OBJECTIVE To investigate the improvement effects and mechanism of Achyranthes bidentata total saponins （ABS） extract on vascular endothelial dysfunction in spontaneously hypertensive rat （SHR） based on cytochrome P450 4A （CYP4A）/20-hydroxyeicosatetetraenoic acid （20-HETE）/G protein-coupled receptor 75 （GPR75） axis. METHODS Ten Wistar- Kyoto rats were taken as the normal control group. Forty SHR were first stratified by systolic blood pressure and then， within each stratum， randomly assigned using a random-number table to the model group （MOD group）， captopril positive control group （CAP group， 10 mg/kg）， ABS low- and high-dose extract groups （ABS-L group， ABS-H group， 60 and 120 mg/kg）， with 10 rats in each group. Animals in each group were given the corresponding drug or equal volume of pure water by gavage， once a day， for 28 consecutive days. After the last administration， systolic blood pressure of rats was measured. The levels of vasoactive substances， inflammatory factors and oxidative stress indicators in serum were measured. The pathological changes of rat thoracic aorta were observed. The level of reactive oxygen species （ROS） in aortic tissue was analyzed. The expressions of endothelial nitric oxide synthase （eNOS）， CYP4A， GPR75， nuclear factor-κB p65 （NF-κB p65）， phosphorylated NF-κB p65， p22phox， and reduced nicotinamide adenine dinucleotide phosphate oxidase 4（NOX4） in thoracic aorta tissue were detected. RESULTS After 28 d of treatment， compared with MOD group， the systolic blood pressure of rats in the ABS-L and ABS-H groups decreased significantly. The levels of 20-HETE， angiotensin Ⅱ， interleukin-1β， interleukin-6， tumor necrosis factor-α， intercellular cell adhesion molecule-1 and malondialdehyde in serum were significantly reduced （P＜0.05 or P＜0.01）， while the levels of nitric oxide， superoxide dismutase， glutathione peroxidase and catalase were significantly increased （P＜0.05 or P＜0.01）. Intimal damage of thoracic aorta was reduced， and endothelial cell morphology was improved. The expressions of ROS， CYP4A， GPR75， p22phox， NOX4 and the phosphorylation level of NF-κB p65 protein in thoracic aorta were down-regulated or reduced （P＜0.05 or P＜0.01）， while the expression of eNOS was up-regulated （P＜0.05 or P＜0.01）. CONCLUSIONS ABS extract may alleviate the inflammatory response and oxidative stress in SHR effectively by down-regulating the expression of CYP4A， reducing the production of 20-HETE， inhibiting the activation of GPR75， and subsequently suppressing the activation of downstream NF-κB and NOX4， thereby improving hypertension-related vascular endothelial dysfunction.

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

OBJECTIVE: To investigate the impact of bone mass and volume of low-density zones beneath the tibial plateau on the maximum von Mises stresses experienced by the cartilage and meniscus in the knee joint. METHODS: The study included one healthy adult volunteer, from whom CT scans were obtained, and one patient diagnosed with knee osteoarthrisis (KOA), for whom X-ray films were acquired. A static model of the knee joint featuring a low-density zone was established based on a normal knee model. In the finite element analysis, axial loads of 1 000 N and 1 800 N were applied to the weight-bearing region of the upper surface of the femoral head for model validation and subsequent finite element studies, respectively. The maximum von Mises stresses in the femoral cartilage, as well as the medial and lateral tibial cartilage and menisci, were observed, and the stress percentage of the medial and lateral components were concurrently analyzed. Additionally, HE staining, as well as alkaline magenta staining, were performed on the pathological specimens of patients with KOA in various low-density regions. RESULTS: The results of model validation indicated that the model was consistent with normal anatomical structures and correlated with previous calculations documented in the literature. Static analysis revealed that the maximum von Mises stress in the medial component of the normal knee was the lowest and increased with the advancement of the hypointensity zone. In contrast, the lateral component exhibited an opposing trend, with the maximum von Mises stress in the lateral component being the highest and decreasing as the hypointensity zone progressed. Additionally, the medial component experienced an increasing proportion of stress within the overall knee joint. HE staining demonstrated that the chondrocyte layer progressively deteriorated and may even disappear as the hypointensity zone expanded. Furthermore, alkaline magenta staining indicated that the severity of microfractures in the trabecular bone increased concurrently with the expansion of the hypointensity zone. CONCLUSION The presence of subtalar plateau low-density zone may aggravate joint degeneration. In clinical practice, it is necessary to pay attention to the changes in the subtalar plateau low-density zone and actively take effective measures to strengthen the bone status of the subtalar plateau low-density zone and restore the complete biomechanical function of the knee joint, in order to slow down or reverse the progression of osteoarthritis.
Humans ; Finite Element Analysis ; Knee Joint/physiology* ; Tibia/anatomy & histology* ; Cartilage, Articular/physiology* ; Menisci, Tibial/physiopathology* ; Tomography, X-Ray Computed ; Osteoarthritis, Knee/diagnostic imaging* ; Weight-Bearing ; Bone Density ; Adult ; Stress, Mechanical ; Male ; Middle Aged ; Biomechanical Phenomena ; Female

