[Incidence of diabetes and influencing factors in HIV-infected individuals after antiretroviral therapy in Dehong Dai and Jingpo Autonomous Prefecture].

Objective: To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong). Methods: The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4. Results: A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions: The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.

[Tokyo Bones Find and human experiments by the army medical school in Tokyo].

More than 100 human bones, known as the Tokyo Human Bones, were found at the previous site of the Army Medical School in Tokyo, Japan, on July 22, 1989. They were located on the northern side of the previous location of the epidemic prevention research unit of the Army Medical School, with the discovery drawing a great deal of international attention. It was suggested that these bones might be from the victims of human experiments during World War II. It was found, in 1991, by Professor Sakura Shuo in Sapporo University, that the time and location of the burial of these bones was consistent with the existence of the Army Military Medical School. Most of these bones were Chinese, Korean and Mongolian races, and they were indeed closely related to the war. At the time they had not been found to be directly related to the human experiments of the Army Medical School, but the evidence left behind on the bones did not indicate gunshot or other war wounds, but evidence of medical experiments. This incident was known as the "Tokyo Bone Incident". Based on the research data on the Tokyo Human Bones internationally in the past 30 years, in particular, the testimony from the staff of the previous Army Medical School in Tokyo and members of the previous Army Medical School in Harbin (Unit 731), it can be concluded that some relationship exists between the Tokyo Human Bones and human experiments. This suggested that the nature of research related to these human bones conducted by the Army Medical School in Tokyo was consistent with those conducted at the Army Medical School in Harbin (Unit 731).

[A survey on the willingness of college students majoring in public health to work in their majors].

Objective: To understand the basic qualities, practitioners will and related influences, of undergraduate, master, and doctoral students majoring in public health (hereinafter referred to as public health students), and explore the influencing factors of practitioners will. Methods: Through the online questionnaire survey, we collected information on the basic qualities of the public health students, their practitioners will and related influencing factors, and their opinions on the current state of public health in China. χ2 test and multi-factor logistic regression were used to analyze the influencing factors of public health students' willingness to engage in public health related work, and word frequency analysis was used to conduct a descriptive analysis of public health students' views on public health in China. Results: A total of 2 081 pieces of valid information were collected, of which 86.54% (1 801/2 081) of the students in the school chose to engage in public health related work in the future. For public health students, the higher the target after-tax monthly income (OR=0.345, 95%CI: 0.158-0.751), the lower the willingness to engage in public health related work in the future; Very satisfied with school employment guidance work (OR=4.072, 95%CI: 1.234-13.436) compared with very dissatisfied, the willingness to engage in public health related work in the future is higher. Conclusion: The willingness of students in public health related majors to engage in public health related majors in China is mainly affected by three factors: payment levels, employment guidance and professional post recognition. It is recommended to appropriately raise the salaries of public health related positions. Strengthening school employment guidance training and professional identity training is conducive to enhancing the willingness of public health students to engage in relevant work in their profession.

[Incidence and influencing factors of AIDS-related and non-AIDS-related deaths after receiving antiretroviral therapy among HIV-positive individuals in Dehong Dai and Jingpo Autonomous Prefecture, 2010-2019].

Objective: To explore the changing trends and influencing factors of AIDS-related and non-AIDS-related deaths after receiving antiretroviral therapy (ART) among HIV-positive individuals in Dehong Dai Jingpo autonomous prefecture (Dehong) from 2010 to 2019. Methods: Based on the Chinese National treatment database, HIV patients who initiated ART from 2010 to 2019 were included in the analysis. The cumulative incidence function was used to estimate the cumulative incidence of AIDS-related death and non-AIDS-related death, respectively. The Fine-Grey model was used to compare the differences between AIDS-related and non-AIDS-related deaths and analyze its influencing factors. Results: A total of 7 068 HIV-positive individuals were included, of which 388 were AIDS-related deaths and 570 were non-AIDS-related deaths. The cumulative mortality rate at years 1, 2, 3, 4, 5, 7 and 9 after receiving ART were 2.27%, 3.46%, 4.47%, 5.03%, 5.84%, 6.61%, 7.40% for AIDS-related deaths, and 1.63%, 3.11%, 4.68%, 6.02%, 7.42%, 10.49%, 12.75% for non-AIDS-related deaths, respectively. In the Fine-Grey model, older age at ART initiation, male, unmarried, injection drug use as the transmission route, lower baseline BMI, lower baseline CD4+ T cell counts, baseline FIB-4 score >3.25, and baseline anemia were risk factors for AIDS-related death. In contrast, age at ART initiation ≥45 years, male, Dai, and Jingpo minority ethnicities, unmarried, injection drug use as the transmission route, lower baseline BMI, baseline FIB-4 score >3.25, baseline eGFR <60 ml·min-1·1.73 m-2, and baseline anemia were risk factors for non-AIDS-related deaths. Conclusions: The cumulative mortality rate was low among HIV-positive individuals after receiving ART in Dehong during 2010-2019. The mortality of non-AIDS-related deaths was higher than that of AIDS-related deaths. There were also differences in the factors influencing AIDS-related and non-AIDS-related deaths and interventions should be intensified to target the influencing factors for non-AIDS-related deaths.

