THBS2 promotes cell migration and invasion in colorectal cancer via modulating Wnt/ß-catenin signaling pathway.

Colorectal cancer (CRC) is the most common human digestive malignancy with a poor prognosis; the pathophysiology of colon cancer involves multiple linkages of regulatory networks. Recently, thrombospondin 2 (THBS2) has been extensively studied for its role in cancer progression. In this study, we evaluated the expression of THBS2 in CRC tissues and studied the possible mechanism by which THBS2 regulates CRC progression. Our results showed that the upregulation of THBS2 in CRC tissues and CRC cell lines and high expression of THBS2 was correlated with poor overall survival. The in vitro experimental data showed that THBS2 overexpression promoted CRC cell growth, invasion, and migration, while THBS2 inhibition exerted tumor-suppressive actions on CRC cells. THBS2 knockdown suppressed the activity of Wnt/ß-catenin signaling. Collectively, the results implied that THBS2 exerted promotional effects on CRC cell proliferation, invasion, and migration, partly by modulating the Wnt/ß-catenin signaling pathway.

XIST knockdown suppresses vascular smooth muscle cell proliferation and induces apoptosis by regulating miR-1264/WNT5A/ß-catenin signaling in aneurysm.

Long non-coding RNAs (lncRNAs) have been ascertained as vital modulators in abdominal aortic aneurysm (AAA) development. In this research, the function and molecular mechanisms of the lncRNA X-inactive specific transcript (XIST) in the evolution of vascular smooth muscle cells (VSMCs) were assessed. Results showed that XIST expression was increased but miR-1264 expression level was reduced in the serum of AAA patients. XIST depletion impeded human aorta VSMCs (HA-VSMCs') ability to proliferate and stimulate apoptosis, while repressing miR-1264 expression through an unmediated interaction. Additionally, the influence of XIST knockdown on apoptosis and proliferation could be rescued by an miR-1264 inhibitor. Subsequent molecular investigations indicated that WNT5A was miR-1264's target, and XIST functioned as a competing endogenous RNA (ceRNA) of miR-1264 to raise WNT5A expression. Further, an miR-1264 inhibitor stimulated the proliferation and suppressed the apoptosis of HA-VSMCs through the activation of WNT/ß-catenin signaling. Taken together, XIST impeded the apoptosis and stimulated the proliferation of HA-VSMCs via the WNT/ß-catenin signaling pathway through miR-1264, demonstrating XIST's underlying role in AAA.

Effects of low-dose aspirin on the prevention of preeclampsia and pregnancy outcomes: A randomized controlled trial from Shanghai, China.

OBJECTIVES: To evaluate the preventive effects of low-dose aspirin on the incidence of preeclampsia and pregnancy outcomes of women at high-risk for preeclampsia. STUDY DESIGN: This prospective randomized clinical trial was conducted at the Obstetrics Department of The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, China. It analyzed data from 1105 high-risk women who were divided into the control group (placebo group) and the aspirin group (including three subgroups: 25 mg, 50 mg and 75 mg). The aspirin group in this study was instructed to take aspirin daily before bedtime beginning in the 12th week of pregnancy. MAIN OUTCOME MEASURES: The primary outcome is the occurrence of preeclampsia. The secondary outcomes included maternal and neonatal outcomes (such as premature delivery, FGR etc.), maternal serum biomarkers (including d-dimers, platelet aggregation rates, etc.) and uterine arterial blood flow resistance. The onset of preeclampsia and pregnancy outcomes were recorded after all participants delivered. RESULTS: Low-dose aspirin significantly reduced the incidence of preeclampsia and early-onset preeclampsia. Aspirin also showed significant dose dependence in preeclampsia prevention. The results of Mantel-Haenszel trend test showed that there was a linear relationship between the dosage and the incidence of preeclampsia and early preeclampsia (P < 0.05). Pearson's results showed that the incidence of preeclampsia and early preeclampsia was negatively correlated with aspirin dosage. There was also a linear relationship between the dosage and the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section (P < 0.05). There was no evidence to suggest differences in the incidence of fetal distress, miscarriage and placental abruption among the four groups. The blood resistance S/D value of uterine artery in early pregnancy was the only independent factor affecting the efficacy of aspirin (OR = 1.405; 95 %CI,1.058-1.867; P = 0.019). CONCLUSION: Low-dose aspirin can prevent preeclampsia and early-preeclampsia. Its efficacy is dose-dependent. It can reduce the rates of postpartum hemorrhage, fetal growth restriction, premature births and cesarean section. The prophylactic effect of aspirin on preeclampsia seemed to be greater in patients with higher blood resistance S/D value of uterine artery during early pregnancy.

