1.Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent.
Xin CHEN ; Xianggang MU ; Lele DING ; Xi WANG ; Fei MAO ; Jinlian WEI ; Qian LIU ; Yixiang XU ; Shuaishuai NI ; Lijun JIA ; Jian LI
Acta Pharmaceutica Sinica B 2024;14(2):729-750
Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
2.Discussion on the status quo and problems of health risk management of hand-transmitted vibration in the workplace
Qian BU ; Lele JIA ; Jingyun LI ; Zhongbin ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):69-72
The risk management in workplace is an important measure to effectively prevent and control the harm of hand-transmitted vibration. Based on the relevant developments at home and abroad, this paper expounds the risk of manual vibration operation in workplace by taking contact assessment and hazard assessment as an example. On this basis, the limit management and hierarchical management related to risk management are discussed, and the existing problems are analyzed.
3.Current status and prospects of health hazards database for chemical hazards
Lele JIA ; Jingyun LI ; Na CHEN ; Zhongbin ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(8):630-636
In order to facilitate technical personnel related to occupational health and safety production to search, obtain, and master information on the hazard classification and health effects of chemical hazards, this article surveyed 14 commonly used foreign databases and 9 commonly used domestic databases, analyzed the characteristics, main content, scope of application, and network resources of each database, and considered the development of database for occupational health hazard of chemical hazards.
4.Clinical value of serum 3′-terminal 2′- O-methylated miR-486-5p assessment for the diagnosis of coronary heart disease
Lele ZHANG ; Jia WU ; Cheng WANG ; Mimi MU ; Yu ZHANG ; Junjun WANG
Chinese Journal of Laboratory Medicine 2024;47(7):798-805
Objective:To detect the 3′-terminal 2′- O-methylation (2′Ome) modified microRNA-486-5p (miR-486-5p) levels in the serum of patients with coronary heart disease (CHD), and evaluate its clinical application value as a biomarker to assist the diagnosis of CHD. Methods:Seventy patients with CHD diagnosed at the Eastern Theater General Hospital from January 2021 to December 2022 and 60 age-and sex-matched healthy people undergoing health examination during the same period were selected for this retrospective case-control study. The Gensini score was calculated based on coronary angiography results, and patients in the coronary artery disease group was categorized into mild-to-moderate stenosis (40 cases) and severe stenosis subgroups (30 cases); Serum biochemical indexes, miR-486-5p and 2′Ome-miR-486-5p expression levels were compared between the CHD group and the healthy control group; correlation of biochemical indices, Gensini score and serum miR-486-5p and 2′Ome-miR-486-5p levels was assessed by using Spearman correlation analysis; and multifactorial logistic regression was used to analyze the impact of serum miR-486-5p and 2′Ome-miR-486-5p levels on CHD and the degree of coronary artery stenosis; evaluation of the diagnostic value of 2′Ome-miR-486-5p levels on the degree of coronary artery disease and coronary artery stenosis was achieved by using ROC curve.Results:Serum miR-486-5p and 2′Ome-miR-486-5p levels were significantly higher in CHD group than in the healthy control group [0.31 (0.17, 0.84) vs 0.21 (0.11, 0.49), Z=2.055, P<0.05; 2.30 (1.32, 5.40) vs 0.86 (0.55, 1.72), Z=5.840, P<0.05]; Serum 2′Ome-miR-486-5p expression levels were higher in both mild-moderate and severe stenosis subgroups than in healthy controls ( P<0.05), and serum 2′Ome-miR-486-5p levels were higher in the severe stenosis subgroup than in the mild-moderate stenosis subgroup [3.54(1.78, 5.44) vs 1.63(1.25, 4.07), Z=-2.053, P<0.05]. Both serum miR-486-5p and 2′Ome-miR-486-5p levels were positively correlated with the Gensini score ( r=0.277 and 0.479, respectively, P<0.05); multifactorial logistic regression analysis showed that serum 2′Ome-miR-486-5p level was an independent influence factor of the degree of coronary stenosis after adjustig for the effects of confounding factors such as age and sex ( OR=1.025, 95% CI 1.002-1.049, P<0.05). ROC curve analysis showed that the area under the ROC curve of serum 2′Ome-miR-486-5p levels for the diagnosis of CHD patients, mild to moderate and severe stenosis were 0.798, 0.752 and 0.859, with sensitivities of 91.4%, 92.5%, and 73.3%, and specificities of 56.7%, 51.7% and 81.7%, respectively, at the optimal cut-off (0.912, 0.863, 2.209). Conclusion:Serum 2′Ome-miR-486-5p level is increased in CHD patients and is an independent predictor of the severity of coronary artery stenosis, which can be used as a biomarker for the diagnosis of patients with CHD.
