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The IBTIS score; a new prognostic rating for arthroscopic arms tenotomies.
We pooled database-specific estimates through random effects meta-analysis. Results Our study overall included 2.6 and 0.46 million users of alpha-1 blockers and of alternative BPH medications. We observed no significant difference in their risks for any of the COVID-19 outcomes, with our meta-analytic HR estimates being 1.02 (95% CI 0.92-1.13) for diagnosis, 1.00 (95% CI 0.89-1.13) for hospitalization, and 1.15 (95% CI 0.71-1.88) for hospitalization requiring intensive services. Conclusion We found no evidence of the hypothesized reduction in risks of the COVID-19 outcomes from the prevalent-use of alpha-1 blockers-further research is needed to identify effective therapies for this novel disease.Angong Niuhuang Pill (ANP) is a famous traditional Chinese patent medicine and is used for treating ischemic or hemorrhagic stroke for centuries. However, the mechanism of action of ANP in stroke treatment has rarely been reported. With increasing evidence for a mechanistic link between acute ischemic stroke and gut microbiota alterations, this study aimed to determine the mechanism of action of ANP in treating acute ischemic stroke from the perspective of the gut microbiota. A mouse model of acute ischemic stroke by middle cerebral artery occlusion (MCAO) was established, and 16S ribosomal RNA (rRNA) gene sequencing and metabolomic analysis were performed on the cecal content samples collected from the sham, model, and ANP-treated MCAO mice. The results showed that ANP significantly ameliorated cerebral infarct volume, improved neurological deficits, and reduced histopathological injuries in the ipsilateral ischemic cortex, hippocampus, and striatum. The latter effects included inhibition of neuronal death, dus, Roseburia, Lachnospiraceae_UCG-006, and Colidextribacter might be a potential anti-stroke therapy.The voltage-gated potassium channel, KV11.1, encoded by the human Ether-à-go-go-Related Gene (hERG), is expressed in cardiac myocytes, where it is crucial for the membrane repolarization of the action potential. Gating of the hERG channel is characterized by rapid, voltage-dependent, C-type inactivation, which blocks ion conduction and is suggested to involve constriction of the selectivity filter. Mutations S620T and S641A/T within the selectivity filter region of hERG have been shown to alter the voltage dependence of channel inactivation. Because hERG channel blockade is implicated in drug-induced arrhythmias associated with both the open and inactivated states, we used Rosetta to simulate the effects of hERG S620T and S641A/T mutations to elucidate conformational changes associated with hERG channel inactivation and differences in drug binding between the two states. Rosetta modeling of the S641A fast-inactivating mutation revealed a lateral shift of the F627 side chain in the selectivity filter into the central channel axis along the ion conduction pathway and the formation of four lateral fenestrations in the pore. Rosetta modeling of the non-inactivating mutations S620T and S641T suggested a potential molecular mechanism preventing F627 side chain from shifting into the ion conduction pathway during the proposed inactivation process. Furthermore, we used Rosetta docking to explore the binding mechanism of highly selective and potent hERG blockers - dofetilide, terfenadine, and E4031. Our structural modeling correlates well with much, but not all, existing experimental evidence involving interactions of hERG blockers with key residues in hERG pore and reveals potential molecular mechanisms of ligand interactions with hERG in an inactivated state.Background Everolimus is one of the key drugs for the treatment of advanced breast cancer. The optimal target concentration range for everolimus therapy in patients with breast cancer has not yet been established. This study aimed to characterize everolimus pharmacokinetics (PK) and determine the relationship between blood concentration and efficacy as well as adverse events in patients with breast cancer. Methods This was a prospective, observational PK study. Patients receiving everolimus between November 2015 and November 2018 at our hospital were enrolled in this study. The whole blood samples for the everolimus assay were collected at least two weeks after initiation of treatment or the last everolimus dose change. PK parameters were estimated using Bayesian analysis. Statistical differences in everolimus trough concentrations between patient cohorts were assessed using the Mann-Whitney test. Progression-free survival was assessed using the Kaplan-Meier method and the log-rank test. Results Eighteen patimus and subsequent dose adjustments will potentially reduce side effects and enhance the therapeutic effect in Japanese patients with advanced breast cancer.Sepsis is a heterogenous and highly complex clinical syndrome, which is caused by infectious or noninfectious factors. Acute kidney injury (AKI) is one of the most common and severe complication of sepsis, and it is associated with high mortality and poor outcomes. Recent evidence has identified that autophagy participates in the pathophysiology of sepsis-associated AKI. Despite the use of antibiotics, the mortality rate is still at an extremely high level in patients with sepsis. Besides traditional treatments, many natural products, including phytochemicals and their derivatives, are proved to exert protective effects through multiple mechanisms, such as regulation of autophagy, inhibition of inflammation, fibrosis, and apoptosis, etc. Accumulating evidence has also shown that many pharmacological inhibitors might have potential therapeutic effects in sepsis-induced AKI. Hence, understanding the pathophysiology of sepsis-induced AKI may help to develop novel therapeutics to attenuate the complications of sepsis and lower the mortality rate. This review updates the recent progress of underlying pathophysiological mechanisms of