1.Nanomaterial-based Therapeutics for Biofilm-generated Bacterial Infections
Zhuo-Jun HE ; Yu-Ying CHEN ; Yang ZHOU ; Gui-Qin DAI ; De-Liang LIU ; Meng-De LIU ; Jian-Hui GAO ; Ze CHEN ; Jia-Yu DENG ; Guang-Yan LIANG ; Li WEI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2024;51(7):1604-1617
Bacterial biofilms gave rise to persistent infections and multi-organ failure, thereby posing a serious threat to human health. Biofilms were formed by cross-linking of hydrophobic extracellular polymeric substances (EPS), such as proteins, polysaccharides, and eDNA, which were synthesized by bacteria themselves after adhesion and colonization on biological surfaces. They had the characteristics of dense structure, high adhesiveness and low drug permeability, and had been found in many human organs or tissues, such as the brain, heart, liver, spleen, lungs, kidneys, gastrointestinal tract, and skeleton. By releasing pro-inflammatory bacterial metabolites including endotoxins, exotoxins and interleukin, biofilms stimulated the body’s immune system to secrete inflammatory factors. These factors triggered local inflammation and chronic infections. Those were the key reason for the failure of traditional clinical drug therapy for infectious diseases.In order to cope with the increasingly severe drug-resistant infections, it was urgent to develop new therapeutic strategies for bacterial-biofilm eradication and anti-bacterial infections. Based on the nanoscale structure and biocompatible activity, nanobiomaterials had the advantages of specific targeting, intelligent delivery, high drug loading and low toxicity, which could realize efficient intervention and precise treatment of drug-resistant bacterial biofilms. This paper highlighted multiple strategies of biofilms eradication based on nanobiomaterials. For example, nanobiomaterials combined with EPS degrading enzymes could be used for targeted hydrolysis of bacterial biofilms, and effectively increased the drug enrichment within biofilms. By loading quorum sensing inhibitors, nanotechnology was also an effective strategy for eradicating bacterial biofilms and recovering the infectious symptoms. Nanobiomaterials could intervene the bacterial metabolism and break the bacterial survival homeostasis by blocking the uptake of nutrients. Moreover, energy-driven micro-nano robotics had shown excellent performance in active delivery and biofilm eradication. Micro-nano robots could penetrate physiological barriers by exogenous or endogenous driving modes such as by biological or chemical methods, ultrasound, and magnetic field, and deliver drugs to the infection sites accurately. Achieving this using conventional drugs was difficult. Overall, the paper described the biological properties and drug-resistant molecular mechanisms of bacterial biofilms, and highlighted therapeutic strategies from different perspectives by nanobiomaterials, such as dispersing bacterial mature biofilms, blocking quorum sensing, inhibiting bacterial metabolism, and energy driving penetration. In addition, we presented the key challenges still faced by nanobiomaterials in combating bacterial biofilm infections. Firstly, the dense structure of EPS caused biofilms spatial heterogeneity and metabolic heterogeneity, which created exacting requirements for the design, construction and preparation process of nanobiomaterials. Secondly, biofilm disruption carried the risk of spread and infection the pathogenic bacteria, which might lead to other infections. Finally, we emphasized the role of nanobiomaterials in the development trends and translational prospects in biofilm treatment.
2.Association between unhealthy lifestyles and hypertension, diabetes and dyslipidemia in old adults in China
Tingting YE ; Ying SHAO ; Bin YU ; Changwei CAI ; Chuanteng FENG ; Peng JIA ; Shujuan YANG
Chinese Journal of Epidemiology 2024;45(3):385-392
Objective:To analyze the individual and cumulative effects of unhealthy lifestyle on the prevalence of hypertension, diabetes and dyslipidemia in old adults in China, and find out the critical lifestyle in the network.Methods:Based on the baseline data of Yunnan Behavior and Disease Surveillance Cohort in 2021, a total of 16 763 older adults aged ≥60 years were included in our study. The unhealthy lifestyle factors including smoking, drinking, unhealthy eating habit, lower physical activity level, abnormal BMI and abnormal waist circumference. We calculated the unhealthy lifestyle score by using the cumulative exposures of each participant. Multiple logistic regression and mixed graphical models were used to describe the association between unhealthy lifestyle and the prevalence of hypertension, diabetes and dyslipidemia.Results:The prevalence of hypertension, diabetes and dyslipidemia were 57.0%, 11.5% and 37.0%, respectively. Most of the unhealthy lifestyles included in the study were risk factors for hypertension, diabetes and dyslipidemia, and the risks of disease increased with the increase of the unhealthy lifestyle score. The participants with the highest score (score: 6) had significantly higher prevalence of hypertension ( OR=3.99, 95% CI: 1.81-8.80), diabetes ( OR=4.64, 95% CI: 1.64-13.15) and dyslipidemia ( OR=4.26, 95% CI: 2.08-8.73) compared with those with lowest score (score: 0). In the network constructed by mixed graphical model, abnormal waist circumference (bridge strength=0.81) and hypertension (bridge strength=0.55) were vital bridge nodes connecting unhealthy lifestyle and hypertension, diabetes and dyslipidemia. Conclusions:The unhealthy lifestyle score was associated with risks for hypertension, diabetes and dyslipidemia. Abnormal waist circumference was the key factor for chronic diseases in old adults.
