Glioma represents the most prevalent malignant tumor of the central nervous system, with chemotherapy serving as an essential adjunctive treatment. However, most chemotherapeutic agents exhibit limited ability to penetrate the blood-brain barrier (BBB). This study introduced a novel dual-targeting strategy for glioma therapy by modulating the formation of nanobody-driven protein coronas to enhance the brain and tumor-targeting efficiency of hydrophobic cisplatin prodrug-loaded lipid nanoparticles (C8Pt-Ls). Specifically, nanobodies (Nbs) with fibrinogen-binding capabilities were conjugated to the surface of C8Pt-Ls, resulting in the generation of Nb-C8Pt-Ls. Within the bloodstream, Nb-C8Pt-Ls could bound more fibrinogen, forming the protein corona that specifically interacted with LRP-1, a receptor highly expressed on the BBB. This interaction enabled a "Hitchhiking Effect" mechanism, facilitating efficient trans-BBB transport and promoting effective brain targeting. Additionally, the protein corona interacted with LRP-1, which is also overexpressed in glioma cells, achieving precise tumor targeting. Computational simulations and SPR detection clarified the molecular interaction mechanism of the Nb-fibrinogen-(LRP-1) complex, confirming its binding specificity and stability. Our results demonstrated that this strategy significantly enhanced C8Pt accumulation in brain tissues and tumors, induced apoptosis in glioma cells, and improved therapeutic efficacy. This study provides a novel framework for glioma therapy and underscores the potential of protein corona modulation-based dual-targeting strategies in advancing treatments for brain tumors.

Objective To explore the relationship between triglyceride-glucose index(TyG)and acute ischemic stroke with large vessel occlusion(AIS-LVO)of anterior circulation.Methods A retrospective study was conducted on patients with anterior circulation AIS-LVO who underwent emergency endovascular thrombectomy at Neurovascular Center of The First Affiliated Hospital of Naval Medical University from Jan.2018 to Dec.2019.According to modified Rankin scale(mRS)score 90 d after operation,the patients were assigned to favorable outcome group(mRS score 0-2)or unfavorable outcome group(mRS score 3-6),and the TyG was compared.According to the median of TyG,the patients were assigned to low-TyG group(TyG＜8.57)or high-TyG group(TyG ≥8.57),and the clinical data,laboratory indexes,and imaging characteristics were compared.Receiver operating characteristic curve was used to evaluate the predictive value of TyG for poor prognosis.Results A total of 135 patients were enrolled,with 72 in the favorable outcome group and 63 in the unfavorable outcome group.The TyG of the unfavorable outcome group was significantly higher than that of the favorable outcome group(8.82+0.63 vs 8.43+0.60,P＜0.001).There were 67 patients in the low-TyG group and 68 in the high-TyG group.Compared with the low-TyG group,the proportion of patients with hyperlipidemia history(P=0.003),systolic blood pressure at admission(P=0.018),fasting blood glucose level(P＜0.001),and triglyceride level(P＜0.001)were significantly higher in the high-TyG group,the infarct core volume was significantly larger(P=0.025),the high density lipoprotein-cholesterol level was significantly lower(P=0.013),and the mRS score 90 d after operation was significantly higher(3[1,5]vs 1[0,5],P=0.049).The TyG had certain predictive value for poor prognosis in anterior circulation AIS-LVO patients(area under curve value=0.662,95％confidence interval 0.571-0.753).Conclusion TyG is elevated in anterior circulation AIS-LVO patients with poor prognosis,and may be a potential prognostic indicator for anterior circulation AIS-LVO patients.

