ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

Objective: To examine the association between academic stress and anxiety-depression comorbidity among college students and the potential moderating effect of physical activity, so as to provide a theoretical basis for the development of evidence based mental health promotion frameworks in higher education institutions. Methods: From October 2022 to June 2024, a total of 7 980 students from 21 universities across five provinces/municipalities in China, including Shanghai, Jiangsu, Zhejiang, Shandong, and Anhui, using a combination of convenience sampling and stratified random cluster sampling. Physical activity, academic stress, anxiety, and depression were assessed by using the 24 hour Movement Behaviors Questionnaire, the Chinese College Students Mental Health Screening Scale, the Generalized Anxiety Disorder-7, and the Center for Epidemiologic Studies Depression Scale, respectively. Binary Logistic regression was used to examine the associations between academic stress and anxiety, depression, and their comorbidity. The PROCESS macro was employed to test the moderating effect of physical activity. Results: The prevalence of anxiety-depression comorbidity among college students was relatively high (11.53%), with significant differences observed across grades and body mass index (BMI) categories ( χ 2=70.30, 24.63, both P <0.01). Binary Logistic regression revealed that, compared with low academic stress, moderate academic stress among male students was significantly associated with greater odds of anxiety ( OR =2.78), depression ( OR =2.75), and anxiety-depression comorbidity ( OR =2.89) (all P <0.01). High academic stress was associated with elevated odds of anxiety ( OR =6.66), depression ( OR =12.81), and anxiety-depression comorbidity ( OR =13.65) (all P <0.01). Among female students, moderate academic stress was associated with anxiety ( OR =2.58), depression ( OR =1.52), and anxiety-depression comorbidity ( OR =1.70) (all P <0.01). High academic stress increased the risk of anxiety ( OR =6.77), depression ( OR =6.81), and anxiety-depression comorbidity ( OR =7.48) (all P <0.05). The moderation analysis indicated that the interaction between total physical activity duration and academic stress had a significant netative moderating effect on anxiety-depression comorbidity among college students ( β =-0.03, P <0.01). Conclusions Academic stress increases the risk of anxiety, depression, and anxiety-depression comorbidity among college students. Physical activity may attenuate the adverse effects of academic stress on anxiety-depression comorbidity.

Objective: To explore the temporal variation in physical health status among college students, analyze the correlation and dose response relationship between body mass index (BMI) and physical fitness indicators, so as to provide a scientific basis for physical health intervention among college students in universities. Methods: A total of 4 910 freshmen in the 2021 grade at Xi an Jiaotong University were selected. The BMI and changes in five physical fitness indicators (50 meter run, endurance run, standing long jump, sit and reach, and pull up or 1 minute sit up) were continuously assessed during follow up evaluations from 2021 to 2024. One way analysis of variance, generalized estimating equation (GEE), and other statistical methods were used to analyze the trends in temporal variation among the physical fitness indicators as well as the correlation characteristics and dose response relationship between BMI and physical fitness. Results: In 2021 the overweight and obesity rates among male freshmen were 20.36 % and 8.62%, respectively, and 12.91% and 2.91% among female freshman, respectively. From 2021 to 2024 the BMI of male and female students showed an upward trend with a significant increase( F =87.29,3.69,both P <0.05). The physical fitness indicators for both male and female students, including the 50 meter run, standing long jump, pull up and 1 minute sit up, first increased and then decreased, the endurance run performance decreased, and the sit and reach performance first decreased and then increased. The GEE model showed that BMI was negatively correlated with the performance of standing long jump, pullup/1 minute sit up, and sit and reach in both male and female students（ β =-1.72，-0.34，-0.15；-0.94，-0.26，-0.12）, and positively correlated with the time of 50 meter run and endurance run（ β =0.05，3.16；0.03，1.86）（all P ＜0.05）. The increase in BMI was associated with physical fitness decline in a non linear dose response relationship, while the sit and reach performance reached a peak at a BMI of approximately 22 kg/m 2, then decreased with the further increase in BMI. Conclusions A significant negative correlation is demonstrated between BMI and physical fitness indicators and male students are more sensitive to changes in BMI. College students should be guided to actively manage their weight and attach importance to physical exercise to improve their physical health.