3.Progress in complex network theory-based studies on the associations between health-related behaviors and chronic non-communicable diseases
Shujuan YANG ; Bin YU ; Shu DONG ; Changwei CAI ; Hongyun LIU ; Tingting YE ; Peng JIA
Chinese Journal of Epidemiology 2024;45(3):408-416
In recent years, the research focus on health-related behavior and chronic non-communicable diseases has shifted from the analysis on independent effects of multiple causes on a single outcome to the evaluation the complex relationships between multiple causes and multiple effects. Complex network theory, an important branch of system science, considers the relationships among factors in a network and can reveal how health-related behaviors interact with chronic diseases through a series of complex network models and indicators. This paper summarizes the definition and development of complex network theory and its commonly used models, indicators, and case studies in the field of health-related behavior and chronic disease to promote the application of complex network theory in the field of health and provide reference and tools for future research of the relationship between health-related behavior and chronic disease.
4.Association between work environment noise perception and cardiovascular diseases, depressive symptoms, and their comorbidity in occupational population
Changwei CAI ; Bo YANG ; Yunzhe FAN ; Bin YU ; Shu DONG ; Yao FU ; Chuanteng FENG ; Honglian ZENG ; Peng JIA ; Shujuan YANG
Chinese Journal of Epidemiology 2024;45(3):417-424
Objective:To explore the association between occupational noise perception and cardiovascular disease (CVD), depression symptoms, as well as their comorbidity in occupational population and provide evidence for the prevention and control of physical and mental illnesses.Methods:A cross-sectional survey design was adopted, based on baseline data in population in 28 prefectures in Sichuan Province and Guizhou Province, and 33 districts (counties) in Chongqing municipality from Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during October to December 2021. A questionnaire survey was conducted to collect information about noise perception, depressive symptoms, and the history of CVD. Latent profile analysis model was used to determine identify noise perception type, and multinomial logistic regression analysis was conducted to explore the relationship between different occupational noise perception types and CVD, depression symptoms and their comorbidity.Results:A total of 30 509 participants were included, the mean age was (36.6±10.5) years, and men accounted for 82.0%. The direct perception of occupational noise, psychological effects and hearing/sleep impact of occupational noise increased the risk for CVD, depressive symptoms, and their comorbidity. By using latent profile analysis, occupational noise perception was classified into four levels: low, medium, high, and very high. As the level of noise perception increased, the association with CVD, depressive symptoms, and their comorbidity increased. In fact, very high level occupational noise perception were found to increase the risk for CVD, depressive symptoms, and their comorbidity by 2.14 (95% CI: 1.73-2.65) times, 8.80 (95% CI: 7.91-9.78) times, and 17.02 (95% CI: 12.78-22.66) times respectively compared with low-level occupational noise perception. Conclusions:Different types of occupational noise perception are associated with CVD and depression symptom, especially in the form of CVD complicated with depression symptom. Furthermore, the intensity of occupational noise in the work environment should be reduced to lower the risk for physical and mental health.
5.Association between unhealthy lifestyles and diabetic dyslipidemia in occupational population and network analysis
Chunlan MA ; Bin YU ; Yunzhe FAN ; Tingting YE ; Changwei CAI ; Bo YANG ; Honglian ZENG ; Peng JIA ; Shujuan YANG
Chinese Journal of Epidemiology 2024;45(3):425-431
Objective:To understand the influence of unhealthy lifestyle on diabetic dyslipidemia and the key influencing factors in occupational population and provided scientific evidence for the prevention of diabetic dyslipidemia.Methods:Based on baseline data and follow-up data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during 2021. Diabetic dyslipidemia was defined as diabetes plus one or more forms of dyslipidemia, and unhealthy lifestyle factors included smoking, alcohol consumption, unhealthy dietary patterns, low physical activity, and abnormal BMI. Multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle scores and diabetic dyslipidemia, network analysis was used to find and explore the key lifestyles influencing glycolipid metabolism.Results:A total of 25 631 subjects were included. People with unhealthy lifestyle score 2 and 3 were 1.93 (95% CI: 1.31-2.86) times and 2.37 (95% CI: 1.60-3.50) times more likely to have diabetes with ≥1 forms of dyslipidemia than those with scores of 0; People with unhealthy lifestyle score 1, 2 and 3 were 1.98 (95% CI: 1.08-3.61) times, 2.87 (95% CI: 1.60-5.14) times and 3.95 (95% CI: 2.22-7.06) times more likely to have diabetes with ≥2 forms of dyslipidemia than those with score 0. Network analysis found that abnormal BMI and HDL-C were the "bridge nodes" that link unhealthy lifestyles with diabetic dyslipidemia. Conclusion:The higher the score of unhealthy lifestyle, the higher the risk for diabetic dyslipidemia, abnormal BMI and HDL-C are key factors influencing the association between unhealthy lifestyle and diabetic dyslipidemia.