[A retrospective cohort study of incidence of anemia and risk factors in HIV/AIDS patients with access to antiretroviral therapy in Dehong Jingpo and Dai Autonomous Prefecture in Yunnan province, 2004-2018].

Objective: To investigate the incidence of anemia and risk factors in HIV/AIDS patients with access to antiretroviral therapy (ART) during 2004-2018 in Dehong Jingpo and Dai Autonomous Prefecture (Dehong). Methods: A retrospective cohort study was conducted in HIV/AIDS patients receiving ART in Dehong during 2004-2018 based on the data extracted from the National HIV/AIDS antiretroviral therapy database. Cox proportional risk model was used to analyze the factors associated with the incidences of anemia and moderate or severe anemia in the HIV/AIDS patients. And the piecewise linear mixed-effects model was used to depict the trajectory of hemoglobin changes over time after initiating ART according to baseline level. Results: A total of 8 044 HIV/AIDS patients were included, in whom 6 337 (78.8%) were without anemia at baseline survey and had a median follow up time of 4.43 (P25, P75: 1.50, 6.71) years. The median follow up time for 1 291 new anemia cases and 293 new moderate or severe anemia cases was 0.16 (P25, P75: 0.07, 1.99) years and 0.48 (P25, P75:0.09, 2.97) years, respectively. The incidence rate of anemia and moderate or severe anemia was 4.40 per 100 person-years and 0.41 per 100 person-years respectively. In multivariable Cox regression analysis, older age, being female, being in Dai and Jingpo ethnic group, baseline BMI <18.5 kg/m2, baseline CD4+T lymphocyte cell counts (CD4) <200 cells/µl, and zidovudine (AZT) -based initial treatment regimen were factors significantly and positively associated with incidence of anemia after treatment. Factors as being female, being in Dai ethnic group, baseline BMI <18.5 kg/m2, mild baseline anemia, and AZT-based initial treatment regimen were significantly and positively associated with incidence of moderate or severe anemia after treatment. Conclusion: The risk for anemia was higher in HIV/AIDS patients with specific characteristics, such as age ≥60 years , being female, being in Dai and Jingpo ethnic groups, lower BMI, CD4 <200 cells/µl, and treatment of AZT, after initiation of ART in Dehong during 2004-2018. Additional efforts are needed to strengthen the screening, prevention and treatment of anemia in this population.

Threshold Heat-Flux Reduction by Near-Resonant Energy Transfer.

Near-resonant energy transfer to large-scale stable modes is shown to reduce transport above the linear critical gradient, contributing to the onset of transport at higher gradients. This is demonstrated for a threshold fluid theory of ion temperature gradient turbulence based on zonal-flow-catalyzed transfer. The heat flux is suppressed above the critical gradient by resonance in the triplet correlation time, a condition enforced by the wave numbers of the interaction of the unstable mode, zonal flow, and stable mode.

[Human experiment study of Unit 731, Japan: take the report "The Research Report on Epidemic Prevention of Army Medical School â ¡: Vol.1, No.36 " as an example].

