Objective To analyze the composition characteristics and biological functions of tumor cell subpopulations in glioblastoma(GBM)through multi-transcriptomics sequencing technology,and explore the hypoxia characteristics and spatial localization features of the mesenchymal-like(MES-like)tumor cell subpopulation in GBM and the influence on malignant biological behaviors.Methods Multi-transcriptomics sequencing data,including single-cell RNA sequencing(scRNA-seq)data(18 patients),bulk RNA sequencing(bulk RNA-seq)and spatial transcriptomics(ST)data of GBM,were employed to define cell subpopulations in GBM,and Gene Ontology(GO)and Gene Set Enrichment Analysis(GSEA)were utilized to analyze their functions.The proportions and locations of cell subpopulations in bulk RNA-seq data were evaluated with BayesPrism deconvolution.Immunofluorescence assay was conducted for verification on 12 paraffin samples of GBM from patients who visited the neurosurgical department of our hospital from 2015 to 2023 and met the pathological diagnostic criteria for GBM(10 males and 2 females,at an average age of 53.50 years and a median age of 54.50 years).pySCENIC was applied to predict specific transcription factors of tumor cell subpopulations.Results Tumor cells in GBM were highly heterogeneous,and could be mainly divided into 4 subpopulations:astrocyte-like(AC-like),neural progenitor-like(NPC-like),oligodendrocyte progenitor-like(OPC-like)and MES-like.Differential gene analysis found that the MES-like tumor cells highly expressed vascular endothelial growth factor A(VEGFA),adrenomedullin(ADM),N-myc downstream regulated 1(NDRG1),insulin like growth factor binding protein 5(IGFBP5),and A-kinase anchoring protein 12(AKAP12)(P<0.001).pySCENIC transcription factor prediction found that the high-active transcription factors of the MES-like tumor cells were AT-rich interaction domain 3A(ARID3A),FOS like 2,AP-1 transcription factor subunit(FOSL2),endothelial PAS domain protein 1(EPAS1),CCAAT enhancer binding protein delta(CEBPD),and CCAAT enhancer binding protein beta(CEBPB)(P<0.05).GO and GSEA enrichment analyses found that the MES-like tumor cells were enriched in hypoxia-related pathways,especially the pathway of cell responses to hypoxia levels(NES=2.437,P<0.001).BayesPrism deconvolution showed that the MES-like tumor cells mainly existed in PAN(Pseudopalisading cells around necrosis)and perinecrotic zone.Immunofluorescence assay confirmed CD44+(CD44 antigen)MES-like tumor cells were mainly located in hypoxia areas with highly expression of hypoxia inducible factor 1 subunit alpha(HIF1α)(P<0.01).Multivariate Cox regression analysis indicated that the MES-like tumor cells were significantly correlated with the adverse prognosis of GBM patients(HR=1.71,95%CI:1.38～2.11,P<0.001).Conclusion Tumor cells in GBM are of highly heterogeneity.They could be mainly divided into 4 subpopulations:AC-like,NPC-like,OPC-like and MES-like.MES-like tumor cells,mainly locating in PAN and perinecrotic zone,are characterized by hypoxia,which can promote the malignant progression of GBM.

Under the background of forensic medicine becoming a first-level discipline,the opportuni-ties and challenges of discipline development coexist.Starting from the actual situation and characteris-tics of local medical colleges and universities,this paper discusses the problems and solutions for the development of forensic medicine discipline from the perspective of building a regional high-level medical university.Combined with the experiences of carrying out forensic medicine education in our college,this paper supplies our thoughts and practices on improving the discipline system,enhancing the ability to serve society,perfecting the talent cultivation model and promoting forensic culture,to provide reference and inspiration for the development of forensic medicine in other universities,jointly promote the advancement of forensic medicine in China to a new stage,and contribute the wisdom and strength of forensic medical experts to the construction of a law-based China,a safe China and a healthy China.

