[Clinical and pathological features of 20 cases of congenital hepatic fibrosis].

Objective: To investigate the clinical and pathological features of congenital hepatic fibrosis (CHF). Methods: The clinical and pathological findings of 20 patients diagnosed with CHF from 2017 to 2023 were retrospectively analyzed. Results: Among the 20 patients, 8 were males and 12 were females with a median age of 21.5 years. Mostly patients were admitted to the hospital with cirrhosis, portal hypertension and upper gastrointestinal bleeding. Pathological features were diffuse fibrosis in the portal area, formation of fibrous septa of varying width, segmentation of the liver parenchyma, with hyperplasia of small bile ducts. Among them, 1 case (5%) was complicated with Caroli's disease, and 1 case (5%) was HNF1α hepatocellular adenoma. IHC GS showed that was positively expressed in acinar region 3 in 75% cases. Conclusion: CHF is mainly manifested by portal hypertension and its complications. Histopathology is the gold standard for diagnosis. The possibility of CHF should be considered first in children and adolescents with portal hypertension but no history of hepatitis, and complicated kidney disease. The positive pattern of acinus-3 region of GS in IHC is helpful for the diagnosis of CHF.

Urban-rural disparity of preventive healthcare utilisation among children under the universal health insurance coverage in Taiwan: a national birth cohort analysis.

OBJECTIVE: In the context of universal health insurance coverage, this study aimed to determine whether urban-rural inequality still exists in preventive health care (PHC) amongst children in Taiwan. STUDY DESIGN: Prospective cohort study. METHODS: A total of 184,117 mothers and their children born in 2009 were identified as the study cohort. The number of children born in urban, satellite and rural areas was 40,176, 57,565 and 86,805, respectively. All children were followed for 7 years, before which a total of seven times PHC were provided by Taiwan's National Health Insurance (NHI) programme. Ordinal logistic regression models were used to associate urbanisation level with the frequency of PHC utilisation. Stratified analyses were further performed in accordance with the children's birth weight and the mothers' birthplace. RESULTS: Children from satellite areas had higher utilisation for the first four scheduled PHC visits. Children living in urban areas received more PHC for the fifth and sixth scheduled visits. Compared with those from rural areas, children in satellite areas exhibited a small but significant increase in odds in PHC utilisation, with a covariate-adjusted odds ratio (aOR) of 1.04 and 95% confidence interval (CI) of 1.02-1.06. By contrast, no significant difference was observed between rural and urban areas (aOR = 1.01). Further stratified analyses suggest more evident urban-rural difference in PHC utilisation amongst children with low birth weight and foreign-born mothers. CONCLUSIONS: Given a universal health insurance coverage and embedded mechanisms in increasing the availability of healthcare resources in Taiwan, a slight urban-rural difference is observed in PHC utilisation amongst children. Hence, sociodemographic inequality in utilisation of PHC still exists. This issue should be addressed through policy intervention.

Research Progress on Forensic Genetics of Facial Morphological Depiction.

ABSTRACT: Forensic DNA phenotyping （FDP） analysis uses DNA from biological samples left in crime scenes to predict individual phenotypic traits, such as geographical origin of ethnic group, height, weight, skin color, hair color and shape, iris color, male baldness, facial morphology, age, etc., thereby providing clues for case investigations. Among these traits, features of facial morphology are relatively more complicated. This paper makes an overall analysis of the measurement and collection of facial morphology, research on facial morphology related genes, forensic application and establishment of facial morphology depiction model, ethical issues, etc., then summarizes the latest research progress on features of facial morphology.

The crucial role of Mn spiral spin order in stabilizing the Dy-Mn exchange striction in multiferroic DyMnO3.

