Usnic Acid Induces Cycle Arrest, Apoptosis, and Autophagy in Gastric Cancer Cells In Vitro and In Vivo.

BACKGROUND Usnic acid (UA), a secondary metabolite, is mainly derived from certain lichen species. Growing evidence suggests that UA has antitumor, anti-oxidative, anti-inflammatory, and other activities in a variety of cancer cells. However, the antitumor effect of UA in gastric cancer cells (GC) is unclear. The aim of this investigation was to assess the antitumor effect of UA in GC cells in vitro and in vivo, and to explore the underlying mechanisms. MATERIAL AND METHODS Cell proliferation was measured by CCK8 assay, the arrest of cell cycle was assessed by flow cytometry, and cellular apoptosis was observed via Hoechst 33258 staining assay. Expression levels of apoptosis-related proteins (activated caspase-3 and PARP, Bax, Bcl2) and autophagy-associated proteins (LC3-II and p62) were verified through Western blot analysis. H&E staining and immunohistochemistry were carried out in the subcutaneously implanted BGC823 tumor model in a nude mouse experiment. RESULTS In vitro, we demonstrated that UA was significantly effective in inducing morphological changes, inhibiting the cell proliferation dose- and time-dependently, arresting the cell cycle phase, promoting cancer cellular apoptosis, and inducing autophagy activity. In vivo, compared to mice treated with 5-FU alone, UA treatment was significantly more effective in suppressing the tumor growth without affecting body weight, and in regulating the amount of Bax and Bcl2 in tumor tissues. CONCLUSIONS UA induces cell cycle arrest and autophagy and exerts anti-proliferative and apoptotic effects by modulating expression of apoptosis-related proteins in stomach neoplasm cells, and has a better antitumor effect compared to 5-Fu in the xenograft model.

Serum Albumin and C-Reactive Protein/Albumin Ratio Are Useful Biomarkers of Crohn's Disease Activity.

BACKGROUND Serum albumin (ALB) may be low during acute inflammation, but it is also affected by nutritional status. Therefore, we hypothesized that ALB and the C-reactive protein/ALB ratio (CRP/ALB) may be associated with disease activity in patients with Crohn's disease (CD). MATERIAL AND METHODS Altogether, 100 patients with CD and 100 age- and sex-matched healthy volunteers were retrospectively enrolled in the current study. The patients with CD were subdivided into patients with active disease (Crohn's Disease Activity Index >150) and those in remission. ALB levels, CRP levels, and lipid profiles were measured. RESULTS ALB and CRP levels and the CRP/ALB ratio were the most useful for differentiating between active and nonactive CD. ALB levels (r=-0.50, P<0.01), CRP levels (r=0.39, P<0.01), and CRP/ALB ratio (r=0.42, P<0.01) all correlated with CD activity. These correlations were more prominent in males. Receiver Operating Characteristic (ROC) analysis indicated that the area under the curve (AUC) representing ALB (0.79) was higher than the AUC representing CRP (0.73) or CRP/ALB ratio (0.75; P>0.05). The AUCs corresponding to ALB level, CRP level, and CRP/ALB ratio were more prominent in males versus females (P<0.05). CRP level (14.55 mg/L), ALB level (34.35 g/L), and CRP/ALB ratio (0.69) had sensitivities of 67.7%, 72.6%, and 59.7%, and specificities of 73.7%, 78.9%, and 81.6%, respectively, for CD activity. CONCLUSIONS In the present retrospective study, we found that ALB level and CRP/ALB ratio were useful biomarkers for identifying CD activity, especially in males. These results suggest that, in addition to inflammation, assessment of patient nutritional status could also aid in identifying CD activity.

