Objective To investigate the effect of diosgenin on the proliferation and apoptosis of breast cancer cells and its potential molecular mechanism. Methods The breast cancer cell line MCF-7 was treated with low, medium, and high doses of diosgenin, and cell proliferation was detected through the MMT method. Flow cytometry was used to detect cell apoptosis. Nuclear-cytoplasmic-protein separation method was applied to detect the subcellular localization of death associated protein (DAXX). qRT-PCR and Western blot were used to detect the expressions of DAXX and c-Jun N-terminal kinase pathway (JNK)-related proteins. Results Diosgenin considerably inhibited the proliferation of MCF-7 cells and promoted cell apoptosis in a concentration-dependent manner. Diosgenin can promote the movement of DAXX from nucleus into the cytoplasm. Diosgenin upregulated the expression of cell surface death receptor (Fas), increased the phosphorylation levels of JNK and mitogen activated protein kinase (p38), and activated the JNK/p38 signaling pathway with concentration dependence. Conclusion Diosgenin inhibits the proliferation and promotes the apoptosis of the breast cancer cell line MCF-7, whose mechanism may be related to the regulation of DAXX subcellular localization and the activation of JNK/p38 signaling pathway.

Objective To investigate the effects of indirubatin derivative E804 on proliferation and migration of non-small cell lung cancer(NSCLC)A549 cells,and to elucidate the possible mechanism of Nrf2-HO-1/GPX4 pathway.Methods Lung cancer A549 cells were used as the cell model.The proliferation and migration of differ-ent specific inhibitors(Nec-1,CQ,Z-VAD,DFO,Fer-1 and Lip-1)in 0,10 μmol/L E804 and 10 μmol/L E804+groups were observed by MTT and cell scratch assay.The contents of reactive oxygen species(ROS)were de-tected by DCFH-DA fluorescence probe method,the contents of Fe2+were detected by colorimetric method,the contents of reduced glutathione(GSH)were detected by spectrophotometry,and the contents of malondialdehyde(MDA)were detected by micromethod.The expression levels of SLC7A11,Transferrin,GPX4,SLC40A1,Nrf2 and HO-1 were detected by Western blot in cells of 0,2.5,5 and 10 μmol/L E804 groups.Results Compared with the control group(0 μmol/L E804),2.5,5 and 10 μmol/L E804 significantly increased intracellular ROS,Fe2+and MDA levels,and decreased intracellular GSH content(P＜0.01).Meanwhile,the expression levels of SLC7A11,GPX4,SLC40A1,Nrf2 and HO-1 significantly decreased(P＜0.01),and the expression level of Transferrin increased(P＜0.05).Compared with the 10 μmol/L E804 group alone,the apoptosis inhibitor(Z-VAD)group and the ferroptosis inhibitor(DFO,Fer-1 and Lip-1)group could significantly reverse the inhibition of proliferation and migration of A549 cells by 10 μmol/L E804(P＜0.01).Conclution E804 can induce ferrop-tosis and inhibit the proliferation and migration of A549 cells,which may be related to the inhibition of Nrf2-HO-1/GPX4 pathway.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

ObjectiveTo investigate the dietary preference and nutritional knowledge needs of the elderly people who dined at meal service sites. MethodsUsing the form of stratified and convenience sampling method with self-designed questionnaire was used， in November 2021， to select 700 elderly people who dine at meal service sites in 7 jurisdictions in Shanghai were selected， and a self-designed questionnaire was used to investigate the basic information. Results91.64% of the elderly surveyed would eat at relatively fixed meal service sites， and the total Dietary Diversity Score （DDS9） was 3.56±1.46. 41.45% of the elderly with diseases preferred unhealthy cooking methods. Only 8.03% of the surveyed seniors said they were unwilling to accept targeted and personalized nutrition tips and reminders. Multivariate logistic regression analysis showed that the probability reaching the “understanding” level of “Food Guide Pagoda for Chinese Residents” and “Four Principles Recommended by the Core Dietary Guidelines for the Elderly” was different in the elderly with different education levels. The willingness of the elderly to expect to receive different nutrition tips and reminders was related to whether they cared about the corresponding contents. There was a statistically significant difference （P<0.05） among the elderly who were concerned about different health problems in terms of the willingness to receive different nutritional tips. There were significant differences in the proportion of elderly people with different health status for intervention （χ²=5.402， P<0.05）. ConclusionThe elderly who dine at meal service sites are highly dependent on the sites， have a low level of dietary diversification， and do not have a high degree of understanding of nutrition-related knowledge， and have a high demand for targeted nutritional interventions. Nutritional interventions for the sick elderly should be piloted through multiple channels.

