High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective:To investigate the correlation between long-term use of low-dose aspirin and Helicobacter pylori(HP)infection in elderly people and its effectiveness on HP eradication and recurrence.Methods:A retrospective analysis was conducted on 2 834 elderly people aged 60 and above who underwent the C 13-or C 14-urea breath test(UBT)for the first time in the Physical Examination Center of the First Hospital of Lanzhou University between March 2010 and December 2019.According to the results of UBT, people were divided into an HP infection group with 1 510 patients and a non-HP infection group with 1 324 patients.Univariate and multivariate Logistic regression analysis were used to investigate the relationship between aspirin use and HP infection.Additionally, in a prospective case-control analysis, 544 elderly hypertensive patients diagnosed with HP infection between March 2015 and December 2020 were selected and divided into an aspirin group(402 cases)and an observation group(142 cases), based on whether aspirin was used.The aspirin group was further divided into a 1 to <2 years group(134 cases), a ≥2 to <5 years group(142 cases)and a ≥5 years group(126 cases)based on the duration of aspirin treatment.The rates of HP eradication, safety and one-year post-treatment HP recurrence with bismuth-containing quadruple therapy were compared. Results:The overall HP infection rate was 53.28%(1 510/2 834).Univariate analysis showed that the infection rate in women was higher than in men[56.86%(584/1 027) vs.51.25%(926/1 807), χ2=8.307, P=0.004].The infection rate in aspirin users was higher than in non-aspirin users[57.29%(920/1 606) vs.48.05%(590/1 228), χ2=23.866, P<0.001], with no significant difference between aspirin use for 1-<2 years, ≥2-<5 years and ≥5 years[60.22%(162/269) vs.56.4%(273/484) vs.56.86%(485/853), χ2=1.166, P=0.558].Fasting blood glucose levels in the HP infection group were higher than in the non-HP infection group[(5.92±1.78)mmol/L vs.(5.77±1.40)mmol/L, t=2.317, P=0.021].Multivariate Logistic regression analysis showed the risk of HP infection in women was higher than in men( OR=1.254, 95% CI: 1.075-1.464, P=0.004).Long-term aspirin use increased the risk of HP infection( OR=1.450, 95% CI: 1.249-1.684, P<0.001).Among the 544 cases selected for eradication therapy, 522 completed the treatment protocol, with 479 achieving successful eradication.The overall eradication rate was 91.76%(479/522)according to per-protocol(PP)analysis and 88.05%(479/544)according to intention-to-treat(ITT).After 1 year, 472 cases underwent reexamination, with an overall recurrence rate of 3.6%(17/472).There was no statistical significance in the eradication rate and recurrence rate among the groups with different durations of aspirin treatment and the observation group. Conclusions:Long-term use of low-dose aspirin increases the risk of HP infection in the elderly, but does not affect the eradication rate and one-year recurrence rate of bismuth-containing quadruple therapy.Therefore, periodic screening and eradication of HP should be performed.

OBJECTIVE To explore the effects and potential mechanism of veratramine （VTM） on the proliferation of human glioblastoma U251 cells. METHODS The network pharmacology methods were adopted to screen the targets of ferroptosis related to the effects of VTM on glioblastoma， and to conduct gene ontology and Kyoto Encyclopedia of Genes and Genosomes enrichment analysis. Using U251 cells as the object， CCK-8 assay， the observation of cell morphological changes， DCFH-DA fluorescence probe method， FerroOrange fluorescence probe method and Western blot assay were used to validate the inhibitory effects of VTM on U251 cell proliferation and its possible mechanism. RESULTS Totally 462 targets of ferroptosis related to the effects of VTM on glioblastoma were screened out； they mainly enriched in biological processes such as oxidative stress and apoptosis， and cellular components such as cytoplasmic vesicles and mitochondrial membranes； they affected molecular functions such as iron ion （Fe2+） binding and DNA transcription processes， as well as iron death and phosphoinositide 3-kinase/protein kinase B signaling pathways. VTM with 40， 60， 80， 100， 120 and 140 μmol/L could significantly reduce the cell survival rate （P＜ 0.01）； VTM with 40， 80 and 120 μmol/L could cause cell atrophy and nuclear fragmentation， significantly inhibit the clone formation， increase the levels of intracellular reactive oxygen species （ROS） and Fe2+ levels， increase the expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） protein to different extents， while down-regulate the expression of glutathione peroxidase 4 （GPX4） protein （P＜0.05 or P＜0.01）. CONCLUSIONS VTM can inhibit the proliferation of U251 cells， and promote the accumulation of intracellular ROS and Fe2+， thus inducing ferroptosis； its mechanism might be related to the regulation of the Nrf2/HO-1/GPX4 signaling pathway.

