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2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(7): 873-877, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31441413

RESUMO

OBJECTIVE: To explore the risk factors affecting prognosis of critically ill patients following cardiac surgery, furthermore, to assess severity and keep alarm earlier. METHODS: A retrospective study was conducted. The clinical data of critically ill patients following cardiac surgery admitted to intensive care unit (ICU) of the Affiliated Hospital of Guizhou Medical University from January 1st 2014 to December 31st 2018 were enrolled. The clinical characteristics, acute physiology and chronic health evaluation II (APACHE II) and the worst laboratory examination within 24 hours after ICU admission, and the duration of mechanical ventilation, length of ICU stay, using continuous renal replacement therapy (CRRT), accepting vasoactive agents such as norepinephrine, dopamine or dobutamine and blood products such as red blood cells, plasma or platelets were recorded. The patients were divided into survival group and dead group based on discharge prognosis, and the difference in clinical data between the two groups was compared. Binary multivariate Logistic regression analysis was used to screen the risk factors affecting the prognosis of critically ill patients following cardiac surgery, and the receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of these risk factors. RESULTS: In total, 97 patients after cardiac operation were admitted to ICU during the five years. Thirty-two patients were excluded owing to age less than 16 years old, no more than 24 hours of the length of ICU stay, without the outcomes of myocardium enzymes or myocardium markers within the first 24 hours or admitted only for pacemaker. Finally, 65 patients met the criteria, with 40 survived and 25 died. Compared with survival group, APACHE II scores, the level of serum uric acid, serum creatinine (SCr), cardiac troponin T (cTnT), brain natriuretic peptide (BNP), procalcitonin (PCT) and the rate of patients accepting CRRT, vasoactive agents and blood products in dead group were significantly increased with significant differences; however, there was no statistically difference in gender, age, body weight index (BMI), distribution of types of cardiac surgery, ratio of patients suffered from hypertension and diabetes, mean arterial pressure (MAP), white blood cell (WBC), coagulation, length of ICU stay, or duration of mechanical ventilation between the two groups. Binary multivariate Logistic regression analysis showed that APACHE II scores [odds ratio (OR) = 1.123, 95% confidence interval (95%CI) = 1.004-1.257, P = 0.043] and cTnT (OR = 1.496, 95%CI = 1.038-2.158, P = 0.031) were the independent risk factors for prognosis of critical ill patients following cardiac surgery. ROC curve analysis showed that APACHE II score and cTnT had predictive value for prognosis of critical ill patients following cardiac surgery, the best was exerted when APACHE II score combined with cTnT, the area under the ROC curve (AUC) was 0.839, the joint prediction probability was 0.42, the sensitivity was 80.0%, and the specificity was 64.0%. CONCLUSIONS: APACHE II score and cTnT may be one of independent risk factors for prognosis of critical ill patients following cardiac surgery, and there will be far more greater predictive value when APACHE II score combined with cTnT.

3.
Front Immunol ; 10: 1746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31428090

RESUMO

Autoimmune bullous dermatoses (AIBD) include a series of typical organ-specific autoimmune diseases characterized by extensive mucocutaneous blisters. It is generally accepted to be caused by pathological autoantibodies that directly target specific adhesion components of the skin or the adjacent mucous membranes. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Recent studies have indicated that the dysfunction of regulatory T cells, regulatory B cells, and complement regulatory proteins that play essential roles in maintaining a healthy immune environment is also closely related to immune disorders in AIBD. It is important to summarize these studies, elucidate the changes in these regulatory immune cells and molecules for the pathogenesis of AIBD, and reveal the mechanisms by which they lose their ability to regulate immune disorders. In this review, we highlight the role of regulatory immune cells and molecules in the pathogenesis of pemphigus vulgaris and bullous pemphigoid, the two most representative forms of AIBD, and indicate issues that should be addressed in future investigations.

