1.Screening for selective TGF-βⅠinhibitors and structure-activity relationship analysis
Long LONG ; Feifei LI ; Xingzhou LI ; Wei CHEN ; Wei LI ; Lili WANG
Journal of International Pharmaceutical Research 2017;44(6):544-550
Objective To screen for selective transforming growth factor β(TGF-β)inhibitors from the compound library, and analyze their structure-activity relationship. Methods The inhibiting activities of 170 compounds to TGF-βpathway were evaluat-ed by the SMAD3 luciferase reporter system;the positive hits were examined for their selectivity towards activin receptor like kinase (ALK)4、ALK5 or ALK7 by a molecule based screening system composed of SMAD3,ATP and the purified kinase domain for ALK4, ALK5 or ALK7;the EGFP-SMAD2 fusion protein redistribution assay was used to confirm the inhibiting effects of positive hits. The structure-activity relationship was analyzed by comparing the docking module of SB431542 with ALK5 kinase domain. Results Fif-teen compounds were found capable of inhibiting luciferase expression downstream of SMAD3 with≥25%inhibitory rate;several of them showed different selectivity towards ALK4,ALK5 and ALK7. Compound 63 selectively inhibited the activity of ALK4 and ALK7 with IC500.234 and 0.370μmol/L,respectively,while compound 64 showed inhibiting activity towards all three kinases with the IC50 values 10,6 and 85 nmol/L for ALK4、ALK5 and ALK7,respectively. In addition,compounds 63 and 64 further inhibited the TGF-β1 induced EGFP-SMAD2 nuclear translocation,with the IC50 values of 0.45 and 6.30μmol/L,respectively. The MTT anti-proliferative assay indicated that compounds 63 and 64 exerted these activities at non-toxic concentrations. The analysis of structure-activity rela-tionship indicated that the compounds sharing a core structure,the 1,2,4-triarylimizazole or 1,3,5-triarylpyrazoline,with the 3,4 methyoenedioxyphenyl,6-methylpyridine and 4-aminocarboxyl substitution groups tended to exhibit better activities. Conclusion The two potent TGF-βpathway inhibitors,63 and 64 are identified through this screening project,of which,63 selectively inhibited the ALK4 and ALK7 activity,while 64 showed inhibiting activity towards all three tested types of ALKs.
2.Advances in the relationships between gastrointestinal microbiota and cancer
Haiyan LI ; Long CHU ; Wei LI ; Zhi XIONG ; Xinya LI
Chinese Journal of Microbiology and Immunology 2016;36(6):477-480
Commensal microorganisms that colonize barrier surfaces of all multicellular organisms exist in harmony with their hosts and have an important effect on both immune and non-immune functions of their hosts. Numerous researches have shown that gastrointestinal microbiota being one of the most important commensal microorganisms plays a critical role in the occurrence, development and treatment of cancer. As-signing causal roles in cancer to specific microbes and microbiotas, unraveling host-microbiota interactions with environmental factors in carcinogenesis, and applying such knowledge to cancer diagnosis and treatment are areas of intensive interest. This review considers how microbes and the microbiota may amplify or miti-gate carcinogenesis, responsiveness to cancer therapeutics, and cancer-associated complications.
3.Relationships among posttraumatic growth, social support, and coping style in women with infertility
Yongju YU ; Li PENG ; Long CHEN ; Ling LONG ; Wei HE ; Jing LI ; Min LI
Chinese Journal of Behavioral Medicine and Brain Science 2013;22(8):707-709
Objective To explore the relationships among posttraumatic growth (PTG),social support,and coping style in women with infertility.Methods 182 women with infertility were recruited in one public hospital department of assisted reproduction technology.Measures included Posttraumatic Growth Inventory (PTGI),Perceived Social Support Scale (PSSS),and Simplified Coping Style Questionnaire (SCQ).Results ① The PTG score of women with infertility was 42.55 ± 16.83,lower than the average level.② Compared with the lower PTG group,the higher PTG group scored significantly higher in social support,positive coping,and negative coping (t =3.867,P< 0.01 ; t =8.452,P< 0.01 ; t =2.817,P< 0.01).③ There were significantly positive correlations among PTG,social support and positive coping (r =0.295-0.515,P < 0.01).④ Positive coping served as a total mediator in the relationship between social support and PTG.Conclusion There are closely correlations among PTG,social support,and positive coping style.Positive coping style significantly mediate the relationship between social support and PTG.
