1.A novel dual-targeting strategy of nanobody-driven protein corona modulation for glioma therapy.
Yupei ZHANG ; Shugang QIN ; Tingting SONG ; Zhiying HUANG ; Zekai LV ; Yang ZHAO ; Xiangyu JIAO ; Min SUN ; Yinghan ZHANG ; Guang XIE ; Yuting CHEN ; Xuli RUAN ; Ruyue LIU ; Haixing SHI ; Chunli YANG ; Siyu ZHAO ; Zhongshan HE ; Hai HUANG ; Xiangrong SONG
Acta Pharmaceutica Sinica B 2025;15(9):4917-4931
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.
2.Relationship between triglyceride-glucose index and acute ischemic stroke with anterior circulation large vessel occlusion
Ruyue LIN ; Jianqiang FAN ; Lijun WANG ; Xiaoxi ZHANG ; Hongjian SHEN ; Pengfei XING ; Lei ZHANG ; Zifu LI ; Yongwei ZHANG ; Pengfei YANG ; Jianmin LIU ; Rui ZHAO
Academic Journal of Naval Medical University 2025;46(4):435-441
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.
3.Outcomes of total cavopulmonary connection in the treatment of functional single ventricle with heterotaxy syndrome: A propensity score matching study
Linjiang HAN ; Xiang LIU ; Jianrui MA ; Ziqin ZHOU ; Jiazichao TU ; Ruyue ZHANG ; Miao TIAN ; Ying LI ; Haiyun YUAN ; Shusheng WEN ; Jimei CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):510-518
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.
4.Network analysis of the association between adverse childhood experiences and mental health status in college students
LIU Ailou, ZHAI Ruyue, ZHANG Libin
Chinese Journal of School Health 2024;45(10):1481-1485
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.
5.Budd-Chiari syndrome with hepatopulmonary syndrome: a case report and literature review
Fengyan TIAN ; Xiao DONG ; Xiaohan HOU ; Ruyue YUAN ; Yuanwei PAN ; Da ZHANG
Chinese Journal of Pediatrics 2024;62(1):71-75
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.
6.The current situation and related factors analysis of hesitancy among women of childbearing age in four provinces of China to receive vaccines containing rubella components
Qiongyu GONG ; Ruyue HU ; Xuan ZHANG ; Xing FANG ; Fanya MENG ; Jing YU ; Lingzhi SHEN ; Wenzhou YU
Chinese Journal of Preventive Medicine 2024;58(3):347-350
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.
7.The absence of GPR108 results in decreased inflammatory response in lipopolysaccharide-induced sepsis mice
Yintao Zhang ; Ping Yang ; Dandan Zang ; Zhenzhen Tu ; Ruyue Xu ; Haisheng Zhou
Acta Universitatis Medicinalis Anhui 2024;59(11):1896-1902
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.
8.The current situation and related factors analysis of hesitancy among women of childbearing age in four provinces of China to receive vaccines containing rubella components
Qiongyu GONG ; Ruyue HU ; Xuan ZHANG ; Xing FANG ; Fanya MENG ; Jing YU ; Lingzhi SHEN ; Wenzhou YU
Chinese Journal of Preventive Medicine 2024;58(3):347-350
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.
9.Effect of procedure time on the outcome and symptomatic intracranial hemorrhage of patients with acute vertebrobasilar artery occlusion underwent endovascular mechanical thrombectomy
Ruyue WANG ; Miaomiao HU ; Yingjie XU ; Pan ZHANG ; Wen SUN
International Journal of Cerebrovascular Diseases 2024;32(12):901-905
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.
10.Evaluation for optimization effects of sperm floating plate
Jie YANG ; Ruyue LIU ; Qi WANG ; Shengjia SHI ; Zhou ZHANG
Chinese Journal of Clinical Laboratory Science 2023;41(10):731-735
Objective To compare the difference between sperm floating plate and density gradient centrifugation combined with swim-up in human sperm preparation.Methods The semen samples were obtained from 50 infertile men in the clinic of Reproductive Medi-cine of Northwest Women's and Children's Hospital excluding azoospermia,severe oligoasthenozoospermia and semen volume less than 2 mL.After semen liquefaction,the differences of sperm concentration,total progressively motile sperm count(TMSC),percentages of progressively motile sperm and normal morphology sperm,recovery rate and DNA fragmentation index(DFI)were measured by both the methods of sperm floating plate and density gradient centrifugation combined with swim-up,and the results were compared.Results Compared with the pre-sorting samples,sperm concentrations[(16.08±13.39)x 106/mL,(8.88±8.06)x 106/mL vs(60.05± 27.21)×106/mL],TMSC[(7.41±6.14)×106,(3.98±3.57)×106vs(22.24±13.74)×106]and DFI[(2.20±3.44)%,(5.20± 10.79)%vs(26.38±13.92)%]in the sorting groups by sperm floating plate and density gradient centrifugation combined with swim-up were decreased significantly,and the percentages of progressive motile sperm[(91.67±4.75)%,(87.86±7.90)%vs(40.21± 16.83)%]and normal morphology sperm[(9.58±5.08)%,(7.72±4.01)%vs(3.58±2.06)%]were increased significantly.Com-pared with the density gradient centrifugation combined with swim-up,the results of sperm floating plate were higher in sperm concen-tration,percentages of progressively motile sperm and normal morphology sperm,TMSC and sperm recovery rate[(30.74±13.70)%vs(17.09±9.20)%],but DFI was lower,time-consuming was shorter[(32.38±1.01)min vs(60.08±2.06)min],and the difference between the two groups was statistically significant(P<0.05).Conclusion The sperm floating plate may have certain clinical applica-tion prospects in the future due to better parameters of sperm preparation than those of density gradient centrifugation combined with swim-up in simple operation and shorter time-consuming.


Result Analysis
Print
Save
E-mail