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.Bioequivalence study of olmesartan medoxomil tablet in Chinese healthy subjects
Na SHAN ; Da-Hai JIANG ; Lin-Lin MIAO ; Zhen-Li REN ; Peng-Bo JIN ; Pei-Qi HAO ; Li AN ; Hong ZHU ; Yong XIN ; Guang-De YANG ; Feng LIU
The Chinese Journal of Clinical Pharmacology 2024;40(20):3033-3037
Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90%confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00%-125.00%.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.
3.Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City.
Yu Xin XIE ; De Liang LYU ; Ke PENG ; Hong Wei XIE ; Yong JIANG ; Xin Bo ZHONG ; Xi Lin WEN ; Zi Wei FU ; Gui Li ZHOU ; Zhi Guang ZHAO ; Yi Chong LI
Chinese Journal of Preventive Medicine 2023;57(7):1011-1017
Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.
Male
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Humans
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Adult
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Female
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Carotid Intima-Media Thickness
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Cardiovascular Diseases
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Reference Values
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Carotid Arteries/diagnostic imaging*
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Ultrasonography, Carotid Arteries
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Risk Factors
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Carotid Artery Diseases
4.Rates and influencing factors of hospitalization after diagnosis among HIV infection cases in Yinzhou district of Ningbo, 2012-2020.
Zi Hui LI ; Qi ZHAO ; De Guang GONG ; Ye Xiang SUN ; Peng SHEN ; Hong Bo LIN ; Na HE
Chinese Journal of Epidemiology 2022;43(4):541-547
Objective: To understand the hospitalization rates and influencing factors after diagnosis among HIV infection cases, based on real-world data in Yinzhou district of Ningbo. Methods: A retrospective cohort study was conducted based on the databases of National AIDS Comprehensive Response Information Management System and Yinzhou Health Information Platform. The information about the following-up results, antiviral treatment data, electronic records of inpatient of the HIV cases reported during 2012-2020 were collected to analyze the rates, causes and influencing factors of hospitalization. Results: Among the 763 HIV infection cases reported in Yinzhou from 2012 to 2020, the hospitalization rate was 6.95% (53/763), and the number of inpatient was 2.59 per 100 person years. The hospitalization rate and the number of hospitalization per 100 person years in HIV infection cases were 3.16% (10/316) and 0.81 in those aged <30 years, 6.07% (15/247) and 1.59 in those aged >30 years, 7.86% (11/140) and 4.05 in those aged >45 years and 28.33% (17/60) and 17.40 in those aged ≥60 years respectively. Logistic multivariate regression analysis indicated that being aged ≥60 years was the influencing factor for hospitalizations in HIV infection cases (аOR=14.44, 95%CI:3.57-58.46). The hospitalization rates due to AIDS related diseases, cardiovascular diseases and metabolic diseases, and other diseases were 1.83% (14/763), 1.05% (8/763), and 3.93% (30/763), respectively. Conclusions: The hospitalization burden due to HIV infection was still mainly caused by those aged ≥60 years in Yinzhou, similar to that in general population and less proportion of hospitalizations were due to AIDS related diseases. The overall increase of hospitalizations due to AIDS was not obvious in Yinzhou.
Acquired Immunodeficiency Syndrome/epidemiology*
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HIV Infections/therapy*
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Hospitalization
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Humans
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Retrospective Studies
5.Impact of regional differences in stroke symptom awareness and low-income status on seeking emergency medical service in China.
Jing YUAN ; Guang-Liang SHAN ; Sheng-De LI ; Chun-Peng GAO ; Li-Ying CUI ; Bin PENG
Chinese Medical Journal 2021;134(15):1812-1818
BACKGROUND:
Unawareness of stroke symptoms and low income are two barriers that affect the seeking of emergency medical service (EMS). This study aimed to assess the effect of unawareness and low income on seeking EMS and to investigate the regional distribution of the unawareness and low-income status and their associations with failing to call EMS in China.
METHODS:
A total of 187,723 samples from the China National Stroke Screening Survey was interviewed cross-sectionally. Four status of awareness and annual income were identified: unaware and low-income, unaware-only, low-income-only, and aware and regular income. The outcomes were whether they intended to call EMS or not. The regional distribution of each status and their associations with not calling EMS were presented.
RESULTS:
The status of unaware and low-income, unaware-only, and low-income-only accounted for 6.3% (11,806/187,673), 11.9% (22,241/187,673), and 21.5% (40,289/187,673) of the total sample, respectively. Not calling EMS was significantly associated with the status of unaware and low-income (odds ratio [OR]: 3.21, 95% confidence interval [CI]: 3.07-3.35), unaware-only (OR: 2.38, 95% CI: 2.31-2.46), and low-income-only (OR: 1.67, 95% CI: 1.63-1.71), compared with the aware and regular income status. The Midwest regions had higher percentages of people in the unaware and low-income status; the East, South, and Central had higher percentages of unaware-only status; the North and Northeast regions had a higher percentage of low-income-only status, compared with other regions.
