To evaluate the application of immediate breast reconstruction (IBR) with silicon prosthetic implantation following bilateral nipple-preserving subcutaneous mammary gland excision in the treatment of young patients with early breast cancer.
We retrospectively analyzed the clinical data of 21 patients with breast cancer who were performed on IBR following bilateral nipple-preserving subcutaneous mammary gland excision in our hospital from January 2006 to March 2011.
The operations were successful in all the 21 patients. Also, the treatment provided a good cosmetic effect. No local recurrence or distant metastasis was found in these 21 patients during the 6-66-month follow-up.
For the young patients with early breast cancer, mammary gland excision on the affected side along with prophylactic excision of the contralateral side, namely IBR following bilateral nipple-preserving subcutaneous mammary gland excision, provides good clinical effectiveness and cosmetological effects.
Breast cancer; prophylactic mastectomy; immediate breast reconstruction
Medium spiny neurons (MSNs) within the nucleus accumbens shell (NAc) function to gate and prioritize emotional/motivational arousals for behavioral output. The neuronal output NAc MSNs is mainly determined by the integration of membrane excitability and excitatory/inhibitory synaptic inputs. Whereas cocaine-induced alterations at excitatory synapses and membrane excitability have been extensively examined, the overall functional output of NAc MSNs following cocaine exposure still poorly defined because little is known about whether inhibitory synaptic input to these neurons is affected by cocaine. Here, our results demonstrate multidimensional alterations at inhibitory synapses in NAc neurons following cocaine self-administration in rats. Specifically, the amplitude of miniature (m) inhibitory postsynaptic currents (IPSCs) was decreased after 21-d withdrawal from 5-d cocaine self-administration. Upon re-exposure to cocaine after 21-day withdrawal, whereas the amplitude of mIPSCs remained down-regulated, the frequency became significantly higher. Furthermore, the reversal potential of IPSCs, which was not significantly altered during withdrawal, became more hyperpolarized upon cocaine re-exposure. Moreover, the relative weight of excitatory and inhibitory inputs to NAc MSNs was significantly decreased after 1-d cocaine withdrawal, increased after 21-d withdrawal, and returned to the basal level upon cocaine re-exposure after 21-d withdrawal. These results, taken together with previous results showing cocaine-induced adaptations at excitatory synapses and intrinsic membrane excitability of NAc MSNs, may provide a relatively thorough picture of the functional state of NAc MSNs following cocaine exposure.
IPSC; EPSC; GABA; accumbens; cocaine; reversal potential
Ras association domain family protein 1A (RASSF1A) is a tumor suppressor gene silenced in cancer. Here we report that RASSF1A is a novel regulator of intestinal inflammation as Rassf1a+/−, Rassf1a−/− and an intestinal epithelial cell specific knockout mouse (Rassf1a IEC-KO) rapidly became sick following dextran sulphate sodium (DSS) administration, a chemical inducer of colitis. Rassf1a knockout mice displayed clinical symptoms of inflammatory bowel disease including: increased intestinal permeability, enhanced cytokine/chemokine production, elevated nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB) activity, elevated colonic cell death and epithelial cell injury. Furthermore, epithelial restitution/repair was inhibited in DSS-treated Rassf1a−/− mice with reduction of several makers of proliferation including Yes associated protein (YAP)-driven proliferation. Surprisingly, tyrosine phosphorylation of YAP was detected which coincided with increased nuclear p73 association, Bax-driven epithelial cell death and p53 accumulation resulting in enhanced apoptosis and poor survival of DSS-treated Rassf1a knockout mice. We can inhibit these events and promote the survival of DSS-treated Rassf1a knockout mice with intraperitoneal injection of the c-Abl and c-Abl related protein tyrosine kinase inhibitor, imatinib/gleevec. However, p53 accumulation was not inhibited by imatinib/gleevec in the Rassf1a−/− background which revealed the importance of p53-dependent cell death during intestinal inflammation. These observations suggest that tyrosine phosphorylation of YAP (to drive p73 association and up-regulation of pro-apoptotic genes such as Bax) and accumulation of p53 are consequences of inflammation-induced injury in DSS-treated Rassf1a−/− mice. Mechanistically, we can detect robust associations of RASSF1A with membrane proximal Toll-like receptor (TLR) components to suggest that RASSF1A may function to interfere and restrict TLR-driven activation of NFκB. Failure to restrict NFκB resulted in the inflammation-induced DNA damage driven tyrosine phosphorylation of YAP, subsequent p53 accumulation and loss of intestinal epithelial homeostasis.