"The Research Report on Epidemic Prevention of Army Medical School Ⅱ: Vol.1, No.36" , the report named "various symptoms and serological responses of human body after receiving ultrasonic cholera vaccine" is one of the declassified materials of Japanese biological warfare. The author is M. D. Watanabe Be. Through detailed analysis of its contents, such as institute of report, test method, test results, and so forth, conclusion is reached that Unit 731 did conduct scientific research based on human-subject experiment to launch biological warfare on human beings. The report mentioned above is one of the most important evidence of crime that Japan conducts biological warfare which violates international convention and contempt bottom line of human basic morals and ethics.

Health-related quality-of-life among patients with premature ovarian insufficiency: a systematic review and meta-analysis.

PURPOSE: To systematically review studies investigating health-related quality-of-life (HrQoL) in patients with premature ovarian insufficiency (POI), to examine questionnaires used and to conduct a meta-analysis of control studies with normal ovarian function. METHODS: Data sources: PubMed, Embase, Web of science, CNKI, and CQVIP, searched from inception until June 2018. The search strategy was a combination of medical (e.g. POI), subjective (e.g. well-being) and methodological (e.g. questionnaires) keywords. PRISMA guidelines were used to assess outcome data quality/validity by one reviewer, verified by a second reviewer. Risk of bias within studies was evaluated. A meta-analysis compared HrQoL in patients and non-patients. Due to measurement differences in the studies, the effect size was calculated as standard mean difference. RESULTS: We identified 6869 HrQoL studies. Nineteen geographically diverse studies met inclusion criteria, dated from 2006, using 23 questionnaires. The meta-analysis included six studies with 645 POI participants (age 33.3 ± 5.47) and 492 normal-ovarian control subjects (age 32.87 ± 5.61). Medium effect sizes were found for lower overall HrQoL (pooled SMD = - 0.73, 95% CI - 0.94, - 0.51; I2 = 54%) and physical function (pooled SMD = - 0.54, 95% CI - 0.69, - 0.39; I2 = 55%). Heterogeneity was investigated. Effect sizes varied for sexual function depending on the measure (SMD = - 0.27 to - 0.74), overall HrQoL (SF-36) had the largest effect size (- 0.93) in one study. The effect sizes for psychological and social HrQoL were small. CONCLUSION: POI is associated with low-to-medium effect size on HrQoL compared to normal ovarian controls. The greatest effects are found in general HrQoL and most sexual function areas. Condition-specific questionnaires and RCTs are recommended for further investigation.

[Prevalence and related factors on diabetes among HIV/AIDS receiving antiretroviral therapy in Dehong Dai and Jingpo Autonomous Prefecture].

Objective: To study the prevalence and correlates of diabetes among HIV/AIDS who were on antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefectures (Dehong), Yunnan province. Methods: The database of HIV/AIDS receiving ART in Dehong was downloaded by using the basic information system of AIDS prevention and control in China. In this cross-sectional study, HIV/AIDS patients who were currently on ART and aged 18 years or above, were consecutively recruited, between July 2017 and June 2018, in Dehong. All the subjects underwent hemoglobin A1c (HbA1c) testing. Patient with diabetes was defined as meeting any of these indicators (HbA1c ≥6.5%, baseline FPG ≥7.0 mmol/L, FPG ≥7.0 mmol/L in the most recent visit). Both univariate and multivariate logistic regression analysis were carried on to evaluate the correlates of diabetes among the HIV/AIDS patients. Results: In total of 4 376 HIV/AIDS patients were included for analysis, with the average age as (43.7±10.1) years, proportion of males as 53.8% (2 356/4 376) and the HCV positive rate as 24.1% (1 055/4 376). The mean years was (8.9±3.8) years after the HIV diagnosis was made, and the mean duration on treatment was (6.8±2.9) years. The prevalence of diabetes was 11.4% (500/4 376). Through multivariate logistic regression analysis, data showed that the risk factors of diabetes of HIV/AIDS on ART were: aged 40 years or above, being male, HCV positive, baseline body mass index ≥24.0 kg/m(2), elevated TG ≥1.70 mmol/L in the most recent visit and baseline antiretroviral regimens under Efavirenz (EFV). Conclusions: Prevalence rate of diabetes appeared higher in HIV/AIDS patients who were on ART in Dehong. Prevention and control measures should be targeted on HIV/AIDS patients who were with risk factors of diabetes as being elderly, male, HCV positive, overweight and higher TG. Further esearch is needed to evaluate the association between the use of EFV and diabetes.

