Objective To investigate the characteristics of pan-immune-inflammation value （PIV），non-high-density lipoprotein cholesterol （non-HDL-C），and interleukin （IL） spectrum and their correlation with the severity of neurological function impairment in elderly patients with acute ischemic stroke. Methods A retrospective analysis was performed for 158 elderly patients with acute ischemic stroke who were hospitalized in our hospital from October 2019 to October 2024，and according to the severity of neurological function impairment，they were divided into non-severe neurological function impairment group with 112 patients and severe neurological function impairment group with 46 patients. The two groups were compared in terms of general clinical data，PIV，non-HDL-C，and ILs. A logistic regression analysis was used to investigate the risk factors for severe neurological function impairment in elderly patients with acute ischemic stroke，and the receiver operating characteristic （ROC） curve was used to evaluate the predictive value of each risk factor. Results Compared with the non-severe neurological function impairment group，the severe neurological function impairment group had a significantly lower level of HDL-C and significantly higher levels of non-HDL-C，PIV，IL-1β，IL-6，and IL-8 （P<0.05）. The multivariate logistic regression analysis showed that HDL-C，non-HDL-C，PIV，IL-1β，IL-6，and IL-8 were influencing factors for severe neurological function impairment in elderly patients with acute ischemic stroke （P<0.05）. The ROC curve analysis showed that the combination of HDL-C，non-HDL-C，PIV，IL-1β，IL-6，and IL-8 had a significantly higher efficiency than each indicator alone in predicting severe neurological function impairment in elderly patients with acute ischemic stroke （Z=4.234，4.411，3.897，4.240，4.001，4.420，all P<0.001）. Conclusion Elderly patients with acute ischemic stroke who have relatively high levels of PIV，non-HDL-C，and pro-inflammatory ILs tend to have severe neurological function impairment.

Diabetic retinopathy(DR)is a prevalent microvascular complication of diabetes and a leading cause of vision loss globally.Although anti-vascular endothelial growth factor(anti-VEGF)therapies remain the clinical mainstay, a significant proportion of patients exhibit suboptimal responses, highlighting the urgent need for novel therapeutic targets. Calcitonin gene-related peptide(CGRP), a multifunctional neuropeptide, is gaining attention due to its roles in vascular regulation, neuroprotection, and immunomodulation. This review summarizes the biological characteristics of CGRP and its receptor-mediated signaling, and explores emerging evidence of CGRP's involvement in DR through its vasodilatory effects and regulatory effect on neurodegenerative disorders and release of inflammatory cytokines. Furthermore, the therapeutic potential of targeting the CGRP pathway in DR is evaluated, especially in cases unresponsive to VEGF inhibition. Despite currently the lack of CGRP-targeted drugs applied for DR, the peptide demonstrates efficacy and safety in other diseases, such as migraine, suggests promising translational opportunities. However, CGRP may play a dual role in different pathological stages of DR, thus its treatment strategy needs to be considered precisely. Future research elucidating the precise mechanisms of CGRP in DR may pave the way for innovative intervention strategies.

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

Disruption of the intestinal mucosal barrier caused by gut dysbiosis and metabolic imbalance is the underlying pathology of inflammatory bowel disease (IBD). Traditional Chinese medicine Wuji Wan (WJW) is commonly used to treat digestive system disorders and showed therapeutic potential for IBD. In this interdisciplinary study, we aim to investigate the pharmacological effects of WJW against experimental colitis by combining functional metabolomics and gut-microbiota sequencing techniques. Treatment with WJW altered the profile of the intestinal microbiota and notably increased the abundance of Lactobacillus, thereby facilitating the conversion of tryptophan into indole-3-acetic acid (IAA) and indoleacrylic acid (IA). These indole derivatives activated the aryl hydrocarbon receptor (AhR) pathway, which reduced colonic inflammation and restored the expression of intestinal barrier proteins. Interestingly, the beneficial effects of WJW on gut barrier function improvement and tryptophan metabolism were disappeared in the absence of gut microbiota. Finally, pre-treatment with the AhR antagonist CH-223191 confirmed the essential role of IAA-mediated AhR activation in the therapeutic effects of WJW. Overall, WJW enhanced intestinal barrier function and reduced colonic inflammation in a murine colitis model by modulating Lactobacillus-IAA-AhR signaling pathway. This study provides novel insights into colitis pathogenesis and presents an effective therapeutic and preventive approach against IBD.

