ObjectiveTo observe the effects of Jiangtang No. 3 prescription on inflammatory pathways and insulin resistance-related indicators in rats with type 2 diabetes mellitus （T2DM）， and to elucidate its molecular mechanism in combating diabetes. MethodsA T2DM rat model was established using a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. Successfully modeled rats were randomly assigned to the model group， metformin group， and low-， medium-， and high-dose Jiangtang No. 3 prescription groups， and a normal group was also set. Daily gavage was administered for 8 weeks as follows： metformin at 0.1 g·kg^-1·d^-1， Jiangtang No. 3 prescription granules at 1.62， 3.24， 6.48 g·kg^-1·d^-1 for the respective dose groups， and sterile water for the normal and model groups. Rat body weight， fasting blood glucose （FBG）， oral glucose tolerance test （OGTT）， and insulin tolerance test （ITT） were measured. After drug intervention， enzyme-linked immunosorbent assay （ELISA） was used to determine serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL）， high-density lipoprotein cholesterol （HDL）， non-esterified fatty acids （NEFA）， interleukin （IL）-1β， IL-18， and insulin （INS）. Hematoxylin-eosin （HE） staining was used to observe morphological changes in adipose tissue. Real-time quantitative PCR was used to detect the mRNA expression of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， NOD-like receptor protein 3 （NLRP3）， Caspase-1， IL-1β， IL-18， and gasdermin D （GSDMD） in adipose tissue. Western blot was used to measure the corresponding protein expression levels. ResultsCompared with the model group， Jiangtang No. 3 prescription groups exhibited significantly increased body weight （P<0.05， P<0.01）， significantly reduced FBG （P<0.05， P<0.01）， significant reductions in TC， TG， NEFA， and LDL （P<0.05， P<0.01）， and a significant increase in HDL （P<0.01）. Serum levels of inflammatory mediators IL-1β and IL-18 were significantly decreased （P<0.01）， the homeostatic model assessment of insulin resistance （HOMA-IR） index was significantly reduced （P<0.05， P<0.01）， and adipose tissue pathology was improved. The protein expression levels of TLR4， NF-κB， NLRP3， Caspase-1， IL-1β， IL-18， and GSDMD were markedly decreased （P<0.05， P<0.01）， and the mRNA expression levels of these indicators were also significantly downregulated （P<0.05， P<0.01）. Some effects were superior to those of the positive control drug metformin， and certain indicators exhibited dose-dependent improvements. ConclusionT2DM rats display significant inflammatory responses， disordered glucose and lipid metabolism， and insulin resistance. Jiangtang No. 3 prescription effectively suppresses inflammatory mediators， improves glucose and lipid metabolism and insulin resistance， and ameliorates pathological changes in adipose tissue. Its mechanism may be related to the regulation of the TLR4/NF-κB/NLRP3 signaling pathway in visceral adipose tissue， thereby influencing downstream inflammatory mediators.

Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective To investigate the effects of goal-directed fluid therapy(GDFT)combined with ultrasound-guided erector spinae plane block(ESPB)on perioperative stress response and postoperative recovery in patients undergoing robot-assisted pedicle screw fixation surgery.Methods Eighty patients scheduled for elec-tive surgery were randomly divided into two groups:control(general anesthesia+conventional fluid management,n=40)and intervention(general anesthesia+GDFT+ESPB,n=40).Heart rate(HR),mean arterial pressure(MAP),serum cortisol(Cor),norepinephrine(NE),blood glucose(GLU)levels,and resting VAS scores were measured and compared between the two groups preoperatively(T?),at screw placement(T?),at end of surgery(T?),30 minutes after extubation(T?),at 24 hours(T?),and 48 hours(T?)postoperatively.Intraoperative fluid volume,remifentanil consumption,postoperative rescue analgesia frequency,time to first ambulation,length of stay,and complications(agitation,nausea and vomiting,respiratory depression)were recorded.Results There were no differences in baseline(T?)indicators between the two groups(P>0.05).The intervention group exhibited significantly lower levels of HR,MAP,Cor,NE,and GLU at T?,T?,and T? compared with the control group(P<0.05),with Cor,NE,and GLU reduced by>30%at T?(P<0.05).Intraoperative fluid volume and remi-fentanil dosage were significantly reduced(both P<0.05).VAS scores and the number of rescue analgesia requests were lower at T?,T?,and T?(P<0.01).Time to first ambulation time and postoperative hospital stay were shortened(both P<0.01).The incidence of agitation,nausea/vomiting and overall complications was lower in the interven-tion group(P<0.05),whereas respiratory depression rates did not differ(P>0.05).Conclusion GDFT plus ESPB can effectively suppress perioperative stress response in robot-assisted spinal surgery,significantly reduce intraoperative opioid dosage and fluid volume,optimize postoperative analgesia,enhance recovery,and lower complication risk.This combination provides an effective ERAS strategy for improving surgical safety and recovery quality.