Objective:To grasp the distribution of fine antigenic epitope profiles of nucleoprotein (NP) and glycoprotein (GP) fragments of Crimean-Congo hemorrhagic fever virus (CCHFV) and to clarify the value of dominant antigenic epitopes in laboratory testing of Crimean-Congo hemorrhagic fever (CCHF).Methods:In a minimal synthetic short peptide consisting of 8 amino acids was segmentally expressed by CCHFV YL04057 strain using a modified bio-peptide synthesis method from 2014 to 2021 in the laboratory of Xinjiang University, College of Life Sciences. Using CCHFV polyclonal antibody or monoclonal antibody 14B7 (IgM) or CCHFV-positive sheep serum as antibodies, the minimal antigenic epitopes (BCEs) with antigenic activity on NP and GP fragments were identified by immunoblotting, and the obtained BCEs with sequence polymorphism were spatially clustered with CCHFV from different regions using the neighbor-joining method to determine the combination mode of BCEs with geographical correlation of regional distribution, to explore its application in establishing serological diagnosis. A prokaryotic expression plasmid (pET-32a), an E. coli expression plasmid (pGEX-KG) and a prokaryotic expression plasmid with an incomplete glutathione (GST188) tag (pXXGST-ST-1) were used to construct and express six dominant antigenic epitopes of different peptide lengths on NP fragments, and an indirect Enzyme-linked immunosorbent assay (ELISA) was established. CCHF sheep serum identified by immunofluorescence assay (IFA) was used as a control, and the specificity, sensitivity and overall compliance of the recombinant proteins with different peptide lengths of antigenic epitopes with IFA assay results were statistically analyzed. Results:CCHFV, NP and GP fragments had a total of 30 antigenically active BCEs, among which the core intermediate fragment NP2 (aa 170 th-305 th), which had a concentration of antigenic epitopes in the NP fragment, has 6 BCEs, and the NP1 (aa 1 st-200 th) and NP3 (aa 286 th-482 nd) at both ends have 9 BCEs; the Gc (aa 1 st-558 th) and Gn (aa 533 th-708 th) fragments of the GP fragment have 14 BCEs and a long antigenic peptide (AP) containing 15 amino acids, and the amino acid sequence homology of the NP fragment BCEs was 97.1% and that of the GP fragment BCEs was 89.1%. There was a significant difference ( P=0.0281, P<0.05). Among the 9 BCEs with sequence polymorphism in the GP fragment, 6 combined BCEs from GnEc1, GnE2, GnE4, GcE3, GcE6 and GcAP-4 (Ap) could cluster 15 CCHFV strains from different regions of the world into 5 geographical taxa, AsiaⅠ, AsiaⅡ, AficaⅠ, AficaⅡ and Europe. The constructs expressing PET-32a-NP (full length), PGEX-KG-NP2 (aa 170 th-305 th), pGEX-KG-NP2-1 (aa 235 th-275 th), PGEX-KG-NP2-1-1 (aa 237 th-256 th), pXXGST-1-NP2-1-2 (aa 250 th-265 th) and PGEX KG-NP2-1-3 (aa 260 th-276 th), six recombinant proteins CCHFV NP rabbit polyclonal antiserum (pAb) Western Blotting reaction positive, 33 sheep sera tested by IFA XHF as a reference, the sensitivity of the assay established by indirect ELISA using the recombinant proteins constructed from two fragments of NP2 and NP2-1 as antigens. The sensitivity, specificity and overall compliance were the best, with 73.4% (11/15) and 66.7% (10/15) for sensitivity, 100% (18/18) and 94.4% (17/18) for specificity, and 87.9% (29/33) and 81.8% (27/33) for overall compliance. Conclusion:CCHFV NP and GP are distributed with a high number of BCEs with antigenic immunoreactivity, among which the dominant antigenic epitopes are of high value in the laboratory serological diagnosis of CCHF.

