Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To investigate the differences in clinical and imaging characteristics of patients with recent small subcortical infarct (RSSI) stratified by different etiological subtypes.Methods:A retrospective, consecutive analysis was conducted on 696 RSSI patients admitted to the West China Hospital, Sichuan University, from January 2019 to May 2024. Based on clinical and imaging data, patients were stratified into 3 etiological subgroups: presumed cerebral small vessel disease (CSVD)-related RSSI, coexisting carrier large artery stenosis, and coexisting proximal extracranial/intracranial large artery stenosis. The clinical characteristics, vascular risk factors, infarct imaging features, and CSVD markers were compared across the 3 groups. Additionally, the differences in clinical and imaging features based on the location of infarcts (anterior vs posterior circulation) and infarct size (<15 mm vs ≥15 mm) were examined. Results:Among the 696 patients, 557 (80.0%) had presumed CSVD-related RSSI, 68 (9.8%) had coexisting carrier large artery stenosis, and 71 (10.2%) had coexisting proximal extracranial/intracranial large artery stenosis. The patients with presumed CSVD-related RSSI were the youngest [60 (53, 69) years], followed by those with coexisting carrier large artery stenosis [64 (55, 69) years] and those with coexisting proximal extracranial/intracranial large artery stenosis [69 (55, 75) years; H=9.523, P=0.013]. Among RSSI patients with coexisting proximal extracranial/intracranial large artery stenosis, the proportion of those with diabetes (38/71, 53.5%) was the highest, whereas the proportion was 210/557 (37.7%) in the presumed CSVD-related group and 31/68 (45.6%) in the group with coexisting carrier large artery stenosis (χ 2=8.027, P=0.023). Patients with RSSI combined with proximal extracranial/intracranial large artery stenosis had more infarction sites in the pons and a higher proportion of proximal infarction. However, there were no significant differences among the 3 groups in terms of infarct size, or CSVD imaging markers. In the anterior versus posterior circulation comparison, patients with posterior circulation RSSI ( n=360) had a significantly higher age of onset [63(55, 72) years vs 60(52, 59) years, U=51 335.500, P<0.001], had higher prevalence of hypertension and diabetes, and showed higher NIHSS scores [3(2, 6) vs 3(1, 5), U=57 840.500, P=0.028]. The anterior circulation group ( n=366) showed a higher proportion of lacunas [152/336 (45.2%) vs 118/360 (32.8%), χ2=11.364, P<0.001], while the posterior circulation group had a greater prevalence of severe perivascular spaces in the basal ganglia [254/360 (70.6%) vs 203/336 (60.4%), χ2=7.879, P=0.005] and deep white matter hyperintensities grading≥2 [124/360 (34.4%) vs 90/336 (26.8%), χ2=4.787, P=0.029]. There were no statistically significant differences in the distribution of infarcts between anterior and posterior circulations or in CSVD imaging markers between RSSI patients with infarction lesions ≥15 mm ( n=290) and <15 mm ( n=406). Conclusions:Approximately 20% of RSSI cases are related to large artery stenosis. These patients tend to be older at onset and have a higher prevalence of diabetes. Compared to presumed CSVD-related RSSI cases, RSSI cases related to large artery stenosis show no significant differences in infarct imaging features and CSVD imaging markers, suggesting that large artery stenosis in RSSI may be an epiphenomenon rather than a direct causative factor.

Objective To explore the effect of evening primrose oil(EPO)on aortic endothelial damage in rats with polycystic ovary syndrome(PCOS),using network pharmacology and in vivo experiments.Methods The potential targets of EPO for improving aortic endothelial injury in PCOS rats were predicted by network pharmacology,and the selected core targets and renin-angiotensin signaling(RAS)pathway were verified by experiments.Fifty-eight female SD rats were divided randomly into a blank group(n=10)and a modeling group(n=48).Rats in the blank group were fed a normal diet and rats in the modeling group received a high-fat diet for 8 weeks.The PCOS model was prepared at week 6 by administration of letrozole(1 mg/(kg·d))for 21 days.Blood was taken from the tail vein after modeling and serum was collected to detect hormone levels.The model rats were then divided randomly into four groups and treated with the corresponding drugs for 6 weeks.Blood,blood vessels,and ovaries were then collected.Tissue morphology was examined by hematoxylin and eosin staining and serum levels of luteinizing hormone(LH),testosterone(T),follicle-stimulating hormone(FSH),endothelin(ET-1),and tumor necrosis factor(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).Serum levels of nitric oxide(NO)were determined by spectrophotometry.Protein expression levels of core targets and RAS pathway-related factors were assessed by western blotting and immunohistochemistry.Results Twenty-five intersection targets of EPO and PCOS were identified by network pharmacological analysis.Kyoto encyclopedia of genes and genomes analysis showed that EPO improved vascular injury in PCOS rats via multiple pathways,including RAS.Serum levels of ET-1,FSH,LH,and T measured by ELISA were significantly decreased after EPO treatment,compared with the model group(P＜0.01).EPO significantly decreased the expression levels of Ang Ⅰ,VEGF-B,AT2R,ET-1,and TNF-α proteins in the aorta(P＜0.01)and significantly increased expression levels of Ang Ⅱ,CD31,and endothelial NO synthase proteins(P＜0.01).Conclusions EPO may ameliorate vascular endothelial injury in PCOS model rats by inhibiting the RAS signaling pathway and by overactivation of the ACE/Ang Ⅱ/AT1 axis.

