1.A novel anti-ischemic stroke candidate drug AAPB with dual effects of neuroprotection and cerebral blood flow improvement.
Jianbing WU ; Duorui JI ; Weijie JIAO ; Jian JIA ; Jiayi ZHU ; Taijun HANG ; Xijing CHEN ; Yang DING ; Yuwen XU ; Xinglong CHANG ; Liang LI ; Qiu LIU ; Yumei CAO ; Yan ZHONG ; Xia SUN ; Qingming GUO ; Tuanjie WANG ; Zhenzhong WANG ; Ya LING ; Wei XIAO ; Zhangjian HUANG ; Yihua ZHANG
Acta Pharmaceutica Sinica B 2025;15(2):1070-1083
Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.
2.Establishment of indirect ELISA based on gD protein of porcine pseudorabies virus and its application in immune evaluation
Yining LIU ; Xiaohang YU ; Jin ZHENG ; Zhenyu YANG ; Shiqing XIE ; Meiting LIN ; Tongtong LIANG ; Ye LUO ; Xinglong YU
Chinese Journal of Veterinary Science 2024;44(10):2116-2122
The aim of this study is to establish a simple and accurate method for vaccine immune e-valuation of porcine pseudorabies virus.In this research,PRV-gD recombinant protein was ex-pressed from mammalian cell HEK-293F as coating antigen,and then the reaction conditions of gD-iELISA were optimized according to checkerboard titration method.The gD-iELISA was used to detect the antibody levels of 211 clinical pig serum samples and the consistency with the neu-tralizing antibody levels wasanalyzed.The results showed that the antigen coating concentration was 0.90 mg/L;the serum to be detected was diluted 1∶100 and incubated at 37 ℃ for 30 min;goat anti-pig IgG-HRP antibody was diluted 1∶55 000 and incubated at 37 ℃ for 30 min;TMB sub-strate was developed at 37 ℃ for 20 min.The method could detect 1∶6 400 diluted PRV positive serum.The results of CSFV,PRRSV,PCV-2,PEDV and FMDV positive sera were all negative by gD-iELISA,and there was no cross-reaction between the method and the above positive sera.The coincidence rate of gD-iELISA and commercial kits was 95.26%,and the intra-and inter-batch co-efficients of variation were both less than 10%.Correlation analysis showed that the correlation coefficient(r)between gD antibody level and neutralizing antibody level was significantly greater than that of gB antibody level,and the gD antibody level had a good linear relationship with the neutralizing antibody level.The results indicated that gD-iELISA was more suitable for vaccine im-mune evaluation of PRV than gB-iELISA.Therefore,the method will have a good prospect of ap-plication in the immunization control of the PRV.
3.Analysis of clinical characteristics and risk factors of shock in patients with acute dichlorvos poisoning
Hongxia GE ; Zhen REN ; Xinglong YANG ; Shu LI ; Qingbian MA
Chinese Journal of Emergency Medicine 2024;33(3):291-296
Objective:The aim of this study was to investigate the clinical characteristics and analyze the risk factors of patients with acute dichlorvos poisoning combined with shock.Methods:The clinical data of patients with acute dichlorvos poisoning admitted to the Peking University Third Hospital and the Fifth Medical Center of the PLA General Hospital between January 2019 and September 2020 were retrospectively analyzed, and demographic data, poisoning, clinical manifestations, laboratory tests, therapeutic measures and clinical outcomes were collected to establish a clinical database. The patients were divided into two groups: the shock group and the non-shock group, and the clinical data were compared between the two groups to analyze the clinical characteristics and prognosis of shock in acute dichlorvos poisoning, and the risk factors of shock in acute dichlorvos poisoning were analyzed by logistic regression.Results:A total of 134 patients who met the criteria for acute dichlorvos poisoning were included in this study; the incidence of shock within 24 hours of admission was 39.6% (53/134), and 11 patients (8.21%) died in hospital; the in-hospital morbidity and mortality rate of patients in the shock group was higher than that in the non-shock group (20.8% vs. 0.0%, P<0.001). Symptoms of sphincter relaxation, coma, hypothermia, and organ function damage were more common in the shock group than in the non-shock group; and shock patients had longer hospitalization, ICU stay, and invasive ventilator use. Binary logistic regression analysis showed that the presence of sphincter relaxation manifestations ( OR=10.888, 95% CI: 1.677-70.684, P=0.012) was an independent risk factor for comorbid shock in patients with acute dichlorvos poisoning, and the use of cholinesterase reanimators ( OR=0.246, 95% CI: 0.072-0.846, P=0.026) was a protective factor for combined shock in patients with acute dichlorvos poisoning. Conclusions:The incidence of shock in patients with acute dichlorvos poisoning is high and affects the clinical prognosis, and the presence of sphincter relaxation and the absence of cholinesterase reenergizers are independent risk factors for combined shock in patients with acute dichlorvos poisoning.