Mesenchymal stem cells-derived exosomes improve pregnancy outcome through inducing maternal tolerance to the allogeneic fetus in abortion-prone mating mouse.

Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. In the present study, bone marrow mesenchymal stem cells were isolated from CBA/J female mice and exosomes were isolated from cell culture medium by ultracentrifugation. CBA/J female mice were paired with male DBA/2 to generate abortion prone mouse model, and CBA/J females paired with male BALB/c mice were used as control. Exosomes were injected through uterine horns into pregnant CBA/J mice on day 4.5 of gestation in abortion-prone matting. On day 13.5 of pregnancy, abortion rates were calculated and the level of transforming growth factor-ß (TGF-ß), interleukin 10 (IL-10), interferon g (IFN-γ), and tumor necrosis factor a (TNF-α) in CD4+ T cells and macrophages in deciduas were evaluated by flow cytometry. Exosomes injection improved the pregnancy outcomes in abortion prone mice. The IL-4 and IL-10 levels on CD4+ T cells were upregulated in the maternal-fetal interface; meanwhile, the TNF-α and IFN-γ levels on CD4+ T cells were reduced. The IL-10 level was increased and IL-12 was reduced on the monocytes that separated from deciduas. miR-101 level was increased in the CD4+ T cells in the deciduas. In conclusion, the treatment of ESCs-derived exosomes modulates T cells' function and macrophages activities in the maternal-fetal interface that resulted in a decreased embryo resorption rate, and provides a therapeutic potential to treat RPL.

Epidemiological survey of sheep as potential hosts for Leishmania in China.

BACKGROUND: Leishmania parasites cause visceral leishmaniasis (VL), an important infectious disease that is endemic to large parts of the world and often leads to epidemics. Sand flies are the primary transmission vector for the parasite in endemic regions. We hypothesized that sheep might serve as an overlooked reservoir for Leishmania transmission to humans due to the asymptomatic nature of infection in many species. As a preliminary test of this hypothesis, the aim of the present study was to investigate sheep in an area of China that is endemic for the desert sub-type of zoonotic VL and establish if they are potential carriers of Leishmania. RESULTS: Sheep tissue samples were collected from abattoirs in VL endemic areas of Jiashi County, China during the non-transmission season. rK39 immunochromatographic tests were performed to detect the presence of the parasite in blood samples. In addition, DNA was extracted from the blood, and used for detection of the Leishmania-specific internal transcribed spacer-1 (ITS-1) genomic region using a nested polymerase chain reaction (PCR) approach. PCR products were further analyzed to identify restriction fragment-length polymorphism patterns and representative sequences of each pattern were selected for phylogenetic analysis. The rK-39 and nested PCR data indicated positive detection rates for Leishmania in sheep of 26.32 and 54.39%, respectively. The phylogenetic analysis revealed that all of the samples belonged to the species L. infantum and were closely related to strains isolated from human infections in the same area. CONCLUSIONS: Sheep could be a potential host for Leishmania in VL endemic areas in China and may be an overlooked reservoir of human VL transmission in this region. To further confirm livestock as a potential host, further verification is required using a sand fly biting experiment.

A retrospective comparative study evaluating the efficacy of adding intra-arterial methotrexate infusion to uterine artery embolisation followed by curettage for cesarean scar pregnancy.