Objective:To examine the relationship between fasting blood glucose(FBG)levels and H. pylori infection, as well as their impact on eradication and recurrence rates.Methods:A total of 1 584 patients with type 2 diabetes, ranging in age from 44 to 91 years old(mean age of 66.6±7.6 years), were included in this study conducted at the Physical Examination Center of the First Hospital of Lanzhou University between March 2010 and December 2019.Of the total participants, 1 063(67.1%)were male and 521(32.9%)were female.Logistic regression analysis was performed to investigate the impact of age, gender, fasting blood glucose, and H. pylori infection on the patients.In the study, 263 patients in the euglycemic control group(HbA1c<7%), 271 patients in the poor glycemic control group(HbA1c≥7%), and 269 patients in the control group underwent H. pylori eradication using bismuth-containing quadruple therapy, and the eradication efficacy, adverse reactions, and recurrence rates were compared after 1 year.Results:In patients with type 2 diabetes, the infection rate of H. pylori was found to be 48.2%.Further regression analysis revealed that poor glycemic control increased the risk of H. pylori infection( OR=1.611, 95% CI: 1.269~2.045, P<0.01). However, the constituent ratio and infection rate of different hypoglycemic drug groups did not show any significant statistical difference.The eradication rate of H. pylori was 90.9%, and there was no significant difference in the eradication rate among different blood glucose groups and control groups.However, after 1 year, the recurrence rate was 3.8%, with a higher rate observed in the poor glycemic control group compared to the euglycemic control group and the control group( P<0.05). There was a statistically significant difference in constipation as the main side effect of eradication therapy between the diabetic group and the control group[25.1%(134/253) vs.16.4%(44/269), P<0.01]. Conclusions:Diabetic patients with fasting hyperglycemia or poor glycemic control are at an increased risk of H. pylori infection.Additionally, these patients have a higher risk of recurrence after eradication.Therefore, it is important for clinicians to closely monitor and manage glycemic control in diabetic patients to reduce the risk of H. pylori infection and improve treatment outcomes.

Objective:To explore the relationship between proactive personality, resilience and achievement motivation of military cadets, and to explore the mediating role of resilience between proactive personality and achievement motivation, as well as the moderating effect of cadets’leading ability on this mediating role.Methods:In this study, 109 military cadets were measured with proactive personality scale, Connor-Davidson resilience scale (CD-RISC) and achievement motivation scale. SPSS 26.0 was used for descriptive statistical analysis and correlation analysis.Results:①There was a significant correlation among the total scores of proactive personality, resilience and achievement motivation ( Ps<0.01). ②Proactive personality could significantly predict the level of achievement motivation ( a=0.454, P<0.001), and resilience could significantly predict the level of achievement motivation ( b=0.231, P=0.019). ③Resilience significantly mediated the relationship between proactive personality and achievement motivation ( c′=0.3, P=0.003). ④Cadets' leading ability moderated the effect of resilience on achievement motivation (index=0.338, 95% CI: 0.057 to 0.881). The mediating effect of resilience between proactive personality and achievement motivation was significant for cadets' leaders (Effect=0.381, 95% CI: 0.085 to 1.005), but not significant for other students (Effect=0.043, 95% CI: -0.069 to 0.252). Conclusion:The proactive personality of military cadets can affect the level of achievement motivation through psychological resilience, which is also moderated by cadre identity, suggesting that military education should improve the level of achievement motivation in many ways.