The value of the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio in predicting carotid atherosclerosis among Chinese individuals with metabolic syndrome: a cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is associated with carotid intima-media thickness (CIMT), which is a good predictor of cardiovascular disease (CVD). However, among individuals with MetS, direct comparative data regarding the utility of the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio to diagnose carotid atherosclerosis are scarce, particularly in Chinese populations. We aimed to determine the relationship between the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio and carotid atherosclerosis among Chinese individuals with MetS. METHODS: We performed a retrospective study of 5822 Chinese participants who underwent a routine health screening examination. Lipid profiles, fasting glucose, fasting insulin, CRP, apoB, apoAΙ and CIMT were measured. RESULTS: We observed that among Chinese individuals with MetS, men (53.95±0.58 ys) developed carotid atherosclerosis at a younger age than women (58.47±1.17 ys) (P<0.001). Both the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio positively correlated with carotid atherosclerosis among Chinese individuals with MetS, particularly among women. Meanwhile, CIMT increased progressively across the quartiles of the non-HDL-C/HDL-C ratio (P for trend, <0.05). Receiver Operating Characteristic (ROC) analysis indicated that the AUC of the apoB/apoAΙ ratio (0.561) was higher than that of the non-HDL-C/HDL-C ratio (0.522) in men (P<0.05) and the AUC of the apoB/apoAΙ ratio (0.640) was lower than that of the non-HDL-C/HDL-C ratio (0.695) in women (P<0.05). Among Chinese individuals with MetS, the AUC of the non-HDL-C/HDL-C ratio was more prominent among women compared with men (P<0.05). CONCLUSION: Our findings indicate that among individuals with MetS, Chinese men develop carotid atherosclerosis at a much younger age than women. There were no significant differences between the apoB/apoAΙ ratio and the non-HDL-C/HDL-C ratio for the prediction of carotid atherosclerosis among Chinese individuals with MetS. Among Chinese individuals with MetS, the utility of the non-HDL-C/HDL-C ratio was found to be greater among women than among men.

A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.

BACKGROUND: The aim of this study was to investigate the possible correlation between levels of serum liver enzymes and impaired fasting glucose (IFG) in Chinese adults and to provide a new perspective for the prevention of pre-diabetes. MATERIAL/METHODS: Serum liver enzymes of the samples including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl transferase (GGT), as well as plasma glucose, blood lipids, and insulin, were measured. The cumulative incidences of IFG between different quartiles of liver enzymes were compared by the chi-square test. A logistic regression model (binary regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence interval (95% CI). RESULTS: The total incidence of IFG was 20.3% and the cumulative incidence of IFG was higher in men compared to women. In both sexes, IFG is more prevalent in higher quartiles of liver enzymes. After adjusting for age, BMI, blood pressure, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), the cumulative incidences of IFG were significantly higher in the highest quartiles of liver enzymes than in the lowest quartiles. A significantly higher cumulative incidence of IFG was found in the highest GGT quartile than in the lowest quartile for woman. CONCLUSIONS: The results of this study suggest that serum liver enzymes are related to the risk of IFG in Chinese adults. We infer that preserving the hepatic function may be an efficient way to prevent the development of IFG, especially in males.

Lipid profile alterations in non-infectious uveitis: correlation with quantitative optical coherence tomography angiography parameters.

BACKGROUND/AIMS: Lipid profiles have been changed in numerous chronic conditions. The impact of uveitis on lipid metabolism remains unclear. METHODS: This is a cross-sectional study included 416 patients with non-infectious uveitis (NIU) and 416 healthy subjects. Standard techniques were used to measure total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDLc), low-density lipoprotein-cholesterol (LDLc) levels. Quantitative optical coherence tomography angiography (OCTA) parameters were obtained from 500 eyes in each group. Correlation analysis examined the relationship between lipid profile and OCTA parameters. RESULTS: Patients with NIU exhibited significantly elevated TC, TG and LDLc levels compared with controls (p=0.003; p<0.001; p<0.001, respectively). Subgroup analysis revealed that HDLc was significantly lower in Behçet's disease (p=0.024) compared with controls. Vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris and optic disk were significantly decreased in NIU eyes (p<0.05, respectively) compared with controls. HDLc exhibited a significant negative correlation with VDs in the whole and parafovea SCP (r=-0.489, p=0.008; r=-0.480, p=0.0026, respectively), while LDLc showed a significant positive correlation with VDs in the whole and parafovea DCP in NIU patients (r=0.576, p=0.032; r=0.267, p=0.034, respectively). CONCLUSIONS: The lipid profile is altered in NIU, and there are correlations between HDLc and LDLc levels and VD as measured by OCTA. Lipid profile analysis may offer valuable insights into evaluating vascular and metabolic aspects of NIU.

