[Objective]To investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism.[Methods]C57BL/6J mice were randomly divided into saline group(Saline)and hypertension group(Ang Ⅱ,which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps),and supplemented daily with nicotinamide mononucleotide(300 mg/kg),a precursor of NAD+.Blood pressure,endothelial relaxation function and pulse wave velocity were measured after 4 weeks.Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro.mtROS levels were detected by immunofluorescence staining.RT-PCR was used to detect the mRNA expression of mtDNA,SIRT3 and isocitrate dehydrogenase 2(IDH2).8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay.The protein expression levels of p-eNOS,eNOS,SIRT3 and IDH2 were detected by Western blot.[Results]NMN supplementation reduced blood pressure(P<0.001)and improved endothelial function and arterial stiffness(P<0.001)in hypertensive mice.In vitro,NMN improved endothelial function in Ang Ⅱ-stimulated endothelial cells(P<0.05)and attenuated mitochondrial oxidative stress levels(P<0.001).Mechanistically,NMN elevated SIRT3 activity(P<0.001),which subsequently enhanced IDH activity(P<0.001)and reduced oxidative stress levels in endothelial cells.Conversely,knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function(P<0.001).[Conclusion]NAD+lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

Objective To analyze the status of protection facilities for key occupational disease hazards in Sichuan Province from 2020 to 2023. Methods Data on protection facilities for occupational disease hazard in enterprises in Sichuan Province from 2020 to 2023 were collected through the "Workplace Occupational Disease Hazard Monitoring System" within the "Occupational Disease Hazard Project Declaration System". A total of 13 081 enterprise reports involving occupational disease hazard factors were analyzed for the implementation of protection facilities for three key hazards: dust, chemical toxins, and noise. Results The overall installation rate of occupational hazard protection facilities among the 13 081 enterprise reports was 68.9%, with a compliance rate of 80.4%. Installation rates for protection facilities for the four occupational hazard factors including dust, organic toxicants, metallic toxicants, and noise were 81.0%, 79.9%, 57.0%, and 57.6%, with compliance rates of 81.9%, 82.1%, 78.7%, and 78.4%, respectively. Significant differences were observed in installation and compliance rates of these protection facilities among the four occupational hazard factors and across different industries (all P<0.01). Both the installation and compliance rates of protection facilities in enterprises improved in each year from 2021 to 2023 compared with 2020 (all P<0.05). Conclusion From 2021 to 2023, the installation and compliance rates of protection facilities for dust, toxic substances, and noise in enterprises in Sichuan Province showed some improvement compared with 2020. However, efforts to enhance engineering controls and protective measures should be strengthened for operations involving dust, metallic toxicants, and noise.

Objective To investigate the preferences of elderly chronic disease patients for"internet+nursing services"and provide references for precisely matching their service needs.Methods A questionnaire on service preferences for elderly chronic disease patients was developed based on a discrete choice experi-ment.Face-to-face questionnaire surveys were conducted with 342 respondents selected by random sampling,and preference outcomes were analyzed using a mixed logit model.Results A total of 342 collected question-naires were valid,resulting in a 100%response rate.Significant differences were observed in all six included attributes(P＜0.05).Senior nurses(β=0.491)provided the highest utility,followed by larger hospital size(β=0.479)and 70%medical insurance reimbursement(β=0.402).Respondents showed the highest willing-ness-to-pay for senior nurses,with 165.1 yuan willingness to pay when switching from junior to senior nur-ses..Conversely,respondents required 86.8 yuan compensation when switching from basic to personalized service packages.Conclusion Preferences for"internet+nursing services"among elderly chronic disease pa-tients are multifactorial,and involving trade-offs among attribute levels during service selection.

