Chronic myelogenous leukemia (CML) is a complex disease with a genetic basis. The genetic association studies (GASs) that have investigated the association between adult CML and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms have produced contradictory and inconclusive results. The aim of this meta-analysis is to provide a relatively comprehensive assessment of the association of these polymorphisms with adult CML risk. A literature search for eligible GAS published before September 15, 2013 was conducted in PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases. Pooled odds ratios (ORs) with their corresponding 95 % confidence intervals (95 % CIs) were used to evaluate the strength of the association under a fixed or random effect model according to heterogeneity test results. All analyses were performed using the Stata software, version 12.0. Twelve case-control studies were included in this meta-analysis with a total of 932 CML patients and 3,465 healthy controls. For MTHFR C677T (dbSNP: rs1801133, C>T), though the pooled ORs were not significant in the overall population, all the ORs greater than 1 suggested an increased risk of CML for carriers of the risk allele. However, stratified analysis based on genotyping method revealed a significant association in the PCR-restriction fragment length polymorphism (RFLP) subgroup, possibly as a result of heterogeneity. For MTHFR A1298C (dbSNP: rs1801131, A>C), the combined results showed that carriers of the C allele may be associated with a decreased risk of adult CML. Stratified analysis showed that the magnitude of this effect was especially significant among Asians, indicating ethnicity differences in adult CML susceptibility. This meta-analysis shows that the C allele of MTHFR A1298C may be associated with a decreased risk in adult CML, especially among Asians, while MTHFR C677T may not be associated with adult CML risk. However, the development of adult CML may be the result of gene-gene and gene-environment interactions, which should be considered in future individual GAS and subsequent meta-analyses.
Objective To investigate the injurious effects and the changes of [Ca~(2+)]_i induced by electromagnetic pulse ~EMP) on hippocampal neurons in vitro. Methods Primary hippocampal neurons in vitro were exposed to EMP~6×10~4V/m,rise time 20ns,pulse width 30μs,5 pulses in 2 minute) radiation. Then the survival rate of neurons was detected with MTT, and the apoptosis and necrosis of neurons were observed with FACS. Fluo-3-AM fluorenscent probe and laser scanning confocal microscopy were employed to detect [Ca~(2+)]_i in neurons as well. Results The survival rate of neurons decreased significantly at 0~6h after radiation(P0.05),then increased gradually after 12h and reached normal level at 24h.The rate of apoptosis increased markedly at 0~12h after EMP and the rate of necrosis increased too. A higher intracellular free calcium ion concentration was seen after EMP. Conclusion EMP caused an overloading of Ca~(2+) in hippocampal cells in vitro. Necrosis and apoptosis of neurons could be found as well.
Abstract Background: Although total hysterectomy (TH)/ radical hysterectomy (RH) + double appendectomy + staging surgery is recommended for patients with stageⅡndometrial cancer (EC), gynecologists disagree on whether to choose TH or RH/ modified radical hysterectomy (mRH) in practice. This study aims to explore whether TH or RH/mRH affect the prognosis of patients with EC. Materials and Methods: 808 stageⅡEC patients who underwent surgery were included in the retrospective analysis. The patients were grouped according to the surgical method (TH, n=434, RH/mRH, n=374) and clinical characteristics were collected. Kaplan-Meier method was used for survival analysis, and P values were calculated by log-rank test. Prognostic analysis was performed by Cox proportional hazards regression models. Results: Patients underwent RH/mRH had worse progression-free survival (PFS) (HR=2.235, 95%CI= 1.159-4.31, P=0.016), TH or RH/mRH does not affect the overall survival (OS) of patients (HR=1.511, 95%CI=0.802-2.845, P=0.201). Postoperative adjuvant therapy will improve PFS (HR=2.209, 95%CI=1.091-4.472, P=0.028). In patients received postoperative adjuvant therapy, RH/mRH is the independent risk factor of PFS (HR=2.328, 95%CI= 1.042-5.203, P=0.039). Neither PFS nor OS are affected by the type of hysterectomy in patients without adjuvant therapy. In addition, the operation time of RH/mRH is longer than that of TH. Conclusion: RH/mRH will not improve PFS and OS in patients with clinical stageⅡEC, but will increase the length of surgery. In clinical treatment, there is no need for gynecologists to implement RH/mRH for patients with stageⅡEC.
Sonic Hedgehog (Shh) signaling plays crucial roles in patterning the ventral neural tube, which is transformed into opposing gradients of repressor and activator forms of Glis. Here, we show that the fine-tuning of the shape of the Gli gradients through non-proteolytic ubiquitination-mediated nuclear exportation plays an important role in the control of local neural cell fate. Loss of RNF220, a ventral neural-specific ubiquitin E3 ligase, leads to ventral expansion of the intermediate V0 and dorsal expansion of the ventral V3 neurons, while reducing the V1, V2, and motor neurons between them. We show that RNF220 interacts with all Glis, either in their activator or repressor forms; induces their K63-linked ubiquitination; and promotes their nuclear export, likely by unmasking a nuclear export signal in the zinc finger domain. We propose that RNF220 works to refine the Gli gradients during neural patterning by limiting the effective Gli levels in the nucleus.
Background: To evaluate whether EQD2(α/β = 3Gy) at 2 cm3 of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm3 of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12–68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2(α/β = 3Gy) at 2 cm3 >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2(α/β = 3Gy) at 2 cm2 of the vagina presented only G0–G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.
