Objective: To explore the influencing factors and network structure of aggressive behaviors among college students based on propensity score matching (PSM), so as to provide precise targeted interventions for the prevention and improvement of aggressive behaviors among college students. Methods: A total of 2 652 college students were selected by convenient sampling method from three colleges in Wuhan, Hubei Province in June 2023. Questionnaire surveys were carried out by using the Buss-Warren Aggression Questionnaire (BWAQ), Ruminative Responses Scale (RRS), Cognitive Emotion Regulation Questionnaire-Chinese Version (CERQ-C), Family APGAR Index (APGAR) ,Brief Fear of Negative Evaluation Scale (BFNES).By bias score matching (PSM) for 1∶1 matching, univariate and multivariate Logistic regression analysis, and network analysis were conducted on the college students. Results: College students with higher levels of ruminant thinking，non adaptive emotional regulation and fear of negative appraisal were more likely to have highly aggressive behaviors（ OR =1.14，1.18，1.06），and those with higher adaptive emotional regulation and family care index were more likely to have highly aggressive behaviors ( OR =0.88，0.82)( P < 0.01 ). Network structure was significantly different between the two groups ( M =0.27, P <0.05). The core affective factors of college students with high levels of aggressive behavior were brooding reflective pondering and symptom rumination( EI =3.50, 3.49, 3.48 )，low aggressive behavior college students core affective factors were adaptive emotion regulation growth and non adaptive emotion regulation( EI =4.37, 4.12, 4.08). Conclusion Factors affecting Chinese college students aggressive behaviors are of different characteristics on different behaviour types, and targeted interventions should be adopted to reduce aggressive behaviors of college students.

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

The cartilage-protective effect of ginkgolide C(GC)on the two modeling modalities was investigated based on joint pain,degree of cartilage pathology,ECM degradation process,and level of inflammatory mediator production in rats.Twenty-five SD rats were selected and randomly di-vided into five groups:the control group(Control group),model 1 group(ACLT group),adminis-tration 1 group(ACLT+GC group),model 2 group(MIA group),and administration 2 group(MIA+GC group.)The rats were euthanized after 4 weeks of the test.Femur,tibia and blood samples were collected from the right hind limb of rats.The degree of pathology in the femur and tibia of rats was assessed by saffron O solid green staining and OARSI score.Immunohistochemis-try was used to detect the expression levels of collagen Ⅱ and MMP-13 in cartilage.ELISA was used to detect the changes in the levels of MMP-3,MMP-13,CTX-Ⅱ,COMP,COX-2,INOS,IL-1β,and TNF-α in the serum of rats.Cold sensitivity test and knee extension vocalization test were conducted to detect the degree of joint pain in rats.ACLT could cause more severe structural dam-age to articular cartilage compared with the MIA group.The OARSI scores and the expression of MMP-13 in femur and tibia,and the serum levels of MMP-13,MMP-3,CTX-Ⅱ,and COMP were higher in the ACLT group than those in the MIA group.However,the levels of inflammatory me-diators COX-2,IL-1β,and TNF-α were significantly lower in the ACLT group than in the MIA group(P＜0.0l).GC intervention reduced the OARSI score(P＜0.05 or P＜0.01)and pain scores,inhibited the ECM matrix degrading enzymes(MMP-13,MMP-3),cartilage metabolism markers(CTX-11,COMP),and inflammatory mediators(COX-2,INOS,IL-1β and TNF-α)ex-pression,and promoted collagen Ⅱ synthesis.Both modeling methods resulted in cartilage damage.In particular,the OA model constructed by ACLT+PMMx method in rats had obvious joint dam-age,which was favorable to investigate the degree of cartilage structural damage.GC attenuated cartilage pathological changes,pain severity and inflammatory response in the rat OA model in both groups,thus exerting a cartilage-protective effect.