Objective To explore the temporal characteristics and correlation between active exercise rehabilitation behaviour and related symptoms in middle-aged chronic obstructive pulmonary disease(COPD)patients,and to provide a basis for constructing a full cycle precision rehabilitation management system.Methods The ecological momentary assessment method was used to select 63 middle-aged COPD patients from the respiratory and critical care medicine department of a tertiary comprehensive hospital in Wuhan from October 15 to December 1,2024,using convenience sampling.Their active exercise rehabilitation behaviour(number of exercise projects,duration)and related symptoms(dyspnea,fatigue,anxiety)were continuously monitored for a week by using baseline survey,daily active exercise rehabilitation behavior assessment questionnaire,daily symptom assessment questionnaire.A multi-layer linear model was used to analyze the dynamic correlation between active exercise rehabilitation behaviour and symptoms.Results 58 patients were included.During the 1-week ecological momentary assessment,the system triggered a total of 1,218 momentary assessments and obtained 1,120 valid responses(with the valid response rate of 91.95％),with patients completing an average of(2.76±0.39)assessments per day.Multilevel linear models showed that momentary dyspnoea,fatigue,anxiety symptoms and baseline kinesiophobia all significantly negatively influenced active exercise rehabilitation behaviour(P＜0.05).Conclusion There are dynamic changes in the active exercise rehabilitation behaviour and related symptoms of middle-aged COPD patients.Nursing staff should establish a precise rehabilitation intervention system based on symptom fluctuations,strengthen patient self-management efficiency through dynamic monitoring and hierarchical management,and achieve long-term optimization of lung rehabilitation effects.

Objective To explore the temporal characteristics and correlation between active exercise rehabilitation behaviour and related symptoms in middle-aged chronic obstructive pulmonary disease(COPD)patients,and to provide a basis for constructing a full cycle precision rehabilitation management system.Methods The ecological momentary assessment method was used to select 63 middle-aged COPD patients from the respiratory and critical care medicine department of a tertiary comprehensive hospital in Wuhan from October 15 to December 1,2024,using convenience sampling.Their active exercise rehabilitation behaviour(number of exercise projects,duration)and related symptoms(dyspnea,fatigue,anxiety)were continuously monitored for a week by using baseline survey,daily active exercise rehabilitation behavior assessment questionnaire,daily symptom assessment questionnaire.A multi-layer linear model was used to analyze the dynamic correlation between active exercise rehabilitation behaviour and symptoms.Results 58 patients were included.During the 1-week ecological momentary assessment,the system triggered a total of 1,218 momentary assessments and obtained 1,120 valid responses(with the valid response rate of 91.95％),with patients completing an average of(2.76±0.39)assessments per day.Multilevel linear models showed that momentary dyspnoea,fatigue,anxiety symptoms and baseline kinesiophobia all significantly negatively influenced active exercise rehabilitation behaviour(P＜0.05).Conclusion There are dynamic changes in the active exercise rehabilitation behaviour and related symptoms of middle-aged COPD patients.Nursing staff should establish a precise rehabilitation intervention system based on symptom fluctuations,strengthen patient self-management efficiency through dynamic monitoring and hierarchical management,and achieve long-term optimization of lung rehabilitation effects.

Objective·To investigate the expression of miR-146a in peripheral blood CD4+T lymphocytes of patients with rheumatoid arthritis(RA)and its correlation with inflammatory cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Methods·A total of 30 active RA patients who received medical treatment and 30 healthy controls who underwent physical examinations at the People's Hospital of Longhua,Shenzhen from August 2019 to July 2021 were selected.Peripheral blood mononuclear cells(PBMCs)and CD4+T lymphocytes were isolated from venous blood extracted from RA patients and healthy controls,respectively.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-146a in peripheral blood CD4+T lymphocytes,and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of TNF-α and IL-6.After transfection of the peripheral blood CD4+T lymphocytes of RA patients with miR-146a mimic,the expression of miR-146a,TNF-α and IL-6 was detected again.The correlations between miR-146a expression and TNF-α and IL-6 expression in RA patients,both before and after transfection,were analyzed by using Pearson correlation coefficient.Results·Before transfection with miR-146a mimic,the expression levels of miR-146a,TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients were significantly higher than those of healthy controls(all P＜0.001).After transfection,the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients was significantly higher,and the expression of TNF-α and IL-6 was significantly lower(all P＜0.001).The results of Pearson correlation analysis showed that the expression of miR-146a in peripheral blood CD4+T lymphocytes of RA patients,both before and after transfection,was positively correlated with the expression of TNF-α and IL-6,respectively(r=0.959,P＜0.001;r=0.916,P＜0.001;r=0.971,P＜0.001;r=0.861,P＜0.001).Conclusion·miR-146a can regulate the levels of TNF-α and IL-6 in peripheral blood CD4+T lymphocytes of RA patients,indicating that miR-146a may play a role in the pathogenesis of RA.