DyMnO3 hosts the less addressed duality of multiferroicity, owing to the Dy-Mn exchange striction and inverse Dzyaloshinskii-Moriya interaction between Mn spin pairs. Although the duality in DyMnO3 has been discussed earlier, there remains a question whether the Mn magnetic sublattice is necessarily multiferroic for generating the Dy-Mn exchange striction. In this work, we investigate the multiferroicity of Dy(Mn1-xFex)O3 (0 ≤ x ≤ 0.1) through detailed magnetic and ferroelectric characterization. It is found that Fe-doping continuously suppresses the independent Dy spin order but instead promotes the Dy-Mn(Fe) coupling. This coupling benefits the Dy-Mn(Fe) exchange striction which remarkably enhances the ferroelectric polarization at a low doping level (x ≤ 0.015), beyond which the Mn spiral spin order breaks down leading to collapse of the macroscopic polarization at x ≥ 0.05. This work discloses the crucial role of Mn spiral spin order in stabilizing the Dy-Mn exchange striction and thus highlights the duality of multiferroicity in DyMnO3.

Association of EGFR and KRAS mutations with expression of p-AKT, DR5 and DcR1 in non-small cell lung cancer.

The activation of AKT is one of the causes of resistance to epidermal growth factor receptor (EGFR)- tyrosine kinase inhibitors (TKIs). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combines with related receptors to trigger apoptosis or protect the cells against TRAIL apoptosis. This research focused on the association of EGFR and KRAS mutations with expression of AKT, p-AKT, DR5 and DcR1 in non-small cell lung cancer. 82 NSCLC patients were included in the study. xTAG liquichip techonolgy (xTAG-LCT) was applied to investigate the genetic mutation of EGFR and KRAS, Quantitative Real-time PCR was used to test the mRNA expression of AKT, DR5 and DcR1 and Western Blot was applied to test the protein expression of AKT, p-AKT, DR5, and DcR1. We found that of 82 patients, 31 cases had EGFR-activating mutations, more common in female, adenocarcinoma, and non-smoker patients; 9 cases had KRAS mutations, frequently found in patients with smoking history. The expression of AKT and p-AKT correlated with staging, tumor differentiation, and lymph node metastasis. The expression of DR5 in phase III and low differentiation tumor was significantly higher than that in phase I+II and high and median differentiation tumor; the expression of DcR1 in phase III and low differentiation tumor was significantly lower than that in phase I+II and high and median differentiation tumor. Compared with EGFR and KRAS wild type, in NSCLC tissue with EGFR and KRAS mutations, the expression of AKT and p-AKT was significantly higher. These results suggest that EGFR and KRAS mutation status was associated with the expression of AKT and p-AKT. AKT, p-AKT, DR5, and DcR1 all took part in the occurrence and development of NSCLC, and may become a reference index to evaluate the prognosis of NSCLC.

[Analysis of prognostic factors of portal hypertension treated with devascularization].

Objective: To explore the prognostic factors of portal hypertension treated with devascularization. Methods: A total of 397 patients with portal hypertension underwent devascularization in Nanjing Drum Tower Hospital from February 1993 to April 2014, among which there were 242 male and 155 female patients with median age of 48 years. The perioperative data were retrospectively collected. Logistic regression was used to find the risk factors which affect the operative complications. Follow-up evaluation was in progress regularly. Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to find out factors which affect the long-term results. Results: All together 397 patients underwent devascularization, in whom 8 patients died perioperative, 389 patients discharged successfully. Logistic regression showed that age (≥48 years) (χ2=4.559, OR=2.048, P=0.033), red color sign before surgery (χ2=4.959, OR=2.129, P=0.026) and without portosystemic collateral vessels reserved (χ2=13.348, OR=5.122, P=0.000) were risk factors of perioperative complications. The follow-up time was (5.7±4.6) years. Totally 27 patients were lost from follow-up, 103 patients died for the disease during follow-up. The survival rate at 1-, 3-, 5-, 10-, 15- and 20-years was 93.6%, 86.9%, 80.1%, 59.3%, 54.1% and 38.5% respectively.Univariate analysis showed that gender (male), age (≥48 years), hemorrhage before surgery (≥500 ml per time), hepatitis virus and without portosystemic collateral vessels reserved were risk factors of the long-term survival (P<0.05). Cox regression analysis showed that age (≥48 years) (χ2=9.850, RR=1.904, P=0.002), hemorrhage before surgery (≥500 ml per time) (χ2=34.402, RR=3.273, P=0.000), hepatitis virus (χ2=7.573, RR=2.525, P=0.006) and without portosystemic collateral vessels reserved (χ2=5.905, RR=1.889, P=0.015) were independent risk factors that affect the long-term survival. Conclusion: Devascularization with portosystemic collateral vessels reserved has favorable perioperative and long-term outcome, and it definitely is a very safe and effective technique for portal hypertension.

