[Relationship and coordination between water pollution control and mosquito breeding].

Change of water environment is strongly associated with mosquito breeding. Because of long-term effectiveness, low cost and high environmental compatibility, ecological pollution control systems have been widely used in water pollution control projects. However, the potential effects of mosquito breeding are likely to cause expansion of mosquito populations and an increase in the risk of transmission of vector-borne diseases, which may become an urgent problem to be solved during the water environment "post-remediation" period. This review summarizes the physical, chemical and biological factors affecting mosquito breeding caused by water environment changes and analyzes the effects of water pollution control approaches on mosquito breeding and the underlying mechanisms, so as to promote the interdisciplinary connections between water pollution control and vector control, and avoid secondary disasters caused by ecological environment restoration, such as mosquito infestation. This review may provide insights into the use of technology combinations and water pollution control approaches in vector control.

Genetic Polymorphism of Y Chromosome Haplogroup D-M174 in East Asian Populations.

ABSTRACT: Objective To explore the genetic polymorphism of Y chromosome D-M174 haplogroup and sub-haplogroups in East Asia. Methods The samples of 1 426 unrelated male individuals from East Asia were collected, and then 7 Y chromosome haplogroup D-M174 and the Y-SNP of its sub-haplogroups were detected with mini-sequencing. The 22 Y-STR genotypes were detected with DNA Typer™ Y26 kit. The haplogroup was analyzed using direct counting method, heatmap, phylogenetic cluster and network graph cluster, and then distribution of genetic polymorphism and the clustering relation between populations and samples of Y chromosome D haplogroup were discussed. Results Haplogroup D-M174 were distributed mostly among Tibetans （40.96%）and Japanese （35.71%）, while less or none were distributed among the surrounding areas of Tibet and other areas. Conclusion The geographical distribution of Y chromosome D-M174 haplogroup in East Asian populations has significant characteristics.

Prognostic significance of preoperative albumin-to-globulin ratio in patients with cholangiocarcinoma.

BACKGROUND: This study aimed to assess the prognostic value of the serum albumin to globulin ratio (AGR) in cholangiocarcinoma patients after surgery. METHODS: We retrospectively enrolled 123 cholangiocarcinoma patients who underwent surgical treatment between June 2003 and September2014 at the Third Affiliated Hospital of Sun Yat-sen University. Univariate and multivariate analyses using the Cox regression model were performed to determine the prognostic value of AGR. RESULTS: Univariate analysis suggested that AGR was a predictive factor for (overall survival) OS but not for recurrence free survival (RFS). After adjustment for other risk factors, multivariate analysis showed that AGR remained independently associated with OS. The optimal cut-off point for AGR was determined to be 1.44. Kaplan-Meier curves showed that there was a significantly lower mean survival time in the low AGR group compared to the high AGR group. A low AGR was found to be significantly associated with high alkaline phosphatase, gamma-glutamyl transpeptidase, total bilirubin levels and an advanced American Joint Committee on Cancer TNM stage, but a low hemoglobin level. CONCLUSION: In summary, patients with higher AGRs have better outcomes than those with lower AGRs. Preoperative AGR can be a reliable marker for evaluating the prognosis of cholangiocarcinoma patients.

Prophylactic inhalation of L-alanyl-L-glutamine enhances heat shock protein 72 and attenuates endotoxin-induced lung injury in rats.

Studies have demonstrated that heat shock protein 70 (HSP70) plays an important role in the protection of stressed organisms. The development of strategies for enhancing HSPs expression may provide novel means of minimizing inflammatory lung conditions, such as acute lung injury. This study aimed to examine the effect of L-alanyl-L-glutamine (GLN) inhalation in enhancing pulmonary HSP72 (inducible HSP70) expression and attenuating lung damage in a model of acute lung injury induced by lipopolysaccharide (LPS) inhalation. The experimental rats were randomly assigned to one of four experimental groups: (1) NS: saline inhalation; (2) NS-LPS: pretreatment by saline inhalation 12 h before LPS inhalation; (3) GLN: glutamine inhalation; (4) GLN-LPS: pretreatment by glutamine inhalation 12 h before LPS inhalation. The results show that GLN compared with saline administration, led to significant increase in lung HSP72 both in non LPS-treated rats and LPS-treated rats. In LPS-treated rats, pretreatment by GLN inhalation produced less lung injury as evidenced by the decrease in lung injury score and dramatic decrease in lactate dehydrogenase (LDH) activity and polymorphonuclear leukocyte cell differentiation counts (PMN %) in the bronchoalveolar lavage fluid. The study indicates that prophylactic glutamine inhalation associated with the enhancement of HSP72 synthesis attenuates tissue damage in experimental lung injury.