4.Neuroprotective mechanism of nicotine in a mouse model of rotenone-induced Parkinson's disease
Xinyue ZHANG ; Liuhui ZHU ; Yu HE ; Ying GUAN ; Zhouhai ZHU ; Hui REN ; Xinglong YANG
Chinese Journal of Tissue Engineering Research 2024;28(35):5612-5617
BACKGROUND:Studies have found that nicotine can activate the dopamine system,slowing the progression of Parkinson's disease,but the specific mechanism is still unclear.Research on the neuroprotective mechanism of nicotine in animal models of Parkinson's disease is lacking. OBJECTIVE:To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson's disease in mice. METHODS:Twenty-eight C57BL/6 mice were randomly divided into vehicle group,rotenone group,autophagy agonist group and nicotine group,with seven mice in each group.Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice,and the autophagy agonist(rapamycin)or nicotine was given before modeling.The spatial exploration function of the mice was observed by open field test.Western blot and Q-PCR were used to detect the expression of α-synuclein,autophagy related factors Beclin-1 and P62,and apoptosis-related factors Bax,Bcl-2 and Cleaved-caspase3 in the nigra of each group.The deposition of mitochondria,autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy.The survival of neurons was observed by Nissl staining.The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION:The open field test showed that the distance,average speed and time of movement were reduced in the rotenone group compared with the solvent group.Compared with the rotenone group,the exercise distance,average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group(P<0.05).The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group.Compared with the rotenone group,the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group.Western blot and Q-PCR results showed that compared with the solvent group,the expressions of α-synuclein and P62 in the rotenone group were increased,while Beclin-1 expression was decreased(P<0.05);compared with the rotenone group,the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group,and the expression of Beclin-1 increased(P<0.05).Compared with the solvent group,the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group(P<0.05);compared with the rothenone group,the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups(P<0.05).To conclude,nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson's disease mouse models by improving autophagy dysfunction and reducing apoptosis.
5.Recent advances in the management of locally advanced head and neck squamous cell carcinoma
Chinese Journal of Radiation Oncology 2024;33(1):72-78
Currently, concurrent chemoradiotherapy is the conventional treatment for locally advanced head and neck squamous cell carcinoma, but the 5-year survival rate of patients is still not high. In recent years, the development of radiotherapy technology has offered more options for patients. In addition, with the improvement of people's living standards, more and more patients begin to pursue the quality of life. There is an urgent need to explore better comprehensive treatment options to improve patient outcomes. In this article, research progress in comprehensive treatment of locally advanced head and neck squamous cell carcinoma was reviewed.
6.Correlation between preoperative coronary angiography and postoperative acute kidney injury in cardiac surgery: A retrospective study in a single center
Changying ZHAO ; Yang YAN ; Tao SHI ; Yongxin LI ; Jing LI ; Wenyan LIU ; Miaomiao LIU ; Xinglong ZHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(12):1820-1825
Objective To explore the relationship between preoperative coronary angiography and postoperative acute kidney injury (AKI) in cardiac surgery. Methods The clinical data of patients who underwent coronary angiography within 30 days before cardiac surgery in the First Affiliated Hospital of Xi’an Jiaotong University from January 2015 to April 2019 were retrospectively analyzed. Univariate analysis and multivariate logistic regression analyses were used to explore the relationship between the interval from preoperative coronary angiography to cardiac surgery and postoperative AKI. Results Finally 1 112 patients were collected, including 700 males and 412 females, with a median age of 61 (55, 66) years. The incidence of postoperative AKI was 40.8% (454/1 112), of which grade 2-3 AKI accounted for 11.9%. Multivariate analysis showed that age (OR=1.049, 95%CI 1.022-1.077, P<0.001), body mass index (OR=1.065, 95%CI 1.010-1.123, P=0.020) and time interval between preoperative coronary angiography and cardiac surgery within 24 hours (OR=1.625, 95%CI 1.116-2.364, P=0.011) were independent predictors of postoperative AKI. Patients who underwent coronary angiography within 24 hours before surgery had a 10.6% higher incidence of postoperative AKI compared to those who underwent angiography ≥24 hours before surgery (P=0.004). Patients who underwent valve surgery with or without coronary artery bypass grafting (CABG) had a higher risk of AKI than those who only underwent CABG. The in-hospital stay of patients who developed AKI was 2 days longer than those without AKI. However, undergoing coronary angiography within 24 hours before cardiac surgery did not prolong the length of ICU stay or hospital stay, nor did it increase the risk of death or renal failure after the operation. Conclusion Undergoing coronary angiography within 24 hours before cardiac surgery increases the risk of postoperative AKI.
7.The Theory,Logic and Path to Realizing the Value of Basic-level Health Services Based on Residents'Active Utilization
Xinglong XU ; Xinyue YANG ; Peiyao LI ; Lülin ZHOU
Chinese Health Economics 2024;43(9):6-11
Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.
8.The Theory,Logic and Path to Realizing the Value of Basic-level Health Services Based on Residents'Active Utilization
Xinglong XU ; Xinyue YANG ; Peiyao LI ; Lülin ZHOU
Chinese Health Economics 2024;43(9):6-11
Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.
9.The Theory,Logic and Path to Realizing the Value of Basic-level Health Services Based on Residents'Active Utilization
Xinglong XU ; Xinyue YANG ; Peiyao LI ; Lülin ZHOU
Chinese Health Economics 2024;43(9):6-11
Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.
10.The Theory,Logic and Path to Realizing the Value of Basic-level Health Services Based on Residents'Active Utilization
Xinglong XU ; Xinyue YANG ; Peiyao LI ; Lülin ZHOU
Chinese Health Economics 2024;43(9):6-11
Aiming at the practical problems of insufficient supply efficiency and low utilization rate of primary health services,it systematically reviewed the research status of residents'participation in the value co-creation of primary health services from the perspective of residents'active utilization.It explores the theoretical framework of realizing the value of primary health service based on residents'active utilization,and deeply analyzes its internal logic.Finally,it puts forward the concrete realization path,that is,multi-subject broadening the health information communication channel,optimizing the health service supply mode according to local conditions,constructing multi-dimensional trust mechanism between doctors and patients,and building a precise digital health management platform.

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