Objective:To explore the mediating effect of job embeddedness and job satisfaction on psycholog-ical capital and organizational silence in clinical nurses.Methods:Totally 412 clinical nurses(145 males and 267 females)were selected and assessed with the Nurse Organizational Silence Assessment Questionnaire(NOSAQ),Psychological Capital Questionnaire-24(PCQ-24),Job Embedding Scale(JES)and Nurses Job Satisfaction Scale(NJSS).SPSS macro program PROCESS and Bootstrap method were used to explore the role of mediation.Results:The NOSAQ scores were negatively correlated with the scores of PCQ-24,JES and NJSS(r=-0.55,-0.59,-0.51,Ps＜0.01).Job embeddedness and job satisfaction played a chain mediating role between psychological capital and organizational silence of clinical nurses(95％CI:-0.26--0.04),and the mediating effect accounted for 14.7％of the total effect.Conclusion:It suggests that organizational silence is closely related to psychological capital,job embeddedness and job satisfaction in clinical nurses.

Objective To investigate the effects of goal-directed fluid therapy(GDFT)combined with ultrasound-guided erector spinae plane block(ESPB)on perioperative stress response and postoperative recovery in patients undergoing robot-assisted pedicle screw fixation surgery.Methods Eighty patients scheduled for elec-tive surgery were randomly divided into two groups:control(general anesthesia+conventional fluid management,n=40)and intervention(general anesthesia+GDFT+ESPB,n=40).Heart rate(HR),mean arterial pressure(MAP),serum cortisol(Cor),norepinephrine(NE),blood glucose(GLU)levels,and resting VAS scores were measured and compared between the two groups preoperatively(T?),at screw placement(T?),at end of surgery(T?),30 minutes after extubation(T?),at 24 hours(T?),and 48 hours(T?)postoperatively.Intraoperative fluid volume,remifentanil consumption,postoperative rescue analgesia frequency,time to first ambulation,length of stay,and complications(agitation,nausea and vomiting,respiratory depression)were recorded.Results There were no differences in baseline(T?)indicators between the two groups(P>0.05).The intervention group exhibited significantly lower levels of HR,MAP,Cor,NE,and GLU at T?,T?,and T? compared with the control group(P<0.05),with Cor,NE,and GLU reduced by>30%at T?(P<0.05).Intraoperative fluid volume and remi-fentanil dosage were significantly reduced(both P<0.05).VAS scores and the number of rescue analgesia requests were lower at T?,T?,and T?(P<0.01).Time to first ambulation time and postoperative hospital stay were shortened(both P<0.01).The incidence of agitation,nausea/vomiting and overall complications was lower in the interven-tion group(P<0.05),whereas respiratory depression rates did not differ(P>0.05).Conclusion GDFT plus ESPB can effectively suppress perioperative stress response in robot-assisted spinal surgery,significantly reduce intraoperative opioid dosage and fluid volume,optimize postoperative analgesia,enhance recovery,and lower complication risk.This combination provides an effective ERAS strategy for improving surgical safety and recovery quality.

AIM:Hepatotoxicity of Brucea javani-ca picryl with broad-spectrum anticancer effect in nude mice based on hepatic drug metabolizing en-zyme CYP450 activity.METHODS:Fifty-six nude mice were randomly divided into blank group,Bru-cea javanica low-dose group(2 mg/kg),Brucea ja-vanica high-dose group(4 mg/kg),and cisplatin group(2 mg/kg),with 14 mice in each group.The blank group was injected with the same amount of normal saline every 3 days for 6 weeks.Calculate the mortality rate of nude mice in each group,ob-serve the general growth state of nude mice,re-cord the weight change of nude mice before and af-ter administration,weigh and record the liver weight after taking materials,and calculate the liv-er coefficient(liver weight/weight mass×100％),ob-serve and record the liver color and morphology.Hematoxylin-eosin(HE)staining was used to ob-serve the pathological changes of liver tissue.De-tection of alanine aminotransferase(ALT),aspar-tate aminotransferase(AST),lactate dehydrogenase(LDH),alkaline phosphatase(AKP)and albumin(ALB)levels in serum of nude mice by ELISA.Real-time PCR and Western blot were used to detect the mRNA and protein expression levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6 and CYP2C9,which were key enzymes of drug metabolism in nude mice liver.RESULTS:Compared with the blank group,the mortality rate of nude mice in the low-dose Brucea javanica bitter alcohol group was 0,the growth state was good,the diet,movement,and mental state were normal,the weight change and liver coefficient ratio were consistent,the liver color was ruddy,the liver lobule morphology was complete under the microscope,the structure was clear,the liver cells were arranged regularly,and there was no inflammatory cell infiltration.There was no significant difference in the content of ALT,AST,LDH,AKP,and ALB.There was no significant difference in the mRNA and protein expression of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9(all P＞0.05).Compared with the blank group,the mortality rate of nude mice in the high-dose group of Brucea javanica bitter alcohol was 14.3％,the growth state was slightly poor,the diet,movement,and mental state were reduced,the weight growth was slow,the liver coefficient ratio was increased,the liver color was reddish brown,some liver lobule boundaries were unclear,a small number of liver cells were loosely arranged,the contents of ALT,AST,LDH,AKP,and ALB were signif-icantly increased,the mRNA levels of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced,and the protein expres-sions of CYP2E1,CYP3A11,CYP1A2,and CYP2D6 were significantly reduced(all P＜0.05 or P＜0.01),but there was no statistical difference in the mRNA and protein expression of CYP2C19,and the pro-tein expression of CYP2C9(P＞0.05).Compared with the blank group,the mortality rate of nude mice in the cisplatin group was 35.7％,the growth state was poor,the diet,action,and mental state were low,the weight gain was less,the liver coefficient ratio was significantly increased,the liver color was dark red,the liver sinusoids and central veins were congested,the hepatocytes were disordered,the nuclei were consolidated and contracted,and the arrangement was loose,the contents of ALT,AST,LDH,AKP,and ALB were significantly increased,and the mRNA and protein expressions of CYP2E1,CYP3A11,CYP2C19,CYP1A2,CYP2D6,and CYP2C9 were significantly reduced(all P＜0.05 or P＜0.01).CONCLUSION:The dose of Brucea javanica bitter alcohol is correlated with hepatotoxicity to nude mice.High doses of Brucea javanica bitter alcohol have hepatotoxicity to nude mice,which may be re-lated to reducing serum levels of ALT,AST,LDH,AKP,and ALB,inhibiting the expression of multiple subtypes of enzymes in the key enzyme CYP450 of liver drug metabolism,and then reducing the me-tabolism of toxic substances.