BACKGROUND: There is a gap in understanding the effects of different acupoints and treatment methods (acupuncture and moxibustion) on microcirculatory changes in the lumbar region. OBJECTIVE: This study aimed to assess the thermal effects of acupuncture at Weizhong (BL40), with acupuncture at Chize (LU5) and moxibustion at both acupoints as control interventions. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: In this randomized controlled trial, 140 healthy participants were equally divided into four groups: acupuncture at BL40 (Acu-BL40), acupuncture at LU5 (Acu-LU5), moxibustion at BL40 (Mox-BL40) and moxibustion at LU5 (Mox-LU5). Participants underwent a 30-minute session of their assigned treatment. Infrared thermal imaging was used to collect temperature data on the areas of interest for analysis. MAIN OUTCOME MEASURES: The primary measure was the change in average temperature of the observed area after the intervention. The secondary measures included periodic temperature changes every 5 min and the temperature changes of the Governor Vessel and Bladder Meridian in the observed area after the intervention. RESULTS: Significant interactions were observed between treatments and acupoints affecting temperature (P < 0.001). The Acu-BL40 group showed a notably higher increase in mean temperature after 30 min compared to the Acu-LU5 and Mox-BL40 groups, with increases of 0.29 (95% confidence interval [CI] = 0.17 to 0.41) and 0.24 (95% CI = 0.08 to 0.41) °C, respectively. CONCLUSION: Acupuncture at BL40 acupoint can significantly increase the mean temperature in the observed area, highlighting the specific thermal effect of acupuncture compared to moxibustion in the lumbar area. This suggests a potential therapeutic benefit of acupuncture at BL40 for managing lumbar conditions. TRIAL REGISTRATION ClinicalTrials.gov (NCT05665426). Please cite this article as: Zheng SY, Wang XY, Lin LN, Liu S, Huang XX, Liu YY, Yu XS, Pan W, Fang JQ, Liang Y. Lumbar temperature change after acupuncture or moxibustion at Weizhong (BL40) or Chize (LU5) in healthy adults: A randomized controlled trial. J Integr Med. 2025; 23(2): 145-151.
Adult ; Female ; Humans ; Male ; Young Adult ; Acupuncture Points ; Acupuncture Therapy ; Body Temperature ; Healthy Volunteers ; Lumbosacral Region/physiology* ; Moxibustion ; Adolescent

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

OBJECTIVE To explore the differences in T lymphocyte subsets of the severe pneumonia(SP)patients among different age groups and analyze its relationship with the prognosis.METHODS A total of 100 patients with SP who were treated in the First Affiliated Hospital of Zhengzhou University from Mar.2018 to Jun.2024 were enrolled in the study and were divided into the youth group with 22 cases(less than 40 years old),the middle age group with 36 cases(aging between 40 and 65 years old)and the old age group with 42 cases(more than 65 years old).The clinical data and the laboratory test indexes were compared among the three groups.The levels of CD3+,CD4+,CD8+and CD4+/CD8+before and after the treatment were compared among the three groups by repeated measures variance method.RESULTS The length of hospital stay of the old age group was longer than those of other two groups;the acute physiology and chronic health evaluation(APACHE)Ⅱ score,clinical pul-monary infection score(CPIS)and the levels of interleukin-6(IL-6),platelets(PLT),white blood cells(WBC),C-reactive protein(CRP)and lactic dehydrogenase(LDH)levels were higher in the old age group than in other two groups(P＜0.05).The levels of CD3+,CD4+,CD8+and CD4+/CD8+of all the three groups were elevated after the treatment,with the highest in the young group after the treatment for 2 months[the CD3+level(56.25±5.21)％,the CD4+level(35.65±2.43)％,the CD8+level(22.33±1.74)％,and the CD4+/CD8+(1.97±0.25)],the lowest in the old age group[after the treatment for 2 months the CD3+level(49.46±2.67)％,the CD4+level(28.45±3.45)％,the CD8+level(15.68±2.23)％,and the CD4+/CD8+(1.46±0.14)],there were significant differences(F=21.830,P=0.045;F=41.870,P=0.024;F=71.914,P=0.014;F=48.463,P=0.020).CONCLUSION The CD3+,CD4+,CD8+and CD4+/CD8+have great clinical significance in diagnosis of SP for different age groups of patients and assessment of illness condition.

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.