Angiomotin decreases lung cancer progression by sequestering oncogenic YAP/TAZ and decreasing Cyr61 expression.

Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.

MTAP is an independent prognosis marker and the concordant loss of MTAP and p16 expression predicts short survival in non-small cell lung cancer patients.

OBJECTIVES: Methylthioadenosine phosphorylase (MTAP), a ubiquitously expressed protein, plays important roles in purine biosynthesis. Locating near to each other on chromosome 9p21-22, codeletion of the MTAP and p16(Ink4A) genes have been reported in non-small cell lung cancer (NSCLC). The aim of this study is to determine the respective prognostic value of MTAP and p16 by considering their correlation in NSCLC patients. MATERIALS AND METHODS: We analyzed MTAP and p16 protein expression by immunohistochemical staining on 99 NSCLC tissue microarray samples. The association between MTAP and p16 expression levels and prognosis were analyzed using the Kaplan-Meier method and Cox proportional hazards model for prognosis. RESULTS: Patients with a low MTAP expression level had poor overall survival (P = 0.010) and disease-free survival (P = 0.002). Low p16 expression indicated a trend toward poor overall survival (P = 0.138) and disease-free survival (P = 0.199). There was a significant positive correlation between MTAP and p16 expression levels (Spearman's ρ = 0.402, P < 0.001). By multivariate analyses, the MTAP expression level retained its independent prognostic power and p16 expression loss of the correlation with prognosis. Concordant loss of MTAP and p16 expression was observed in 24 out of 99 patients (24.2%). Patients with concordant loss of MTAP and p16 expression had the worst prognosis compared to patients with high expression of both markers. CONCLUSION: MTAP expression is an independent prognostic factor and has greater prognostic significance than p16 expression in NSCLC. Concordant loss of MTAP and p16 expression indicates poor outcomes in lung cancer patients.

Endoplasmic reticulum ribosome-binding protein 1 (RRBP1) overexpression is frequently found in lung cancer patients and alleviates intracellular stress-induced apoptosis through the enhancement of GRP78.

Lung cancer is the leading cause of cancer deaths and is the most occurring malignancy worldwide. Unraveling the molecular mechanisms involved in lung tumorigenesis will greatly improve therapy. During early tumorigenesis, rapid proliferating tumor cells require increased activity of endoplasmic reticulum (ER) for protein synthesis, folding and secretion, thereby are subjected to ER stress. Ribosome-binding protein 1 (RRBP1) was originally identified as a ribosome-binding protein located on the rough ER and associated with unfolding protein response (UPR). In this report, we investigated the role of RRBP1 in lung cancer. RRBP1 was highly expressed in lung cancer tissue, as compared with adjacent normal tissues as assessed by immunohistochemistry (IHC) using lung cancer tissue array (n=87). Knockdown of RRBP1 by short-hairpin RNAs caused ER stress and significantly reduced cell viability and tumorigenicity. This effect was associated with a significant reduction in the expression of glucose-regulated protein 78 (GRP78). UPR regulator GRP78, an anti-apoptotic protein that is widely upregulated in cancer, has a critical role in chemotherapy resistance in some cancers. According to our results, cells with a higher level of RRBP1 were more resistant to ER stress. Ectopic expression of RRBP1 alleviated apoptosis that was induced by the ER-stress agent tunicamycin, 2-deoxy-D-glucose (2DG) or doxorubicin via enhancing GRP78 protein expression. A strong correlation was observed between the expression of RRBP1 and GRP78 in tumor biopsies using the database GSE10072. Our results also indicated that RRBP1 may involve in the regulation of mRNA stability of UPR components including ATF6 and GRP78. Taken together, RRBP1 could alleviate ER stress and help cancer cell survive. RRBP1 is critical for tumor cell survival, which may make it a useful target in lung cancer treatment and a candidate for the development of new targeted therapeutics.

Hypertension among HIV-infected adults receiving highly active antiretroviral therapy (HAART) in Malaysia.

There are increasing researches about non-communicable disease such as elevated blood pressure among people living with HIV before and after initiation of highly active antiretroviral therapy (HAART). This cross-sectional study was designed to determine the prevalence of hypertension and associated risk factors among 340 HIV-infected patients on antiretroviral therapy at a Malaysian public hospital providing HIV-related treatment. Data on socioeconomic background, anthropometry, medical history and dietary intake of the patients were collected. Hypertension is defined as blood pressure >=130/85 (mm Hg). Prevalence of hypertension was 45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024-1.078), higher body mass index (OR 1.18, 95%CI 1.106-2.71), bigger waist circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070, 95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95%CI 0.845-2.100) and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were significant risk factors for hypertension (p<0.001). After adjusting for other variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124, p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with hypertension. None of the antiretroviral therapy and immunologic factors was linked to hypertension. In conclusion hypertension among PLHIV was linked to the well-known risk factors such as age, gender and body mass index. With HAART, people can live longer by making monitoring and control of some reversible factors, especially excessive weight gain for maintaining quality of life.

TOPK/PBK promotes cell migration via modulation of the PI3K/PTEN/AKT pathway and is associated with poor prognosis in lung cancer.

We integrated four gene expression profile data sets, namely two different pair-matched stage I lung adenocarcinoma data sets, secondary metastatic tumors vs benign tumors and lung tumor metastasizes to the brain, and we identified one kinase, T-LAK Cell-Originated Protein Kinase (TOPK), as a putative gene that promotes metastasis. To delineate the role of TOPK in lung cancer, we showed that overexpression of TOPK, but not a catalytically inactive form of TOPK, can enhance the migration and invasion of lung fibroblasts or cells with low TOPK expression. In addition, TOPK-induced cell migration was shown to be a PI3K/AKT-dependent event. TOPK concurrently promoted AKT phosphorylation at Ser(473) and decreased the phosphatase and tensin homolog (PTEN) levels, whereas TOPK knockdown had the reverse effects. LY294002, a PI3K inhibitor, did not inhibit the TOPK-induced decrease in PTEN, and co-expression of PTEN significantly reduced TOPK-induced AKT phosphorylation in a dose-dependent manner; these results indicate that the TOPK-mediated PTEN decrease has an upstream role in regulating PI3K/AKT-stimulated migration. Using immunohistochemical analysis of lung cancer tissue samples, we showed that a high TOPK expression level correlates strongly with reduced overall and disease-free survivals. Moreover, an inverse correlation between TOPK and PTEN expression was present and is consistent with the biochemical findings. Finally, a combination of high TOPK and low PTEN expression was inversely correlated with overall and disease-free survivals, independent of other pathologic staging factors. Our results suggest that TOPK is a potential therapeutic target in lung cancer that promotes cell migration by modulating a PI3K/PTEN/AKT-dependent signaling pathway; they also suggest that high TOPK expression, either alone or in combination with a low level of PTEN, may serve as a prognostic marker for lung cancer.

The mode of reproductive-derived Spink (serine protease inhibitor Kazal-type) action in the modulation of mammalian sperm activity.

The reproductive-derived serine protease inhibitor Kazal-type (Spink) has been identified in seminal plasma, and Spink-spermatozoa binding has been illustrated in many mammalian species including human. We used mice as experimental animal to study the mode of Spink action in the modulation of mammalian sperm activity. A Spink3-binding zone was cytochemically stained on the sperm head at apical hook separated from intact acrosome, whether the cells were capacitated or not. The Spink3-spermatozoa binding neither changed the population of cells in the uncapacitated, capacitated and acrosome-reacted status nor affected the capacitation-related protein phosphorylation and cell motility enhancement. Despite that, the Spink-spermatozoa interaction resulted in decreasing the intracellular calcium concentration ([Ca(2+)](i)) of the cell head and suppressing both the acrosome reaction induced by Ca(+2) ionophore A23187 and the cell fertility. Furthermore, Spink3 seen on the head of spermatozoa in the uterine cavity after coitus could be removed by the trypsin-like activity in the uterine fluid of oestrous females, and free Spink3 in the uterine cavity suppressed the protease activity. We integrated our data to shed light on the molecular mechanism of how Spink and its inhibiting protease are interplayed to modulate the activity of mammalian spermatozoa during their transit in the reproductive tract.

Medical students' attitudes toward abortion education: Malaysian perspective.