PURPOSE: The study aimed to compare the efficacy of intra-arterial methotrexate (MTX) infusion combined with uterine artery embolisation (UAE) and uterine curettage with that of UAE and curettage without MTX infusion for the treatment of cesarean scar pregnancy (CSP). METHODS: In this retrospective study, data of CSP patients admitted from January 2011 to July 2015 were obtained from electronic patient records. Clinical information at baseline and after treatment were extracted and analyzed. RESULTS: A total of 93 CSP patients were included, with 57 patients receiving UAE followed by curettage (UC) and 36 patients receiving intra-arterial MTX infusion followed by UAE and curettage (MUC). The baseline characteristics were not significantly different between the two groups. Without additional intervention, 32 (88.9%) patients were successfully treated by MUC, and 49 (86.0%) patients were successfully treated by UC, defined by discontinued ectopic conceptus growth, normalized serum ß-human chorionic gonadotropin (ß-hCG) level, ceased vaginal bleeding and preservation of uterus, with no significant difference between the two groups. Additionally, intra-operative blood loss volume and post-operative bleeding events were not significantly different between the two groups. However, serum ß-hCG decline on the first day after surgery was significantly promoted, and the hospitalization length and the time needed for serum ß-hCG normalization were significantly shortened by addition of intra-arterial MTX infusion. CONCLUSIONS: Adding intra-arterial MTX to UAE and curettage significantly promoted post-operative recovery, though success rate and bleeding events were not significantly affected, suggesting that addition of intra-arterial MTX might not be necessary.

[Epidemiological Analysis of Imported Malaria in Xinjiang from 2004 to 2015].

Objective: To analyze the epidemiological characteristics of imported malaria in Xinjiang. Methods: The information of reported malaria cases and epidemiological records from various sources in Xinjiang Uygur Autonomous Region from 2004 to 2015 was collected. The epidemiological characteristics of malaria cases were analyzed. Results: Seventy-seven malaria cases were reported in Xinjiang from 2004 to 2015, and all were imported cases. In detail, 42 cases （54.5%） were reported during the time period of 2004-2009, with 24 laboratory diagnosed and 18 clinically diagnosed; 35 cases （45.5%） were reported from 2010 to 2015, with 27 laboratory diagnosed and 8 clinically diagnosed. Among the 51 cases with laboratory diagnosis, 18 were falciparum malaria, 31 were vivax malaria, and 2 unidentified. The male-to-female ratio was 6.7 ∶ 1（P<0.05）. The age range of the patients was 14-75 years （39.7 ± 13.3 years）, comprising 26.0% （20/77） for the range of 31-40 years and 24.7% （19/77） for the range of 41-50（P>0.05 among the age groups）. From the perspective of case sources, 28 cases （36.4%） were imported from Africa and 49 cases（63.6%） from Asia (including other provinces of China). The interval from onset to final diagnosis ranged 1-320 days. Only 3 patients（3.9%） were diagnosed within 24 h, and 59 patients（76.6%） were not diagnosed until or over one week. In addition, 28 cases（36.4%） were reported by medical institutions at the provincial level, 15 cases（19.5%） were reported by medical institutions at the prefecture level, 5 cases（6.5%） were reported by the Center for Disease Control and Prevention, and the rest 29 cases（37.7%） were reported at the county level or below. No secondary transmission was found. Conclusion: Most of the imported malaria cases during 2004-2015 were diagnosed with laboratory tests, reported by medical institutions, and were from Africa and Asia.

[Epidemiological Survey of Echinococcosis in Xinjiang Uygur Autonomous Region in 2012].

