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1.
Sci China Life Sci ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33481164

RESUMO

Kidney is a major target organ in both antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). The etiology of antiphospholipid syndrome nephropathy associated lupus nephritis (APSN-LN) is intricate and remains largely unrevealed. We proposed in present work, that generation of antiphospholipid antibodies (aPLs), especially those directed towards the oxidized neoepitopes, are largely linked with the redox status along with disease progression. Moreover, we observed that compromised antioxidative capacity coincided with turbulence of inflammatory cytokine profile in the kidney of male NZW×BXSB F1 mice suffered from APSN-LN. SM934 is an artemisinin derivative that has been proved to have potent immunosuppressive properties. In current study, we elaborated the therapeutic benefits of SM934 in male NZW×BXSB F1 mice, a murine model develops syndrome resembled human APS associated with SLE, for the first time. SM934 treatment comprehensively impeded autoantibodies production, inflammatory cytokine accumulation and excessive oxidative stress in kidney. Among others, we interpreted in present work that both anti-inflammatory and antioxidative effects of SM934 is closely correlated with the enhancement of Nrf2 signaling and expression of its targets. Collectively, our finding confirmed that therapeutic strategy simultaneously exerting antioxidant and anti-inflammatory efficacy provide a novel feasible remedy for treating APSN-LN.

2.
Nat Commun ; 12(1): 523, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483518

RESUMO

The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O2 by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O2 nanoeconomizer pHPFON-NO/O2 to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O2 interacts with the acidic tumor microenvironment to release NO for endogenous O2 conservation; second, it releases O2 in response to mild photothermal effect to enable exogenous O2 infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This "reducing expenditure of O2 and broadening sources" strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.

3.
Mol Cell Biol ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468559

RESUMO

Susceptibility to breast cancer is significantly increased in individuals with germ line mutations in RECQ1, a gene encoding a DNA helicase essential for genome maintenance. We previously reported that RECQ1 expression predicts clinical outcomes for sporadic breast cancer patients stratified by estrogen receptor (ER) status. Here, we utilized an unbiased integrative genomics approach to delineate a cross talk between RECQ1 and ERα, a known master regulatory transcription factor in breast cancer. We found that expression of ESR1, the gene encoding ERα, is directly activated by RECQ1. More than 35% of RECQ1 binding sites were co-bound by ERα genome-wide. Mechanistically, RECQ1 cooperates with FOXA1, the pioneer transcription factor for ERα, to enhance chromatin accessibility at the ESR1-regulatory regions in a helicase activity-dependent manner. In clinical ERα-positive breast cancers treated with endocrine therapy, high RECQ1 and high FOXA1 co-expressing tumors were associated with better survival. Collectively, these results identify RECQ1 as a novel cofactor for ERα and uncover a previously unknown mechanism by which RECQ1 regulates disease-driving gene expression in ER-positive breast cancer cells.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33421578

RESUMO

OBJECTIVES: Diagnostic delay of tuberculosis (TB) is an important but underappreciated problem. Our study aimed to analyse the patient pathway and possible risk factors of the long diagnostic delay (LDD). METHODS: We enrolled 400 new bacteriologically diagnosed patients with pulmonary TB from 20 hospitals across China. LDD was defined as the interval between the initial-care-visit and the diagnosis confirmation exceeding 14 days. Its potential risk factors were investigated by multivariate logistic regression and multilevel logistic regression. Hospitals in China were classified by increasing size, from level 0 to 3. TB laboratory equipment in hospitals were also evaluated. RESULTS: The median diagnostic delay was 20 days (IQR: 7-72 days), and 229 of 400 patients (57.3%, 95% CI 52.4-62.1) had LDD. Fifteen percent of participants were diagnosed at the initial-care-visit. Compared to level 0 facilities, choosing level 2 (OR 0.27, 95% CI 0.12-0.62, p = 0.002) and level 3 facilities (OR 0.34, 95% CI 0.14-0.84, p = 0.019) for the initial-care-visit was independently associated with less LDD. Equipping with smear, culture, and Xpert at intial-care-visit simultaneously also helped avoiding LDD. (OR 0.28, 95% CI 0.09-0.82, p = 0.020). The multilevel logistic regression yielded similar results. Availability of smear, culture, and Xpert was lower in level 0-1 facilities than in level 2-3 facilities (p<0.001, respectively). CONCLUSIONS: Most patients failed to be diagnosed at the initial-care-visit. Patients who went to low-level facilities initially had a higher risk of LDD. Improving TB laboratory equipment especially at low-level facilities is urgently needed.