Genetic variants annotated to the hedgehog interacting protein (HHIP) are robustly associated with chronic obstructive pulmonary disease (COPD). Hhip haploinsufficiency in mice leads to increased susceptibility towards the development of emphysema following exposure to chronic cigarette smoke (CS). To explore the molecular pathways which contribute to increased susceptibility, we performed metabolomic profiling using high performance liquid chromatography tandem mass spectroscopy (LC/MS-MS) on plasma, urine, and lung tissue of Hhip +/- heterozygotes and wild type (Hhip +/+) C57/BL6 mice exposed to either room-air or CS for six months. Univariate comparisons between groups were made with a combined fold change ≥2 and Student's t-test p-value < 0.05 to denote significance; associations with mean alveolar chord length (MACL), a quantitative measure of emphysema, and gene-by-environment interactions were examined using empiric Bayes-mediated linear models. Decreased urinary excretion of cotinine despite comparable plasma levels was observed in Hhip +/- heterozygotes; a strong gene-by-smoking association was also observed. Correlations between MACL and markers of oxidative stress such as urinary methionine sulfoxide were observed in Hhip +/- but not in Hhip +/+ mice. Metabolite set enrichment analyses suggest reduced antioxidant capacity and alterations in macronutrient metabolism contribute to increased susceptibility to chronic CS-induced oxidative stress in Hhip haploinsufficiency states.
Objective To investigate the influence of laparoscopic D3 lymphadenectomy combined with pelvic autonomic nerve preservation on the urinary function of male patients with rectal cancer. Methods From August 2006 to August 2007, 119 male patients with rectal cancer who had been admitted to Southwest Hospital were assigned to open surgery group (n=59) and laparoscopic group (n=60) according to the random number table. Three months after the operation, the urinary function of patients was assessed by urodynamics investigation and international prostate symptom score (IPSS). Differences in measurement data were compared with paired t test. Results There was no significant difference in IPSS between laparoscopic group (10.9±2.9) and open surgery group (11.5±3.1) (t=-1. 309, P>0.05). The maximum flow rate, voided volume, residual urine volume, detrusor contraction pressure and maximum urethral pressure were 15.2 ml/s, 150.1 ml, 6.1 ml, 43.3 cm H2O (1 cm H2O=0.098 kPa) and 77.5 cm H2O in laparoscopic group, and 15.0 ml/s, 140.9 ml, 6.4 ml, 45.6 cm H2O and 72.3 cm H2O in open surgery group, with no statistical difference between the 2 groups (t=1.22, -2.12, -1.73, -1.35, -1.64, P>0.05). Conclusions Laparosceopic D3 lymphadenectomy combined with pelvic autonomic nerve preservation is relatively safe in preserving urinary function, and its efficacy is comparable to that of open surgery.
Key words:
Rectal neoplasms; Laparoscopes; Autonomic nerve preservation; D3 lymphadenectomy; Urinary function
The growth differentiation factor-15 (GDF-15) may be involved in atherosclerosis. However, the role of GDF-15 in atherosclerosis remains unclear. The main goal of this study was to verify the role and mechanism of GDF-15 in atherogenesis. We first compared the serum GDF-15 level between patients with coronary atherosclerosis and healthy people. And then one ApoE−/− mouse model of atherosclerosis was used to explore the effects of GDF-15 on oxidized low-density lipoprotein (oxLDL) accumulation, atherosclerosis-related gene expression, and lipid accumulation-related protein expression in mouse macrophages. As a result, the level of serum GDF-15 in patients with coronary atherosclerosis was significantly higher than that in healthy people. In the mouse model, GDF-15 expression was elevated in the core of plaque, and it was secreted mainly by the macrophages. In addition, GDF-15 decreased oxLDL-induced lipid accumulation and inflammation activation in macrophages. GDF-15 decreased the mRNA expressions of CD36, LOX1, and TLR4 that are associated with lipoprotein accumulation in macrophages. Further study showed that GDF-15 might suppress oxLDL-induced lipoprotein accumulation via inhibiting CD36 and LOX1 and decrease inflammation in macrophages by inhibiting TLR4. Thus, GDF-15 may suppress atherosclerosis and plaque formation by inhibiting lipoprotein accumulation and inflammation activation.
<div>Abstract<p>The aim of this work was to evaluate the risk factors for recurrence in young patients with atypical endometrial hyperplasia and early-stage endometrioid adenocarcinoma after fertility-sparing treatments (FST). A retrospective case–control study was designed. Patients with atypical endometrial hyperplasia and early-stage endometrioid adenocarcinoma who received FSTs from January 2010 to December 2017 were reviewed. All patients who met the inclusion criteria were divided into a recurrence group and a control group. Risk factors for recurrence- and disease-free survival were evaluated by logistic regression analysis and Cox regression analysis. A total of 127 patients were included, 53 patients in the recurrence group and 74 patients in the control group. No deaths occurred during the follow-up time. The rate of successful pregnancy was 62.5% in the control group and 20.5% in the recurrence group after complete remission (CR) of the primary disease. In a multivariate regression model, after adjusting for other factors, menstruation cycle, progestin type, and regular maintenance treatments after CR were the main risk factors for disease recurrence. Gonadotropin-releasing hormone agonist was mainly used to treat obese patients and was associated with longer progression-free survival (PFS) time compared with that in patients who received high-dose oral progestin such as megestrol acetate [risk ratio (RR), 2.158; 95% confidence interval (CI), 0.948–4.913]. Regular oral progestin also significantly prolonged the PFS time (RR, 4.726; 95% CI, 2.672–8.359). The progestin type used in treatment and regular maintenance treatment of young patients with atypical endometrial hyperplasia and early-stage endometrioid adenocarcinoma after CR might be correlated with disease recurrence.</p></div>
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