OBJECTIVE: To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells. METHODS: The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP RESULTS: Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP CONCLUSION Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.
Animals ; Apoptosis/drug effects* ; Cell Cycle/drug effects* ; Cell Line, Tumor ; Humans ; Leukemia ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Telomerase/metabolism* ; Telomere/metabolism*

Objective　The active protein of traditional Chinese medicine has anti-tumor effect, and salvia miltiorrhiza is an important anti-tumor traditional Chinese medicine. Here, the effect of Salvia miltiorrhiza lectin protein (SMLP) on the apoptosis of gastric cancer cells was studied.　Methods　SMLP expressed and purified from prokaryotic cells was used to treat the gastric cancer cells SGC-7901. The experiment was divided into the control group (untreated) and the SMLP treatment group (final concentration of 10 μmol / L of SMLP was treated for 24 h). Real-time RT-PCR and Western blot were used to detect the changes of apoptosis gene expression. Flow cytometry and Hoechst staining were applied to detect the apoptotic status. Caspase-3 and Caspase-9 activity assay kits were used to detect the apoptotic level.　Results　The result of RT-PCR showed that the mRNA level of Bax in the SMLP treatment group was significantly higher than in the control group (1.00±0.12 vs 0.67±0.10）(P<0.05). After treatment with SMLP to gastric cancer cells, the activity and expression level of cleaved Caspase-3 and Caspase-9 were increased significantly compared with the control group (P<0.05). The cell nucleus in the control group was bigger and rounder, with smooth surface and uniform staining, whilst in the SMLP-treated group, the cell nucleus became deeper with pyknosis, representing typical morphological characteristics of apoptosis. The early apoptosis level in the control group was 6.55%, and the SMLP treatment group reached 10.18%, showing an increase in the level of apoptosis.　Conclusion　SMLP expressed and purified in vitro can promote the apoptosis of gastric cancer cells, which is of great significance for further revealing the function of plant lectin and investigating the anti-tumor effect on the protein of traditional Chinese medicine.

Objective To observe the efficacy and safety of DAAs in treating HCV patients with HIV/HCV co-infection.Method 53 patients were divided into groups based on HCV genotype. Sofosbuvir + Ledipasvir regime were used for 1b and 6a subtypes; sofosbuvir+Daclatasvir regime were used for 3a, 3b and those cannot be typed; all the patients diagnosed with cirrhosis were also administrated with ribavirin. The course of treatment for all patients is 12 weeks.Results All 53 patients completed HCV treatment, the overall SVR rate of DAAs treatment rate was 98.1%(52/53), failure rate 1.9%(1/53) ; SVR rate of DAAs treatment among non-cirrhosis patients was 100%(41/41) ; SVR rate of DAAs treatment among cirrhosis patients was 91.7%(11/12), failure rate 8.3%(1/11) . After treatment, ALT and AST levels of DAAs treatment patients were decreased (P＜0.05), while CD4 level increased (P＜0.05) . Main adverse effects are: 12 patients had gastrointestinal symptoms (22.6%) ; 6 had nausea, vomiting (11.3%), 4 had diarrhea (7.6%), 1 had mild rash (1.9%), and 5 had elevated serum total bilirubin (9.4%) . Conclusion The overall SVR rate among DAA treatment for HIV/HCV co-infected patients is high (98.1%) with broad indications. Even patients with cirrhosis are eligible. It yielded optimistic outcomes among different gene subtypes, and effectively improved liver function and CD4 level. With oral administration, short regime course, and mild adverse effects, patients can tolerate well, indicating its effectiveness and safety.

OBJECTIVETo investigate the relationship among serum reproductive hormone levels, serum homocysteine (Hcy) levels, metabolic syndrome (MS), and the components of MS in middle-aged and elderly males.

METHODSUsing the cluster and stratified sampling methods and a unified structured questionnaire, we conducted a survey among 948 men aged 40 - 80 years in the rural community, measured their basic physical parameters, and obtained their reproductive hormone levels, serum Hcy concentrations, and metabolism-related indicators. We collected 868 valid questionnaires along with their serum samples, divided the subjects into an MS and a non-MS control group in a 1:1 ratio, and measured their serum Hcy concentrations.

RESULTSAmong the subjects included, 132 were diagnosed with MS. Nonparametric tests showed statistically significant differences between the MS and non-MS groups in the waist circumference (WC), waist-hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) (P < 0.05), but not in age (P > 0.05). Significant differences were also observed between the two groups in the levels of serum tT, SHBG, LH, and FTI (P < 0.05) , but not in the concentrations of serum Hcy (P > 0.05). The concentration of serum Hcy exhibited no correlation with BMI, SBP, DBP, FBG, TG, and HDL-C (P > 0.05) and had no influence on MS.

CONCLUSIONThe concentration of serum Hcy is not significantly correlated with MS, nor with its components. The levels of male serum reproductive hormones are associated both with MS and with its components.