4.
Stroke ; : STROKEAHA119025732, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31409268

RESUMO

Background and Purpose- In patients with symptomatic intracranial atherosclerotic stenosis, identifying the underlying stroke mechanisms may inform secondary prevention. We aimed to propose reproducible classification criteria for stroke mechanisms based on routine neuroimaging in symptomatic intracranial atherosclerotic stenosis and explore their clinical implications. Methods- We recruited patients with acute ischemic stroke attributed to 50% to 99% intracranial atherosclerotic stenosis in anterior circulation from 2 centers. Two investigators independently classified probable stroke mechanisms as parent artery atherosclerosis occluding penetrating artery, artery-to-artery embolism, hypoperfusion, and mixed mechanisms, with prespecified criteria based on infarct topography and magnetic resonance/computed tomography angiography. These stroke mechanisms were correlated with features of the patients at baseline and recurrent ischemic stroke in the same territory or relevant transient ischemic attack within 1 year. Results- Among 153 patients recruited, the most common stroke mechanisms were isolated hypoperfusion (35.3%) and mixed mechanism of artery-to-artery embolism and hypoperfusion (37.3%) that was associated with higher incidence of dyslipidemia (P=0.045) and hypertension (P=0.033) than patients with other stroke mechanisms. The proposed criteria showed substantial to excellent intrarater and interrater reproducibilities (κ, 0.791-0.908). Overall, 31 patients received interventional treatment of the diseased intracranial artery; 122 received medical treatment, among whom a mixed mechanism of artery-to-artery embolism and hypoperfusion at baseline was associated with higher risk of ischemic stroke in the same territory within 1 year (24.4% versus 7.8%; hazard ratio, 3.40; 95% CI, 1.25-9.20; log-rank P=0.010) than other mechanisms combined. Conclusions- Artery-to-artery embolism and hypoperfusion commonly coexist in ischemic stroke attributed to intracranial atherosclerotic stenosis, which may be associated with higher risk of stroke relapse.

5.
J Cell Biol ; 218(9): 3134-3152, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31371388

RESUMO

Regulated growth plate activity is essential for postnatal bone development and body stature, yet the systems regulating epiphyseal fusion are poorly understood. Here, we show that the tissue inhibitors of metalloprotease (TIMP) gene family is essential for normal bone growth after birth. Whole-body quadruple-knockout mice lacking all four TIMPs have growth plate closure in long bones, precipitating limb shortening, epiphyseal distortion, and widespread chondrodysplasia. We identify TIMP/FGF-2/IHH as a novel nexus underlying bone lengthening where TIMPs negatively regulate the release of FGF-2 from chondrocytes to allow IHH expression. Using a knock-in approach that combines MMP-resistant or ADAMTS-resistant aggrecans with TIMP deficiency, we uncouple growth plate activity in axial and appendicular bones. Thus, natural metalloprotease inhibitors are crucial regulators of chondrocyte maturation program, growth plate integrity, and skeletal proportionality. Furthermore, individual and combinatorial TIMP-deficient mice demonstrate the redundancy of metalloprotease inhibitor function in embryonic and postnatal development.

6.
Biomed Res Int ; 2019: 4589056, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467892

RESUMO

Objective: To evaluate and compare the effects of repetitive transcranial magnetic stimulation (rTMS) over the right pars triangularis of the posterior inferior frontal gyrus (pIFG) and the right posterior superior temporal gyrus (pSMG) in global aphasia following subacute stroke. Methods: Fifty-four patients with subacute poststroke global aphasia were randomized to 15-day protocols of 20-minute inhibitory 1 Hz rTMS over either the right triangular part of the pIFG (the rTMS-b group) or the right pSTG (the rTMS-w group) or to sham stimulation, followed by 30 minutes of speech and language therapy. Language outcomes were assessed by aphasia quotient (AQ) scores obtained from the Chinese version of the Western Aphasia Battery (WAB) at baseline and immediately after 3 weeks (15 days) of experimental treatment. Results: Forty-five patients completed the entire study. The primary outcome measures include the changes in WAB-AQ score, spontaneous speech, auditory comprehension, and repetition. These measures indicated significant main effect between the baseline of the rTMS-w, rTMS-b, and sham groups and immediately after stimulation (P<0.05). Compared with the sham group, the increases were significant for auditory comprehension, repetition, and AQ in the rTMS-w group (P<0.05), whereas the changes in repetition, spontaneous speech, and AQ tended to be higher in the rTMS-b group (P<0.05). Conclusions: Inhibitory rTMS targeting the right pIFG and pSTG can be an effective treatment for subacute stroke patients with global aphasia. The effect of rTMS may depend on the stimulation site. Low-frequency rTMS inhibited the right pSTG and significantly improved language recovery in terms of auditory comprehension and repetition, whereas LF-rTMS inhibited the right pIFG, leading to apparent changes in spontaneous speech and repetition.

