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*

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To investigate the expression of microRNA-508-3p(miR-508-3p)in epithelial ovarian cancer(EOC)tissue,its impact on the migration and invasion of ovarian cancer cells,and its regulatory relationship with zinc-finger E-box-binding homeobox 1(ZEB1).Methods The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected.SKOV3 cells were divided into the NC mimic group(transfected with NC mimic),miR-508-3p mimic group(transfected with miR-508-3p mimic),si-NC group(transfected with si-NC),si-ZEB1 group(transfected with si-ZEB1)and co-transfection group(co-transfected with si-ZEB1 and miR-508-3p mimic).The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues,adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction.The Transwell assay was used to detect the cell migration and invasion abilities.Results The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40,the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95,and the differences were statistically significant(all P＜0.01).The migration cell number of the NC mimic,miR-508-3p mimic,si-NC,si-ZEB1 and co-transfection groups was 633.00±32.49,319.20±19.89,650.40±25.85,375.00±17.25 and 129.40±17.10;the invasion cell number was 527.20±25.01,288.60±16.68,520.00±25.83,293.40±18.37 and 76.60±8.76;the relative expression levels of miR-508-3p were 1.05±0.37,3.94±1.21,1.01±0.21,1.26±0.34 and 3.40±0.41;the relative expression levels of ZEB1 mRNA were 1.00±0.04,0.58±0.05,1.00±0.08,0.54±0.07 and 0.29±0.03,respectively.The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group,between the si-NC group and the co-transfection group(P＜0.01,P＜0.05).Conclusion MiR-508-3p is lowly expressed in EOC cancer tissue,and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.

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.

Outpatient services reflect the overall management level of hospitals and is a key link affecting patients′ healthcare experiences. To address the challenges faced by traditional outpatient services and meet patients′ diverse medical needs, a tertiary hospital implemented personalized outpatient services in March 2024. By utilizing information technologies such as big data and artificial intelligence, patient profile and a personalized service knowledge base was constructed, and a personalized outpatient service platform was built (including various functional modules such as intelligent guidance, pre consultation, abnormal indicator management, and full course management, as well as intelligent recommendation engines). This platform could provide personalized health guidance, customer service, and diagnosis and treatment services for outpatient throughout the entire process from pre-diagnosis to post diagnosis.After the launch of the personalized outpatient service platform, patient satisfaction in the oncology and pediatric departments increased from 90% and 86% in May 2024 to 94% and 91% in May 2025, respectively. From May 2024 to May 2025, the intelligent customer service addressed 740 000 patient inquiries, with a resolution rate of 90%. The online conversion rate (the proportion of patients switching from offline visits to online follow-ups relative to the total number of offline visits during the same period) rose from 37% in May 2023 to 43% in May 2025. The platform had enhanced the quality and efficiency of outpatient services, effectively improved patients′ healthcare experiences, and could serve as a reference for other hospitals seeking to upgrade their outpatient services.

AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.