Glioblastoma(GBM)stands as one of the most aggressive brain tumors,and its pharmacological therapy is severely limited due to the presence of the blood-brain barrier(BBB).Nose-to-brain drug delivery has emerged as a promising approach for directly targeting the central nervous system(CNS)by circumventing the BBB.The nasal cavity is anatomically partitioned into the vestibular,olfactory,and respiratory regions.Nanomedicines can efficiently transport to the CNS through the olfactory pathway of the olfactory region and the trigeminal nerve pathway of the respiratory region.In recent years,nanodelivery platforms in nasal administration for treating GBM have garnered widespread attention,primarily involving polymers,liposomes,inorganic metal nanoparticles,and so on.The advancement of these technologies presents novel avenues and selections for overcoming the BBB,enhancing drug delivery efficacy,and improving the prognosis of GBM patients.

Objective To explore the mechanism of Wumei pill on ulcerative colitis(UC)in mice based on the anti oxidative stress pathway of nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE).Methods Seventy SPF male C57BL/6 mice were randomly divided into the control group,the UC group,the mesalazine group(MES group,0.82 g/kg MES),the low dose Wumei pill group(WMW-L group,5 g/kg crude drug),the middle dose Wumei pill group(WMW-M group,10 g/kg crude drug),the high dose Wumei pill group(WMW-H group,20 g/kg crude drug)and the high dose Wumei pills+Nrf2 inhibitor ML-385 group(WMW-H+ML-385 group,Wumei pills crude drug 20 g/kg+20 mg/kg ML-385),with 10 rats in each group.The disease activity index(DAI)score and colonic mucosa injury score were performed in mice after the last administration.Pathological changes of colonic mucosa in mice were observed by HE staining.The levels of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α)and IL-6 in serum and colon tissue of mice were measured by enzyme-linked immunosorbent assay(ELISA).The content of malondialdehyde(MDA)in serum and colon tissue of mice was determined by thiobarbituric acid colorimetry(TBA).The activity of superoxide dismutase(SOD)in serum and colon tissue of mice was measured by xanthine oxidase method.The activity of glutathione peroxidase(GSH-px)in serum and colon tissue of mice was determined by direct method with dithiodinitrobenzoic acid(DTNB).The positive expression of Nrf2 in colon tissue of mice was observed by immunohistochemistry.The expression of heme oxygenase-1(HO-1)and NAD(P)H:quinone oxidoreductase-1(NQO1)proteins in colon tissue of mice were detected by Western blot assay.Results Compared with the control group,the DAI score,colonic mucosa injury score,colonic histopathology score,levels of IL-1β,TNF-α,IL-6 and MDA in serum and colonic tissue,and expression levels of Nrf2,HO-1 and NQO1 protein in colonic tissue of mice were increased in the UC group,levels of SOD and GSH-px in serum and colon tissue decreased(P＜0.05),the colon mucosa of mice was seriously damaged.Compared with the UC group,changes of corresponding indexes were contrary to the above in the MES group,the WMW-M group and the WMW-H group.However,the expression levels of Nrf2,HO-1 and NQO1 proteins in colon tissue were increased(P＜0.05),and the damage of colon mucosa in mice was alleviated.Changes of the above indexes were dose-dependent in the WMW-L group,the WMW-M group and the WMW-H group.There were no significant differences in the above indexes between the WMW-H group and the MES group.ML-385 attenuated the improvement effect of high dose Wumei pill on colon mucosa injury.Conclusion Wumei pill may alleviate the colon mucosal damage of UC mice by activating Nrf2/ARE antioxidant stress pathway.