7.
Adv Exp Med Biol ; 1155: 13-24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468382

RESUMO

Taurine is a sulfur-containing amino acid which has strong activities in enhancing immunity. Gut microbiota is closely interrelated with intestinal mucosal immunity, but the effects and mechanisms of taurine on intestinal microbiota and mucosal immune cells under an immunosuppressive condition remain unclear. This study was conducted to investigate the effect of taurine on gut microbiota and immune cells in Peyer's patches (PPs) of dexamethasone (Dex)-induced immunosuppressive mice. Mice (4-week-old, Male) were randomly divided into three groups: the Control group (n = 12), the Dex-induced immunosuppressive model group (n = 12) and the taurine intervention group (n = 12). The model was established by Dex injection for 7 days and the taurine intervention group was gavaged 100 mg/kg soluble taurine for 30 days. The changes of intestinal microbiota and immune cells in PPs were tested by denaturing gradient gel electrophoresis (DGGE) and flow cytometry, respectively. Results showed that the microbiota in immunosuppressive mice was obvious different compared with control group, in which, the Lachnospiraceae and Ruminococcaceae groups were significantly reduced, and their reduction were reversed after taurine intervention. Compared to the control group, the total cell number in PPs, as well as the subsets of CD3+ cells (T cells), CD19+ cells (B cells) in model groups were significantly lower, and they were dramatically improved after taurine treatment. Our results suggested that taurine has a positive effect on i ntestinal homeostasis of the immunosuppressive mice.

8.
Adv Exp Med Biol ; 1155: 381-390, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468416

RESUMO

Taurine (2-aminoethanesulfonic acid) has positive effects on the formation of immune systems. In this study, we evaluated the effects of taurine on the development of T lymphocyte subpopulations in thymus of immunosuppresive mice. The immunosuppressed mice model was established by intraperitoneal injection of dexamethasone (Dex) for 7 days. Mice (male, Kunming strain) were randomly divided into three groups, the normal control group (Cont.), the Dex-induced immunosuppressive model group (Dex + PBS), and the taurine intervention group (Dex + TAU). Taurine was administered at a dose of 200 mg/kg for 30 days or until euthanasia. Total cell numbers in the thymi of mice were evaluated by cell count, and the flow cytometry was used to determine the proportion of different cell subsets. Our results showed that the size and weight of thymi of Dex + PBS group were significantly smaller than those of Cont. group, and taurine administration efficiently increased the thymus index. Taurine also significantly increased the number of CD4- CD8- double negative (DN), CD4+ CD8+ double positive (DP), CD4+ single positive (CD4+) and CD8+ SP (CD8+) cells compared with the Dex + PBS group, but did not affect the CD4+/CD8+ cell ratio in thymus of Dex-induced immunoseppressive mice. Our results suggested that taurine has a positive effect on thymus differentiation in Dex-induced immunosuppressive mice.

9.
Pathol Res Pract ; : 152562, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31387805

RESUMO

Interleukin-17 F (IL-17F) is a pro-inflammatory cytokine that participate in inflammatory responses. Studies showed that IL-17F is likely involved in tumor development, but the biological function of IL-17F in non-small cell lung cancer (NSCLC) is unclear. The aim of this study was to explore the biological role of IL-17F in NSCLC and investigate its correlation with biological markers CD31, P53, Ki-67 and E-cadherin. Paraffin-embedded tumor tissues from 55 NSCLC patients were collected to detect proteins expression using immunohistochemistry (IHC). 12 normal lung tissues samples were used as control. IHC results showed that the expression of IL-17F in NSCLC cells (61.8%) was significantly higher compared with normal lung tissues (25.0%) (P < 0.05). The expression of IL-17F was positively associated with tumor differentiation and negatively associated with lymph node metastasis and TNM staging (P all < 0.05). Multivariate analysis showed that IL-17F expression was an independent factor associated with TNM staging (P < 0.01). Pearson's correlation analysis showed a negative correlation between IL-17F and CD31 expression and a positive correlation between IL-17F and E-cadherin expression (P all < 0.05). There was no relationship between IL-17 F and P53 or Ki-67 expression in NSCLC tissues (P > 0.05). These data suggest that IL-17 F may be considered as a potential marker for predicting the progression of NSCLC.

