Objective: To optimize the technology and process for recovering immune cells from discarded leukocyte filter through reverse flushing, and to investigate the effects of different reverse flushing solutions and physical conditions (temperature, soaking, and ultrasound) on the cell recovery rate. Additionally, to evaluate the feasibility and quality of isolating and culturing NK cells from the recovered cells. Methods: Normal saline, PBS, and PBS-EDTA were used as reverse flushing solutions to backwash the filter, and the white blood cell recovery rates were compared. The reverse flushing efficiency was optimized by adjusting the temperature of the reverse flushing solution, filter soaking treatment and ultrasonic treatment. The Ficoll separation method was employed to isolate peripheral blood mononuclear cells (PBMCs) from the elution solution and conduct in vitro expansion and culture. Lymphocyte subsets were identified and quantified using flow cytometry. Results: The physiological saline served as the backflush fluid was the most stable. The reverse temperature had a significant impact on the recovery rate of white blood cell subgroups. The recovery rates of lymphocytes and monocytes at 37℃ were significantly higher than those at 4℃ [(35.56±5.55)% vs (22.88±0.31)%, (32.42±4.82)% vs (8.00±1.6)%, t=5.581 and 5.758, respectively, both P<0.001)], and at 25℃ [(35.56±5.55)% vs (22.42±6.13)%, t=5.904, P<0.001; (32.4±4.82)% vs (21.11±1.23)%, t=2.629, P=0.030)]. The recovery rates of white blood cell subgroups after 37℃ immersion were higher than those after direct reverse flow at 37℃, but the difference was not statistically significant (P>0.05). The recovery rate of cells after ultrasonic immersion at 25℃ was further increased compared to that after immersion at 25℃, but the difference was not statistically significant (P>0.05). The purity of the NK cells obtained through sorting reached (94.2±4.5)%, and the viability was (94.8±0.9)%. After 15 days of culture, the cell count was expanded approximately 450 times, yielding more than 10 /mL highly active NK cells. Conclusion: By optimizing the backflushing process, immune cells can be efficiently recovered from discarded filters. The 37℃ backflow liquid has the best backflow effect; soaking and ultrasonic treatment can be used as auxiliary methods to improve recovery rates. The NK cells from this source have high purity, good activity, and strong expansion ability, and can be used as a reliable cell source for immunotherapy research, and in line with the circular economy concept of resource reuse.

Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

Objective:To investigate the application effect of a novel zipper device in wound healing after incision and drainage of cuta-neous abscesses in children,and to explore its optimal intervention timing.Methods:A total of 50 children who attended the outpatient service of Department of Pediatric surgery from September 2023 to September 2024 were enrolled and divided into two groups accord-ing to the parity of the date of visit.The 26 children with the odd date of visit were enrolled as experimental group,and the 24 children with the even date of visit were enrolled as control group.The same anti-infective dressings were used for wound dressing in both groups after incision and drainage,and when there was a significant reduction in wound exudate and the fresh granulation tissue emerged at wound base,the zipper device was used for the children in the experimental group,and dressing change was performed for the children in the control group until the wound was completely healed.The two groups were compared in terms of wound healing time,healing rate,and the total costs of dressing change,and the multiple linear regression model and the restricted cubic spline(RCS)model were used to analyze the association between the in-tervention time of the zipper device and wound healing time.Re-sults:Compared with the control group,the experimental group had a significantly shorter wound healing time,a significantly higher wound healing rate,and significantly lower total costs of dressing change(P<0.001).The multiple linear regression model showed that the infection size of skin abscess and the intervention time of the zipper device were strongly associated with wound healing time(P<0.05).After adjustment for infection size,the RCS model analysis showed a significant linear dose-response relationship between intervention time and wound healing time(Pnonlinear=0.406),and wound healing time shortened with the reduction in intervention time(P<0.001).Conclusion:The application of the novel zipper device can help with the healing of cutaneous abscesses in children,and it is recommended to apply the device as early as possible after control of wound infection,in order to promote early wound healing.