Basic fibroblast growth factor promotes macaque follicle development in vitro.

Fertility preservation is an important type of frontier scientific research in the field of reproductive health. The culture of ovarian cortices to i) initiate primordial follicle growth and ii) procure developing follicles for later oocyte maturation is a promising fertility preservation strategy, especially for older women or cancer patients. At present, this goal remains largely unsubstantiated in primates because of the difficulty in attaining relatively large follicles via ovarian cortex culture. To overcome this hurdle, we cultured macaque monkey ovarian cortices with FSH, kit ligand (KL), basic fibroblast growth factor (bFGF), and/or epidermal growth factor (EGF). The various factors and factor combinations promoted primordial follicle development to different extents. Notably, both bFF (bFGF, 100 ng/ml and FSH, 50 ng/ml) and KF (KL, 100 ng/ml and FSH, 50 ng/ml) contributed to the activation of primordial follicles at day 12 (D12) of culture, whereas at D18, the proportions of developing follicles were significantly higher in the bFF and KF groups relative to the other treatment groups, particularly in the bFF group. Estradiol and progesterone production were also highest in the bFF group, and primary follicle diameters were the largest. Up until D24, the bFF group still exhibited the highest proportion of developing follicles. In conclusion, the bFGF-FSH combination promotes nonhuman primate primordial follicle development in vitro, with the optimal experimental window within 18 days. These results provide evidence for the future success of human ovarian cortex culture and the eventual acquisition of mature human follicles or oocytes for fertility restoration.

Epidemiology of childhood Type 1 diabetes in Taiwan, 2003 to 2008.

AIMS: To report the annual incidence rate and the socio-demographic and clinical characteristics of childhood Type 1 diabetes in Taiwan in the period 2003-2008. METHODS: A total of 1306 incident cases of childhood (0-14 years) Type 1 diabetes were identified from Taiwan's National Health Insurance claim datasets from the period 2003-2008. The temporal trend of the incidence rate of Type 1 diabetes and the features of hospitalizations in the first year after diagnosis were investigated. The associations of patient characteristics, child population density and the urbanization level of the residential areas with the risk of Type 1 diabetes were assessed using Poisson regression analysis. RESULTS: The annual incidence rate was stable, irrespective of age and gender, with a mean annual incidence rate of 5.3 per 100 000 children. Girls were more likely than boys to develop Type 1 diabetes (6.0 vs 4.7 per 100 000 children) and the incidence rate increased with age. There was no apparent geographic variation in the incidence rates. Despite the 60% decrease in the rate of admission (from 11.0 to 5.8%) over the study period, ketoacidosis remained the major diabetes complication leading to admission for childhood Type 1 diabetes. The multivariate analysis suggested that female gender and older age were significant predictors of the incidence of Type 1 diabetes, whereas the population density of children and the urbanization levels of the residential areas were not. CONCLUSIONS: Girls and older children should receive particular attention when formulating preventive strategies targeting Type 1 diabetes. Additionally, clinicians should still carefully optimize the management of children with Type 1 diabetes to further reduce the occurrence of ketoacidosis.

CXCR4 heterogeneous expression in esophageal squamous cell cancer and stronger metastatic potential with CXCR4-positive cancer cells.