10.
Leuk Lymphoma ; : 1-10, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31298062

RESUMO

Early/upfront radiation was associated with improved survivals compared with late radiation for early-stage NK/T-cell lymphoma (NKTCL) in the old era when anthracycline-base chemotherapy (CT) prevailed. However, in the modern era of effective l-asparaginase/gemcitabine-based CT, the optimal timing of radiation is unclear. In this study, 75 patients with newly diagnosed NKTCL, who were treated with combined involved-field intensity-modulated radiotherapy and GDP (gemcitabine, dexamethasone, and cisplatin) were retrospectively reviewed, including 45 from the RT + CT group and 30 from the CT + RT ± CT group. Compared with CT + RT ± CT, RT + CT sequence achieved superior progression-free survival (5-year PFS: 81.6% vs. 56.0%, p = .017) and locoregional control (LRC) (90.8% vs. 66.9%; p = .020). Responses, overall survivals or adverse event incidences did not differ across the groups. Upfront RT was a powerful prognostic variable for favorable PFS (HR 0.302; 95% CI: 0.125-0.729; p = .008). It indicated that upfront RT administration remains vital in enhancing LRC and survival for localized NKTCL in the modern era.

11.
BMC Surg ; 19(1): 81, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277627

RESUMO

BACKGROUND: Vascularized free fibular flaps have been the "workhorses" for reconstruction of many kinds of bone defects. Nevertheless, there is no consensus regarding the optimal wound closure method for fibular donor sites. This study aimed to compare prognostic outcomes of primarily closures (PC) and skin grafts (SG) for fibular donor sites. METHODS: Studies regarding donor-site outcomes of PC versus SG in patients undergoing free fibular flap procedures were included. Two authors individually searched PubMed, Web of Science, EMBASE, Cochrane Library and clinicaltrials.gov up to February 2019, extracted the data and assessed quality of each selected article. Ultimately, The incidences of donor-site morbidities were evaluated. RESULTS: Five studies with a total of 119 patients were included in our analysis. No significant differences were found with respect to the rates of donor-site problems between the PC and SG groups. CONCLUSIONS: Fibular flap patients undergoing PC and SG wound closures may have similar donor-site outcomes. Additional large-scale studies are necessary to draw a solid conclusion.

12.
Cancer Med ; 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31305011

RESUMO

BACKGROUND: Cervical cancer is a major public health concern in China. We report the end-of-study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04-human papillomavirus (HPV)-16/18 vaccine in Chinese women aged 18-25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported. METHODS: Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of AS04-HPV-16/18 vaccine or Al(OH)3 (control) at Months 0-1-6. Vaccine efficacy against HPV-16/18 infection and cervical intraepithelial neoplasia (CIN), cross-protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according-to-protocol efficacy (ATP-E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC-E; vaccine N = 2987; control N = 2985) and TVC-naïve (vaccine N = 1660; control N = 1587). RESULTS: In initially HPV-16/18 seronegative/DNA-negative women, vaccine efficacy against HPV-16/18-associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP-E, 88.7% (95% CI: 18.5, 99.7) in the TVC-E, and 100% (95% CI: 17.9, 100) in the TVC-naïve. Cross-protective efficacy against incident infection with HPV-31, HPV-33 and HPV-45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP-E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and anti-HPV-18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group. CONCLUSIONS: This is the first large-scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV-16/18-associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China. TRIAL REGISTRATION: NCT00779766.

13.
ACS Appl Mater Interfaces ; 11(30): 27378-27385, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31267733

RESUMO

Photoacoustic microscopy (PAM) can measure optical absorption-based molecular specificities within tissues. Despite the diffraction-limited lateral resolution in optical-resolution photoacoustic microscopy (OR-PAM), the ongoing challenge is poor axial resolution because of an insufficient ultrasound detection bandwidth, which hampers PAM volumetric imaging. We propose polarization-differential surface plasmon resonance (SPR) sensing for broadband and high-sensitivity photoacoustic (PA) detection, allowing OR-PAM with comparable resolution along lateral and axial directions. This sensor possesses an estimated noise-equivalent-pressure sensitivity of ∼477 Pa over an approximately linear pressure response up to 107 kPa. Moreover, an improved PA detection bandwidth of ∼173 MHz permits an axial resolution (∼7.6 µm) that approaches the lateral resolution (∼4.5 µm) of our OR-PAM system. The capability in spatially isometric micrometer-scale resolution enables in vivo volumetric label-free imaging of the microvasculature of a mouse ear. The SPR sensing technology promises broader applications of PAM in biomedical studies such as microcirculation.

