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1.
BMC Cardiovasc Disord ; 20(1): 109, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138662

RESUMO

BACKGROUND: Patients with coronary chronic total occlusion (CTO) require effective antiplatelet therapy after percutaneous coronary intervention (PCI). Ticagrelor has more pronounced platelet inhibition than clopidogrel. However, the most appropriate dose of ticagrelor in East Asian populations remains unclear. METHOD: We compared ticagrelor (180 mg loading dose, 90 mg twice daily thereafter and 120 mg loading dose, 60 mg twice daily thereafter) and clopidogrel (300 mg loading dose, 75 mg daily thereafter) for prevention of cardiovascular events in 525patients with CTO undergoing PCI. RESULTS: The rate of in-hospital major adverse cardiac and cerebral events (MACCE) was not different between the groups. At 1-year follow-up, target vessel revascularization (TVR) in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.047); TVR was significantly decreased in 60 mg ticagrelor compared to standard dose clopidogrel (p = 0.046). At 1-year follow-up, overall MACCE in both ticagrelor groups were significantly lower than that in the clopidogrel group (p = 0.023). Kaplan-Meier analysis showed MACCE-free survival was significantly higher in both ticagrelor groups than in the clopidogrel group (p = 0.024). During hospitalization, minor bleeding was significant increased in the 90 mg ticagrelor group (p = 0.021). At 1-year follow-up, risk of major and minor bleeding were significantly increased in the 90 mg ticagrelor group. CONCLUSION: In East Asian patients with CTO undergoing PCI, 60 mg ticagrelor was as effective as 90 mg, at the same time significantly reduced risk of bleeding.

2.
Zhen Ci Yan Jiu ; 45(2): 136-40, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144924

RESUMO

OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) of single-acupoint Zusanli (ST36) and multi-acupoints Zusanli (ST36), Shangjuxu (ST37) and Neiguan (PC6) in promoting the recovery of gastrointestinal movement in laparoscopic cholecystectomy (LC) patients undergoing general anesthesia. METHODS: A total of 70 LC patients (American Society of Anesthesiologists [ASA] grade I and II) were recruited and randomly divided into control (n=23), single ST36 (n=23) and ST36+ST37+PC6 (n=24) groups. The patients in the control group only received routine basic treatments (postoperative fasting and water deprivation, intravenous drip of biotics, water-electrolyte and acid-base balancing, oxygen uptake, etc). EA (10 Hz, 5 mA, 30 min every time) was applied to the abovementioned single-acupoint or multi-acupoints groups before, and 4, 22, 34 and 46 h after the operation. The time-points of postoperative borborygmus recovery, first anal exhaust and defecation, post-operative abdominal distension (mild, moderate and severe), nausea and vomiting (grade Ⅰ, Ⅱ, Ⅲ and Ⅳ) at 6, 24 and 48 h after surgery were recorded and analyzed. RESULTS: Compared to the control group, the time of borborygmus recovery, first anal exhaust and defecation were markedly earlier in both single ST36 and ST36+ST37+PC6 groups (P<0.01, P<0.05, P<0.001). The number of patients who had mild plus moderate abdominal distention, and nausea (grade Ⅱ+Ⅲ) at 24 h after ope-ration was significantly lower in both single ST36 and ST36+ST37+PC6 groups than in the control group (P<0.05). No significant differences were found between the two EA groups in the time of borborygmus recovery, first anal exhaust and defecation, and in the number of patients with mild plus moderate abdominal distention and those with nausea (P>0.05). CONCLUSION: EA of both single ST36 and ST36+ST37+PC6 can promote gastrointestinal function recovery in LC patients, without remarkable difference between them.