4.The study of dual energy X-ray absorptiometry on body composition components in obesity
Zhongkui HUANG ; Wei CHEN ; Liling LONG ; Xiaoyang LI
Chinese Journal of Radiology 2009;43(6):579-584
Objective To study the correlation of the bone mineral density (BMD) and the body composition components of body mass index (BMI), FAT and LEAN in Chinese obesity. Methods There were 150 cases in obesity group diagnosed by BMI, including 75 males[ median age 46 years, mean weight (89. 64±8. 33) kg] and 75 females[ median age 45 years, mean weight (77.23±6. 85) kg]. There were 150 persons with normal BMI in the control group, including 75 males [ ( median age 47 years, mean weight (62. 34±5.72) kg] and 75 females [ median age 45 years, mean weight (50. 16±5.06) kg]. The body height and weight of 300 persons in two groups were measured respectively and, simultaneously calculated the BMI. These data and the body composition parameters measured by the dual energy X-ray absorptiometry (DEXA) in these two groups were compared and analyzed. The data obtained used two-sample t-test analysis, bi-variable correlation used Pearson linear correlation analysis and multi-variable correlation used multiple linear regression analysis. Results FAT of arms, legs, trunk and total body of male cases in obesity group was (2.90±0.57), (7.48±1.46), ( 15.67±3.05 ), ( 30.92±5.94 ) kg respectively, FAT% was ( 30.9±5.1 ) %, ( 30.6±5.8 ) %, ( 37. 3±4.7 ) %, ( 35.1±4.4 ) % respectively, it was significantly higher than that in control group [ FAT was ( 1.12±0. 64 ), (3.27±1.22), (6. 71±3. 29 ), ( 11.61± 5. 16) kg respectively,FAT% was( 15.4±4. 8)%, ( 16. 5±5.0)%, (21.8±5.8)%, ( 18.6±5. 3)% respectively] ,P <0. 01 ;LEAN of trunk and total body of male cases in obesity group was (27.65±4. 08), (57. 09±7.08 ) kg respectively ; BMD was ( 0. 99±0. 09 ), ( 1.22±0. 09 ) g/cm2 respectively, it was significantly higher than that in control group [ LEAN was ( 22. 89±1.68 ), (48.89 s 3.72 ) kg respectively, BMD was( 0. 89±0. 07 ), ( 1.15±0. 06 ) g/em2 respectively ], P < 0. 01 ; LEAN of arms and legs of male cases in obesity group was(6.22±0.92), (17.31±2.65) kg respectively; BMD was(0.92±0. 04), (1.31±0. 09)g/cm2 respectively,and there were no statistical significance compared with those in control group [ LEAN was ( 5.99±0. 72 ), ( 16. 83±1.67 ) kg respectively, BMD was ( 0. 90±0. 08 ), ( 1.29± 0.09) g/cm2 respectively]. FAT of arms, legs, trunk and total body of females in obesity group was (3.78±1.53), ( 12. 61±3.72), ( 17. 56±2. 59), (33.71±6. 96) kg respectively, FAT% was (33.8± 4.0)%,(40. 1±6.9)%,(43.9±4.9)%, (43.5±4.2)% respectively, LEAN was(7.28±0.94), ( 14. 40 ±2. 05 ), ( 20. 71±3.08 ), ( 43.43±5.69 ) kg respectively, BMD was ( 0. 86±0. 08 ), ( 1.27± 0. 12),(0.95±0. 14), (1.19±0.09)g/cm2 respectively, they were significantly higher than those in control group [ FAT was(2. 04±0. 79), (3.79±0. 94), (6. 89±2. 56), ( 14. 68±3.57) kg respectively, FAT% was (27. 2±4. 5 ) %, ( 29. 6±3.9 ) %, ( 31.0±3.8 ) %, ( 25.9±4. 9 ) % respectively, LEAN was (5. 25±0. 63), ( 10. 65±1.44), ( 16. 65±1.50), (33. 10±3.22) kg respectively, BMD was (0. 78± 0. 04), ( 1.11±0. 09), ( 0. 82±0. 07 ), ( 1.05±0. 07 ) g/cm2 respectively ], P < 0. 01. Conclusion The significantly increasing of fat tissue in all parts of body is a major cause of change of body composition components in obesity. FAT in the trunk increases more obviously than that in other parts of the body in both males and females. The change of distribution of FAT and LEAN can obviously influence BMD.