14.
Environ Res ; 176: 108568, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288195

RESUMO

Malaria is a serious public health threat in Yunnan Province of China and has been frequently reported in some endemic regions, such as Tengchong County, with high morbidity. It is essential to analyze the characteristics of malaria cases and identify vulnerable populations. Previous studies about vulnerable populations have mostly used a statistical grouping method to count frequence from a single aspect rather than defined clustered groups. Based on descriptive analysis of the temporal variation and demographic structure of the populations with malaria infection, we used a k-prototypes clustering algorithm to cluster vulnerable populations in Tengchong County in three dimensions, according to sex, age, and occupation. The results indicated that a high incidence of malaria occurred mainly in young male farmers and young or middle-aged male migrant workers. Imported cases, low education level, lack of mosquito bite prevention, and risk behaviors contributed to the high malaria incidence in these groups. Double verification ensured the reliability of this method and reasonability of the results. In addition, we highlighted the importance of targeting prevention and control of malaria for vulnerable groups. We provided suggestions of policies and measures to be implemented by regional governments and at household and individual levels for farmers and migrant workers respectively. Using the k-prototypes clustering algorithm, we efficiently identified those populations at greatest risk of malaria infection. Our results may serve as scientific guidance for targeted malaria prevention and control in Yunnan Province.

15.
Proc Natl Acad Sci U S A ; 116(31): 15398-15406, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31308234

RESUMO

Flexible biocompatible electronic systems that leverage key materials and manufacturing techniques associated with the consumer electronics industry have potential for broad applications in biomedicine and biological research. This study reports scalable approaches to technologies of this type, where thin microscale device components integrate onto flexible polymer substrates in interconnected arrays to provide multimodal, high performance operational capabilities as intimately coupled biointerfaces. Specificially, the material options and engineering schemes summarized here serve as foundations for diverse, heterogeneously integrated systems. Scaled examples incorporate >32,000 silicon microdie and inorganic microscale light-emitting diodes derived from wafer sources distributed at variable pitch spacings and fill factors across large areas on polymer films, at full organ-scale dimensions such as human brain, over ∼150 cm2 In vitro studies and accelerated testing in simulated biofluids, together with theoretical simulations of underlying processes, yield quantitative insights into the key materials aspects. The results suggest an ability of these systems to operate in a biologically safe, stable fashion with projected lifetimes of several decades without leakage currents or reductions in performance. The versatility of these combined concepts suggests applicability to many classes of biointegrated semiconductor devices.

16.
Aging (Albany NY) ; 11(12): 4159-4182, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31241467

RESUMO

Aging-associated loss of skeletal muscle mass and force increases the risk of falls, impairs mobility, and leads to a reduced quality of life. High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) for improving morphological and metabolic adaptations of skeletal muscle in older adults, but the underlying mechanism is unknown. Aged female rats underwent HIIT and MICT for 8 months, and their differential impacts on skeletal muscle proteome were investigated. HIIT resulted in a larger improvement in grip strength and fiber cross-sectional area, with similar increases in inclined plane performance and time to exhaustion. Proteomic analysis showed that common training adaptations of both protocols included changes to muscle contraction, focal adhesion signaling, mitochondrial function, apoptosis and regeneration, and anti-oxidation, whereas protein processing in the endoplasmic reticulum and adipocytokine signaling were specifically altered in the MICT and HIIT groups, respectively. Immunoblotting showed that upregulation of the adiponectin/AMPK signaling pathway may be associated with improvements in autophagy, oxidative stress, mitochondrial function, and apoptosis in aged skeletal muscle following HIIT. Thus, understanding the molecular differences in training adaptations from these two exercise modalities may aid in combatting sarcopenia.

