1.Discovery of novel butyrylcholinesterase inhibitors for treating Alzheimer's disease.
Zhipei SANG ; Shuheng HUANG ; Wanying TAN ; Yujuan BAN ; Keren WANG ; Yufan FAN ; Hongsong CHEN ; Qiyao ZHANG ; Chanchan LIANG ; Jing MI ; Yunqi GAO ; Ya ZHANG ; Wenmin LIU ; Jianta WANG ; Wu DONG ; Zhenghuai TAN ; Lei TANG ; Haibin LUO
Acta Pharmaceutica Sinica B 2025;15(4):2134-2155
Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC50 = 0.049 μmol/L, huBuChE IC50 = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.
2.Distribution characteristics and long-term change trend of body mass index in Chinese older adults aged 65 years and above
Li QI ; Chen CHEN ; Sirui CHEN ; Zhipei LI ; Sixin LIU ; Jinhui ZHOU ; Jiahao CHEN ; Hao QIAN ; Chun TAN ; Xianglong DAI ; Ziyue ZHU ; Jun WANG ; Xi MENG ; Wenhui SHI ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(6):908-915
Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.
3.Distribution characteristics and long-term change trend of body mass index in Chinese older adults aged 65 years and above
Li QI ; Chen CHEN ; Sirui CHEN ; Zhipei LI ; Sixin LIU ; Jinhui ZHOU ; Jiahao CHEN ; Hao QIAN ; Chun TAN ; Xianglong DAI ; Ziyue ZHU ; Jun WANG ; Xi MENG ; Wenhui SHI ; Yuebin LYU ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(6):908-915
Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.
4.Development and Governance Strategy of Chinese Materia Medica Industry from the Perspective of Multi-chain Integration: A Case Study of Polygonati Rhizoma Industry in Anhui Province
Aiyu LI ; Zhiying LIU ; Zhipei FENG
Chinese Journal of Modern Applied Pharmacy 2024;41(9):1258-1266
OBJECTIVE
To put forward the governance for the development of Chinese materia medica industry by studying the multi-chain docking and integration mechanism based on the investigation and analysis of Polygonati Rhizoma industry in Anhui province.
METHODS
Based on the theory of multi-chain integration, this research defines the connotation of multi-chain integration, proposes the mechanism of multi-chain integration, and takes Anhui Polygonati Rhizoma industry as a case to sort out the mechanism of inter-chain docking and integration in industrial development, and puts forward the management strategy of industrial development accordingly.
RESULTS
The precise docking of the industrial chain, value chain, innovation chain, information chain, capital chain and policy chain was explored. Leading enterprises, scientific research units, financial institutions, industry organizations, government departments five inter-chain contact points, docking to promote multi-chain integration.
CONCLUSION
This research promotes industrial multi-chain integration from five aspects: leading enterprises to promote product development, scientific research institutions to promote innovation, financial departments to increase capital investment, industry organizations to build information exchange platforms, and government departments to increase policy support, for government to promote the development of effective Chinese materia medica industry reference theory instruction value and reality significance.
5.Clinical value of RT-3D-TEE in assessing the disease condition of patients with mitral valve prolapse combined with mitral regurgitation
Tingting XU ; Wei LIU ; Hao ZHANG ; Ping CHEN ; Zhipei WANG
China Medical Equipment 2024;21(11):66-70
Objective:To investigate clinical value of real time three-dimensional transesophageal echocardiography(RT-3D-TEE)in assessing patients with mitral valve prolapse(MVP)combined with mitral regurgitation(MR).Methods:The clinical data of 99 patients with MVP that combined with MR,who admitted to CANGZHOU People's Hospital from February 2020 to October 2023 and were confirmed by RT-3D-TEE,were retrospectively analyzed.According to two dimensional(2D)comprehensive method,they were divided into mild MR group(43 cases)and moderate-severe MR group(56 cases)as the degree of disease condition.The RT-3D-TEE parameters of the two groups were compared.The combined predictive indexes of RT-3D-TEE parameters were obtained by logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn to analyze the values of single and combined RT-3D-TEE parameter in assessing the degree of disease condition of MVP patients with MR.Result:The anterolateral to posteromedial diameter(DAIPm),anterior-to-posterior diameter(DAP),nonplanarity angle(θNPA),annulus area in 3D(A3D),annulus perimeter(AP),total valve leaflet area of mild MR group were respectively(3.20±0.39)cm,(2.82±0.26)cm and(115.77±12.60)°,(6.90±1.28)cm2,(9.36±0.83)cm and(7.71±1.46)cm2,which were significantly less than those[(3.66±0.36)cm,(3.24±0.40)cm,(125.41±13.23)°,(7.99±1.59)cm2,(10.47±1.15)cm