Assuntos
Colecistectomia Laparoscópica , Eletroacupuntura , Pontos de Acupuntura , Anestesia Geral , Humanos , Náusea
3.
Echocardiography ; 37(3): 421-428, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32112477

RESUMO

BACKGROUND: Despite speckle tracking echocardiography (STE) has emerged as a sensitive technique for identifying myocardial dysfunction, there are little data available on the appropriate timing to perform STE in the serial assessment after anthracycline administration. Moreover, further uncertainty is increased in the context of STE application in diffuse large B-cell lymphoma (DLBCL) research, as most recommendations are inferred by studies conducted primarily in breast cancer. OBJECTIVE: This study aimed to determine whether early measurement of strain parameters derived by STE could predict the development of cardiotoxicity. METHODS: Sixty-five patients were included in the final analysis. The patients were evaluated at baseline, after the third cycle and sixth-eighth cycle, and during follow-up. Global longitudinal strain (GLS) was analyzed using STE, and left ventricular ejection fraction (LVEF) was calculated by real time 3D echocardiography (RT3DE). RESULTS: There was a significant decrease in GLS after the third cycle of chemotherapy and remained decreased during subsequent follow-up, whereas LVEF decreased only at follow-up. A percentage reduction in GLS of 13.8% between baseline and the third cycle of chemotherapy was the best predictor of further LVEF reduction. CONCLUSION: Earlier monitoring timing and more accurate assessment methods might be helpful in the prevention of irreversible heart failure.

4.
Sci Total Environ ; 719: 137479, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32135332

RESUMO

Biocrusts are common biotic components in dryland ecosystems worldwide, they contain diverse soil organisms and effectively enhance soil stability and perform a series of key ecological functions. However, the geographical pattern of microbial communities in biocrusts is rarely assessed, despite it is closely related to the spatial variation of ecosystem functions in drylands. We assessed soil bacterial communities in biocrusts across four ecosystems (Gobi, desert, desert steppe and grassland) in a precipitation gradient (16-566 mm yr-1) in northern China. Bacterial OTU number and phylogenetic diversity did not linearly increase with decreasing aridity, they were significantly lower in Gobi and similar among desert, desert steppe and grassland. Soil bacterial community composition in Gobi and desert were different than those in desert steppe and grassland, and they were similar between Gobi and desert, this suggests the key role of habitat in structuring soil bacterial communities. The geographic pattern of soil bacterial communities was strongly influenced by both geographic distance and environmental factors. The first explanatory factor for the geographic variation of bacterial community dissimilarity differed among four ecosystems, being aridity in Gobi and desert, precipitation in desert steppe, and soil inorganic nitrogen in grassland. The geographic pattern of the bacterial functional group profile showed a similar pattern with community composition across four ecosystems, and the groups of containing mobile elements and gram negative bacteria were more abundant in drier habitats of Gobi and desert. Our results reveal the non-linear changes in diversity, composition and functional group of soil bacterial communities in biocrusts across the precipitation gradient from hyper-arid to semi-humid regions, and suggest that the geographic distance and habitat-specific environmental factors determine the distribution of soil bacterial communities in different ecosystems.

5.
AIDS ; 34(5): 797, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32167994
6.
Gut ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32213556

RESUMO

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

7.
Drug Des Devel Ther ; 14: 1127-1141, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214798

RESUMO

Introduction: Ulcerative colitis (UC) is a chronic and inflammatory bowel disease. UC-associated colorectal cancer (UC-CRC) is one of the most severe complications of long-standing UC. In the present study, we explored the effects of miR-370-3p on UC-CRC in vivo and investigated its underlying mechanisms in vivo and in vitro. Methods: Azoxymethane (AOM) and dextran sodium sulfate (DSS) were used to induce UC-CRC in C57BL/6 mice. AOM/DSS-induced mice were treated with 5×108 pfu miR-370-3p overexpressing-adenovirus via tail-vein injection every two weeks. Results: We found that miR-370-3p significantly improved the body weights and survival rates and inhibited the tumorigenesis of UC-CRC in AOM/DSS mice. Mechanically, miR-370-3p inhibited AOM/DSS-induced inflammatory response by decreasing tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) through targeting toll-like receptor 4 (TLR4), as demonstrated by down-regulation of TLR4, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and phosphorylated epidermal growth factor receptor (pEGFR). miR-370-3p decreased the expression of tumor-associated proteins, including p53, ß-catenin, and ki67 in AOM/DSS-treated mice. Additionally, miR-370-3p remarkably inhibited epithelial-mesenchymal transition (EMT) via increasing E-cadherin expression and reducing N-cadherin and Vimentin expression in vivo. Further studies showed that miR-370-3p repressed proliferation and EMT of colon cancer cells in vitro. Moreover, we proved that miR-370-3p decreased the expression of tumor-associated proteins and reversed EMT by regulating ß-catenin in colon cancer cells. Conclusion: Taken together, miR-370-3p alleviated UC-CRC by inhibiting the inflammatory response and EMT in mice, which suggested miR-370-3p as a novel potential target for UC-CRC therapy.