BACKGROUND: One of the most important treatment modalities for non-small cell lung cancer (NSCLC) is immune checkpoint inhibitor. Nevertheless, a small percentage of patients do not respond well to these therapies, highlighting the significance of identifying important CD8+ T cell subsets for immunotherapy and creating trustworthy biomarkers. The purpose of this study is to assess the potential utility of TIM3+CD8+ T cells as new biomarkers by examining their expressions in various areas of the NSCLC tumor microenvironment. METHODS: Based on biopsy techniques, tumor tissue samples were obtained from patients with NSCLC and categorized into tumor central and non-central regions. Using flow cytometry, the infiltration of TIM3+CD8+ T cells and the surface expression of programmed cell death 1 (PD-1) on these cells were examined, and their correlations with the effectiveness of immunotherapy were assessed. RESULTS: The non-central region of tumor tissues had considerably larger infiltration of TIM3+CD8+ T lymphocytes compared to the non-central region (P<0.0001). This pattern was found in both subgroups with tumor diameters ≥3 cm or <3 cm (P<0.01). In comparison to TIM3-CD8+ T cells, TIM3+CD8+ T cells showed higher levels of PD-1 (P<0.001), with more PD-1+TIM3+CD8+ T cells invading the non-central region (P<0.01). Clinical responders to immunotherapy had considerably lower infiltration levels of TIM3+CD8+ T cells in the tumor non-central region compared to non-responders, with lower levels correlated with better clinical outcomes (P<0.01), while no correlation was identified in the tumor central region (P>0.05). According to reciever operating characteristic (ROC) curve analysis, TIM3+CD8+ T cells in the tumor non-central region had an area under the curve (AUC) of 0.9375 for predicting the effectiveness of immunotherapy, which was considerably higher than that of TIM3+CD8+ T cells in the tumor central region and programmed cell death ligand 1 (PD-L1) [tumor proportion score (TPS)]. CONCLUSIONS In the tumor microenvironment of NSCLC, TIM3+CD8+ T cells show regional distribution patterns. The expression of this cell population in the non-central region of the tumor microenvironment may be a biomarker for predicting the effectiveness of immunotherapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Lung Neoplasms/metabolism* ; Hepatitis A Virus Cellular Receptor 2/immunology* ; Tumor Microenvironment/immunology* ; CD8-Positive T-Lymphocytes/metabolism* ; Male ; Female ; Middle Aged ; Aged ; Adult ; Programmed Cell Death 1 Receptor/metabolism* ; Immunotherapy ; Clinical Relevance

Objective To investigate the clinical value of auditory brainstem response(ABR)wave Ⅰ latency and 1 000 Hz acoustic immittance in the assessment of middle ear function in infants.Methods A total of 74 infants who were born within 6 months of age from 2020 to 2021 were selected,with a total of 148 ears.According to the click ABR(hereinafter referred to as ABR)threshold,they were divided into mild group(56 ears),moderate group(14 ears)and normal group(78 ears).The ABR wave Ⅰ latency and 1 000 Hz acoustic immittance results were ana-lyzed respectively.Results The Kappa values between ABR wave Ⅰ latency and 1 000 Hz tympanometry in infants of mild and moderate groups were 0.708 and 0.650,respectively.There was no significant difference in the detec-tion rate of middle ear function abnormality(P＞0.05)in infants with mild and moderate threshold impairment within 6 months of age.The paried Chi-square test showed a significant difference between the ABR wave Ⅰ latency and 1 000 Hz acoustic immittance in infants with normal threshold at 6 month of age(P＜0.05),with a Kappa val-ue of 0.297.Conclusion The middle ear function could be evaluated by ABR wave Ⅰ latency or 1 000 Hz acoustic immittance in 6-month-old infants with mild or moderate abnormality.For infants with normal ABR threshold,1 000 Hz acoustic immittance and the latency of ABR wave Ⅰ need to be cross-verified.