Postbiotics: emerging therapeutic approach in diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients that poses a serious risk as it can cause substantial visual impairment and even vision loss. Due to the prolonged onset of DR, lengthy treatment duration, and limited therapeutic effectiveness, it is extremely important to find a new strategy for the treatment of DR. Postbiotic is an emerging dietary supplement which consists of the inactivate microbiota and its metabolites. Numerous animal experiments have demonstrated that intervention with postbiotics reduces hyperglycemia, attenuates retinal peripapillary and endothelial cell damage, improves retinal microcirculatory dysfunction, and consequently delays the progression of DR. More strikingly, unlike conventional probiotics and prebiotics, postbiotics with small molecules can directly colonize the intestinal epithelial cells, and exert heat-resistant, acid-resistant, and durable for storage. Despite few clinical significance, oral administration with postbiotics might become the effective management for the prevention and treatment of DR. In this review, we summarized the basic conception, classification, molecular mechanisms, and the advances in the therapeutic implications of postbiotics in the pathogenesis of DR. Postbiotics present great potential as a viable adjunctive therapy for DR.

Gypenoside A-loaded mPEG-PLGA nanoparticles ameliorate high-glucose-induced retinal microvasculopathy by inhibiting ferroptosis.

Diabetic retinopathy (DR) is one of the chronic microvascular complications of type 2 diabetes mellitus (T2DM), which will cause retinal detachment and blindness without ideal therapies. Gypenoside A (GPA) are the main bioactive compound from Gynostemma pentaphyllum, and have various pharmacological effects. However, it suffered from poor bioavailability and potential cardiotoxicity in the clinical application. To overcome those limitations, in this study, nearly spherical nanoparticles (GPA-NP) with a mean particle size of 140.6 ± 22.4 nm were prepared by encapsulating GPA into mPEG-PLGA. This encapsulation efficiency was 84.4 ± 6.9 %, and the drug load was 4.02 %±0.35 %. The results showed that GPA-NP displayed more prolonged GPA release and higher bioavailability in vitro than GPA. GPA-NP obviously reduced the levels of oxidative stress markers and inflammatory cytokines in both retinal tissues of DR mice and high glucose-exposed HRMEC better than GPA alone. Mechanismly, GPA blocked the Nrf2-Keap1 interaction by binding with Kelch domain of Keap1 via alkyl and hydrogen bonds. Therefore, GPA-NP exerted more potent protectivity effects against high glucose-induced retinal microvascular endothelial ferroptosis in vitro and in vivo by activating Nrf2/HO-1/GPX4 pathway. It could be a promising therapeutic agent for preventing DR.

Gender and ethnic disparities of HIV and syphilis seroconversions in a 4-year cohort of injection drug users.

This study assessed gender and ethnic disparities of HIV and syphilis seroconversions in a cohort of injection drug users (IDUs) in Southwest China. A cohort of HIV-seronegative IDUs was followed up from November 2002 to January 2007. The average seroincidence for HIV and syphilis was 2.2 and 4.2 per 100 person-years (PYs), respectively. Multivariable Poisson regression models indicated that the predictors for incident HIV seroconversion included non-Han minority ethnic groups (RR: 5.2; 95% CI: 1.9-14.4) and injecting drugs > or = 7 times/week in the past 3 months (RR: 3.6; 95% CI: 1.4-9.8). The predictors for incident syphilis seroconversion included female (RR: 4.1; 95% CI: 1.8-9.3) and being married or cohabiting (RR: 2.7; 95% CI: 1.2-5.9). These findings suggested that HIV continues to spread among IDUs, especially among Yi and other minority ethnic groups, and frequent risky injections might be the major diver of the epidemic. Female IDUs are disproportionally affected by syphilis. Further research is needed to better understand the ethnicity disparity for HIV and gender disparity for syphilis.

