1.Dihydromyricetin mitigates abdominal aortic aneurysm via transcriptional and post-transcriptional regulation of heme oxygenase-1 in vascular smooth muscle cells.
Weile YE ; Pinglian YANG ; Mei JIN ; Jiami ZOU ; Zhihua ZHENG ; Yuanyuan LI ; Dongmei ZHANG ; Wencai YE ; Zunnan HUANG ; Jiaojiao WANG ; Zhiping LIU
Acta Pharmaceutica Sinica B 2025;15(3):1514-1534
Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.
2.Effectss of persistent obesity on lung function in school age children
Chinese Journal of School Health 2024;45(4):549-553
Objective:
To analyze the impact of persistent obesity on their lung function, so as to offer insights for implementing intervention measures to increase lung function in obese school age children.
Methods:
A total of 335 children from the Sheyang Mini Birth Cohort established in 2009 in Yancheng City, Jiangsu Province, who participated in the follow up at the ages of 7 years (2016) and 10 years (2019), were selected as the study participants. Physical measurements including height, weight, and lung function were recorded. According to the World Health Organization standard, that is, gender and age specific to correct the body mass index to calculate the body mass index Z score, was used to evaluate the obesity status of children at the age of 7 and 10. Children were divided into four groups, including sustained non obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Meanwhile, the lung function prediction equations recommended by the Global Lung Function Initiative were used to standardize the lung function indexes of children. Pulmonary function differences among these groups were examined, and the relationship between childhood obesity and pulmonary function was longitudinally analyzed using generalized estimating equations.
Results:
The prevalence of obesity were 9.0% and 16.1% at the age of 7 and 10 years, respectively. The proportion of both newly classified and persistent obesity group were 8.1%, respectively. The forced expiratory volume in one second (FEV 1) and forced vital capacity (FVC) were (1 269.90±202.70) and (1 415.70±230.00) mL, respectively, at the age of 7 years. FEV 1 and FVC at the age of 10 years were (1 440.80±403.20) and (1 555.60±517.60) mL, respectively. Cross sectional analysis at age 7 showed that forced expiratory flow at 75% vital capacity (FEF 75 ) ( β=-0.52, 95%CI =-0.96--0.07) and maximal mid expiratary flow (MMEF) ( β=-0.45, 95%CI =-0.89--0.00) were significantly lower in obese children compared to their non obese peers ( P < 0.05). Longitudinal analysis indicated that obese children had lower levels of lung pulmonary function, with a statistically significant difference in FEV 1 ( β=-0.44, 95%CI=-0.85--0.02, P <0.05). There was no significant difference among the various obesity groups ( P >0.05), while gender stratified results revealed significant reductions in FEV 1/FVC in newly classified obese girls at age 10 years ( β=-1.76, 95%CI =-3.13--0.38) and in MMEF in persistently obese girls at age 10 years ( β=-1.44, 95%CI = -2.79- -0.09) ( P <0.05).
Conclusion
Obesity may contribute to reduced lung function levels in school aged children, with newly classified and persistent obesity having more pronounced effects on lung function in girls.
3.Not Available.
Weile YE ; Jiaojiao WANG ; Peter J LITTLE ; Jiami ZOU ; Zhihua ZHENG ; Jing LU ; Yanjun YIN ; Hao LIU ; Dongmei ZHANG ; Peiqing LIU ; Suowen XU ; Wencai YE ; Zhiping LIU
Acta Pharmaceutica Sinica B 2024;14(1):1-19
Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.