Objective:To explore the mediating effect of job embeddedness and job satisfaction on psycholog-ical capital and organizational silence in clinical nurses.Methods:Totally 412 clinical nurses(145 males and 267 females)were selected and assessed with the Nurse Organizational Silence Assessment Questionnaire(NOSAQ),Psychological Capital Questionnaire-24(PCQ-24),Job Embedding Scale(JES)and Nurses Job Satisfaction Scale(NJSS).SPSS macro program PROCESS and Bootstrap method were used to explore the role of mediation.Results:The NOSAQ scores were negatively correlated with the scores of PCQ-24,JES and NJSS(r=-0.55,-0.59,-0.51,Ps＜0.01).Job embeddedness and job satisfaction played a chain mediating role between psychological capital and organizational silence of clinical nurses(95％CI:-0.26--0.04),and the mediating effect accounted for 14.7％of the total effect.Conclusion:It suggests that organizational silence is closely related to psychological capital,job embeddedness and job satisfaction in clinical nurses.

OBJECTIVE To predict and validate the potential mechanisms of Kaixinsan(KXS)in ameliorating neuroinflammation in Alzheimer's disease(AD).METHODS Network pharmacology was employed to identify core anti-inflammatory components and key inflammatory targets of KXS for AD.Gene ontology(GO)functional annotation,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and molecular docking were performed.Based on these findings,male SD rats were used to establish an AD model via chronic D-galactose induction.The effects of KXS on AD rats were evaluated,including quantitative behavioral score,learning and memory parameters(escape latency,platform crossings,platform quadrant distance and time),organ indexes(heart,liver,spleen,thymus),histopathological alterations in the hippocampus,and expressions of inflammation-related pathway proteins and their upstream/downstream regulators.RESULTS Core anti-inflammatory components of KXS for AD included gomisin B,panaxytriol,gomisin A,enhydrin,vulgarin and panaxydol,while key inflammatory targets involved nuclear factor-kappa B subunit 1(NFKB1),nuclear factor-κB p65(NF-κB p65),interleukin-1β(IL-1β),IL-6,Toll-like receptor 4(TLR4),tumor necrosis factor,nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3(NLRP3)and caspase-1(CASP1).GO and KEGG pathway enrichment involved inflammatory response,phosphorylation and the NF-κB signaling pathway.Molecular docking confirmed strong binding affinities between core components and key targets.Animal experiments demonstrated that,compared to the model group,KXS significantly alleviated histopathological damage(e.g.,neuronal shrinkage,reduced Nissl bodies in hippocampal CA1,CA3,and DG regions),increased organ indexes(except for liver index)and Nissl-stained positive cells,improved learning and memory performance,and reduced behavioral scores(at the 8 and 12 weeks of the experiment)and protein expression of NF-κB p65,phosphorylated NF-κB p65,TLR4,NLRP3,CASP1 and IL-1β.CONCLUSIONS KXS effectively mitigates neuroinflammation,reduces hippocampal neuronal injury,and enhances learning and memory ability in AD rats,potentially through suppressing the NF-κB signaling pathway and its upstream/downstream regulators.

To explore the correlation between human body fat distribution and carotid athero-sclerosis.