Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3'-substituents at the 11-side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a-b, alkenes 7a-b and sophoridinic amines 14a-b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells.

Eleven old male patients with hyperuricemia were collected ( hyperuricemia group,65-90 years old ).10 healthy middle-aged males ( middle-aged group,30-40 years old) and 10 healthy old males ( older group 60-70 years old ) with normal blood uric acid level were used as controls.All of the subjects were given low purine content diet ( 250 mg/d ) for 3 days followed by high purine content diet ( 800 mg/d ) consecutively for another three days.The samples of fasting blood and 24 h urine were collected for assay.The results showed that there were no significant changes of serum uric acid ( UA ) concentration in three groups after low purine content diet.But the levels of serum UA in three groups all increased significantly after high purine content diet,and the change was higher in hyperuricemia group than middle-aged group [ ( 507.7 ± 108.1 vs 378.9 ± 80.1 ) μmol/L,P＜0.05 ].24 h urine uric acid excretion in three groups was all significantly decreased after low purine content diet and increased after high purine content diet.After high purine content diet,24 h urine uric acid was lower in hyperuricemia group than middle-aged group [ ( 2.99 ± 1.21 vs 3.62 ± 1.02 ) mmol/24 h,P＜0.05 ].Blood urea nitrogen levels in all subjects decreased after low purine content diet and increased after high purine content diet ( P＜0.05 or P＜0.01 ).Creatinine clearance rate in hyperuricemia group was decreased after high purine content diet compared with baseline [ (75.3 ± 20.3 vs 80.7 ±20.0) ml/min ],and there were no significant changes in other groups after low and high purine content diet.24 h urine protein in hyperuricemia group was higher than middle-aged group ( P＜0.05 ),and increased after high purine content diet with significant difference ( P＜0.05 ).These results suggest that high purine content diet and decreased by renal uric acid clearance mainly contribute to hyperuricemia in old people.

This study was conducted on the basis of informed consent of subjects and was approved by the ethical review committee concerned. 527 pregnant women voluntarily participated in this project for the investigation of cardiac reserve mobilizing condition. Using the digital technique of heart sound signal processing, we measured the heart rate (HR), the ratio of the first heart sound to the second heart sound (S1/S2)and the ratio of diastolic to systolic duration (D/S) during pregnancy. There was significant difference of HR and S1/S2 between the group of non-pregnant (G1), the group of 28-36 pregnant weeks (G2), and the group of 37-42 pregnant weeks (G3) (HR, S1/S2: G1 vs G2, G1 vs G3: P < 0.01). HR of the pregnant women increased with the increase of pregnant weeks. D/S decreased with the increase of pregnant weeks. There was significant difference of D/S between G1, G2, and G3 (G1 vs. G2: P < 0.01; G1 vs. G3: P < 0.01). There was also significant difference of D/S between G2 and G3 (G2 vs. G3: P < 0.05). Everybody in the non-pregnant women group was found to have D/S > or = 1.30; 64.33% of pregnant women were found to have 1.00 < D/S < 1.30, whereas 3.05% of pregnant women were found to have D/S < 1.00. These data revealed that the heart burden of the pregnant woman increased with the increase of pregnant weeks and the mobilization of cardiac reserve.
Adult ; Female ; Heart ; physiology ; Heart Rate ; physiology ; Heart Sounds ; Humans ; Phonocardiography ; methods ; Pregnancy ; physiology ; Pregnancy Trimester, Third ; physiology ; Signal Processing, Computer-Assisted ; Young Adult

Objective To study the outcomes and influencing factors of the conversion from normal glucose tolerance -hyperinsulinemia (NCT-HINS) to diabetes in the population of a community in Beijing.Methods All the subjects investigated received 75 g oral glucose tolerance test (OGTT) for diabetes screening carried out in May, 2006 and May, 2008. Data were calculated to analyze the outcomes and influencing factors of the conversion. HINS was diagnosed if fasting serum insulin & 15 mIU/L and/or 2-hour serum insulin after glucose loading ≥ 80 mIU/L Results The prevalence of NGT-HINS in the community in 2006 and 2008 was 5.28% and 8.67% (P<0.01) respectively and that of diabetes mellitus (DM) and impaired glucose regulation (IGR) was 3.52% , 6.56% in 2006 and 4.42% ,6.47% in 2008.The probability of the conversion from NGT-HINS to IGR and DM was 18.6% and 2.3% , being much higher than that from normal glucose tolerance- normoinsulinemia (NGT-NINS) (5.4% and 0.7% , P <0.01). However, the probability of the conversion from NGT-HINS to DM was 2.3% , which was much lower than that from IGR (26.3% , P <0.01). The reason might be that individuals with NGT-HINS had a higher waist circumference, BMI, fasting plasma glucose, 2 h plasma glucose and TG but a lower HDL-C than individuals with NGT-NINS in 2006. The HOMA β-cell function index/HOMA insulin resistance index (HBCI/IR) of individuals with NGT-HINS was much lower than that of individuals with NGT-NINS, but much higher than that of individuals with IGR. Logistic regression analysis showed that age, TG and HBCI/IR were the major influencing factors of the conversion from NGT to glucose metabolic disorders.Conclusions The probability of conversion from NGT to DM was increased remarkably when HINS was diagnosed. The reason might be that individuals with NGT-HINS suffered more metabolic risk factors and had a decreased β-cell function. Therefore, individuals with NGT-HINS should be paid attention to in diabetes prevention study.