Objective To comprehensively analyze the clinical outcomes of total cavopulmonary connection (TCPC) in the treatment of functional single ventricle combined with heterotaxy syndrome (HS). Methods A retrospective analysis was conducted on the patients with functional single ventricle and HS who underwent TCPC (a HS group) in Guangdong Provincial People's Hospital between 2004 and 2021. The analysis focused on postoperative complications, long-term survival rates, and identifying factors associated with patient survival. Early and late postoperative outcomes were compared with matched non-HS patients (a non-HS group). Results Before propensity score matching, 55 patients were collected in the HS group, including 42 males and 13 females, with a median age of 6.0 (4.2, 11.8) years and a median weight of 17.0 (14.2, 28.8) kg. Among the patients, there were 53 patients of right atrial isomerism and 2 patients of left atrial isomerism. Eight patients underwent TCPC in one stage. TCPC procedures included extracardiac conduit (n=39), intracardiac-extracardiac conduit (n=14), and direct cavopulmonary connection (n=2). Postoperative complications included infections in 27 patients, liver function damage in 19 patients, and acute kidney injury in 11 patients. There were 5 early deaths. The median follow-up time was 94.7 (64.3, 129.8) months. The 1-year, 5-year, and 10-year survival rates were 87.2%, 85.3%, and 74.3%, respectively. After propensity score matching, there were 45 patients in the HS group and 81 patients in the non-HS group. Compared to the non-HS group, those with HS had longer surgical and mechanical ventilation time, higher infection rates (P<0.05), and a 12.9% lower 10-year survival rate. Multivariate Cox regression analysis identified asplenia was a risk factor for mortality (HR=8.98, 95%CI 1.86-43.34, P=0.006). Conclusion Compared to non-HS patients, patients with HS have lower survival rates after TCPC, and asplenia is an independent risk factor for the survival of these patients.

Objective: To investigate the relationship between adverse childhood experiences (ACEs) and mental health status through network analysis in college students, so as to provide empirical evidence for the development of targeted intervention programs. Methods: From October to November 2023, a survey was conducted on 1 974 college students from three universities in Hubei Province by using ACEs Questionnaire and Symptom Checklist-90 (SCL-90). The network analysis method was used to construct a network structure to analyze the association between ACEs and SCL-90 symptom factors among college students. Results: The network structure of SCL-90 symptom factors and ACEs was stable, each forming a relatively tight cluster; there were 89 non zero edges between ACEs and SCL-90 symptom factors. Emotional neglect-depression played a significant pathway role in connecting the ACEs and SCL-90 symptom factors network. Depression, anxiety, and interpersonal sensitivity of SCL-90 symptom factors had the highest centrality in the ACEs and SCL-90 symptom factors network. Emotional neglect and physical neglect in ACEs and depression and psychoticism in SCL-90 symptom factors had a high node bridge expected influence, acting as Touchpoints to activate the whole network. Conclusion Early identification and intervention of emotional and physical neglect, with a focus on depression, anxiety, and interpersonal sensitivity symptoms of childhood neglected individuals, which is beneficial for improving the overall mental health level of college students.

Objective: To investigate the effect of G protein-coupled receptor 108(GPR108) gene knockout on systemic inflammation in lipopolysaccharide(LPS)-induced sepsis mice. Methods: Male C57BL/6 mice and GPR108 gene knockout mice were randomly divided into 4 groups: WT group, WT-LPS group, KO group, KO-LPS group. The physiological characteristics of mice in different groups were observed, and the morphological changes of liver and lung tissues were observed. Macrophages were extracted from bone marrow and subjected to flow cytometry to detect their M1 polarization status. The expression levels of IL-6 in liver and lung tissues, macrophages, and serum were also measured. Results: KO-LPS group mice showed significant liver and lung tissue damage, with a significantly greater number of bone marrow-derived macrophages polarizing towards M1 in the KO-LPS group compared to the WT-LPS group. Additionally, at the tissue, cellular, and serum levels, the expression of IL-6 in the KO-LPS group mice was significantly higher than that in the WT-LPS group mice(P<0.05). Conclusion During the systemic inflammatory infection induced by LPS in mice, the lack of GPR108 exacerbates the systemic inflammatory response. GPR108 has an inhibitory effect on the inflammatory response in mice with LPS-induced sepsis.

