Pharmacokinetics of Anti-rheumatic Drugs Methotrexate and Tofacitinib with its Metabolite M9 in Rats by UPLC-MS/MS.

Background: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The clinical efficacy and safety of an administered tofacitinib, either monotherapy or in combination with conventional synthetic disease-modifying anti-rheumatic drugs, mainly methotrexate (MTX), have been evaluated. The high plasma concentration with delayed medicine clearance may affect the liver and/or kidney functions.

The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization study.

Background: Ankylosing spondylitis (AS) is one of several disorders known as seronegative spinal arthritis (SpA), the origin of which is unknown. Existing epidemiological data show that inflammatory and immunological factors are important in the development of AS. Previous research on the connection between immunological inflammation and AS, however, has shown inconclusive results.

FOXM1 transcriptional regulation of RacGAP1 activates the PI3K/AKT signaling pathway to promote the proliferation, migration, and invasion of cervical cancer cells.

Background: Cervical cancer (CC) is the most common gynecological tumor disease in women, which occurs at the junction of cervical squamous columnar epithelium. We investigated the effect and mechanism of transcription factor FOXM1 synergizing RacGAP1 in the proliferation, migration, and invasion of CC cells.

Methods: Here, we analyzed the correlation between FOXM1 and RacGAP1 and the clinicopathological features of 68 CC patients.

Thyroid dysfunction and risk of cutaneous malignant melanoma: a bidirectional two-sample Mendelian randomization study.

Background: Epidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction of these effects are yet unknown. By using a bidirectional two-sample Mendelian randomization (MR) methodology, we hoped to further investigate the causal link between thyroid dysfunction and CMM in this work.

Methods: A genome-wide association study (GWAS) of 9,851,867 single nucleotide polymorphisms (SNPs) in a European population was used to develop genetic tools for thyroid dysfunction.

Risk factor analysis of conversion in laparoscopic liver resection for intrahepatic cholangiocarcinoma.

Background: The risk factors of patients with intrahepatic cholangiocarcinoma (ICC) requiring conversion to open surgery have not been adequately studied. This study aimed to determine the risk factors and postoperative outcomes of conversion in patients with ICC.

Methods: From May 2014 to September 2022, Unplanned conversions were compared with successful LLRs.

Risk factors for surgical site infection after closed proximal humerus fractures.

Proximal humerus fractures are common in clinical practice, and there are relatively a few studies on postoperative incision infections of such fractures. The purpose of this study was to explore the risk factors for surgical site infection (SSI) after internal fixation in patients with closed proximal humerus fractures. Patients with closed proximal humerus fractures who underwent surgery from January 2016 to January 2022 were retrospectively analysed.

Renal function as risk factor for diabetic foot ulcers: A meta-analysis.

The meta-analysis aimed to assess renal function (RF) as a risk factor for diabetic foot ulcers (DFUs). Using dichotomous or contentious random or fixed effect models, the outcomes of this meta-analysis were examined, and the odds Ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. 16 examinations from 2004 to 2023 were enrolled for the present meta-analysis, including 808 914 individuals with diabetes mellitus (DM).

Bioinformatics analysis identifies potential m6A hub genes in the pathogenesis of intracerebral hemorrhage.

Background: Intracerebral hemorrhage (ICH) is a type of stroke associated with a high rate of disability and mortality. The role of N6-methyladenosine (m6A) in ICH remains unclear.

Methods: Screening of m6A DEGs by differentially expressed genes (DEGs) analysis.

3, 4-Benzopyrene (Bap) aggravated abdominal aortic aneurysm formation by targeting pyroptosis in smooth muscle cells through ET-1 mediated NLRP3-inflammasome activation.

According to epidemiological studies, smoking is one of the leading causes of the high incidence of abdominal aortic aneurysms (AAA).3,4-Benzopyrene (Bap) is a by-product of coal tar and tobacco combustion produced by the incomplete combustion of organic fuels. It is an essential component of both automobile exhaust and tobacco smoke, it is also an important member of the air pollutants.

Primary microcephaly gene CENPE is a novel biomarker and potential therapeutic target for non-WNT/non-SHH medulloblastoma.

Background: Non-WNT/non-SHH medulloblastoma (MB) is one of the subtypes with the highest genetic heterogeneity in MB, and its current treatment strategies have unsatisfactory results and significant side effects. As a member of the centromere protein (CENP) family, centromeric protein E (CENPE) is a microtubule plus-end-directed kinetochore protein. Heterozygous mutations in CENPE can leads to primary microcephaly syndrome.

circ-Gucy1a2 Protects Mice from Cerebral Ischemia-Reperfusion Injury by Attenuating Neuronal Apoptosis and Mitochondrial Membrane Potential Loss.

Cerebral ischemia-reperfusion (I/R) injury (CI/RI) is a severe problem in patients with cerebral ischemia. The current study explored the influences of circular (circ)-Gucy1a2 on neuronal apoptosis and mitochondrial membrane potential (MMP) in the brain tissue of CI/RI mice. Forty-eight mice were randomized into the sham group, transient middle cerebral artery occlusion (tMCAO) group, lentivirus negative control (LV-NC) group, and LV-Gucy1a2 group.

Optogenetic engineered umbilical cord MSC-derived exosomes for remodeling of the immune microenvironment in diabetic wounds and the promotion of tissue repair.

Background: Angiogenesis and tissue repair in chronic non-healing diabetic wounds remain critical clinical problems. Engineered MSC-derived exosomes have significant potential for the promotion of wound healing. Here, we discuss the effects and mechanisms of eNOS-rich umbilical cord MSC exosomes (UCMSC-exo/eNOS) modified by genetic engineering and optogenetic techniques on diabetic chronic wound repair.