[Prognostic factors analysis of Ki-67, α-SMA expression in retroperitoneal leiomyosarcoma].

Objective: To investigate the expression and prognostic value of alpha smooth muscle actin(α-SMA) and Ki-67 in retroperitoneal leiomyosarcoma. Methods: Fifty retroperitoneal leiomyosarcoma patients who underwent operation in Chinese People's Liberation Army General Hospital from May 2002 to December 2015 were retrospectively analyzed. There were 14 males and 36 females form 21 to 79 and an average age of 48. Kaplan-Meier estimations and Cox regression analyses were performed. Results: Of the 50 cases, 45 patients underwent complete resection, and others are not. The overall 1, 3, 5-year survival rates were 86.0%, 46.0% and 28.0%, respectively. Tumor size, extent of resection, pathological stage, and expression levels of Ki-67 and alpha smooth muscle actin (α-SMA) were closely related to the survival of retroperitoneal leiomyosarcoma patients (all P<0.05), respectively. Multivariate analysis showed that pathological grade and degree of surgical resection were independent risk factors in the prognosis of patients (P<0.05). Conclusion: The high expression of α-SMA and Ki-67 are indicators of poor prognosis in retroperitoneal leiomyosarcoma, which can be used as a potential survival predictor in patients with retroperitoneal leiomyosarcoma.

Reducing Surgical Site Infection with Negative-Pressure Wound Therapy After Open Abdominal Surgery: A Prospective Randomized Controlled Study.

BACKGROUND AND AIMS: Surgical site infection, in particular superficial incision infection, is a common type of complication following abdominal surgery. Negative-pressure wound therapy has been confirmed to reduce the incidence of surgical site infection in various surgeries, but there are few prospective randomized studies into its application to abdominal surgery. MATERIAL AND METHODS: A prospective randomized controlled study was conducted in which patients with abdominal surgery and open surgery were randomly divided into a negative-pressure wound therapy experimental group and a gauze-covering control group. Information about demographic data, type of surgery, surgical sites, incision treatment outcomes, surgical site infection factors, and follow-up was recorded. RESULTS: From May 2015 to December 2015, 71 patients were enrolled in this study, including 33 in the experimental group and 38 in the control group. There were 10 cases of incision complications, all superficial infections, with an incidence of 14.1%. The surgical site infection incidence was statistically different between the experimental and control groups (3.0% vs 23.7%, p = 0.031). Multivariate logistic regression analysis showed that incision length ⩾20 cm increased the surgical site infection incidence (odds ratio value of 15.576, p = 0.004) and that the application of negative-pressure wound therapy reduced the surgical site infection incidence (odds ratio value of 0.073, p = 0.029). CONCLUSION: Negative-pressure wound therapy can reduce the incidence of surgical site infection in open abdominal surgery.

[Drug resistance and influencing factors in adult AIDS patients receiving antiretroviral treatment in Dehong, Yunnan province].

OBJECTIVE: To investigate the incidence of drug resistance in adult AIDS patients receiving antiretroviral treatment(ART)and influencing factors in Dehong prefecture, Yunnan province during 2012-2014. METHODS: For this cohort study, all the AIDS patients aged over 15 and receiving ART in Dehong were screened for HIV drug resistance in 2012, and 3 715 patients who had received ART for more than 6 months were enrolled for 12 months and 24 months follow up. RESULTS: Among the 3 715 patients, 56.6% were males, 72.6% were aged 26-45 years and 76.0% were married. The main treatment regimen was nevirapine(NVP)+ lamivudine(3TC)+ zidovudine(AZT)(38.2%). A total of 3 556 patients(95.7%)received at least one viral load testing during the two years follow-up, among them 253(7.1%)patients had VL≥1 000 copies/ml, in which 211(83.4%)received drug resistance related gene mutation testing, the results indicated that the drug resistance developed in 52 and 39 patients in 2013 and 2014(1.43 per 100 person years and 0.88 per 100 person years)respectively. The overall HIV drug incidence was 1.13 per 100 person years. Multivariate regression analysis indicated that age ≤25 years, to be infected through drug use, treatment regimen as D4T+ 3TC +NVP and baseline CD4(+) T cells ≤200 cells/µl were the risk factor of HIV drug resistance. Eleven HIV gene subtypes were detected in the 82 patients with newly developed drug resistance, CRF_BC was predominant(31.7%), followed by CRF01_AE(22.0%)and C(19.5%). Ten patients were infected with mixed subtypes of CRF_BC/B', CRF_BC/CRF_01B and CRF_BC/C. Most of the 82 patients were resistant to NRTIs and NNRTIs, the main mutation loci were M184V and K103N. CONCLUSIONS: The incidence of drug resistance in adult AIDS patients receiving ART was relatively low in Dehong. However, it is necessary to conduct the health education in young people and drug users to improve the treatment compliance and strengthen the surveillance for HIV drug resistance.

Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus.

We investigated the effects of type 1 diabetes mellitus (T1DM) on endothelial progenitor cells (EPCs) at the molecular level and assessed the therapeutic potential of folic acid (FA) in DM. We downloaded the gene expression profile of the EPCs from T1DM patients before and after treatment with FA and from healthy controls. We identified the differentially expressed genes (DEGs) in the EPCs from T1DM patients before and after a four-week period of FA treatment and compared them with those obtained from the healthy subjects by using limma package in R language. Then, functional annotation of the DEGs was performed using the online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) based on the Kyoto Encyclopedia of Genes and Genomes database. The expression of 696 genes was altered in the EPCs from T1DM patients compared to those from the healthy controls. These genes were mainly involved in the pathways associated with immune response. FA can normalize majority of the altered gene expression profiles of EPCs from T1DM patients to resemble those of healthy subjects, albeit with some side effects. FA can be a potential therapeutic agent for the treatment of T1DM. However, focused efforts are required to ensure that the dose of FA falls within the permissible pharmacological range.

Differential processing of neuropeptide proprotein in human breast adenocarcinoma.

BACKGROUND: The processing of proprotein convertase (PC)-mediated neuropeptide plays a very important role in carcinogenesis and tumor proliferation. AIM: To investigate proneuropeptide processing mechanism in tumorigenesis and tumor proliferation. MATERIALS AND METHODS: The expression and processing profiles of PC1, carboxypeptidase E (CPE), PC2, GHRH, or neuropeptide Y (NPY) gene and protein level were investigated between 42 human breast tumor tissues and 21 tumor-adjacent normal tissues. RESULTS: Gene analyses indicated that the proPC1, CPE, or preproNPY gene had higher expression in the breast tumor tissues, whereas the proPC2 or preproGHRH gene showed lower expression in the tissues. Protein analyses showed that the proPC1, PC1, CPE, GHRH, and preproNPY proteins were upregulated in the tumor tissues, whereas the proPC2, PC2, preproGHRH, and NPY proteins were down-regulated in them. The tissue results were highly corroborated with the serum data from the tumor patients and healthy women. CONCLUSIONS: The higher PC1 and CPE expressions as well as the transformation of more proGHRH into active GHRH peptide suggest stronger PC1/CPE-mediated neuropeptide processing in the tumor, whereas the lower PC2 expression as well as the transformation of less proNPY into active NPY peptide suggests a weak PC2-mediated processing in it. The alterations of the convertase expressions and processing show that there is a differential proprotein processing system in the tumor, which leads to the abnormal distributions of species, ratio, and concentration of (pro)peptide(s) in the microenvironment of cells. The latter may contribute to cancer progression.

Long-distance fiber-optic point-sensing systems based on random fiber lasers.

We find that the random fiber laser (RFL) without point-reflectors is a temperature-insensitive distributed lasing system for the first time. Inspired by such thermal stability, we propose the novel concept of utilizing the RFL to achieve long-distance fiber-optic remote sensing, in which the RFL offers high-fidelity and long-distance transmission for the sensing signal. Two 100 km fiber Bragg grating (FBG) point-sensing schemes based on RFLs are experimentally demonstrated using the first-order and the second-order random lasing, respectively, to verify the concept. Each sensing scheme can achieve >20 dB optical signal-to-noise ratio (OSNR) over 100 km distance. It is found that the second-order random lasing scheme has much better OSNR than that of the first-order random lasing scheme due to enhanced lasing efficiency, by incorporating a 1455 nm FBG into the lasing cavity.

Facile synthesis of superparamagnetic Ni-Fe ultrafine nanoalloy nanoparticles with equilibrium ordered phase structure via a sol-gel process.

