The SNP rs961253 in 20p12.3 Is Associated with Colorectal Cancer Risk: A Case-Control Study and a Meta-Analysis of the Published Literature

Background: Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer death worldwide. A single nucleotide polymorphism (SNP), rs961253 located in 20p12, was firstly described to be associated with the increased risk of CRC in a genome-wide association study; however, more recent replication studies yielded controversial results. Methodology/Principal Findings: A hospital-based case-control study in a Chinese population was firstly performed, and then a meta-analysis combining the current and previously published studies were conducted to explore the real effect of rs961253 in CRC susceptibility. In the Chinese population including 641 cases and 1037 controls, per-A-allele conferred an OR of 1.60 (95 % CI = 1.26–2.02) under additive model. In the meta-analysis including 29859 cases and 29696 controls, per-Aallele have an OR of 1.13 (95 % CI = 1.09–1.18) under a random-effects model due to heterogeneity (P = 0.019). Nevertheless, the heterogeneity can be totally explained by ethnicity, with the tau 2 reduced to 0 after including ethnicity in metaregression model. In stratified analysis by ethnicity, per-A-allele had ORs of 1.34 (95 % CI = 1.20–1.50) and 1.11 (95% CI = 1.08–1.14) for Asian and European, respectively, without heterogeneity. Modest influence of each study was observed on overall estimate in sensitive analysis, and evident tendency to significant association was seen in cumulative analysis over time, together indicating the robust stability of the current results

KIN10 promotes stomatal development through stabilization of the SPEECHLESS transcription factor

Stomata are epidermal structures that modulate gas exchanges between plants and the atmosphere. The formation of stomata is regulated by multiple developmental and environmental signals, but how these signals are coordinated to control this process remains unclear. Here, we showed that the conserved energy sensor kinase SnRK1 promotes stomatal development under short-day photoperiod or in liquid culture conditions. Mutation of KIN10, the catalytic α-subunit of SnRK1, results in the decreased stomatal index; while overexpression of KIN10 significantly induces stomatal development. KIN10 displays the cell-type-specific subcellular location pattern. The nuclear-localized KIN10 proteins are highly enriched in the stomatal lineage cells to phosphorylate and stabilize SPEECHLESS, a master regulator of stomatal formation, thereby promoting stomatal development. Our work identifies a module links connecting the energy signaling and stomatal development and reveals that multiple regulatory mechanisms are in place for SnRK1 to modulate stomatal development in response to changing environments

A prospective phase II study of L-asparaginase- CHOP plus radiation in newly diagnosed extranodal NK/T-cell lymphoma, nasal type

Purpose: To explore the efficacy and safety of L-asparaginase in newly-diagnosed extranodal nature killer (NK)/T -cell lymphoma (ENKTL), we conducted a prospective phase II study of L-asparaginase, cyclophosphamide, vincristine, doxorubicin and dexamethasone (CHOP-L) regimen in combination with radiotherapy. Patients and methods: Patients with newly diagnosed ENKTL and an ECOG performance status of 0 to 2 were eligible for enrollment. Treatment included 6-8 cycles of CHOP-L (cyclophosphamide, 750 mg/m(2) day 1; vincristine, 1.4 mg/m(2) day 1 (maximal dose 2 mg), doxorubicin 50 mg/m(2) day 1; dexamethasone 10 mg days 1-8; L-asparaginase 6000 u/m(2) days 2-8). Radiotherapy was scheduled after 4-6 cycles of CHOP-L regimen, depending on stage and primary anatomic site. The primary endpoint was complete response (CR) rate. Results: A total of 38 eligible patients were enrolled. The median age was 40.5 years (range, 15 to 71 years). Their clinical characteristics were male to female ratio, 24: 14; Ann Arbor stage I, 20; II, 11; III, 3; IV, 4. CR and overall response rates were 81.6% (95% CI, 69.3% to 93.9%) and 84.2%, respectively. With a median follow-up of 25 months, the 2-year overall survival, progression-free survival and disease-free survival rates were 80.1% (95% CI, 73.3% to 86.9%), 81% (95% CI, 74.5% to 87.5%) and 93.6% (95% CI, 89.3% to 97.9%), respectively. The major adverse events were myelosuppression, liver dysfunction, and digestive tract toxicities. Grade 3 to 4 leukopenia and neutropenia were 76.3% and 84.2%, respectively. No treatment-related death was observed. Conclusion: CHOP-L chemotherapy in combination with radiotherapy is a safe and highly effective treatment for newly diagnosed ENKTL.OncologyHematologySCI(E)9ARTICLEnull