BackgroundSevere mental disorders are characterized by high recurrence rate， high disability rate， high rates of harmful incidents， and low treatment-seeking rate， with affected patients demonstrating increased frequencies of dangerous behaviors. Ningxia Hui Autonomous Region has implemented community management for patients with severe mental disorders across the region since 2004， while the current status and regional characteristics of the managed patients remain unclear. ObjectiveTo analyze the current status of management and treatment of patients with severe mental disorders in Ningxia Hui Autonomous Region， and to explore their regional distribution characteristics， so as to provide references for optimizing regional prevention and control strategies. MethodsPatients with severe mental disorders diagnosed and registered in the Severe Mental Disorder Management Information Platform of Ningxia Hui Autonomous Region from August 1， 2011 to December 31， 2021 were selected. Patients' basic information， management indicators， and treatment metrics were extracted from the platform， followed by descriptive statistical analysis of the corresponding data. ResultsAs of December 31， 2021， the permanent resident population of Ningxia Hui Autonomous Region was 6 946 540， with 29 787 registered patients with severe mental disorders. The majority of the patients were female （50.25%）， aged 18-59 years （79.01%）， with educational level of junior high school or below （84.63%）， married （52.87%）， farmers （56.01%）， and diagnosed with schizophrenia （55.91%）， while ethnic minority patients accounted for a relatively high proportion （31.35%）. In 2021， the reported prevalence rate of severe mental disorders in Ningxia Hui Autonomous Region was 0.43%， with standardized management and regular medication adherence rates at 90.39% and 66.34%， respectively. The standardized management rate in 8 counties/districts （36.36%） was lower than the average level of Ningxia Hui Autonomous Region， while 10 counties/districts （45.45%） showed below-average medication adherence rates， of which 6 counties/districts（60.00%） were located in the south-central region. ConclusionPatients with severe mental disorders in Ningxia Hui Autonomous Region are predominantly young and middle-aged adults with low level of education， and those in the central-southern region demonstrate lower medication adherence. ［Funded by Key Research and Development Program Project of Ningxia Hui Autonomous Region （number， 2023BEG02029）］

Objective To investigate the characteristics and correlation between peak oxygen uptake(VO?peak)and heart rate recov-ery(HRR)during cardiopulmonary exercise test(CPET)in patients with coronary borderline lesions.Methods From January,2022 to January,2024,183 patients with coronary borderline lesions in Beijing Bo'ai Hospital were divided into low cardiorespiratory fitness(LCF)group(n=61),moderate cardiorespiratory fitness(MCF)group(n=62)and high cardiorespiratory fitness(HCF)group(n=60)based on VO?peak.Their characteristics and CPET parameters including VO?peak,exercise-phase heart rate(HR1,HR2,HR3),and post-exercise heart rate recovery(HRR1,HRR2,HRR3)were analyzed.Results After adjusting for age and body mass index,analysis of covariance showed that the peak heart rate,HR1,HR2 and HR3 were the lowest in LCF group(F>5.388,P<0.01).Repeated-measures analysis of variance showed that the inter-and intra-group effects were significant in HRR(F>14.561,P<0.001).Partial correlation analy-sis showed that VO?peak positively correlated with HRR1(r=0.404,P<0.001),HRR2(r=0.379,P<0.001)and HRR3(r=0.425,P<0.001).Conclusion In patients with coronary artery borderline lesions,VO?peak demonstrated a significant inverse correlation with HRR,the lower the VO?peak,the more delays of HRR.

