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.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

The application of sensors to the monitoring of spinal morphology and motion was reviewed in terms of the research object and monitoring index.The present situation of the application of sensors was introduced,such as inertial sensor,stretchable strain sensor and electromagnetic sensor.The deficiencies of sensors applied to the monitoring of spinal morphology and motion were analyzed,and the future directions of the application were pointed out.[Chinese Medical Equipment Journal,2025,46(6):105-110]

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms. METHODS: Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA). RESULTS: Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation. CONCLUSION Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; 23(4): 398-414.
Animals ; Male ; Rats, Sprague-Dawley ; STAT3 Transcription Factor/metabolism* ; alpha7 Nicotinic Acetylcholine Receptor/metabolism* ; Janus Kinase 2/metabolism* ; Atrial Fibrillation/metabolism* ; Vagus Nerve/physiopathology* ; Rats ; Acupuncture Therapy ; Signal Transduction ; Macrophages/metabolism* ; Inflammation/therapy*

Aim To examine the pathogenesis of disul-fide death gene in vascular dementia(VD)by bioin-formatics analysis of disulfide death differentially ex-pressed genes(DEGs)combined with experimental verification.Methods The death DEGs of disulfide were screened and their correlation was analyzed.The VD patients data in the data set were analyzed by clus-tering and typing and gene set variation.The clustering risk of DEGs was tested with a nomogram model,and the optimal learning model was predicted.After the es-tablishment of VD rat model,water maze test,HE stai-ning and RT-qPCR detection were performed to verify the results of health information.Results Four DEGs including SLC7A11 were obtained,which had antago-nistic or synergistic interaction with each other.The genetic data could be divided into two subtypes with significant differences.After typing,VD disulfide DEGs were mainly concentrated in GnRH signaling pathways.The accuracy of the nomogram prediction model was high.Generalized linear was the best ma-chine learning model.Compared with the sham opera-tion group,the escape latency of rats in the model group was prolonged,the number of crossing platforms decreased,the relative mRNA expression levels of Slc3a2 and Slc7a11 decreased,and LRPPRC in-creased.Conclusions SLC7A11 and other disulfide death DEGs and its related GnRH signaling pathway may be an important part of the pathogenesis of VD di-sulfide death.SLC3A2,LRPPRC and SLC7A11 can be used as characteristic genes in the regulation of VD by disulfide death,which may affect VD progression through the regulation of disulfide death.

Objective To explore the correlation between visceral fat area(VFA)and triglyceride-glucose(TyG)index in people with normal body mass index(BMI)based on quantitative CT(QCT).Methods Totally 1 358 healthy adults with normal BMI who underwent QCT body composition measurement were retrospectively enrolled and divided into normal visceral fat group(normal group,VFA＜100 cm2,n=509),mild visceral fat accumulation group(mild group,100 cmn2≤VFA＜150 cm2,n=431)and severe visceral fat accumulation group(severe group,VFA≥150 cm2,n=418)according to VFA measured with QCT.Pearson and Spearman correlation analysis were performed to observe correlations of TyG index with general data and body composition in 20-40,41-60,61-90 years old men and women with normal BMI,respectively.Multiple linear regression analysis was performed to screen the independent impact factors of TyG index in normal BMI people.Results Low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),glutamic-pyruvic transaminase(GPT),VFA and subcutaneous fat area(SFA)of men with normal BMI at different age stages were weakly-lowly positively correlated with TyG index(r=0.143-0.459,all P＜0.05),while high-density lipoprotein cholesterol(HDL-C)were weakly-lowly negatively correlated with TyG index(r=-0.410--0.222,all P＜0.05).LDL-C,VFA and SFA of women with normal BMI at different age stages were weakly-lowly positively correlated with TyG index(r=0.206-0.495,all P＜0.05).GPT,TC,VFA and liver fat content(LFC)were all independent risk factors,while HDL-C was independent protective factor for TyG index in people with normal BMI(all P＜0.05).Conclusion VFA was positively correlated with TyG index in people with normal BMI.Measurement of abdominal body composition based on QCT combined with lipid indexes had certain potential for predicting insulin resistance and relative metabolic diseases in abdominal obese people.

