1.Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
Kaijun JIN ; Minjie LIU ; Chunlin ZHUANG ; Erik DE CLERCQ ; Christophe PANNECOUQUE ; Ge MENG ; Fener CHEN
Acta Pharmaceutica Sinica B 2020;10(2):344-357
In order to improve the positional adaptability of our previously reported naphthyl diaryltriazines (NP-DATAs), synthesis of a series of novel biphenyl-substituted diaryltriazines (BP-DATAs) with a flexible side chain attached at the C-6 position is presented. These compounds exhibited excellent potency against wild-type (WT) HIV-1 with EC values ranging from 2.6 to 39 nmol/L and most of them showed low nanomolar anti-viral potency against a panel of HIV-1 mutant strains. Compounds and had the best activity against WT, single and double HIV-1 mutants and reverse transcriptase (RT) enzyme comparable to two reference drugs (EFV and ETR) and our lead compound NP-DATA (). Molecular modeling disclosed that the side chain at the C-6 position of DATAs occupied the entrance channel of the HIV-1 reverse transcriptase non-nucleoside binding pocket (NNIBP) attributing to the improved activity. The preliminary structure-activity relationship and PK profiles were also discussed.
2.Effect of high dose irradiation on thermoluminescence detector
Shuzhou RUAN ; Zhixin ZHAO ; Wenyi ZHANG ; Kaijun SU ; Xinxin PANG ; Fang WANG ; Yulian LIU ; Menghui HUO ; Changxin YAN ; Ling JIAO
International Journal of Biomedical Engineering 2019;42(4):342-345
Objective To investigate effect of high dose irradiation on the performances of thermolumines-cence detectors (LiF:Mg, Cu, P). Methods The high-dose irradiated thermoluminescence detector was annealed by a thermoluminescence annealing furnace until the annealing was completed, and then the annealed thermoluminescent detector was irradiated 0.5Gy by 137Cs irradiator to verify the accuracy of the thermoluminescentdetector. Results The thermoluminescence detector after high-dose irradiation could not be completely annealed under the temperature condition of 240 ℃, and it could be completely annealed at a high temperature as 400℃. After 0.5 Gy irradiation by 137Cs irradiator, the measurement results of the annealed thermoluminescence detector were significantly smaller, and the dose response and dispersion of the detector were also changed significantly. Conclusions After a more than 5 Gy irradiation, the crystal structure of the thermoluminescence detector has changed, and a high temperature peak above 240 ℃ has appeared, which leads to the failure to completely anneal at normal temperature. Therefore, the thermoluminescence detector can no longer be used for dosimetry after high-dose irradiation.
3.Analysis of factors affecting the prognosis of neonatal cholestasis
Xiufang YANG ; Guosheng LIU ; Kaijun ZHENG ; Qiang LIN ; Jian CHEN ; Huijuan HUANG
Chinese Journal of Postgraduates of Medicine 2018;41(6):481-485
Objective To analyze the influential factors of the prognosis of neonatal cholestasis. Methods The data on 106 newborns with neonatal cholestasis collected from January 1, 2009 to June 30, 2016 was collected and analyzed retrospectively. All cases were divided into cure group (99 patients) and improvement group (7 patients) according to the effect of oral ursodeoxycholic acid therapy and comprehensive medical treatment. There was no cure for invalid case. The clinical features, course of disease and curative effect were observed. The levels of total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (γ-GT), total bile acid (TBA) were compared between two groups. The ratio of neonatal bacterial infection, cytomegalovirus (CMV) infection, sex, total intravenous nutrition (more than 7 d), perinatal hypoxia, premature birth, maternal complicated intrahepatic cholestasis of pregnancy (ICP) were compared between two groups. Multiple Logistic regression analysis was used to analyze the prognosis factors of neonatal cholestasis. Results The levels of serum ALT, AST, γ-GT, TB, DB and TBA in improvement group were significantly higher than those in cure group, the course of disease in improvement group was significantly longer than that in cure group, there were significant differences (P<0.05). A strong linear correlation was showed between course of disease and the levels of serum ALT, AST, TB, DB and TBA (tALT=13.050, tAST=14.696, tTB=12.771, tDB=13.776, tTBA=12.019, P < 0.05). Multiple Logistic regression analysis showed that the prognosis of neonatal cholestasis was associated with bacterial infection, CMV infection, total intravenous nutrition (more than 7 d) and premature ( OR=9.375, 7.909, 11.333, 11.333, P < 0.05). Conclusions The higher the level of serum TB, DB, TBA, ALT and AST, the longer the course of the disease. Bacterial infection, CMV infection, total venous nutrition( ≥ 7 d) and premature are the risk factors of the prognosis of neonatal cholestasis. Therefore, prevention of neonatal bacterial and CMV infection, reduction of the occurrence of preterm delivery and reduction of the total parenteral nutrition time are very important to improve the prognosis of neonatal cholestasis.
