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.

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.

Objective:To investigate the predictive value of the National Institutes of Health Stroke Scale (NIHSS) score at 24 h after endovascular treatment on the outcomes in patients with acute basilar artery occlusion (ABAO).Methods:Consecutive patients with ABAO received endovascular treatment at the Department of Neurology, Shengli Oilfield Central Hospital from January 2019 to December 2020 were retrospectively included. According to the modified Rankin Scale scores at 90 days after onset, the patients were divided into a good outcome group (0-3) and a poor outcome group (4-6), as well as a survival group and a death group. The demographic and clinical data between the groups were compared respectively. Multivariate logistic regression analysis was use to identify independent influencing factors for clinical outcomes and mortality. The predictive value of postprocedural 24 h NIHSS score on the outcomes was evaluated using the receiver operating characteristic (ROC) curves. Results:A total of 35 patients with ABAO were included. Their age was 62 years (interquartile range, 56-66 years), and 28 patients were males (80%); 19 (54.3%) had a good outcome, 16 (45.7%) had a poor outcome, and 7 (20.0%) died. Univariate analysis showed that there were statistically significant differences in hypertension, low-density lipoprotein cholesterol, fasting blood glucose, collateral circulation grading, vascular recanalization, and postprocedural 24 h NIHSS scores between the good outcome group and the poor outcome group (all P<0.05). Multivariate logistic regression analysis showed that the postprocedural 24 h NIHSS score was independently correlated with the poor outcome (odds ratio 1.131, 95% confidence interval 1.017-1.258; P=0.023). Multivariate analysis did not find the independent influencing factors for death. ROC curve analysis showed that the area under the curve of the postprocedural 24 h NIHSS score for predicting poor outcome was 0.814 (95% confidence interval 0.668-0.960; P=0.011). The optimal cutoff value was 19 points, and the corresponding sensitivity and specificity were 85.7% and 71.4% respectively. Conclusions:In patients with ABAO receiving endovascular treatment, the postprocedural 24 h NIHSS score has good predictive value for poor outcomes at 90 d after procedure.

Cerebrovascular diseases and cardiovascular diseases are among the top causes of death worldwide. In recent years, the concept of "brain-heart co-treatment" has gradually gained popularity. Cerebrovascular and cardiovascular diseases have similar pathological foundations, pathogenesis, comorbidities, and treatment methods. However, there is currently limited research on whether the two have a chronological order of the first onset and which is the index event of the other. However, elucidating the above issues is of great significance for the secondary prevention of cardiocerebrovascular diseases. This article reviews the correlation of onset time and influencing factors for ischemic stroke and myocardial infarction.

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 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.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

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.

Objective To evaluate the effect of traditional Chinese medicine nursing technology among patients with ulcerative colitis.Methods Totally 170 patients with ulcerative colitis were recruited.All patients received routine treatment and received transitional care in inpatient department including diet guidance,illness response and anal guidance on contraction exercise,etc.What's more,the observation group implemented traditional Chinese medicine nursing techniques,including auricular pressure paste,acupuncture point application,acupressure,moxibustion,etc.After 7 and 14 days,we compared the patients' disease activity,sleep quality by Grading scale for Traditional Chinese Medicine symptoms and signs of ulcerative colitis,improved Mayo question,Pittsburgh Quality Sleep Index(PQSI).Results On the 7th and 14th day after intervention,the scores of symptoms and signs in the observation group were (9.73 ± 3.49),(4.54 ± 2.75) points,lower than those in the control group (10.72 ± 4.00),(8.22 ±3.06) points,and the difference was statistically significant (t =1.973,7.878,P =0.042,0.000).On the 14th day after intervention,the Mayo score of observation group was (3.33 ± 1.82) points,lower than that of control group (4.56 ± 1.77) points.The difference was statistically significant (t =4.278,P =0.000).The PSQI score of observation group was (5.67 ± 2.87) points,lower than that of control group (8.53 ± 3.13)points.The difference was statistically significant (t =5.934,P =0.000).Conclusions Traditional Chinese medicine transitional care could effectively improve the symptom of disease and sleep quality among patients with ulcerative colitis.

Objective To analyze the disease spectrum of abdominal external hernia during medical selection of flying cadets and compare the medical standards between US Air Force and Chinese PLA Air Force in order to improve the system of medical selection.Methods The data about abdominal external hernia among flying cadets during Chinese PLAAF medical selection between 2012 and 2015 were retrospectively analyzed and compared with the medical standards of the USAF flying cadets.Results Twenty-nine candidates were eliminated because of hernia,including 4 cases of hiatal hernia,3 cases of umbilical hernia and 22 cases of inguinal hernia.4.70% of the candidates were eliminated because of hernia disease.Empirical research showed difference in hernia standards between China and the USA.Conclusion Compared with Chinese medical selection standards,the USAF standards give more weight to whether the symptoms of disease impact air safety and efficiency.Our medical selection standards need to be improved by learning from foreign practices.