BACKGROUND:Carboxylesterase 1 and inflammatory factors play a crucial role in regulating lipid metabolism and glucose homeostasis.However,the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats remain to be revealed. OBJECTIVE:To investigate the effects of different exercise intensity interventions on carboxylesterase 1 and inflammatory factors in skeletal muscle of type 2 diabetic rats. METHODS:Thirty-two 8-week-old male Sprague-Dawley rats were randomly divided into normal control group(n=12)and modeling group(n=20)after 1 week of adaptive feeding.Rat models of type 2 diabetes mellitus were prepared by high-fat diet and single injection of streptozotocin.After successful modeling,the rats were randomly divided into diabetic control group(n=6),moderate-intensity exercise group(n=6)and high-intensity intermittent exercise group(n=6).The latter two groups were subjected to treadmill training at corresponding intensities,once a day,50 minutes each,and 5 days per week.Exercise intervention in each group was carried out for 6 weeks.After the intervention,ELISA was used to detect blood glucose and blood lipids of rats.The morphological changes of skeletal muscle were observed by hematoxylin-eosin staining.The mRNA expression levels of carboxylesterase 1 and inflammatory cytokines were detected by real-time quantitative PCR.The protein expression levels of carboxylesterase 1 and inflammatory cytokines were detected by western blot and immunofluorescence. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,insulin resistance index in the diabetic control group were significantly increased(P<0.01),insulin activity was decreased(P<0.05),and the mRNA and protein levels of carboxylesterase 1,never in mitosis gene A related kinase 7(NEK7)and interleukin 18 in skeletal muscle tissue were upregulated(P<0.05).Compared with the diabetic control group,fasting blood glucose,triglyceride,low-density lipoprotein cholesterol,and insulin resistance index in the moderate-intensity exercise group and high-intensity intermittent exercise group were down-regulated(P<0.05),and insulin activity was increased(P<0.05).Moreover,compared with the diabetic control group,the mRNA level of NEK7 and the protein levels of carboxylesterase 1,NEK7 and interleukin 18 in skeletal muscle were decreased in the moderate-intensity exercise group(P<0.05),while the mRNA levels of carboxylesterase 1,NEK7,NOD-like receptor heat protein domain associated protein 3 and interleukin 18 and the protein levels of carboxylesterase 1 and interleukin 18 in skeletal muscle were downregulated in the high-intensity intermittent exercise group(P<0.05).Hematoxylin-eosin staining showed that compared with the diabetic control group,the cavities of myofibers in the moderate-intensity exercise group became smaller,the number of internal cavities was reduced,and the cellular structure tended to be more intact;the myocytes of rats in the high-intensity intermittent exercise group were loosely arranged,with irregular tissue shape and increased cavities in myofibers.To conclude,both moderate-intensity exercise and high-intensity intermittent exercise can reduce blood glucose,lipid,insulin resistance and carboxylesterase 1 levels in type 2 diabetic rats.Moderate-intensity exercise can significantly reduce the expression level of NEK7 protein in skeletal muscle,while high-intensity intermittent exercise can significantly reduce the expression level of interleukin 18 protein in skeletal muscle.In addition,the level of carboxylesterase 1 is closely related to the levels of NEK7 and interleukin 18.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

As a virtual shared space based on advanced technologies such as virtual reality(VR),augmented reality(AR),mixed reality(MR),artificial intelligence(AI),and 5th generation mobile communication technology,the metaverse has revolutionized all walks of life,including medicine.Extended reality(XR)and AI technologies are gradually becoming one of the mainstream directions of technological development,among which interventional radiology based on imaging data has shown great potential in the field of metaverse medicine.XR technology not only plays a significant role in improving the efficiency and accuracy of interventional diagnosis,but also has multi-dimensional impacts on doctors'clinical skills training,doctor-patient communication,patient education,postoperative rehabilitation,and overall medical development.At present,the construction of metaverse medicine is still in its early stage,and the practitioners engaged in interventional medicine can use XR and AI technology to improve their clinical skills and to enhance the doctor-patient communication ability,thus,to further improve the medical environment and promote the progress of disciplines as well as the comprehensive development of metaverse medicine including interventional diagnosis and treatment.