Surveys of transmitted HIV drug resistance in 7 geographic Regions in China, 2008-2009.

In 2003, antiretroviral therapy became available free of charge in China's public health sector. During 2008 and 2009, 10 surveys to classify transmitted human immunodeficiency virus drug resistance (HIVDR) were conducted in 7 regions in 5 provinces (autonomous regions and municipalities) according to World Health Organization guidance. In 2008, transmitted HIVDR was classified as low (<5%) to nucleoside reverse-transcriptase inhibitors, nonnucleoside reverse-transcriptase inhibitors, and protease inhibitors in 6 surveys performed in 6 regions. In 2009, 3 of 4 surveys showed low rates of transmitted HIVDR to all drug classes, and 1 survey showed moderate (5%-15%) rates of transmitted protease inhibitor resistance. In China, routine surveillance of transmitted HIVDR should continue and be expanded to other regions of the country.

Impact of methadone on drug use and risky sex in China.

This study examined the impact of methadone on drug-using and risky sexual behaviors among 557 heroin injection drug users in one of the first methadone programs in China. Structured questionnaires were administered to collect data on methadone utilization, drug use, and risky sexual behaviors. Blood samples were tested for blood-borne infections. Multivariate logistic analyses revealed that, among opioid-addicted individuals, methadone participants were less likely to use or inject drugs and share needles than nonparticipants. They also were less likely to have multiple sexual partners or have unprotected sex. Those currently enrolled in methadone maintenance had lower risk of using and injecting drugs than those who were no longer receiving methadone. Data suggest positive, short-term impact on these important behaviors, but further studies are needed to examine the long-term impact of methadone treatment on disease rates.

Association of prehypertension and hyperhomocysteinemia with subclinical atherosclerosis in asymptomatic Chinese: a cross-sectional study.

OBJECTIVES: Comorbid hypertension and hyperhomocysteinemia is an important risk factor for carotid atherosclerotic plaque formation. We put forward the hypothesis that the subjects with comorbid prehypertension and hyperhomocysteinemia also had an increased risk of subclinical atherosclerosis, using carotid intima-media thickness (CIMT) as the marker of the atherosclerotic process. METHODS: A total of 4102 asymptomatic Chinese subjects aged 18-60 years were divided into four groups according to blood pressure (BP) and homocysteine (HCY) level: the control group without prehypertension or hyperhomocysteinemia, isolated prehypertension group, simple hyperhomocysteinemia group and prehypertension with hyperhomocysteinemia group. Serum lipids, fasting blood glucose (FBG), HCY and CIMT were measured. RESULTS: There was significant difference in the positive rates of increased CIMT among four groups. Compared with the controls, the subjects in the other three groups had a higher risk of increased CIMT (isolated prehypertension group, OR 2.049, 95% CI 1.525 to 2.754; simple hyperhomocysteinemia group, OR 2.145, 95% CI 1.472 to 3.125; prehypertension and hyperhomocysteinemia group, OR 3.199, 95% CI 2.362 to 4.332). However, by multiple logistic regression analysis, only comorbid prehypertension and hyperhomocysteinemia was independently associated with increased CIMT (OR 1.485, 95% CI 1.047 to 2.108, P<0.05). CONCLUSIONS: Comorbid prehypertension and hyperhomocysteinemia was an independent risk factor of subclinical atherosclerosis in asymptomatic Chinese, but isolated prehypertension or hyperhomocysteinemia was not. Therefore, combined intervention for prehypertension and hyperhomocysteinemia may contribute to decrease the incident of cardiovascular disease.

Variability of metabolic risk factors associated with prehypertension in males and females: a cross-sectional study in China.