Objective:To investigate the value of a deep learning model based on diffusion-weighted imaging (DWI) in quick identification of the TOAST etiology classification in patients with acute ischemic stroke (AIS).Methods:In this cross-sectional study, imaging and clinical data of 504 patients with AIS admitted to the First Affiliated Hospital of Xinjiang Medical University from March 2023 to February 2024 were retrospectively reviewed. Using the TOAST etiology classification, there were 252 large artery atherosclerosis type and 252 small-artery occlusion type. The 504 cases were divided into a training set ( n=302), a validation set ( n=101) and a test set ( n=101) using stratified randomization in the ratio of 6∶2∶2. All cases had DWI data. A DenseNet network framework was used to construct DenseNet models by optimizing the model configurations of different layers. Three DenseNet models with different layers (121, 169, 201) were constructed, named DenseNet169 model, DenseNet121 model, and DenseNet201 model. The data enhancement, Adam optimizer and cross-entropy loss function methods were used to improve the convergence speed and robustness of the model, and to balance the positive and negative sample imbalance problem. Independent sample t-test or χ2 was used to compare the clinical data of patients with large artery atherosclerosis type and small-artery occlusion type AIS. Receiver operating characteristic curves and area under the curve (AUC) were performed to evaluate the efficacy of each model in identification of patients with large artery atherosclerosis type and small-artery occlusion type AIS. Results:There were statistically significant differences in age, National Institutes of Health Stroke Scale score at admission, and stenosis or occlusion of large vessels between patients with large artery atherosclerosis type and small-artery occlusion (all P<0.05). In the test set, the AUC, sensitivity, accuracy, and F1 score values of the DenseNet201 model for discriminating patients with large artery atherosclerosis type AIS and small-artery occlusion type AIS (0.826, 0.902, 0.743, 0.780, respectively) were higher than those of DenseNet121 (0.801, 0.647, 0.723, 0.702, respectively) and DenseNet169 model (0.778, 0.882, 0.733, 0.769). Conclusions:The deep learning models based DWI constructed in this study can help with the TOAST etiology classification of AIS cases. DenseNet201 model shows the best and stable performance in the deep learning-based classification.

Background Flurochloridone (FLC) is toxic to male reproduction and can induce apoptosis of testicular tissue and supporting cells under oxidative stress. Of particular concern is whether nuclear factor-erythrocyte 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway and nuclear factor kappa B (NFκB) signaling pathway participate this process. Objective To observe apoptosis of testicular tissue and sertoli TM4 cells and alterations of Nrf2/HO-1 and NFκB signaling pathways in mice treated with FLC in vivo/in vitro. Methods (1) Animal experiment. Testis samples were harvested from male C57BL/6 mice after 28-day FLC (0, 3, 15, 75, and 375 mg·kg⁻¹ per day) exposure via oral route. Malondialdehyde (MDA) and superoxide dismutase (SOD) in homogenate of testicular tissue were measured by colorimetry. Apoptosis of testicular tissue was evaluated by TUNEL staining. Expression and distribution of Nrf2 and NFκB were detected by immunohistochemistry. Protein expression levels of Nrf2, HO-1, NAD(P)H: quinone oxidoreductase 1 (NQO1), NFκB, inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ), and phosphorylated recombinant inhibitory subunit of nuclear factor kappa-B alpha (P-IκBα) in testicular tissue homogenate were determined by Western blotting. (2) Cell experiment. TM4 cell lines were treated with 40, 80, 120, 160, and 200 μmol·L⁻¹ FLC for 6 h, and cell viability was detected by CCK-8. After 6 h exposure to 40, 80, and 160 μmol·L⁻¹ FLC, the apoptosis rate was detected by flow cytometry, and the protein expression levels of Nrf2, HO-1, NQO1, NFκB, IKKβ, and IκBα were detected by Western blotting. Results (1) Animal experiment. Apoptosis occurred in the interstitial and basal parts of spermatogenic tubules in male C57BL/6 mice after 28 days of oral FLC exposure. Compared with the control group, the MDA level in testicular tissue of the 375 mg·kg⁻¹ FLC-treated group was significantly increased (P<0.05), and the SOD activity was significantly decreased (P<0.05). After 375 mg·kg⁻¹ FLC exposure, apoptosis occurred in the interstitial and basal parts of spermatogenic tubules. The results of immunohistochemistry showed the expression of Nrf2 and NFκB in the interstitium and basal part of spermatogenic tubules of the treated groups. Compared with the control group, the protein levels of Nrf2, NQO1, P-IκBα, NFκB, and IKKβ in the 15, 75, and 375 mg·kg^-1 groups were significantly increased (P<0.001), and the HO-1 protein level was significantly increased in the 375 mg·kg⁻¹ group (P<0.001). (2) Cell experiment. Compared with the control group, the TM4 cell viabilities in the 40, 80, 120, 160, and 200 μmol·L⁻¹ FLC-treated groups significantly decreased (P<0.01). The apoptosis rates were significantly increased (P<0.05), and the apoptosis rates increased from 5.7% in the control group to 7.4%, 9.4%, and 11.7% in the 40, 80, and 160 μmol·L⁻¹, respectively. The Nrf2 protein level in the 40 μmol·L⁻¹ group was significantly increased (P<0.01), while the levels significantly decreased in the 80 and 160 μmol·L⁻¹ groups (P<0.01). The HO-1 protein levels in the 40, 80, and 160 μmol·L⁻¹ groups were significantly increased (P<0.01). The level of NQO1 protein in the 40 μmol·L⁻¹ group was significantly increased (P<0.01). The NFκB protein levels were significantly increased in the 80 and 160 μmol·L⁻¹ groups (P<0.001). The IκBα protein levels were significantly decreased in all treated groups (P<0.001). The IKKβ protein had no significant change. Conclusion FLC induces testicular tissue apoptosis, and the process affects Nrf2/HO-1 signaling pathway and NFκB signaling pathway. The in vitro study confirms that FLC could induce apoptosis of TM4 cells and activate Nrf2/HO-1 and NFκB signaling pathways.