OBJECTIVE To explore the effect and mechanism of Buyang huanwu decoction （BYHWD） on mitochondrial dynamics in rats with cerebral ischemia-reperfusion injury （CIRI）. METHODS CIRI rats were randomly divided into CIRI group， low-dose BYHWD （L-BYHWD， intragastric administration of 3.15 mg/kg BYHWD） group， high-dose BYHWD （H-BYHWD， intragastric administration of 12.60 mg/kg BYHWD） group， positive control （intraperitoneal administration of 150 mg/kg Extract of Ginkgo biloba leaves injection） group， H-BYHWD+solvent control （intragastric administration of 12.60 mg/kg BYHWD+ intraperitoneal injection of 20 mg/kg DMSO） group and H-BYHWD+Compound C （intragastric administration of 12.60 mg/kg BYHWD+intraperitoneal injection of 20 mg/kg Compound C） group， with 15 rats in each group. Additionally， 15 rats were assigned to the sham operation group. All rats received the corresponding medications or saline solution via intragastric administration or intraperitoneal injection once daily for 4 consecutive weeks. After the last administration， the cerebral infarct volume of rats was measured； the ultrastructure of mitochondria in endothelial cells in the ischemic penumbra （IP） region was observed； the mitochondrial membrane potential was evaluated； the fluorescence colocalization area ratio of optic atrophy 1 （OPA1） to cluster of differentiation 31 （CD31） in the IP region was detected； the expressions of mitofusin 2 （MFN2）， OPA1， mitochondrial fission 1 protein （Fis1）， and proteins related to the AMP-activated protein kinase （AMPK）/dynamin-related protein 1 （Drp1） pathway in the IP region were determined. RESULTS Compared with the sham operation group， mitochondria in endothelial cells of the IP region in brain tissue of rats in the CIRI group were swollen， mostly spherical， with fractured cristae and severe vacuolation； the percentage of cerebral infarct volume， Fis1 expression level and phosphorylation level of Drp1 were increased significantly （P＜0.05）， while mitochondrial membrane potential in the IP region， fluorescence colocalization area ratio of OPA1 to CD31， the expressions levels of MFN2 and OPA1， and phosphorylation level of AMPK were significantly decreased （P＜0.05）. These indicators were improved in the L-BYHWD group， H-BYHWD group， and positive control group， M025） compared with the CIRI group （P＜0.05）. Compared with the H-BYHWD group and H-BYHWD+solvent control group， the above indicators of rats in the H-BYHWD+Compound C group showed significant reversal（P＜0.05）. There was no statistically significant difference in the above indicators between the H-BYHWD+solvent control group and the H-BYHWD group （P＞0.05）. CONCLUSIONS BYHWD may improve CIRI by activating the AMPK/Drp1 pathway and ameliorating mitochondrial dynamic disorders.

OBJECTIVES: To investigate the expression levels of marginal zone B and B1-cell-specific protein (MZB1) in pan-cancer and its association with patient prognosis and tumor microenvironment (TME). METHODS: MZB1 expression data, clinicopathological parameters, and survival data from 33 cancer types were extracted from the UCSC database for analyzing the correlations of MZB1 with clinical stage, patient prognosis, immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). MZB1 gene mutations in pan-cancer were assessed using cBioPortal online database, and the value of MZB1 for cancer diagnosis was evaluated using ROC curve analysis. MZB1 expression levels in myeloid leukemia and renal carcinoma cells were detected using RT-qPCR and Western blotting, and the effect of MZB1 knockdown on cell proliferation was examined using EdU assay. RESULTS: MZB1 was significantly overexpressed in 20 cancer types, including kidney renal clear cell carcinoma (KIRC), breast invasive carcinoma, and acute myeloid leukemia. Its expression was associated with TNM stage, clinical stage, overall survival, and progression-free survival in multiple cancers. In most tumors, MZB1 expression was correlated significantly with immunomodulatory genes, immune checkpoint genes, tumor stemness, immune cell infiltration, TMB, and microsatellite instability. Gene amplification was the predominant mutation type of MZB1 in pan-cancer, and MZB1 showed high diagnostic value for skin cutaneous melanoma, KIRC, and head and neck squamous cell carcinoma. MZB1 was highly expressed in different myeloid leukemia cell lines and renal carcinoma cell lines, and MZB1 knockdown significantly suppressed the proliferation of HL60 and 769-P cells. CONCLUSIONS MZB1 is highly expressed in a variety of tumors, and its aberrant expression affects the occurrence and prognosis of many tumors, suggesting its potential as a novel tumor biomarker and immunomodulatory target.
Humans ; Prognosis ; Tumor Microenvironment ; Neoplasms/pathology* ; Cell Line, Tumor ; Mutation ; Kidney Neoplasms ; Microsatellite Instability ; Cell Proliferation ; Carcinoma, Renal Cell

