Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study.

Background: To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate.

Methods: In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion.

Circ_0066881 targets miR-144-5p/RORA axis to alleviate LPS-induced apoptotic and inflammatory damages in human periodontal ligament cells.

Circular RNAs (circRNAs) are involved in the regulation of various diseases, including periodontitis. The objective of this study was to analyze the biological role and regulatory mechanism of circ_0066881 in LPS-induced periodontal ligament cells (PDLCs). Circ_0066881, microRNA-144-5p (miR-144-5p) and retinoid acid-related orphan receptor A (RORA) levels were determined using reverse transcription-quantitative PCR (RT-qPCR) assay.

A potential model of systemic sclerosis with pulmonary hypertension induced by monocrotaline plus bleomycin.

Objective: The lack of a well-established animal model limits the clarification of the detailed mechanisms of the pathogenesis of systemic sclerosis with pulmonary hypertension (SSc-PH) and the development of effective treatments for it.

Methods: In this study, New Zealand rabbits were injected with monocrotaline (MCT), bleomycin (BLM), and MCT plus BLM, respectively. Three and six weeks after the first injection, the mean pulmonary artery pressure (mPAP) was measured.

Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D.

Dorzagliatin add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone.

The efficacy and safety of keverprazan, a novel potassium-competitive acid blocker, in treating erosive oesophagitis: a phase III, randomised, double-blind multicentre study.

Background: Keverprazan is a novel potassium-competitive acid blocker (P-CAB) with a strong acid-suppressive capacity that may provide clinical benefit in acid-related diseases.

Aims: This study aimed to explore the non-inferior efficacy and safety of keverprazan to lansoprazole in treating erosive oesophagitis (EO).

Methods: This was a phase III, randomised, double-blind multicentre study.

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis.

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC).

The pathogenesis of amyotrophic lateral sclerosis: Mitochondrial dysfunction, protein misfolding and epigenetics.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with multiple complex mechanisms involved. Among them, mitochondrial dysfunction plays an important role in ALS. Multiple studies have shown that mitochondria are closely associated with reactive oxygen species production and oxidative stress and exhibit different functional states in different genetic backgrounds.

Circ_0043947 contributes to interleukin 1β-induced injury in chondrocytes by sponging miR-671-5p to up-regulate RTN3 expression in osteoarthritis pathology.

Objective: Osteoarthritis (OA) is a chronic joint disease featured by articular cartilage degeneration and damage. Accumulating evidence have demonstrated the pivotal regulatory roles of circular RNAs in OA pathology. However, the role of circ_0043947 in OA progression and its associated mechanism remain largely unknown.

Nanoparticle-Delivered microRNA-153-3p Alleviates Myocardial Infarction-Induced Myocardial Injury in a Rat Model.

Although microRNA-153-3p (miR-153-3p) has been demonstrated to confer protective roles in ischemia/reperfusion injury, its potential role in myocardial infarction (MI) remains undefined. Small-molecule modifiers and nanoparticles loaded with microRNAs (miRNAs) have emerged as potential therapeutic reagents for MI treatment. In this study, we prepared liposome nanoparticles, hyaluronic acid (HA)-cationic liposomes (CLPs) complex, for the delivery of miR-153-3p and delineated the mechanistic actions of miR-153-3p modified by nHA-CLPs in MI-induced injury.

Neutrophils Promote Tumor Progression in Oral Squamous Cell Carcinoma by Regulating EMT and JAK2/STAT3 Signaling Through Chemerin.

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. In the tumor microenvironment, tumor-associated neutrophils (TANs) can promote tumor growth, invasion, and metastasis. The aim of our study was to explore the relationship between neutrophils infiltration and Chemerin expression in tumor cells, as well as their relationship with the clinicopathological parameters and clinical prognosis of 74 cases of OSCC.

BarH-like homeobox 2 represses the transcription of keratin 16 and affects Ras signaling pathway to suppress nasopharyngeal carcinoma progression.

Nasopharyngeal carcinoma (NPC) refers to a malignancy initiating from the superior mucosal epithelium of the nasopharynx. Optimal therapies for NPC are still needed. In this investigation, we attempted to explore whether BarH-like homeobox 2 (BARX2), a well-known tumor suppressor, had anti-cancer properties on NPC, and the possible mechanisms.

[High expression of miR-3682-3p is an unfavorable prognostic factor of hepatocellular carcinoma].

Objective: To investigate the expression of miR-3682-3p in hepatocellular carcinoma (HCC) and its correlation with clinical parameters and prognosis of HCC.

