of ITGA5 in UVM using multiple experimental techniques, including CCK8, transwell, wound healing assay, and colony formation assay.Results: There are three genes in the prognostic risk model (ADAMTS10, ADAMTS14, and ITGA5). After validation, we determined that the model is quite reliable and accurately forecasts the prognosis of UVM patients. Immunotherapy is more likely to be beneficial for UVM patients in the high-risk group, whereas the survival advantage may be greater for UVM patients in the low-risk group. Knockdown of ITGA5 expression was shown to inhibit the proliferation, migration, and invasive ability of UVM cells in vitro experiments.Conclusion: The 3-BMRGs feature model we constructed has excellent predictive performance which plays a key role in the prognosis, informing the individualized treatment of UVM patients. It also provides a new perspective for assessing pre-immune efficacy.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects.Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.

Osteoarthritis (OA) is a degenerative disease found in middle-aged and elderly people, which seriously affects their quality of life. The anti-inflammatory and anti-apoptosis pharmacological effects of salvianolic acid A (SAA) have been shown in many studies. In this study, we intended to explore the anti-inflammatory and anti-apoptotic effects of SAA in OA. We evaluated the expression of pro-inflammatory mediators and cartilage matrix catabolic enzymes in chondrocytes by ELISA, Griess reaction, immunofluorescence, and Western blot, which includes nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), MMPs (MMP-3, MMP-13), and ADAMTS-5. Bax, Bcl-2, and cleaved caspase-3 were also measured by Western blot methods. The results of this experiment in vitro showed that SAA not only inhibited the production of inflammatory mediators induced by IL-1β and the loss of cartilage matrix but also reduced the apoptosis of mouse chondrocytes induced by IL-1β. According to the results of immunofluorescence and Western blot, SAA inhibited the activation of the NF-κB pathway and MAPK pathway. The results of these in vitro experiments revealed for the first time that SAA down-regulated the production of inflammatory mediators and inhibited the apoptosis of mouse chondrocytes and the degradation of extracellular matrix (ECM), which may be attributed to the inhibition of the activation of NF-κB and MAPK signaling pathways. In the in vivo experiments, 45 mice were randomly divided among three groups (the sham group, OA group, and OA + SAA group). The results of animal experiments showed that SAA treatment for eight consecutive weeks inhibited further deterioration of OA. These results demonstrate that SAA plays an active therapeutic role in the development of OA.

Mesangial proliferative glomerulonephritis (MPGN) is the most common type of chronic kidney disease in China, characterized by mesangial cell proliferation and inflammatory response. Paeoniflorin, an effective composition extracted from Radix Paeoniae Alba, has been used for various kinds of kidney diseases. However, there are no studies reporting the effects of paeoniflorin on MPGN. The present study aims to investigate whether paeoniflorin plays a role in MPGN and confirm the underlying molecular mechanisms. Our results manifested that paeoniflorin strongly restrained 24 h urinary protein and promoted renal function and dyslipidemia in a MPGN rat model. Moreover, paeoniflorin attenuated mesangial cell proliferation and inflammation both in MPGN rats and human mesangial cells (HMCs) treated with lipopolysaccharide (LPS). In detail, paeoniflorin decreased the number of mesangial cells and expressions of proliferation marker Ki67 in MPGN rats. Paeoniflorin also inhibited HMC proliferation and blocked cell cycle progression. In addition, the contents of inflammatory factors and the expressions of macrophage marker iNOS were decreased after paeoniflorin treatment. Furthermore, we found that the protective effect of paeoniflorin was accompanied by a strong inhibition of the phosphatidylinositol 3-kinase (PI3K)/AKT/glycogen synthase kinase (GSK)-3β pathway. Paeoniflorin enhanced the inhibitory effect of PI3K inhibitor LY294002 and suppressed the activated effect of PI3K agonist insulin-like growth factor 1 (IGF-1) on PI3K/AKT/GSK-3β pathway. In conclusion, these results demonstrated that paeoniflorin ameliorates MPGN by inhibiting mesangial cell proliferation and inflammatory response through the PI3K/AKT/GSK-3β pathway.