8.
Sci Rep ; 10(1): 5623, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221398

RESUMO

To facilitate the utility of SNP-based genotyping, we developed a new method called target SNP-seq which combines the advantages of multiplex PCR amplification and high throughput sequencing. Compared with KASP, Microarrays, GBS and other SNP genotyping methods, target SNP-seq is flexible both in SNPs and samples, yields high accuracy, especially when genotyping genome wide perfect SNPs with high polymorphism and conserved flanking sequences, and is cost-effective, requiring 3 days and $7 for per DNA sample to genotype hundreds of SNP loci. The present study established a DNA fingerprint of 261 cucumber varieties by target SNP-seq with 163 perfect SNPs from 4,612,350 SNPs based on 182 cucumber resequencing datasets. Four distinct subpopulations were found in 261 Chinese cucumber varieties: the north China type, the south China type, the Europe type, and the Xishuangbanna type. The north China type and Xishuangbanna type harbored lower genetic diversity, indicating greater risk of genetic erosion in these two subpopulations. Furthermore, a core set of 24 SNPs was able to distinguish 99% of the 261 cucumber varieties. 29 core cucumber backbone varieties in China were identified. Therefore, target SNP-seq provides a new way to screen out core SNP loci from the whole genome for DNA fingerprinting of crop varieties. The high efficiency and low cost of target SNP-seq is more competitive than the current SNP genotyping methods, and it has excellent application prospects in genetic research, as well as in promoting plant breeding processes in the near future.

9.
J Gene Med ; : e3179, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32119160

RESUMO

BACKGROUND: The present study aimed to investigated the expression pattern of long noncoding RNA LINC00858 (LINC00858) in gastric cancer (GC) patients and its feasibility as a new prognostic biomarker. METHODS: We examined LINC00858 expression in GC tissues and matched normal tissues from 189 patients using a quantitative reverse transcription-polymerase chain reaction. The correlations of LINC00858 levels in GC patients with clinicopathologic features were analyzed using a chi-squared test. The influence of LINC00858 on the overall survival rate of GC patients was precisely calculated using Kaplan-Meier methods (log rank tests). Multivariate Cox regression assays were carried out for the identification of the independent risk factors for GC. RESULTS: We observed that LINC00858 was distinctly up-regulated in GC tissues compared to adjacent non-tumor specimens (p < 0.01). Higher expression of LINC00858 in GC was found to be associated with TNM stage (p = 0.003) and lymphatic metastasis (p = 0.007). Using Kaplan-Meier assays, we found that patients with high expression levels of LINC00858 had a distinctly poor overall survival and disease-free survival compared to those with low expression levels of LINC00858 (p = 0.0102). Multivariate analyses confirmed that LINC00858 (p < 0.05) was an independent prognosis factor for GC patients. CONCLUSIONS: The data obtained in our study indicate that LINC00858 may be used as a novel prognostic indicator in GC patients.