CONCLUSION
The existence of the regional difference in unawareness and low income justifies the specific stroke education strategies for the targeted regions and population.
China
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Emergency Medical Services
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Humans
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Odds Ratio
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Socioeconomic Factors
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Stroke
6.The Application of the Technique in the Protection of PCI
Qi LAI ; Xue-Feng GUANG ; Cheng-De HE ; Zhi-Peng CHEN ; Shu-Nan JING ; Jie FANG
Journal of Kunming Medical University 2018;39(8):39-42
Objective To explore the treatment of percutaneous coronary intervention (PCI), and to comparatively study on the protection of side support by using the active and passive expansion technique.Method 78 patients with coronary artery disease were protected by using balloon technique, there were two groups: the active expansion group (n=41) and the side support balloon (n=37), the TIMI classification、myocardial perfusion rating (MBG), TIMI myocardial perfusion rating (TMP) and the incidence of marginal vascular interlayer were observed and analyzed. Results After the main support was put in, the proportion of patients with side branches of TIMI、 MBG and TMP was at level 3 and the proportion of patients with active balloon expansion was 93%, the margin expansion group was 84%, the difference was not statistically significant (P>0.05); the incidence of intersecting vascular interlayer in active dilatation group was 24%, the margin expansion group was 8%, and there were statistical differences (P<0.05). Conclusions Using the technique of holding balloon to protect the side branches, both the active expansion of the side support balloon and the expansion of the side support balloon can significantly reduce the risk of the main stent placement in the posterior branch of the blood vessel, however the incidence of side branch vascular interlayer was lower.
7.Effect of Qiangjing Tablets on the MAPK signaling pathway in SD rats with asthenospermia.
Guang-Sen LI ; Pei-Hai ZHANG ; Jian CAI ; Xiao-Peng HUANG ; Xu-Jun YU ; Liang DONG ; Yao-Dong YOU ; Di-Ang CHEN ; Lei ZHANG ; De-Gui CHANG
National Journal of Andrology 2018;24(5):436-441
ObjectiveTo investigate the effects of Qiangjing Tablets (QJT) on sperm quality and the MAPK signaling pathway in the SD rat model of asthenospermia (AS).
METHODSA total of 100 male SD rats were randomly divided into five groups of equal number, blank control, AS model control, high-dose QJT, medium-dose QJT, and low-dose QJT. All the rats were intragastrically administered ORN at 200 mg/kg/d for establishment of the AS model except those in the blank control group, which were given 1% CMC sodium solution at 1 ml/100 g by gavage. Meanwhile the animals of the high-, medium-, and low-dose QJT groups were gavaged with QJT at 6700, 3300 and 1700 mg/kg/d, respectively, qd 6 days a week for 20 days. Then the testis issue and the apoptosis of the testicular cells were observed under the electron microscope, the expression of vimentin in the testis was determined with the immunohistochemical SP method, that of ERK1/2 detected by Western blot, and the concentration of TGF-β1 in the semen measured by ELISA.
RESULTSThe AS model controls showed round nuclei of spermatocytes, homogeneously distributed chromatins, broken or lost mitochondria, and expanded rough endoplasmic reticulum in the testis tissue. In comparison, the rats of the high-, medium-, and low-dose QJT groups exhibited round nuclei of spermatocytes, homogeneously distributed chromatins, and well-structured mitochondria, rough endoplasmic reticulum and ribosome, which were all similar those of the blank controls. Compared with the blank controls, the AS model rats manifested significantly increased expressions of ERK1/2 (1.00 ± 0.00 vs 1.26 ± 0.10, P<0.01) and vimentin (0.16 ± 0.01 vs 0.17 ± 0.01, P<0.01) and apoptosis rate of cells in the testis tissue ([9.20 ± 3.07] vs [42.20 ± 9.17] %, P<0.01), but decreased level of TGF-β1 in the semen ([627.67 ± 26.07] vs [566.73 ± 68.44] ng/ml, P<0.05). In comparison with the model controls, the rats of the high- and medium- -dose QJT groups presented remarkably down-regulated expressions of ERK1/2 (1.26 ± 0.10 vs 1.14 ± 0.08, P<0.01; 1.26 ± 0.10 vs 1.18 ± 0.05, P<0.05) and vimentin (0.17 ± 0.01 vs 0.16 ± 0.01, P<0.01; 0.17 ± 0.01 vs 0.17 ± 0.09, P<0.05) and decreased rate of cell apoptosis ([42.20 ± 9.17] vs [21.60 ± 5.94] %, P<0.01; [42.20 ± 9.17] vs [33.95 ± 6.39] %, P<0.05). The concentration of TGF-β1 in the semen was markedly lower in the high-dose QJT than in the AS model control group ([621.78 ± 30.80] vs [566.73 ± 68.44] ng/ml, P < 0.05).