Objective: To understand the endemic status of echinococcosis in Xinjiang Uygur Autonomous Region, to provide scientific basis for planning and promoting control measures in this region. Methods Eight hundred people of all age ranges were examined in each of the selected agricultural area, pastoral area, pastoral-agricultural area, and township area of 92 counties in 14 prefectures in Xinjiang during March and October of 2012, resulting in a total of 3 200 people surveyed in each county. B ultrasonic abdominal scan was performed, accompanied by serum antibody detection for suspected cases. Methods: Eight hundred people of all age ranges were examined in each of the selected agricultural area, pastoral area, pastoral-agricultural area, and township area of 92 counties in 14 prefectures in Xinjiang during March and October of 2012, resulting in a total of 3 200 people surveyed in each county. B ultrasonic abdominal scan was performed, accompanied by serum antibody detection for suspected cases. Results: A total of 293 140 people were examined. The overall morbidity was 0.14%（407/293 140）. The morbidity in the north region was 0.18%（290/158 985, 71.25%of all the cases）, and that in the south region was 0.09%（117/134 155, 28.75% of all the cases）（P<0.05 between the regions）. The cases were mainly distributed in Urumqi City（19.90%, 81/407）, Tarbagatai Prefecture（13.27%, 54/407）, Yili Kazak Autonomous Prefecture（13.02%, 53/407） and Changji Hui Autonomous Prefecture（9.83%, 40/407）. The prevalence was higher in Mongolian［0.42%（21/5 045）］ and Kirgiz ［0.35%（32/9 045）］ than in other ethnic groups（0.07%-0.22%）（P<0.05）. There was no significant difference in prevalence between males［0.13%（195/144 715）］ and females［0.14%（212/148 425）］ （P>0.05）. The prevalence was lowest in the 0-9 year group［0.07%（7/10 754）］, and higher in the the age groups of 70-79［0.27%（33/12 310）］ and 80-99 years［0.28%（7/2 461）］, showing a trend of elevation with ageing. Further, the cases were mainly in the population of 30-49 years（43%, 175/407）. The prevalence was higher in the uneducated［0.25%, 39/15 470］ than in the educated populations（0.06%-0.14%）（P＜0.05）, and higher in pastoralists［0.29%, 63/22 074］ than in populations with other occupations（0.00%-0.13%）（P<0.05）. The prevalence in pastoral area, agricultural area, pastoral-agricultural area, and township area was 0.16%（70/44 247）, 0.16%（181/113 016）, 0.12%（88/70 610） and 0.10%（68/65 267）, respectively. The township area had the lowest prevalence, which was significantly different from both the pastoral area and the agricultural area (P<0.05). Conclusion: Echincoccosis is widely distributed in Xinjiang, with more cases in the north.

[Epidemiological Survey on Human Intestinal Protozoa in Xinjiang Uygur Autonomous Region in 2015].

Objective: An epidemiological survey was made on human intestinal protozoa in Xinjiang Uygur Autonomous Region (Xinjiang) to evaluate recent control achievements and provide basis for making specific control strategies. Methods: Regions in Xinjiang were categorized by types of ecological system and geographical characteristics into five ecological areas（types I-V） according to the National Ecological Function Stratification issued by the Ministry of Environment Protection and Chinese Academy of Science and Technology. Stratification sampling was made in each ecological area. Feces from human of all ages were collected for morphological identification of protozoan species using the Iodine Liquid Direct Smear Method. Results: In the five ecological areas, 26 886 people from 132 survey sites in 39 counties (cities) were examined, with an examination rate of 81.47% （26 886/33 000）. The infection rate was 0.32%（85/26 886）. Four species of intestinal protozoa were detected, i.e., Entamoeba histolytica, Giardia lamblia, Blastocystis hominis, and Entamoeba coli, with an infection rate of 0.22% （60/26 886）, 0.03% （9/26 886）, 0.01% （2/26 886） and 0.61% （17/26 886）, respectively. Of the five areas, the type IV area had the highest infection rate of 0.75%（28/3 758）（P<0.05）. Besides, the infection rate was higher in males （0.24%, 33/13 623） than that in females （0.39%, 52/13 263） （P<0.05）, higher in age ranges of 21-30（1.40%, 16/3 959） and 31-40 years（0.46%, 22/4 799） than other age groups （P>0.05）, higher in housewives （0.48%, 2/418） than those with other occupations, higher in the Hui group （0.61%, 15/2 445） than that in other ethnic groups, as well as highest in populations with a primary education level （0.37%, 35/9 375） and lowest in those with a college level or above（0.20%, 8/3 945）. Conclusion: The human intestinal protozoa infection was at a low level in Xinjiang in 2015.