CXCR4 belongs to a family of G protein-coupled cell surface receptors and has been proved to a prognostic marker in a various tumors, including esophageal squamous cell cancer. In this study, we analyzed CXCR4 expression in tumor tissue and metastatic tumor tissues of lymph node by immunohistochemistry. CXCR4 was found to be an independent factor of patients' survival and heterogeneously expressed in tumor tissues. Compared with the primary tumor tissues, the scores of CXCR4 expression were significantly higher in corresponding metastatic tumor tissues of lymph nodes (P < 0.01). It was suggested CXCR4-positive cells were prone to migrate to lymph nodes. In the further experiments in vitro, we confirmed heterogeneous expression of CXCR4 in esophageal squamous cell cancer cell lines (KYSE70, Ec109, and CaES17) by flow cytometry analysis. Meanwhile, two subpopulations were isolated from Ec109 based on CXCR4 membrane expression by fluorescence-activated cell sorting. CXCR4-positive cells showed stronger migration ability in Boyden chamber assay than CXCR4 negative ones (P < 0.01). However, no significant difference of cell proliferation was found between the two subpopulations in colony formation assay (P > 0.05). We concluded that CXCR4 might be a key molecule in esophageal squamous cell cancer metastasis.

Bioinformatics analyses combined microarray identify the desregulated microRNAs in lung cancer.

BACKGROUND: MicroRNAs (miRNAs) play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis. Deregulated miRNAs are found in blood cells of cancer patients recently. AIM: This study aims to screen the differentially expressed miRNAs (DE-miRNAs) which could discriminate lung cancers from non-cancerous lung tissues as well as molecular signatures that differ in tumor histology. MATERIALS AND METHODS: miRNA expression profiles of GSE17681 was downloaded from Gene Expression Omnibus database. Three test methods were used to identify DE-miRNAs between lung cancer tissue and healthy controls. Target genes of DE-miRNAs were retrieved from three databases and mapped to KEGG to investigate their roles in lung cancer. Further, a protein-protein interaction (PPI) network was constructed used STRING and Cytoscape. RESULTS: A total of 17 DE-miRNAs were identified. Among them, hsa-miR-339-5p draw specific attention. Pathway analysis revealed that target genes of RASSF1 and KRAS play roles as oncogene or tumor suppressor gene in the progression of lung cancer. Besides, Target genes of RASSF1 and ERBB4 formed a module in the PPI network. Functional analysis suggested biological process of response to hypoxia was significantly enriched. CONCLUSIONS: hsa-miR-339-5p play important role in the regulation of lung cancer and it may be potential to be used as biomarker to predict lung cancer progression.

Increased risk of severe acute pancreatitis in patients with diabetes.

AIMS: We prospectively assessed the age- and sex-specific incidence rates and relative risks of overall and severe acute pancreatitis in Taiwanese with diabetes. METHODS: The study cohort included age- and-sex-matched groups of patients with (n = 547,554) and without (n = 584,373) diabetes. Incidence rate was estimated under Poisson assumption and relative risks of acute pancreatitis and severe acute pancreatitis, based on modified Atlanta criteria, were indicated by hazard ratios estimated from Cox proportional hazard regression models. RESULTS: Over an 8-year follow-up period, the incidence of acute pancreatitis was 2.98 and 1.68 per 1000 person-years for patients with and without diabetes, respectively, representing a covariate adjusted hazard ratio of 1.53 (95% confidence interval 1.49-1.58). Diabetes was associated with a significantly elevated risk of acute pancreatitis in all sex and age stratifications, with the highest hazard ratio noted for study subjects aged < 45 years (men 2.37; women 2.95). Diabetes was also significantly associated with an increased hazard ratio of severe acute pancreatitis [1.46 (1.36-1.57)], and especially of acute pancreatitis with local complications [1.65 (1.14-2.39)]. CONCLUSIONS: Diabetes is associated with an increased risk of overall and severe acute pancreatitis, and the relation is stronger in women and young patients.

Correlation between antimicrobial consumption and resistance among Staphylococcus aureus and enterococci causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009.