Objective To investigate the effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten(PTEN)/phosphoinositide 3 kinase(PI3K)/protein kinase B(AKT)pathway on renal tissuecell apoptosis in diabetic kidney disease(DKD)rats.Methods The DKD rat model was constructed by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).72 rats were divided into normal control group(NC),DKD model group(DKD),miR-130a agonist negative control group(NC agomir),and miR-130a agonist group(miR-130a agomir),miR-130a agomir+ PTEN overexpression negative control group(miR-130a agomir+pcDNA),and miR-130a agomir+ PCDNA-PTEN overexpression group(miR-130a Agomir + PCDNA-PTEN),with12 rats in each group.Urinary microalbumin kit was used to detect 24 h urine albumin(UAlb).Fasting blood glucose(FBG),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by automatic biochemical analyzer.Pathological changes of renal tissue were detected by HE staining.The levels of serum IL-6 and TNF-α were detected by ELISA.The apoptosis of renal tissue was detected by TUNEL staining.The expression of miR-130a was detected by qRT-PCR,and the expression of B-cell lymphoma-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2)and PTEN/PI3K/AKT pathway were detected by Western blot.Dual luciferase reporter gene experiment was used to verify the targeting relationship between miR-130a and PTEN.Results Compared with DKD and NC agomir groups,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression in miR-130a agomir group were decreased(P＜0.05).The expressions of miR-130a,Bcl-2,p-Akt/AKT protein were increased(P＜0.05).Compared with miR-130a agomir group,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression were increased in miR-130a agomir+pcDNA-PTEN group(P＜0.05).The expression of Bcl-2,p-Akt/AKT protein decreased(P＜0.05).Conclusion Overexpression of miR-130a may inhibit renal cell apoptosis in DKD rats by down-regulating PTEN to activate PI3K/AKT pathway.

Objective:To analyze the clinical and pathological features of adolescent- onset primary nephrotic syndrome (PNS) in children (10 years≤age≤18 years), so as to explore the renal biopsy indications in adolescent-onset PNS.Methods:It was a single-center retrospective observational study. The clinical and pathological data of adolescent-onset PNS (age≥10 years) who underwent renal biopsy in Children's Hospital Affiliated to Nanjing Medical University from December 2004 to June 2022 were analyzed retrospectively.Results:A total of 110 children were included in the study, including 76 males (69.1%) and 34 females (30.9%), with the onset age ranging from 10 years to 14 years and 9 months. Forty-nine cases (44.5%) were accompanied by hematuria, including 14 cases (12.7%) of gross hematuria and 35 cases (31.8%) of microscopic hematuria. Twenty-five cases (22.7%) had hypertension, 19 cases (17.3%) had renal insufficiency, and 4 cases (3.6%) had low complement C3 at the onset. Fifty-two cases (47.3%) were steroid sensitive nephrotic syndrome and 58 cases (52.7%) were steroid resistant nephrotic syndrome. Biopsy results showed that minimal change disease(MCD) was the most common histopathological subtype (47.3%, 52 case), followed by focal segmental glomerulosclerosis (FSGS) in 22 cases (20.0%), IgA nephropathy (IgAN) in 17 cases (15.5%), membranous nephropathy (MN) in 7 cases (6.4%), mesangial proliferative glomerulonephritis in 5 cases (4.5%), IgM nephropathy in 4 cases (3.6%), membranous proliferative glomerulonephritis in 2 cases (1.8%), and C1q nephropathy in 1 case (0.9%). Among 44 children with simple type nephrotic syndrome, the pathological type was mainly MCD (77.3%), and 66 children with nephritic type nephrotic syndrome were mostly non-MCD (72.7%), such as IgAN, FSGS, MN, etc. If there are two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency or low C3 levels, the proportion of non-MCD would further increase to 92.0%(23/25). The pathological type of patient with gross hematuria or low C3-emia was non-MCD. The frequency of hematuria (69.0% vs. 17.3%, χ2=29.619, P<0.001), hypertension (31.0% vs. 13.5%, χ2=4.821, P=0.028) and renal insufficiency (24.1% vs. 9.6%, χ2=4.047, P=0.044) in non-MCD group was significantly higher than those in MCD group. Conclusions:If the clinical manifestation of PNS in adolescent over 10 years old is simple type nephrotic syndrome, the histopathological lesion is mostly MCD, and most of them are steroid sensitive. It is recommended to give hormone treatment first, and then perform renal biopsy if steroid resistance occurs; If the clinical manifestation is nephritic type nephrotic syndrome, the histopathological lesion is mostly non-MCD, especially those with gross hematuria or low C3-emia, or those have two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency and hypocomplement C3-emia, a kidney biopsy should be performed at onset.