Adult ; Aged ; Blood Pressure ; Body Mass Index ; Homocysteine ; blood ; Humans ; Luteinizing Hormone ; blood ; Male ; Metabolic Syndrome ; blood ; diagnosis ; Middle Aged ; Reproduction ; Rural Population ; Sex Hormone-Binding Globulin ; metabolism ; Surveys and Questionnaires ; Testosterone ; blood ; Thyroxine ; blood ; Waist Circumference ; Waist-Hip Ratio

BACKGROUNDThe prevalence of chronic kidney disease (CKD) and prediabetes has increased in China, and at different rates in different locations. Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.

METHODSA total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method. An estimated glomerular filtration rate (eGFR), albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006. Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes, and association of insulin resistance (IR) with CKD and prediabetes was analyzed.

RESULTSThe age-standardized prevalence of CKD was 12.5%, eGFR < 60 ml×min(-1)×1.73 m(-2) was 2.7% and ACR (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes. Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.

CONCLUSIONCKD and prediabetes have become a major public health problem in Zhuhai, Southern China; insulin resistance may be an important risk factor.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State ; epidemiology ; Prevalence ; Renal Insufficiency, Chronic ; epidemiology ; Risk Factors ; Surveys and Questionnaires

BACKGROUNDLeft main coronary artery (LMCA) stenosis has been recognized as a risk factor for early death among patients undergoing coronary artery bypass grafting (CABG). This study aimed to assess if LMCA lesions pose an additional risk of early or mid-term mortality and/or a major adverse cardiac and cerebrovascular event (MACCE) after off-pump coronary artery bypass grafting (OPCABG), compared with non-left main coronary artery stenosis (non-mainstem disease).

METHODSFrom January 1, 2009 to December 31, 2010, 4869 patients had a primary isolated OPCABG procedure at Beijing Anzhen Hospital. According to the pathology of LMCA lesions, they were retrospectively classified as a non-mainstem disease group (n = 3933) or a LMCA group (n = 936). Propensity scores were used to match the two groups, patients from the non-mainstem disease group (n = 831) were also randomly selected to match patients from the LMCA group (n = 831). Freedom from MACCE in the two groups was calculated using the Kaplan-Meier method.

RESULTSThe difference in the mortality and the rate of MACCE during the first 30 days between the non-mainstem disease group and the LMCA group did not reach statistical significance (P = 0.429, P = 0.127 respectively). With a mean follow-up of (12.8 ± 7.5) months and a cumulative follow-up of 1769.6 patient-years, the difference in the freedom from MACCEs between the two groups, calculated through Kaplan-Meier method, did not reach statistical significance (P = 0.831).

CONCLUSIONAnalysis of a high volume of OPCABG procedures proved that LMCA lesions do not pose additional early and mid-term risk to OPCABG. Therefore, a LMCA lesion is as safe as non-mainstem disease lesion during the OPCABG procedure.

Adult ; Aged ; Coronary Artery Bypass, Off-Pump ; adverse effects ; mortality ; statistics & numerical data ; Coronary Artery Disease ; surgery ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo investigate the mechanism of serum testosterone reduction, its relationship with metabolism, changes in the number and morphology of Leydig cells and endocrine function in aging male rats.

METHODSThe levels of serum total testosterone (tT), LH, FSH, HDL, LDL, TG, TC, Glu, INS, IRG and LP were determined in young (9 mo) and aging rats (12, 15, 18 and 21 mo), with 6 in each group. The morphological changes of Leydig cells were observed under the microscope. The concentrations of testosterone secreted from the cultured Leydig cells with the stimulation of hCG and Forskolin were assayed. The apoptosis rates of Leydig cells were detected by TUNEL. The visceral fat was isolated and weighed, and the Lee's index calculated. All the above indexes were recorded and compared among different age groups.

RESULTSThe aging rats showed a significant decrease in the levels of serum tT and TSI ([1.26 +/- 0.65] ng/ml and [0.07 +/- 0.65] ng/mIU) as compared with the young rats ([3.24 +/- 0.38] ng/ml and [0.21 +/- 0.01] ng/mIU) (P < 0.01). Obvious differences were found in the morphology of Leydig cells among different age groups. The T secretion of Leydig cells at 24, 48 and 72 h in aging rats was markedly decreased (P < 0.05) while their TUNEL positive rate remarkably increased in the aging rats (17.36% +/- 1.31%) compared with the young ones (7.02% +/- 1.05%) (P < 0.05). There were statistically significant differences between the young and aging rats in all the biochemical parameters including IRG, HDL, LDL, TG, TC and visceral fat content (P < 0.05), except the levels of serum Glu, INS and LP (P > 0.05).

CONCLUSIONThe serum T level and secreting capacity of Leydig cells are significantly lower in aging rats than in young ones, and the metabolic parameters undergo regular changes with the decreasing level of serum T. The reduction of testosterone in aging male rats may be associated with the decreased secreting capacity and number of Leydig cells and declined function of the pituitary.