10.
Med Sci Monit ; 26: e920350, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32145061

RESUMO

BACKGROUND The aim of this study was to investigate the clinical characteristics and the risk factors associated with anti-tuberculosis (anti-TB) drug-induced liver injury (DILI). MATERIAL AND METHODS This retrospective study enrolled 140 hospitalized patients diagnosed with anti-TB DILI during January 2009 to December 2015. We assessed the baseline characteristics and performed regular follow-up up to the 24th week to assess the possible risk factors associated with the condition. RESULTS The study population was 58.6% male and 41.4% female patients; 20.7% were diagnosed with grades 4-5 DILI and 79.3% with grades 1-3 DILI. Female patients were significantly more likely to be diagnosed with grades 4-5 DILI than with grades 1-3 DILI (58.6% vs. 36.9%, p=0.036). Patients treated with a multidrug anti-TB regimen were more commonly affected with grades 4-5 DILI (86.2% vs. 68.5%, p=0.045). A significant number of patients who reinitiated anti-TB therapy suffered severe liver injury in comparison to patients with grades 1-3 DILI (41.4% vs. 10.8%, P<.001). Laboratory examinations revealed significantly higher values for total bilirubin (TBL), International normalized ratio (INR), and Hy's law (P<.001) in the grades 4-5 group compare to the grades 1-3 group. CONCLUSIONS Female gender, combination therapy for antitubercular drugs (isoniazid, rifampicin and pyrazinamide), re-challenge were the risk factors associated with the severity of anti-TB DILI.


Assuntos
Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Adulto , Antituberculosos/uso terapêutico , Feminino , Humanos , Isoniazida/efeitos adversos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirazinamida/efeitos adversos , Pirazinamida/uso terapêutico , Estudos Retrospectivos , Rifampina/efeitos adversos , Rifampina/uso terapêutico , Fatores de Risco , Tuberculose/tratamento farmacológico , Adulto Jovem
11.
Biomed Res Int ; 2020: 1852070, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190653

RESUMO

Background: Percutaneous endoscopic transforaminal discectomy (PETD) is regarded as a viable alternative option for upper lumbar disc herniation (LDH). However, few studies have evaluated PETD for upper LDH, and no study has compared the advantages of endoscopic procedures versus conventional surgery. The present study was aimed at comparing the surgical outcome and safety of PETD versus conventional open lumbar discectomy in the treatment of upper LDH. Methods: Data from 42 patients treated for upper LDH from July 2015 to July 2018 were retrospectively analyzed, including 21 patients treated with PETD (PETD group) and 21 patients treated with conventional posterior lumbar discectomy (open group). The two groups were compared regarding demographic information, physical examination, radiological evaluations, and perioperative indicators. The clinical outcomes were assessed in accordance with the Oswestry Disability Index (ODI), visual analog scale (VAS), and modified MacNab criteria. Results: The postoperative ODI and VAS scores were significantly improved in both groups compared with the preoperative baseline values (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (P < 0.001), and the satisfactory rate was 90.5% in both groups in accordance with the modified MacNab criteria. There were no significant differences between the two groups in the clinical outcomes and complication rate (. Conclusions: PETD has a similar outcome to the conventional surgical method for the treatment of upper LDH but provides the typical advantages of minimally invasive procedures such as reduced iatrogenic injury, minimal activity restrictions, and accelerated ambulation recovery postoperatively.