Objective To analyze the correlations of autoimmune diseases(AIDs)with the risk of developing pancreatic endocrine and exocrine diseases.Methods A total of 451,497 participants from the UK Biobank were recruited,with the primary outcomes being pancreatic endocrine and exo-crine diseases.International Classification of Diseases 9/10(ICD9/10)codes were used to define each AIDs,the pancreatic endocrine and exocrine diseases.Multivariable Cox proportional hazards models were employed to assess the relationships between AIDs and pancreatic endocrine and exocrine diseases,with adjustments for age,gender,ethnicity,Townsend deprivation index,smoking,alcohol consumption,body mass index,waist circumference,hip circumference,hypertension,dyslipidemia,and gallstones.Results A total of 415,497 participants were included,among which 37,482 de-veloped pancreas-related diseases during follow-up.Among patients with AIDs,the proportions of those with pancreatic exocrine and endocrine diseases were significantly increased(P＜0.05).Rheumatoid arthritis[HR(95％CI):1.438(1.161 to 1.781)],ankylosing spondylitis[HR(95％CI):1.675(1.009 to 2.780)],ulcerative colitis[HR(95％CI):1.335(1.037 to 1.719)],and Crohn's disease[HR(95％CI):1.530(1.154 to 2.028)]were all associated with an increased risk of de-veloping pancreatic exocrine diseases(all P＜0.05);additionally,rheumatoid arthritis[HR(95％CI):1.119(1.004 to 1.248)],ulcerative colitis[HR(95％CI):1.324(1.175 to 1.491)],sys-temic sclerosis[HR(95％CI):2.08(1.355 to 3.191)],and Crohn's disease[HR(95％CI):1.394(1.197 to 1.624)]were also associated with an increased risk of developing pancreatic en-docrine diseases(all P＜0.05).Conclusion Overall AIDs and some specific AIDs are associated with an increased risk of developing pancreatic endocrine and exocrine diseases,and early preven-tion of pancreatic diseases in patients with AIDs should be emphasized in clinical practice.

Tumor's occurrence and development are closely related to metabolic abnormalities. Central Carbon Metabolism (CCM) is the core network of biological metabolism, and its abnormal activation drives tumor cell proliferation, invasion, and immune escape. Hedyotidis Herba is a classic anti-tumor conventional Chinese materia medica. Its active components interfere with the core links of CCM (glycolysis, tricarboxylic acid cycle and pentose phosphate pathway) by targeting key signaling pathways such as PI3K/Akt, AMPK, P53, Wnt/β-catenin, MAPK, Nrf2 and TGF-β, so as to inhibit the energy metabolism of tumor cells, regulate the acidification state of microenvironment, block the production of metabolic precursors, and curb tumor cell metastasis and immune escape.

Objective To construct a nomogram prediction model for predicting hemoglobin A1c(HbA1c)failure in type 2 diabetes mellitus(T2DM)patients.Methods A total of 936 inpatients with T2DM admitted to the Department of Endocrinology of the Affiliated Hospital of Shandong Second Medical University from January 2021 to January 2022 were selected as the research objects and divided into the non-standard group(HbA1c≥7%,n=801)and the standard group(HbA1c<7%,n=135).Univariate analysis was used to screen the related factors of HbA1c failure.Logistic regression multivariate model was used to analyze the influencing factors of HbA1c failure in T2DM patients.The R language was used to construct a nomogram,and the area under the receiver operating characteristic(ROC)curve(AUC)was used to evaluate the predictive ability of the model.The C-index and Hosmer-Lemeshow test were used to evaluate the discrimination and calibration of the model.Results There were statistically significant differences in triglyceride(TG),low-density lipoprotein cholesterol,direct bilirubin,urinary albumin/creatinine ratio(UACR),self-monitoring of blood glucose(SMBG),meat and vegetable pairing,hot pot,whole grain and animal viscera consumption between the two groups(P<0.05).Logistic regression analysis showed that TG(OR 1.699,95%CI 1.298～2.222),UACR(OR 1.003,95%CI 1.001～1.005),SMGB(OR 0.480,95%CI 0.313～0.735),more meat and less vegetables(OR 1.432,95%CI 1.062～1.931)were the influencing factors of HbA1c failure.The AUC of the nomogram prediction model based on the influencing factors was 0.711,with C-index 0.710(95%CI 0.663～0.758)and good calibration(χ2=11.185,P=0.191).Conclusions The nomogram prediction model for HbA1c failure in T2DM patients established based on TG,UACR,SMGB,meat and vegetarian mix has good discrimination and calibration,which can provide certain reference value for warning of poor blood glucose control.