Ni-Fe nanoalloy nanoparticles with an average grain size of 4 nm in diameter have been prepared by a sol-gel method under a hydrogen atmosphere where ethanol and oleic acid have been used as solvent and surfactant, respectively. X-ray diffraction (XRD) and selected area electron diffraction (SAED) examinations of the nanoparticles show the occurrence of (111), (200), (220) and (311) diffraction peaks and rings, meaning that the nanoparticles have a face-centered-cubic phase structure. Moreover, a superlattice diffraction peak and a diffraction ring/spot can also be observed in XRD and SAED results, indicating the formation of an equilibrium ordered L1(2) phase structure. The as-prepared Ni-Fe nanoalloy particles show typical superparamagnetic behavior at room temperature and the blocking temperature of the nanoparticles is determined to be about 50 K.

Toxicity of a novel anti-tumor agent 20(S)-ginsenoside Rg3: a 26-week intramuscular repeated administration study in rats.

The purpose of this study is to investigate the potential subchronic toxicity of 20(S)-Ginsenoside Rg3(Rg3), by a 26-week repeated intramuscular administration in rats. Rg3 was administrated to rats at dose levels of 0, 4.2, 10.0 or 20.0 mg/kg/day. There was no treatment-related mortality and, at the scheduled autopsy, dose-dependent increases in the absolute and relative spleen weights, of both the 10.0 mg/kg and 20.0 mg/kg dose groups were observed. Absolute and relative kidney weights were significantly elevated in the female 10.0 mg/kg dose group and in the male 20.0 mg/kg dose group. Hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) count and in the percentage of neutrophils, but a decrease in the percentage of lymphocytes, in rats treated with doses of 10.0/20.0 mg/kg. These effects were completely reversible during the recovery period, and no other adverse effects were observed. It was concluded that the 26-week repeated intramuscular dose of Rg3 caused increases in the spleen and kidney weights, WBC counts and in the percentage of neutrophils, but a decrease in the percentage of lymphocytes, with doses of 10.0 or 20.0 mg/kg/day. The no-observed-adverse-effect level for rats was considered to be 4.2 mg/kg/day.

MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses liver cancer cell growth in vitro and in vivo.

MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and have great potential for the diagnosis and treatment of cancer. However, the roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma by comparison of miRNA expression profiles in cancerous hepatocytes with normal primary human hepatocytes, and 37 dysregulated miRNAs were screened out by twofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patterns between the cancerous and normal hepatocytes were clearly different. Among the 13 miRNAs, we found that miR-375 was significantly downregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancer cells decreased cell proliferation, clonogenicity, migration/invasion and also induced G1 arrest and apoptosis. To unveil the molecular mechanism of miR-375-mediated phenotype in hepatoma cells described above, we examined the putative targets using bioinformatics tools and found that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated that miR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and western blot analysis showed that miR-375 expression was inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor properties. Ectopic expression of AEG-1, conversely, could partially reverse the antitumor effects of miR-375. In a mouse model, therapeutic administration of cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could significantly suppress the growth of hepatoma xenografts in nude mice. In conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and in vivo, and highlight the therapeutic potential of miR-375 in HCC treatment.

Toxicity of a novel anti-tumor agent 20(S)-ginsenoside Rg3: a 26-week intramuscular repeated administration study in Beagle dogs.

The potential subchronic toxicity of a dammarane-type triterpenoid saponin with antitumor effect, 20(S)-Ginsenoside Rg3, was studied repeated intramuscular administration in Beagle dogs over a 26-week period. 20(S)-Ginsenoside Rg3 was administrated intramuscularly at 0, 0.70, 2.86 or 7.20 mg/kg/day doses for 26 weeks in both male and female dogs (n = 4 for male and female dogs for each dose). During the test period as well as during the 8-week recovery period, clinical signs, mortality, body weights, food consumption, respiratory frequency, electrocardiogram, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined. In dogs treated with doses of 2.86 or 7.20 mg/kg, hematological investigations revealed a dose-dependent increase in the total white blood cell (WBC) count and in the percentage of neutrophils, but a decrease in the percentage of lymphocytes. These effects were completely reversed during the recovery period, and no other adverse effects were observed. The no-observed-adverse-effect levels for both male and female dogs were considered to be 7.20 mg/kg/day.