4.Study on the relationship between thyroid imaging reporting and data system and the Bethesda system for reporting thyroid cytopathology
Hao ZHANG ; Xuedong ZHANG ; Liping CHENG ; Xianbin ZHAO ; Kaijun LIU ; Hailin ZHANG
Chinese Journal of Postgraduates of Medicine 2018;41(11):998-1001
Objective To compare effect between thyroid imaging reporting and data system (TI-RADS) and the Bethesda system for reporting thyroid cytopathology (TBSRTC) in the qualitative diagnosis of thyroid nodule. Methods The clinical data of 665 patients with thyroid nodule (1 598 nodules) from April 2013 to October 2016 were retrospectively analyzed. TBSRTC and TI-RADS were used for qualitative diagnosis of thyroid nodule before operation. Pathological diagnosis was performed after the operation. The diagnostic effect of TI-RADS and TBSRTC were assessed, and the factors leading to the diagnostic errors were analyzed. Results Of 1 598 thyroid nodules, the pathological diagnosis showed that benign nodules were in 202, and malignant thyroid nodules were in 1 396. The diagnostic sensitivity and 85.64%(173/202) vs. 74.75%(151/202) and specificity of malignant nodules by TBSRTC were significantly higher than that by TI-RADS: 91.76% (1 281/1 396) vs. 87.11% (1 216/1 396), and there was statistical difference (P<0.01). The diagnosis positive rate of malignant nodules with diameter<1 cm by TBSRTC was significantly higher than that by TI-RADS: 77.63% (59/76) vs. 47.37% (36/76), and there was statistical difference (P<0.01); there was no statistical difference in diagnosis positive rate of malignant nodules with diameter ≥ 1 cm between 2 methods (P>0.05). Univariate analysis result showed that the diameter of thyroid nodules in patients with TI-RADS false negative was significantly smaller than that in patients with benign thyroid nodules: (1.01 ± 0.48) cm vs. (1.51 ± 0.45) cm, the incidence of malignant thyroid nodules combined with other thyroid diseases was significantly higher than that in patients with benign thyroid nodules: 41.18% (21/51) vs. 11.32% (158/1 396), and there were statistical differences (P<0.05); the rate of thyroid dysfunction in patients with TBSRTC false positive was significantly higher than that in patients with malignant thyroid nodules: 18.26% (21/115) vs. 6.93% (14/202), and there was statistical difference (P<0.05). Conclusions The qualitative diagnosis of thyroid nodule requires the cross-reference of TI-RADS and TBSRTC, and the combination of other clinical indicators of patients can improve the detection rate of malignant thyroid nodules.
6.Treatment of thoracolumbar tuberculosis by transforaminal endoscopic debridement combined with allograft and percutaneous internal fixation
Zhengping ZHANG ; Kaijun WANG ; Xiaoming WANG ; Xingang WANG ; Guangru CHEN ; Wanli FENG ; Qinpeng ZHAO ; Tuanjiang LIU ; Hua GUO ; Jianming WEI ; Dingjun HAO
Chinese Journal of Orthopaedics 2018;38(8):468-476
Objective To discuss the feasibility,the advantages and disadvantages,the clinical efficacy and the indications of minimally invasive transforaminal endoscopic debridement combined with allograft and posterial percutaneous internal fixation for thoracolumbar spinal tuberculosis.Methods All of 22 patients with thoracolumbar tuberculosis treated in our department from January 2012 to December 2013 were retrospectively reviewed.There are 11 male and female cases separately,with an average age of 54.1 ±10.2 years and with an average disease duration of 5.3 ± 1.9 months.Endoscopic lesion removal and allograft bone grafting combined with posterial percutaneous immobilization were performed on all these cases.The data of these patients were complete,and all patients had been followed up for more than 36 months.The clinical and radiographic results were recorded and analyzed.Results In this group,22 patients were followed-up for 41.9±2.5 months(36-48 months).The spinal kyphosis was not improved 3 months after surgery (t=0.3546,P=0.7029),but the amount of blood loss (30.5±7.9 ml) was less in the operation,the amount of postoperative analgesics(0.3±0.1 g) was low and the bed time(1.5±0.3 days) was short.No recurrence and no internal fixation failure was found after long term follow-up.Good clinical outcomes were achieved with the fusion rate reached above grade 2 in all patients(95.5%) except one.The neuralgia was relieved,and the spinal cord injury was recovered to ASIA E.The VAS score and SF-36 score which were recorded 1 month and 3 months after operative were all improved significantly compared with those before operation,and patients' life quality in the early period after operation was excellent.The incidence of complications was low(9.0%),and the patients were satisfied with the treatment process.Conclusion It may be a potential way to treat spinal tuberculosis with minimally invasive transforaminal endoscopic debridement combined with allograft and percutaneous internal fixation,which could be a powerful supplement to other therapeutic measures,and is worthy of further research and development.