【Objective】 To investigate the psychological status of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and to analyze the effects of anxiety on the total National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) in patients in Ngari Prefecture of Tibet. 【Methods】 CP/CPPS patients treated during Oct.2019 and Oct.2021 were involved and divided into anxiety group and non-anxiety group. The non-anxiety group received routine drug treatment, while the anxiety group received drugs and psychological intervention. 【Results】 A total of 117 patients were involved, including 68 in the anxiety group and 49 in the non-anxiety group. There were no statistical differences between the two groups in terms of age, body mass index (BMI), marital status, smoking history, and education level (P>0.05). The total NIH-CPSI score in the anxiety group (18.53±3.47) was higher than that in non-anxiety group (15.67±3.33), which was mainly manifested by the increase of pain and decrease of quality of life scores. Further stratification of anxiety level revealed that quality of life score and total NIH-CPSI score increased as anxiety symptoms worsened. After drug treatment, pain and urination symptoms were improved in the non-anxiety group, but the quality of life score and total NIH-CPSI score did not change significantly. After psychological intervention, the anxiety group had lower total NIH-CPSI score and other scores. 【Conclusion】 It is not uncommon for CP/CPPS patients to have a comorbidity of anxiety. The increase in the total NIH-CPSI score is caused by the increase of pain score and decrease of quality of life score. Active psychological intervention can improve anxiety, urinary symptoms, pain symptoms and quality of life.

Objective:To conduct quality evaluation and content analysis of adult postoperative nausea and vomiting (PONV) guidelines, so as to provide reference for management of clinical PONV.Methods:Web of Science, Embase, PubMed, UpToDate, SinoMed, Wanfang Database, China National Knowledge Infrastructure, VIP, domestic and foreign clinical practice guidelines and related professional association websites were systematically searched, and the search period was from database establishment to May 6, 2022. Four researchers independently evaluated the guidelines that met the inclusion and exclusion criteria using a clinical guideline research and evaluation system, and summarized the recommendations of the guidelines.Results:Finally, a total of 15 guidelines were included in this study. The overall quality evaluation of the guide was 3 A-level recommendations and 12 B-level recommendations. The average standardization percentages for 6 areas were 81.57% for scope and purpose, 49.91% for participants, 65.38% for rigor, 89.54% for clarity, 34.86% for applicability and 55.42% for independence. A total of 18 recommendations were summarized from five aspects, such as team and organizational management, PONV risk assessment, baseline risk reduction, multimodal prevention of PONV and effectiveness evaluation and monitoring.Conclusions:The guidelines for PONV management mainly come from foreign countries. It is recommended that clinical personnel should learn from foreign guidelines and combine them with domestic clinical situations to localize the recommended opinions and guide the development of clinical practice.

Sodium glucose cotransporter 2 inhibitor (SGLT2i) emerged as a new hypoglycemic agent, which can inhibit glucose reabsorption and thus play a hypoglycemic role. Recent studies have shown that SGLT2i not only lowers blood glucose, but also has a protective effect on the cardiovascular system, which may benefit patients with heart failure.The specific mechanism of action is still not fully elucidated. This paper aims to summarize the latest research results of SGLT2i in the treatment of heart failure, and analyze the possible mechanisms for clinical guidance.