This study aims to screen the diagnostic biomarkers for fecal antigen of Echinococcus granulosus(E.granulosus)in dogs with high specificity and sensitivity.The sheep-derived EgPSC artificially infected dogs were collected,and the negative and positive fecal samples of dogs with E.granulosus were prepared by arecoline hydrobromide leakage method.Polyclonal antibody,negative fecal antigen-polyclonal antibody conjugates and positive fecal antigen-polyclonal antibody conju-gates were purified by ammonium sulfate precipitation and affinity chromatography,three groups of samples were detected by ELISA and Western blot,LC-MS/MS and bioinformatics analysis were performed on the three groups of samples.The positive fecal antigen-polyclonal antibody con-jugate was used as the treatment group,the polyclonal antibody and the negative fecal antigen-polyclonal antibody conjugates were used as the control groups to screen the unique peptides of the treatment group.ELISA and Western blot showed that only the positive fecal antigen-polyclonal antibody conjugates were positive.According to LC-MS/MS and bioinformatics analysis,11 unique peptides were screened out only in the treatment group.Among them,3 proteins were related to E.granulosus,namely dysferlin,integrator complex 9 and diagnostic antigen gp50,which were mem-brane-associated proteins,INT complex components and diagnostic antigens.This study has pre-liminarily screened out three candidate canine E.granulosus fecal antigen diagnostic markers,pro-viding a reference for further exploration of diagnostic standards for E.granulosus,screening of echinococcosis target genes,and vaccine development.

The Diagnosis-Intervention Packet(DIP)payment exerts notable effects on hospitals' economic operations.As centralized hubs of high-quality medical resources,tertiary hospitals face a functional mismatch with the provision of services for primary care diseases.By analyzing the admission and payment practices for primary care diseases in sample hospitals in Henan Province,it identifies key challenges,including inadequate alignment between healthcare payment reform policies and management systems,weak foundational capabilities in hospital health insurance informatization,and insufficient awareness of health insurance policies among medical staff.It is recommended that hospitals should strengthen communication and coordination with health insurance administration agencies to foster positive interactions between healthcare providers and insurers;continuously advance in-house health insurance informatization and enhance data governance capabilities;improve strategic awareness and innovate value-based health insurance management models.

Osteosarcoma is a highly aggressive primary bone tumor that predominantly affects children and adolescents.Conventional treatment modalities are often hindered by issues such as high recurrence rates and the development of drug resistance.Proteolysis-Targeting Chimeras(PROTACs)represent an innovative therapeutic strategy for osteosarcoma,which are designed to selectively degrade pathogenic proteins.This article offers a comprehensive analysis of the mechanisms underlying PROTACs,their tar-geted applications in osteosarcoma—including bromodomain and ultra-terminal domain targeting—and the associated challenges,such as delivery efficiency and off-target toxicity.Additionally,it suggests optimi-zation strategies for bone-targeted delivery(such as using DNA nanoflowers as carriers)and combination therapies(like targeted therapy and chemotherapy),informed by recent research findings,thereby provi-ding a theoretical framework for clinical translation.

This article reports a patient with long-term ulcerative colitis (UC) who was initially diagnosed as eosinophilic gastroenteritis due to a increase in peripheral blood eosinophils. During the diagnosis and treatment process, acute myocardial infarction was repeatedly induced. The patient was eventually diagnosed as UC complicated by amoebic infection and improved after anti-infective therapy. Through case analysis and literature review, this article discusses the diagnosis and treatment strategies for UC complicated by rare opportunistic infections.