Exploration of KIR genes and hematological-related diseases in Chinese Han population.

The function of natural killer (NK) cells has previously been implicated in hematopoietic-related diseases. Killer immunoglobulin-like receptors (KIR) play an important role in NK cells after hematopoietic stem cell transplantation. To explore the immunogenetic predisposition of hematological-related diseases, herein, a multi-center retrospective study in China was conducted, analyzing and comparing 2519 patients with hematopathy (mainly, acute lymphoblastic leukemia, acute myeloid leukemia, aplastic anemia, and myelodysplastic syndrome) to 18,108 individuals without known pathology. Genotyping was performed by polymerase chain reaction with specific sequence primers (PCR-SSP). As a result, we discovered four genes including KIR2DL5 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS1 (OR: 0.74, 95% CI 0.59-0.93; Pc = 0.0405), 2DS3 (OR: 0.58, 95% CI 0.41-0.81; Pc = 0.0180), and 3DS1 (OR: 0.74, 95% CI 0.58-0.94; Pc = 0.0405) to be protective factors that significantly reduce the risk of aplastic anemia. Our findings offer new approaches to immunotherapy for hematological-related diseases. As these therapies mature, they are promising to be used alone or in combination with current treatments to help to make blood disorders a manageable disease.

Differential requirements of IQUB for the assembly of radial spoke 1 and the motility of mouse cilia and flagella.

The T-shaped radial spoke (RS) is a protein complex attached to the A microtubule of the outer doublet microtubules, and it extends toward the central pair (CP). It modulates the beat frequency, amplitude, and waveform of the flagella and cilia by serving as a mechanochemical signal transducer between the CP and dyneins. In humans, RS defects cause primary ciliary dyskinesia, but the structural components of triple RSs (RS1, RS2, and RS3) in mammals remain to be elucidated in detail. Here, we introduce a mouse model that lacked the entire RS1 in sperm flagella, due to the deletion of Iqub, while the tracheal cilia possessed intact triple RSs. Furthermore, the absence of IQUB only resulted in male infertility, owing to the sperm motility defect. Based on the mouse model, the RS1 compositions are identified in sperm flagella. In summary, this study elucidates the RS1 components and function in mammalian flagella.

Overexpressed DAAM1 correlates with metastasis and predicts poor prognosis in breast cancer.

Recent studies have reported that dishevelled-associated activator of morphogenesis 1 (DAAM1) is remarkably essential for mediating cell migration and invasion in breast cancer (BrCa). Nonetheless, the definite expression profile of DAAM1 in BrCa patients and the impact on metastasis of BrCa in vivo have not been explored up to now. The differential expression of DAAM1 in BrCa and adjacent tissues was assessed via immunohistochemistry (IHC) staining. The metastatic capacities of BrCa SUM-1315 cells were examined in BALB/c nude mice. Besides, the prognostic values of DAAM1 mRNA in BrCa were explored based on Kaplan-Meier (KM) plotter. The expression of DAAM1 protein was notably overexpressed in BrCa tissues compared with that in paired normal breast tissues. The high expression of DAAM1 in BrCa tissues was significantly associated with lymph-node metastasis. Furthermore, DAAM1 overexpression promoted the invasive capacity of BrCa cells and stimulated lung metastatic extent in vivo. We also found that overexpressed DAAM1 mRNA was significantly associated with poor relapse-free survival (RFS), overall survival (OS), distance-metastasis-free survival (DMFS), and post-progression survival (PPS). Our findings reveal that DAAM1 might be a novel therapeutic target to manage the deteriorated metastasis of BrCa and identified DAAM1 as a promising biomarker for unfavorable prognosis in BrCa patients.

Identification of five hub genes as monitoring biomarkers for breast cancer metastasis in silico.