This study investigated the correlation between antibiotic consumption and resistance among Staphylococcus aureus and enterococci causing healthcare-associated infections at a university hospital in Taiwan from 2000 to 2009. Overall, the trend of total consumption (defined daily dose [DDD] per 1,000 patient-days) of glycopeptides, including vancomycin and teicoplanin, significantly increased during 2000 to 2003 and remained stable during 2004-2009. Vancomycin consumption significantly increased during 2003 and decreased after 2004. A significant decrease in the resistance rate with time was found for oxacillin- and gentamicin-resistant S. aureus. In contrast, the rates of vancomycin- and teicoplanin-resistant enterocci increased significantly. A significant correlation was found between the increased use of extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, carbapenems and the decreased prevalence of methicillin-resistant S. aureus (MRSA). In contrast, the increased use of teicoplanin, extended-spectrum cephalosporins, ß-lactam-ß-lactamase inhibitor combinations, and carbapenems was correlated with the increased prevalence of vancomycin-resistant enterococci (VRE). In conclusion, this 10-year study in a single institution identified different correlations between the prescription of antibiotics and the resistance rates of MRSA and VRE. Strict implementation of infection control policy based on these correlates would be helpful in decreasing the presence of these multidrug-resistant pathogens in hospitals.

The expression of CXCR4 and its relationship with matrix metalloproteinase-9/vascular endothelial growth factor in esophageal squamous cell cancer.

Esophageal cancer (EC) is a highly aggressive neoplasm with poor prognosis. The main reason for this disappointing outcome is the strong behavior of esophageal cancer cell's invasion and metastasis. CXC chemokine receptor 4 (CXCR4) was found to be expressed in many tumors and significantly correlated with invasion, angiogenesis, metastasis, and prognosis. In the present study, we investigated the expressions of CXCR4, matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF) in esophageal squamous cell cancer (ESCC) and analyzed the relationship among the three proteins. Sections of paraffin-embedded tissues were obtained from 127 patients with ESCC undergoing esophagectomy at Zhongshan Hospital, Fudan University in 2005. The CXCR4, MMP-9, and VEGF expressions in EC tissues were evaluated according to the immunohistochemical staining area and intensity. The correlations between patients' prognosis and covariates were analyzed by Kaplan--Meier method (univariate analysis) and Cox regression (multivariate analysis). The overall expression rate of CXCR4, MMP-9, and VEGF was 88.2%, 93.7%, and 79.5%, respectively. CXCR4 expression was significantly associated with tumor grade, tumor size, tumor depth, regional lymph node metastasis, and tumor, node, metastasis (TNM) stage (P < 0.05). MMP-9 expression was significantly associated with age and tumor grade (P < 0.05). VEGF expression was significantly associated with tumor grade, tumor depth, and TNM stage (P < 0.05). CXCR4 expression was positively correlated with MMP-9 expression (P < 0.01, r= 0.365) and VEGF expression (P < 0.01, r= 0.380). However, there was no significant correlation between MMP-9 and VEGF expression (P > 0.05). In univariate analysis, CXCR4 expression, tumor size, tumor depth, lymph node metastasis, and TNM stage were correlated with patients' prognosis (P < 0.05); in multivariate analysis, tumor size and lymph node metastasis were the independent factors of poor prognosis. CXCR4 was highly expressed in ESCC and correlated with MMP-9, VEGF, clinicopathological features and prognosis. We speculated CXCR4 play an important role during the progression of this disease and there might be some regulatory mechanism existing between CXCR4 and MMP-9/VEGF in ESCC.

Hepatocellular carcinoma progression is protected by miRNA-34c-5p by regulating FAM83A.

OBJECTIVE: To elucidate the role of microRNA-34c-5p (miRNA-34c-5p) in the progression of hepatocellular carcinoma (HCC) and the indicated mechanism. PATIENTS AND METHODS: Relative levels of miRNA-34c-5p and FAM83A in HCC tissues and cell lines were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Their influences on clinical features in HCC patients were analyzed. Kaplan-Meier method was introduced for assessing the relationship between miRNA-34c-5p and overall survival in HCC. After overexpression of miRNA-34c-5p in HepG2 and HB611 cells, we detected proliferative, migratory and invasive abilities by cell counting kit-8 (CCK-8) and transwell assay. The interaction between miRNA-34c-5p and FAM83A was explored by Dual-Luciferase reporter assay. Finally, their co-regulation on HCC cell phenotypes was examined. RESULTS: MiRNA-34c-5p was downregulated in HCC tissues, especially stage III+IV cases. Its level was correlated to tumor size, tumor number and TNM staging in HCC. Overexpression of miRNA-34c-5p inhibited proliferative, migratory and invasive abilities in HepG2 and HB611 cells. In addition, miRNA-34c-5p targeted on FAM83A and negatively regulated its level. Overexpression of FAM83A could reverse the inhibitory effects of miRNA-34c-5p on malignant phenotypes of HCC cells. CONCLUSIONS: By negatively regulating FAM83A level, miRNA-34c-5p alleviates the progression of HCC.