12.
BMC Med Res Methodol ; 20(1): 54, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131746

RESUMO

BACKGROUND: Claims-based algorithms are commonly used to identify sepsis in health services research because the laboratory features required to define clinical criteria may not be available in administrative data. METHODS: We evaluated claims-based sepsis algorithms among adults in the US aged ≥65 years with Medicare health insurance enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Suspected infections from baseline (2003-2007) through December 31, 2012 were analyzed. Two claims-based algorithms were evaluated: (1) infection plus organ dysfunction diagnoses or sepsis diagnoses (Medicare-Implicit/Explicit) and (2) Centers for Medicare and Medicaid Services Severe Sepsis/Septic Shock Measure diagnoses (Medicare-CMS). Three classifications based on clinical criteria were used as standards for comparison: (1) the sepsis-related organ failure assessment (SOFA) score (REGARDS-SOFA), (2) "quick" SOFA (REGARDS-qSOFA), and (3) Centers for Disease Control and Prevention electronic health record criteria (REGARDS-EHR). RESULTS: There were 2217 suspected infections among 9522 participants included in the current study. The total number of suspected infections classified as sepsis was 468 for Medicare-Implicit/Explicit, 249 for Medicare-CMS, 541 for REGARDS-SOFA, 185 for REGARDS-qSOFA, and 331 for REGARDS-EHR. The overall agreement between Medicare-Implicit/Explicit and REGARDS-SOFA, REGARDS-qSOFA, and REGARDS-EHR was 77, 79, and 81%, respectively, sensitivity was 46, 53, and 57%, and specificity was 87, 82, and 85%. Comparing Medicare-CMS and REGARDS-SOFA, REGARDS-qSOFA, and REGARDS-EHR, agreement was 77, 87, and 85%, respectively, sensitivity was 27, 41, and 36%, and specificity was 94, 92, and 93%. Events meeting the REGARDS-SOFA classification had a lower 90-day mortality rate (140.7 per 100 person-years) compared with the Medicare-CMS (296.1 per 100 person-years), REGARDS-qSOFA (238.6 per 100 person-years), Medicare-Implicit/Explicit (219.4 per 100 person-years), and REGARDS-EHR classifications (201.8 per 100 person-years). CONCLUSION: Claims-based sepsis algorithms have high agreement and specificity but low sensitivity when compared with clinical criteria. Both claims-based algorithms identified a patient population with similar 90-day mortality rates as compared with classifications based on qSOFA and EHR criteria but higher mortality relative to SOFA criteria.

13.
Oxid Med Cell Longev ; 2020: 2786139, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184914

RESUMO

It is generally accepted that the amyloid ß (Aß) peptide toxicity contributes to neuronal loss and is involved in the initiation and progression of Alzheimer's disease (AD). Cold-inducible RNA-binding protein (CIRBP) is reported to be a general stress-response protein, which is induced by different stress conditions. Previous reports have shown the neuroprotective effects of CIRBP through the suppression of apoptosis via the Akt and ERK pathways. The objective of this study is to examine the effect of CIRBP against Aß-induced toxicity in cultured rat primary cortical neurons and attempt to uncover its underlying mechanism. Here, MTT, LDH release, and TUNEL assays showed that CIRBP overexpression protected against both intracellular amyloid ß- (iAß-) induced and Aß 25-35-induced cytotoxicity in rat primary cortical neurons. Electrophysiological changes responsible for iAß-induced neuronal toxicity, including an increase in neuronal resting membrane potentials and a decrease in K+ currents, were reversed by CIRBP overexpression. Western blot results further showed that Aß 25-35 treatment significantly increased the level of proapoptotic protein Bax, cleaved caspase-3, and cleaved caspase-9 and decreased the level of antiapoptotic factor Bcl-2, but were rescued by CIRBP overexpression. Furthermore, CIRBP overexpression prevented the elevation of ROS induced by Aß 25-35 treatment by decreasing the activities of oxidative biomarker and increasing the activities of key enzymes in antioxidant system. Taken together, our findings suggested that CIRBP exerted protective effects against neuronal amyloid toxicity via antioxidative and antiapoptotic pathways, which may provide a promising candidate for amyloid-based AD prevention or therapy.