[Hydatidosis Prevalence in 6- to 12-year-old Children in Southern Xinjiang].

Objective: To understand the hydatidosis prevalence in 6- to 12-year-old children in southern Xinjiang Uygur Autonomous Region and provide scientific basis for formulation of control measures. Methods: One primary school was selected from each of the pastoral area, pastoral-agricultural area, agricultural area, and township area in 42 counties （cities） of southern Xinjiang, using the stratified sampling method. With the consent of their parents, B ultrasonic abdominal scan and venous blood collection were performed on all the children （6-12 years） in the selected schools. Serum level of echinococcus antibody IgG was determined by ELISA. Hydatidosis prevalence and the serum level of IgG in these children were analyzed. Results: A total of 80 429 children were examined from 168 primary schools. B ultrasonic scan revealed hydatidosis in 9 children （0.01%）, comprising 3 cases in Kezhou, 2 in Aksu, 2 in Bazhou, and 2 in Kashi. ELISA results showed that 4 189 children were positive for serum IgG, with a positive rate of 5.21%. The positive rate was highest in Kashi （8.41%, 2 143/25 495）, followed by Aksu （5.69%, 913/16 051）, with significant difference between different areas （χ2=977.303， P<0.01）. The positive rate was lowest in 6-year children （2.13%, 44/2 065） and highest in 11-year children （5.68%, 822/14 462） （χ2=48.221, P<0.01）. In addition, the positive rate was highest in Uighur children（5.19%, 3 899/75 115）, followed by Mongolian children （4.27%, 68/1 592）, with no significant difference between ethnic groups （χ2=4.072, P>0.05）. Among the children of residents, children with a nomadic lifestyle, and children settled in winter and living in a nomadic lifestyle in summer, hydatidosis occurred in 7 residents and 2 children who settled in winter and living in a nomadic lifestyle in summer; and the positive rate of serum antibody was 5.45% （184/77 512）, 2.97% （3/101）, 0.07% （2/2 816）, respectively（χ2=148.609, P<0.01）. Conclusion: There is a low hydatidosis prevalence in 6- to 12-year-old children in southern Xinjiang, but the positive rate of serum echinococcus IgG in kashgar region, Uighur ethnicity, and children of the resident group are relatively high.

[Investigation on the Outbreak of Visceral Leishmaniasis in 2014 in Jiashi County of Xinjiang].

OBJECTIVE: To understand the epidemiological characteristics of visceral leishmaniasis (VL) outbreak in Jiashi County of Xinjiang Uygur Autonomous Region in 2014, and provide basis for VL prevention and control strategies. METHODS: Data on VL epidemic situation in Xinjiang from July 1, 2009 to June 30, 2015 were collected from Chinese CDC Infectious Disease Reporting Information Management System (reporting system). On-site epidemiological investigation was conducted in October, 2014, among children under 3 years in 23 villages in Gholtoghrak Township and Koxawat Township in Jiashi County, regions that had dramatically increased reports of VL cases from July 1. For suspected cases who showed symptoms such as fever and hepato-splenomegaly, blood (20 µl) was collected through fingerstick (with parental guardian consent) for rk39 immunochromatographic strip testing. Chil- dren with positive results were given sodium stibogluconate treatment (6x200 mg/kg, intravenously). RESULTS: A total of 637 VL cases were reported in Xinjiang from July 1, 2009 to June 30, 2015. Among the 192 cases reported from July 1, 2014 to June 30, 2015 in Xinjiang, cases from Jiashi County occupied 86.46% (166/192) of the cases. The number of VL cases in Jiashi County showed a trend of increase since the first report in August, with a total number of 114 in October, November and December. The 166 cases in Jiashi County had an age range of 23 days-8 years, with those under one year accounting for 95.18%(158/166). The 113 cases in Gholtoghrak Township of the County had an age range of 23 days-3 years, with those under one year accounting for 96.46% (109/113). The age--distribution of VL casess in the County accorded with the characteristic of the desert type. On-site investigation of 833 children in the 23 villiages revealed 11 children with positive results of rk39 immunochromatographic strip testing out of 14 suspected cases, all recovered after one course of sodium stibogluconate treatment. CONCLUSION: In 2014, VL outbreak occurs in Jiashi County with 95% of the cases being children under one year old. This outbreak was identified to be the desert type.