Objective To investigate cardiac reserve function and pregnant results of preeclampsia.Methods Pregnant women chosen by randomized table and hospitalized in the department of obstetrics of the first affiliated hospital of Chongqing MedicaI University were involved in this study from January to December,2008.Sixty-nine cases of normal pregnant women were divided into 3 groups:normal group 1(20cases),normal group 2(26 cases)and normal group 3(23 cases).The normal group number 1 to number 3 were paired to gestational hypertension(20 cases),mild preeclampsia(26 cases)and severe preeclampsia (23 cases),respectively.The digital technique of heart sound signal processing WaS used to measure cardiac reserve function parameters including the heart rate(HR),the ratio of the amplitude of the first heart sound to the second heart sound(S1/S2)and the ratio of diastolic to systolic duration(D/S)of pregnant women.The pregnant results were also recorded.Results (1)The ratio of S1/S2 in the group of severe preeclampsia 4.5±3.2 was significantly bigher than the group of gestational hypertension 2.2±1.1 and normal group 32.2±1.1(P＜0.01).The ratio of D/S of the group of severe preeclampsia 1.1±0.3 Was significantly lower than the group of gestational hypertension 1.4±0.3 and normal group 31.4±0.2(P＜0.01).(2)All cases of the normal group number 1 to number 3 and the group of gestational hypertension were found the ratio of D/S≥1.00,whereas 1 case(1/26,4%)of the group of mild preeclampsia and 4 cases(4/23.17%)of the group of severe preeclampsia were found the ratio of D/S＜1.00.(3)The two cases of the pregnant wornen(including one woman died of cardiac arrest)with S1/S2＞5.00 and D/S＜1.00,who were in the group of severe preeclampsia,were sent to Intensive Care Unit after delivery.There were 4 cases(4/26,15%)and 6 cages(6/23,26%)of 1 minute Apgar score less than 7,7 cases(7/26,27%)and 6 cases(6/23,26%)sent to neonatal Intensive Care Unit,2 cases(2/26,8%)and 4 cases(4/23,17%)of neonatal death in the group of mild preeclampsia and in the group of severe preeclampsia,respectively.All newborns in the normal group number 1 to number 3 and the group of gestational hypertension were normal.Conclusions The cardiac reserve function of a pregnant woman with preeelampsia is decreased with the severity of preeclampsia and the parturient and neonatal results get worse.The distal technique of heart sound signal processing is a safe,harmless,simple and effective tool to measure cardiac reserve funotion of preeclampsia,and is worthy of widely used clinically.

Objective To evaluate the safety of mefformin in the treatment of elderly type 2 diabetes mellitus(T2DM). Methods Two hundred and forty-three cases of elderly T2DM hospitalized from Jan.1996 to Dec. 2006 were reviewed; the changes of fasting blood glucose(FBG), postprandial blood glucose (PBG), glycosylated hemoglobin (HbA1c), liver and renal function and blood lactic acid were evaluate before and after treatment. Results The mean time of treatment with mefformin was (6.6±3.9) years (3 months-21 years)in these 243 cases. The levels of FBG, PBG and HbAlc significantly reduced after treatment with mefformin only in 43 cases (17.7%), mefformin combined with other oral hypoglycemic drugs in 124 cases (51.0%) and mefformin combined with insulin in 76 cases (31.3%). There was only 18.1% of the cases with normal range ( > 80 ml/min) of creatinine clearance rate (Ccr), and 25.8% of the cases with Ccr≤50 ml/min. The liver and renal function as well as the blood lactic acid had no significant change after treatment no matter in total cases or in different groups separated by Ccr.Conclusions Mefformin is safety in the treatment of elderly T2DM patients. Ageing is not the contraindication of mefformin. To the patients with high risk, we should monitoring the level of blood lactic acid.

Objective:To investigate whether the habenula takes part in the depressor effect of losartan.Methods:Arterial blood pressure,heart rate and the unit dischargings of habenular neurons in rat were recorded simultaneously.Results:Arterial blood pressure was apparently decreased by 10 mg/kg losartan intraperitoneally(ip),but heart rate did not change;63.64% (21/33) unit dischargings of habenular neurons was increased in the rate of discharges.Conclusion:The depressor effect of losartan (ip) may be involved in the excitation of habenular neurons by lsoartan(ip).