Objective To explore the pathogenic mechanisms of Legionella pneumophila(L.pneumophila)infection inhibiting the fusion of endosome-lysosome fusion in mouse macrophages.Methods Twelve C57 mice were randomly divided into control group and L.pneumophila infection group(n=6 each).After anesthesia,an equal volume of physiological saline or L.pneumophila solution was administered nasally.Body weight changes were monitored for 3 consecutive days,and the lungs were extracted to assess injury.Hematoxylin and eosin(HE)staining and immunohistochemical staining were performed to observe the pathological characteristics of lung tissue in both groups.Transcriptome sequencing was utilized to analyze differentially expressed genes(DEGs)and associated signaling pathways in lung tissues.Mouse bone marrow macrophages(BMDMs)were isolated and co-cultured with L.pneumophila,with infection status confirmed by immunofluorescence staining.Transcriptome sequencing was employed to analyze DEGs and enriched related signaling pathways before and after infection.Core genes involved in the post-infection signaling pathway were identified,and the consistency of their mRNA expression levels in vivo and in vitro was verified using RT-qPCR.The expression of relevant proteins was detected by Western Blotting,and bacterial proliferation assays were conducted to evaluate the intracellular replication of L.pneumophila.Results Compared with control group,the body weight of mice in L.pneumophila infection group significantly decreased(P<0.001)on the second and third day post-infection.Edema and red hepatoid degeneration were observed in both left and right lung tissues,with lesion areas spreading from the hilum to the lung periphery.HE staining revealed increased inflammatory cell infiltration in the alveolar spaces,thickening of alveolar septa and increased fibrin exudation in L.pneumophila infection group.Immunohistochemistry results showed a significant increase in myeloperoxidase(MPO)activity in the lung tissue infected mice(P<0.001).Transcriptome sequencing identified 2550 DEGs,with 1444 up-regulated genes and 1106 down-regulated genes.KEGG enrichment analysis indicated that these DEGs were mainly involved in pathways related to tumor necrosis factor,rheumatoid arthritis,Rap1,PI3K-Ak,and phagosome pathways.Immunofluorescence results showed in vitro proliferation of L.pneumophila within mouse BMDMs.Transcriptome sequencing identified 2550 DEGs,including 1677 up-regulated genes and 873 down-regulated genes.KEGG enrichment analysis showed that enrichment in pathway related to transcription dysregulation in cancer,PI3K-Akt and phagosome pathways.Thirteen core genes,including tubulin β1(Tubb1),were identified from the overlap between mouse lung tissue and BMDMs.RT-qPCR results demonstrated a significant decrease in Tubb1 expression in both lung tissue and BMDMs infected with L.pneumophila(P<0.001).Western Blotting results revealed significant decreases in Rab7,Tubb1,and LAMP2 protein expression(P<0.05),and increases in iNOS and MPO expression(P<0.05).Intracellular proliferation experiments indicated that L.pneumophila gradually increased within BMDMs over time.Conclusion The potential mechanism of L.pneumophila infection in mouse macrophages involves the down-regulation of Rab7/Tubb1/LAMP2 which inhibits the endosome-lysosome fusion.

This review delves into the pivotal role of necrotic apoptosis in Alzheimer's disease(AD),with a focus on treatment strategies,drug development,prospects,and challenges,highlighting its significance in the progression of the disease.Firstly,necrotic apoptosis plays a crucial role in the pathogenesis of AD,particularly in association with the abnormal metabolism of β-amyloid(Aβ)and Tau proteins.The primary focus of drug design is to regulate the metabolism pathways of these two proteins to slow down or inhibit the progression of necrotic apoptosis.Secondly,the progress in drug development further emphasizes the importance of necrotic apoptosis in treating AD.Current research mainly focuses on drugs that affect the metabolism of Aβ and Tau proteins,such as lecanemab.Still,inconsistent result underscore the necessity for a more comprehensive understanding of the molecular mechanisms of necrotic apoptosis.Finally,the prospects and challenges of necrotic apoptosis research in AD are thoroughly discussed.A deeper understanding of necrotic apoptosis contributes to a better comprehension of the pathological mechanisms of AD but also may reveal new therapeutic targets.However,challenges such as multifactorial influences and the selection of treatment timing necessitate further in-depth research in the future.In conclusion,this review advocates for future research to deepen the understanding of the molecular mechanisms of necrotic apoptosis,enhance research on treatment strategies,gain a deeper understanding of its cross-regulation with other cell death pathways,and promote collaboration between basic research and clinical practice to advance the comprehensive understanding and treatment of Alzheimer's disease and necrotic apoptosis.