Antimicrobial Resistance Mechanisms in Carbapenem-Resistant Clinical Strains Isolated in Shanghai, China.

Carbapenems, as the preferred treatment for multidrug-resistant , are increasingly facing issues of insufficient therapeutic efficacy. This study aims to investigate the antimicrobial resistance mechanisms of clinical isolates to carbapenems. The whole genome sequencing revealed various β-lactamase genes, including the intrinsic genes and , as well as the acquired (n = 6), and (n = 10) in 40 carbapenem-resistant (CRPA) isolates.

STRaM: A genetic framework for improved cell product provenance for research and clinical translations.

Multiple assessment checks are required to handle the increasingly complex engineered-cell and cell-line provenance. To manage the biosafety and efficacy demands, we developed a bioinformatic pipeline for de novo profiling of short tandem repeats and mutations (STRaM) to identify and track homologous edited/engineered cells. The core technology of STRaM comprises an error-sensing bioinformatic pipeline with 3 analysis modules (STR analysis, STR flanking analysis and EMS analysis) for profiling, and an integrated assessment system with three indices for the respective reporting of identity, purity and genetic modifications of tested cells.

Molecular Characterization of Carbapenemase Genes in Carbapenem-Resistant Klebsiella pneumoniae Isolates.

Carbapenemase genes play important role in the formation and dissemination of carbapenem-resistant Klebsiella pneumoniae (CRKP). The aim of this study was to investigate the distribution of carbapenemase genes in clinical CRKP isolates. Eighty-three clinical CRKPs were collected and antimicrobial susceptibility testing was conducted.

Subchronic Chlorpyrifos Exposure Induces Thyroid Follicular Cell Pyroptosis to Exacerbate Thyroid Toxicity by Modulating Nrf2/Keap1/NF-κB Pathway in Male Mice.

Purpose: Chlorpyrifos (CPF), a widely used organophosphate pesticide in agriculture, particularly in China, has raised significant environmental and health concerns due to its persistence and bioaccumulation. While CPF-induced toxicity in multiple organ systems has been documented, its long-term impact on thyroid homeostasis and the underlying mechanisms remain poorly understood. This study aimed to investigate the subchronic effects of CPF on thyroid function and elucidate the underlying mechanisms of CPF-induced thyroid toxicity.

Changes in antibiotic use associated with the National Centralized Drug Procurement policy in China from 2019 to 2023.

This study used prescription data from four medical institutions in representative cities in Central, Western and Eastern China, focusing on changes in antibiotic use under the National Centralized Drug Procurement Policy (NCDP) and calculating the contribution of NCDP and non-NCDP varieties to the changes. In outpatient settings, NCDP policy had little impact on the antibiotic prescription rate. Changes in antibiotic utilization rates were predominantly driven by non-NCDP varieties, particularly newer-generation antibiotics with enhanced therapeutic profiles.

GSDME-mediated pyroptosis in microglia exacerbates demyelination and neuroinflammation in multiple sclerosis: insights from humans and cuprizone-induced demyelination model mice.

Demyelination, a hallmark of multiple sclerosis (MS), disrupts neural conduction due to myelin sheath degradation. Microglia-mediated inflammation plays a pivotal role in this process, with emerging evidence implicating gasdermin E (GSDME) in neuroinflammation and neurodegeneration. However, the specific role of GSDME in MS remains unclear.

A Novel Theranostic Strategy for Malignant Pulmonary Nodules by Targeted CECAM6 with Zr/I-Labeled Tinurilimab.

Lung adenocarcinoma (LUAD) constitutes a major cause of cancer-related fatalities worldwide. Early identification of malignant pulmonary nodules constitutes the most effective approach to reducing the mortality of LUAD. Despite the wide application of low-dose computed tomography (LDCT) in the early screening of LUAD, the identification of malignant pulmonary nodules by it remains a challenge.

Development and biological evaluation of a novel CEACAM6-targeted PET tracer for distinguishing malignant nodules in early-stage lung adenocarcinoma.

