Objective To explore the clinical features of fulminant type 1 diabetes mellitus (FT1DM). Methods The clinical data of 6 patients with FT1DM who were hospitalized in Jinshan Hospital of Fudan University from April 2020 to August 2024 were retrospectively analyzed. Their data were compared with that of 30 patients diagnosed with non-fulminant type 1 diabetes mellitus (NFT1DM) and diabetic ketosis or diabetic ketoacidosis (DKA) who were admitted to the hospital during the same period. The clinical characteristics of FT1DM were summarized. Results All 6 patients with FT1DM were male, with a disease course of 2.00 (1.75, 4.00) d. Three cases exhibited a history of prior infection, four tested positive for glutamic acid decarboxylase antibody (GADA), and five developed severe DKA. The glycated hemoglobin A_1C (HbA_1C) was (6.30±0.67) %, fasting C-peptide (FCP) was 0.07 (0.03, 0.15) ng/mL, 2-hour postprandial C-peptide (2h-CP) was 0.09 (0.03, 0.16) ng/mL. At discharge, all 6 patients received 4-injection insulin regimen, with a dose (0.69±0.15) U·kg⁻¹·d⁻¹. The body mass index (BMI), blood glucose/HbA_1C, blood potassium/HbA_1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2h-PG), high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), serum creatinine, and blood potassium levels in the FT1DM group were higher than those in the NFT1DM group (P＜0.05), while HbA_1C and glycated albumin (GA) levels were lower than NFT1DM group (P＜0.05). Conclusions FT1DM usually presents with an acute onset of DKA, may be accompanied by a history of preceding infection, and GADA can be positive. Patients with FT1DM have elevated blood glucose/HbA_1C, blood potassium/HbA_1C, FPG, 2h-PG, hs-CRP, ALT, serum creatinine, blood potassium levels, and require insulin therapy, while the HbA_1C and GA levels are lower.

Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.

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.

Objective To explore the risk factors associated with the development of acute respir-atory distress syndrome(ARDS)in patients with severe traumatic brain injury(sTBI)and to construct and validate a risk prediction model for ARDS in these patients.Methods Clinical data from 371 sTBI patients admitted to Yangzhou Affiliated Hospital of Yangzhou University between January 2017 and December 2023 were retrospectively collected.Patients were randomly divided into modeling group(n=259)and validation group(n=112)at a 7-to-3 ratio.A nomogram model was constructed after screening for risk factors using the Least Absolute Shrinkage and Selection Operator(LASSO)and multivariate Logistic regression analysis.Model performance was evaluated using the receiver operating characteristic(ROC)curve,area under the curve(AUC),Hosmer-Lemeshow test,calibration curve,and deci-sion curve analysis(DCA).Results Statistically significant differences were observed in heart rate,respiratory rate,pupil size,percutaneous oxygen saturation(SpO2),Glasgow Coma Scale(GCS)score,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,head Ab-breviated Injury Scale(AIS)score,chest AIS score,emergency intubation,pulmonary infection,associated chest trauma,midline shift,blood transfusion within 12 hours of admission,fluid intake within 24 hours of admission,shock,mechanical ventilation,hemoglobin level,hematocrit,white blood cell count,prothrombin time,international normalized ratio,total protein,albumin,serum calcium,oxygenation index,and base excess between the two groups(P＜0.05).Multivariate Lo-gistic regression analysis revealed that SpO2,pulmonary infection,and fluid intake within 24 hours of admission were predictors of ARDS in sTBI patients.The Hosmer-Lemeshow test results for the modeling and validation groups showed good fit(x2=10.373,P=0.240;x2=13.21,P=0.105).DCA results for both groups indicated net benefit at threshold probabilities ranging from 0％to 72％and 0％to 50％,respectively.Conclusion SpO2,pulmonary infection,and fluid in-take within 24 hours of admission are risk factors for ARDS in sTBI patients.The model constructed using these factors demonstrates good performance and provides a reliable tool for clinical screening of high-risk ARDS populations among sTBI patients.