Ixodes scapularis transmits the agent of human granulocytic anaplasmosis, among other pathogens. The mechanisms used by the tick to control Anaplasma phagocytophilum are not known. We demonstrate that the I. scapularis Janus kinase (JAK)–signaling transducer activator of transcription (STAT) pathway plays a critical role in A. phagocytophilum infection of ticks. The A. phagocytophilum burden increases in salivary glands and hemolymph when the JAK-STAT pathway is suppressed by RNA interference. The JAK-STAT pathway exerts its anti-Anaplasma activity presumably through STAT-regulated effectors. A salivary gland gene family encoding 5.3-kDa antimicrobial peptides is highly induced upon A. phagocytophilum infection of tick salivary glands. Gene expression and electrophoretic mobility shift assays showed that the 5.3-kDa antimicrobial peptide–encoding genes are regulated by tick STAT. Silencing of these genes increased A. phagocytophilum infection of tick salivary glands and transmission to mammalian host. These data suggest that the JAK-STAT signaling pathway plays a key role in controlling A. phagocytophilum infection in ticks by regulating the expression of antimicrobial peptides.
Physical stability during storage and against processing such as dehyration/rehydration are the cornerstone in designing delivery vehicles. In this work, mono-, di- and tri-saccharides were enzymatically conjugated to phosphatidyl group through a facile approach namely phospholipase D (PLD) mediated transphosphatidylation in a biphasic reaction system. The purified products were structurally identified and the connectivities of carbohydrate to phosphatidyl moiety precisely mapped by 1H, 31P, 13C NMR pulse sequences and LC-ESI-FTMS. The synthetic phosphatidyl saccharides were employed as the sole biomimetic component for preparation of nanoliposomes. It was found that the critical micelle concentration (CMC) of phosphatidyl saccharides increases as more bulky sugar moiety (mono- to tri-) is introduced. Phosphatidyl di-saccharide had the largest membrane curvature. In comparison to the zwitterionic phosphatidylcholine liposome, all phosphatidyl saccharides liposomes are anionic and demonstrated significantly enhanced stability during storage. According to the confocal laser scan microscopy (CLSM) and atom force microscopy (AFM) analyses, the nanoliposomes formed by the synthetic phosphatidyl saccharides also show excellent stability against dehydration/rehydration process in which most of the liposomal structures remained intact. The abundance hydroxyl groups in the saccharide moieties might provide sufficient H-bondings for stabilization. This work demonstrated the synthesized phosphatidyl saccharides are capable of functioning as enzymatically liable materials which can form stable nanoliposomes without addition of stabilizing excipients.
Horizontal connections in the primary visual cortex have been hypothesized to play a number of computational roles: association field for contour completion, surface interpolation, surround suppression, and saliency computation. Here, we argue that horizontal connections might also serve a critical role of computing the appropriate codes for image representation. That the early visual cortex or V1 explicitly represents the image we perceive has been a common assumption on computational theories of efficient coding (Olshausen and Field 1996), yet such a framework for understanding the circuitry in V1 has not been seriously entertained in the neurophysiological community. In fact, a number of recent fMRI and neurophysiological studies cast doubt on the neural validity of such an isomorphic representation (Cornelissen et al. 2006, von der Heydt et al. 2003). In this study, we investigated, neurophysiologically, how V1 neurons respond to uniform color surfaces and show that spiking activities of neurons can be decomposed into three components: a bottom-up feedforward input, an articulation of color tuning and a contextual modulation signal that is inversely proportional to the distance away from the bounding contrast border. We demonstrate through computational simulations that the behaviors of a model for image representation are consistent with many aspects of our neural observations. We conclude that the hypothesis of isomorphic representation of images in V1 remains viable and this hypothesis suggests an additional new interpretation of the functional roles of horizontal connections in the primary visual cortex.