Aging ; Animals ; Leydig Cells ; cytology ; metabolism ; secretion ; Male ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood ; metabolism

Objective To analyze the main factors that influence the hospitalization expenses in patients undergone transsphenoidal pituitary tumor resection so as to provide basis for the development of clinical pathways and the control of irrational increase in medical expenses.Methods Data of patients undergone transsphenoidal pituitary tumor resection in our hospital in the years of 2008 and 2009 was collected.Statistical analysis was performed by using multinomial linear regression analysis.Results The major factors influencing the hospitalization expenses in pafients undergone transsphenoidal pituitary tumor resection included drug fees,material fees in operation,inspection fees and length of stay.Conclusions Avoiding overtreatment,reasonably lowering the drug fees,material fees in operation and inspection fees,as well as reducing the length of stay were the key to the control of the excessive growth of hospitalization expenses in patients undergone transsphenoidal pituitary tumor resection.

OBJECTIVETo investigate the incidence of late onset of hypogonadism (LOH) in males as well as the sensitivity, specificity and applicability of the androgen deficiency in aging males (ADAM) questionnaire and the aging males' symptoms (AMS) scale in Chinese males based on the community population data.

METHODSA total of 1 498 old and middle-aged healthy males attended the ADAM and AMS investigations, of whom 434 received the measurement of the concentration of serum reproductive hormones, the positive rate of LOH screening, the rate of androgen deficiency, the clinical incidence of LOH, and the sensitivity and specificity of ADAM and AMS by tT and fT cut-off. The symptom evaluation cut-off value of the AMS score was optimized using the ROC curve.

RESULTSAlthough 5 of the subjects had previously received irregular testosterone supplement, none of them was given or actively sought for androgen therapy at the time of the investigation. Among the 40 - 69 years old males, the mean positive rates of LOH screening by ADAM and AMS were 80.77% and 32.34%, and the mean androgen deficiency rates obtained by tT and fT cut-off were 14.02% and 43.69%. The mean clinical incidences of LOH in the ADMA- and AMS-positive subjects were 37.85% and 15.42%. According to the fT cut-off, the sensitivities of ADAM and AMS were 86.63% and 35.29%, and their specificities were 24.48% and 63.49%, respectively. The symptom evaluation cut-off value of the AMS score optimized by the ROC curve was 19.5.

CONCLUSIONThe sensitivity and specificity of ADAM and AMS in the Chinese population are basically consistent with the results of most studies abroad, while the positive rate of LOH screening, the rate of androgen deficiency and the clinical incidence of LOH obviously higher in the former than those reported in other studies. Both ADAM and AMS are applicable to the Chinese population. The former is advantageous for its high sensitivity, time saving and easy operation, and therefore suitable for screening LOH, while the latter can be used for monitoring therapeutic efficacy.

Adult ; Aged ; Asian Continental Ancestry Group ; Humans ; Hypogonadism ; diagnosis ; Male ; Mass Screening ; methods ; Middle Aged ; Sensitivity and Specificity ; Surveys and Questionnaires

OBJECTIVETo investigate the changes of serum reproductive hormones with male aging and to compare the differences in the hormone levels among different age groups or between township and rural males of the same age group.

METHODSUsing cluster and stratified sampling, we recruited 434 healthy old and middle-aged (40-69 years) males, 198 from the township and 236 from the rural communities. We determined the concentrations of serum total testosterone (tT), luteinizing hormone (LH) and sex hormone binding globulin (SHBG), free testosterone (fT), bio-available testosterone (Bio-T), and obtained the testosterone secretion index (TSI) and free testosterone index (fTI). Meanwhile, we included fifty-nine 20-39 years old males from the same communities in a control group.

RESULTSWith the increase of age, the serum tT levels did not change significantly, while the levels of serum LH and SHBG increased, and those of fT, Bio-T, TSI and fTI decreased gradually. Statistically significant differences were found among the four different age groups in all the parameters of reproductive hormones (P < 0.01), except in the serum tT level (P > 0.05). The serum tT level was not significantly correlated with aging and LH (P > 0.05). Serum LH and SHBG had a marked positive correlation with aging, and SHBG with LH (P < 0.01), while fT, Bio-T, TSI and fTI were negatively correlated with aging and the LH level (P < 0.01). Serum LH, TSI and fTI showed statistical differences (P < 0.05), while fT and Bio-T exhibited extremely significant differences (P < 0.01) between the township and rural males in the 40 -49 yr group, and in the same age group, the increase rates of serum LH and SHBG and reduction rates of fT, Bio-T, TSI and fTI were higher in the rural men than in the township residents. However, the results were just the opposite in the 50 - 59 and 60 - 69 yr groups.

CONCLUSIONThe levels of serum LH, SHBG, fT, Bio-T, TSI and fTI changed with aging in a gradientmanner in the old and middle-aged males, but no significant changes were observed in the level of serum tT. There were statistical differences in many parameters of serum reproductive hormones among different age groups or between township and rural males.

Adult ; Age Factors ; Aged ; Aging ; metabolism ; China ; Humans ; Luteinizing Hormone ; blood ; Male ; Middle Aged ; Rural Population ; Serum Albumin ; metabolism ; Sex Hormone-Binding Globulin ; metabolism ; Testosterone ; blood ; Urban Population ; Young Adult