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.

OBJECTIVES: To investigate the effect of interferon-λ1 (IFN-λ1) on glucocorticoid (GC) resistance in human bronchial epithelial cells (HBECs) stimulated by respiratory syncytial virus (RSV). METHODS: HBECs were divided into five groups: control, dexamethasone, IFN-λ1, RSV, and RSV+IFN-λ1. CCK-8 assay was used to measure the effect of different concentrations of IFN-λ1 on the viability of HBECs, and the sensitivity of HBECs to dexamethasone was measured in each group. Quantitative real-time PCR was used to measure the mRNA expression levels of p38 mitogen-activated protein kinase (p38 MAPK), glucocorticoid receptor (GR), and MAPK phosphatase-1 (MKP-1). Western blot was used to measure the protein expression level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic ratio of GR was calculated. RESULTS: At 24 and 72 hours, the proliferation activity of HBECs increased with the increase in IFN-λ1 concentration in a dose- and time-dependent manner (P˂0.05). Compared with the RSV group, the RSV+IFN-λ1 group had significant reductions in the half-maximal inhibitory concentration of dexamethasone and the mRNA expression level of p38 MAPK (P<0.05), as well as significant increases in the mRNA expression levels of GR and MKP-1, the level of GR in cell nucleus and cytoplasm, and the nuclear/cytoplasmic GR ratio (P<0.05). CONCLUSIONS IFN-λ1 can inhibit the p38 MAPK pathway by upregulating MKP-1, promote the nuclear translocation of GR, and thus ameliorate GC resistance in HBECs.
Humans ; p38 Mitogen-Activated Protein Kinases/genetics* ; Glucocorticoids/pharmacology* ; Receptors, Glucocorticoid/analysis* ; Dual Specificity Phosphatase 1/physiology* ; Dexamethasone/pharmacology* ; Drug Resistance/drug effects* ; Respiratory Syncytial Viruses ; Interferons/pharmacology* ; MAP Kinase Signaling System/drug effects* ; Epithelial Cells/drug effects* ; Signal Transduction/drug effects* ; Cells, Cultured

A 14-year-old boy was admitted to the hospital due to a single episode of afebrile seizure and four hours of impaired consciousness. Three months prior to admission, he had a history of bilateral uveitis. Cerebrospinal fluid analysis revealed a mild elevation in white blood cell count. Cranial magnetic resonance imaging and contrast-enhanced scans showed multiple abnormal signals in both cerebral hemispheres, with punctate and nodular enhancement. Susceptibility-weighted imaging revealed multiple punctate hemorrhages within lesions in the bilateral frontal and left parietal lobes, suggestive of vasculitis. Brain biopsy demonstrated inflammatory granulomatous lesions. No secondary causes were identified, and the final diagnosis was granulomatous primary central nervous system vasculitis. The patient's condition improved after treatment with methylprednisolone sodium succinate and mycophenolate mofetil. This report describes a rare case of granulomatous central nervous system vasculitis in a child and provides valuable insights for the diagnosis and treatment of this disease.
Humans ; Male ; Vasculitis, Central Nervous System/diagnosis* ; Adolescent ; Magnetic Resonance Imaging ; Granuloma/diagnosis*

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.

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*

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.