OBJECTIVETo investigate the cell biological mechanism of koumine-induced apoptosis of human colonic adenocarcinoma cells.

METHODSThe effects of LoVo cell koumine on the membrane potential, mitochondrial membrane potential, concentration of cytosolic free calcium, reactive oxygen species (ROS) and gap junctional intercellular communication was observed by laser scanning confocal microscopy.

RESULTS AND CONCLUSIONKoumine lowered the membrane potential and mitochondrial membrane potential of LoVo cells and decreased the concentration of free cytosolic calcium, which was increased to a level higher than the basal one after addition of EDTA. Koumine also increased the reactive oxygen species and enhanced the gap junctional intercellular communication of LoVo cells. These findings may explain the possible mechanisms of koumine-induced LoVo cell apoptosis.

Adenocarcinoma ; metabolism ; pathology ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Cell Communication ; drug effects ; Cell Line, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Gap Junctions ; drug effects ; metabolism ; Humans ; Indole Alkaloids ; pharmacology ; Membrane Potential, Mitochondrial ; drug effects ; Microscopy, Confocal ; Reactive Oxygen Species ; metabolism

OBJECTIVETo investigate effects of garlic oil (GO), age and sex on n-hexane metabolism in rats.

METHODSThe Wistar rats were used as experimental animals. (1) Intragastric administration: n-hexane group (3000 mg/kg n-hexane), GO treated group (80 mg/kg GO ig. an hour earlier than 3000 mg/kg n-hexane), then blood was taken from tails of rats at 8, 12, 16, 20, 24, 28, 32 h points after n-hexane administration. (2) Intraperitoneal injection: n-hexane group (1000 mg/kg n-hexane), GO treated group (80 mg/kg GO ig. an hour earlier than 1000 mg/kg n-hexane), then took blood was taken from tails of rats at 8, 12, 16, 20, 24, 28 h points after n-hexane injection. (3) 7 rats each group of 6, 8, 10 weeks age were administrated by 3000 mg/kg n-hexane intragastrically, then were taken blood from tails at 16, 20, 24 h points after administration. (4) 7 male and 7 female rats of 8 weeks age were administrated by 3000 mg/kg n-hexane intragastrically, then were taken blood from tails at 16, 20, 24, 28 h points after administration. The gas chromatography was used to determine the metabolite 2, 5-hexanedione concentration of n-hexane in serum and 2, 5-hexanedione concentration was compared between GO and no GO treated rats, different ages and different sexes.

RESULTS(1) Intragastric administration: 2, 5-hexanedione concentrations in serum of n-hexane group and GO treated group had the peak 19.2 and 12.3 µg/ml at 20h and 24 h points. Compared with n-hexane group, the serum 2, 5-hexanedione concentration of GO treated group was lower at time points prior to peak and 2, 5-hexanedione eliminating process was slower after peak. (2) Intraperitoneal injection: effects of GO on the serum 2, 5-hexanedione concentrations was very similar to intragastric administration, 2, 5-hexanedione concentrations in serum of n-hexane group and GO treated group had the peak 15.0 and 6.7 µg/ml at 12 h and 16 h points. (3) Comparison of the serum 2, 5-hexanedione concentrations of different weeks age rats: The serum 2, 5-hexanedione concentrations of 6, 8, 10 weeks age rats were 25.5, 15.0, 12.8 µg/ml each (8, 10 weeks age significantly lower than 6 weeks age) at 16 h point; at 20 h point, they were 24.7, 18.3, 15.0 µg/ml each (10 weeks age significantly lower than 6 weeks age); at 24 h point, they were 11.0, 14.7, 8.1 µg/ml each (10 weeks age significantly lower than 8 weeks age). (4) Comparisons of the serum 2, 5-hexanedione concentrations of different sex rats: the serum 2, 5-hexanedione concentrations of male and female rats were 22.5, 17.2 µg/ml each at 16 h point (different significantly); at 20, 24, 28 h points, they were 27.6, 22.9 µg/ml, 24.6, 19.1 µg/ml, 19.1, 13.8 µg/ml each (different non-significantly).