Methods: We conducted a bioinformatics analysis of the expression of miR-3682-3p in HCC and its correlation with the patients' survival, and examined its expression in 18 pairs of fresh and 90 pairs of paraffin-embedded HCC and adjacent tissues using real-time fluorescence quantitative PCR and in situ hybridization, respectively. The correlation of miR-3682-3p expression in HCC with the clinical parameters and prognosis of the patients was analyzed.

ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through mA-PKM2-Mediated Glycolysis and Enhances Chemosensitivity.

Objective: N-Methyladenosine (mA) is the most prevalent RNA epigenetic modulation in eukaryotic cells, which serves a critical role in diverse physiological processes. Emerging evidences indicate the prognostic significance of mA regulator ZC3H13 in hepatocellular carcinoma (HCC). Herein, this study was conducted for revealing biological functions and mechanisms of ZC3H13 in HCC.

The Effect of Plasma Triglyceride-Lowering Therapy on the Evolution of Organ Function in Early Hypertriglyceridemia-Induced Acute Pancreatitis Patients With Worrisome Features (PERFORM Study): Rationale and Design of a Multicenter, Prospective, Observational, Cohort Study.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes.

Diagnostic Value of SonoVue Contrast-Enhanced Ultrasonography in Nipple Discharge Based on Artificial Intelligence.

This paper aims to explore the application value of SonoVue contrast-enhanced ultrasonography based on deep unsupervised learning (DNS) in the diagnosis of nipple discharge. In this paper, a new model (ODNS) is proposed based on the unsupervised learning model and stack self-coding network. The ultrasonic images of 1,725 patients with breast lesions in the shared database are used as the test data of the model.

The therapeutic efficacy and safety of traditional Chinese medicine injection combined with low-molecular-weight heparin on the acute lower extremity deep venous thrombosis: A protocol for systematic review and network meta-analysis.

Background: Lower extremity deep venous thrombosis (LEDVT) of lower extremities is one of the common clinical diseases. Lack of a timely treatment in the acute stage easily causes pulmonary embolism, thus seriously threatening patients' life. Low-molecular-weight heparin (LMWH), as a new generation of heparin-based anticoagulant and antithrombotic drug, is now commonly used in the clinical treatment of acute lower extremity deep venous thrombosis (ALEDVT).

Carnosic Acid Induces Antiproliferation and Anti-Metastatic Property of Esophageal Cancer Cells via MAPK Signaling Pathways.

Background: Carnosic acid (CA) is a polyphenolic diterpene extracted from rosemary. Reports have shown that CA possesses anticancer activity. However, whether CA inhibits esophageal squamous cell carcinoma, an aggressive type of esophageal cancer, remains untested.

Bosentan combined with sildenafil in the treatment of COPD patients with pulmonary arterial hypertension.

Objective: To explore the impacts of bosentan combined with sildenafil on chronic obstructive pulmonary disease (COPD) patients with pulmonary arterial hypertension (PAH).

Methods: From April 2019 to October 2020, 90 COPD patients with PAH diagnosed in our hospital were recruited and divided into groups A and B. The patients in group A (50 cases) were treated with bosentan combined with sildenafil, and the patients in group B (40 cases) were administered bosentan combined with iloprost solution for inhalation.

Frequency of and risk factors for intensive care unit-acquired sacrum pressure injuries in critically ill patients: A multicenter cross-sectional study in China.

Rationale Aims And Objectives: Hospital-acquired pressure injuries (HAPI) prolong hospital stays and are an important health problem worldwide. The aim of this study was to assess the frequency of and risk factors for intensive care unit (ICU)-acquired pressure injuries (IAPI) on the sacrum in critically ill patients in China.

Methods: We performed a multicenter, cross-sectional survey of IAPI on the sacrum in 23 adult ICUs in 19 hospitals in China.

Activation of mTOR mediates hyperglycemia-induced renal glomerular endothelial hyperpermeability via the RhoA/ROCK/pMLC signaling pathway.

Objective: Hyperglycemia is associated with albuminuria and renal glomerular endothelial dysfunction in patients with diabetic nephropathy. The mTOR and RhoA/ROCK signaling pathways are involved in glomerular filtration barrier (GFB) regulation, but their role in high glucose (HG)-induced GFB dysfunction in human renal glomerular endothelial cells (HRGECs) has not been investigated. This study aimed to investigate the mechanisms of HG-induced GFB dysfunction in vitro.