Lung cancer represents one of the most prevalent malignant tumors globally, and its treatment has entered the era of targeted therapy. The epidermal growth factor receptor (EGFR) mutation is a common type of genetic mutation in non-small cell lung cancer (NSCLC), while c-ros oncogene 1 receptor tyrosine kinase (ROS-1) fusion mutation is a rare mutation site. Currently, there are few case reports on the coexistence of EGFR and ROS-1 gene mutations. This study reports a case of NSCLC with coexisting EGFR and ROS-1 gene mutations, aiming to provide relevant treatment strategies for clinical practice.
.
Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/genetics* ; Mutation ; Protein-Tyrosine Kinases/genetics* ; Proto-Oncogene Proteins/genetics* ; Male ; Middle Aged ; Female

The development of artificial intelligence(AI)technology has promoted major changes in the field of immunology innovation and teaching reform.Traditional teaching classrooms are developing towards digital and intelligent teaching models.In order to improve high-quality education,cultivate AI thinking and comprehensive ability of graduate students,optimize current situations of traditional large classes and diversified characteristics of student,the AI technology is used to analyze the learning situation of students before class.Next,differentiated intelligence allocates digital learning materials according to the results of pre-class survey analysis,adopts"Research on scientific literature-based flipped classroom"teaching methods,carries out differentiated assessment methods,and finally the personalized teaching mode of doctoral students is implemented.This teaching strategy of deep integration of artificial intelligence and personalization can provide theoretical support and practical guidance for the subsequent reform and innovation in the immunology classroom and meet the needs of personalized training for PhD doctoral talents.

Objective:To investigate the status of work-related musculoskeletal disorders (WMSDs) in male large-scale mechanical maintenance workers, and to explore the relationship between WMSDs and thyroid indexes.Methods:From April to July 2022, male front-line maintenance workers in a large-scale mechanical maintenance enterprise who participated in occupational health examination were selected as the study subjects ( n=2036). The occurrence of WMSDs was investigated by questionnaire. The levels of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) in serum were detected. χ2 test, t-test and Mann-Whitney U test were used to detect thyroid diseases and hormone levels of workers in WMSDs group and non-WMSDs group, and binary logistic regression model was used to analyze the relationship between thyroid disease, T3, T4, TSH and WMSDs. Results:The incidence of WMSDs among the male large-scale mechanical maintenance workers was 73.18% (1490/2036). The rate of thyroid disease in WMSDs group was higher than that in non-WMSDs group [8.26% (123/1490) vs. 4.95% (27/546), χ 2=6.42, P=0.011], and the TSH value was lower than that in non-WMSDs group[1.66 (1.23, 2.26) μIU/ml vs. 1.75 (1.30, 2.42) μIU/ml, Z=-2.40, P=0.019]. There were no significant differences in the levels of T3, T4 and abnormal levels of 3 hormones between the two groups ( P>0.05). After accounting for individual and occupational factors, workers with thyroid disease had an increased risk of WMSDs ( OR=1.656, 95% CI: 1.072-2.559, P=0.023), while workers with increased TSH had a decreased risk of WMSDs ( OR=0.897, 95% CI: 0.823-0.977, P=0.013) . Conclusion:The incidence of WMSDs in male workers of large-scale mechanical maintenance is high, and its incidence may be related to thyroid index. Thyroid disease may be a risk factor for WMSDs, and increased TSH may be a protective factor for WMSDs.