BackgroundChildhood represents a critical stage for cognitive development. Accurate assessment of children's cognitive abilities and understanding their developmental characteristics are essential for promoting healthy growth. However， traditional cognitive assessment methods typically rely on manual administration， presenting limitations such as low efficiency and insufficient engagement. These methods struggle to meet the assessment needs of children and are difficult to scale up for large-scale applications. ObjectiveTo develop a digital cognitive assessment tool for children， so as to provide a more convenient approach for evaluating children's cognitive functions. MethodsBased on classic psychological paradigms （Stroop Task， N-back， digit span， spatial orientation， and face-name matching）， a digital cognitive assessment tool was developed. This tool includes five tasks including color matching， shape matching， greening the home， great collector， and face-name matching， designed to assess core cognitive functions such as inhibitory control， working memory， short-term memory， spatial orientation， and semantic processing， respectively. From August 2024 to March 2025， a total of 750 students aged 9–12 yeas old from a primary school in Chengdu were enrolled and assessed using the digital cognitive assessment tool. Three months later， 40 children were randomly selected for retesting using both the digital tool and its corresponding standardized psychological paradigms. Pearson correlation analysis was conducted to examine the correlation between the pre-test and retest scores of the digital cognitive assessment tool， as well as the correlation between the digital cognitive task scores and the corresponding psychological paradigm assessment results， in order to evaluate the reliability and validity of the digital cognitive assessment tool. Additionally， differences in scores across the cognitive tasks were compared among children of different age groups and genders. ResultsA total of 699 valid samples were included. The younger age group consisted of children aged 9–10 years old （n=460）， while the older age group comprised those aged 11–12 years old （n=239）. There were 356 boys （50.93%） and 343 girls （49.07%）. In the reliability analysis， the Pearson correlation coefficients between the pre-test and retest scores of each assessment task ranged from 0.732 to 0.970 （P<0.01）， indicating statistically significant results. In the validity analysis， the Pearson correlation coefficients between each task and its corresponding standard cognitive test ranged from 0.679 to 0.988 （P<0.01）. In the color-matching task， both the main effects of age and gender were statistically significant （F=31.071， 21.198， P<0.01）. In the shape-matching task， the main effects of age， gender， and their interaction were all statistically significant （F=20.933， 5.926， 4.318， P<0.05 or 0.01）. In the greening the home task， the main effect of age was significant （F=5.243， P=0.023）. In the great collector task， the main effect of age was significant （F=33.697， P<0.01）. In the face-name matching task， only the main effect of gender was significant （F=27.016， P<0.01）. Further analysis showed that within the female group， older group scored significantly higher than younger group in five tasks（P<0.05 or 0.01）. Within the male group， younger group scored lower than older group in both the color-matching and great collector tasks （P<0.05 or 0.01）. Within the younger group， boys scored significantly higher than girls in color-matching and shape-matching tasks （P<0.01）. In the older group， girls scored significantly higher than boys in face-name matching task （P<0.01）. ConclusionThe digital cognitive assessment tool developed in this study demonstrates good reliability and validity. The development of cognitive functions in children aged 9–12 years old showed significant differences in age and gender， with specific developmental trajectories across different cognitive dimensions. At younger ages， boys outperformed girls in inhibitory control and working memory tasks， though this advantage diminished with age. At older ages， girls exhibited superior performance in semantic processing compared with boys.

BACKGROUND:In recent years,research on the interaction mechanism between the immune system and the skeleton in postmenopausal osteoporosis has become a hot topic.However,the impact of changes in key immune-related cytokine expression on postmenopausal osteoporosis remains unclear and requires further exploration. OBJECTIVE:To investigate the differential expression of immune-related cytokines in bone marrow mesenchymal stem cells of mice with postmenopausal osteoporosis by bioinformatics methods. METHODS:Postmenopausal osteoporosis mouse model was established through ovariectomy.Bone marrow mesenchymal stem cells were obtained by the whole bone marrow adherence method and passaged to passage 2.RayBio L-Series Mouse Antibody Array 308 Glass Slide Kit immune-related factor antibody chip was used to detect the differentially expressed proteins in bone marrow mesenchymal stem cells from ovariectomy and sham-operation mice.Gene ontology,Kyoto Encyclopedia of Genes and Genomes enrichment analysis,and protein-protein interaction network analysis were performed to screen common Hub genes by MCC,EPC,and MNC algorithms. RESULTS AND CONCLUSION:This study identified a total of 68 differentially expressed genes.Gene ontology analysis revealed that the differentially expressed genes were enriched in terms including"immune system processes","extracellular regions",and"signal receptor binding".Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the differentially expressed genes were mainly enriched in"cytokine-cytokine receptor interactions","tumor necrosis factor signaling pathways",and"chemokine signaling pathways".Further screening was performed by constructing a protein-protein interaction network analysis of these 68 differentially expressed genes to identify 8 Hub genes.The violin plot and correlation matrix showed that the expression levels of these 8 Hub genes were significantly down-regulated in the ovariectomy group compared to the sham-operation group.These results demonstrated that there was differential expression of immune-related factors in bone marrow mesenchymal stem cells of postmenopausal osteoporosis mice,and key genes involved in cytokine-cytokine receptor interactions,immune system-related processes,and potential targeted signaling pathways and cellular biological processes were identified,providing new promising targets for the diagnosis,treatment,and prevention of postmenopausal osteoporosis.