5.
Cancer Cell Int ; 21(1): 55, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451320

RESUMO

BACKGROUND: Resistance to drug therapy is a major impediment for successful treatment of patients suffering from breast cancer (BC). Tamoxifen (TAM) is an extensively used therapeutic agent, which substantially reduces the risk of recurrence and associated mortality in BC. This study demonstrated that exosomal transfer of microRNA-9-5p (miR-9-5p) enhanced the resistance of MCF-7 cells to TAM. METHODS: Initially, BC-related differentially expressed genes (DEGs) and their upstream regulatory miRNAs were identified. The TAM-resistant MCF-7 (MCF-7/TAM) cell line and the non-medicated sensitive MCF-7 cell line were formulated, followed by isolation of the exosomes. Next, the apoptosis rate of exosome-treated MCF-7 cells was determined after co-culture with TAM. The interaction between miR-9-5p and ADIPOQ was identified by a combination of bioinformatic analysis and luciferase activity assay. In order to validate the effect of miR-9-5p and ADIPOQ on TAM resistance in the MCF-7 cells in vitro and in vivo, miR-9-5p was delivered into the exosomes. ADIPOQ and miR-9-5p were identified as the BC-related DEG and upstream regulatory miRNA. RESULTS: Exosomes derived from the MCF-7/TAM cells could increase the resistance of MCF-7 cells to TAM. Notably, miR-9-5p altered the sensitivity of BC cells to TAM. In addition, ADIPOQ was negatively regulated by miR-9-5p. Furthermore, MCF-7/TAM cell-derived miR-9-5p inhibited the apoptosis of MCF-7 cells, and promoted the cell resistance to TAM. In vivo experiments in nude mice ascertained that the tumor injected with exosomal miR-9-5p showed improved resistance to TAM. CONCLUSIONS: Exosomal transfer of miR-9-5p augmented the drug resistance of BC cells to TAM by down-regulating ADIPOQ, suggesting its functionality as a candidate molecular target for the management of BC.

6.
Cell Rep ; 34(1): 108576, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406428

RESUMO

Type 2 diabetes mellitus (T2DM) is recognized as a chronic, low-grade inflammatory disease characterized by insulin resistance and pancreatic ß cell dysfunction; however, the underlying molecular mechanism remains unclear. Here, we report a key ß cell-macrophage crosstalk pathway mediated by the miRNA-29-TNF-receptor-associated factor 3 (TRAF3) axis. ß cell-specific transgenic miR-29a/b/c mice are predisposed to develop glucose intolerance and insulin resistance when fed a high-fat diet (HFD). The metabolic effect of ß cell miR-29 is largely mediated through macrophages because either depletion of macrophages or reconstitution with miR-29-signaling defective bone marrow improves metabolic parameters in the transgenic mice. Mechanistically, our data show that miR-29 promotes the recruitment and activation of circulating monocytes and macrophages and, hence, inflammation, via miR-29 exosomes in a TRAF3-dependent manner. Our results demonstrate the ability of ß cells to modulate the systemic inflammatory tone and glucose homeostasis via miR-29 in response to nutrient overload.