5.Discussion on the status quo and problems of health risk management of hand-transmitted vibration in the workplace
Qian BU ; Lele JIA ; Jingyun LI ; Zhongbin ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(1):69-72
The risk management in workplace is an important measure to effectively prevent and control the harm of hand-transmitted vibration. Based on the relevant developments at home and abroad, this paper expounds the risk of manual vibration operation in workplace by taking contact assessment and hazard assessment as an example. On this basis, the limit management and hierarchical management related to risk management are discussed, and the existing problems are analyzed.
6.Current status and prospects of health hazards database for chemical hazards
Lele JIA ; Jingyun LI ; Na CHEN ; Zhongbin ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(8):630-636
In order to facilitate technical personnel related to occupational health and safety production to search, obtain, and master information on the hazard classification and health effects of chemical hazards, this article surveyed 14 commonly used foreign databases and 9 commonly used domestic databases, analyzed the characteristics, main content, scope of application, and network resources of each database, and considered the development of database for occupational health hazard of chemical hazards.
7.Association between serum high-density lipoprotein subtype 3 cholesterol levels and coronary artery diseases severity and in-stent restenosis
Jia WU ; Lijun XUE ; Xiaoyang YU ; Yuxiao ZHOU ; Lele ZHANG ; Junjun WANG
Chinese Journal of Laboratory Medicine 2023;46(7):681-688
Objective:To explore the association between serum high density lipoprotein subtype 3 cholesterol (HDL3-C) levels and the severity and in-stent restenosis of patients with coronary artery disease.Methods:124 patients with coronary artery diseases and 62 healthy controls were included in this clinical case-control retrospective study. Participants were hospitalized from November 2020 to November 2021 at Jinling Hospital, Medical School of Nanjing University were enrolled. Patients with coronary artery disease were as follows: 28 patients with acute coronary syndrome and 96 patients with stable coronary heart disease. Serum HDL3-C levels as well as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were determined. According to the coronary artery angiography results of all patients at the time of admission, Gensini scores were calculated and patients were divided into in-stent restenosis group ( n=22), no in-stent stenosis group ( n=23) and non-stent implantation group ( n=79). The correlation between HDL3-C levels and other parameters was analyzed by Pearson or Spearman correlation analyses. Multivariate Logistic regression analyses were used to determine the impact of HDL3-C on the in-stent restenosis of coronary artery diseases. Results:Compared with controls, serum levels of HDL3-C and HDL-C were significantly decreased in patients with coronary artery diseases (all P<0.05). There was a significantly negative correlation between HDL3-C levels and Gensini scores ( r=-0.201, P=0.043). Among patients with coronary artery disease, serum levels of HDL3C, TC and TG in the in-stent restenosis group were significantly lower than in no in-stent stenosis group as well as than in the non-stent implantation group (all P<0.05). Multivariate Logistic regression analyses showed that after adjusting for age, sex, lipid-lowering drugs and TC, TG, LDLC parameters, HDL3-C ( OR=0.885, 95% CI 0.791-0.990, P=0.033) and HDL-C ( OR=0.018, 95% CI 0.001-0.426, P=0.013) levels were both independently associated with the occurrence of coronary artery disease; only HDL3-C levels (no in-stent stenosis group as the reference: OR=0.833, 95% CI 0.698-0.994, P=0.042; non-stent implantation group as the reference: OR=0.812, 95% CI 0.685-0.963, P=0.017) were independently associated with the presence of in-stent restenosis ( P<0.05). Conclusions:Serum HDL3-C levels are decreased in patients with coronary artery disease, especially in patients with in-stent restenosis. HDL3-C levels are associated with the severity of coronary artery lesions and the presence of in-stent restenosis of coronary arteries.
8.Hand-transmitted vibration and occupational health
Zhongbin ZHANG ; Qian BU ; Lele JIA
Journal of Environmental and Occupational Medicine 2022;39(11):1193-1197
The hand-arm vibration disease due to widespread hand-transmitted vibration operations is difficult to cure and seriously affects the health and quality of life of patients. Focusing on the prevention and control of hand-transmitted vibration and its occupational hazards, advances in occupational health relevant to hand-transmitted vibration were reviewed from the aspects of occupational hazard status, health impact, exposure monitoring, prevention and control of hand-transmitted vibration, as well as health surveillance, diagnosis, and treatment of hand-arm vibration disease. In addition, further suggestions on prevention and control of occupational hazards related with hand-transmitted vibration were prospected.
