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.

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.

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.

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.

Objective To investigate the iodide uptake by U251 glioma cell lines which were transfered with both human sodium/iodide symporter (hNIS) and human thyroperoxidase (hTPO) genes. Methods Recombinant adenosine virus AdTPO was constructed through cloning, recombination, packaging and amplifying. The viral titers were calculated after purification. The protein expression of AdTPO was tested by Western-Blotting and the recombinant plasmids PcDNA3. 1/hNIS were constructed. After hNIS gene was transfected into human glioma cell lines U251 through liposome, the cell lines with stable hNIS expression (hNIS-U251) selected by G418 antibiotics were defined as hNIS-U251 group. Then, hTPO was transducted into hNIS-U251 with adenosine virus (AdTPO-hNIS-U251 group). U251 cells with no plasmid were used as the control group (U251). Cultured cells from each group were studied for 125I uptake as well as 125I efflux rate. Student-Newman-Keuls in multiple range test was used. Results AdTPO-hNIS-U2.51 with stable expression was successfully established by transfecting hNIS and hTPO genes into human glioma cell lines. The 125I uptake by AdTPO-hNIS-U251, hNIS-U251 and U251 cell lines was (74 647.53 ±3605.88), (55 769.96 ±4353.26) and ( 507.67 ± 57.69 ) counts/min, respectively ( F = 836. 17, P ＜ 0.05 ). The uptake compacity by AdTPO-hNIS-U251 was 147 fold higher than that by U251 (q =55.64, P＜0.01 ) and 1.3 fold higher that by hNIS-U251 (q = 14. 17, P ＜0.01 ). 125I efflux rate was prolonged in AdTPO-hNIS-U251 group and its effective half time was 13 min. Conclusion Enhanced 125I uptake by the human glioma cell lines can be achieved with combined transfection of hNIS and hTPO genes.

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.

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.

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

Objective To evaluate the effect of hydrogen-rich saline on the expression of phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) during cerebral ischemia-reperfusion (I/R) in rats.Methods Seventy-two adult male Sprague-Dawley rats,weighing 220-250 g,were randomly divided into 3 groups (n =20 each) using a random number table:sham operation group (group S),I/R group and hydrogen-rich saline group (group I/RH).Cerebral ischemia was induced in chloral hydrate-anesthetized rats by 2 h middle cerebral artery occlusion in I/R and I/RH groups.The artery was only exposed but not occluded in group S.At 3 days before operation and immediately after onset of reperfusion,hydrogen-rich saline (0.6 mmol/L) 10 ml/kg was intraperitoneally injected in group I/RH,while the equal volume of normal saline was given in S and I/R groups.Neurological deficits were blindly assessed and scored at the end of 24 h reperfusion.The animals were then sacrificed,and brains were removed for microscopic examination and for determination of the cerebral infarct size (by TTC),brain water content,cell apoptosis (by TUNEL),and expression of p38MAPk and phosphor-p38MAPK (p-p38MAPK) (by immunohistochemistry and Western blot).Apoptosis index was calculated.Results Compared with group S,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly increased,and the expression of p38MAPK and p-p38MAPK was up-regulated in I/R and I/RH groups.Compared with group I/R,neurological deficit score,apoptosis index,brain water content and cerebral infarct size were significantly decreased,and the expression of p38MAPK and p-p38MAPK was down-regulated in group I/RH.The pathological changes of cerebral tissues were significantly attenuated in group I/RH as compared with group I/R.Conclusion Hydrogen-rich saline can reduce cell apoptosis through inhibiting p-p38MAPK expression,thus attenuating cerebral I/R injury in rats.

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.