1.Activity of cyclic diguanylate (c-di-GMP) in bacteria and the study of its derivatives.
Acta Pharmaceutica Sinica 2012;47(3):307-12
Cyclic diguanylate (c-di-GMP) is a ubiquitous second messenger present in a wide variety of bacteria, which is responsible for cell differentiation, biofilm formation, pathogenic factor generation, and so on. The level of c-di-GMP in bacteria is regulated by two opposing active domains, diguanylate cyclase (DGC) and phosphodiesterase (PDE), which are present in the same bifunctional protein, and in charge of the synthesis and the degradation of c-di-GMP, respectively. The target of c-di-GMP in the bacterial cell consists of PilZ domain and GEMM riboswitch, the only riboswitch that involved in signal transduction. This article gives an overview of c-di-GMP, focusing on its metabolic pathway, regulatory mechanism, biological function of c-di-GMP, and the synthesis of c-di-GMP analogues and their biological activity.
2.Design and synthesis of photoaffinity biotin labelled 2'-O-propargyl-guanosine.
Luxin NA ; Xin LIU ; Zhuoming MENG ; Zhu GUAN ; Lihe ZHANG ; Zhenjun YANG
Acta Pharmaceutica Sinica 2015;50(1):59-63
Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.
3.Research progress on chemical composition, analytical methods, and pharmacological effects of Ophiopogon polysaccharides
Luxin ZHANG ; Xueqian ZHOU ; Dekun LI ; Dazheng ZHOU ; Yuewu YANG ; Boyang YU ; Aichun JU
Drug Evaluation Research 2017;40(2):279-284
The main ingredients of Ophiopogonjaponicas include steroidal saponins,flavonoids,polysaccharides,and so on,but the research on polysaccharides is relatively less.This particle will mainly review the chemical composition,analytical methods,and pharmacological effects of Ophiopogon polysaccharides.The Ophiopogon polysaccharides contain a variety of substances,such as MDG-1,Md-1,Md-2,OJP-1,etc;The main analysis methods were sulfuric acid method,phenol-sulfuric acid method,3,5-dinitrosalicylic acid (DNS) colorimetric method,and near-infrared spectroscopy combined with partial least squares regression method.Ophiopogon polysaccharides can effectively improve the cardiovascular system diseases,with antihypoxia,anti-inflammatory,antitumor,anti-oxidation,and other pharmacological effects.
4.Comparative study of lateral position and half lithotomy position in Asian proximal femur intramedullary nail antirotation system internal fixation for treatment of elderly patients with femoral inter-trochanteric fractures
Xiaohua ZHANG ; Shuqing ZHOU ; Bowen YANG ; Luxin YU ; Ming ZHU ; Youxin LIAO ; Jian YE ; Qiuwen ZHU
Chinese Journal of Trauma 2020;36(6):503-508
Objective:To compare the therapeutic effect of lateral position and half lithotomy position in Asian proximal femur intramedullary nail antirotation system (PFNA-II) for treating the elderly patients with femoral intertrochanteric fractures.Methods:A retrospective case control study was made on 141 patients with femoral intertrochanteric fractures admitted to Jiangjin Central Hospital from January 2016 to September 2017, including 54 males and 87 females, aged 65-99 years (mean, 80.4 years). According to AO classification, there were 42 patients with type A1 fractures, 88 with type A2 and 11 with type A3. Of all, 74 patients were stabilized by PFNA-II internal fixation in lateral position (lateral position group) and 67 patients by PFNA-II internal fixation in half lithotomy position (half lithotomy position group). The postural placement time, total incision length, operative time, intraoperative blood loss, fluoroscopy frequency, tip-apex distance, reduction quality, fracture healing time, postoperative complications and Harris hip function at 12 months after surgery were compared between the two groups.Results:All patients were followed up for 12-18 months (mean, 12.5 months), except that 13 patients were lost after 9 months, an average of 12.5 months. There were no statistically significant differences in postural placement time, operative time, fracture healing time, and Harris hip score between the two groups ( P>0.05). While significant differences were seen between lateral position group and half lithotomy position group regarding the incision length [(6.5±1.3)cm vs. (7.5±1.5)cm], intraoperative blood loss [(84.3±3.1)ml vs. (90.4±3.9)ml], fluoroscopy frequency [(13.1±1.9)times vs. (11.2±1.2)times], tip-apex distance [(20. 6±2.2)mm vs. (24.4±1.8)mm], good rate of reduction quality (80% vs. 85%) and implant related complications (5% vs. 2%) ( P<0.05 or 0.01). Conclusion:For treatment of elderly patients with intertrochanteric fractures, compared to the lateral position, the half lithotomy position in PFNA-II internal fixation can reduce frequency of fluoroscopy, improve quality of fracture reduction and reduce implant-related complications.
5.Clinical analysis of metagenome next-generation sequencing for diagnosing invasive fungal disease in patients with early stage of hematopoietic stem cell transplantation
Yuhan JI ; Mingyue PAN ; Xiaoyu LAI ; Lizhen LIU ; Jimin SHI ; Yanmin ZHAO ; Jian YU ; Luxin YANG ; Yi LUO
Journal of Army Medical University 2024;46(4):311-318
Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0%(95%CI:64.1%~75.9%)and 20.0%(95%CI:11.9%~32.5%),respectively,while those of the fungal infection patients were 54.5%(95%CI:49.5%~69.5%)and 36.4%(95% CI:15.5%~70.3%),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.