In vitro activities of moxifloxacin and tigecycline against bacterial isolates associated with intraabdominal infections at a medical center in Taiwan, 2001-2006.

A total of 569 nonduplicate isolates recovered from patients with community-onset or hospital-onset intraabdominal infections (IAIs) from 2001 to 2006 were studied. These included 28 Staphylococcus aureus and 541 Gram-negative isolates (33.6% Escherichia coli, 29.0% Klebsiella pneumoniae, 8.1% Acinetobacter baumannii, and 6.3% Pseudomonas aeruginosa). Minimum inhibitory concentrations (MICs) of the isolates to moxifloxacin, imipenem, and ciprofloxacin were determined using the agar dilution method and to tigecycline using the broth microdilution method. Extended-spectrum beta-lactamase (ESBL) producers were found in 15.5% (29 out of 182) of E. coli, 15.3% (24 out of 157) of K. pneumoniae, and 15.4% (2 out of 13) of K. oxytoca isolates. More than 85% of Enterobacteriaceae were susceptible to moxifloxacin, but this percentage was lower among E. coli (78%). The percentage of E. coli (K. pneumoniae) isolates that were not susceptible to moxifloxacin was 6% (0%) in 2001, 39% (17%) in 2003, and 21% (14%) in 2006. Tigecycline exhibited good in vitro activities against all S. aureus and >95% of all Enterobacteriaceae tested. Among the 24 isolates of ESBL-producing K. pneumoniae, 4 had tigecycline MICs > or = 2 microg/ml. Eighty percent of A. baumannii isolates exhibited tigecycline MICs of < or = 2 microg/ml. This study found that moxifloxacin and tigecycline exhibited good in vitro activity against bacterial isolates causing IAIs.

Crystalline nanotubes of gamma-AlOOH and gamma-Al2O3: hydrothermal synthesis, formation mechanism and catalytic performance.

Crystalline nanotubes of gamma-AlOOH and gamma-Al(2)O(3) have been synthesized. An anionic surfactant-assisted hydrothermal process yields gamma-AlOOH nanotubes, and appropriate calcination treatment of the gamma-AlOOH nanotubes yields gamma-Al(2)O(3) nanotubes. The nanotubes were characterized by XRD, SEM, TEM, TG-DSC, FTIR and nitrogen adsorption-desorption techniques. Both the gamma-AlOOH and gamma-Al(2)O(3) nanotubes are crystalline, with a representative length of approximately 500 nm and diameters of 20-40 nm. The gamma-Al(2)O(3) nanotubes exhibit a very high mesoporous specific surface area (SSA) of 201.0 m(2) g(-1) and a high mesopore volume of 0.68 cm(3) g(-1) with an average mesopore size of 27.7 nm, as well as a high microporous SSA of 186.0 m(2) g(-1) and a micropore volume of 0.08 cm(3) g(-1) with an average micropore size of 0.53 nm. The formation process was discussed and a possible mechanism was proposed, in which a lamellar phase was first formed by camphorsulfonic anions and Al(III) species, and then rolled up to form the crystalline nanotubes under the hydrothermal condition. The catalytic performance of the obtained gamma- Al(2)O(3) nanotubes was tested by using the dehydration of ethanol to ethylene as a probe reaction and it was shown that the obtained gamma- Al(2)O(3) nanotubes catalyst possesses a higher catalytic activity compared with the gamma- Al(2)O(3) nanoparticles.

A spatiotemporal statistical model of the risk factors of human cases of H5N1 avian influenza in South-east Asian countries and China.