BACKGROUND: There has been minimal research on the role of benevolent childhood experiences (BCEs) and how such events may offer protection from the insidious effects of adverse childhood experiences (ACEs) or later in life. OBJECTIVES: This research aims to learn how BCEs and ACEs interact to affect adolescents' psychological distress. METHODS: Cross-sectional survey was conducted in three cities (Xuzhou, Nanjing, and Wuhan) in China from March 2021 to May 2021. Latent class analysis (LCA) was used to classify the patterns of ACEs and BCEs. We adopted hierarchical multivariable regression to examine the influences of ACEs and BCEs on depression and suicidal ideation. RESULTS: To explore the relationship between childhood experience and suicidal ideation and depression, LCA revealed three patterns of ACEs: (1) emotional abuse (10.57%); (2) high ACEs (0.55%); and (3) low ACEs classes (88.88%). Adolescents with emotional abuse (depression: OR = 3.82, 95%CI = 2.80-5.22, P < 0.001; suicidal ideation: OR = 5.766, 95%CI = 3.97-8.38, P < 0.001) and high ACEs class (suicidal ideation: OR = 5.93, 95%CI = 1.19-29.66, P < 0.05) had an increased risk of psychological distress (reference: low ACEs). LCA revealed four patterns of BCEs: (1) relationship support (14.54%); (2) low BCEs (4.85%); (3) high BCEs (55.34%); and (4) high quality of life classes (25.28%). Adolescents with a high quality of life (depression: OR = 0.09, 95%CI = 0.05-0.16, P < 0.001; suicidal ideation: OR = 0.22, 95%CI = 0.12-0.40, P < 0.001) and high BCEs (depression: OR = 0.05, 95%CI = 0.03-0.09, P < 0.001; suicidal ideation: OR = 0.15, 95%CI = 0.09-0.26, P < 0.001) protected the mental health of adolescents (reference: low BCEs). CONCLUSIONS High ACEs and emotional abuse classes were significantly associated with poorer mental health symptoms, including suicidal ideation and depression. In contrast, high BCEs and high quality of life classes were associated with better mental health. These findings point out that it is more necessary to identify and support victims of ACEs, and it is urgent to increase BCEs in early childhood.
Adolescent ; Humans ; Cross-Sectional Studies ; Depression ; East Asian People ; Latent Class Analysis ; Quality of Life ; Suicidal Ideation ; Adverse Childhood Experiences

Objective: To investigate the association of sleep quality, depressive symptoms and their interaction with non suicidal self injury (NSSI) among rural middle school students, so as to provide a reference for early prevention and control of NSSI among rural middle school students. Methods: A multi stage cluster sampling method was used to randomly select four rural middle schools in Xuzhou, Jiangsu Province. A total of 1 723 middle school students were investigated according to the principle of grade stratification and class random selection. Paper questionnaires (including demographic factors, Non Suicidal Self Injury Short Scale, Pittsburgh Sleep Quality Index, Patient Health Questionnare-9) were used to conduct the questionnaire survey. Logistic regression model was used to analyze the association of sleep quality, depressive symptoms and their interaction with NSSI among rural middle school students. Results: Totally 30.5% of middle school students had NSSI. Univariate results showed that girls (33.0%) had a higher incidence of NSSI than boys(27.3%), and those with sleep disorders and depressive symptoms had a higher incidence of NSSI, which was 46.8%, 43.6%. The results of multivariate Logistic regression showed that the risk of NSSI in students with sleep disorder was 1.80 times that in those without sleep disorder( OR 95%CI=1.42-2.28, P <0.01). The risk of NSSI in students with depressive symptoms was 3.32 times higher than that in those without depressive symptoms( OR 95%CI=2.60-4.24, P <0.01). The interaction results showed that there was additive interaction between sleep disturbance and depressive symptoms on the occurrence of NSSI behavior in rural middle school students, and the relative excess risk, attributable proportion and synergy index were 1.80, 0.30 and 1.57, respectively. Conclusion Sleep disorder and depressive symptoms are risk factors for NSSI among rural middle school students, and there is additive interaction between them.

Bacillus cereus belongs to Gram-positive bacteria, which is widely distributed in nature and shows certain pathogenicity. Different B. cereus strains carry different subsets of virulence factors, which directly determine the difference in their pathogenicity. It is therefore important to study the distribution of virulence factors and the biological activity of specific toxins for precise prevention and control of B. cereus infection. In this study, the hemolysin BL triayl was expressed, purified, and characterized. The results showed that the bovine pathogenic B. cereus hemolysin BL could be expressed and purified in the prokaryotic expression system, and the bovine pathogenic B. cereus hemolysin BL showed hemolysis, cytotoxicity, good immunogenicity and certain immune protection in mice. In this study, the recombinant expression of hemolysin BL triayl was achieved, and the biological activity of hemolysin BL of bovine pathogenic ceroid spore was investigated. This study may facilitate further investigating the pathogenic mechanism of B. cereus hemolysin BL and developing a detection method for bovine pathogenic B. cereus disease.
Cattle ; Animals ; Mice ; Bacterial Proteins/metabolism* ; Bacillus cereus/metabolism* ; Hemolysin Proteins/metabolism* ; Virulence Factors/metabolism* ; Enterotoxins/metabolism*

New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional "down" conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD "up". Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern.
Angiotensin-Converting Enzyme 2 ; Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 ; Epitopes ; Humans ; SARS-CoV-2/genetics* ; Spike Glycoprotein, Coronavirus/genetics*