Coronavirus disease 2019 (COVID-19) has spread rapidly around the world. In order to diagnose COVID-19 more quickly, in this paper, a depthwise separable DenseNet was proposed. The paper constructed a deep learning model with 2 905 chest X-ray images as experimental dataset. In order to enhance the contrast, the contrast limited adaptive histogram equalization (CLAHE) algorithm was used to preprocess the X-ray image before network training, then the images were put into the training network and the parameters of the network were adjusted to the optimal. Meanwhile, Leaky ReLU was selected as the activation function. VGG16, ResNet18, ResNet34, DenseNet121 and SDenseNet models were used to compare with the model proposed in this paper. Compared with ResNet34, the proposed classification model of pneumonia had improved 2.0%, 2.3% and 1.5% in accuracy, sensitivity and specificity respectively. Compared with the SDenseNet network without depthwise separable convolution, number of parameters of the proposed model was reduced by 43.9%, but the classification effect did not decrease. It can be found that the proposed DWSDenseNet has a good classification effect on the COVID-19 chest X-ray images dataset. Under the condition of ensuring the accuracy as much as possible, the depthwise separable convolution can effectively reduce number of parameters of the model.
Betacoronavirus ; Coronavirus Infections ; diagnostic imaging ; Deep Learning ; Humans ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; X-Rays

BACKGROUND: We previously showed that the expression of follistatin-like protein 1 (FSTL1) was significantly down-regulated in metastatic clear-cell renal cell carcinoma (ccRCC). In this study, we aimed to characterize the role of FSTL1 in the development of ccRCC. METHODS: The effects of FSTL1 on cell activity and cell cycle were investigated in ccRCC cell lines with altered FSTL1 expression. Gene expression microarray assays were performed to identify the major signaling pathways affected by FSTL1 knockdown. The expression of FSTL1 in ccRCC and its effect on postoperative prognosis were estimated in a cohort with 89 patients. RESULTS: FSTL1 knockdown promoted anchorage-independent growth, migration, invasion, and cell cycle of ccRCC cell lines, whereas FSTL1 overexpression attenuated cell migration. FSTL1 knockdown up-regulated nuclear factor-κB (NF-κB) and hypoxia-inducible factor (HIF) signaling pathways, increased epithelial-to-mesenchymal transition, up-regulated interleukin-6 expression, and promoted tumor necrosis factor-α-induced degradation of NF-κB inhibitor (IκBα) in ccRCC cell lines. FSTL1 immunostaining was selectively positive in epithelial cytoplasm in the loop of Henle, and positive rate of FSTL1 was significantly lower in ccRCC tissues than in adjacent renal tissues (P < 0.001). The multivariate Cox regression analysis showed that the intratumoral FSTL1 expression conferred a favorable independent prognosis with a hazard ratio of 0.325 (95% confidence interval 0.118-0.894). HIF-2α expression was negatively correlated with FSTL1 expression in ccRCC specimens (r = - 0.229, P = 0.044). Intratumoral expression of HIF-2α, rather than HIF-1α, significantly predicted an unfavorable prognosis in ccRCC (log-rank, P = 0.038). CONCLUSIONS FSTL1 plays a tumor suppression role possibly via repressing the NF-κB and HIF-2α signaling pathways. To increase FSTL1 expression might be a candidate therapeutic strategy for metastatic ccRCC.
Adult ; Aged ; Aged, 80 and over ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Carcinoma, Renal Cell ; genetics ; pathology ; Cell Line, Tumor ; Cell Movement ; genetics ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; genetics ; Female ; Follistatin-Related Proteins ; genetics ; Gene Expression Regulation, Neoplastic ; genetics ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; Male ; Middle Aged ; NF-kappa B ; genetics ; Neoplasm Metastasis ; Signal Transduction ; genetics ; Tumor Suppressor Proteins ; genetics

Health science popularization industrialization is a necessary choice for the development of health popularization business.However,in the process of health science popularization industrialization,there exists certain difficulties to balance the contradiction between profitability and public welfare.In theory,the public welfare goal of health science popularization can be realized by industrial profitability means;therefore,the ethical dilemma about it can be solved.In the policy practice,the government may be the main body of the health popularization while profit-making organizations may carry out the health popularization.The government can promote the health popularization industrialization by purchasing health popularization from the relative organizations.

Traditional Chinese surgical treatment "suture-dragging" therapy is based on medical thread therapy and tight seton drainage in combination of minimal invasive surgical principle. It can preserve the integrity of anal sphincter musculature involved in fistulous tract or abscess and maintain anal function. This article not only describes in detail about the operation points and mechanisms of "suture-dragging" therapy of anorectal fistula, but also reviews the application and modification of anorectal disease.
Abscess ; Drainage ; Humans ; Rectal Fistula ; Suture Techniques ; Sutures