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.

Objective To analyze the clinical characteristics,treatment,and prognosis of immune checkpoint inhibitor-related diabetes mellitus(ICI-DM).Methods The clinical characteristics,laboratory examinations,treatment regimens,and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed.Relevant literatures were retrieved from domestic and foreign databases such as PubMed,CNKI,and VIP.The clinical characteristics of ICI-DM were summarized based on the literature results.Results All 10 patients were PD-1 inhibitor users,including 5 males and 5 females,with a median age of 54.5(51.3,64.0)years and a body mass index(BMI)of(22.0±2.15)kg/m2.Among them,9 cases(90.0%)were fulminant type 1 diabetes mellitus(FT1DM);9 cases(90.0%)had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events(CTCAE).The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as"three more and one less"(polyuria,polydipsia,polyphagia,and weight loss)in all patients was 145.5(110.5,204.8)days,and the medication duration was 6.0(4.3,7.8)cycles.The average blood glucose level of the 10 patients at the time of consultation was 25.3(10.0-41.4)mmol/L,and the glycated hemoglobin(HbA1c)level was 8.0%(6.6%-10.9%).Eight patients had fasting and 2-hour C-peptide levels<0.1 ng/ml(fasting C-peptide from<0.010 to 0.067 ng/ml,2-hour C-peptide from<0.010 to 0.077 ng/ml).Nine of the 10 patients were negative for diabetes autoantibodies,while 1 was not tested.All 10 patients were successfully treated with insulin and other therapies.During the follow-up after discharge,all patients still relied on insulin treatment,and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge.Literature review revealed that ICI-DM was more common in PD-1 inhibitor users,with clinical mainly manifested as diabetic ketoacidosis(DKA)(65.4%)and diabetic ketosis(13.1%).Patients had severely impaired pancreatic islet function and required long-term insulin treatment,and some cases were complicated by thyroid or pituitary dysfunction.Conclusions ICI-DM typically presents as FT1DM,often manifesting with DKA or diabetic ketosis at onset.It is characterized by severe and irreversible loss of pancreatic islet function,necessitating lifelong insulin therapy.To enable early detection and prompt treatment,close monitoring of blood glucose is essential during ICI treatment.

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*

OBJECTIVE: Recaticimab (SHR-1209) significantly reduces low-density lipoprotein cholesterol levels. However, its effect on glucose metabolism remains unclear. This study aimed to evaluate its effect on glycemic parameters in a Chinese population. METHODS: Recaticimab versus placebo was administered in a 5:1 ratio to 110 hyperlipidemia patients who were followed up for 24 weeks. Glycated hemoglobin (HbA1c) levels were measured at baseline every 12 weeks. Fasting plasma glucose (FPG) levels were measured at baseline at week 1, 3, 5, 8, 12, 16, 20, and 24. Repeated-measures mixed-effects models were used to determine the longitudinal association between reacticimab and FPG and HbA1c levels. RESULTS: Among the 81 participants with normal glucose metabolism, HbA1c levels significantly decreased ( F = 4.568, P = 0.036). In the 29 participants with abnormal glucose metabolism, a significant time effect was observed for FPG levels ( F = 2.492, P = 0.016). For participants with normal and abnormal glucose metabolism, no significant group × time interaction effects on FPG or HbA1c levels were identified. CONCLUSION Recaticimab showed no adverse glycemic effects in participants with normal or abnormal glucose metabolism, indicating its safety in patients with or without diabetes.
Humans ; Male ; Female ; Blood Glucose/drug effects* ; Middle Aged ; Double-Blind Method ; Hyperlipidemias/blood* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; PCSK9 Inhibitors ; Glycated Hemoglobin ; Aged ; Adult ; Proprotein Convertase 9

The introduction of non-vitamin K antagonist oral anticoagulant (NOAC) into clinical use heralds a new age for anticoagulation therapy in patients with atrial fibrillation (AF).However,anticoagulation-related bleeding is currently a major challenge in the anticoagulation process.Assessing the risk of anticoagulation-related bleeding is an important part for the management of patients with AF.Clinical risk factor scores have moderate ability to predict the risk of anticoagulation-related bleeding.To improve the anticoagulation safety of NOACs,additional clinical and biological markers and genetic polymorphisms should be considered to enhance the predictive capability for anticoagulation-related bleeding.This review summarizes the challenges in the management of anticoagulation therapy,with emphases on the bleeding risk scores,biomarkers,clinical indicators,and genetic loci currently used to guide the risk assessment of anticoagulation-related bleeding in AF patients.This review is expected to provide research insights and reference frameworks for predicting and evaluating the bleeding risk associated with NOACs.
Humans ; Atrial Fibrillation/drug therapy* ; Anticoagulants/therapeutic use* ; Hemorrhage/chemically induced* ; Risk Assessment ; Administration, Oral ; Risk Factors

Objective To explore the relationships of cognitive impairment with cardiovascular death and all-cause death in menopausal women with hypertension.Methods A total of 4 595 natural-menopausal women with hypertension screened in Wuyuan County of Jiangxi Province from July to August 2018 were selected as the research subjects,and a follow-up investigation of death information was completed from June to August 2022.According to the baseline mini-mental state examination(MMSE)score,all subjects were allocated into a normal cognitive function group and a cognitive impairment group.The basic characteristics and the cumulative risk of death evaluated by the Kaplan-Meier curve were compared between two groups.The multivariate Cox regression model was adopted to analyze the effect of cognitive function on death,and the relationship between MMSE score and death was fitted by the restricted cubic spline.Results A total of 4 595 subjects with the mean age of(65.1±8.4)years were included in this study,in which and 1 859(40.5%)patients with cognitive impairment were detected.During a mean follow-up period of(3.9±0.4)years,199 all-cause deaths were collected,including 102 cardiovascular deaths.The normal cognitive function group and the cognitive impairment group had the cumulative all-cause death rates of 2.6%and 6.9%and the cumulative cardiovascular death rates of 1.0%and 4.0%,respectively.The Kaplan-Meier curve showed that the cumulative risks of all-cause death(χ²=47.287,P<0.001)and cardiovascular death(χ²=45.169,P<0.001)in the cognitive impairment group were higher than those in the normal cognitive function group.The results of multivariate Cox regression analysis indicated that compared with the normal cognitive function group,the cognitive impairment group had increased risks of all-cause death(HR=1.75,95%CI=1.28-2.39,P<0.001)and cardiovascular death(HR=2.56,95%CI=1.61-4.09,P<0.001).The results of the restricted cubic spline curve fitting showed that the MMSE score had linearly negative correlations with the risk of all-cause death(P_all<0.001, P n o n - l i n e a r i t y=0.519)and cardiovascular death(P_all<0.001, P n o n - l i n e a r i t y=0.195).Conclusion Cognitive impairment is an independent risk factor for all-cause death and cardiovascular death in menopausal women with hypertension,and early identification of cognitive impairment in this population is essential for timely intervention.
Humans ; Female ; Cognitive Dysfunction ; Hypertension/complications* ; Aged ; Middle Aged ; Menopause ; Proportional Hazards Models ; Risk Factors ; Cardiovascular Diseases/mortality* ; Cause of Death ; Kaplan-Meier Estimate

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes

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