Escherichia coli biofilm is a complex membrane aggregation produced by the adhesion and secretion of extracellular polymeric substances by E. coli cells aggregated on specific media. Pathogenic E. coli will evade the immune system and the impact of various harmful factors in the environment after the formation of biofilm, causing sustained and even fatal damage to the host. Cyclic diguanosine monophosphate (c-di-GMP) is a second messenger ubiquitous in bacteria and plays a crucial role in regulating biofilm formation. This paper reviewed the recent studies about the role of c-di-GMP in the movement, adhesion, and EPS production mechanism of E. coli during biofilm formation, aiming to provide a basis for inhibiting E. coli biofilm from the perspective of c-di-GMP.
Bacterial Proteins/genetics* ; Biofilms ; Cyclic GMP/analogs & derivatives* ; Escherichia coli/metabolism* ; Escherichia coli Proteins/metabolism* ; Gene Expression Regulation, Bacterial

Objective:To analyze the risk factors of deep venous thrombosis (DVT) in patients with tibial plateau fracture during preoperative period.Methods:From July 2017 to October 2019, a total of 264 patients undergoing surgeries of tibial plateau fractures were enrolled. Duplex ultrasonography (DUS) during hospitalization was used to screen for DVT of the bilateral lower extremities. Patients were divided into DVT group and non-DVT group according to results of DUS. Data on demographics, comorbidities, injury-related data, fracture type, laboratory biomarkers were collected and compared between groups with and without DVT.Results:The incidence of preoperative DVT was 39.0% (103/264) among 264 patients with traumatic tibial plateau fractures, and distal thrombosis predominated in DVT group. There were 103 cases in DVT group. 55 were males and 48 were females. The average age was 54.00±11.12. According to the Schatzker classification of tibial plateau fractures, 7 cases belonged to type I, 37 to type II, 2 to type III, 11 to type IV, 29 to type V, and 17 to type VI. There were 161 cases in non-DVT group. 89 were males and 72 were females. The average age was 48.57±13.25. According to the Schatzker classification of tibial plateau fractures, 23 cases belonged to type I, 76 to type II, 2 to type III, 10 to type IV, 33 to type V, and 17 to type VI. Univariate analysis showed that age ( t=3.451, P=0.001), the type of tibial plateau fracture ( χ2=8.314, P=0.004), D-dimer ( χ2=18.552, P<0.001), APTT ( t=2.869, P=0.004), ALB ( t=2.292, P=0.023) and Hb ( t=1.983, P=0.048) were statistically different than those in non-DVT group. Multivariate analysis showed age ( OR=1.033, 95% CI: 1.009, 1.058; P=0.007), the type of tibial plateau fracture ( OR=1.829, 95% CI: 1.014, 3.299; P=0.045) and D-dimer ( OR=1.914, 95% CI: 1.057, 3.464; P=0.032) were independent risk factors. Conclusion:The incidence of DVT in patients with tibial plateau fractures during preoperative period is high, and distal thrombosis is the main part of venous thrombosis of lower extremity. The type of tibial plateau fracture, age and the level of D-dimer are independent risk factors of preoperative DVT in patients with tibial plateau fractures.

Objective:To analyze the clinical and prognostic characteristics in patients with eosinophilic granulomatosis with polyangitis (EGPA).Methods:The clinical data of 146 EGPA patients hospitalized in Peking Union Medical College Hospital from 2000 to 2019 were analyzed retrospectively, including clinical manifestations, laboratory results, treatment, complications and outcome at discharge. Birmingham Vasculitis activity score-V3 (BVAS-V3) was used to evaluate disease activity.Results:The ratio of male to female was 1.8∶1 with average age (41.7±16.1) year-old. The median time from disease onset to diagnosis was 18(6, 60) months (0.5~450). The most common clinical manifestations were lung [121(82.9%)] and nose/paranasal sinuses [119(81.5%)] involvement. The positive rate of anti-neutrophil cytoplasmic antibody (ANCA) was 24.7%, mainly peripheral (P)-ANCA/myeloperoxidase (MPO)-ANCA. Compared with ANCA-negative patients, the ANCA-positive patients had a higher incidence of renal involvement and nervous system involvement (66.7% vs. 20.9%, 80.6% vs. 51.8%, P<0.001), fever and optic neuropathy (66.7% vs. 40.9%,8.3% vs. 0, P<0.05), more active disease [median BVAS-V3 25(18,30)vs. 19(14,24), P=0.001] and more elevated erythrocyte sedimentation rate [40.5(20.5,82.8)mm/1h vs. 25.0(13.3,50.8)mm/1h, P=0.006] and C-reactive protein [37.1(11.8,72.9)mg/L vs.13.5(3.4,66.1)mg/L, P=0.036]. More ANCA-negative patients had pleural effusion (20.9% vs. 5.6%, P<0.04) compared with ANCA-negative patients. Pulmonary infection was the most common complication. A total of 12 EGPA patients (8.2%)achieved remission and 6 patients (4.1%)died or discharged themselves from the hospital. Conclusion:EGPA is a rare small vessel vasculitis. The clinical manifestations and outcomes are heterogenous. The mortality rate of EGPA is high.