6.Mediating effects of body mass index and lipid levels on the association between alcohol consumption and hypertension in occupational population
Shu DONG ; Bin YU ; Bo YANG ; Yunzhe FAN ; Yao FU ; Chuanteng FENG ; Honglian ZENG ; Peng JIA ; Shujuan YANG
Chinese Journal of Epidemiology 2024;45(3):440-446
Objective:To investigate the association between alcohol consumption and hypertension and SBP, DBP and the mediating effects of body mass index (BMI) and lipid level in occupational population, and provide reference for the intervention and prevention of hypertension.Methods:Based on the data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd., the information about the demographic characteristics, behavior and lifestyle, blood pressure and lipids level of the participants were collected through questionnaire survey, physical examination and blood biochemical test. Logistic/linear regression was used to analyze the association between alcohol consumption and hypertension, SBP and DBP. The individual and joint mediating effects of BMI, HDL-C, LDL-C, TG, and TC were explored through causal mediating analysis. A network analysis was used to explore the correlation between alcohol consumption, BMI and lipid levels, and hypertension.Results:A total of 22 887 participants were included, in whom 1 825 had newly detected hypertension. Logistic regression analysis found that current/former drinkers had a 33% increase of risk for hypertension compared with never-drinkers ( OR=1.33, 95% CI:1.19-1.48). Similarly, alcohol consumption could increase SBP ( β=1.05, 95% CI:0.69-1.40) and DBP ( β=1.10, 95% CI:0.83-1.38). Overall, BMI and lipid levels could mediate the associations between alcohol consumption and hypertension, SBP and DBP by 21.91%, 28.40% and 22.64%, respectively. BMI and TG were the main mediators, and they were also the two nodes with the highest edge weight and bridge strength centrality in the network of alcohol consumption, BMI, lipid levels and hypertension. Conclusions:Alcohol consumption was associated with increased risk for hypertension, and BMI and TG were important mediators and key nodes in the network. It is suggested that paying attention to the alcohol consumption, BMI and TG might help prevent hypertension in occupational population.
7.Effect of long-term care insurance on incidence of falls in old people with disability based on difference-in-differences method
Hongyun LIU ; Chuanteng FENG ; Bin YU ; Hua MA ; Yihong BAI ; Peng JIA ; Qingyu DOU ; Shujuan YANG
Chinese Journal of Epidemiology 2024;45(5):673-678
Objective:To analyze the effect of long-term care insurance on the incidence of falls in old people with disability, and the modification effect of different living arrangements.Methods:Based on the discharge diagnosis records of the hospitalization in urban residents who applied for long-term care insurance in Chengdu from July 2014 to June 2021, those who received long-term care insurance were selected as the intervention group and those who received no long-term care insurance were selected as the control group, the changes in the incidence of falls before and after the long-term care were analyzed using difference-in-differences method, and the modification effects of different living arrangements were explored using stratified analysis.Results:Long-term care insurance significantly reduced the risk for monthly incidence of falls in older adults [average treatment effects on treated (ATT) = -1.21% (95% CI: -1.82%--0.60%)], and the effect increased over time (ATT=-1.26%, 95% CI: -1.93%--0.59%). Long-term care insurance had a significant effect on reducing the incidence of falls in old people living with spouses/family members (ATT=-0.92%, 95% CI: -1.47%--0.37%) and in nursing facilities/hospitals (ATT=-2.10%, 95% CI: -3.81%--0.40%), but it had no significant effect in those living alone. Conclusions:Long-term care insurance can effectively reduce the incidence of falls in old people with disability, showing a positive effect. Living with family members or in nursing facilities/hospitals has a modification effect of the implementation of long-term care insurance policy. It is necessary to pay attention to key populations in the future and expand the coverage of long-term care insurance.