Color tuning; multiplicative gain; feedback; boundary; surface; figure-ground; contextual modulation; response latency; color filling-in
Estrogen-related genes and the fat mass and obesity-associated (FTO) gene play a critical role in estrogen metabolism, and those polymorphisms are associated with a poor prognosis in breast cancer. However, little is known about the association between these polymorphisms and the efficacy of anastrozole. The aim was to investigate the impact of the genetic polymorphisms, CYP19A1, 17-β-HSD-1 and FTO, on the response to anastrozole in metastatic breast carcinoma (MBC) and to evaluate the impact of those polymorphisms on various clinicopathologic features. Two-hundred seventy-two women with hormone receptor-positive MBC treated with anastrozole were identified retrospectively. DNA was extracted from peripheral blood and genotyped for five variants in three candidate genes. Time to progression was improved in patients carrying the variant alleles of rs4646 when compared to patients with the wild-type allele (16.40 months versus 13.52 months; p = 0.049). The rs4646 variant alleles were significantly associated with longer overall survival (37.3 months versus 31.6 months; p = 0.007). This relationship was not observed with the rs10046, rs2830, rs9926298 and rs9939609 polymorphisms. The findings of this study indicate that rs4646 polymorphism in the CYP19A1 gene may serve as a prognostic maker of the response to anastrozole in patients with MBC who are treated with anastrozole.
metastatic breast carcinoma; aromatase gene; anastrozole; prognosis; polymorphism
Background and Objective
Conflicting results were found between the I-gel™ and the LMA-Supreme™ during anesthesia, so we conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effectiveness and safety of the I-gel™ vs. the LMA-Supreme™during anesthesia.
A comprehensive search was conducted using Pubmed, EMbase, ISI Web of Knowledge, the Cochrane Library, China Journal Full-text Database, Chinese Biomedical Database, Chinese Scientific Journals Full-text Database, CMA Digital Periodicals, and Google scholar to find RCTs that compare the LMA-S™ with the i-gel™during anesthesia. Two reviewers independently selected trials, extracted data, and assessed the methodological qualities and evidence levels. Data were analyzed by RevMan 5.0 and comprehensive meta-analysis software.
Ten RCTs were included. There were no significant differences in oropharyngeal leak pressures (mean difference [MD] 0.72, 95% confidence interval [CI] –1.10 2.53), device placement time (MD –1.3, 95%CI –4.07 1.44), first attempt insertion success (risk ratio [RR] 1.01, 95% CI 0.9 1.14), grade 3 and 4 fiberoptic view (RR 0.89, 95%CI 0.65 1.21), and blood on removal (RR 0.62, 95%CI 0.32 1.22) between the i-gel™ and the LMA-Supreme™, respectively. However, the LMA-Supreme™was associated with easier gastric tube insertion (RR 1.17, 95%CI 1.07 1.29), and more sore throat (RR 2.56, 95%CI 1.60 4.12) than the i-gel™ group.
The LMA-Supreme™ and i-gel™ were similarly successful and rapidly inserted. However, the LMA-Supreme™ was shown to be easier for gastric tube insertion and associated with more sore throat compared with the i-gel™.
B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8+ T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients’ survival and metastasis.
Various statistical methods have been used for data analysis in alcohol treatment studies. Trajectory analyses can better capture differences in treatment effects and may provide insight on the optimal duration of future clinical trials and grace periods. This improves on the limitation of commonly used parametric (e.g., linear) methods that cannot capture non-linear temporal trends in the data.
We propose an exploratory approach, using more flexible smoothing mixed effects models, more accurately to characterize the temporal patterns of the drinking data. We estimated the trajectories of the treatment arms for data sets from two sources: a multi-site topiramate study, and the Combined Pharmacotherapies (acamprosate and naltrexone) and Behavioral Interventions study.
Our methods illustrate that drinking outcomes of both the topiramate and placebo arms declined over the entire course of the trial but with a greater rate of decline for the topiramate arm. By the point-wise confidence intervals, the heavy drinking probabilities for the topiramate arm might differ from those of the placebo arm as early as week 2. Furthermore, the heavy drinking probabilities of both arms seemed to stabilize at the end of the study. Overall, naltrexone was better than placebo in reducing drinking over time, yet was not different from placebo for subjects receiving the combination of a brief medical management and an intensive combined behavioral intervention.
