Publications by authors named "Keying Zhu"

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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • Macrophages in dorsal root ganglia (DRG) are traditionally studied for their roles in pain and nerve injury, but they also monitor blood vessels by sampling macromolecules from the bloodstream.
  • The vasculature in the DRG has unique properties that change along the arteriovenous axis, and macrophages interact with this specialized endothelial structure, which is influenced by their ability to engulf materials and regulate blood vessel permeability.
  • Two types of perivascular macrophages were identified in the DRG: CD163+ macrophages, which are locally maintained, play a crucial role in monitoring blood vessels, and respond differently to inflammation, highlighting a new understanding of macrophages in the neurovascular environment.
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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).

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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.

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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.

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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.

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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.

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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.

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Article Synopsis
  • TRPV1 is a cation channel activated by capsaicin, and its role in demyelinating diseases like multiple sclerosis was studied, showing increased expression during demyelination in a mouse model.
  • TRPV1 deficiency worsened motor dysfunction and demyelination, while activation with capsaicin improved behavior and helped in remyelination by enhancing microglial activity.
  • The study suggests that TRPV1 plays a crucial role in regulating microglial functions during demyelination, making it a potential therapeutic target for conditions like multiple sclerosis.
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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).

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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.

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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.

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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).

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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.

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Article Synopsis
  • Targeting microglia, a type of myeloid cell, is crucial for treating neuroinflammatory diseases like multiple sclerosis (MS), and researchers are exploring topoisomerase 1 (TOP1) inhibitors as potential therapies.
  • Studies show that inhibiting TOP1 with drugs like camptothecin (CPT) and topotecan (TPT) reduces inflammation in microglia and helps alleviate neuroinflammation in living organisms.
  • An innovative nanosystem, MyloGami, designed to specifically deliver TPT to myeloid cells, significantly decreases inflammation and slows the progression of MS, suggesting that TOP1 inhibition in these cells could be a viable treatment strategy for neuroinflammatory disorders.
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Article Synopsis
  • Fluorescent reporter labeling and promoter-driven Cre-recombinant technologies have been important for studying microglia using the Cx3cr1 mouse strain, which helps understand various physiological and pathological processes.
  • The study employed several methods, including immunohistochemistry and RNA sequencing, to identify a unique subpopulation of microglia, named Cx3cr1CreEyfp microglia, that exhibited differential characteristics compared to other microglia.
  • The findings indicate that this subpopulation can escape genetic depletion and proliferate significantly, highlighting the need for caution when interpreting results from Cx3cr1 mouse strains in research on microglial behavior.
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Aims: Accumulating evidence indicates that serum- and glucocorticoid-inducible kinase 1 (SGK1) plays a role in the development of metabolic syndrome via a poorly understood mechanism. This study aimed to investigate the direct effect of SGK1 on insulin sensitivity in adipose tissue.

Materials And Methods: We ectopically expressed or silenced SGK1 in adipocytes via lentiviral transfection, measured glucose uptake and evaluated insulin signalling using western blotting.

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Demyelinating pathology is common in many neurological diseases such as multiple sclerosis, stroke, and Alzheimer's disease and results in axonal energy deficiency, dysfunctional axonal propagation, and neurodegeneration. During myelin repair and also during myelin homeostasis, mutual regulative processes between axons and myelin sheaths are known to be essential. However, proficient tools are lacking to characterize axon-myelin interdependence during (re)myelination.

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Anti-inflammatory drugs such as dexamethasone (DEX) are commonly administered to cancer patients along with anticancer drugs, however, the effect of DEX on human cancers is poorly understood. In this article, we have tailored self-assembled nanoparticles derived from hyaluronic acid (HA) wherein, anti-inflammatory DEX was used as a hydrophobic moiety for inducing amphiphilicity. The HA-DEX micelles were subsequently loaded with chemotherapeutic agent, doxorubicin (DOX) (HA-DEX-DOX) and was utilized to deliver drug cargo to human cancer cells expressing different levels of CD44 receptors.

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Microglia, predominant parenchymal resident macrophages in the central nervous system (CNS), are crucial players in neurodevelopment and CNS homeostasis. In disease conditions, pro-inflammatory microglia predominate over their regulatory counterparts, and are thus a potential immunotherapeutic target. It has been well documented that microglia can be effectively depleted using both conditional genetic -diphtheria toxin receptor (DTR)/diphtheria toxin subunit A (DTA) animal models and pharmacological colony-stimulating factor 1 receptor (CSF1R) inhibitors.

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Multiple sclerosis (MS) is a chronic neuroinflammatory disorder of the central nervous system (CNS) that usually presents in young adults and predominantly in females. Microglia, a major resident immune cell in the CNS, are critical players in both CNS homeostasis and disease. We have previously demonstrated that microglia can be efficiently depleted by the administration of tamoxifen in mice, with ensuing repopulation deriving from both the proliferation of residual CNS resident microglia and the engraftment of peripheral monocyte-derived microglia-like cells.

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