INTRODUCTION: Prehypertension is highly prevalent. However, very few studies have evaluated the association of various metabolic risk factors in those with prehypertension and, more importantly, possible differences based on gender. MATERIAL AND METHODS: Data of clinical characteristics were collected from 3891 subjects. Risk factors were analyzed by multiple logistic regression analysis. The areas under receiver operating characteristic curves were compared to assess the discriminatory value of metabolic parameters for predicting prehypertension. RESULTS: The incidence of prehypertension was 55.9% (66.9% of men, 41.1% of women). Prehypertensives showed clusters of metabolic associations including changes in the levels of plasma high-density lipoprotein cholesterol (OR = 1.550), triglycerides (OR = 1.141) and fasting blood glucose (OR = 1.320) after adjusting for age, sex, body mass index and smoking. The metabolic associations also showed differences based on gender. For instance, higher total cholesterol (OR = 1.602) was the most evident risk factor in men with prehypertension, while higher triglycerides (OR = 1.314) and lower high-density lipoprotein cholesterol (OR = 1.729) were the main risk factors in women. CONCLUSIONS: Our study suggests that risk associations of prehypertension show gender differences. These results emphasize the importance of health education, active management of blood pressure and timely and effective treatment of abnormal lipid profile in subjects with prehypertension.

Low PG I/II ratio as a marker of atrophic gastritis: Association with nutritional and metabolic status in healthy people.

A low pepsinogen (PG) I/II ratio can be used to detect atrophic gastritis (AG). Recent research has found that the PG I/II ratio is associated with several nutritional and metabolic disorders. The aim of this study is to investigate the relationship between the PG I/II ratio and biochemical markers in a Chinese population.In total, 1896 participants in a gastric cancer screening program underwent a health screening test that included assessment of serum pepsinogens. Subjects with PG I/II < 3.0 were considered as having atrophic gastritis. Associations between the PG I/II ratio and biochemical markers reflecting glucose and lipid metabolism, liver, kidney and thyroid functions were evaluated using SPSS software version 20.The prevalence of atrophic gastritis was 5.3% and increased with age but did not differ between sexes. Albumin, ferritin, and total and direct bilirubin were significantly lower in patients with AG than in those without AG, whereas age, total bile acid, and amylase were significantly higher. Albumin, ferritin, and triglyceride correlated positively with the PG I/II ratio, while age, total bile acid, blood urea nitrogen, amylase, aspartate aminotransferase, creatine kinase, and lactate dehydrogenase correlated inversely with the PG I/II ratio. Logistic regression analysis demonstrated that age, total bile acid, total protein, and ferritin correlated independently with AG.Low PG I/II ratio is not only a marker of atrophic gastritis but also an indicator of nutritional and metabolic status. Special attention should be paid to the metabolism of iron, protein, and bile acid in patients with a low PG I/II ratio.

Quantification of glycocholic acid in human serum by stable isotope dilution ultra performance liquid chromatography electrospray ionization tandem mass spectrometry.

A rapid, accurate and sensitive stable isotope dilution ultra performance liquidchromatography electrospray ionization tandem mass spectrometry (ID-UPLC-ESI-MS/MS) method for the determination of glycocholic acid (GCA) in human serum was developed and validated. Serum samples were spiked with D5-glycocholic acid and then pretreated with protein precipitation. The analysis was performed on a Waters BEH C18 column (100 mm×2.1mm, 1.7µm), followed by ESI-MS/MS detection in negative ion mode under multiple reaction monitoring mode. The calibration curves covered a concentration range from 0.2 to 400ng/mL. The limit of detection and limit of quantification was 0.01ng/mL and 0.05ng/mL, respectively. The method showed satisfactory precision on intra-day (2.3-6.1%) and inter-day (2.4-4.6%) analyses and achieved good recovery at three spiked levels (103.7-114.3%). Moreover, this established method was successfully applied for quantification of GCA in serum samples from healthy volunteers, patients with hepatocellular carcinoma (HCC) and patients with other cancers. We demonstrated that the level of GCA in patients with HCC was significantly higher not only than that in healthy controls, but also than that in patients with other cancer, whereas no significant difference of GCA level was observed between healthy control group and other cancers group.

Genotypic analysis of the protease and reverse transcriptase of HIV type 1 isolates from recently infected injecting drug users in western China.