9.Effects of hand-transmitted vibration on fingertip terminal nerve: A meta-analysis
Qian BU ; Jingyun LI ; Na CHEN ; Lele JIA ; Zhongbin ZHANG ; Dingxin LONG
Journal of Environmental and Occupational Medicine 2022;39(11):1220-1225
Background Hand-transmitted vibration is one of the most common occupational hazards and is closely related to symptoms of fingertip terminal nerve damage. Objective To analyze the effects of hand-transmitted vibration on the terminal nerve of fingertips. Methods We systematically searched literature about the effects of hand-transmitted vibration on fingertip terminal nerve at home and abroad. The outcome index was the number (rate) of fingertip terminal nerve symptoms reported by the vibration group and the control group, such as finger numbness and finger tingling, and the search period was from database inception to December 2021. The quality of cross-sectional studies was assessed using the criteria recommended by the Agency for Healthcare Research and Quality (AHRQ), and the quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). NoteExpress 3.2 was used for literature management, and Excel 2003 was used for data collection and extraction. RevMan 5.4.1 software was used for statistical analysis, and random effect model was used to calculate the OR value of pooled effects and to draw forest plots. Subgroup analysis was carried out according to the working years with vibration exposure. At the same time, sensitivity analysis was performed after excluding studies with the largest weight and funnel plots were generated to evaluate publication bias. Results A total of 3619 articles were retrieved, and 39 articles were finally included, including 29 Chinese articles and 10 English articles; 36 cross-sectional studies and 3 cohort studies. In total, 8399 subjects were studied, including 5673 cases in the vibration exposure group and 2726 cases in the control group. Random effect model was used to merge the included literature. The results of meta-analysis showed that compared with the control group, hand-transmitted vibration was significantly associated with the self-reported occurrence of finger numbness (OR=8.29, 95%CI: 5.43-12.66), finger tingling (OR=7.50, 95%CI: 4.78-11.77), finger swelling (OR=8.25, 95%CI: 4.06-16.76), finger stiffness (OR=10.71, 95%CI: 3.60-31.87), finger trembling (OR=5.11, 95%CI: 2.60-10.04), hand weakness (OR=11.05, 95%CI: 3.98-30.68), hand sweating (OR=2.70, 95%CI: 1.64-4.43), hand coldness (OR=3.54, 95%CI: 2.42-5.18) (P<0.01). The subgroup analysis showed that the odds ratios of both finger numbness and finger tingling increased in the early and middle stages of vibration exposure (<5 years and 5-10 years of exposure duration)(finger numbness: OR=11.11, 19.07; finger tingling: OR=4.70, 16.55, respectively)(P<0.01), and decreased in the late stage of vibration exposure (10-15 years and ≥15 years of exposure duration) (finger numbness: OR=9.57, 2.30; finger tingling: OR=5.71, 6.00, respectively) (P<0.01). The results of sensitivity analysis showed a stable pooled effect (OR=13.96, 95%CI: 4.85-40.13, Z=4.89, P<0.01). The funnel plot results showed positive publication bias. Conclusion Occupational exposure to hand-transmitted vibration can cause finger numbness, finger tingling, finger swelling, finger stiffness, finger trembling, hand weakness, hand sweating, and hand coldness.
10.Advances on nervous system impairment induced by hand-transmitted vibration
Qian BU ; Jingyun LI ; Na CHEN ; Lele JIA ; Dingxin LONG ; Zhongbin ZHANG
Journal of Environmental and Occupational Medicine 2022;39(11):1237-1241
Hand-transmitted vibration is one of the most common physical harmful factors in the workplace,and the hand-arm vibration syndrome caused by it lacks effective treatment, and seriously affects the physical and mental health of the involved workers. As an important target for hand-transmitted vibration, the nervous system has attracted increasing attention from scholars, and much progress has been made in recent years in studying the effects of hand-transmitted vibration on nervous system function. Based on related literature at home and abroad, this paper introduced the hand-transmitted vibration-associated damage in peripheral, autonomic, and central nervous systems, and then explored the associated influence factors, like vibration frequency, environment temperature, and individual factors. The potential directions for further research were also proposed.

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