5.Therapeutic Effects of Berberine Capsule on Patients with Mild Hyperlipidemia.
Li WANG ; Long-yun PENG ; Guo-hong WEI ; Hui GE
Chinese Journal of Integrated Traditional and Western Medicine 2016;36(6):681-684
OBJECTIVETo observe the therapeutic effects of Berberine Capsule (BC) on patients with mild hyperlipidemia.
METHODSTotally 102 mild hyperlipemia patients were recruited. All patients were suggested to have proper diet and physical activity as basic therapy for 1 month of run-in period. Totally 97 patients completed it. Then they were randomly assigned to the berberine group (the treatment group, 49 cases) and the placebo group (the control group, 48 cases). Patients in the treatment group took BC 300 mg, while those in the control group took placebo 300 mg, thrice per day for 3 successive months. Then placebos and BC were interrupted for 2 months (as washout period). All subjects received only diet control and physical activity during washout period. After washout period, placebos and BC were re-administered to all patients in the same way for 3 months. Body mass index (BMI), fasting plasma glucose (FPG), TG, TC, LDL-C, and HDL-C were assessed after run-in period, washout period, at month 1, 2, 3 after the first therapy, at month 1, 2, 3 after second treatment, respectively.
RESULTSCompared with the end of run-in period, TG, TC, and LDL-C decreased, and HDL-C increased in the treatment group (P < 0.05) after first 3 months of treatment. Compared with 3 months after the first therapy, TG, TC, and LDL-C increased and HDL-C decreased in the treatment group after washout period (P < 0.05). Compared with the end of wash- out period, TC and LDL-C decreased in the treatment group at month 2 after second treatment (P < 0.05); TG, TC, and LDL-C decreased (P < 0.01, P < 0.05), and HDL-C increased (P < 0.05) at month 3 after second treatment. Compared with the control group at month 3 after second treatment, TG, TC, and LDL-C all decreased, and HDL-C increased in the treatment group (all P < 0.05).
CONCLUSIONBC was effective in improving blood lipid level in mild hyperlipidemia patients.