Objective:To investigate the antidepressant mechanism of Ziziphi Spinosae Semen and Albiziae Flos through network pharmacology,molecular docking,and cellular experiments.Methods:Active compounds and targets were identified using TCMSP,BATMAN-TCM,GeneCards,and OMIM databases,followed by standardization via the Uniprot database.A Venn diagram was created using venn2.1.0,and a protein-protein interaction(PPI)network was constructed with Cytoscape 3.8.2 and STRING to identify core targets.GO functional and KEGG pathway enrichment analyses were performed using R language.Molecular docking was validated using AutoDock Vina,and the key path-ways and targets were verified by constructing an in vitro model.Results:Twelve active components of Ziziphi Spinosae Semen and Albiziae Flos act on 109 potential depression targets.GO and KEGG analyses identified 2,439 and 163 en-tries,respectively.Based on degree value and enrichment level,core targets such as transcription factor JUN,AKT1,IL-6,and pathways including AGE-RAGE and PI3K/AKT were identified.Molecular docking demonstrated a favorable binding affinity between the active components and core targets.Cellular experiments revealed that serum containing Ziziphi Spinosae Semen and Albiziae Flos at low,medium,and high doses alleviated CORT-induced PC12 cell damage,increased Cell viability,and reduced apoptosis rates.It also upregulated PI3K/AKT pathway protein expression and downregulated endoplasmic reticulum stress related apoptotic protein expression,with more pronounced improvements observed in the medium and high-dose groups(all P＜0.01).Conclusion:The antidepressant effects of Ziziphi Spi-nosae Semen and Albiziae Flos are largely achieved by activating the PI3K/AKT signaling pathway and inhibiting exces-sive ERS,which in turn reduces neuronal apoptosis.

Objective To investigate the diagnostic value of neutrophils CD64(nCD64)index,C reactive protein(CRP),interleukin-6(IL-6)and procalcitonin(PCT)in viral and bacterial upper respiratory tract infections.Methods Patients with upper respiratory tract infection treated in Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University from January 2023 to January 2024 were selected as study objects.According to the results of etiological examination,they were divided into bacterial infection group(46 cases)and viral infection group(58 cases).The levels of nCD64 index,CRP,IL-6 and PCT before medication were compared between two groups.Receiver operating characteristic(ROC)curve was used to evaluate the value of infection markers in the differential diagnosis of bacterial and viral upper respiratory tract infections.Results The levels of CRP,nCD64 index,IL-6 and PCT in bacterial infection group were significantly higher than those in viral infection group(P＜0.01).ROC curve results showed that the area under the curve(AUC)of nCD64 index,CRP,PCT and IL-6 to distinguish the two types of infection were 0.818,0.776,0.692 and 0.654,respectively,and the combined AUC of four indexes was 0.870.Conclusion nCD64 index,CRP,IL-6 and PCT are closely related to the pathogen types of patients with upper respiratory tract infection,and the combined detection of all indicators can improve the diagnostic efficiency of upper respiratory tract infection types.