Objective:To summarize the clinical features and prognosis of Budd-Chiari syndrome with hepatopulmonary syndrome (HPS) in children.Methods:The clinical data of a child who had Budd-Chiari syndrome with HPS treated at the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in December 2016 was analyzed retrospectively. Taking "Budd-Chiari syndrome" and "hepatopulmonary syndrome" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2023. Combined with this case, the clinical characteristics, diagnosis, treatment and prognosis of Budd-Chiari syndrome with HPS in children under the age of 18 were summarized.Results:A 13-year-old boy, presented with cyanosis and chest tightness after activities for 6 months, and yellow staining of the skin for 1 week. Physical examination at admission not only found mild yellow staining of the skin and sclera, but also found cyanosis of the lips, periocular skin, and extremities. Laboratory examination showed abnormal liver function with total bilirubin 53 μmol/L, direct bilirubin 14 μmol/L, and indirect bilirubin 39 μmol/L, and abnormal blood gas analysis with the partial pressure of oxygen of 54 mmHg (1 mmHg=0.133 kPa), the partial pressure of carbon dioxide of 31 mmHg, and the alveolar-arterial oxygen gradient of 57 mmHg. Hepatic vein-type Budd-Chiari syndrome, cirrhosis, and portal hypertension were indicated by abdominal CT venography. Contrast-enhanced transthoracic echocardiography (CE-TTE) was positive. After symptomatic and supportive treatment, this patient was discharged and received oxygen therapy outside the hospital. At follow-up until March 2023, there was no significant improvement in hypoxemia, accompanied by limited daily activities. Based on the literature, there were 3 reports in English while none in Chinese, 3 cases were reported. Among a total of 4 children, the chief complaints were dyspnea, cyanosis, or hypoxemia in 3 cases, and unknown in 1 case. There were 2 cases diagnosed with Budd-Chiari syndrome with HPS at the same time due to respiratory symptoms, and 2 cases developed HPS 1.5 years and 8.0 years after the diagnosis of Budd-Chiari syndrome respectively. CE-TTE was positive in 2 cases and pulmonary perfusion imaging was positive in 2 cases. Liver transplantation was performed in 2 cases and their respiratory function recovered well; 1 case received oxygen therapy, with no improvement in hypoxemia; 1 case was waiting for liver transplantation.Conclusions:The onset of Budd-Chiari syndrome with HPS is insidious. The most common clinical manifestations are dyspnea and cyanosis. It can reduce misdiagnosis to confirm intrapulmonary vascular dilatations with CE-TTE at an early stage. Liver transplantation is helpful in improving the prognosis.

The survey on the hesitant status of rubella-containing vaccine (RCV) vaccination was conducted among 2 141 women of childbearing age in four provinces, Liaoning, Jiangsu, Zhejiang, and Anhui, from May 2017 to March 2018. Among the 2 141 study participants, a total of 38.21% (818) of women of childbearing age were aware of rubella and 21.25% (455) of women of childbearing age knew about RCV. Among the 455 women of childbearing age who were aware of RCV, 262 (57.58%) were willing to be vaccinated with RCV; 304 women of childbearing age (66.81%) tended to be vaccinated with RCV free of charge. Among the 193 women of childbearing age who did not want to be vaccinated or did not decide whether they preferred to be vaccinated with RCV, no one around them was vaccinated (89, 46.11%) and fear of vaccine safety (70, 36.27%) were the main reasons for hesitation to receive RCV.

The survey on the hesitant status of rubella-containing vaccine (RCV) vaccination was conducted among 2 141 women of childbearing age in four provinces, Liaoning, Jiangsu, Zhejiang, and Anhui, from May 2017 to March 2018. Among the 2 141 study participants, a total of 38.21% (818) of women of childbearing age were aware of rubella and 21.25% (455) of women of childbearing age knew about RCV. Among the 455 women of childbearing age who were aware of RCV, 262 (57.58%) were willing to be vaccinated with RCV; 304 women of childbearing age (66.81%) tended to be vaccinated with RCV free of charge. Among the 193 women of childbearing age who did not want to be vaccinated or did not decide whether they preferred to be vaccinated with RCV, no one around them was vaccinated (89, 46.11%) and fear of vaccine safety (70, 36.27%) were the main reasons for hesitation to receive RCV.