OBJECTIVES: This article aims to quantify the risk factors associated with the human cases of H5N1 avian influenza in South-east Asian countries and China; a dangerous region for this disease that has the potential for a pandemic outbreak. STUDY DESIGN: A statistical model with time and spatial dimensions was built to capture the international spread patterns of this disease. METHODS: The grid search method was used to fit the model with 2004-2006 data. The grid search approach is a simple procedure that allows the fit of any function to data. RESULTS: This study found that: (1) when the number of domestic H5N1 human cases increases by one person in a certain time period, the chance that the country will have a human case in the next period increases by 22.10%; (2) when the number of human cases in a neighbouring country increases by one person in a certain time period, the chance that the country will have a human case in the next period increases by 1.62%; (3) when the number of avian cases in a neighbouring country increases by one, the chance that the country will have a human case increases by 0.02%; (4) as the human population increases by one unit, the chance that the country will have a human case increases by 0.10%; (5) when the quantity of imported poultry increases by 1000 metric tons, the chance that the country will have a human case increases by 0.03%; (6) when the outbreak of the disease among domestic birds increases by one, the chance that the country will have a human case increases by 0.19%; and finally (7) when the number of birds destroyed increases by 1000, the chance that the country will have a human case decreases by 0.30%. CONCLUSIONS: These findings shed new light on the spatiotemporal characteristics of the epidemic, and thus need to be taken into consideration in interdisciplinary and scientific discussion of the disease.

Differential molecular markers of primary lung tumors and metastatic sites indicate different possible treatment selections in patients with metastatic lung adenocarcinoma.

PURPOSE: Detecting different molecular markers in primary tumors and metastases may provide therapeutic information. Here we investigated differences between primary tumors and four metastatic sites of lung adenocarcinoma in the biomarkers' features and discussed potential therapeutic implications. METHODS: A total of 228 patients with metastatic lung adenocarcinoma were analyzed for EGFR, KRAS, BRAF and PIK3CA mutations detected by xTAG liquidchip technology (xTAG-LCT), as well as ERCC1, TYMS, RRM1, TUBB3, STMN1, TOP2A and VEGFR1-3 mRNA expression detected by branched DNA-liquidchip technology (bDNA-LCT). RESULTS: Higher rates of low ERCC1 (35.6 vs. 20.3%, P = 0.0105), RRM1 (23.3 vs. 13.0%, P = 0.0437), STMN1 (72.2 vs. 42.8%, P = 0.0000) and high VEGFR2 (34.4 vs. 18.8%, P = 0.0078) mRNA expression were found in EGFR-mutated tumors, suggesting possible benefit from platinum, gemcitabine, taxanes or VEGFR2 inhibitors. Primary lesions showed low ERCC1 (31.6 vs. 18.5%, P = 0.0271), TYMS (17.6 vs. 7.6%, P = 0.0300), TUBB3 (16.9 vs. 7.6%, P = 0.0415), STMN1 (62.1 vs. 42.9%, P = 0.0065) and high TOP2A (48.7 vs. 33.1%, P = 0.0262) mRNA expression and higher KRAS mutations (25.7 vs. 14.1%, P = 0.0350), suggesting platinum, taxanes, pemetrexed, anti-TOP2A agents and resistant to anti-EGFR therapies. Liver metastases showed absence of low TYMS expression, indicating insensitivity to pemetrexed-based regimen. Pleura metastases harbored higher rates of high VEGFR2 expression (50.0 vs. 19.1%, P = 0.0127). Lymph node metastases presented higher rates of high VEGFR2 expression (37.5 vs. 19.1%, P = 0.0253) and EGFR mutations (59.4 vs. 34.4%, P = 0.0011), suggesting use of anti-VEGFR2 and anti-EGFR therapies. CONCLUSION: Molecular profiling of 228 lung adenocarcinomas determined a significant difference between biomarkers such as EGFR and KRAS subtypes at primary and metastatic sites. Our results serve as a reference for individual treatment based on different potential targets in metastatic lung adenocarcinoma directed by molecular profiling.