CONCLUSIONGO reduces production of 2, 5-hexanedione in serum generated by n-hexane in rats; the metabolic capacity of low age rats on n-hexane is stronger than high age ones.

Age Factors ; Animals ; Antioxidants ; pharmacology ; Female ; Garlic ; Hexanes ; metabolism ; Hexanones ; blood ; Male ; Plant Oils ; pharmacology ; Rats ; Rats, Wistar ; Sex Factors

OBJECTIVETo observe serum uric acid (UA) level distribution and explore risk factors of hyperuricemia (HUA) in a large cohort of active and retired employees underwent physical examination.

METHODSPhysical examination was arranged for 21 700 active and retired employees from May 2010 to September 2011, 16 416 employees were examined and complete examination data were obtained in 14 044 subjects. The distribution characteristics of UA level and correlations of UA level and HUA prevalence rate with gender, age, body mass index (BMI), systolic pressure (SBP), diastolic pressure (DBP), fasting blood-glucose (FPG), serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were analyzed.

RESULTSHUA prevalence rate was 11.2% in this cohort, which was significantly higher in males (15.8%) than in females (4.1%, P < 0.05). The UA level and the HUA prevalence rate presented a "J" curve relationship with aging and positively correlated with BMI, SBP, DBP, TG, LDL-C, TC and FPG while negatively correlated with HDL-C. Multiple linear regression analysis showed that SBP, BMI, FPG, TG, and LDL-C were independent risk factors while HDL-C and female gender were the protective factors of HUA(all P < 0.01). Aging and high DBP were independent risk factors of HUA for females (all P < 0.05) and LDL-C was risk factor of HUA for males (P < 0.05).

CONCLUSIONSSerum UA level presents a "J" wave relationship with aging. The risk factors of HUA are increased SBP, BMI, FPG, TG, LDL-C while the protective factors of HUA are female gender and high HDL-C.

Adult ; Aged ; Female ; Humans ; Hyperuricemia ; epidemiology ; Male ; Middle Aged ; Physical Examination ; Prevalence ; Risk Factors ; Uric Acid ; blood

OBJECTIVETo investigate the relationship between renal clear cell carcinoma and type 2 diabetes mellitus (DM).

METHODSTwo hundreds and sixty-four patients with renal clear cell carcinoma and four hundred controls who suffered from non-urinary system, non-neoplastic or non-hormone-related disorders, were enrolled from January 2008 to December 2012. The incidence of diabetes between the 2 groups and the relationship between renal clear cell carcinoma and duration of diabetes were compared, moreover, renal clear cell carcinoma patients with DM were compared with patients without DM for their clinical features, laboratory examinations and histological characteristics.

RESULTSThe comparison of renal clear cell carcinoma group and control group: the incidence of DM in the two groups were 19.7% and 12.8% respectively, and the difference was significant (&chi;(2) = 5.86, P < 0.05, OR = 1.68). In the renal clear cell carcinoma group, the proportion of patients with DM diagnosed within 2-4 years was 4.92%, which were significant higher than those in the control group 1.70% (&chi;(2) = 5.49, P < 0.05, OR = 2.91). And men with diabetes had high occurrence risk 86% of renal clear cell carcinoma (OR = 1.86, 95%CI: 1.09-3.15). The comparison of diabetes patients subgroup and non-diabetic patients subgroup in renal clear cell carcinoma group: in respect of clinical features, greatest tumor diameter in the two subgroups were (4.9 ± 2.3) cm and (4.2 ± 2.1) cm respectively, and the difference was significant (t = 1.96, P < 0.05). However, there was no significant difference in terms of age, gender and cancer location between the two subgroups (P > 0.05). In respect of laboratory examinations, serum creatinine in the two subgroups were (72 ± 20) µmol/L and (65 ± 17) µmol/L, and the difference was significant (t = 2.34, P < 0.05); serum urea nitrogen in the 2 subgroups were (7.1 ± 2.1) mmol/L and (6.0 ± 1.5) mmol/L respectively, and the difference was significant too (t = 1.47, P < 0.05). In respect of histological characteristics, the proportion of well differentiated clear cell carcinoma were 80.8% and 81.1% respectively, and the difference was significant (&chi;(2) = 4.23, P < 0.05). The proportion of stage II were 25.0% and 27.8% respectively and the difference was significant (&chi;(2) = 4.08, P < 0.05).