BACKGROUND: Breast cancer is one of the most common endocrine cancers among females worldwide. Distant metastasis of breast cancer is causing an increasing number of breast cancer-related deaths. However, the potential mechanisms of metastasis and candidate biomarkers remain to be further explored. RESULTS: The gene expression profiles of GSE102484 were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to screen for the most potent gene modules associated with the metastatic risk of breast cancer, and a total of 12 modules were identified based on the analysis. In the most significant module (R2 = 0.68), 21 network hub genes (MM > 0.90) were retained for further analyses. Next, protein-protein interaction (PPI) networks were used to further explore the biomarkers with the most interactions in gene modules. According to the PPI networks, five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) were identified as key genes associated with breast cancer progression. Furthermore, the prognostic value and differential expression of these genes were validated based on data from The Cancer Genome Atlas (TCGA) and Kaplan-Meier (KM) Plotter. Receiver operating characteristic (ROC) curve analysis revealed that the mRNA expression levels of these five hub genes showed excellent diagnostic value for breast cancer and adjacent tissues. Moreover, these five hub genes were significantly associated with worse distant metastasis-free survival (DMFS) in the patient cohort based on KM Plotter. CONCLUSION: Five hub genes (TPX2, KIF2C, CDCA8, BUB1B, and CCNA2) associated with the risk of distant metastasis were extracted for further research, which might be used as biomarkers to predict distant metastasis of breast cancer.

DAAM1-mediated migration and invasion of ovarian cancer cells are suppressed by miR-208a-5p.

Ovarian cancer (OvCa) has the highest morbidity among all gynecologic cancers worldwide, and its distant metastasis is one of main causes for the poor prognosis of OvCa patients. Our previous studies have reported that DAAM1-involved signaling pathways play vital roles in metastasis of breast cancer. However, whether DAAM1 participates in OvCa migration and/or invasion is still unknown. The impact of DAAM1 on cell migration and invasion in OvCa was evaluated by wound healing assay and Boyden chamber assay. The specific miRNA targeting DAAM1 was predicted by bioinformatics methods and verified by dual-luciferase activity assay. The miR-208a-5p expression levels in OvCa tissues and the impacts of miR-208a-5p on cell migration and invasion were also assessed, respectively. High expression of DAAM1 was associated with distant metastasis in OvCa. Silence of DAAM1 by siRNA blocked the migration and invasion of OVCAR-3 cells. MiR-208a-5p directly targeted DAAM1 and was shown a decreased expression in metastatic OvCa tissues. Elevated expression of miR-208a-5p inhibited the migration and invasion of OVCAR-3 cell which can be rescued by DAAM1 overexpression. Our data suggest that miR-208-5p/DAAM1 axis participates in OvCa migration and invasion and may be a novel clinical target to limit OvCa metastasis.

Unusual cause of lesions in the descending duodenum and liver: A case report and review of literature.

The descending duodenum is rarely involved in Schistosoma japonicum (S. japonicum) infection. Here, we report a case of acute Schistosoma infection, which presented with abdominal pain, abdominal distension and irregular fever. Tumor-like lesions were observed in the descending duodenum. Simultaneously, heterogeneity in hepatic perfusion was demonstrated by dynamic computed tomography scanning. Biopsy of the descending duodenum showed the deposition of Schistosoma eggs. Following administration of the antihelminthic drug praziquantel, the patient showed rapid clinical improvement. In conclusion, we report a patient with acute S. japonicum infection presenting as tumor-like lesions in the descending duodenum and heterogeneity of blood perfusion in liver parenchyma.

The Impacts of Regulations and Financial Development on the Operations of Supply Chains with Greenhouse Gas Emissions.

To establish a micro foundation to understand the impacts of greenhouse gas (GHG) emission regulations and financial development levels on firms' GHG emissions, we build a two-stage dynamic game model to incorporate GHG emission regulations (in terms of an emission tax) and financial development (represented by the corresponding financing cost) into a two-echelon supply chain. With the subgame perfect equilibrium, we identify the conditions to determine whether an emission regulatory policy and/or financial development can affect GHG emissions in the supply chain. We also reveal the impacts of the strictness of GHG emission regulation, the financial development level, and the unit GHG emission rate on the operations of the supply chain and the corresponding profitability implications. Managerial insights are also discussed.

Etiologic and epidemiologic analysis of hand, foot, and mouth disease in Guangzhou city: a review of 4,753 cases

