Causal relationship between rheumatoid arthritis and epilepsy in a European population: a univariate and multivariate Mendelian randomization study.

Background: Several previous studies have reported an association between rheumatoid arthritis (RA) and epilepsy, but the causal relationship is unclear. The aim of this study was to assess the connection between RA and epilepsy in a European population using Mendelian randomization (MR).

Methods: Genome-wide association study summary data on RA and epilepsy from European populations were included.

Discovery of the Highly Selective and Potent STAT3 Inhibitor for Pancreatic Cancer Treatment.

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Unfortunately, targeting STAT3 with small molecules has proven to be very challenging, and for full activation of STAT3, the cooperative phosphorylation of both tyrosine 705 (Tyr705) and serine 727 (Ser727) is needed. Further, a selective inhibitor of STAT3 dual phosphorylation has not been developed.

Interpretable prediction model for assessing diabetes complication risks in Chinese sufferers.

Aims: With growing concerns over complications in diabetes sufferers, this study sought to develop an interpretable machine learning model to offer enhanced diagnostic and treatment recommendations.

Methods: We assessed coronary heart disease, diabetic nephropathy, diabetic retinopathy, and fatty liver disease using logistic regression, decision tree, random forest, and CatBoost algorithms. The SHAP algorithm was employed to elucidate the model's predictions, offering a more in-depth understanding of influential features.

Prediction of musculoskeletal pain after the first intravenous zoledronic acid injection in patients with primary osteoporosis: development and evaluation of a new nomogram.

Objective: To construct a new prediction nomogram to predict the risk of musculoskeletal pain in patients with primary osteoporosis who receive zoledronic acid intravenously for the first time.

Method: Clinical data of 368 patients with primary osteoporosis who received the first intravenous injection of zoledronic acid in our hospital from December 2019 to December 2022 were studied. Patients were divided into a musculoskeletal pain group (n = 258) and a non-musculoskeletal pain group (n = 110) based on the presence or absence of musculoskeletal pain 3 days after injection.

Operational and Intervention Effects of Targeted Tuina in Lumbar Intervertebral Disc Degeneration Model Rabbits.

Tui Na or massage therapy alleviates symptoms related to intervertebral disc degeneration (IDD). However, precise, repeatable, standardized instructions for Tuina manipulation are lacking. This study establishes IDD model rabbits induced by fibrous ring puncture, creates targeted Tuina stimulation protocols at the acupuncture points in the lumbar region, and describes in detail the operation methods and requirements of kneading, pointing, and flicking.

Effects of acupuncture on cartilage p38MAPK and mitochondrial pathways in animal model of knee osteoarthritis: A systematic evaluation and meta-analysis.

Background: Most previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms have not been systematically reviewed. Acupuncture modulates cytokines to attenuate cartilage extracellular matrix degradation and apoptosis, key to the pathogenesis of KOA, but the mechanisms are complex.

Objectives: The purpose of this study is to assess the efficacy of acupuncture quantitatively and summarily in animal studies of KOA.

Selectively Targeting STAT3 Using a Small Molecule Inhibitor is a Potential Therapeutic Strategy for Pancreatic Cancer.

Purpose: Pancreatic cancer is the worst prognosis among all human cancers, and novel effective treatments are urgently needed. Signal transducer and activator of transcription 3 (STAT3) has been demonstrated as a promising target for pancreatic cancer. Meanwhile, selectively targeted STAT3 with small molecule remains been challenging.

Discovery of a Highly Potent and Orally Bioavailable STAT3 Dual Phosphorylation Inhibitor for Pancreatic Cancer Treatment.

Increasing evidence has demonstrated that STAT3 phosphorylation at Tyr and Ser is closely associated with the progression and poor prognosis of pancreatic cancer. Herein, we report the function-based screening, SAR studies, and biological activity evaluation of a series of novel STAT3 dual phosphorylation inhibitors with an indole-containing tetra-aromatic heterocycle scaffold. Our efforts led to the discovery of optimal compound among the investigated ones, showing desirable ADME properties and highly potent antitumor activities and .

Discovery of a Novel Potent STAT3 Inhibitor HP590 with Dual p-Tyr/Ser Inhibitory Activity for Gastric Cancer Treatment.

Accumulating evidence has documented that STAT3 phosphorylation at Tyr and Ser jointly promotes the initiation and progression of gastric cancer. However, most reported STAT3 inhibitors have mainly focused on suppressing STAT3 phosphorylation at Tyr while ignoring the tumorigenic effects of phosphorylation at Ser. Herein, we described the design, synthesis, and structure-activity relationship studies on a series of triaromatic heterocyclic derivatives as potent dual phosphorylation STAT3 inhibitors.

A novel small-molecule activator of unfolded protein response suppresses castration-resistant prostate cancer growth.

Androgen receptor-targeted therapy improves survival in castration-resistant prostate cancer (CRPC). However, almost all patients with CRPC eventually develop secondary resistance to these drugs. Therefore, alternative therapeutic approaches for incurable metastatic CRPC are urgently needed.