Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

The historical development of endogenous wind （内风） is traced with time as the thread， based on the progression of factors such as syndromes， causes of disease， and pathogenesis. It is believed that the concept of wind syndrome originated in The Inner Canon of Yellow Emperor （《黄帝内经》）， encompassing both exogenous wind （外风） and endogenous wind syndrome. Over time， exogenous wind syndrome gradually evolved into mild syndromes and severe syndromes， while endogenous wind syndrome emerged from severe syndromes of exogenous wind. Endogenous wind syndrome has both syndrome and pathogenic attributes， and its theoretical system has gradually become more refined. Based on the theories of ancient and modern medical practitioners， and combining the holistic perspectives with Xiang （象） thinking， it is proposed that endogenous wind has both physiological and pathological distinctions. The physiological endogenous wind refers to the liver's moderate dispersing and regulating function， which helps to distribute qi （气）， blood， and body fluids， while pathological endogenous wind arises from abnormal liver dispersal. Therefore， in clinical practice， different treatment methods， such as tonifying， unblocking， and warming， can be applied according to the differentiation of deficiency and excess in the pathogenesis.

Objective:To investigate mental health literacy and advance care planning(ACP)condition,their influencing fac-tors,and their correlation in elderly patients with coronary heart disease(CHD).Methods:General data of 500 elderly CHD patients admitted in the Second Affiliated Hospital of Chinese PLA Air Force Military Medical University between January 2020 and December 2021 were collected.Mental health literacy and ACP condition were assessed.Multivariate linear regres-sion was used to analyze their influencing factors,and Pearson method was used to analyze their association.Results:Total score of Multicomponent Mental Health Literacy(MHL)was(10.78±2.57)points,and total score of Advance Care Plan-ning Readiness Scale(ACPRS)was(71.41±4.84)points in the 500 elderly CHD patients.Multivariate linear regression a-nalysis indicated that level of disease uncertainty had negative impact on MHL score,presence of spouse and trust in medical care had positive impact on MHL score(P＜0.05 or＜0.01);number of complications had negative impact on ACPR score,while presence of spouse and family mean monthly income had positive impact on ACPRS score(P＜0.05 or＜0.01).Pearson correlation analysis indicated that MHL score was positively correlated with ACPRS score(r=0.476,P＜0.001).Conclusion:Both mental health literacy and ACP status need to be improved in elderly CHD patients.They are posi-tively correlated with each other.Presence of spouse,number of complications and trust in medical care are the important influencing factors.Therefore,medical staff can take targeted measures to improve ACP readiness and mental health quality.

Objective:This study aims to explore the rehabilitation effect of continuous rehabilitation management based on Internet thinking on patients with coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods:This randomized controlled study enrolled 100 CHD patients admitted in Second Affiliated Hospi-tal of Chinese PLA Air Force Military Medical University between October 2020 and December 2021.They were di-vided into control group(n=50)and intervention group(n=50).Patients in control group received routine reha-bilitation nursing mode,compared to those in intervention group applying"Internet+"continuous rehabilitation nursing intervention program,both groups were intervened for 3 months.Cardiac function,cardiopulmonary exer-cise test indexes,depression,medication compliance,quality of life and incidence of adverse cardiovascular events within 1-year follow-up were compared between two groups.Results:Compared with patients in control group after 3 months,those in intervention group had significant higher oxygen uptake at anaerobic threshold(VO2@AT)[(11.75±0.39)ml·kg-1·min-1 vs.(10.17±0.76)ml·kg-1·min-1],peak oxygen uptake(Peak VO2)[(17.87±0.72)ml·kg-1·min-1 vs.(16.66±0.24)ml·kg-1·min-1],left ventricular ejection fraction(LVEF)[(51.15±2.42)％vs.(44.09±1.94)％],scores of Morisky Medication Adherence Scale(MMAS-8)[(5.29±0.30)points vs.(4.11±0.27)points]and Seattle Angina Questionnaire(SAQ)[(85.50±4.37)points vs.(73.27±2.53)points],and significant lower left ventricular end-diastolic diameter(LVEDd)[(40.51±0.41)mm vs.(46.64±0.99)mm],score of Patient Health Questionnaire-9(PHQ-9)[(7.67±0.85)points vs.(9.66±1.43)points]and total incidence of adverse cardiovascular events within 1-year follow-up(4.00％vs.16.00％)(P＜0.05 or＜0.01).Conclusion:Internet continuous rehabilitation intervention could improve car-diopulmonary exercise capacity and cardiac function,help to improve their quality of life and relieve depression,and reduce the risk of adverse cardiovascular events in CHD patients after PCI.