OBJECTIVES: This study aimed to review etiological and epidemiological data for hand, foot, and mouth disease (HFMD) cases that occurred between 2008 and 2010 in Guangzhou City, to help develop and implement precautionary measures applicable for future outbreaks. METHODS: The characteristics of 4,753 HFMD episodes were retrospectively reviewed in 4,636 patients reported between 2008 and 2010 by the Guangdong Women and Children's Hospital, which is the national enterovirus monitoring agent and the designated hospital in China for treating severe HFMD. RESULTS: Out of 4,753 incident episodes reviewed, 525 patients were hospitalized; 60% were males. Most patients (93.8%) were children under 5 years old, with a median age at onset of 2.4 years. HFMD incidence peaked in April/May and September/October. From the total, 1,067 (22.4%) infections were positive for human enterovirus 71 (HEV71), 1,094 (23.0%) were positive for coxsackievirus A16 (CA16), and 941 (19.8%) were positive for other common enteroviruses. In contrast, 1,666 (35.0%) cases were negative to HEV71, CA16, and other common enteroviruses. Cross-correlation coefficients demonstrated associations between the number of cases, seasonal temperatures, and humidity. Among hospitalized cases, HEV71 was positive in 261 (24.5%), and 42 (3.9%) critical cases were positive for HEV71. CONCLUSION: Seasonal fluctuations and HEV71 and CA16 were the two key factors influencing the Guangzhou HFMD epidemic. The infection predominantly affected children younger than 5 years old.

Alterations in the processing of non-drug-related affective stimuli in abstinent heroin addicts.

Long-term exposure to drug may alter the neural system associated with affective processing, as evidenced by both clinical observations and behavioral data documenting dysfunctions in emotional experiences and processing in drug addicts. Although many imaging studies examined neural responses to drug or drug-related cues in addicts, there have been few studies explicitly designed to reveal their neural abnormalities in processing non-drug-related natural affective materials. The present study asked abstinent heroin addicts and normal controls to passively view standardized affective pictures of positive, negative, or neutral valence and compared their brain activities with functional MRI. Compared to normal controls, addicts showed reduced activation in right amygdala in response to the affective pictures, consistent with previous reports of blunted subjective experience for affective stimuli in addicts. Furthermore, in two visual cortical areas BA 19 and 37, while the controls showed greater responses to positive pictures than to negative ones replicating literature findings, the addicts showed the opposite pattern. The results reveal a complex pattern of altered processing of non-drug-related affective materials in addicts showing both heightened and blunted neural responses in different brain regions and for different stimulus valence. The present study highlights the importance of brain imaging research on drug addicts' processing of affective stimuli in understanding disruptions in their emotion circuitry.

[Effect of vascular endothelial growth factor small interfering RNA (siRNA) on retinal microvascular endothelial cells under hypoxia condition in vitro].

OBJECTIVE: To explore VEGF siRNA's effect on the immature fetal retinal microvascular endothelial cells in vitro. METHOD: The fresh retinal micrangium was primarily cultured to obtain microvascular endothelial cells. CoCl2 was used to simulate oxygen-deficient conditions. siRNA directed against human VEGF was designed and chemically synthesized. There were 3 groups in our experiment: VEGF siRNA group, hypoxia control group, and negative siRNA control group. The fetal retinal micrangium vascular endothelial cells were transfected by using liposome. The expression levels of VEGF mRNA and protein were evaluated by RT-PCR and Western blotting 24, 48, 72 h after transfection, cell proliferation was evaluated by MTT method. RESULT: The expression levels of VEGF mRNA decreased by 21.05%, 79.67%, and 90.48% 24 h, 48 h, and 72 h after transfection as compared to those in hypoxia control group, the expression level of VEGF protein had decreased by 14.58%, 66.97%, and 81.61% as compared to those in hypoxia control group. The siRNA could decrease cell proliferation under hypoxia too, the multiplication rate after 12, 24, 48, and 72 h decreased by 15.0%, 42.9%, 78.3% and 65.9%. CONCLUSION: VEGF siRNA could down-regulate the expression of VEGF in immature fetal retinal microvascular endothelial cells and suppressed cell proliferation. Application of siRNA to inhibit expression of VEGF may be a hopeful way to prevent and cure ROP.

Peripheral pulmonary nodules: relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression.