7.
Curr Med Imaging ; 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33397242

RESUMO

INTRODUCTION: Epithelioid sarcoma (ES) is a rare histopathological type of soft tissue sarcoma. They are subcutaneous soft tissue masses that tend to arise in extremity sites (the classic type, formerly referred to as distal type) or proximal midline region of the body (the proximal type), such as the perineum, genital tract, and pelvis. The head and neck regions are rarely affected by ES, but the infratemporal fossa (ITF) is extremely rare. ES involving the ITF has not been reported before in literature. In this paper, the imaging features of ES were reviewed in detail, and the anatomical structure and epidemiology of ITF were briefly introduced. SOURCES: We performed a systematic search from 3 databases, CNKI(China National Knowledge Internet), FMRS(Foreign Medical Literature Retrieval Service, Shenzhen METSTR Technology CO., Led. China), and PubMed, to obtain literature from January 1970 to July 2020. Epithelioid sarcoma, head and neck regions, infratemporal fossa, diagnostic imaging, anatomy, MRI, and CT were used as keywords for advanced retrieval. A study had to be found eligible for inclusion to be closely related to ES and/or ITF. A total of 129 related pieces of literature were retrieved successfully, of which 37 were closely related to this study. The case report in this article is from the Affiliated Hospital of North Sichuan Medical College. The present study was approved by the institutional review board of the Affiliated Hospital of North Sichuan Medical College and a written informed consent for the publication of the case was obtained from the patient. CASE PRESENTATION: A 33-year-old man accidentally found a slowly growing, painless mass in the left cheek more than a month ago. On plain computed tomography (CT) scan of the outpatient department, an oval slightly low-density mass with well-defined and uniform boundary in the infratemporal fossa was revealed, and on the contrast-enhanced scan, it was homogeneous and moderately enhanced. Initially, the CT appearance favored benign lesions. However, the possibility of a malignant tumor can not be excluded completely. Finally, the patient was referred to the inpatient department a tumor arose from IF and underwent a selective operation. The tumor was completely removed. Histologic findings were compatible with epithelioid sarcoma. Post-operatively, the patient received 2 cycles of radiotherapy, and there was no evidence of recurrence after 6 months follow-up. CONCLUSION: The imaging manifestations of ES are various. The anatomic structure of ITF is complex and the pathological types are various. It should be very careful in the qualitative diagnosis of tumors from the ITF, and advanced imaging techniques will be useful in imaging diagnosis.

8.
Bioresour Technol ; 324: 124651, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33422692

RESUMO

Traditional surfactants have been reported to enhance enzymatic saccharification of lignocellulose, however, it is important to transfer these findings to a system that uses a high-efficiency and low-toxicity natural surfactant instead. In this work, a novel hybrid method involving use of the natural surfactant (humic acid, HA) during mild acid (H2SO4) pretreatment was developed for waste wheat straw (WWS) biorefinery. The HA was found to help remove lignin up to 40.6%, and hemicellulose up to 96.2%. As a result of these changes, the enzymatic hydrolysis efficiency reached as high as 92.9%. The success of enzymatic digestion was partly attributed to the improved accessibility of cellulose to cellulase and changes in lignocellulose structures. We anticipate that these findings will be used to further evaluate HA as a beneficial surfactant in biorefinery pretreatment processes, and perhaps spur others to identify other natural surfactants that may prove even more effective.

9.
Int Immunopharmacol ; 91: 107334, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412493

RESUMO

Psoriasis is the most prevalent inflammatory skin disorders, affecting 1-3% of the worldwide population. We previously reported that topical application of methyl 4-(adenin-9-yl)-2-hydroxybutanoate (DZ2002), a reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, was a viable treatment in murine psoriatic skin inflammation. In current study, we further explored the mechanisms of DZ2002 on keratinocyte dysfunction and skin infiltration, the key pathogenic events in psoriasis. We conducted genome-wide DNA methylation analysis in skin tissue from imiquimod (IMQ)-induced psoriatic and normal mice, demonstrated that topical administration of DZ2002 directly rectified aberrant DNA methylation pattern in epidermis and dermis of psoriatic skin lesion. Especially, DZ2002 differentially regulated DNA methylation of GATA3 and LCN2 promoters, which maintained keratinocytes differentiation and reduced inflammatory infiltration in psoriatic skin respectively. In vitro studies in TNF-α/IFN-γ-elicited HaCaT manifested that DZ2002 treatment rectified compromised keratinocyte differentiation via GATA3 enhancement and abated chemokine expression by reducing LCN2 production under inflammatory stimulation. Chemotaxis assays conducted on dHL-60 cells confirmed that suppression of LCN2 expression by DZ2002 was accompanied by CXCR1 and CXCR2 downregulation, and contributed to the inhibition of CXCL8-driven neutrophils migration. In conclusion, therapeutic benefits of DZ2002 are achieved through differentially regulating DNA methylation of GATA3 and LCN2 promoters in psoriatic skin lesion, which efficiently interrupt the pathogenic interplay between keratinocytes and infiltrating immune cells, thus maintains epidermal keratinocytes differentiation and prevents dermal immune infiltration in psoriatic skin.