Objectives:To investigate the relationship between procedure time (PT) and outcome in patients with acute vertebrobasilar artery occlusion (VBAO) underwent endovascular mechanical thrombectomy (EMT), and to evaluate whether symptomatic intracranial hemorrhage (sICH) plays a mediating role in this relationship.Methods:Patients with acute VBAO underwent EMT treatment at 65 comprehensive stroke centers in 15 provinces of China from December 2015 to June 2022 were included retrospectively. PT was defined as the time from puncture to the first successful recanalization or termination of procedure (if recanalization was not successful). The main outcome measure was the functional outcome evaluated using the modified Rankin Scale at 90 days after onset, 0-3 was defined as good outcome and >3 was defined as poor outcome. The secondary outcome measure was sICH. Multivariate logistic regression analysis was used to determine the independent influencing factors of functional outcome and sICH. Mediation analysis was use to determine whether sICH affected the association between PT and functional outcome. Results:A total of 2 353 patients with acute VBAO underwent EMT treatment were enrolled, including 1 764 males (71.1%), aged 64.0±12.2 years. The baseline National Institutes of Health Stroke Scale score was 21.16±10.03 (median 22, interquartile range, 13-28), the baseline posterior circulation Alberta Stroke Project Early CT Score was 8.36±1.56 (median 8, interquartile range 7-10), and the baseline Basal Artery CT Angiography Score was 5.15±2.52 (median 5, interquartile range, 3-7). One hundred and sixty-nine patients (7.2%) had sICH; 1 061 (45.1%) had good outcome, while 1 292 (54.9%) had poor outcome. Multivariate logistic regression analysis showed that a longer PT was significantly independently associated with the poor outcome at 90 days (odds ratio 1.238, 95% confidence interval 1.144-1.340; P<0.001), but not independently associated with sICH. The mediation effect analysis showed that longer PT did not directly increase the risk of sICH ( P=0.077), and the explanation of sICH for the association between PT and poor outcome was limited. This suggested that a longer PT also promote the poor outcome through other pathways, such as ischemic injury. Conclusion:Longer PT is an independent predictor of poor outcome in patients with acute VBAO at 90 days after EMT, and sICH is not the main mediating factor for poor outcome caused by longer PT.

Objective:To investigate the effectiveness and safety of bortezomib combined with conventional chemotherapy regimens for treatment of relapsed/refractory acute B lymphoblastic leukemia (B-ALL).Methods:Twenty patients with relapsed/refractory B-ALL treated with bortezomib combined with chemotherapy in Jiaozuo People's Hospital Affiliated to Xinxiang Medical College, Jiaozuo Coal Industry Group Central Hospital and the Second People's Hospital of Jiaozuo from September 2021 to June 2022 were collected, and their treatment response and prognosis were retrospectively analyzed.Results:The median age of the 20 patients was 49.5 years old (25.0-58.5 years old); 12 were male and 8 were female; 12 were relapsed and 8 were refractory. All patients completed 1 course of bortezomib (1.6 mg/m 2, subcutaneous injection on days 2 and 16) combined with chemotherapy. Before bortezomib treatment, there were 0 case of complete remission (CR), 7 cases of partial remission (PR) and 13 cases of non-remission (NR) in 20 patients, the objective remission rate (ORR) was 35% (7/20), and all were positive for minimal residual disease (MRD). After bortezomib treatment, there were 13 cases of CR, 3 cases of PR and 4 cases of NR, and the ORR was 80% (16/20); the MRD of all patients decreased, among which 13 cases (65%) turned to negative; the differences were statistically significant when comparing CR rate, ORR and MRD negative conversion rate before and after bortezomib treatment ( χ2 values were 65.41, 8.83 and 19.30, all P < 0.05). Four of the 20 patients developed central nervous system infiltration despite bone marrow remission, and one died from post-chemotherapy infection. Myelosuppression occurred in all patients, the incidence of infection was 90% (18/20), and the incidence of digestive system adverse effects was 75% (15/20). Conclusions:Bortezomib combined with conventional chemotherapy regimens is effective and well tolerated in the treatment of relapsed/refractory ALL, and has the potential to enable patients with multi-drug resistant relapse to overcome resistance and to achieve deep remission.