7.Study on the effect of serum uric acid on metabolic disorders
Li LIU ; Qing ZHANG ; Kun SONG ; Yan LIU ; Jing CUI ; Xiaoyan GONG ; Kaijun NIU
Chinese Journal of Health Management 2018;12(3):216-224
Objective To evaluate the prediction value of serum uric acid level in the occurrence of multiple metabolic disorders.Methods The subjects are from the Health Management Centre,Tianjin Medical University General Hospital.Four kinds of metabolic diseases,namely type 2 diabetes mellitus,hypertension,hyperlipidemia,and nonalcoholic fatty liver disease (NAFLD),were analyzed by four-cohort analysis.Sample sizes were 56 915,47 387,31 431,and 35 203.The average follow-up time for each cohort was (3.56±2.32),(3.31±2.24),(2.70±1.95),(2.90± 1.76) years,respectively.In each cohort,the population was divided into two groups,depending on the occurrence of type 2 diabetes,hypertension,hyperlipidemia,and NAFLD during follow-up.All relevant variables were tested for baseline and follow-up,including laboratory tests,lifestyle questionnaire,and physical examination.Statistical analysis by Cox proportional hazard regression model was performed for the relationships between the fifth percentile of the distribution of serum uric acid levels and incidence of type 2 diabetes,hypertension,hyperlipidemia,and NAFLD.Results During the follow-up period,the incidence of type 2 diabetes,hypertension,hyperlipidemia,and NAFLD were 3.5%,17.6%,33.4%,and 15.7%,respectively.After adjustment for confounding factors,with the increase in serum uric acid level,the hazard ratios (95%CI) of type 2 diabetes were 1.00,0.82 (0.70,0.95),0.80 (0.69,0.92),0.77 (0.67,0.88),and 0.83 (0.72,0.95) (P=0.02).Meanwhile,higher risk of hypertension,hyperlipidemia,and NAFLD were associated with elevated serum uric acid level.In the group with the highest serum uric acid level in each cohort,the hazard ratio (95%CI) of hypertension,hyperlipidemia,and NAFLD were 1.17 (1.09,1.25),1.20 (1.13,1.28),and 1.56 (1.43,1.70),respectively (P< 0.01),as compared to the group with the lowest level.Conclusion Serum uric acid levels have a positive predictive value for the occurrence of hypertension,hyperlipidemia,and NAFLD,but have a negative predictive value for type 2 diabetes.
8.Relationship between white blood cell count and nonalcoholic fatty liver disease in an adult population
Kun SONG ; Haiyan XU ; Zuolin LU ; Hongbin SHI ; Li LIU ; Qing ZHANG ; Kaijun NIU
Chinese Journal of Health Management 2017;11(3):201-205
Objective To investigate the relationship between white blood cell count (WBC) and the prevalence of simple fatty liver disease (SFL) and nonalcoholic steatohepatitis (NASH). Methods We designed a large scale cross-sectional study in an adult population. Participants were selected from Tianjin Medical University's General Hospital-Health Management Centre. The diagnoses of simple fatty liver disease and nonalcoholic steatohepatitis were based on liver ultrasonography and serum alanine aminotransferase concentration. A total of 37507 subjects (8644 SFL and 2557 NASH) were included in this study. Multiple logistic regression analysis was used to assess whether the quartiles of WBC were associated with the prevalence of simple fatty liver disease and nonalcoholic steatohepatitis. Results After adjusting for potential confounders, the odds ratios (95% confidence interval) of simple fatty liver disease and nonalcoholic steatohepatitis for increasing quartiles of WBC were: simple fatty liver disease, 1.00 (reference), 1.37 (1.24, 1.50), 1.70 (1.55, 1.86) and 2.09 (1.90, 2.29) (P for trend<0.0001);nonalcoholic steatohepatitis, 1.00 (reference), 1.39 (1.16, 1.66), 1.69 (1.43, 1.99) and 2.13 (1.81, 2.50) (P for trend<0.0001). Conclusions This study proves the correlation between WBC and the prevalence of simple fatty liver disease and nonalcoholic steatohepatitis. Further study is needed to clarify whether WBC has a predictive value for the occurrence of nonalcoholic fatty liver disease.