The estimated trajectory plots clearly showed non-linear temporal trends of the treatment with different medications on drinking outcomes and offered more detailed interpretation of the results. This trajectory analysis approach is proposed as a valid exploratory method for evaluating efficacy in pharmacotherapy trials in alcoholism.
Alcohol research; clinical trial; grace periods; splines; mixed model
Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family, which regulates actin dynamics. Increasing evidence suggests that mitochondrial translocation of cofilin appears necessary for the regulation of apoptosis.
We report that allyl isothiocyanate (AITC) potently induces mitochondria injury and apoptosis. These events were accompanied by a loss of polymerized filamentous actin (F-actin) and increase in unpolymerized globular actin (G-actin). AITC also induces dephosphorylation of cofilin through activation of PP1 and PP2A. Only dephosphorylated cofilin binds to G-actin and translocates to mitochondria during AITC-mediated apoptosis. Mechanistic study revealed that interruption of ROCK1/PTEN/PI3K signaling pathway plays a critical role in AITC-mediated dephosphorylation and mitochondrial translocation of cofilin and apoptosis. Our in vivo study also showed that AITC-mediated inhibition of tumor growth of mouse leukemia xenograft model is in association with dephosphorylation of cofilin.
These findings support a model in which induction of apoptosis by AITC stems primarily from activation of ROCK1 and PTEN, and inactivation of PI3K, leading in turn to activation of PP1 and PP2A, resulting in dephosphorylation of cofilin, which binds to G-actin and translocates to mitochondria, culminating in the dysfunction of mitochondria, release of cytochrome c and apoptosis.
Allyl isothiocyanate; Apoptosis; Cofilin; ROCK1; PI3K; Leukemia
A number of studies evaluated the association of intracellular adhesion molecule-1 (ICAM-1) K469E (rs5498, A/G) gene polymorphism with diabetic microvascular complications (DMI) including diabetic nephropathy (DN) and diabetic retinopathy (DR) in different populations. However, the results of individual studies remain conflicting.
A comprehensive search was conducted to identify all eligible studies of the above-mentioned associations. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were assessed using the fixed or random effect model.
Seven studies involving 3411 subjects were included. Overall, the meta-analysis showed a significant association of the A allele with increased risk of DMI susceptibility in a recessive model (OR = 1.37, 95% CI 1.04–1.80, P = 0.02). In the subgroup analysis stratified by ethnicity, significant association was found in Asians but not in Caucasians (OR = 1.78, 95% CI 1.13–2.81, P = 0.01; OR = 1.10, 95% CI 0.79–1.54, P = 0.58, respectively). Moreover, it showed a significant association between the A allele and risk of DN in a recessive model (OR = 1.25, 95% CI 1.02–1.55, P = 0.04).
This meta-analysis suggested that the K469E polymorphism in ICAM-1 gene might affect individual susceptibility to DMI and showed a discrepancy in different ethnicities. Further investigations are needed to validate the association.
Due to the paucity of direct evidence, we aimed to evaluate whether the association between postload plasma glucose levels (ppGlucose) and long-term risk of mortality from coronary heart disease was independent of or attributable to genes and common environment.
Methods and Findings
From the prospective National Heart, Lung, and Blood Institute (NHLBI) Twin Study, we included 903 middle-aged male twins, who were nondiabetic, free of coronary heart disease at baseline (1969–1973), and followed for up to 38 years for coronary heart, cardiovascular, and all-cause mortality. Frailty survival models were used to estimate hazard ratio (HR) for various associations: overall (equivalent to singleton population association), within-pair (controlling for genes and environment common to co-twins), and between-pair association (reflecting influences of common factors). Overall associations were statistically significant for coronary heart and cardiovascular but not all-cause deaths after controlling for known risk factors. The associations were not statistically significant in within-pair analyses. The within-pair association was not statistically different by zygosity for specific and all-cause death risk. After the full adjustment for known risk factors, HR (95% confidence interval) for within-pair association was 1.07 (0.90, 1.28), 1.06 (0.94, 1.19), and 0.99 (0.94, 1.05) for coronary heart, cardiovascular, and all-cause mortality, respectively. The fully adjusted between-pair associations were statistically significant for specific and all-cause death risk: a 50 mg/dL increase in the mean value of ppGlucose for a twin pair was associated with a raised death risk [HR (95% confidence interval) 1.15 (1.02, 1.30), 1.10 (1.02, 1.20), and 1.05 (1.01, 1.09) for coronary heart, cardiovascular, and all-cause mortality, respectively]. Between-pair association was significant in dizygotic but not in monozygotic twins.