4.A Lean Operation Management Model for Public Hospital is Constructed Based on Evidence Based Deci-sion-Making
Yaojun ZHAO ; Leichao WANG ; Jianjun LI ; Shua JIANG ; Li ZHENG ; Wenwen LIU ; Zihan MU ; Zhiping GUO
Chinese Hospital Management 2024;44(3):5-8
Comprehensively improving the new efficiency of high-quality development of public hospitals is the key top-level design for deepening the reform of public hospitals during the"14th Five-Year Plan"period.In view of the changes in the macro environment faced by public hospitals in recent years,such as the cancellation of the addi-tion of pharmaceutical consumables and the deep promotion of the reform of payment methods,as well as the out-standing problems existing at the micro level of public hospital operation,such as the separation of diagnosis and treatment business from economic operation activities,extensive decision-making methods,unreasonable alloca-tion of resources and urgent optimization of processes.By referring to relevant theories such as value management theory,a new"trinity"public hospital lean operation management model based on"integration of industry and fi-nance,lean operation and evidence-based decision-making"is explored and constructed.It breaks the relatively parallel operation barriers of clinical diagnosis and treatment business and economic operation management,innovates a new method of linear staff management with the integration of industry and finance,gives full play to the role of experts in governing hospitals,and integrates the professional committee system driven by"technology+manage-men"into the hospital decision-making staff system to provide data evidence-based basis for assisting the hospital leadership to make scientific decisions.
5.Investigation on natural penetrating radiation along the Qinghai-Tibet Railway
Guowen ZHENG ; Yantao QU ; Chuangao WANG ; Zhiping LUO ; Ling CHEN
Chinese Journal of Radiological Health 2024;33(3):288-292
Objective To investigate the natural penetrating radiation levels along the Qinghai-Tibet Railway, and to preliminarily evaluate the doses received by the railway employees and passengers. Methods Natural penetrating radiation was measured at 15 typical locations with different altitudes along the railway and in the carriages of a train from Lhasa to Xining using high-pressure ionization chamber RSS131, sodium iodide radiation dose rate meter MARS1561, and neutron ambient dose equivalent rate meter LB6411. Results The levels of terrestrial gamma radiation, cosmic ray ionization components, and neutron radiation were 21.5-246.6 nGy/h, 79.8-225.5 nGy/h, and 24.5-101 nSv/h, respectively. The effective dose of natural penetrating radiation received by passengers and crew on a train from Lhasa to Xining was 4.82 μSv. Conclusion Comparison with the empirical formula and verification of method reliability confirm the accuracy of the measurement. Our results provide a primary understanding of the radiation levels along the Qinghai-Tibet Railway and the radiation doses received by passengers, which can be used as a basis for the regulatory authorities.
6.Disease burden of acute viral hepatitis in Guangdong Province, 1990-2019
Jiamin QIU ; Fangfang ZENG ; Chen CHENG ; Huiyan WEN ; Shiqi HUANG ; Dan LIU ; Jinlei QI ; Peng YIN ; Maigeng ZHOU ; Ying XU ; Zhiping LIU ; Qingsong MEI ; Heng XIAO ; Zheng XIANG ; Xiaofeng LIANG
Chinese Journal of Epidemiology 2024;45(3):365-372
Objective:To examine the burden and trends of acute viral hepatitis in Guangdong Province from 1990 to 2019, and provide reference evidences for hepatitis prevention and control in the province.Methods:Data on acute viral hepatitis (hepatitis A, B, C, and E) in Guangdong from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The incidence, prevalence, mortality, and disability-adjusted life years (DALY) data were analyzed by age and gender, and the estimated annual percentage change (EAPC) was calculated to describe the changing trends in disease burden.Results:From 1999 to 2019, the standardized incidence, prevalence, mortality, and DALY of acute viral hepatitis in Guangdong were higher than the national averages. In 2019, 51.43% (2 245 087/4 365 221) of acute viral hepatitis cases in Guangdong Province were mainly attributed to hepatitis B, and 77.18% (106/138) of deaths were due to acute hepatitis B. In different age groups, except for acute hepatitis B, which was more common in adults, the incidence rates of other types of viral hepatitis such as hepatitis A, B, and E showed an overall decreasing trend with age. The mortality rates of different types of acute viral hepatitis, except for the <5 age group, increased with age. The overall incidence and mortality rates of acute viral hepatitis were higher in men than in women.Conclusions:The overall burden of acute viral hepatitis in Guangdong declined in 2019, but remained higher than the national level. Further efforts are needed to strengthen hepatitis prevention and screening in different population in Guangdong Province, especially in children and the elderly.
7.Application of rapid daily quality assurance for pencil beam scanning proton therapy system
Renchao ZHENG ; Xiaoguang LU ; Weiqing WU ; Zhiping XIAO ; Fei LIU ; Guangyuan HU ; Xianglin YUAN
Chinese Journal of Medical Physics 2024;41(10):1206-1210
Objective To analyze the daily quality assurance(QA)measurement results of IBA Sphinx Compact device on the Mevion compact pencil beam scanning proton therapy system for evaluating its clinical application value in proton therapy.Methods The daily QA measurement of Mevion S250i proton therapy system was carried out with Sphinx Compact device for 30 consecutive days,and the measurement results were analyzed.Results The average deviation between the positioning laser and the image center was(0.42±0.27)mm in 30 days.All of the proximal and distal depth errors of the high-and low-energy pencil beams were within 0.50 mm.The position deviation of all the spots measured did not exceed 1.00 mm,and the size deviation was less than 7.5%.The deviation between the image center and the beam center was not more than 0.75 mm.The relative deviation of the flatness of the rectangular field was about 0.5%.The deviation of the output dose of the square field was within 1.0%.Conclusion The proton system daily QA measurement items recommended by AAPM TG-224 report can be accurately and rapidly measured with Sphinx Compact device.The device is a practical and efficient daily QA tool with high practical value in clinic.
8.The calibration of CT modeling for proton therapy treatment planning system
Renchao ZHENG ; Xiaoguang LU ; Weiqing WU ; Zu'an ZHENG ; Zhiping XIAO ; Junchao LI ; Xianglin YUAN
Chinese Journal of Radiation Oncology 2024;33(10):935-941
Objective:To verify and calibrate the CT modeling curves of three CT devices in RayStation proton treatment planning system (TPS).Methods:CT-mass density (CT-MD) curves were established by CT Hounsfield units of different tissue substitute materials obtained by scanning the model with CT equipment. CT-stopping power (CT-SP) curves were established by calculation based on the chemical composition of various human tissues. The equivalent water thickness of tissue substitute modules was calculated with different CT modeling curves in TPS. The actual equivalent water thickness of various modules was measured by a Bragg peak detector, and compared with the calculated values of TPS to verify the accuracy of different CT models.Results:The differences of CT modeling curves were significantly different under different tube voltage scanning protocols. Compared with CT-MD curves, CT-SP curves based on the stoichiometric calibration were more suitable for proton dose calculation. However, the values of stopping power corresponding to high CT values still needed to be optimized, and the calculation error after calibration was less than 3%.Conclusion:The method of verifying and calibrating CT unit curves of proton TPS is described, proving that the CT-SP curves after stoichiometric calculation are more suitable for proton dose calculation.
9.Wheel-shaped polyoxometalates as nanozymes for autophagy-augmented and phototherapy-involved cancer nanotherapy.
Jun MIAO ; Xiaofeng FAN ; Yining SHAO ; Yalei ZHANG ; Cailing CHEN ; Hongrui TIAN ; Shujun LI ; Zhiping ZHENG ; Xiaoqian XU
Journal of Pharmaceutical Analysis 2024;14(12):101018-101018
Image 1.
10.Correlation between triglyceride-glucose index and high on-treatment platelet reactivity during clopidogrel treatment in patients with ischemic stroke
Haoxuan CHEN ; Li YANG ; Zhenzhen LOU ; Yibo ZHAN ; Huiying OUYANG ; Guixian CHEN ; Changlin ZHANG ; Hui MAO ; Xiaojun LI ; Zhiping HUANG ; Zequan ZHENG ; Haoyou XU ; Longlong WEN ; Min ZHAO ; Yuanqi ZHAO
International Journal of Cerebrovascular Diseases 2023;31(4):253-258
Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.


Result Analysis
Print
Save
E-mail