Purpose: Low-dose CT (LDCT) screening effectively reduces lung adenocarcinoma (LUAD) mortality. However, accurately evaluating the malignant potential of indeterminate lung nodules remains a challenge. Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6), a potential biomarker for distinguishing benign pulmonary nodules from LUAD, may be leveraged for noninvasive positron emission tomography (PET) imaging to aid LUAD diagnosis.

A DNA robotic switch with regulated autonomous display of cytotoxic ligand nanopatterns.

The clustering of death receptors (DRs) at the membrane leads to apoptosis. With the goal of treating tumours, multivalent molecular tools that initiate this mechanism have been developed. However, DRs are also ubiquitously expressed in healthy tissue.

MINK1 deficiency stimulates nucleus pulposus cell pyroptosis and exacerbates intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration, induced by aging and irregular mechanical strain, is highly prevalent in the elderly population, serving as a leading cause of chronic low back pain and disability. Evolving evidence has revealed the involvement of nucleus pulposus (NP) pyroptosis in the pathogenesis of IVD degeneration, while the precise regulatory mechanisms of NP pyroptosis remain obscure. Misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1), a serine-threonine protein kinase, has the potential to modulate the activation of NLRP3 inflammasome, indicating its pivotal role in governing pyroptosis.

Acupuncture for poststroke coma: A systematic review and meta-analysis.

Background: Despite being widely applied in clinical practice, the wake-promoting effect of acupuncture in poststroke coma patients remains controversial.

Objective: This study aimed to evaluate the efficacy of acupuncture for the treatment of poststroke coma.

Methods: Randomized controlled trials (RCTs) of acupuncture for treating poststroke coma were identified in PubMed, Cochrane Library, EMBASE, CNKI, WanFang and VIP up to 25 November 2023.

Sanguinarine modulates microglial function via PPARγ activation and protects against CNS demyelination.

Microglia aggregate in regions of active inflammation and demyelination in the CNS of multiple sclerosis (MS) patients and are considered pivotal in the disease process. Targeting microglia is a promising therapeutic approach for myelin repair. Previously, we identified two candidates for microglial modulation and remyelination using a Connectivity Map (CMAP)-based screening strategy.

Clinicopathologic Features and Prognosis of Female Early Breast Cancer With HER2 Low Expression: A Propensity Score Matched Analysis.

Background: Metastatic breast cancer (MBC) patients with low expression of human epidermal growth factor 2 (HER2) have been proven to benefit from HER2 targeted therapy. We aimed to determine how HER2-low status affected survival and metastatic risk as well as how it affected pathological complete response (pCR) in neoadjuvant chemotherapy (NAC) patients.

Methods: According to the results of immunohistochemistry (IHC) and in situ hybridization (ISH) testing, 321 female patients were sorted into HER2-low (IHC 1+/2+ with ISH negative) and HER2-zero (IHC 0) groups using propensity score matching (PSM).

Nomogram for predicting survival in patients with mucinous breast cancer undergoing chemotherapy and surgery: a population-based study.

Background: The prognosis of patients with mucinous breast cancer (MuBC) is affected by several factors, but the low incidence of MuBC makes it difficult to conduct extensive and in-depth studies. This study was designed to establish a prognostic model and verify its accuracy in patients with MuBC after chemotherapy and surgery to help develop personalized treatment strategies.

Materials And Methods: Patients with MuBC who underwent chemotherapy and surgery from 2004 to 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database.

Antigen receptor stimulation induces purifying selection against pathogenic mitochondrial tRNA mutations.

Pathogenic mutations in mitochondrial (mt) tRNA genes that compromise oxidative phosphorylation (OXPHOS) exhibit heteroplasmy and cause a range of multisyndromic conditions. Although mitochondrial disease patients are known to suffer from abnormal immune responses, how heteroplasmic mtDNA mutations affect the immune system at the molecular level is largely unknown. Here, in mice carrying pathogenic C5024T in mt-tRNAAla and in patients with mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) syndrome carrying A3243G in mt-tRNALeu, we found memory T and B cells to have lower pathogenic mtDNA mutation burdens than their antigen-inexperienced naive counterparts, including after vaccination.

Deep brain stimulation of the subthalamic nucleus improves sleep in Parkinson disease patients: A systematic review and meta-analysis.