and(9.38±1.81)cm2]of moderate-severe MR group,respectively,and the differences of these indicators between two groups were significant(t=6.092,5.965,3.670,3.680,5.333,4.929,P<0.05).The involution-index of mild group was(26.39±4.39),which was significantly larger than that(22.94±3.65)of moderate-severe MR group(t=4.264,P<0.05).There were no significant differences in valve annulus height(H),angle of anterior leaflet(θAnt)and angle of posterior leaflet(θPost)between the two groups(P>0.05).The area under curve(AUC)values of ROC curve of DAIPm,DAP,θNPA,involution-index,A3D,AP and Total valve leaflet area were respectively 0.818,0.831,0.712,0.737,0.704,0.806 and 0.765 in assessing the disease degree of MVP patients with MR.The AUC value of combined detection of them was 0.990.Conclusion:DAIPm,DAP,θNPA,involution-index,A3D,AP and Total valve leaflet area of RT-3D-TEE parameters had a certain value in assessing the disease degree of MVP patients with MR,and the assessment value of combined detection is higher.
6.Advances in bioremediation of polycyclic aromatic hydrocarbons contaminated soil.
Meilin ZHENG ; Yinghao ZHAO ; Lili MIAO ; Xiyan GAO ; Zhipei LIU
Chinese Journal of Biotechnology 2021;37(10):3535-3548
Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent pollutants that are widely distributed in the environment. Due to their stable structure and poor degradability, PAHs exhibit carcinogenic, teratogenic, and mutagenic toxicity to the ecological environment and organisms, thus increasing attentions have been paid to their removals and remediation. Green, safe and economical technologies are widely used in the bioremediation of PAHs-contaminated soil. This article summarizes the present status of PAHs pollution in soil of China from the aspects of origin, migration, fate, and pollution level. Meanwhile, the types of microorganisms and plants capable of degrading PAHs, as well as the underlying mechanisms, are summarized. The features of three major bioremediation technologies, i.e., microbial remediation, phytoremediation, and joint remediation, are compared. Analysis of the interaction mechanisms between plants and microorganisms, selection and cultivation of stress-resistant strains and plants, as well as safety and efficacy evaluation of practical applications, are expected to become future directions in this field.
Biodegradation, Environmental
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Polycyclic Aromatic Hydrocarbons/toxicity*
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Soil
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Soil Microbiology
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Soil Pollutants
7.Decursin inhibits EC109 cells proliferation via suppression of JAK2/STAT3 signaling pathway
Changkang KE ; Yuying LIU ; Zhipei ZHANG ; Jiao ZHANG ; Yifang ZHU ; Jinwei LIU ; Ziqian WANG ; Jinbo ZHAO ; Xiaofei LI
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(4):230-236
Objective To investigate whether decursin(Dec) could inhibit EC109 cells proliferation by suppression of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in human esophageal squamous cell carcinoma.Methods The EC109 cells were treated with Dec(20,40,and 80 pmmol/L) for48 h.The cell viability was evaluated by MTT;the apoptotic cells was labelled by TUNEL;the mitochondrial oxidative stress level was detected by fluorescent staining;and western blotting was used to analyze the proteins of JAK2/STAT3 signaling and apoptosis in EC109 cells,respectively.After co-application of JAK2 / STAT3 antagonist(AG490),the inhibitory ability of Dec to EC109 was observed from the in vivo and in vitro levels.Results Compared to the control group,different concentrations of Dec dose-dependently down-regulated expressions of p-JAK2 [(55.89 ± 6.04) %] and p-STAT3 [(45.27 ± 8.65) %],repressed EC109 cell activity(0.43 ± 0.078),increased apoptotic rate[(35.31 ± 8.41)%],reduced MMP levels[(37.23 ± 6.89)%],promoted reactive oxygen species(ROS) [(231.81 ± 19.63)%],decreased glutathione (GSH) activity [(46.78 ± 6.91)%,P<0.05].However,Dec did not significantly affect the activity of the normal esophageal epithelium HET-1A cells(P >0.05).Meanwhile,Dec obviously leaded to reduction of Bcl2,increment of Bax,and augment of Caspase-3 cleavage (P <0.05).Additionally,the inhibitory effect of Dec on EC109 was specifically intensified after co-application of AG490 in vivo and in vitro levels(P <0.05).Conclusion Dec can fight against human esophageal squamous cell carcinoma in vitro and in vivo via activation of mitochondrial oxidative stress-induced apoptosis which was mediated by JAK2/STAT3 pathway.