Objective: To discover molecular markers associated with lung adenocarcinoma diagnosis/prognosis and drug resistance through screening of differentially expressed genes based on published chip data in gene expression databases using bioinformatics methods. Methods: Comprehensive analysis was performed in available mRNA microarray datasets including lung adenocarcinoma tissues dataset GSE32863 and lung adenocarcinoma taxane-platin resistance dataset GSE77209 from the gene expression omnibus(GEO) database. Gene ontology enrichment analysis, gene pathway enrichment analysis and protein interaction network analysis were performed based on significantly correlated genes. The expression level of genes was validated in the cancer genome atlas(TCGA) dataset. Survival differences were assessed by the log-rank test in TCGA lung adenocarcinoma dataset. Based on the publications genomics of drug sensitivity in cancer(GDSC) database in CellMiner cross database(CellMiner CDB), Pearson correlation analysis was used to analyze the correlation between differentially expressed genes and the half-maximal inhibitory concentration(IC50) of anticancer drugs. Results : There were a total of 77 genes which had a different expression in resistance lung adenocarcinoma cells and lung adenocarcinoma cancer tissues. The functional enrichment analysis showed that these co-different expression genes were mainly enriched in microtubule, extracellular exosome, cell cycle and signaling by nuclear receptors. Protein-protein interactions(PPI) network screened 6 most connected genes as molecular complex(MCODE). Among the MCODE, overexpressed ubiquitin conjugating enzyme E2 T(UBE2T), kinesin family member 20A(KIF20A), PCNA clamp associated factor(KIAA0101), pituitary tumor-transforming gene 1(PTTG1) and NIMA related kinase 2(NEK2) were associated with poor outcomes. Survival analysis results showed that these five genes were upregulated in lung adenocarcinoma tissues and drug-resistant cells and were significantly associated with poor prognosis in lung adenocarcinoma patients. Drug sensitivity analysis results suggested that high expression of PTTG1 and UBE2T was significantly associated with sensitivity to multiple anticancer drugs, including paclitaxel and docetaxel. RT-PCR validation showed that PTTG1 andUBE2T were highly expressed in docetaxel-resistant cells A549-TXR and H358-TXR. Conclusion PTTG1 andUBE2T holds the potential to be chemoresistance markers in lung adenocarcinoma.

OBJECTIVES: To explore the therapeutic mechanism of Arctium lappa extract for treatment of Post-Viral Pneumonia Pulmonary Fibrosis (PPF). METHODS: The chemical constituents of Arctium lappa extracts were identified using UHPLC-Q-TOF-MS/MS. Mouse models of pulmonary fibrosis established by tracheal instillation of bleomycin were treated with Arctium lappa extract, and body weight changes were recorded and lung tissue pathology was examined using HE and Masson staining. Metabolomics analysis was used to identify the differential metabolites and the associated metabolic pathways in the treated mice. The common targets of viral pneumonia and pulmonary fibrosis were acquired from the publicly available databases, and the core targets and active constituents were screened using the protein-protein interaction (PPI) network, GO and KEGG enrichment analyses, and molecular docking, and a "gene-metabolite" regulatory network was constructed. The expressions of the core targets were detected in the lung tissues of the treated mice using Western blotting. RESULTS: Fifty-three chemical constituents were identified from Arctium lappa extract. In the mouse models of pulmonary fibrosis, treatment with Arctium lappa extract significantly improved weight loss and ameliorated lung inflammation and fibrosis. The differential metabolites in the treated mice were enriched in energy metabolism pathways involving citrate cycle, pentose phosphate pathway, glycolysis, tryptophan metabolism, glutamate metabolism and glutathione metabolism, which regulated the production of energy metabolism intermediates. Twenty-three key active compounds (mostly lignans and phenolic acids) and 82 core targets were screened, which were associated with the non-canonical Smad signaling pathways (including PI3K/AKT, HIF-1, MAPK, and Foxo) that participated in the regulation of energy metabolism. Arctium lappa extract also regulated the expressions of epithelial-mesenchymal transition (EMT)‑related proteins (fibronectin, vimentim, and Snail, etc.) and inhibited MAPK signaling pathway activation. CONCLUSIONS Preliminary findings suggest that Arctium lappa treats fibrosis by regulating metabolism to inhibit EMT and involves the modulation of non-canonical Smad signaling pathways, such as MAPK providing theoretical support for its clinical application and further research in treating PPF.
Arctium/chemistry* ; Animals ; Pulmonary Fibrosis/metabolism* ; Mice ; Metabolomics ; Network Pharmacology ; Plant Extracts/pharmacology* ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic