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.

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.

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.

[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.

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.

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.

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.

Hepatic migration of a catheter fragment followed by disconnection of a totally implantable venous access port.

Totally implantable venous access ports (TIVAPs) are frequently used in oncology patients who require long-term courses of chemotherapy. We report a silent, but potentially hazardous complication of catheter fracture and hepatic migration in a 64-year-old male. The patient presented with a painful, rapid swelling of subcutaneous tissue around the port area during a saline flush. A chest radiograph showed that the disconnected catheter had separated from the port and was no longer in its original location. A chest CT scan revealed that the disconnected catheter was found to be embolized to the right atrium, inferior vena cava and right hepatic vein. The patient was treated successfully with percutaneous transfemoral retrieval of the catheter under fluoroscopic guidance. To our knowledge, there have been no previous reports of migration of the fractured catheter of a TIVAP into the right hepatic vein. This case highlights that the integrity of TIVAPs should be ascertained before chemotherapeutic drugs are administered.

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.

Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan.

Previous studies have found that having a first-degree blood relative with lung cancer was a possible predictor of lung cancer risk, but some studies have indicated that the association is non-significant or only significant for a subset of the studied population. To determine the familial aggregation and whether there is any evidence for a gene controlling the susceptibility to developing lung cancer in female non-smokers, multiple logistic regression methods for estimating covariate effects and maximum likelihood segregation analyses were performed using data from 216 female non-smoking lung cancer probands (2328 individuals) in a population-based case-control study. Having a family history of lung cancer was found to be a significant predictor of lung cancer for non-smoking females (Adjusted Odds Ratio (OR)=5.7, 95% Confidence Interval (CI)=1.9-16.9). Having a female relative with lung cancer (adjusted OR=14.4, 95% CI=2.7-75.5) was more strongly associated with the lung cancer risk than was having a male relative with lung cancer. This association was stronger for probands aged less than 60 years at onset (adjusted OR=11.2, 95% CI=2.2-56.9). All of the Mendelian models fitted the data significantly better than the sporadic (no major type) model or the environmental model (P<0.00l). The Mendelian codominant models provided the best fit of the data for the early onset probands and showed a stronger effect for a major susceptibility locus for non-smoking lung cancer probands. The results of this study provide evidence that a rare autosomal codominant gene may influence the risk lung cancer in non-smoker and is responsible for the familial aggregation observed in non-smoking lung cancer patients.

Efficacy of media enriched with nonlactate-generating substrate for organ preservation: in vitro and clinical studies using the cornea model.

BACKGROUND: Using a rabbit cornea model, our recent study demonstrated that Chen Medium (CM), an isotonic media enriched with nonlactate-generating high-energy substrates, is very effective for organ preservation. In the present study, the efficacy of CM is further evaluated with human corneas METHODS: The effectiveness of CM and Optisol for preserving the endothelial integrity of human corneas in vitro was evaluated by scanning electron microscopy. Clinical efficacy was evaluated in a total of 83 patients: 10 patients with keratoconus grafted randomly with either CM- or Optisol-stored cornea of the same donor, and 73 patients with various conditions grafted with CM-stored corneas. After surgery, visual acuity and quality of the graft were monitored for up to 4.6 years. RESULTS: The scanning electron microscopic study revealed that after 11-day storage at 4 degrees C, the CM-stored cornea had only marginal disruptive changes, 9.4+/-1.1%, in endothelial cells, as opposed to 42.4+/-4.6% of the Optisol-stored cornea. All 78 CM-stored corneas, including 67 with 12.2- to 17.7-hr death-to-storage time, 3-7.6 days of storage time, and initial marginal quality before storage, were successfully transplanted. These grafts were thin and clear, with an excellent epithelial integrity and without significant changes in endothelial cell density. Five Optisol-stored corneas were also successfully grafted; one of them, however, was edematous for about 4 weeks, and all the grafts were slightly thicker with substantial endothelial cell loss. CONCLUSION: Using a cornea model, present and recent studies show that CM is very effective for preserving tissue viability and endothelial integrity. Previous study revealed that CM-stored tissues maintained high levels of ATP and metabolic function, with suppression of lactate formation and accumulation. Thus, these findings support the concept that preservation of tissue viability is closely associated with the ability of the tissues to retain metabolic activity, to generate ATP efficiently, and to prevent acidosis effectively during storage.

Quantitative cytochemical differences between young and old patients with lung cancer.

In order to study differences in the tumor growth and frequency of metastases between younger and older patients with lung cancer, we investigated the nuclear DNA and nuclear protein according to age by means of cytophotometry after combined staining with Feulgen and Naphthol Yellow S. On the basis of Feulgen-Naphthol Yellow S staining method, 13 patients less than 40 years old and 16 patients older than 70 years were investigated. Our results showed no significant difference in nuclear DNA contents between young and old patients, but there were significantly higher nuclear protein contents (p less than 0.05) and nuclear protein to nuclear DNA (NP/DNA) ratios (p less than 0.001) in young patients than in old patients. This suggests that young patients may have higher tumor proliferation (high nuclear protein contents and NP/DNA ratios). The lower nuclear protein content and NP/DNA ratio of older cases is in keeping with the general phenomenon of slower tumor growth and less frequent metastases in such cases.

Lifetime environmental exposure to tobacco smoke and primary lung cancer of non-smoking Taiwanese women.

BACKGROUND: For a female population with a high lung cancer mortality rate, such as Taiwanese women, who smoke relatively rarely, but live in an environment with high male smoking prevalence, the risk and population burden of lung cancer due to environmental tobacco smoke (ETS) are relatively important. METHODS: An age-matched case-control study was designed to investigate the effects of cumulative environmental exposure to tobacco smoke during childhood and adult life on lung cancer risk among non-smoking women in Taiwan. Information on passive smoking from all possible sources and life periods were obtained from interviews with 268 and 445 lifetime non-smoking cases and controls. Conditional logistic regression and synergism 'S' index were applied to the data to assess the independent and joint effects of passive smoking in different life stages while controlling for possible confounding variables. RESULTS: Risks of contracting lung cancer among women near-distantly exposed to the highest level of ETS in childhood (>20 smoker-years) and in adult life (>40 smoker-years) were 1.8-fold (95% CI: 1.2-2.9) and 2.2-fold (95% CI: 1.4-3.7) higher than that among women being never exposed to ETS, and the two variables accounted for about 37% of tumours in this non-smoking female population. Children were found to be more susceptible to ETS than adults and such early exposure was found to modify the effect of subsequent tobacco smoke exposure in adult life based on an additive interaction model. CONCLUSIONS: Environmental tobacco smoke exposure occurring in childhood potentiates the effect of high doses of exposure in adult life in determining the development of lung cancer. Smoking prohibition would be expected to protect about 37% of non-smoking Taiwanese women against lung cancer.

Bronchoalveolar carcinoma: factors affecting survival.

One hundred thirty-four consecutive patients (65 men and 69 women) underwent pulmonary resection for bronchoalveolar carcinoma. Mean age was 65 years. Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and wedge excision in 19. Only 10 patients had lymph node metastases (7.5%). The neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in stage II, 9 were in stage IIIa, and 1 was in stage IIIb. There were two operative deaths (1.5%). Thirty-nine complications occurred in 31 patients. Median follow-up was 5.1 years. Recurrent bronchoalveolar carcinoma developed in 45 patients. Five- and 10-year survival for patients in stage I was 75.2% and 62.0%, respectively. Survival for patients with T1 N0 M0 neoplasms was identical to expected survival and was 90.5% at 5 years, as compared with 55.4% for patients with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease, and 0.0% for patients with bilateral disease (p less than 0.0001). Other significant factors adversely affecting survival included the presence of signs and symptoms, diffuse malignant invasion, mucin-producing tumors, and the histological absence of scar. We conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases. Early aggressive pulmonary resection is safe and offers the potential for cure. The presence of bilateral cancer, however, is ominous.

Hemispheric differentiation and category width.

This study concerns the relationship between a cognitive style dimension, category width, and hemispheric differentiation. When lists of word pairs were presented simultaneously in a dichotic listening task to broad and narrow categorisers (all female, right-handed), both groups of subjects recalled more words presented to the right ear than those presented to the left ear; indicating left hemisphere's superiority in verbal processing. Both broad and narrow categorisers recalled a similar number of words in the right ear (left hemisphere), but the former recalled significantly more words in the left ear than did the latter. This finding is interpreted as meaning that narrow categorisers rely predominantly on the left hemisphere in verbal processing, and that in comparison with narrow categories, there is greater right hemispheric involvement in processing in the case of broad categorisers. The implication of this finding in terms of the differential processing strategies adopted by the two groups of individuals is discussed.