8.Cognition on healthcare-associated infection management among 173 hospital directors in Shaanxi Province
Hongliang DONG ; Zhipei YANG ; Lei SHEN ; Ning JIANG ; Fangfei LIU ; Yao SUO
Chinese Journal of Infection Control 2017;16(9):820-824
Objective To understand the cognition about healthcare-associated infection(HAI) management among directors in secondary and above hospitals in Shaanxi Province.Methods Questionnaire survey was adopted to investigate hospital directors who participated in The third session of Shaanxi Provincial HAI management training course for hospital directors.Results A total of 181 questionnaires were distributed, 173 (95.58%) were qualified.74.57% of surveyed hospitals were secondary hospitals, 61.85% were comprehensive hospitals, 67.05% of respondents received HAI training in recent 3 years, 81.50% and 55.49% of hospital directors thought the main factors influencing the HAI management were health care workers'' awareness on HAI and leaders'' attention respectively.58.96%, 60.12%, and 46.82% of hospital directors thought the director of HAI management department should have intermediate and above professional title, bachelor degree or above education, and preventive medicine professional requirements respectively.The awareness rate of HAI management-related knowledge was 86.71%, difference in awareness rate of HAI management-related knowledge among respondents of different job, gender, and HAI training in recent 3 years were all significantly different(all P<0.05).Conclusion Hospital directors'' cognition on HAI management affect the development of HAI work, strengthen the training on HAI knowledge among administrators can improve hospital administrators'' awareness on HAI prevention and control.
9.Development of bioremediation in China--a review.
Chinese Journal of Biotechnology 2015;31(6):901-916
The development of bioremediation for contaminated soil in China during past 30 years was briefly reviewed, mainly including the developing stages, bioremediation techniques/strategies and their applications, and isolation, screening and characterizations of microbial strains for bioremediation as well as their efficiencies in bioremediation of contaminated soils. Finally, future development of bioremediation techniques/strategies and their applications were also discussed.
Biodegradation, Environmental
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China
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Environmental Pollution
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Soil Microbiology
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Soil Pollutants
10.Expression and correlation of ABCG2 and V-ATPase in NSCLC
Boya LIU ; Zhipei ZHANG ; Xiaofei LI ; Yingchun DENG ; Kunxiang GAO ; Hong XU ; Peng WANG ; Qingshu CHENG
Cancer Research and Clinic 2009;21(12):806-809
Objective To investigate the expressions of ABCG2 and V-ATPase in NSCLC and their expression rates in pathological classification, TNM stages and pathological grades and the expression correlation between ABCG2 and V-ATPase. Methods Expressions of ABCG2 and V-ATPase were accessed with EnVinsion immunohistochemistry in tumor samples from 92 NSCLC patients. The corresponding data was analyzed statistically. Results Expressions of ABCG2 and V -ATPase were found both in the lung adenocarcinoma and lung squamous cell cancer, and the difference between these two kinds of tumors was significant (P =0.003,0.000). ABCG2 expression was significantly different among TNM stages of lung adenocarcinoma (P=0.004) as well as among pathological grades of lung adenocarcinoma (P =0.028) and squamous cell carcinoma (P =0.000), while no significant difference was found among TNM stages of squamous cell lung carcinoma. The level of V-ATPase expression was associated with TNM stages of lung adenocarcinoma (P =0.026) and pathological grades of lung squamous cell carcinoma (P =0.002), however, among TNM stages of lung squamous cell carcinoma and pathological grades of lung adenocarcinoma, the difference was not significant. Additionally, the significant correlation was found between expression of ABCG2 and V-ATPase in all samples, adenocarcinoma and squamous cell carcinoma (P<0.001). Conclusion The significant correlation is found between expression of ABCG2 and V-ATPase, which indicate that they may co-work to participate in the mechanism of anticancer drug resistance.


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