Objective:To summarize the long-term efficacy of nicotinamide in treating pediatric early-onset progressive encephalopathy with brain edema and (or) leukoencephalopathy-2 (PEBEL2) caused by NAXD gene variation .Methods:This was a case report conducted from February 2019 to January 2025. The long-term efficacy of nicotinamide was observed by following up a child with PEBEL2 who received the treatment in the Department of Neurology, Beijing Children′s Hospital Affiliated to Capital Medical University. The clinical data included changes in skin lesions, neurological symptoms. The modified Rankin scale (mRS) was used to evaluate the recovery of neurological function.Results:A boy was diagnosed with PEBEL2 caused by NAXD gene variation via genetic testing at Beijing Children′s Hospital Affiliated to Capital Medical University in February 2019, when he was 4 years and 6 months of age. Immediately after diagnosis, nicotinamide treatment was initiated at an initial dose of 100 mg/d, which was increased by 100 mg per week and gradually increased to 500 mg/d; meanwhile, other therapeutic drugs were gradually discontinued. After 1 year and 8 months of treatment, the child′s skin lesions had completely resolved; at the 2-year follow-up, dystonia in both upper limbs and swallowing dysfunction was alleviated significantly; by 2.5-year follow-up, his cognitive function also showed improvement. When the child was treated with 500 mg/d for 3 years, a rash appeared around the mouth. After the dose was reduced to 250 mg/d, the rash resolved, and the dose of 250 mg/d was maintained until the last follow-up. At the last follow-up in January 2025, the child was 10 years and 5 months of age. His mRS score decreased from 5 (before treatment) to 4. During the 6-year of continuous nicotinamide treatment, the child′s condition remained stable without progression. Drug-related skin rashes occurred, but no severe drug-related adverse reactions were observed.Conclusions:PEBEL2 is a treatable mitochondrial disease. Nicotinamide treatment can effectively improve skin lesions and neurological symptoms in PEBEL2 patients, and the long-term administration demonstrates a favorable safety profile.

Background and Aims:Mucinous adenocarcinoma of the colorectum(MAC)is a distinct histologic subtype of colorectal cancer characterized by high malignancy and low diagnostic accuracy of preoperative biopsy,posing challenges for clinical decision-making.Given the critical role of the inflammatory microenvironment in tumor progression,this study aimed to develop and validate a nomogram model integrating preoperative systemic inflammatory indicators and clinical features to improve the preoperative diagnosis of MAC.Methods:Clinical data of 293 patients with colorectal cancer who underwent radical resection between June 2017 and June 2022 at the First Affiliated Hospital of the University of South China were retrospectively analyzed.Based on postoperative pathology,patients were classified into the mucinous adenocarcinoma(MAC)group and the non-specific adenocarcinoma(AC)group.Propensity score matching(PSM,1∶1)was used to balance age,T stage,and N stage.Differences in preoperative inflammatory indices were compared between groups.Univariate and multivariate logistic regression analyses were performed to identify independent predictors of MAC,which were incorporated into a diagnostic nomogram.The model's discrimination,calibration,and clinical utility were evaluated using the area under the receiver operating characteristic curve(AUC),calibration plots,and decision curve analysis(DCA).Results:Among the 293 patients,46 had MAC and 247 had AC,with a preoperative colonoscopic diagnostic rate of 54%for MAC.After PSM(43 pairs),platelet count,platelet lymphocyte ratio(PLR),systemic immune inflammation index(SII),inflammation related prognostic index(IPI),and systemic inflammation score(SIS)were significantly higher in the MAC group,while lymphocyte monocyte ratio(LMR)was lower(all P<0.05).Multivariate analysis identified tumor location,maximum tumor diameter,and preoperative IPI as independent predictors.The AUCs of the nomogram in the training(n=206)and validation(n=87)cohorts were 0.759(95%CI=0.662-0.856)and 0.776(95%CI=0.649-0.903),respectively.Calibration plots showed good agreement between predicted and observed probabilities,and DCA demonstrated satisfactory clinical applicability.Conclusion:A nomogram model integrating tumor location,tumor size,and preoperative IPI was successfully developed and validated for preoperative diagnosis of colorectal MAC.This model provides a practical,quantitative tool with good predictive performance to assist clinicians in individualized treatment planning,particularly for patients ineligible for surgical biopsy.