Loss of p53 enhances NF-κB-dependent lamellipodia formation.

Tumor suppressor p53 prevents tumorigenesis and tumor growth by suppressing the activation of several transcription factors, including nuclear factor-κB (NF-κB) and STAT3. On the other hand, p53 stimulates actin cytoskeleton remodeling and integrin-related signaling cascades. Here, we examined the p53-mediated link between regulation of the actin cytoskeleton and activation of NF-κB and STAT3 in MCF-7 cells and mouse embryonic fibroblasts (MEFs). In the absence of p53, STAT3 was constitutively activated. This activation was attenuated by depleting the expression of p65, a component of NF-κB. Integrin ß3 expression and lamellipodia formation were also downregulated by NF-κB depletion. Inhibition of integrin αvß3, Rac1 or Arp2/3, which diminished lamellipodia formation, suppressed STAT3 activation induced by p53 depletion. These results suggest that loss of p53 leads to STAT3 activation via NF-κB-dependent lamellipodia formation. Our study proposes a novel role for p53 in modulating the actin cytoskeleton through suppression of NF-κB, which restricts STAT3 activation.

p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion.

Oncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Ras-driven invasion. However, its mechanism remains poorly understood. Here we show that p53 induces activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton. Oncogenic Ras increases accumulation of p53 in the cytoplasm, which promotes the translocation of p38 mitogen-activated protein kinase (MAPK) into mitochondria and induces phosphorylation of HtrA2/Omi. Concurrently, oncogenic Ras also induces mitochondrial fragmentation, irrespective of p53 expression, causing the release of HtrA2/Omi from mitochondria into the cytosol. Phosphorylated HtrA2/Omi therefore cleaves ß-actin and decreases the amount of filamentous actin (F-actin) in the cytosol. This ultimately down-regulates p130 Crk-associated substrate (p130Cas)-mediated lamellipodia formation, countering the invasive phenotype initiated by oncogenic Ras. Our novel findings provide insights into the mechanism by which p53 prevents the malignant progression of transformed cells.

[Retrospective analysis of echinococcosis surgerical cases in Xinjiang from 2005 to 2013].

UNLABELLED: [Abstract] OBJECTIVE: To analyze the situation of echinococcosis surgerical cases in Xinjiang Uygur Autonomous Region from 2005 to 2013. METHODS: The surgery cases of echinococcosis in Xinjiang from 2005 to 2013 were collected, and analyzed with SPSS 17.0 and Epi Info 3.5.3 software. RESULTS: A total of 8 639 hydatid disease cases were reported during 2005-2013 from 94 counties (cities and districts) of 14 prefectures (municipalities) in the Region. The average number of annual operation cases were 960 cases (8,639/9 years), and the annual incidence was 4.40/100,000 (960/21.81 million). 82.8% (7,152/8,639) of report cases came from northern Xinjiang area with an incidence of 7.59/100,000, and 17.2% (1,487/8,639) distributed in southern Xinjiang area with an incidence of 1.58/100,000. There were 373 cases (4.4%, 373/8,639) reported in 2005, and increased to 1434 cases (16.5% 1,434/8,639) in 2013 (P<0.05). The cases mainly distributed in Yili Kazak Autonomous Prefecture (2,028 cases), Tarbagatai Prefecture (1,218 cases), Changji Hui Autonomous Prefecture (1,179 cases), and Urumqi City (1,128 cases) of the northern Xinjiang area. There were 4,557 male (52.8%, 4,557/8,639) and 4 082 famale patients (47.3%, 4,082/8,639)(P<0.05). The age distribution showed a single-peak curve, and more patients concentrated in the age group of 31-40 years, accounting for 26.2% (2,265/8,639). Among 8,639 cases, farmers accounted for 47.9% (4 134/8 639). CONCLUSION: The nunber of surgical cases of echinococcosis increases every year in Xinjiang since 2005, and the distribution of the disease shows a trend from the agricultural and pastoral areas to the towns.