The armadillo repeat containing 5 (ARMC5) gene is part of a family of protein-coding genes that are rich in armadillo repeat sequences, are ubiquitously present in eukaryotes, and mediate interactions between proteins, playing roles in various cellular processes. Current research has demonstrated that reduced expression or absence of the ARMC5 gene in various tumor tissues can lead to uncontrolled cell proliferation, thereby inducing a range of diseases. The ARMC5 gene was initially extensively studied in the context of bilateral macronodular adrenocortical disease (BMAD), with harmful pathogenic variants in ARMC5 identified in approximately 50% of BMAD patients. With advancing research, scientists have discovered that ARMC5 pathogenic variants may also have potential effects on other diseases and could be associated with increased susceptibility to certain cancers. This review aims to present the latest research progress on how the ARMC5 gene plays its role in tumors. It outlines the basic structure of ARMC5 and the regions where it functions, as well as the diseases currently proven to be associated with ARMC5. Moreover, some evidence suggests its relation to embryonic development and the regulation of immune system activity. In conclusion, the ARMC5 gene is a crucial focal point in genetic and medical research. Understanding its function and regulation is of great importance for the development of new therapeutic strategies related to diseases associated with its pathogenic variants.
Humans ; Neoplasms/genetics* ; Armadillo Domain Proteins/genetics* ; Animals ; Genetic Predisposition to Disease ; Cytoskeletal Proteins/genetics* ; Tumor Suppressor Proteins/genetics*

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

ObjectiveTo comprehensively elucidate the potential mechanisms of Xiao Xumingtang （XXMT） combined with electroacupuncture （EA） collaboratively in alleviating cerebral ischemia/reperfusion （I/R） injury. MethodThe rat model of cerebral I/R injury was established using the modified suture-occluded method. Seven days after modeling， rats in the XXMT+EA groups were administered XXMT at low （15 g·kg^-1）， medium （30 g·kg^-1）， and high （60 g·kg^-1） doses， alongside daily 20-min EA treatment （stimulating acupoints GV14 and GV20）. Cerebral infarction and neuronal damage were evaluated using the Zea Longa test score， TTC staining， and TUNEL staining. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of NOD-like receptor hot protein domain related protein 3 （NLRP3）， Gasdermin D （GSDMD）， cysteinyl aspartate specific proteinase-1 （Caspase-1）， interleukin-1β （IL-1β）， and interleukin-18 （IL-18） in the ischemic area of the cerebral cortex. ResultCompared with the sham group， the I/R group showed a significant increase in neurological deficit scores and infarct volume （P<0.01）， along with a higher apoptosis rate of cortical neurons and elevated mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. In contrast， the medium- and high-dose XXMT combined with EA treatment significantly reduced neurological deficit scores and infarct volume （P<0.01）， and decreased the apoptosis rate of cortical neurons as well as the mRNA and protein expression levels of NLRP3， GSDMD， Caspase-1， IL-1β， and IL-18 （P<0.05）. The improvement showed a dose-dependent relationship with XXMT. ConclusionThe combined use of XXMT and EA can exert neuroprotective effects by modulating the NLRP3/GSDMD/Caspase-1 signaling pathway， thereby reducing neurological deficits， minimizing brain infarct size， and improving cortical neuronal damage.