Berberine ; therapeutic use ; Blood Glucose ; analysis ; Body Mass Index ; Capsules ; Humans ; Hyperlipidemias ; drug therapy ; Lipids ; blood
6.Effects and Mechanisms of Xuebijing on Early Sepsis Induced Acute Lung Injury in Rats
Wei WANG ; Yuxiang ZHANG ; Hongshan LI ; Long YANG ; Zheng WANG
Progress in Modern Biomedicine 2017;17(25):4820-4823
Objective:To investigate the effects and mechanisms of Xuebijing injection on early sepsis induced acute lung injury and explore a new therapy.Methods:Thirty healthy male Sprague-Dawley rats were randomly divided into 3 groups:Sham group(n=10),NS group (NS 4mL/kg n=10),Xuebijing Group(Xuebijing 4mL/kg n=10).Cecal ligation and puncture (CLP) was used to duplicate severe sepsis model.At 6h after CLP,the rats were sacrificed,the lungs were resected and histopathological characteristic was observed by transmission electron microscopy technique.The change of the lung wet/dry (W/D) weight ratio were studied.Meanwhile,the lungs were resected for detection of ET-1,iNOS,MMP-9,TIMP-1 mRNA with reverse transcription-polymerase chain raction (RT-PCR).Results:The changes of pulmonary alveoli and the interstitial edema as well as lung tissue in Xuebijing group were better than those of NS group.The change of lung wet/dry (W/D) weight ratio in septic rats showed was significantly increased at 6 h after CLP (vs Sham group:5.37± 0.12 vs 4.33± 0.06,P<0.01).The lung W/D was significantly decreased in XBJ group (vs NS group:4.67± 0.09 vs 5.37± 0.12,P<0.05).The expressions in XBJ group lung tissue of ET-1 (0.511 ± 0.111 vs 0.705± 0.122,P<0.01),iNOS(0.45610.075 vs 0.548± 0.098,P<0.05)、MMP-9 (0.617± 0.079 vs 0.732± 0.131,P<0.05),TIMP-1 (0.438± 0.043 vs 0.515± 0.049,P <0.01) mRNA were significantly decreased than those in NS group.And the expressions of ET-1 (0.705± 0.122vs 0.400± 0.033,P<0.01),iNOS (0.548± 0.098 vs 0.334± 0.027,P<0.01),MMP-9(0.732± 0.131 vs 0.352± 0.061,P<0.01),TIMP-1(0.515± 0.049 vs 0.365± 0.068,P<0.01) mRNA in NS group were significantly increased compared with those in the sham group.Conclusions:Xuebijing could protect against sepsis induced acute lung injury,which might be related with the decrease ofET-1,iNOS,MMP-9 and TIMP-1 mRNA expressions.
7.Maternal and neonatal perinatal outcomes in pregnancies after in vitro fertilization and natural pregnancy: a systematic: a meta analysis
Ling LONG ; Liren HE ; Chuan YE ; Yuyan LI ; Wei HE
Chongqing Medicine 2017;46(16):2228-2232
Objective To systematically evaluate maternal perinatal complications and neonatal outcomes after in vitro fertili zation and embryo transplantation(IVF-ET).Methods The computer retrieval was performed on the databases of PubMed,Cochrane library,EMbase,CNKI,Wanfang and Chinese biomedical literature database.The articles on the comparison between IVF and natural pregnancy were included.The RevMan5.3 software was adopted to conduct the meta analysis.Results Twenty-three articles conforming to the requirements were included,including 1 312 651 cases,among them 113 044 cases were IVF and 1 199 607 cases were naturalpregnancy.IVF mother's age was larger than that of natural pregnancy,while the gestational weeks were smaller than those of natural pregnancy,the newborn birth weight was lighter than that of natural pregnancy(P<0.05);the probability of pregnancy-induced hypertension (PIH),placenta previa,postpartum hemorrhage and gestational diabetes mellitus (GDM) occurrence in IVF mother were higher than that of natural pregnancy (P<0.05);the rate of multiple and cesarean section in IVF mothers were higher than that of natural pregnancy (P<0.05);the occurrence rates of small for gestational age(SGA),low birth weight infants,stillbirth and premature in IVF were higher than those of natural pregnancy (P<0.05).Conclusion The maternal perinatal complications in IVF are higher than those of natural pregnancy,and the birth outcomes in IVF are worse than those of natural pregnancy.