The positive association between ppGlucose and long-term coronary heart mortality risk is largely explained by factors shared between co-twins, including familial factors; however, within-pair effects cannot be absolutely excluded.
Women with breast cancer treated with aromatase inhibitors (AIs) may experience musculoskeletal symptoms that lead to discontinuation of effective therapy. The purpose of the current study is to evaluate the clinical and genetic predictors for AIs-related musculoskeletal adverse events(MS-AEs).
Methodology and Principal Findings
We recruited 436 postmenopausal Chinese Han women receiving adjuvant AIs therapy for early-stage hormone-sensitive breast cancer. Patients completed a self-administered questionnaire assessing the presence of musculoskeletal symptoms that started or worsened after initiating AIs. 27 single nucleotide polymorphisms (SNP) of ESR1, ESR2 and PGR were analyzed by Sequenom MassARRAY assays and /or PCR-based TaqMan assays.Of the 436 enrolled women, 206 cases experienced musculoskeletal symptoms.Patients who received taxane chemotherapy were more than two times more likely than other patients to have AIs-related MS-AEs. Genetic assay had showed that only two ESR1 SNPs, rs2234693 and rs9340799 were associated with AIs-related MS-AEs.TT genotype and the T allele in rs2234693 was statistically significantly lower in AIs-Related MS-AEs group than controls (P = 0.001; P = 9.49E-7). The frequency of AA genotype and the A allele in rs9340799 was higher (P = 2.20E-5; P = 3.09E-4).
Conclusions and Significance
Our results suggested that prior taxane-based chemotherapy was the clinical predictor, while rs2234693 and rs9340799 were the genetic predictors for AIs-related MS-AEs.
Clinically, recurrence and life-threatening complications are challenging problems for chronic suppurative osteomyelitis of the jaw (CSOJ), but there is no quantitative analysis or report about the causes of or risk factors for the two problems to date. Doctors identify the causes or risk factors only through clinical experience. We performed a retrospective study of 322 patients with CSOJ to quantificationally analysed the risk factors for the abovementioned two problems by logistic regression analysis.
A retrospective study of 322 patients hospitalized with CSOJ was performed. The socio-demographic and clinical characteristics were recorded. The risk factors for the above two problems were analyzed by logistic regression analysis. Frequency and percentage were used to indicate descriptive research factors. A univariate logistic regression analysis was performed to calculate the odds ratio (OR) and to identify independent risk factors. The independent risk factors were further identified by multivariate logistic regression analysis.
An age from 6–12 years or > 65 years, pre-admission antibiotic administration, a lesion at the mandibular ramus, concurrent maxillofacial space infection (MSI), and conservation of pathogenic teeth were found to be risk factors for recurrence. An age > 65 years, admission temperature > 39 degree Celsius, admission white blood cell (WBC) count >15×109/L, pre-admission antibiotic administration, concurrent MSI, pre-existing diabetes, and respiratory difficulty were found to be risk factors for life-threatening complications.
The results indicate that doctors should remain mindful of the risk factors listed above, and the management of CSOJ should be increasingly aggressive when the above risk factors are present, especially when the lesion is located at the mandibular ramus. In addition, pathogenic teeth must be extracted, and antibiotics should be administered properly.
Chronic suppurative osteomyelitis of the jaw; Recurrence; Life-threatening complications; Risk factors; Logistic regression analysis
The purpose of this study was to review the results of external fixation combined with vacuum sealing drainage (VSD) to treat patients who sustained tibial and fibular fractures in the Wenchuan earthquake.
We retrospectively analysed 179 cases (of which 85 were classified as Gustilo grade III) of open comminuted fracture of the tibia and fibula caused by the Wenchuan earthquake. The patients were followed up for an average of 15 months; detailed records were kept on their function and recovery.
