National cohort study on cardiometabolic index and incident stroke in middle-aged and older adults in China.

Unlabelled: Background The Cardiometabolic Index (CMI), a novel marker integrating central obesity and lipid metabolism, serves as a comprehensive indicator of metabolic health. While CMI has been linked to metabolic disorders like diabetes and cardiovascular diseases, its role in predicting stroke risk remains unclear. This study examines the association between CMI and stroke risk in Chinese adults aged 45 and older, highlighting its potential as a predictive tool for public health.

Functional evaluation of novel compound heterozygous variants in SLC12A3 of Gitelman syndrome.

Background: Gitelman syndrome (GS) is an inherited renal tubular disorder characterized by hypokalemic alkalosis and hypomagnesemia, due to biallelic pathogenic variants in the solute carrier family 12 member 3 (SLC12A3) gene encoding a sodium-chloride (Na-Cl) cotransporter (NCC). This work aimed at identifying SLC12A3 variants in the GS pedigree and reveal the effect of the mutations on protein structure and function.

Methods: Whole-exome sequencing (WES) and Sanger sequencing were performed in the pedigree.

Metabolic parameter of baseline 18 F-FDG PET/CT with PINK models improve the prediction of treatment outcome in extranodal NK/T-cell lymphoma treated with P-GEMOX chemotherapy.

The aim of this study was to investigate the prognostic value of baseline PET/CT parameters alone and combined with clinical features in Extranodal Natural killer/T-cell lymphoma (ENKTL) patients treated with P-GEMOX regimen (pegaspargase, gemcitabine and oxaliplatin). A total of 97 patients were retrospectively evaluated. The relationships between baseline PETCT metabolic parameters and survival were tested using Cox regression analysis and receiver operating characteristic(ROC) curve analysis was employed to evaluate the optimal cut-off value of these parameters.

Next-Generation Sequencing of Chinese Children with Congenital Hearing Loss Reveals Rare and Novel Variants in Known and Candidate Genes.

Hearing loss (HL) is the most common disorder in newborns with a highly heterogeneous genetic background. Despite significant progress in screening and identifying genes related to congenital hearing loss, there are still candidate genes implicated in HL that remain undiscovered. We investigated HL in 43 Chinese families by segregating bilateral sensorineural HL via whole-exome sequencing (WES) and Sanger sequencing.

Water and chloride as allosteric inhibitors in WNK kinase osmosensing.

Osmotic stress and chloride regulate the autophosphorylation and activity of the WNK1 and WNK3 kinase domains. The kinase domain of unphosphorylated WNK1 (uWNK1) is an asymmetric dimer possessing water molecules conserved in multiple uWNK1 crystal structures. Conserved waters are present in two networks, referred to here as conserved water networks 1 and 2 (CWN1 and CWN2).

PTBP1 Regulates DNMT3B Alternative Splicing by Interacting With RALY to Enhance the Radioresistance of Prostate Cancer.

Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa.

Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study.

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%.

Assessment of treatment outcomes: cytoreductive surgery compared to radiotherapy in oligometastatic prostate cancer - an in-depth quantitative evaluation and retrospective cohort analysis.

Background: The management of oligometastatic prostate cancer, defined by its few metastatic sites, poses distinct clinical dilemmas. Debates persist regarding the most effective treatment approach, with both cytoreductive surgery and radiotherapy being key contenders. The purpose of this research is to thoroughly evaluate and compare the effectiveness of these two treatments in managing patients with oligometastatic prostate cancer.

MT1G, an emerging ferroptosis-related gene: A novel prognostic biomarker and indicator of immunotherapy sensitivity in prostate cancer.

Background: Prostate cancer is a leading cause of cancer-related deaths in men worldwide. Despite advances in treatment strategies, there is still a need for novel therapeutic targets and approaches. Ferroptosis has emerged as a critical process in the development and progression of several cancers, including prostate cancer (PCA).

Water and chloride as allosteric inhibitors in WNK kinase osmosensing.

Osmotic stress and chloride regulate the autophosphorylation and activity of the WNK1 and WNK3 kinase domains. The kinase domain of unphosphorylated WNK1 (uWNK1) is an asymmetric dimer possessing water molecules conserved in multiple uWNK1 crystal structures. Conserved waters are present in two networks, referred to here as conserved water networks 1 and 2 (CWN1and CWN2).

TSPAN18 facilitates bone metastasis of prostate cancer by protecting STIM1 from TRIM32-mediated ubiquitination.

Background: Bone metastasis is a principal cause of mortality in patients with prostate cancer (PCa). Increasing evidence indicates that high expression of stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE) significantly activates the calcium (Ca) signaling pathway and is involved in multiple steps of bone metastasis in PCa. However, the regulatory mechanism and target therapy of STIM1 is poorly defined.

Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening.

Introduction: WNK [with no lysine (K)] kinases are serine/threonine kinases associated with familial hyperkalemic hypertension (FHHt). WNKs are therapeutic targets for blood pressure regulation, stroke and several cancers including triple negative breast cancer and glioblastoma. Here, we searched for and characterized novel WNK kinase inhibitors.