BackgroundThere exist differences in the subjective and objective cognitive functions of patients with depressive disorder， ane there are limited research on influencing factors of such phenomenon currently. ObjectiveTo explore the differences in subjective and objective cognitive function in patients with depressive disorder as well as influencing factors， and to provide references for further understanding of cognitive impairment in patients with depressive disorder. MethodsA total of 77 patients with depressive disorder who received outpatient or inpatient treatment in the Fourth People's Hospital of Chengdu from January 13， 2022 to December 11， 2023 were selected for the study. These patients also met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition（DSM-5）. Various tools were employed to assess patients in this study： Montgomery-Asberg Depression Rating Scale （MADRS） for the depressive symptoms， Perceived Deficits Questionnaire for Depression （PDQ-D） and Chinese Version of Brief Neurocognitive Test Battery （C-BCT） for the subjective and objective cognitive function， Sheehan Disability Scale （SDS） for the social function， and Clinical Global Impression-Severity of Illness（CGI-SI） for the severity of patient's condition. Pearson correlation analysis was used to examine the correlation of subjective and objective cognitive function and their differences with age， years of education， MADRS total score， SDS total score， and CGI-SI score. Multiple linear regression was used to explore the influencing factors of the differences between subjective and objective cognitive function. ResultsThere was a statistically significant difference in the total PDQ-D scores and the difference of subjective and objective cognitive function （D value） between depressive patients with and without medication （t=-4.228， -2.392， P<0.05 or 0.01）. There was no statistically significant correlation in subjective and objective cognitive function in patients with depressive disorder （r=-0.148， P>0.05）. Negative correlations can be observed between the PDQ-D total score and age or years of education （r=-0.333， -0.369， P<0.01）. The PDQ-D total score was positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.487， 0.637， 0.434， P<0.01）. D value was negatively correlated with age and years of education （r=-0.411， -0.362， P<0.01）， while positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.259， 0.468， 0.299， P<0.05 or 0.01）. Age （β=-0.328， P<0.01） and SDS total score （β=0.409， P<0.01） were two predictive factors for D value. ConclusionThe difference between subjective and objective cognitive function among patients with depressive disorder is related to several factors including age， years of education， severity of symptoms and impairment of social function. ［Funded by Surface Project of National Natural Science Foundation of China （number， 62173069）； Technological Innovation 2030-Major Project of "Brain Science and Brain-Like Research" （number， 2022ZD0211700）； Key R&D Support Program and Major Application Demonstration Project of Chengdu Science and Technology Bureau （number， 2022-YF09-00023-SN）］