After caring for the life-threatening injuries; fractures were treated by external fixation, with VSD used on the surface or in the cavity of the wound after debridement. Antibiotics were administered on the basis of drug sensitivity test results. After the infection had been controlled and healthy granulation tissue had developed, the patients underwent secondary suture, free skin grafting, or skin flap transfer.
Good results can be achieved when external fixation combined with vacuum sealing drainage were used to treat open comminuted fractures of tibia and fibula in the Wenchuan earthquake.
The aim of this study was to compare the results of a new technique for low, multidirectional locked nailing with closed reduction and minimally invasive plating in the treatment of distal tibial metadiaphyseal fractures.
Forty-six matched patients were divided according to age, gender, Injury Severity Score, and fracture pattern into group A (expert tibial nailing) and group B (minimally invasive plating). Then, the patients were followed up, and the clinical and radiographic results were retrospectively analysed.
The mean followed-up was 24.7 ± 2.7 months in group A and 25.8 ± 2.8 months in group B. No patient had nonunion, shortening, hardware breakdown, or deep-seated infection. Patients in group A had a significantly shorter mean operating time, hospital stay, full weight-bearing time and union time (76 ± 16.6 vs. 90 ± 20.3 minutes, p = 0.000; 5.8 ± 2.1 vs. 8.9 ± 3.1 days, p = 0.000; 9.0 ± 1.4 vs. 11.1 ± 1.7 weeks, p = 0.000; and 21.3 ± 3.5 vs. 23.1 ± 3.6 weeks, p = 0.047, respectively). Three patients in group A and one patient in group B presented with malalignment (p = 0.608). The mean Olerud-Molander Ankle score was 89.0 ± 7.1 in group A and 87.6 ± 8.4 in group B (p = 0.478).
Distal tibia metadiaphyseal fractures may be treated successfully with low, multidirectional locked nails or plates. However, low, multidirectional locked nailing may represent a superior surgical option, since it offers advantages in terms of mean operating time, hospital stay, full weight-bearing time and union time.
The measurement and control strategy of a piezo-based platform by using strain gauge sensors (SGS) and a robust composite controller is investigated in this paper. First, the experimental setup is constructed by using a piezo-based platform, SGS sensors, an AD5435 platform and two voltage amplifiers. Then, the measurement strategy to measure the tip/tilt angles accurately in the order of sub-μrad is presented. A comprehensive composite control strategy design to enhance the tracking accuracy with a novel driving principle is also proposed. Finally, an experiment is presented to validate the measurement and control strategy. The experimental results demonstrate that the proposed measurement and control strategy provides accurate angle motion with a root mean square (RMS) error of 0.21 μrad, which is approximately equal to the noise level.
piezo-based platform; ultra-precision angle motion; robust composite control
The evidence that the variants GCK rs1799884, GCKR rs780094, MTNR1B rs10830963 and G6PC2 rs560887, which are related to fasting plasma glucose levels, increase the risk of type 2 diabetes mellitus (T2DM) is contradictory. We therefore performed a meta-analysis to derive a more precise estimation of the association between these polymorphisms and T2DM.
All the publications examining the associations of these variants with risk of T2DM were retrieved from the MEDLINE and EMBASE databases. Using the data from the retrieved articles, we computed summary estimates of the associations of the four variants with T2DM risk. We also examined the studies for heterogeneity, as well as for bias of the publications.
A total of 113,025 T2DM patients and 199,997 controls from 38 articles were included in the meta-analysis. Overall, the pooled results indicated that GCK (rs1799884), GCKR (rs780094) and MTNR1B (rs10830963) were significantly associated with T2DM susceptibility (OR, 1.04; 95%CI, 1.01–1.08; OR, 1.08; 95%CI, 1.05–1.12 and OR, 1.05; 95%CI, 1.02–1.08, respectively). After stratification by ethnicity, significant associations for the GCK, MTNR1B and G6PC2 variants were detected only in Caucasians (OR, 1.09; 95%CI, 1.02–1.16; OR, 1.10; 95%CI, 1.08–1.13 and OR, 0.97; 95%CI, 0.95–0.99, respectively), but not in Asians (OR, 1.02, 95% CI 0.98–1.05; OR, 1.01; 95%CI, 0.98–1.04 and OR, 1.12; 95%CI, 0.91–1.32, respectively).