10.
Chemosphere ; 263: 127991, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32854012

RESUMO

Comprehensive observations have been carried out in Beijing to investigate the impact of the Clean Air Action implemented in 2013 on changes in aerosol chemistry characteristics in heating seasons of 2016-2017 and 2017-2018. Results showed that PM2.5, SO2, NO2, NH3, O3 and CO concentrations decreased by 40.9%, 46.0%, 29.0%, 40.6%, 11.0% and 44.4%, respectively. Significant decreases were also observed for NO3- (32.5%), SO42- (52.9%), NH4+ (56.0%), Cl- (64.6%) and K+ (68.2%), on average. Enhanced PM2.5 pollution has changed from sulfate-driven to nitrate-driven. The decrease in SO2 was more significant than NO2 as a response to one reason of the larger decrease in SO42- concentration. The formation of sulfate was dominated by heterogeneous reactions in two heating seasons. Low pH could facilitate more efficient conversion of SO2 to sulfate. Photochemical reactions played a much more important role in the formation of nitrate in the second heating season, especially in the daytime. The major source regions for sulfate and nitrate were identified by back trajectories and the potential source function (PSCF). More nitrate was brought into Beijing when air masses coming from polluted regions in the southwest prevailed in 2017-2018 heating season. Thus, regional joint prevention and control are of great importance in the achievement of an effective reduction in PM2.5 pollution in the future.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Material Particulado/análise , Aerossóis/análise , Ar , Poluição do Ar/análise , Pequim , China , Poluição Ambiental , Calefação , Nitratos/análise , Estações do Ano , Sulfatos/análise
11.
J Ethnopharmacol ; 265: 113345, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32890713

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Periploca sepium Bunge (P. sepium) is used in traditional Chinese medicine (TCM) for the treatment of autoimmune diseases, particularly rheumatoid arthritis. Periploca sepium periplosides (PePs), isolated from the root bark of P. sepium, characterized as the cardiac glycosides-free pregnane glycosides fraction, is expected to possess therapeutic potential on inflammatory arthritis. AIM OF THE STUDY: The current study is designed to evaluate the anti-nociceptive, anti-inflammatory and anti-arthritic activities effects of the PePs. MATERIALS AND METHODS: The anti-nociceptive activity of PePs was examined in the writhing test and hot-plate test in mice. The anti-inflammatory activity of PePs was determined by the 2, 4-dinitro-1-fluorobenzene (DNFB)-induced ear edema model and the carrageenan induced paw edema model in mice. The anti-arthritic activity of PePs was investigated by evaluating the joint inflammation and arthritis pathology in rat adjuvant induced arthritis (AIA) and murine collagen induced arthritis (CIA). Phytohaemagglutinin M (PHA-M) -elicited human peripheral blood mononuclear cells (PBMCs) were further applied to assess the suppressive activity of PePs on IFN-γ and IL-17 production. RESULTS: PePs treatment markedly decreased the acetic acid-induced visceral nociceptive response and increased the hot-plate pain threshold. Further, oral administration of PePs exhibited anti-inflammatory activity by decreasing DNFB-induced ear edema in mice and carrageenan-induced paw edema in rats. Moreover, oral treatment of PePs ameliorated joint swelling and attenuated bone erosion in rodent arthritis, and the therapeutic benefits were partially attributed to the suppression of proinflammatory cytokines such IFN-γ and IL-17. Moreover, PePs suppressed the proliferation as well as IFN-γ and IL-17 secretion in PHA-M-elicited human PBMCs in a concentration dependent manner. CONCLUSIONS: Taken together, our results justified the traditional use of Periploca sepium Bunge for the treatment of diseases associated with inflammation and pain.

12.
Sci Total Environ ; 761: 144182, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33360547

RESUMO

Industrialization and urbanization are expected to increase the release of silver nanoparticles (AgNPs) into aquatic ecosystems. However, it remains to be determined how AgNPs influence nitrogen transformation and the underlying mechanism in natural water bodies. Here, the impact of AgNPs on nitrogen cycling in water-sediment system of a hypereutrophic lake was studied and the mechanism of nitrogen transformation was investigated in terms of the nitrogen functional enzymes and genes. Following 7 days of water-sediment microcosm experiments, the levels of total nitroten (TN) and organic nitrogen (OrgN) were significantly increased by 50 mg/L Ag+ treatment when compared with the non-Ag control (P < 0.05). In contrast, the levels of TN and Org-N were both slightly decreased by AgNPs treatments (0.5 and 50 mg/L). Additionally, the levels of NO3--N were evidently reduced with the presence of AgNPs (P < 0.05). Further, our data proved that enzymes and those enzyme encoding genes involved in the nitrogen transformation may directly responsible for the alterations of nitrogen transformation. Overall, our work suggested that the short-term exposure to AgNPs might cause hormetic effects on nitrogen-transforming microorganisms in hypereutrophic lakes, and have a potential to result in non-negligible changes in the nitrogen cycling of hypereutrophic lakes.