The partial pol gene was analyzed to determine circulating HIV-1 subtypes and the prevalence of drug resistance among recently infected injecting drug users in the west of China. Phylogenetic and bootscanning analyses showed that all 25 sequences belonged to CRF07_BC. No major drug resistance mutations were found, while the CRF07_BC sequences harbored a few highly prevalent polymorphic positions in both the protease and reverse transcriptase regions. It is notable that D60E, L63P and I93L substitutions, which were more common in HIV-1 isolates from PI-treated than untreated patients, were present in most of the isolates. Compared with subtype B, the CRF07_BC strains had a decreased genetic barrier for the V106M mutation, which is selected by efavirenz and leads to high-level resistance to all present nonnucleoside RT inhibitors. Further studies are needed to determine the impact of genetic features of CRF07-BC on antitretroviral susceptibility and evolution of drug resistance mutations.

Association of platelet-monocyte aggregates with platelet activation, systemic inflammation, and myocardial injury in patients with non-st elevation acute coronary syndromes.

BACKGROUND: Platelet-monocyte aggregates (PMA) and C-reactive protein (CRP) are increased in unstable coronary disease. The interrelation of PMA with platelet activation, systemic inflammation, and their association with markers of myocardial injury has not been studied extensively. HYPOTHESIS: The study was undertaken to evaluate the association of CRP, PMA, and cardiac troponin I (cTnI) in patients admitted with non-ST elevation acute coronary syndromes (NSTE-ACS). METHODS: In all, 69 consecutive patients with NSTE-ACS, 58 patients with stable angina pectoris (SAP), and 46 control patients without coronary artery disease were selected; PMA, sP-selectin, sCD40L inter leukin, (IL)-6, CRP, and cTnI concentrations were measured in these patients at the time of admission. Patients with NSTE-ACS were classified into two groups: those with troponin normal (cTnI < 0.06 ng/ml) and those with troponin elevation (cTnI > or = 0.06 ng/ml). Their risk for clinical in-hospital cardiac events (death and nonfatal myocardial infarction) was analyzed. RESULTS: Compared with SAP and control, patients with NSTE-ACS exhibited higher levels of PMA, sP-selectin, sCD40L, IL-6, and CRP. All these parameters were found to be higher (p < 0.001 ) in patients with troponin elevation than in those with normal troponin. There was a significant relationship between PMA and CRP (r =0.628, p < 0.001) and cTnI (r = 0.557, p < 0.001) in patients with NSTE-ACS. Logistic analysis further demonstrated that the presence of elevated PMA, CRP, and cTnI levels each confers and increases risk of future cardiac events. CONCLUSIONS: Levels of PMA and CRP were significantly increased in patients with NSTE-ACS, especially in those with troponin elevation. This increase is strongly related to the risk of in-hospital cardiac events. A panel of PMA, CRP, and cTnI may provide important information additional to current laboratory data for the treatment of NSTE-ACS.

Continued spread of HIV among injecting drug users in southern Sichuan Province, China.

OBJECTIVE: To estimate HIV prevalence among injecting drug users (IDUs) in a drug trafficking city in southwest Sichuan Province, China. METHODS: A total of 314 IDUs was invited to participate in the cross-sectional survey in 2004 through community outreach recruitment and peer referrals. Blood sample was taken for HIV antibody testing and a structured questionnaire was administered to collect information on socio-demographics, drug using and sexual behaviors. RESULTS: HIV prevalence among IDUs was 17.8% (56/314), about one half higher than that in previous survey in 2002 (11.3%, 43/379). Yi and other minority ethnicity (Odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7-5.8; P < 0.001), and total times of sharing injecting equipment 1-9 times versus none, OR, 2.7; 95% CI 1.2-6.2; P = 0.02; and > or = 10 times versus none, OR, 7.5; 95% CI, 3.2-17.7; P < 0.001) were independent risk factors for HIV infection. CONCLUSION: IDUs with high prevalence rates of HIV and equipment sharing behavior in the drug trafficking city may serve a source for further spread of HIV to other areas in China. The increasing trend of HIV epidemic among IDUs underscores the urgency of scaling up interventions.