14.
BMC Infect Dis ; 20(1): 224, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171271

RESUMO

BACKGROUND: Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block. METHODS: A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori's methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section. RESULTS: The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p < 0.01). Of all patients infected with HIV, 390 (86.1%) were males. This proportion was significantly higher than that of non-HIV-infected patients [65/136 (47.8%)] (p < 0.01). The major causes of cervical lymphadenopathy in HIV positive patients were mycobacterial infection (38.4%), reactive hyperplasia (28.9%), non-specific inflammation (19.9%), and malignant lesions (4.2%). In contrast, the most common causes in HIV negative patients were reactive hyperplasia (37.5%), malignancy (20.6%), non-specific inflammation (19.1%) and mycobacterial infection (12.5%). Opportunistic infections such as non-tuberculous mycobacteria (4.2%), cryptococcosis (1.5%), Talaromyces marneffei (1.5%) and other fungi (0.4%) were found only in HIV-infected individuals. Non-Hodgkin's lymphoma (2.4%) was the most common malignant lesion in patients with HIV infection, followed by Kaposi's sarcoma (0.9%) and metastatic squamous cell carcinomas (0.7%). However, the most common malignancy in non-HIV-infected patients was metastatic carcinomas (14%) including small cell carcinomas, adenocarcinomas, squamous cell carcinomas and hepatocellular carcinoma, which were noticeably greater than the HIV patients (p < 0.01). CONCLUSIONS: There were significantly different causes of cervical lymphadenopathy in HIV infected and non-HIV infected patients. FNAC was a useful diagnostic method for differential diagnosis of cervical lymphadenopathy.

15.
Hum Vaccin Immunother ; : 1-12, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186974

RESUMO

Vaccination against hepatitis B is the most effective strategy to control HBV infection. The first licensed hepatitis B vaccine was developed by the purification of hepatitis B surface antigen (HBsAg) from plasma of asymptomatic HBsAg carriers. Then, the recombinant DNA technology enabled the development of recombinant hepatitis B vaccine. A series of three doses vaccine can elicit long-term protection more than 30 y. Concurrent use of hepatitis B immunoglobulin and hepatitis B vaccine has substantially reduced the mother-to-child transmission of HBV, nearly zero infection in children of carrier mother with negative hepatitis B e antigen (HBeAg) and 5-10% infection in children of HBeAg-positive mothers. By the end of 2018, 189 countries adopted universal hepatitis B vaccination program, which has dramatically reduced the global prevalence of HBsAg in children <5 y of age, from 4.7% in the prevaccine era to 1.3% in 2015. However, the implementation of universal hepatitis B vaccination in some regions is suboptimal and timely birth dose vaccine is not routinely administered in more than half of newborn infants. Optimal worldwide universal hepatitis B vaccination requires more efforts to overcome the social and economic challenges.

16.
EBioMedicine ; 53: 102677, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32114389

RESUMO

BACKGROUND: Endothelial cells (ECs) function as an instructive platform to support haematopoietic stem cell (HSC) homeostasis. Our recent studies found that impaired bone marrow (BM) ECs are responsible for the defective haematopoiesis in patients with poor graft function (PGF), which is characterised by pancytopenia post-allotransplant. Although activated autophagy was reported to benefit ECs, whether EC autophagy plays a critical role in supporting HSCs and its effect on PGF patients post-allotransplant remain unclear. METHODS: To evaluate whether the autophagy status of ECs modulates their ability to support haematopoiesis, human umbilical vein endothelial cells (HUVECs) and primary BM ECs derived from healthy donors were subjected to knockdown or overexpression of Beclin-1 (an autophagy-related protein). Moreover, BM ECs derived from PGF patients were studied. FINDINGS: Beclin-1 knockdown significantly reduced the haematopoiesis-supporting ability of ECs by suppressing autophagy, which could be restored by activating autophagy via Beclin-1 upregulation. Moreover, autophagy positively regulated haematopoiesis-related genes in HUVECs. Subsequently, a prospective case-control study demonstrated that defective autophagy reduced Beclin-1 expression and the colony-forming unit (CFU) plating efficiency in BM ECs from PGF patients compared to matched patients with good graft function. Rapamycin, an autophagy activator, quantitatively and functionally improved BM ECs from PGF patients in vitro and enhanced their ability to support HSCs by activating the Beclin-1 pathway. INTERPRETATION: Our results suggest that the autophagy status of ECs modulates their ability to support haematopoiesis by regulating the Beclin-1 pathway. Defective autophagy in BM ECs may be involved in the pathogenesis of PGF post-allotransplant. Rapamycin provides a promising therapeutic approach for PGF patients. FUNDING: Please see funding sources.