Abstract: To investigate the effect and mechanism of pituitary adenylate cyclase activated peptide recombinant 13 peptide(PACAP13) on thymus at cell, organ and individual levels. Methods: Thymic epithelial cells(TEC) and bone marrow mesenchymal stem cells(MSC) were culturedin vitro, lymphocyte group, lymphocyte+TEC group, lymphocyte+MSC group and lymphocyte+TEC+MSC group were set up to detect the proliferation of lymphocytes in each group treated by PACAP13 peptide, and contents of cytokines interleukin(IL)-1, IL-2, IL-6 and transforming growth factor(TGF) in culture medium were detected. Dexamethasone(Dex) was added to induce cell apoptosis, and Annexin V-FITC/PI flow cytometry double staining was used to detect the effect of PACAP13 peptide on cell apoptosis. Thymus group, thymus+ TEC group, thymus+ MSC group, thymus+ TEC+ MSC group were set up, and PACAP13 peptide was added, the content of signal joint T cell receptor rearrangement excision cricles(sjTREC) in thymus was detected by real-time quantitative PCR(qRCR). The pristane-induced lupus model mice were randomly divided into model group and PACAP13 group. Model group was injected with 0.9% saline, and PACAP13 group was injected with PACAP13 peptide, thymus and spleen sjTREC levels were detected by qPCR, serum lupus-related autoantibodies were detected by ELISA and thymus-related mRNA expression levels were detected by reverse transcription quantitative PCR(qRT-RCR). Results: Compared with the lymphocyte group, the proliferation rate of thymus lymphocytes in the lymphocyte+TEC group, lymphocyte+ MSC group, lymphocyte+ TEC+ MSC group increased, and the apoptosis rate decreased(P<0.05), compared with the control group, the proliferation rate of lymphocytes in the PACAP13 group increased, the rate of apoptosis decreased, and the cytokines IL-1, IL-2, IL-6 and TGF in the cell culture medium increased(P<0.05). Compared with the thymus group, thymus+ TEC group, thymus+ MSC group, thymus+ TEC+ MSC group increased the content of thymus sjTREC, compared with the control group, PACAP13 peptide group thymus sjTREC content increased. Compared with the model group, the content of sjTREC in the thymus and spleen of lupus mice in the PACAP13 group increased(P<0.05), thymus mRNA expression level of AIRE, Fezf2, Foxp3 and TGF-β increased(P<0.01), and CXCL13 mRNA expression level decreased(P<0.01), the autoantibodies of anti-dsDNA antibody, anti-RNP/sm antibody and ANA decreased in serum(P<0.05). Conclusion Compared with the lymphocyte group, the proliferation rate of thymus lymphocytes in the lymphocyte+TEC group, lymphocyte+ MSC group, lymphocyte+ TEC+ MSC group increased, and the apoptosis rate decreased(P<0.05), compared with the control group, the proliferation rate of lymphocytes in the PACAP13 group increased, the rate of apoptosis decreased, and the cytokines IL-1, IL-2, IL-6 and TGF in the cell culture medium increased(P<0.05). Compared with the thymus group, thymus+ TEC group, thymus+ MSC group, thymus+ TEC+ MSC group increased the content of thymus sjTREC, compared with the control group, PACAP13 peptide group thymus sjTREC content increased. Compared with the model group, the content of sjTREC in the thymus and spleen of lupus mice in the PACAP13 group increased(P<0.05), thymus mRNA expression level of AIRE, Fezf2, Foxp3 and TGF-β increased(P<0.01), and CXCL13 mRNA expression level decreased(P<0.01), the autoantibodies of anti-dsDNA antibody, anti-RNP/sm antibody and ANA decreased in serum(P<0.05).

Objective:To investigate the predictive value of fasting blood glucose on clinical outcome after intravenous thrombolysis in patients with severe acute ischemic stroke (AIS).Methods:From January 2016 to November 2020, consecutive patients with severe AIS receiving intravenous thrombolysis in the Department of Neurology, Shengli Oilfield Central Hospital were enrolled retrospectively. Severe AIS was defined as the baseline National Institutes of Health Stroke Scale (NIHSS) score ≥15. The primary endpoint was the clinical outcome evaluated according to the modified Rankin Scale at 90 d after onset. 0-2 was defined as a good outcome and a score of >2 were defined as a poor outcome. The secondary endpoint events were any intracranial hemorrhage and symptomatic intracranial hemorrhage (sICH). Intracranial hemorrhage was defined as any local or distant parenchymal hemorrhage shown by craniocerebral imaging during the hospitalization. sICH was defined as any intracranial hemorrhage and the NIHSS score increased by ≥4 within 7 d after treatment. Univariate and multivariate logistic regression analysis were used to determine the independent influencing factors of various endpoint events. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of fasting blood glucose levels for endpoint events. Results:A total of 113 patients with severe AIS treated with intravenous thrombolysis were included, and 73 (64.6%) had a poor outcome; 29 (25.7%) had intracranial hemorrhage, of which 10 (8.8%) were sICH. Multivariate analysis showed that fasting blood glucose was the independent risk factors for poor outcome (odds ratio [ OR] 1.451, 95% confidence interval [ CI] 1.053-2.000; P=0.023) and sICH ( OR 1.235, 95% CI 1.013-1.504; P=0.036). The ROC curve analysis showed that the area under the curve of fasting blood glucose predicting poor clinical outcome at 90 d after onset was 0.731 (95% CI 0.637-0.824), the optimal cut-off value was 6.25 mmol/L, and the corresponding sensitivity and specificity were 63.0% and 82.5% respectively. The area under the curve of fasting blood glucose predicting sICH was 0.728 (95% CI 0.577-0.878), the optimal cut-off value was 7.98 mmol/L, and the corresponding sensitivity and specificity were 70.0% and 77.7% respectively. Conclusion:Fasting blood glucose is an independent predictor of sICH and poor outcome at 90 d after onset in patients with severe AIS receiving intravenous thrombolysis.