8.Effectiveness of TCM Health Management for Myocardial Infarction based on Tertiary Management System: A Single-arm Cohort Study of 255 Patients
Hongxin GUO ; Mingjun ZHU ; Rui YU ; Xingyuan LI ; Guangcao PENG ; Xinlu WANG ; Jianru WANG ; Bin LI ; Qifei ZHAO ; Yongxia WANG
Journal of Traditional Chinese Medicine 2024;65(8):821-829
ObjectiveTo evaluate the efficacy of TCM health management based on tertiary management system for patients with myocardial infarction (MI). MethodsA total of 277 patients with non-acute MI were enrolled and given comprehensive TCM health management strategies including health education, lifestyle adjustment, risk factors control, medication and TCM appropriate techniques management through a tertiary management system with "the patient as the core, village/community physicians as the main executive body, and tertiary TCM hospital specialists as the leading body", for a period of 12 months by using a prospective single-arm cohort study. Through patient reporting and medical records surveys, various indicators before and after 12-month management were collected and compared. The primary efficacy indicators were readmission rate and recurrent exacerbation rate, and the secondary efficacy indicators included disease awareness-related indicators, lifestyle behavior-related indicators, cardiovascular risk factor-related indicators and Canadian cardiovascular society (CCS) cardiac function classification. ResultsA total of 255 patients completed the study and were included in the final analysis. The recurrent exacerbation and readmission rates of patients after management were 23.14% (59 cases) and 20.25% (49 cases), respectively, significantly lower than 36.08% (92 cases) and 53.72% (130 cases) before management (P<0.05). Except for knowledge on diabetes diagnostic criteria with no significant difference before and after management (P>0.05), awareness of other knowledge with regard to the prevention and treatment of cardiovascular and cerebrovascular diseases were improved after management (P<0.01), as well as the total score (P<0.01). In terms of daily life behaviors, the rates of salty diet, sweet diet and greasy diet were significantly lower than baseline, while the rate of moderate exercise was significantly higher (P<0.05 or P<0.01); the rates of ongoing smoking and vigorous exercise were not significantly changed (P>0.05). For cardiovascular risk factors, patients' total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, total depression assessment scale score, and total anxiety assessment scale score were significantly reduced after management (P<0.01). Systolic blood pressure and body mass index (BMI) were both higher after management (P<0.05 or P<0.01), and there was no statistically significant difference in diastolic blood pressure (P>0.05). In terms of the cardiovascular disease risk factors reaching the standard levels, the rate of LDL cholesterol <1.8 mmol/L significantly increased (P<0.01), while the rate of BMI <24 kg/m2 and the rate of systolic blood pressure <140 mmHg both decreased significantly (P<0.05 or P<0.01) from baseline; the diastolic blood pressure and rate of fasting glucose <7.0 mmol/L were not significantly changed (P>0.05). The patients' CCS cardiac function classification was significantly reduced (P<0.05). ConclusionTCM health management based on the tertiary management system can enhance MI patients' awareness of the disease, change poor lifestyle habits, reduce risk factors such as blood lipids and blood glucose, improve anxiety and depression, increase activity tolerance, and reduce their recurrence exacerbation and readmission rates, which is worthy of clinical promotion.
9.Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)gene-transfected hepatic stellate cells
LIU HONGYI ; ZHOU YUANYUAN ; GUO PENG ; ZHENG XIONGWEI ; CHEN WEIBIN ; ZHANG SHICHAO ; FU YU ; ZHOU XU ; WAN ZHENG ; ZHAO BIN ; ZHAO YILIN
Journal of Zhejiang University. Science. B 2024;25(6):499-512
Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal failure.However,it has poor elasticity and compliance,leading to stenosis and thrombosis.The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial cells.Studies have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM fibers.Furthermore,mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure.Based on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV infection.Subsequently,these HBX-HSCs were implanted into a polycaprolactone-polyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold.We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization.Then,the vessel scaffold was implanted into a rabbit's neck arteriovenous fistula model.It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit's body.Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.
10.Design, synthesis and antituberculosis activity of 2-aryl substituted benzothiopyranone compounds
Xia-xia TANG ; Wen-yi LI ; Peng LI ; Bin WANG ; Yu LU ; Hai-hong HUANG ; Gang LI
Acta Pharmaceutica Sinica 2024;59(4):987-996
A novel series of 2-aryl substituted benzothiopyranone compounds was designed and synthesized based on our previously obtained benzothiopyranone scaffold with significant antituberculosis activity. All target compounds were evaluated for their antimycobacterial activity and preliminary druggability was subsequently investigated for some selected compounds with good activity. The results indicated that most compounds showed good activity against

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