(99m)Tc-YIGSR as a receptor tracer in imaging the Ehrlich ascites tumor-bearing mice as compared with (99m)Tc-MIBI.

The validity of (99m)Tc-YIGSR, a novel receptor radio-tracer, in imaging the Ehrlich ascites tumor was evaluated. YIGSR, a pentapeptide of laminin, was labeled with (99m)Tc by using a bifunctional chelator S-Acetly-NH(3)-MAG(3). The MIBI was labeled with (99m)Tc by following the kit instruction. The mice of tumor group were intravenously injected 1-2 mCi of (99m)Tc-YIGSR or (99m)Tc-MIBI via caudal vein, immobilized and imaged under a Gamma camera. The same procedure was performed in mice of blockade group, in which the unlabeled YIGSR was previously injected to block the receptor-recognition sites, and inflammation group serving as control. The reverse-phase Sep-Pak C(18) chromatogram was found to have an essentially complete conjugation between YIGSR and S-Acetly-NH(3)-MAG(3). The conjugated YIGSR could be radio-labeled successfully with (99m)Tc at room temperature and neutral pH, with a radio-labeling yield of 62%. Without the chelator S-Acetly-NH(3)-MAG(3), the YIGSR was labeled with (99m)Tc at an efficiency of 4%. The imagological study revealed obvious tumor accumulation of (99m)Tc-YIGSR 15 min after the injection, and the uptake peaked after 3 h with a tumor-to-muscle ratio (T/M) of 11.36. The radio-tracer was slowly cleared up and resulted in a T/M of 3.01 at the 8th h after the injection. As for blocked group, the tumor uptake of radiotracer was significantly lower, with the highest T/M being 4.61 after 3 h and 0.89 after 8 h. The T/M was 3.72 at the 3rd h and 1.29 at the 8th h after the (99m)Tc-YIGSR injection in the inflammatory group. The T/M was significantly higher in tumor group than in inflammatory group or control group (P<0.001). In the 99mTc-MIBI group, the T/M was 1.40 at the 3rd h and 0.55 at the 8th h after the injection, which showed a significant difference as compared with (99m)Tc-YIGSR (P<0.001). It is concluded that YIGSR can be successfully radiolabelled by using S-Acetly-NH(3)-MAG(3). (99m)Tc-YIGSR has many advantages in tumor imaging, such as quick and clear visualization, high sensitivity and specificity, and satisfactory target/non-target ratio (N/NT). It promises to be tumor radio-tracer.

[Factors associated with retention in a community-based methadone maintenance treatment among heroin addicts].

OBJECTIVE: To explore factors associated with retention in a community-based methadone maintenance treatment (MMT) among heroin addicts in Xichang of Sichuan province. METHODS: All 206 heroin addicts were first admitted to MMT community-based program between March to September 2004. Baseline data of patients characteristics, social function, drug using behaviors, sexual behaviors, dose of methadone and retention were collected. RESULTS: Up to Oct, 2005, all 206 patients contributed 8.98 +/- 5.74 person-months of following-up. The retention rates were 58.7% after 6 months and 34.6% after 12 months respectively. Cox proportional hazard regression model indicated that the employed (HR, 0.60; 95% CI, 0.39 - 0.92), helping family to do housework in past 30 days more than once a day (HR, 0.59; 95% CI, 0.42 - 0.82) and previous self-detoxification > or = 3 times (HR, 0.65; 95% CI, 0.47 - 0.91) were independently associated with retention. CONCLUSION: We should give individual counseling to help heroin addicts increasing compliance.

Metabolic enzymes: key modulators of functionality in cancer stem-like cells.

Cancer Stem-like Cells (CSCs) are a subpopulation of cancer cells with self-renewal capacity and are important for the initiation, progression and recurrence of cancer diseases. The metabolic profile of CSCs is consistent with their stem-like properties. Studies have indicated that enzymes, the main regulators of cellular metabolism, dictate functionalities of CSCs in both catalysis-dependent and catalysis-independent manners. This paper reviews diverse studies of metabolic enzymes, and describes the effects of these enzymes on metabolic adaptation, gene transcription and signal transduction, in CSCs.