BACKGROUND: Abortion is a serious public health issue, and it poses high risks to the health and life of women. Yet safe abortion services are not readily available because few doctors are trained to provide such services. Many doctors are unaware of laws pertaining to abortion. This article reports survey findings on Malaysian medical students' attitudes toward abortion education and presents a case for including abortion education in medical schools. METHODS AND RESULTS: A survey on knowledge of and attitudes toward abortion among medical students was conducted in two public universities and a private university in Malaysia in 2011. A total of 1,060 students returned the completed questionnaires. The survey covered about 90% of medical students in Years 1, 3, and 5 in the three universities. About 90% of the students wanted more training on the general knowledge and legal aspects of abortion, and pre-and post-abortion counseling. Overall, 75.9% and 81.0% of the students were in favor of including in medical education the training on surgical abortion techniques and medical abortion, respectively. Only 2.4% and 1.7% were opposed to the inclusion of training of these two methods in the curriculum. The remaining respondents were neutral in their stand. Desire for more abortion education was associated with students' pro-choice index, their intention to provide abortion services in future practice, and year of study. However, students' attitudes toward abortion were not significantly associated with gender, type of university, or ethnicity. CONCLUSIONS: Most students wanted more training on abortion. Some students also expressed their intention to provide abortion counseling and services in their future practice. Their desire for more training on abortion should be taken into account in the new curriculum. Abortion education is an important step towards making available safe abortion services to enable women to exercise their reproductive rights.

Detection of patients presenting with adverse drug events in the emergency department.

BACKGROUND: Adverse drug events (ADE) have been studied widely in hospitalised and emergency department (ED) patients. Less is known about the ED visits of drug-related injury in Taiwan. This study seeks to determine the incidence, risk and patient outcomes of ADE in an ED population. METHODS: We conducted a prospective observational cohort study of patients 18 years and older presenting to the ED of an urban, tertiary medical centre. ED visits between 1 March 2009 and 28 February 2010 identified by investigators for suspected ADE were further assessed by using the Naranjo Adverse Drug Reaction probability scale. Outcomes (ED disposition, injury severity and preventability) and associated variables (triage, gender, drug category, number of drugs, Charlson comorbidity index score and ADE mechanism) were measured. RESULTS: Of 58,569 ED visits, 452 patients (0.77%) had physician-documented ADE. 24% of patients with ADE were hospitalised with life-threatening conditions, with a mortality rate of 10.0%. The majority of ADE were considered preventable (73.4%), and the unintentional overdose was the most common cause. Cardiovascular agents accounted for the most ADE (25.8%) and consisted of 65.3% of ADE in patients aged 65,years and older. Risk factors for ADE-related hospitalisation were elderly age (odds ratio (OR) 1.9, 95% confidence interval (CI) 1.1-3.4), severity of ADE (OR 6.9, 95% CI 3.3-14.5) and higher Charlson comorbidity index scores (OR 3.4, 95% CI 2.0-5.7). CONCLUSION: ADE-related ED visits are not uncommon in Taiwan and many cases are preventable. ED-based surveillance may provide useful information for monitoring outpatient ADE.

Nutritional status of children living with HIV and receiving antiretroviral (ARV) medication in the Klang Valley, Malaysia.

INTRODUCTION: Nutrition and HIV are closely related. Any immune impairment as a result of HIV leads to malnutrition, which in turn, can also lead to reduced immunity, thus contributing to a more rapid progression to AIDS. METHODS: This cross-sectional study determined the nutritional status of children living with HIV and are receiving antiretroviral medication in the Klang Valley. A total of 95 children aged one to eighteen years old were recruited between September 2008 and February 2009. Data collected included socio-economic status, anthropometric measurements, dietary intake, medical history and serum levels of selected micronutrients specific for immunity. RESULTS: The mean age of the children was 8.4 +/- 3.9 years and the mean duration on antiretroviral medications was 68.3 +/- 38.3 months. Anthropometric assessment found that 9.5% of the children were underweight and 31.6% were overweight. In contrast, 20.8% were stunted and 14.6% severely stunted. Biochemical indicators showed that 10.4% had deficiency in vitamin A while 12.5% had deficiency in selenium. Total cholesterol and HDL-C levels were found to be low in 30.5% and 10.5% of the children respectively. CONCLUSION: Dietary assessment showed almost all the children did not achieve the recommended energy intake for their age groups and almost half of the children did not achieve the RNI for selenium and vitamin A. This study provides an insight on the nutritional status of children living with HIV.

The polymorphisms of C-reactive protein gene modify the association between central obesity and lung function in taiwan asthmatics.

High-sensitivity C-reactive protein (hs-CRP) concentrations and obesity are proposed to have a significant relationship with impairment of lung function, but little has been reported to date on the association between CRP gene and lung function. We studied the association of three tagSNPs (tag single nucleotide polymorphisms) of CRP gene and their interactions with central obesity on lung function. A total of 384 asthmatic adults and 384 controls who were 1:1 matched by sex and age were recruited for this study. Three tagSNPs polymorphisms for CRP rs1417938, rs1800947 and rs1205 were selected from HapMap data and genotyping by using TaqMan allelic discrimination assay. A questionnaire interview, body composition and pulmonary function tests were performed. CRP single nucleotide polymorphisms (SNPs) did not increase the risk of asthma, but CRP rs1205 CC genotype significantly decreased the predictive value of forced vital capacity (FVC) in the asthma group (adjusted mean change = -7.54%, 95% CI = -13.82 to -1.25%). Waist-to-hip ratio, not body mass index, also decreased the predictive value of FVC in asthmatics. The subjects with central obesity who carried CRP SNPs have a significant reduction effect in lung function. The current results suggest that central obesity may play a major role in lung function, and these effects were modified significantly by the polymorphisms for CRP gene.