Background: Sleep disorders significantly affect the quality of life in Parkinson disease (PD) patients. Deep brain stimulation of the subthalamic nucleus has been reported to improve motor symptoms and decrease medication usage. However, the impact of subthalamic nucleus deep brain stimulation (STN-DBS) on sleep quality in PD patients remains to be definitively determined.

Microglial aryl hydrocarbon receptor enhances phagocytic function via SYK and promotes remyelination in the cuprizone mouse model of demyelination.

Multiple sclerosis (MS) is an inflammatory-mediated demyelinating disease of the central nervous system (CNS). Although studies have demonstrated that microglia facilitate remyelination in demyelinating diseases, the underlying mechanisms are still not fully characterized. We found that aryl hydrocarbon receptor (AhR), an environment sensor, was upregulated within the corpus callosum in the cuprizone model of CNS demyelination, and upregulated AhR was mainly confined to microglia.

A prognostic nomogram based on risk assessment for invasive micropapillary carcinoma of the breast after surgery.

Purpose: Invasive micropapillary carcinoma (IMPC) is one of the rare subtypes of breast cancer. This study aimed to explore a predictive nomogram model for IMPC prognosis.

Methods: A total of 1855 IMPC patients diagnosed after surgery between 2004 and 2014 were identified from the Surveillance, Epidemiology and End Results (SEER) database to build and validate nomogram.

Sex difference in response to non-small cell lung cancer immunotherapy: an updated meta-analysis.

Background: Studying sex differences in the efficacy of immunotherapy may contribute to the practice of the precision medicine, especially in non-small cell lung cancer (NSCLC), a kind of cancer with sexual bimorphism.

Methods: Published randomized controlled trials (RCTs), published by PubMed, Medline, Embase, and Scopus, before 15 June 2022, testing immunotherapy (CTLA-4 or PD-1/L1 inhibitor alone, combination or with chemotherapy) versus non-immunotherapy (receiving chemotherapy or placebo only) were included to assess different efficacy between males and females. The primary endpoint was overall survival (OS).

Association of cesarean section with risk of childhood leukemia: A meta-analysis from an observational study.

Recent studies suggest that children born via cesarean section (CS) are predisposed to immune-mediated diseases later in life. The association between CS and childhood leukemia was investigated in this meta-analysis of observational studies. Two researchers independently searched PubMed, Web of Science, Embase, and Cochrane Library for literature on the association between CS and childhood leukemia before February 2022.

Prognostic Factor Analysis and Model Construction of Triple-Negative Metaplastic Breast Carcinoma After Surgery.

Objective: The study aimed to analyze the prognostic factors of patients with triple-negative (TN) metaplastic breast carcinoma (MpBC) after surgery and to construct a nomogram for forecasting the 3-, 5-, and 8-year overall survival (OS).

Methods: A total of 998 patients extracted from the Surveillance, Epidemiology, and End Results (SEER) database were assigned to either the training or validation group at random in a ratio of 7:3. The clinical characteristics of patients in the training and validation sets were compared, and multivariate Cox regression analysis was used to identify the independent risk variables for the OS of patients with TN MpBC after surgery.

Suboptimal immune recovery and associated factors among people living with HIV/AIDS on second-line antiretroviral therapy in central China: A retrospective cohort study.

The introduction and scale-up of antiretroviral therapy (ART) have contributed to significantly improved patients with acquired immune deficiency syndrome (AIDS) quality of life and prolongs their survival. This has occurred by suppressing viral replication and recovering the CD4 cell count. However, some patients do not normalize their CD4 cell count, despite suppression of the viral load (VL).

Comparison of hybrid coronary revascularization versus coronary artery bypass grafting in patients with multivessel coronary artery disease: a meta-analysis.

Background: Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) are widely used in the treatment of coronary heart disease, but the best revascularization method for multivessel coronary artery disease (MVD) patients is still controversial. Hybrid coronary revascularization (HCR), together with CABG and PCI, have been proved to be feasible methods, but the long-term effect of HCR is not as clear as CABG.

Method: By October 2020, we retrieved articles from PubMed, Web of science, EMBASE and Cochrane library databases.