CONCLUSIONSDM is closely related with renal clear cell carcinoma and DM may be a possible risk factor for the tumor. And for elderly patients with diabetes who appear waist discomfort or hematuria, a careful examination of kidney is important to make early diagnosis, give timely treatment and improve survival prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Renal Cell ; complications ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; complications ; Female ; Humans ; Incidence ; Kidney Neoplasms ; complications ; Male ; Middle Aged ; Prognosis

OBJECTIVETo investigate the relationship of sperm morphology with reproductive hormones in infertile men and the pathogenesis of teratozoospermia.

METHODSThis study included 90 infertile men aged 25 - 40 years. We measured their testis volumes using the Prader orchidometer, conducted routine semen analyses according to the WHO laboratory standard, and determined the concentrations of reproductive hormones and sex hormone-binding globulin (SHBG) by chemiluminescence and the levels of free testosterone (FT) and bioavailable testosterone (BioT).

RESULTSAll the subjects showed normal sperm concentration. Based on the results of semen morphology analysis, the 90 infertile men were equally divided into groups 1 (morphologically normal sperm <4%), 2 (morphologically normal sperm > or = 4% and <10%), and 3 (morphologically normal sperm > or = 10%), with no significant differences in age among the three groups (P>0.05). The volumes of the left testis were (14.27 +/- 3.65) ml, (16.90 +/- 3.57) ml and (14.57 +/- 3.57) ml, respectively (P = 0.006 group 1 vs group 2, P = 0.741 group 1 vs group 3, P = 0.014 group 2 vs group 3), and those of the right testis were (14.60 +/- 3.70) ml, (16.60 +/- 3.35) ml and (14.67 +/- 3.54) ml, respectively (P = 0.050). There were no significant differences among the three groups in prolactin, follicle-stimulating hormone, luteinising hormone, estradiol, total testosterone and SHBG, (P>0.05). The levels of serum FT were (0.25 +/- 0.07) nmol/L, (0.29 +/- 0.07) nmol/L and (0.31 +/- 0.13) nmol/L (P = 0.086 group 1 vs group 2, P= 0.010 group 1 vs group 3, P= 0.364 group 2 vs group 3), and those of BioT were (5.81 +/- 1.58) nmol/L, (6.78 +/- 1.55) nmol/L and (7.29 +/- 3.02) nmol/L, respectively (P = 0.086 group 1 vs group 2, P = 0.010 group 1 vs group 3, P = 0.364 group 2 vs group 3). The percentage of morphologically normal sperm was positively correlated with the levels of serum FT and BioT (P<0.05).

CONCLUSIONThe higher the levels of serum FT and BioT, the higher the percentage of morphologically normal sperm, which suggests that serum FT and BioT might be involved in the pathogenesis of teratozoospermia.

Adult ; Estradiol ; blood ; Follicle Stimulating Hormone ; blood ; Humans ; Infertility, Male ; blood ; physiopathology ; Luteinizing Hormone ; blood ; Male ; Prolactin ; blood ; Semen ; Semen Analysis ; Sex Hormone-Binding Globulin ; metabolism ; Sperm Count ; Spermatozoa ; abnormalities ; Testis ; Testosterone ; blood

BACKGROUNDThe domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate.

METHODSThe study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment.

DISCUSSIONThe study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).
Adenine ; analogs & derivatives ; therapeutic use ; Adult ; Antiviral Agents ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; immunology ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Male ; Medicine, Chinese Traditional ; Organophosphonates ; therapeutic use ; Young Adult