8.Evaluation of ligamentum teres hepatis with multi-slice spiral CT:an initial experience
Wei CHEN ; Xueying LONG ; Wenzheng LI ; Xiaojun LIU
Chinese Journal of General Surgery 2001;0(08):-
Objective To recognize the features of the ligamentum teres hepatic(LTH) in multi-slice spiral CT,and to preliminarily explore its clinical value.Methods A total of 130 patients without liver disease underwent abdominal scanning with a 16-slice spiral CT scanner.LTHs,as focused points,were observed by using postprocessing techniques such as multi-planar reformation(MPR),slab maximum intensity projection(slab-MIP) and slab volume rendering(slab-VR).Results The LTH was detected by multi-slice spiral CT in 90.8%(118/130).On these oblique-sagittal MPR,slab-MIP and slab-VR images,LTH presentedas slightly high density smooth cord-like structure in accordance with its anatomical morphology and position.The mean diameter of fissure portion of normal LTH was(5.44?0.96) mm(range 3.2-7.2 mm) measured at its middle region,and that of free portion of normal LTH was(3.43?0.91) mm(range 1.6-6.0 mm).Conclusions Multi-slice spiral CT demonstrates the LTH clearly,and has a potentialto evaluate the LTH before abdominal operation in which the LTH is to be used as an autogenous repairmaterial.
9.Design and clinical application of HZ-01-A level detector and pressure monitor
Jingwen LI ; Cun LONG ; Song LOU ; Xiguang WEI
Chinese Journal of Tissue Engineering Research 2010;14(30):5686-5689
BACKGROUND: Mortality related to cardiopulmonary bypass can be lowered by intra-operative monitoring system.Monitoring liquid level and pressure is extremely indispensable for examination of cardiopulmonary bypass(CPB).OBJECTIVE: To design a CPB safety system including an arterial line pressure monitor and low-level sensor,and to evaluate its safety and effects in clinical settings.METHODS: The safety system was composed of pressure transducer,photoelectric transmitter,photoelectric detector,core controller,and liquid crystal display.The principles of reflection and refraction were applied to the design of level sensor.The pressure measurements were converted into electronic signals and processed.According to two principles above-mentioned,fluid level detector and pressure monitor were designed.Thirty patients with the age of 1-75 years receiving cardiac surgery with cardiopulmonary bypass were enrolled.The arterial line pressure at different pump flows was measured and the alarm function of the level sensor was also validated.RESULTS AND CONCLUSION: Cardiopulmonary bypass arterial line pressure increased with the pump flow.Arterial line pressure detected by HZ-01-A safety system also increased with the pump flow increasing,which was highly related to the pump pressure.HZ-01-A safety system could alarm when the arterial line pressure and reservoir level exceeded the pre-determined thresholds.HZ-01-A safety system could be safely and effectively applied to clinical cardiopulmonary bypass and improve bypass safety by accurately detecting the pressure and reservoir level.
10.Application of diffusion tensor imaging in brain tumors
Wei LI ; Wansheng LONG ; Xuemao LUO ; Xiaoqin CAI ; Manqiong CHEN
Journal of International Oncology 2011;38(10):797-800
Objective To study the characteristics of diffusion tensor imaging (DTI) in brain tumor and it's diagnosis and differential diagnosis value.Methods Thirty-nine patients with brain tumors proven by pathologically (10 meningioma,17 glioma,12 metastatic tumors) were enrolled,by using Philips Achieva 1.5 T MRI,conventional MRI and DTI were underwent on them,fractional anisotropy (FA) maps,apparent diffusion coefficient (ADC) maps and three dimensional white matter fiber bundle map were reconstructed in the workstation.The core substance of the tumor area and the contralateral mirror area were selected as the region of interest,and FA and ADC values of them were measured,and t test was performed.Results The FA values of meningioma,metastases tumors and gliomas were 0.36 ± 0.08,0.28 ± 0.03,0.18 ± 0.06,respectively,and the differences among them were significant( P < 0.05).The ADC values of meningioma,metastases tumors and gliomas were 1.72 ± 0.10,1.52 ± 0.22,1.34 ± 0.14,respectively,and the differences among them were significant( P < 0.05).Conclusion DTI has high clinical value in identification of meningiomas,metastatic tumors and glioma.