AIM: To investigate the effects of antitumor drug paclitaxel(PTX)on the proliferation, apoptosis, cell cycle, cell morphology, and related protein expression of Müller cells, and to evaluate its potential toxicity to the retina.METHODS:Müller cells were cultured in vitro and divided into two groups: control group(normal medium)and PTX group. Retinal Müller cells were treated with different concentrations of PTX(0.005, 0.05, 0.5 and 5mg/L)for varying durations(12, 24, 36, 48 and 72h). The CCK8 method was used to assess the effects of different concentrations of PTX and treatment duration on the proliferation Müller cells. Flow cytometry was employed to investigate the impact of different concentrations of PTX on Müller cells apoptosis and cell cycle arrest. Immunofluorescence was used to observe morphological changes in Müller cells. The effects of PTX on the expression of apoptosis-related proteins and aquaporins were analyzed by Western blot and qRT-PCR.RESULTS: PTX exhibits the ability to inhibit the proliferation of Müller cells when cultured in vitro. The efficacy of this inhibition was found to be dependent on both the concentration of the drug and the duration of the stimulation. Higher concentrations of the drug and longer stimulation times resulted in a weaker ability of the cells to proliferate. Additionally, PTX also induces apoptosis in Müller cells, with increased drug concentrations and longer stimulation times leading to higher apoptosis rates. Flow cytometry analysis demonstrates that PTX arrests Müller cells in the G2-M phase of the cell cycle. Moreover, there is a distinct change in cell morphology, with a shift from the typical appearance characterized by clear and slender fibrous structures to a rounder morphology, accompanied by a significant decrease in cell numbers. Further, our findings reveal that there is a transient increase in the expression of cytoinflammatory factors following drug treatment compared to the control group. However, discontinuation of drug stimulation can alleviate this heightened expression. In treated cells, the expression of the CA XIV protein is upregulated compared to the control group, while the expression of vascular endothelial growth factor(VEGF)is downregulated(P<0.05). Additionally, the levels of inflammatory factors in the PTX group are significantly higher than those in the control group(P<0.05), suggesting that PTX has the potential to disrupt the retinal barrier function.CONCLUSION: PTX affects the proliferation and apoptosis of Müller cells, with the effects dependent on stimulation duration and drug concentration. In addition, PTX blocks the Müller cell cycle at the G2-M phase and alters cell morphology, leading to a transient upregulation of inflammatory factors and affecting the integrity of the retinal barrier. These findings indicate the potential toxicity of the antitumor drug PTX to the retina.

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g^-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.
Humans ; East Asian People ; Neoplasms/pathology* ; Antibodies, Monoclonal, Humanized/therapeutic use*

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.