Synthesis and Structural Characterization of Novel Trihalo-sulfone Inhibitors of WNK1.

With No lysine (K) [WNK] kinases are structurally unique serine/threonine protein kinases that have therapeutic potential for blood pressure regulation and cancer. A novel class of trihalo-sulfone compounds was identified by high-throughput screening. Trihalo-sulfone emerged as an effective inhibitor of WNK1 with an IC value of 1.

The emerging role of anti-PD-1 antibody-based regimens in the treatment of extranodal NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis.

Purpose: Anti-PD-1 antibody (anti-PD-1 mAb) showed favorable outcomes in some patients with relapsed/refractory (r/r) extranodal NK/T-cell lymphoma (ENKTL). However, the role of anti-PD-1 antibody in NK/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHS) remains unclear. Here, we evaluated the efficacy and toxicity of anti-PD-1 antibody-based treatment in NK/T-LAHS patients.

Characteristics of Coal Porosity Changes before and after Triaxial Compression Shear Deformation under Different Confining Pressures.

It is important to explore the changes in coal pores in response to triaxial compression and shear deformation for coal mine gas drainage and efficient coalbed methane mining. To study the variation in coal pores depending on stress, first, a mechanical analysis was carried out, and then the characteristics of coal samples before and after triaxial compression were quantitatively analyzed combined with low-temperature nitrogen adsorption experiments. The compressive strength of the coal samples with a high elastic modulus is significantly greater than that of coal samples with a low elastic modulus.

Characterization of amphoteric bentonite-loaded magnetic biochar and its adsorption properties for Cu and tetracycline.

To realize simultaneous adsorption of heavy metal and antibiotic pollutants by a BC-based recyclable material, FeO magnetic biochar (MBC) was prepared by co-precipitation method. Then different ratios of dodecyl dimethyl betaine (BS-12)-modified bentonite (BS-B) were loaded on the surfaces of biochar (BC) and MBC to prepare BS-B-loaded BC and MBC composites, called BS-B/BC and BS-B/MBC, respectively. The physicochemical and structural properties of the composites were characterized by scanning electron microscopy, Fourier transform infrared spectrometry, thermogravimetric analysis, specific surface area (S) analysis, and vibrating sample magnetometry, and the adsorption efficiencies of BS-B/BC and BS-B/MBC to Cu and tetracycline (TC) were studied.

The beneficial effect of Escalated-R-CHOP-21 for the treatment of diffuse large B-cell lymphoma in elderly male patients: A propensity-matched cohort study.

Purpose: Some studies have indicated that using 500 mg/m rituximab combined with CHOP-14 may be beneficial for elderly men but not women with diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the potential benefit of escalated doses of rituximab with CHOP-21 as the first-line treatment in male patients with DLBCL.

Methods: We performed a retrospective cohort study to analyze the survival benefit of rituximab 500 mg/m plus the CHOP-21 regimen (Escalated-R-CHOP-21) as the first-line treatment compared with using rituximab 375 mg/m plus the CHOP-21 regimen (Standard-R-CHOP-21) in men with DLBCL.

Effect of miR-25 on Proliferation of Nasopharyngeal Carcinoma Cells through Wnt/-Catenin Signaling Pathway.

Objective: To investigate the biological role and potential mechanism of miR-25 in nasopharyngeal carcinoma.

Methods: The expression of miR-25 in nasopharyngeal carcinoma cell lines was detected by qRT-PCR. The effect of inhibition of miR-25 expression on the proliferative activity of nasopharyngeal carcinoma cell line HONE-1 was examined by CCK-8 method.

CREBBP cooperates with the cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) exhibits frequent inactivating mutations of the histone acetyltransferase CREBBP, highlighting the attractiveness of targeting CREBBP deficiency as a therapeutic strategy. In this study, we demonstrate that chidamide, a novel histone deacetylase (HDAC) inhibitor, is effective in treating a subgroup of relapsed/refractory DLBCL patients, achieving an overall response rate (ORR) of 25.0% and a complete response (CR) rate of 15.

VISTA and PD-L1 synergistically predict poor prognosis in patients with extranodal natural killer/T-cell lymphoma.

Although PD-1/PD-L1 blockade therapy confers salutary effects across cancer types, their efficacy in Extranodal Natural killer/T-cell lymphoma (ENKTCL) patients is limited and unpredictable. Here, we comprehensively evaluated the expression profile of a panel of immune-regulatory makers to identify novel prognostic biomarkers and/or therapeutic targets for this malignancy. Using immunohistochemistry and multiplex immunofluorescence, we found that the expression of VISTA (88.

WD repeat domain 5 promotes chemoresistance and Programmed Death-Ligand 1 expression in prostate cancer.

Advanced prostate cancer (PCa) has limited treatment regimens and shows low response to chemotherapy and immunotherapy, leading to poor prognosis. Histone modification is a vital mechanism of gene expression and a promising therapy target. In this study, we characterized WD repeat domain 5 (WDR5), a regulator of histone modification, and explored its potential therapeutic value in PCa.