18.
Aging (Albany NY) ; 122020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32209731

RESUMO

Alzheimer's disease (AD) is associated with the accumulation and deposition of a beta-amyloid (Αß) peptide in the brain, resulting in increased neuroinflammation and synaptic dysfunction. Intranasal delivery of targeted drugs to the brain represents a noninvasive pathway that bypasses the blood-brain barrier and minimizes systemic exposure. The aim of this study was to evaluate the therapeutic effect of intranasally delivered 9-cis retinoic acid (RA) on the neuropathology of an AD mouse model. Herein, we observed dramatically decreased Αß deposition in the brains of amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice (APP/PS1) treated intranasally with 9-cis RA for 4 weeks compared to that in the brains of vehicle-treated mice. Importantly, intranasal delivery of 9-cis RA suppressed Αß-associated astrocyte activation and neuroinflammation and ultimately restored synaptic deficits in APP/PS1 transgenic mice. These results support the critical roles of Αß-associated neuroinflammation responses to synaptic deficits, particularly during the deposition of Αß. Our findings provide strong evidence that intranasally delivered 9-cis RA attenuates neuronal dysfunction in an AD mouse model and is a promising therapeutic strategy for the prevention and treatment of AD.

19.
Nanoscale ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32207754

RESUMO

Photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization has emerged as a versatile and highly-efficient method for the polymerization of more activated monomers including N,N-dimethylacrylamide and methyl acrylate, and less activated monomers including N-vinylpyrrolidone and vinyl acetate, whilst imposing composition, sequence and spatiotemporal regulation. Although significant progress has been achieved in terms of ability to regulate PET-RAFT polymerization through the implementation of myriad environmental cues, it is still a great challenge to introduce multiple external switches within a single catalyst to accomplish logic toggling of controlled radical polymerization (CRP). Herein, we report the synthesis and characterization of Fe3O4@aSiO2@PNMIr Janus nanocomposites coupled with immobilized heteroleptic iridium(iii) complexes for heterogeneous catalysis of PET-RAFT polymerization. With this catalytic nanoarchitecture, we demonstrate multi-stimuli switching of CRPs using three different external physical manipulations: light "ON"/"OFF", magnet "OUT"/"IN" and temperature "LOW"/"HIGH". In addition, these magnetic Janus nanocomposites endowed radical polymerization with various attractive characteristics such as compatibility of myriad monomer formulations including "more activated" and "less activated" monomers, unique oxygen tolerance and ppm-level catalyst dosage. Logic-controlled polymerization with Fe3O4@aSiO2@PNMIr nanocomposites provides a straightforward, robust and user-friendly strategy for realizing multiplexed external switching of polymer propagation using a single nanocatalyst without the involvement of exogenous reagents.

20.
Proc Natl Acad Sci U S A ; 117(11): 6092-6102, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32127472

RESUMO

The KLHL14 gene acquires frequent inactivating mutations in mature B cell malignancies, especially in the MYD88L265P, CD79B mutant (MCD) genetic subtype of diffuse large B cell lymphoma (DLBCL), which relies on B cell receptor (BCR) signaling for survival. However, the pathogenic role of KLHL14 in DLBCL and its molecular function are largely unknown. Here, we report that KLHL14 is in close proximity to the BCR in the endoplasmic reticulum of MCD cell line models and promotes the turnover of immature glycoforms of BCR subunits, reducing total cellular BCR levels. Loss of KLHL14 confers relative resistance to the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and promotes assembly of the MYD88-TLR9-BCR (My-T-BCR) supercomplex, which initiates prosurvival NF-κB activation. Consequently, KLHL14 inactivation allows MCD cells to maintain NF-κB signaling in the presence of ibrutinib. These findings reinforce the central role of My-T-BCR-dependent NF-κB signaling in MCD DLBCL and suggest that the genetic status of KLHL14 should be considered in clinical trials testing inhibitors of BTK and BCR signaling mediators in DLBCL.

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