Our meta-analyses demonstrated that GCKR rs780094 variant confers high cross-ethnicity risk for the development of T2DM, while significant associations between GCK, MTNR1B and G6PC2 variants and T2DM risk are limited to Caucasians.
To report the results of combined vitrectomy, lensectomy and silicone oil (SO) tamponade in treating primary rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD).
A retrospective, consecutive and case series study of 21 subjects with concurrent RRD associated with CD was conducted. All subjects underwent a standard three-port 20G pars plana vitrectomy (PPV) with lensectomy and silicone oil tamponade. Mean follow-up time was 8 months (rang from 4 to 19 months). The primary and final anatomic success rate, visual acuity and final intraocular pressure(IOP) were recorded and analyzed.
Of 21 subjects, 8 were women and 13 were men. Age at presentation ranged from 22 to 75 years (mean 57.4 years). The presenting vision ranged from light perception to 0.15. The initial IOP ranged from 3mmHg to 12mmHg (mean 6.2mmHg). All eyes were phakic except one pseudophakic. No intraocular lens was implanted during the primary surgical intervention. Fifteen of 21 (71.4%) eyes had retina reattached after one operation. Six eyes had recurrent inferior retinal detachment due to proliferation. Five of them were successfully reattached after one or more additional operations. Mean IOP at final follow-up was 15.2mmHg (range from 8mmHg to 20mmHg). One case declined for further operation. The final reattachment rate was 95.2%. Visual acuity improved in 19 (90.5%) eyes, was unchanged in 1 (4.8%) eye and decreased in 1 (4.8%) eye.
Combination of vitrectomy, lensectomy and silicone tamponade is an effective method in treating RRD associated with CD, reducing the incidence of postoperative hypotony.
choroidal detachment; lensectomy; rhegamatogenous retinal detachment; vitrectomy; silicone oil
Obstructive sleep apnea (OSA) in children is associated with obesity, insulin resistance, and elevated baseline inflammation as measured by high-sensitivity C-reactive protein (hsCRP). Our goal was to evaluate whether inflammation increases overnight among children suspected of having OSA and to determine whether worsened inflammation is associated with the degree of OSA severity, obesity, and/or insulin resistance.
Twenty-three children with clinical suspicion of OSA underwent a sleep study. Levels of hsCRP were tested the evening before and morning after the sleep study. Fasting insulin and glucose levels were measured from which the homeostasis model of insulin resistance (HOMA-IR) was calculated. Linear correlations were performed to evaluate relationships between hsCRP levels at baseline and change overnight (ΔhsCRP) vs. HOMA-IR, body mass index (BMI) z-score, and sleep study parameters related to O2 saturation and the apnea-hypopnea index (AHI).
Among children with OSA and the entire cohort, hsCRP values were correlated with HOMA-IR and BMI z-scores. HOMA-IR but not BMI z-score correlated with ΔhsCRP overnight in the entire cohort. Sleep study parameters, including AHI mean O2 saturation overnight, REM O2 nadir, and non-REM O2 nadir were not correlated with hsCRP or ΔhsCRP overnight.
Among children being evaluated for OSA, degree of insulin resistance may be an important determinant of increased systemic inflammation overnight. Sleep study markers did not correlate with ΔhsCRP, leaving uncertain the role of OSA in increasing inflammation overnight. Further studies are needed to explore these associations and their potential mechanisms.
Obstructive sleep apnea; Inflammation; hsCRP; Obesity; Insulin resistance; Oxygen desaturation; Adolescents
The transition from α-helical to β-hairpin conformations of α-syn12 peptide is characterized here using long timescale, unbiased molecular dynamics (MD) simulations in explicit solvent models at physiological and acidic pH values. Four independent normal MD trajectories, each 2500 ns, are performed at 300 K using the GROMOS 43A1 force field and SPC water model. The most clustered structures at both pH values are β-hairpin but with different turns and hydrogen bonds. Turn9-6 and four hydrogen bonds (HB9-6, HB6-9, HB11-4 and HB4-11) are formed at physiological pH; turn8-5 and five hydrogen bonds (HB8-5, HB5-8, HB10-3, HB3-10 and HB12-1) are formed at acidic pH. A common folding mechanism is observed: the formation of the turn is always before the formation of the hydrogen bonds, which means the turn is always found to be the major determinant in initiating the transition process. Furthermore, two transition paths are observed at physiological pH. One of the transition paths tends to form the most-clustered turn and improper hydrogen bonds at the beginning, and then form the most-clustered hydrogen bonds. Another transition path tends to form the most-clustered turn, and turn5-2 firstly, followed by the formation of part hydrogen bonds, then turn5-2 is extended and more hydrogen bonds are formed. The transition path at acidic pH is as the same as the first path described at physiological pH.