17.
Mol Immunol ; 112: 312-321, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229844

RESUMO

Precise glycosylation plays a crucial and distinctive role in thymic T cell development. The core fucosylation is dramatically up-regulated at the transition from CD4-CD8- (DN) to CD4+CD8+ (DP) in the thymic development. Ablation of core fucosylation in T cells did reduce the size of the thymus due to a significant loss of CD4+ SP, CD8+ SP and DP thymocytes in core fucosyltransferase (Fut8) knockout (Fut8-/-) mice. T cell receptors (TCRs) are heavily core fucosylated glycoproteins. Loss of core fucosylation of TCR contributed to the reduced phosphorylation of ZAP70 (pZAP70) in Fut8-/- DP cells was observed. Compare to the Fut8+/+OT-II DP thymocytes, pZAP70 was significantly reduced in Fut8-/- OT-II DP thymocytes with OVA323-339 stimulation. Also, the pZAP70 of Fut8+/+OT-I DP thymocytes with OVA257-264 stimulation was remarkably attenuated by treatment of the fucosidase. Upon anti-CD3/CD28 Abs stimulation, the increased apoptosis was found in Fut8-/- thymocytes compared with Fut8+/+ thymocytes. Moreover, the TCRhiCD69hi (post-positive selection thymocytes) was markedly depleted in the Fut8-/- thymus without any stimulation. The expression of CD5 was significantly down-regulated on the DP cells in the Fut8-/- thymus. Our results therefore demonstrate that ablation of core fucosylation results in the abnormal T cell development due to the attenuated signaling via TCR.

18.
Int J Legal Med ; 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31139909

RESUMO

Analysis of the characteristics and genetic basis of the anomalous short tandem repeat (STR) pattern encountered in forensic cases has been shown to be useful for analysing STR profiles in routine forensic casework. Here, we report biallelic patterns at several X-chromosome STR (X-STR) loci in human males revealed by forensic parameters investigation using the commercial AGCU X19 Kit. The presence of these patterns was verified by reanalysis using new samples and bidirectional Sanger sequencing of the singleplex polymerase chain reaction (PCR) products. And the genetic basis for their production was inferred based on the relative peak heights at the amelogenin locus and the affected locus (DXS10159, DXS10134 and DXS10079) and the normalised peak height ratios between the affected locus and adjacent loci relative to the control sample 9947A. The inference results suggested that two cases of biallelic pattern at the DXS10159 locus would be caused by local duplications, while in the other two cases, both the biallelic patterns at loci DXS10134 and DXS10079 would be due to somatic mutations. One case where the male showed a biallelic pattern at the DXS10159 locus (Xp11.21) was further analysed. Quantitative PCR (qPCR) revealed a microduplication (< 0.2 Mb) spanning at least 13.9 kb in Xp11.21 encompassing the DXS10159 locus. Finally, a workflow for analysing anomalous STR patterns was summarised. In conclusion, this study is a detailed report of X-STR biallelic patterns in human males, which serves as an effective complement to the database and provides an example for the analysis of anomalous STR patterns.

19.
Plant Physiol Biochem ; 141: 83-94, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31136934

RESUMO

Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc), is one of the most devastating diseases in bananas resulting in significant loss of Cavendish bananas production worldwide. Here we show the agronomic traits and the resistance of 'Guijiao 9' in the field trials from 2012 to 2017. And then we dissect and compare the transcriptome response from these two cultivars (cv. 'Guijiao 9' and cv. Williams) in an attempt to understand the molecular basis that contribute to the enhanced Foc tropical race 4 (Foc-TR4) resistance. 'Guijiao 9' is a Cavendish cultivar with strong resistance to Foc-TR4, which was reflected in a lower disease severity and incidence in glasshouse and field trails, when compared to the susceptible cultivar Williams. Gene expression profiles of 'Guijiao 9' and Williams were captured by performing RNA-Seq analysis on 16 biological samples collected over a six day period post inoculation with Foc-TR4. Transcriptional reprogramming in response to Foc-TR4 was detected in both genotypes but the response was more drastic in 'Guijiao 9' than in Williams. Specific genes involved in plant-pathogen interaction and defense signaling including MAPK, calcium, salicylic acid, jasmonic acid and ethylene pathways were analyzed and compared between 'Guijiao 9' and Williams. Genes associated with defense-related metabolites synthesis such as NB-LRR proteins, calmodulin-binding protein and phenylpropanoids biosynthesis genes were significantly up-regulated in 'Guijiao 9' resistant to Foc-TR4 infection. Taken together, this study highlights the important roles of plant hormone regulation and defense gene activation in mediating resistance in 'Guijiao 9'.

20.
J Natl Cancer Inst ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31086947

RESUMO

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.

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