CONCLUSIONSQiangjing Tablets could improve semen quality in asthenospermia rats by acting against oxidative stress.
Animals ; Apoptosis ; Asthenozoospermia ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Mitogen-Activated Protein Kinases ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Semen ; Semen Analysis ; Signal Transduction ; Spermatozoa ; Testis ; metabolism ; ultrastructure ; Transforming Growth Factor beta1 ; metabolism ; Vimentin ; metabolism
8.Understanding Qi Running in the Meridians as Interstitial Fluid Flowing via Interstitial Space of Low Hydraulic Resistance.
Wei-Bo ZHANG ; De-Xian JIA ; Hong-Yan LI ; Yu-Long WEI ; Huang YAN ; Peng-Na ZHAO ; Fei-Fei GU ; Guang-Jun WANG ; Yan-Ping WANG
Chinese journal of integrative medicine 2018;24(4):304-307
Qi, blood and the meridians are fundamental concepts in Chinese medicine (CM), which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.
Acupuncture Points
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Connective Tissue
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physiology
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Extracellular Fluid
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physiology
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Extracellular Space
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physiology
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Humans
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Meridians
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Qi
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Water
9.Development and evaluation of a rapid PCR detection kit for Ophiocordyceps sinensis.
Fei-Xia HOU ; Jing CAO ; Sha-Sha WANG ; Xi WANG ; Yuan YUAN ; Cheng PENG ; De-Guang WAN ; Jin-Lin GUO
China Journal of Chinese Materia Medica 2017;42(6):1125-1129
Ophiocordyceps sinensis is a valuable traditional Chinese medicine. Due to resource shortage, expensive price and huge market demand, there are many adulterants of O. sinensis in markets. Therefore, it is necessary to establish a rapid and effective method for distinguishing O. sinensis. Based on the species-specific PCR of O. sinensis, this study developed a detection kit by optimizing the components and evaluated the specificity, detection limit, repeatability and shelf life of the kit. The results showed that when the quality of O. sinensis accounted for more than 1/200 of that mixture, it could be detected successfully. Moreover, only O. sinensis could be amplified and glowed bright green fluorescence under ultraviolet light. The kit was still in effect when it was placed at 37 ℃ for three days, which indicated that it was stable and effective for one year stored in 4 ℃. The kit in the same batch under different operation conditions, and in different batch under the same operation conditions gave the same result and accuracy, which showed good repeatability of the kit. It is simple, rapid and accurate to distinguish O. sinensis from its adulterants using the kit, and lays the foundation for commercialization of traditional Chinese medicine fast detection kit.
10.Effects of insulin-like peptide 6 on renal fibrosis and calcification in unilateral ureteral obstruction mice
Lei GAO ; yong Shi WU ; Dan JIANG ; Ying WANG ; yong Yong LI ; wei De WANG ; lei Guang CHANG ; Peng ZHANG ; Zheng QIN ; ying Dong ZHANG
Journal of Shanghai Jiaotong University(Medical Science) 2017;37(12):1616-1622
Objective·To investigate the effects of insulin-like peptide 6 (Insl6) on renal fibrosis and calcification in unilateral ureteral obstruction (UUO) mice. Methods·Twenty-four SPF male mice with genotypic background of C57BL/6 were divided into Sham (n=8), UUO+saline (n=8) and UUO+Insl6 (n=8) groups randomly. Mice were sacrificed 10 days after operation and renal tissues of surgical side were obtained. Sirus red staining, Masson staining and alizarin red S staining were used to verify the level of collagen and calcium deposition. TGF-β1 expression was determined by Western blotting. Realtime-PCR was used for determining TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression. Results·Compared with sham group, fibrotic area especially collagen Ⅰ , calcium deposition, TGF-β1 protein, and TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression in UUO+saline group significantly increased (all P<0.05). As compared with UUO+saline group, fibrotic area especially collagen Ⅰ, calcium deposition, TGF-β1 protein, and TGF-β1, BMP2, Col1a1, and Col2a1 mRNA expression in UUO+Insl6 group significantly decreased (all P<0.05). Conclusion·Insl6 inhibits UUO-induced renal fibrosis and calcification, which may be related to regulation of TGF-β1, collagen Ⅰ , BMP2 and collagen Ⅱ expression levels.

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