Parkinson’s disease; α-syn12 peptide; α-β transition mechanism; different pH
Background and Objective
The impact of perioperative allogenenic blood transfusion (ABT) on clinical outcomes for hepatocellular carcinoma (HCC) is conflicting and unclear. The aim of this meta-analysis is to evaluate the association between ABT and HCC clinical outcomes. Outcomes evaluated were all-cause death, tumor recurrence and postoperative complications.
Relevant articles were identified through MEDLINE search (up to November 2012). Meta-analyses were performed by using the fixed or random effect models. Study heterogeneity was assessed by Q-test and I2 test. Publication bias was evaluated by funnel plots, Egger′s and Begg’s test.
A total of 5635 cases from 22 studies finally met our inclusion criteria. Meta-analysis indicated HCC patients with ABT had an increased risk of all-cause death at 3 and 5 years after surgery (respectively: OR = 1.92, 95% CI, 1.61–2.29,P<0.001; OR = 1.60, 95% CI, 1.47–1.73,P<0.001 ) compared with those without ABT. The risk of tumor recurrence was significantly higher for ABT cases at 1, 3 and 5 years (respectively: OR = 1.70, 95% CI, 1.38–2.10, P<0.001; OR = 1.22, 95% CI, 1.08–1.38, P<0.001; OR = 1.16, 95% CI, 1.08–1.24, P<0.001). The HCC cases with ABT significantly increased postoperative complications occurrence compared with non-ABT cases (OR = 1.78,95% CI, 1.34–2.37, P<0.001).
The findings from the current meta-analysis demonstrated that ABT was associated with adverse clinical outcomes for HCC patients undergoing surgery, including increased death, recurrence and complications. Therefore, ABT should not be performed if possible.
High translocation speed of a DNA strand through a nanopore is a major bottleneck for nanopore detection of DNA molecules. Here, we choose MgCl2 electrolyte as salt solution to control DNA mobility. Experimental results demonstrate that the duration time for straight state translocation events in 1 M MgCl2 solution is about 1.3 ms which is about three times longer than that for the same DNA in 1 M KCl solution. This is because Mg2+ ions can effectively reduce the surface charge density of the negative DNA strands and then lead to the decrease of the DNA electrophoretic speed. It is also found that the Mg2+ ions can induce the DNA molecules binding together and reduce the probability of straight DNA translocation events. The nanopore with small diameter can break off the bound DNA strands and increase the occurrence probability of straight DNA translocation events.
Nanopore; DNA sequencing; Translocation speed
Cerebral ischemia is the most common cerebrovascular disease worldwide. Recent studies have demonstrated that curcumin had beneficial effect to attenuate cerebral ischemic injury. However, it is unclear how curcumin protects against cerebral ischemic injury. In the present study, using rat middle cerebral artery occlusion model, we found that curcumin was a potent PPARγ agonist in that it upregulated PPARγ expression and PPARγ-PPRE binding activity. Administration of curcumin markedly decreased the infarct volume, improved neurological deficits, and reduced neuronal damage of rats. In addition, curcumin suppressed neuroinflammatory response by decreasing inflammatory mediators, such as IL-1β, TNF-α, PGE2, NO, COX-2, and iNOS induced by cerebral ischemia of rats. Furthermore, curcumin suppressed IκB degradation that was caused by cerebral ischemia. The present data also showed that PPARγ interacted with NF-κB-p65 and thus inhibited NF-κB activation. All the above protective effects of curcumin on cerebral ischemic injury were markedly attenuated by GW9662, an inhibitor of PPARγ. Our results as described above suggested that PPARγ induced by curcumin may play a critical role in protecting against brain injury through suppression of inflammatory response. It also highlights the potential of curcumin as a therapeutic agent against cerebral ischemia.