Degradation of Internalized αvβ5 Integrin Is Controlled by uPAR Bound uPA: Effect on β1 Integrin Activity and α-SMA Stress Fiber Assembly

Myofibroblasts (Mfs) that persist in a healing wound promote extracellular matrix (ECM) accumulation and excessive tissue contraction. Increased levels of integrin αvβ5 promote the Mf phenotype and other fibrotic markers. Previously we reported that maintaining uPA (urokinase plasminogen activator) bound to its cell-surface receptor, uPAR prevented TGFβ-induced Mf differentiation. We now demonstrate that uPA/uPAR controls integrin β5 protein levels and in turn, the Mf phenotype. When cell-surface uPA was increased, integrin β5 levels were reduced (61%). In contrast, when uPA/uPAR was silenced, integrin β5 total and cell-surface levels were increased (2–4 fold). Integrin β5 accumulation resulted from a significant decrease in β5 ubiquitination leading to a decrease in the degradation rate of internalized β5. uPA-silencing also induced α-SMA stress fiber organization in cells that were seeded on collagen, increased cell area (1.7 fold), and increased integrin β1 binding to the collagen matrix, with reduced activation of β1. Elevated cell-surface integrin β5 was necessary for these changes after uPA-silencing since blocking αvβ5 function reversed these effects. Our data support a novel mechanism by which downregulation of uPA/uPAR results in increased integrin αvβ5 cell-surface protein levels that regulate the activity of β1 integrins, promoting characteristics of the persistent Mf

Study of Problems and Countermeasures on Ethical Review of Research in China

With the rapid development of biotechnology, ethical issues of scientific activities are more and more serious, while the ethical review as the main means of suppressing research ethics problems, it also has many problems in the process of practice. This article from the ethics review committee’s organizational structure, operation specifications, capacity, the scope of review and external regulation summarize the main problems of China's research ethics review, and on this basis, we put forward the corresponding countermeasures, hoping to provide certain reference of our country's research ethics review practice, and to better safeguard the healthy development of our country's scientific research

Atypical genital herpes in a child: a case report

A case of atypical genital herpes in a child is reported. A 2-year-old girl presented with blisters sized from rice to green bean and some erosion on the vulva, bilateral medial femur and perianal area for 3 days. Some blisters appeared umbilicated with thick wall, clear fluid and erosion, but without lymphadenopathy. Herpes simplex virus Ⅱ-DNA and serum HSV-Ⅱ IgM were positive. A diagnosis of genital herpes was made. Lesions were improved after one week of antiviral therapy. No recurrence was observed during 1-year follow-up

Correlation between women's sub-health and reproductive diseases with pregnancies and labors

AbstractObjectiveTo investigate whether female sub-health conditions and reproductive diseases are associated with pregnancies and labors.MethodsA cross-sectional survey was performed by using a structured questionnaire. A total of 1343 women aged 35 years or younger in six urban areas of Chengdu were included in the study. According to the Screening Criteria of sub-health conditions, these women were categorized into three groups: postpartum healthy group, sub-healthy group, and reproductive disease group. Data were double-entered using EpiData and then analyzed by SPSS.ResultsPregnancy and labor were correlated with postpartum sub-health conditions. The number of pregnancies was negatively correlated with women's postnatal health but was positively correlated with the incidence of postpartum reproductive diseases.ConclusionsThe number of pregnancies and labors is probably an important factor leading to sub-health conditions and the occurrence of reproductive diseases in women. Avoiding or reducing unwanted pregnancies and labors, enhancing the awareness of health among childbearing-age women are effective measures for preventing sub-health conditions