Objective:Based on multivariate analysis of the influencing factors of fecal pollution after radical re-section in children with congenital megacolon,a risk prediction model was constructed and evaluated.Methods:A total of 200 children with Hirschsprung's disease who underwent radical surgery at Nanyang Central Hospital of Henan Province from June 2020 to June 2023 were selected,and all children were followed up for 1 year.According to the occurrence of postoperative fecal incontinence,the children were divided into the non-occurrence group and the oc-currence group.Univariate Logistic regression analysis was performed on all possible influencing factors,and the back-ward stepwise regression method was used to screen out the relevant factors affecting postoperative fecal inconti-nence in children with Hirschsprung's disease after radical surgery.A risk prediction model was constructed based on these relevant factors,and its efficacy was verified using calibration curves,the Hosmer-Lemeshow test,and ROC curves.Results:Postoperative fecal incontinence occurred in 19.50%(39/200)of the children.A statistically signifi-cant difference was observed between the non-occurrence group and the occurrence group in terms of the following data(P＜0.05):age,preoperative nutritional support,need for auxiliary defecation before surgery,length of the dis-eased intestinal segment,educational level of caregivers,preoperative hypoproteinemia,resection range,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative enterocolitis,and post-operative anal dilatation therapy.Multivariate Logistic regression analysis showed that preoperative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,educational level of caregivers,postoperative diet compliance of the children,postoperative defecation training of the children,postoperative entero-colitis,and postoperative anal dilatation therapy were all independent influencing factors for postoperative fecal inconti-nence in children with Hirschsprung's Disease after radical surgery(P＜0.05).Among these factors,the educational level of caregivers was the strongest predictor of postoperative fecal incontinence in children with Hirschsprung's dis-ease after radical surgery.Results of the calibration curve showed that the concordance index of the risk prediction model for postoperative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.837.The Hosmer-Lemeshow test results indicated no statistically significant difference between the predicted values and the actual values of risk prediction(P＜0.05),suggesting that the model had a good fit and high prediction accuracy.Re-sults of the ROC curve showed that the area under the curve(AUC)of the risk prediction model for predicting postop-erative fecal incontinence in children with Hirschsprung's Disease after radical surgery was 0.887(95%CI:0.762～1.000,P＜0.05),with a sensitivity of 0.914,a specificity of 0.763,and a Youden index of 0.677.These findings indicate that the risk prediction model has moderate discriminative ability and good predictive performance.Conclusion:Preop-erative nutritional support,need for auxiliary defecation before surgery,length of the diseased intestinal segment,edu-cational level of caregivers,postoperative diet compliance of children,postoperative defecation training of children,postoperative enterocolitis,and postoperative anal dilatation therapy are all independent influencing factors for postop-erative fecal incontinence in children with Hirschsprung's disease after radical surgery.The risk prediction model for postoperative fecal incontinence in children with Hirschsprung's disease after radical surgery,established based on multivariate analysis,is helpful for early identification of high-risk groups and timely implementation of individualized in-tervention measures.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

This paper aimed to use non-targeted urine metabolomics to reveal the potential biomarkers of toxicity in rats with hepatic injury induced by aqueous extracts of Dictamni Cortex(ADC). Forty-eight SD rats were randomly assigned to a blank group and high-dose, medium-dose, and low-dose ADC groups, with 12 rats in each group(half male and half female), and they were administered orally for four weeks. The hepatic injury in SD rats was assessed by body weight, liver weight/index, biochemical index, L-glutathione(GSH), malondialdehyde(MDA), and pathological alterations. The qPCR was utilized to determine the expression of metabolic enzymes in the liver and inflammatory factors. Differential metabolites were screened using principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA), followed by a metabolic pathway analysis. The Mantel test was performed to assess differential metabolites and abnormally expressed biochemical indexes, obtaining potential biomarkers. The high-dose ADC group showed a decrease in body weight and an increase in liver weight and index, resulting in hepatic inflammatory cell infiltration and hepatic steatosis. In addition, this group showed elevated levels of MDA, cytochrome P450(CYP) 3A1, interleukin-1β(IL-1β), and tumor necrosis factor-α(TNF-α), as well as lower levels of alanine transaminase(ALT) and GSH. A total of 76 differential metabolites were screened from the blank and high-dose ADC groups, which were mainly involved in the pentose phosphate pathway, tryptophan metabolism, purine metabolism, pentose and glucuronic acid interconversion, galactose metabolism, glutathione metabolism, and other pathways. The Mantel test identified biomarkers of hepatotoxicity induced by ADC in SD rats, including glycineamideribotide, dIDP, and galactosylglycerol. In summary, ADC induced hepatotoxicity by disrupting glucose metabolism, ferroptosis, purine metabolism, and other pathways in rats, and glycineamideribotide, dIDP, and galactosylglycerol could be employed as the biomarkers of its toxicity.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Biomarkers/metabolism* ; Liver/metabolism* ; Drugs, Chinese Herbal/adverse effects* ; Female ; Chemical and Drug Induced Liver Injury/metabolism* ; Glutathione/metabolism* ; Humans