sepsis-associated AKI, focuses specifically on autophagy, and summarizes the potential therapeutic effects of phytochemicals and pharmacological inhibitors.The incidence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly worldwide; however, there are currently limited treatments for NAFLD. The disease spectrum includes simple fatty liver, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and progression to hepatocellular carcinoma (NASH-HCC). The therapeutic effects of NAFLD remain controversial. Although researchers have conducted studies on the pathogenesis of NAFLD, its pathogenesis and anti-NAFLD mechanisms have not been fully elucidated. Previous studies have found that flavonoids, as natural substances with extensive pharmacological activity and good therapeutic effects, have excellent antioxidant, anti-inflammatory, metabolic disease improvement, anti-tumor, and other properties and can significantly alleviate NAFLD. Flavonoids could be further developed as therapeutic drugs for NAFLD. In this paper, the pathogenesis of NAFLD and the mechanisms of flavonoids against NAFLD are summarized to provide a theoretical basis for screening flavonoids against non-alcoholic liver injury.Diabetic kidney disease (DKD) is one of the major causes of end-stage renal disease (ESRD). To evaluate the efficacy and safety of different types of mineralocorticoid receptor antagonists (MRAs) in diabetic kidney disease patients, we conducted this network meta-analysis by performing a systematic search in PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane Library, and Clinicaltrials.gov. A total of 12 randomized clinical trials with 15,492 patients applying various types of MRAs covering spironolactone, eplerenone, finerenone, esaxerenone, and apararenone were included. ALK inhibitor The efficacy outcomes were the ratio of urine albumin creatine ratio (UACR) at posttreatment vs. at baseline, change in posttreatment estimated glomerular filtration (eGFR) vs. at baseline, and change in posttreatment systolic blood pressure (SBP) vs. at baseline. The safety outcome was the number of patients suffering from hyperkalemia. High-dose finerenone (MD -0.31, 95% CI -0.52, -0.11), esaxerenone (MD -0.54, 95% CI -0.72, -0.30), and apararenone (MD -0.63, 95% CI -0.90, -0.35) were associated with a superior reduction in proteinuria in patients with DKD. Regarding the change in eGFR, the results of all drugs were similar, and finerenone may have potential superiority in protecting the kidney. Compared with placebo, none of the treatments was associated with a higher probability of controlling systolic blood pressure during treatment. Moreover, spironolactone, esaxerenone, and 20 mg of finerenone presented a higher risk of hyperkalemia. This Bayesian network meta-analysis was the first to explore the optimal alternative among MRAs in the treatment of DKD and revealed the superiority of 20 mg of finerenone among MRAs in treating DKD. Systematic Review Registration PROSPERO, identifier (CRD42022313826).Atherosclerosis (AS) and the accompanied cardiovascular diseases (CVDs) were the leading cause of death worldwide. Recently, the association between CVDs, gut microbiota, and metabolites had aroused increasing attention. In the study, we headed our investigation into the underlying mechanism of ginsenoside Rc (GRc), an active ingredient of ginsenosides used for the treatment of CVDs, in apolipoprotein E-deficient (ApoE-/-) mice with high-fat diet (HFD). Seven-week-old male ApoE-/- mice were randomly divided into four groups the normal control (NC) group, the HFD group, the GRc group (40 mg/kg/d), and the atorvastatin (Ato) group (10 mg/kg/d). Atherosclerotic injury was evaluated by aortic lesions, serum lipid levels, and inflammatory factors. The composition of gut microbiota and fecal metabolite profile were analyzed using 16S rRNA sequence and untargeted metabolomics, respectively. The results showed that GRc significantly alleviated HFD-induced aortic lesions, reduced serum levels of total cholesterol (TC)ry, regulated microbial and metabolomic changes in HFD-induced ApoE-/- mice, and suggested a potential correlation among gut microbiota, metabolites, and atherosclerotic injury regarding the mechanisms of GRc against AS.Background Mesalazine is the first-line inflammatory bowel disease (IBD) treatment. However, it can cause fatal cardiotoxicity. We aimed to analyze the clinical characteristics of mesalazine-induced cardiotoxicity and provide evidence for clinical diagnosis, treatment, and prevention. Methods We collected Chinese and English literature on mesalazine-induced cardiotoxicity from 1970 to 2021 for retrospective analysis. Results A total of 52 patients (40 males and 12 females) were included, with a median age of 24.5 years (range 9-62) and a median onset time of 14 days (range 2-2880). Cardiotoxicity manifested as myocarditis, pericarditis, and cardiac pericarditis. The main clinical manifestations are chest pain (82.7%), fever (46.2%), and respiratory symptoms such as dyspnea and cough (40.4%). The levels of troponin T, creatine kinase, C-reactive protein, leukocyte count, erythrocyte sedimentation rate, and other biochemical markers were significantly increased. Cardiac imaging often suggests myocardial infarction, pericardial effusion, myocardial necrosis, and other symptoms of cardiac injury. It is essential to discontinue mesalamine immediately in patients with cardiotoxicity. Although corticosteroids are a standard treatment option, the benefits remain to be determined. Re-challenge of mesalamine should be carefully considered as cardiotoxic symptoms may reoccur. Conclusion Mesalazine may cause cardiotoxicity in patients with inflammatory bowel disease, which should be comprehensively diagnosed based on clinical manifestations, biochemical indicators, and cardiac function imaging examinations. Mesalazine should be immediately discontinued, and corticosteroids may be an effective treatment for cardiotoxicity.
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