Endemic characteristics of infantile visceral leishmaniasis in the People's Republic of China.

BACKGROUND: Visceral leishmaniasis (VL) was once a severe parasitic disease in China. Thanks to the great efforts of integrated control, VL was eliminated in most epidemic areas, except for certain western provinces (autonomous region) at the end of 1950s. From then on, VL gained less attention and has seemed to spread, especially in the last 15 years. Infants are the most important population threatened by VL. However, there have been few studies on the endemic characteristics of infantile VL in China. METHODS: Infantile VL cases were collected from the online National Infectious Diseases Reporting System (NIDRS). Statistical description and inference was used to reveal the endemic characteristics in gender, age group, time and regionalism. Spatial analysis was carried out to explore the high risk area for infantile VL in China. RESULTS: A total of 1093 infantile VL cases were reported from 2006 to 2012. There was no statistically significant difference in gender over time. The minimum, maximum and mean age of these cases was 1.1, 35.9 and 13.8 months, respectively. Among them 86.92% were under 2 years of age, and there was a statistically significant difference among age groups over time. An incidence peak appeared in 2008-2009, most cases were distributed in the months September to December, and there was a tail-raising effect in the coming two months of the next year. More than 98% of cases were reported in Xinjiang Uygur Autonomous Region, Gansu Province and Sichuan Province, accounting for 61.02%, 32.75% and 4.57%, respectively. A total of 56 counties reported infantile VL cases, with the cumulative incidence ranging from 0.02 to 24.57%. There were two main zones of high endemicity for infantile VL in China. The monthly incidence clearly coincides with the number of towns where infantile VL cases were reported. Three fatalities were reported during the study period, the case fatality rate was 2.75‰. CONCLUSIONS: The endemic situation of infantile VL is serious, and there are several active foci of infantile VL prevalence in China. VL has emerged as a severe threat to infants of endemic regions in China.

Sesquiterpenoids from Chloranthus multistachys.

An 8,9-seco-lindenane disesquiterpenoid, chloramultiol G, four eudesmane sesquiterpenoids, ent-(3R)-3-hydroxyatractylenolide III and multistalactones A-C, and four guaiane sesquiterpenoids, (1R,4S,5R,8S,10S)-zedoalactone A and multistalactones D-F, along with 14 known compounds, were isolated from whole plant tissues of Chloranthus multistachys. Their structures were established by extensive NMR experiments in conjunction with mass spectrometry. Except for chloramultiol G, the absolute stereochemistries of the other eight were confirmed by single-crystal X-ray crystallography and CD spectra. Nine compounds were tested for cytotoxicity against five human tumor cell lines and for antifungal activity against four microorganisms in vitro, but all were inactive.

[Preliminary application of moving percentile method on surveillance and early-warning on visceral leishmaniasis in endemic areas].