Objective:To investigate the value of 3.0T magnetic resonance imaging(MRI)in the assessment for clinically pathologic features of prostate cancer(PCa).Methods:The case data of 102 PCa patients who were confirmed by histology in The Second Affiliated Hospital of Bengbu Medical University from April 2020 to July 2024 were retrospectively analyzed.51 PCa patients of them were included in cancer group,and 51 patients with prostatic hyperplasia were included in hyperplasia group.Multi-parametric MRI was implemented in all patients.Imaging performance was scored by using Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1).The distribution of scores between the two groups was compared and analyzed.The correlations between the PI-RADS v2.1 scores and PCa clinically pathological features which included Gleason scores,serum prostate specific antigen(PSA)level,tumor staging and aggressiveness were analyzed and explored by using Spearman correlation analysis.The diagnostic efficacy of the 3.0T MRI technique for PCa was analyzed by using the receiver operating characteristic(ROC)curve.Results:The PI-RADS v2.1 score of cancer group was 4(4,5)scores,which was significantly higher than 2(3,4)scores of hyperplasia group,and the difference of that between two groups was significant(U=369.5,P<0.05).The rate of high scores(4,5 scores)of cancer group was more than that of hyperplasia group in the distribution of scores,and the difference of that between two groups was significant(x2=51.220,P<0.05).In patients of cancer group,PI-RADS v2.1 score showed significant correlation with serum PSA level,Gleason score,tumor staging and aggressiveness(P<0.05),respectively,and they were significant(r=0.815,0.723,0.693,P<0.05).ROC curve analysis showed that the area under curve(AUC)value of PI-RADS v2.1 score was 0.858(95%CI:0.783-0.932)in diagnosing PCa,which can effectively distinguish PCa and prostate hyperplasia.It had higher diagnostic efficacy,which was higher than that of serum PSA.Conclusions:3.0T MRI has favorable accuracy in diagnosing PCa,and it can be used as a noninvasive test method to diagnose and assess pathological features of tumor.

Objective To explore the mechanism of Tongdu Xingshen acupuncture,the clinical efficacy,systemic inflammatory response,blood-brain barrier and intestinal flora in patients with cognitive impairment after ischemic stroke(IS)were studied.Methods Thirty patients(3 cases shedding)with cognitive impairment after IS were included as the disease group,including patients before treatment as the disease group,patients after Tongdu Xingshen acupuncture treatment as the electroacupuncture group,and 30 healthy controls(3 cases shedding)were included as the healthy group.In the electroacupuncture group,on the basis of the basic treatment,Tongdu Xingshen acupuncture was applied,which was 30 min each time,once a day for 14 days.The MMSE,MoCA and MBI scores of the three groups were observed.The fecal and serum samples from all study subjects were collected,and 16S rDNA sequencing technology and ELISA were used to detect the changes of proinflammatory factors IL-6,IL-1β,TNF-α and S100β in serum in intestinal flora and feces.Results Compared with the healthy group,the MMSE,MoCA,and MBI score of patients in the disease group decreased significantly(P<0.05),serum proinflammatory factors and S100β protein content increased significantly(P<0.05),and the Shannon index(P<0.01)and Simpson index(P<0.001)increased significantly.Compared with the disease group,the MMSE,MoCA,and MBI score of the EA group increased significantly(P<0.05),the serum levels of proinflammatory factors and S100β decreased significantly(P<0.05),Shannon index and Simpson index decreased(P>0.05).The dominant bacterial flora in the healthy group mainly included Bacteroides,Bifidobacterium,Bacteroides,Faecalibacterium,Bifidobacteriaceae,Ruminococcaceae,and Bacteroides and other beneficial bacteria(P<0.05).The dominant flora in the disease group included Proteobacteria,Enterobacteriaceae,Escherichia,Klebsiella and other opportunistic bacteria(P<0.05),while the dominant flora in the EA group was consistent with the healthy group,the relative abundance of beneficial bacteria increased significantly(P<0.05),and the relative abundance of opportunistic bacteria decreased significantly(P<0.05).Spearman correlation analysis found that beneficial bacteria were positively correlated with clinical efficacy related indicators,but with serum proinflammatory factors and the content of S100β was negatively correlated.Conclusion Tongdu Xingshen acupuncture can regulate the diversity of intestinal flora to increase the abundance of Bacteroides,Bifidobacterium,Faecalibacterium,and other beneficial bacteria,regulate the intestinal microecological balance,Thereby regulating systemic inflammation and blood-brain barrier function,which plays a role in improving cognitive function.