6.Risk assessment of dietary exposure to 3-monochloropropane-1,2-diol esters in infant formula powders in Shanghai
Luxin QIN ; Baozhang LUO ; Hua CAI ; Jingjin YANG ; Danping QIU ; Hong LIU ; Chunfeng WU
Journal of Environmental and Occupational Medicine 2023;40(6):700-704
Background Chloropropanol esters (MCPDE) have attracted much attention in recent years as a kind of new contaminant found in various refined oils. The pollution of 3-monochloropropane-1,2-diol esters (3-MCPDE) is the most prominent. 3-MCPDE is hydrolyzed in organisms to 3-monochloropropane-1,2-diol which has been shown to have reproductive toxicity, nephrotoxicity, and potential carcinogenicity. Infant formula powders can be polluted by 3-MCPDE when refined edible oils are added during production. Objective To assess the risk of exposure to 3-MCPDE related to the consumption of infant formula powders for children aged 0-3 years in Shanghai market using the food consumption data and the data of 3-MCPDE contamination in these foods. Methods Gas chromatography-mass spectrometry was used to determine 3-MCPDE in 133 samples of infant formula powders in Shanghai. Using a multistage stratified random sampling method, a total of 807 infants and toddlers aged 0-3 years were randomly selected from each district/rural/town in Shanghai, including 208 children aged 0-6 months, 276 children aged 6-12 months, and 323 children aged 12-36 months. The food consumption data was investigated using food frequency questionnaire (FFQ) distributed by combining telephone inquiries and face-to-face interviews among guardians. Population's probability distributions of 3-MCPDE exposure were assessed by @Risk 7.5 software and Monte Carlo simulation algorithm. According to the dietary intake assessment model and the tolerable daily intake (TDI) of 3-MCPDE of 2.00 μg·(kg·d)−1 proposed by the European Food Safety Authority (ESFA), a risk assessment of exposure to 3-MCPDE was conducted for infants and toddlers aged 0 to 3 years old in Shanghai who consumed 3-MCPDE via infant formula powders. Results The average concentration of 3-MCPDE in 133 samples of infant formula powders was 0.115 mg·kg−1 with a positive rate of 100.00%. Among different types of formula powders, infant formula powders for infants of 0-6 months had the highest concentrations of 3-MCPDE and fat [0.136 mg·kg−1 and 25.2 g (per 100 g sample) in average respectively]. There was a positive correlation between fat concentration and 3-MCPDE concentration in the samples (r=0.438, P<0.05). The average consumption of infant formula powders of 807 infants aged 0-3 years was 88.3 g·d−1. Among all investigated age groups, the average consumption of infant formula powders by infants aged 0-6, 6-12, and 12-36 months was 87.7, 98.3, and 80.1 g·d−1 respectively. The dietary exposure to 3-MCPDE from infant formula powders of infants aged 0-3 years averaged 0.83 μg·(kg·d)−1 for general intake level or valued 1.44 μg·(kg·d)−1 using the 95 percentile for high intake level. Exposure decreased with increasing age and was highest in infants 0-6 months of age, whose general and high intake levels were 1.41 and 2.34 μg·(kg·d)−1, respectively. The risk population defined with the exposure higher than the TDI proposed by EFSA were proportioned to be 13.90% and 0.50% in infants aged 0-6 months and 6-12 months respectively, indicating a risk that cannot be ignored, and no risk in infants aged 12-36 months. Conclusion Among the investigated infants aged 0-3 years in Shanghai, those aged 0-6 months are at a high risk of exposure to 3-MCPDE. In view of the sensitivity of infants to pollutant exposure, the risk of exposure to 3-MCPDE should be highly concerned.
7.Risk assessment of cadmium exposure of Shanghai residents based on different dietary exposure assessment methods
Hua CAI ; Baozhang LUO ; Luxin QIN ; Danping QIU ; Jingjin YANG ; Xia SONG ; Biyao XU ; Zhenni ZHU ; Hong LIU ; Chunfeng WU
Shanghai Journal of Preventive Medicine 2024;36(3):224-229
ObjectiveTo conduct comprehensive assessment of internal and external cadmium exposure and health risks for Shanghai residents. MethodsCadmium levels in food samples were calculated by employing two dietary exposure assessment methods, total diet study (TDS) and food frequency questionnaire (FFQ), to estimate the daily dietary cadmium exposure of Shanghai residents. The provisional tolerable monthly intake (PTMI) of cadmium set by joint food and agriculture organization/WHO expert committee on food additives (JECFA) was applied to evaluate the health risk. Differences in dietary and urinary cadmium were compared by rank-sum test among different regions, age, gender, smoking status, and BMI groups, and the association between internal and external cadmium exposure was investigated by correlation analysis. ResultsThe mean value of urinary cadmium for 1 300 respondents was 0.542 μg·L-1. Urinary cadmium was higher in the population in central urban and urban-rural fringe areas than in the suburban area, higher in the older age group than in the younger age group, and higher in the smoking group than in the non-smoking group (all P<0.01). The two assessment methods showed that the mean values of daily dietary cadmium exposure for Shanghai residents were 0.306 and 0.090 μg·kg-1, with 3.69% and 0.85% of Shanghai residents exceeding the PTMI, respectively. Correlation analyses showed that dietary exposure to cadmium based on the FFQ method was positively correlated with the urinary cadmium level when smoking status, age, gender, and BMI were adjusted. ConclusionDietary exposure to cadmium of Shanghai residents is mainly derived from vegetables, aquatic products, cereals and potatoes, and is overall at a low-risk level. Dietary exposure assessment based on FFQ and risk monitoring data can effectively estimate long-term cadmium exposure.