OBJECTIVE: To apply moving percentile method on surveillance and early-warning on visceral leishmaniasis in Kashgar Region and evaluate its effect. METHODS: Incidence data of visceral leishmaniasis in Kashgar Region were collected from the National Web-based Infectious Diseases Report System. Monthly detection was carried out by using moving percentile method. The 50th percentile (P50), 70th percentile (P70) and 90th percentile (P90) of historical baseline data were calculated for drawing a control chart, and P70 was adopted as the warning threshold to determine whether an epidemic would appear. If the number of cases in one month is higher than the corresponding P70 of historical baseline data, the warning signal will be generated. The sensitivity, specificity and positive predictive value were calculated for the evaluation of early-warning effect. RESULTS: During the study period, 61.0% cases were reported in the year of 2008 and 2009, the incidence peak was from September to December, accounting for 51.9%, and infants under 3 years old were the population most threatened by visceral leishmaniasis, accounting for 62.7%. A total of 58 detections were performed, and 17 warning signals were generated by the threshold on P70. Among them, the numbers of cases in 9 detections were higher than the corresponding P90 of historical-baseline data. Based on the actually epidemic status of visceral leishmaniasis in study period, according to the threshold on P70, a total of 10 warning signals of 11 epidemics were detected, and the sensitivity of the warning model was 90.9% (10/11). 7 wrongly signals of 47 non-epidemics were detected, and the specificity was 85.1% (40/47). 10 of 17 signals were proved to be correct, and the positive predictive value was 58.8% (10/17). CONCLUSION: The moving percentile method can effectively perform surveillance and early-warning on visceral leishmaniasis in Kashgar Region.

NBS1 deficiency promotes genome instability by affecting DNA damage signaling pathway and impairing telomere integrity.

Studies revealed that Nijmegen Breakage Syndrome protein 1 (NBS1) plays an important role in maintaining genome stability, but the underlying mechanism is controversial and elusive. Our results using clinical samples showed that NBS1 was involved in ataxia-telangiectasia mutated (ATM)-dependent pathway. NBS1 deficiency severely affected the phosphorylation of ATM as well as its downstream targets. BrdU proliferation assay revealed a delay of NBS cells in inhibiting DNA synthesis after Doxorubicin (Dox) treatment. In addition, under higher concentrations of Dox, NBS cells exhibited a much lower level of apoptosis compared to their normal counterparts, indicating a resistance to Dox treatment. Accelerated telomere shortening was also observed in NBS fibroblasts, consistent with an early onset of cellular replicative senescence in vitro. This abnormality may be due to the shelterin protein telomeric binding factor 2 (TRF2) which was found to be upregulated in NBS fibroblasts. The dysregulation of telomere shortening rate and of TRF2 expression level leads to telomere fusions and cellular aneuploidy in NBS cells. Collectively, our results suggest a possible mechanism that NBS1 deficiency simultaneously affects ATM-dependent DNA damage signaling and TRF2-regulated telomere maintenance, which synergistically lead to genomic abnormalities.

MicroRNA-519d targets MKi67 and suppresses cell growth in the hepatocellular carcinoma cell line QGY-7703.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the translation of target mRNA transcripts. In this study, we demonstrated that miR-519d was downregulated in human HCC and could suppress growth of the human HCC cell line QGY-7703. Bioinformatics analysis indicated that MKi67 was a putative target of miR-519d. In an EGFP reporter system, we confirmed that MKi67 was a direct target gene of miR-519d. Furthermore, knockdown of MKi67 inhibited QGY-7703 cell growth. These findings indicate that miR-519d targets the MKi67 transcript and suppresses HCC cell growth, suggesting that miR-519d has a tumor suppressive role in human HCC pathogenesis.

[Computational approaches to microRNA discovery].

microRNAs (miRNAs) are endogenous non-coding RNAs of ~21 nucleotides in length discovered in recent years. They are involved in diverse pathways and play an important role in gene regulation in plants and animals. There are two main groups of approaches to miRNA discovery, which are cDNA cloning and computational identification. Since some miRNAs are expressed at a low level and the expression of many miRNAs has spatio-temporal specificity, it is difficult to find them through cDNA cloning. However, computational approaches can predict the miRNAs specifically expressed or with low abundance, which is complement to cDNA cloning. Computational approaches have hence gained wide attention. In this review, the computational approaches to miRNA discovery were summarized. According to their intrinsic characteristics, computational approaches were categorized into five classes: (1) homology search; (2) prediction based on comparative genomics; (3) scoring candidates using the sequence and structure characteristics; (4) prediction combined with targets; and (5) prediction with machine learning. The principles of each class of the approaches and their advantages and limitations in miRNA discovery were discussed. Finally, the future direction in miRNA discovery was pointed out.