9.Relationship between the infection rate of Helicobacter pylori and frequency of capsicum intake in dietary pattern
Hongbin SHI ; Qing ZHANG ; Kaijun NIU ; Kun SONG ; Li LIU
Chinese Journal of Health Management 2017;11(1):52-55
Objective To explore the association between the infection rate of Helicobacter pylori (Hp) and intake frequency of capsicum in dietary pattern. Methods A total of 914 health check-up participants were recruited from Tianjin Medical University General Hospital (male: 510,female:404). All participants were asked about the intake frequency of capsicum. Diagnostic criteria of the Hp infection included positive C13 breath test. Results The intake frequency of capsicum was ≥2 times/week, 1 time/week and <1 time/week. The infection rate of Hp was 56.08%, 49.04% and 48.29%. After adjusting for covariates, compared with the≥2 times/week, the odds ratios(95%confidence interval)of intake frequency of capsicum 1 time/week and <1 time/week: the frequency of capsicum intake ≥2 times/week was 1.00 (reference), the frequency of capsicum intake 1 time/week was 0.57(0.33-0.97) and the frequency of capsicum intake<1 time/week was 0.69(0.42-1.14) in men;the frequency of capsicum intake≥2 times/week was 1.00 (reference), the frequency of capsicum intake 1 time/week was 1.01(0.54-1.88), and the frequency of capsicum intake<1 time/week was 0.71(0.41-1.23) in women. Conclusions This study found that food intake frequency of capsicum≥2 times/week was associated with the infection rate of Hp in men. But similar relationship was not observed in women.
10.Relationship between serum uric acid and dietary patterns in Tianjin residents
Li LIU ; Qing ZHANG ; Kun SONG ; Xiaoyan GONG ; Jing CUI ; Ying GAO ; Kaijun NIU
Chinese Journal of Health Management 2017;11(1):40-46
Objective To investigate the relationships between different dietary patterns and serum uric acid in Tianjin residents. Method By cross-sectional study design, 11282 subjects were studied via lifestyle questionnaires (including a valid food frequency questionnaire), physical examination and laboratory tests. Using factor analysis method to establish the dietary patterns, and relationships between different dietary patterns and serum uric acid were analyzed. Results Factor analysis showed 3 kinds of dietary patterns, including eastern dietary pattern, vegetable diets and Tianjin dietary pattern. There were more males in hyperuricemic population, who have a higher BMI, waist circumference, blood lipids, blood pressure and blood sugar levels, and also higher proportion of metabolic syndrome, smokers and alcohol drinkers. In addition, hyperuricemia patients had a higher level of social status and income. After adjustments for age, sex, BMI, smoking habits, alcohol consumption, hypertension, hyperlipidemia, education level, occupational status, energy intake, physical activity and metabolic syndrome, logistic regression analysis showed the odds ratio (95%confidence interval) for hyperuricemia across the quartiles of 3 dietary patterns as follows: 1.00, 1.07 (0.91, 1.25), 0.96 (0.82, 1.14), 1.12 (0.94, 1.33);1.00, 1.03 (0.88, 1.21), 1.04 (0.88, 1.23), 1.00 (0.84, 1.19); 1.00, 1.28 (1.08, 1.52), 1.40 (1.22, 1.71), 1.37 (1.15, 1.63), respectively. Significantly positive correlation was shown between Tianjin dietary pattern and hyperuricemia. Conclusion Tianjin residents' Tianjin dietary pattern is closely related to serum uric acid levels. Tianjin dietary patterns have characteristics of high calorie, high fat, high protein. Healthy eating habits have significant importance to prevent occurrence of hyperuricemia.

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