Role of gender disparity of circulating high-sensitivity C-reactive protein concentrations and obesity on asthma in Taiwan.

BACKGROUND: Several studies have suggested that the association between obesity and asthma may be stronger in females than in males, but the reason is still unclear. OBJECTIVE: The aim of this study was to investigate whether differences in high-sensitivity C-reactive protein (hs-CRP) levels explain why obesity is associated with asthma in females but not in males. METHODS: This study prospectively enrolled 754 subjects ≥ 18 years old from hospital-based asthma patients and population-based controls. We measured adiposity factors [body mass index (BMI), waist circumference and waist-hip ratio], hs-CRP and total IgE levels. RESULTS: After adjusting for potential confounding factors, we found a significant association between BMI and asthma in females with a significant interaction of gender and BMI on asthma (χ(2) =10.2, P=0.004). If hs-CRP was added to the logistic model, the interaction was attenuated but still significant (χ(2) =7.02, P=0.03). After adjusting for BMI, we did not find that circulating hs-CRP concentrations were significantly associated with asthma in males and females. CONCLUSION: We found that BMI was associated with asthma in females, but our results do not support the suggestion that hs-CRP levels contribute significantly to the link between obesity and asthma with respect to gender disparity.

Signalling pathway of isophorone diisocyanate-responsive interleukin-8 in airway smooth muscle cells.

This study is the first to analyse the soluble factors secreted by the bronchial epithelium after exposure to isophorone diisocyanate (IPDI) that are responsible for increasing migration and proliferation of primary normal human bronchial smooth muscle cells (BSMCs). We treated immortalised, nontumorigenic human bronchial epithelial cells (cell line BEAS-2B) and primary normal human bronchial epithelial cells (HBEC) with IPDI, and then collected the conditioned culture media (IPDI-BEAS-2B-CM and IPDI-HBEC-CM, respectively), which was added to BSMCs. Exposure of BEAS-2B cells and HBECs to IPDI increased interleukin (IL)-8 production. Culture of BSMCs with IPDI-BEAS-2B-CM and IPDI-HBEC-CM increased BSMC proliferation and migration, which are major features in asthma-related airway remodelling. Induction of BSMC proliferation and migration by IPDI-BEAS-2B-CM and IPDI-HBEC-CM was associated with increased focal adhesion kinase (FAK), Src, extracellular signal-regulated kinase (ERK)1/2 and AKT activation. Blocking FAK with a specific inhibitor significantly decreased BSMC migration and proliferation by inhibiting ERK1/2 activation. FAK and ERK1/2 inhibitor also decreased IPDI-BEAS-2B-CM-, IPDI-HBEC-CM- and recombinant human IL-8-mediated BSMC proliferation and migration, whereas blocking Rnd3 using small interfering RNA failed to affect BSMC proliferation, suggesting that Rnd3 was only involved in the regulation of BSMC migration. Our study suggests that inhibition of IL-8 or IL-8-mediated FAK/ERK/Rnd3 signalling is an attractive therapeutic target for IPDI-mediated asthma.

Generalized convulsion resulted in hyperammonemia during treatment with tranexamic acid for hemoptysis.

BACKGROUND: Tranexamic acid is commonly used to treat various kinds of bleeding disorders. It has been shown to cause severe convulsions in animal experiments. AIMS: We report a patient who experienced a single convulsive seizure that resulted in transient hyperammonemia during treatment with tranexamic acid. CASE REPORT: A 68-year-old man was admitted and received tranexamic acid for persistent hemoptysis. After 5 days of admission, clonic convulsions that progressed to generalized seizures were noted following the intravenous administration of the tranexamic acid. Elevated ammonia level (233 µmol/l) was found. No further seizures occurred after immediate discontinuation of the drug. No other cause of seizures was found. The ammonia level on the following day normalized even without any treatment for the hyperammonemia. CONCLUSIONS: This case highlights that generalized convulsion is a very rare, but serious adverse effect of tranexamic acid. Generalized convulsion should be considered as a potential cause of transient hyperammonemia.