Objective To investigate the correlation of blood lipid metabolism abnormity and other components of metabolic syndrome on angiocardiopathy and cerebrovascular diseases in the elderly people. Methods The clinical data of elderly people, who underwent medical examination during 1996 to 2005 in the General Hospital of PLA, were retrospectively analyzed. Based on the analysis, the co-existence of blood lipid disorders with glucose metabolic abnormity, hypertension and obesity, as well as their influence on cardio-cerebrovascular diseases were further analyzed. Results The prevalence of blood lipid metabolic disturbance was 69.6%, in which the prevalence of hyper-cholesteremia and hyper-triglyceride were 23.6% and 21.7%, respectively. The prevalence of hyper-cholesteremia accompanied by hyper-triglyceride (mixed group) was 19.3%, that of hyper-triglyceride with lower high density lipoprotein cholesterol was 5.03%, while it was 30.4% in the normal group. There was a higher risk of having the above abnormal condition in patients with type 2 diabetes mellitus (T2DM) and obesity, and they were more frequently complicated by hypertension in the hyper-triglyceride group (70.8%). When the patients with lipid metabolic disturbance were complicated by T2DM, hypertension and obesity, the prevalence of cardiovascular or cerebrovascular diseases increased. The prevalence of CHD was higher in the patients with hyper-cholesteremia and hypertension or diabetes, and incidence of both CHD and CVD was higher in the patients with hyper-triglyceride and either one of hypertension, diabetes or obesity. Conclusion There is high prevalence of lipid metabolic disturbance (more than two thirds) and other components of metabolic syndrome, and high risk of suffering from cardiovascular or cerebrovascular diseases in elderly people. The aging patients with hyper-triglyceride are vulnerable to cardiovascular or cerebrovascular diseases, and more attention should be paid in clinical practice in future.

Objective To analyze the significance of the waistline (WC), body mass index (BMI) and hyperinsulinaemia (HIns) on evaluating the metabolic syndrome. Methods The data of routine clinical examination were collected from the mid-aged and senile individuals (middle-senile group) who received oral glucose tolerance test (OGTT) for diabetes screening, and from a group of subjects who received annual OGTT for diabetes screening (mature group). Data were collected by a specialized person, input into a special computer database, and then analyzed with SAS 5.0 software by specialized staffs. Abnormal WC and BMI were determined according to IDF and CDS criteria. HIns was determined if fasting insulin (FIns) ≥15mU/L and 2-hour insulin after glucose burdening (2hPIns) ≥80mU/L. Results In the middle-senile group, the abnormality frequencies of WC and HIns as well as overall insulin level were obviously higher than that in the mature young group. The abnormality frequency of BMI was higher in mature young group. A higher detection rate of HIns existed in intolerance glucose test (IGT) and normal glucose test (NGT). The coincidence of WC and BMI diagnostic criteria were 77.5% and 74.3%, respectively, on evaluating with or without obesity in the middle-senile group and mature young group. When only WC criterion was used for evaluating the existence of insulin resistance, there would be 28.2% of missed diagnosis rate for MS patients. Conclusion WC, BMI and HIns are all risk factors for abnormal glucose metabolism, hypertension and dyslipidemia. There is different prevalence among different populations. The combination of WC, BMI and HIns might be more helpful for identifying MS at early stage.

Objective To study the relationships between serum uric acid levels in adult male patients with the risk factors of metabolic syndrome and insulin resistance.Methods In the persons undergone health check up in General Hospital of PLA in 2006,blood pressure(BP),body mass index(BMI),waistline,total and HDL cholesterol,serum triglycerides,fasting blood glucose(FBG),serum creatine(Cr)and uric acid(SUA)concentrations were measured.To the subjects without diabetes mellitus,75g oral glucose tolerance test(75g-OGTT)was given.Comparison was made on the components of MS between high SUA group(HUA)and normal SUA group(NUA).Logistic regression analysis was made to examine the relationship between UA and the symptom components of MS.The subjects without diabetes mellitus were then divided into 4 groups according to SUA levels,and then the relationships were analyzed between the levels of symptom components and the prevalence of MS among the different SUA groups.Results The mean age of the 1399 adult males was 56.3 ? 21.0 years.Among them the patients with hyperuricemia accounted for 14.37%.The levels of BMI,waistline,triglyceride,low density lipoprotein cholesterol,FBG,post prandial blood glucose(PBG),SBP and DBP were higher in HUA than that in NUA,while the HDL-C was lower.The incidence of MS in HUA group was higher with an increased SUA level compared with that in NUA group(P