BACKGROUND: The aim of this study is to investigate the relationship between 16-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF (vascular endothelial growth factor) expression in patients with benign and malignant pulmonary nodules, and differential diagnosis between benign and malignant pulmonary nodules. METHODS: Sixty-four patients with benign and malignant pulmonary nodules underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for TDC (time density curve), perfusion parametric maps, and the respective perfusion parameters. Immunohistochemical findings of MVD (microvessel density) measurement and VEGF expression was evaluated. RESULTS: The shape of the TDC of peripheral lung cancer was similar to those of inflammatory nodule. PH (peak height), PHpm/PHa (peak height ratio of pulmonary nodule to aorta), BF (blood flow), BV (blood volume) value of peripheral lung cancer and inflammatory nodule were not statistically significant (all P > 0.05). Both showed significantly higher PH, PHpm/PHa, BF, BV value than those of benign nodule (all P < 0.05). Peripheral lung cancer showed significantly higher PS (permeability surface) value than that of inflammatory nodule and benign nodule (all P < 0.05). BV, BF, PS, MTT, PH, PHpm/PHa, and MVD among three groups of peripheral lung cancers were not significantly (all P > 0.05). In the case of adenocarcinoma, BV, BF, PS, PHpm/PHa, and MVD between poorly and well differentiation and between poorly and moderately differentiation were statistically significant (all P < 0.05). The peripheral lung cancers with VEGF positive expression showed significantly higher PH, PHpm/PHa, BF, BV, PS, and MVD value than those of the peripheral lung cancer with VEGF negative expression, and than those of benign nodule with VEGF positive expression (all P < 0.05). When investigating VEGF negative expression, it is found that PH, PHpm/PHa, and MVD of inflammatory nodule were significantly higher than those of peripheral lung cancer, PS of inflammatory nodule were significantly lower than that of peripheral lung cancer (all P < 0.05). PH, PHpm/PHa, BF, and BV of benign nodule were significantly lower than those of inflammatory nodule (all P < 0.05), rather than PS and MTT (mean transit time) (all P > 0.05). PH, PHpm/PHa, BV, and PS of benign nodule were significantly lower than those of peripheral lung cancer (all P < 0.05). In the case of VEGF positive expression, MVD was positively correlated with PH, PHpm/PHa, BF, BV, and PS of peripheral lung cancer and PS of benign nodule (all P < 0.05). CONCLUSION: Multi-slice spiral CT perfusion imaging closely correlated with tumor angiogenesis and reflected MVD measurement and VEGF expression. It provided not only a non-invasive method of quantitative assessment for blood flow patterns of peripheral pulmonary nodules but also an applicable diagnostic method for peripheral pulmonary nodules.

Peripheral lung cancer: relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and cyclin D1 expression.

The aim of this study was to investigate the relationship between 16-slice spiral CT perfusion imaging and tumor angiogenesis and cyclin D1 expression in patients with peripheral lung cancer. Fifty-eight patients with peripheral lung cancer underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was analyzed for time density curve (TDC), perfusion parametric maps, and the respective perfusion parameters. Correlation between the respective perfusion parameters and immunohistochemical findings of microvessel density measurement and cyclin D1 expression was evaluated.

[Survey of health status and healthcare service demand of perimenopausal women in Guangdong].

OBJECTIVE: To understand the health status and healthcare service demand of perimenopausal women in Guangdong Province so as to explore the mode and methods for implementing climacteric and senectitude healthcare. METHOD: Using the method of stratified and cluster sampling and according to the geographical features of Guangdong Province, we selected 4 500 perimenopausal women aged 40-65 years from 5 relatively small cities (representatives of the urban areas) and 4 counties (representatives of the rural areas) for this survey. RESULTS: The average age of natural menopause was 48.6 years in this cohort of women, and was 48.9 years in women from the urban areas and 48.3 years in those from the rural areas. The total incidence of diseases was similar in the urban and rural areas (38.5% vs 39.5%), accounting for an incidence of 39% in the total subjects. The 6 most prevalent diseases were bone and joint disease (12.5%), hypertension (9.2%), myoma of the uterus (6.8%), gastric or duodenal ulcer (5.2%), cardiac disease (2.7%) and diabetes mellitus (2.2%). In bone and joint disease, knee joint disease and lumbar vertebrae disease were the commonest (34.3% vs 32.8%), and the incidence of bone fracture was 2.5%. Perimenopausal syndrome had a prevalence rate of 68.1%, and the most distressful symptoms were sleeplessness, muscular, bone and joint pain, fidgety, dizziness, of which 86.8% were mental symptoms and 86.0% body symptoms. Women(71.2%) with perimenopausal symptoms received no medical treatment, and only 20.5% had ever sought medical care in the department of obstetrics and gynecology, often taking traditional Chinese medicines (53.9%). Only 1.4% of the symptomatic women received hormone therapy, the rate varied from 1.0% in the rural areas to 1.8% in the urban areas. CONCLUSION: Perimenopausal syndrome and its related diseases severely affect the physical and mental health of perimenopausal women, who demand extensive healthcare services.