Maternal separation leads to dynamic changes of visceral hypersensitivity and fecal metabolomics from childhood to adulthood.

We assessed dynamic changes in visceral hypersensitivity and fecal metabolomics through a mouse model of irritable bowel syndrome (IBS) from childhood to adulthood. A mouse model of IBS was constructed with maternal separation (MS) in early life. Male mice aged 25, 40, and 70 days were used.

Efficacy of Mesenchymal Stem Cell Therapy on Lupus Nephritis and Renal Function in Systemic Lupus Erythematosus: A Meta-Analysis.

Purpose: The purpose of this meta-analysis is to determine the efficacy of mesenchymal stromal/stem cell (MSC) transplantation therapy on lupus nephritis (LN) and renal function of patients with systemic lupus erythematosus (SLE).

Methods: Articles that reported the data of MSC therapy on the renal function as well as disease activity of LN in patients with SLE were searched in PubMed, Web of Science, Embase and the Cochrane Library. Mean difference for disease activity and laboratory parameters were pooled to evaluate the efficacy of MSC, and incidence was pooled for clinical remission, death and severe adverse event.

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway.

Exosomes secreted by glioma cells can carry a number of bioactive molecules. As the most abundant noncoding RNA in exosomes, microRNAs (miRNAs) are involved in signaling between tumor cells in a number of ways. In addition, hypoxia is an important feature of the microenvironment of most tumors.

Triglyceride-glucose index is associated with metabolic syndrome in women with polycystic ovary syndrome.

Objective: To explore the correlation of triglyceride-glucose index (TyG) index with metabolic syndrome (MetS) and metabolic risk factors, and to assess the predictive value of TyG for MetS in women with PCOS.

Methods: This is a retrospective cross-sectional study that included 819 women diagnosed with PCOS and 3122 women without PCOS from January 2018 to December 2021. The definition of MetS adopted in this study was the International Diabetes Federation (IDF) criteria.

Total knee arthroplasty in patients with Parkinson's disease: A systematic review and meta-analysis protocol.

Background: Parkinson's disease (PD) patients have been shown to have various musculoskeletal problems, the postoperative outcomes of total knee arthroplasty procedure might be less predictable if performed on a patient who has PD. We conducted a protocol for systematic review and meta-analysis to evaluate the functional outcomes, activity levels, mortalities, implant survival rates, and complications of total knee arthroplasty in patients with PD.

Methods: This study follows the guideline of the preferred reporting items for systematic reviews and meta-analyses protocols and has been registered on the International Prospective Register of Systematic Reviews with CRD42022375885.

The effect of transcranial magnetic stimulation on the recovery of attention and memory impairment following stroke: a systematic review and meta-analysis.

Background: Previous studies indicated inconsistent results for the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on attention and memory impairment following stroke.

Methods: Randomized controlled trials (RCTs) on TMS for the treatment of stroke were retrieved from Online databases. Data were analyzed by RevMan 5.

Superior treatment efficacy of neuromodulation rehabilitation for upper limb recovery after stroke: a meta-analysis.

Background: This study aims to explore the treatment efficacy of different motor rehabilitation interventions for upper limb impairment recovery.

Research Design & Methods: Publications were searched in PubMed and Embase. 4 grouped motor rehabilitation treatments (training, technological intervention, pharmacological intervention, and neuromodulation) were compared.

Analysis between high risk of myocardial infarction with non-obstructive coronary artery disease in single center and occurrence of major adverse cardiovascular events.

Objective: To investigate and compare the general information, medication, and the occurrence time of major adverse cardiovascular events (MACE) between patients with myocardial infarction with non-obstructive coronary artery myocardial infarction (MINOCA) and those with obstructive coronary artery disease (MICAD).

Methods: A total of 325 acute myocardial infarction (AMI) patients were included (MINOCA: n = 31; MICAD: n = 294). The general information and medication of patients were recorded, including age, gender, prevalence of type 2 diabetes, left ventricular ejection fraction (LVEF), proportion of mitral regurgitation, cTn level, triglyceride level, electrocardiogram (ECG) findings, and drugs used (statins, drugs improving ventricular remodeling, antiplatelet drugs).

Establishment and validation of individualized clinical prognostic markers for LUAD patients based on autophagy-related genes.

There is considerable heterogeneity in the genomic drivers of lung adenocarcinoma, which has a dismal prognosis. Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model.

A high throughput method for Monitoring of Sorafenib, regorafenib, cabozantinib and their metabolites with UPLC-MS/MS in rat plasma.

As multi-targeted tyrosine kinase inhibitors, sorafenib, regorafenib and cabozantinib are widely used in hepatocellular carcinoma (HCC) for systemic therapies with anti-proliferative and anti-angiogenic effects. Nevertheless, adverse effects or insufficient efficacy appear frequently due to the plasma concentration with individual variability of these drugs. To ensure the curative effect and safety by therapeutic drug monitoring (TDM), this study developed a high throughput method to quantify sorafenib, regorafenib, cabozantinib and their active metabolites in plasma simultaneously.

Causal associations between gut microbiome and cardiovascular disease: A Mendelian randomization study.

Background: Observational studies have shown gut microbiomes were associated with cardiovascular diseases (CVDs), but their roles remain controversial, and these associations have not yet been established causally.

Methods: Two-sample Mendelian randomization (MR) was used to investigate whether gut microbiome had a causal effect on the risk of CVDs. To obtain comprehensive results, we performed two sets of MR analyses, one with single nucleotide polymorphisms (SNPs) that smaller than the genome-wide statistical significance threshold (5 × 10) as instrumental variables, and the other with SNPs that lower than the locus-wide significance level (1 × 10).