BackgroundBariatric surgery has emerged as an important tool in the management of obesity. Some patients undergoing bariatric surgery are prone to develop emotional abnormalities and have abnormally elevated concentrations of inflammatory factors level in peripheral blood， whereas current domestic research focusing on the impact of preoperative emotional states and peripheral blood inflammatory factors level on weight loss effect remains limited. ObjectiveTo explore the correlation of preoperative emotional abnormalities with the effectiveness of bariatric surgery in obese patients， and to provide theoretical basis for improving the clinical efficacy of bariatric surgery. MethodsEighty-one obese patients scheduled for bariatric surgery at gastrointestinal surgery Department of West China Hospital， Sichuan University from December 30， 2022 to June 30， 2023 were enrolled and assessed using Hamilton Depression Scale-17 item （HAMD-17） and Hamilton Anxiety Scale （HAMA）. Patients who scored 7 or above on HAMD-17 or HAMA or had a history of previous depression or anxiety diagnoses were classified into emotional abnormality group （n=34）， and samples who scored less than 7 on HAMD-17 and HAMA and were free of history of previous depression and anxiety diagnoses were set as non-emotional abnormality group （n=47）. The data were collected by the self made questionnaire. Patients were subjected to complete the assessment of Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）， Eating Disorder Inventory （EDI） and Pittsburgh Sleep Quality Index （PSQI）. Laboratory tests including peripheral blood C-reactive protein （CRP） and interleukin-6 （IL-6）. Body weight and height assessed in the early morning after an overnight fasting period were recorded in all participants at 1- and 6-month after surgery through outpatient clinic visits or telephone follow-up. Pearson correlation coefficient was used to examine relationship among body mass index （BMI）， preoperative emotional states and peripheral blood inflammation mediators. ResultsAmong 81 obese patients， 62 completed the study， including 27 cases in emotional abnormality group and 35 cases in non-emotional abnormality group. Emotional abnormality group scored higher on BSI-CV （current）， BSI-CV （worst）， EDI and PSQI， and detected higher levels of CRP and IL-6 compared with non-emotional abnormality group （Z=2.677， 2.975， t=3.573， 4.035， 1.990， 2.799， P<0.05 or 0.01）. For BMI， there was no significant group effect and time×group interaction effect （P>0.05）， but a significant time effect （F=227.740， P<0.01）. Within emotional abnormality group， BMI at the baseline， 1- and 6-month after surgery showed a positive correlation with IL-6 level （r=0.419， 0.510， 0.559， P<0.05 or 0.01）， BMI at 6-month after surgery was positively correlated with HAMD-17 total score （r=0.390， P<0.05）， and ΔBMI% at 6-month after surgery was negatively correlated with HAMD-17 total score （r=-0.421， P<0.05）. Within non-emotional abnormality group， baseline BMI was positively correlated with IL-6 level （r=0.338， P<0.01）. ConclusionThe short-term effect of bariatric surgery may be comparable in obese patients with or without emotional abnormalities， while it cannot be ruled out whether the outcome of bariatric surgery is related to the severity of preoperative depression.

AIM:To investigate the effect of plate-let(PLT)on angiogenesis in hepatocellular carcino-ma and the intervention effect of Cinobufagin(CBG).METHODS:Firstly,we screened the suitable co-incubation ratio of PLT and hepatocellular carci-noma cells,prepared conditioned medium,and de-termined the half inhibitory concentration of Cinob-ufagin;then,we set up a control group(human um-bilical vein endothelial cells(EC)+conventional me-dium),a crosstalk group(EC+CM_HP(strip culture prepared by crosstalk of HUH7 and PLT)),and an in-tervention group(EC+CM_HP+CBG).The migration,tube-formation and sprouting capacity of EC and the level of vascular endothelial growth factor(VEGF)in co-cultured supernatant were evaluated by scratch assay,tube-formation assay,budding as-say and ELISA assay.Western blot was used to de-tect the expression of VEGFR2 and p-VEGFR2,and reverse verification was performed with inhibitors.A subcutaneous transplantation tumour model of hepatocellular carcinoma in nude mice was estab-lished,with Model group,Model+CBG group and Model+Apa group.The collagen expression of the transplantation tumour was observed by Masson staining,and the expression levels of vascular endo-thelial markers CD31 and CD34 were detected by immunofluorescence.RESULTS:When PLT:HUH7=200,the activity of HUH7 was the strongest,and the crosstalk between HUH7 and PLT significantly promoted the proliferation of EC(P＜0.01).Com-pared with Control group,the migration,tube-for-mation and budding ability of Crosstalk group were enhanced,and those of Intervention group were lower than those of Crosstalk group(P＜0.01).The expression level of VEGF in the supernatant of Crosstalk group was higher than that of Control group,while that of Intervention group was lower than that of Crosstalk group(P＜0.01).The expres-sion level of p-VEGFR2 protein in Crosstalk group was significantly higher than that of Control group,but the expression level of Intervention group was lower than that of Crosstalk group(P＜0.01).Large collagen fibre deposition was seen in the Model group,and CBG intervention significantly reduced collagen fibre deposition in the transplanted tu-mour tissues.CD31 and CD34 expression was pres-ent in the hepatocellular carcinoma transplanted tumour tissues in the Model group,and CBG inter-vention significantly reduced the expression of CD31 and CD34 in the liver cancer transplanted tu-mour tissues(P＜0.01).CONCLUSION:PLT enhances angiogenesis in hepatocellular carcinoma,and CBG may inhibit its tube-forming ability via the VEGF/VEGFR2 pathway.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.