Assuntos
Nanopartículas Metálicas , Poluentes Químicos da Água , Ecossistema , Lagos , Nanopartículas Metálicas/toxicidade , Nitrogênio/análise , Prata/análise , Prata/toxicidade , Água , Poluentes Químicos da Água/toxicidade
13.
Materials (Basel) ; 13(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255465

RESUMO

Water-foamed asphalt is capable of improving the workability of asphalt mixture. It has been extensively used for its energy-saving and emission-reducing features. Water plays an essential part in improving the workability of water-foamed asphalt mixture. However, there is still lack in profound studies of moisture dissipation of the water-foamed asphalt over time and its influence on workability. In this study, the evolutions of residual water content and rotational viscosity of the water-foamed asphalt with time were respectively measured by the analytical balance and modified rotational viscometer (RV). The atomic force microscopy (AFM) analysis was conducted to discuss the mechanism of viscosity reduction of water-foamed asphalt. The results showed that moisture evaporation is significantly influenced by the foaming water content and ambient temperature, which results in the different stabilizing time of water-foamed asphalt. When water-foamed asphalt was stabilized, the residual water inside the asphalt was less than 0.01% relative to the asphalt mass. The AFM analysis showed that the foaming process changed the distribution of wax in the water-foamed asphalt resulting in reduction of viscosity. The viscosity reduction of asphalt is highly related to the initial foaming water content. After the foaming process, the viscosity keeps stable and is independent of moisture dissipation.

14.
Front Med (Lausanne) ; 7: 575439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282889

RESUMO

Background: Severe acute respiratory syndrome (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), has become a global pandemic in the past months. An overall defined treatment has not yet been established. Therefore, it is important to summarize and report treatment experiences and identify patient groups that have a significantly higher risk of an adverse clinical outcome. Methods: Two hundred thirty-nine COVID-19 patients were recruited from January 25 to February 15, 2020. Demographic, clinical, laboratory, treatment management, and outcome data obtained from patients' medical records were evaluated. Results: Patients who recovered from PCR positive to negative within 2 weeks had significantly lower erythrocyte sedimentation rate (ESR) and higher C-reactive protein (CRP) levels than those recovered post 2 weeks. During antiviral treatment, COVID-19 patients with older age, comorbidities, and corticosteroid treatment required a significantly longer time to turn from PCR positive to negative COVID-19 result. Conclusion: PCR tests are of great importance to evaluate the recovery of COVID-19-positive patients, and ESR could be an indirect indicator to monitor SARS-COV-2 activity. Furthermore, our data suggest that older age, the existence of comorbidities, and corticosteroid treatment of COVID-19 patients during antiviral treatment could prolong the duration of conversion from SARS-COV-2 positive to negative.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33337357

RESUMO

OBJECTIVE: To investigate the diagnostic value of core-needle biopsy (CNB) guided by contrast-enhanced ultrasound (CEUS) in cervical tuberculous lymphadenitis (CTL). METHODS: 178 patients with pathological confirmation of CTL were retrospectively enrolled. All of them had undergone CNB prior to the final surgery. According to the different ways of puncture guidance, they were divided into two groups: conventional ultrasound (US) group (n = 81) and CEUS group (n = 97). The comparison of diagnostic efficacy between two groups was compared and analyzed. RESULTS: Among the 178 patients, 146 were directly diagnosed as CTL by CNB, including 59 patients in CEUS group and 87 patients in US group. The diagnostic accuracy were 89.7% (87/97) and 72.8% (59/81), respectively (P <  0.01). For subgroup analyses, differences among diagnostic efficacy ascribed to the different guiding methods were significant in medium size group (>2.0 cm and ≤3.0 cm) and large size group (>3.0 cm), 91.7% for CEUS group vs. 69.0% for US group (P <  0.05) and 84.4% for CEUS group vs. 57.7% for US group (P <  0.05), respectively. CONCLUSIONS: In the diagnosis of CTL, compared with the US-guided CNB, CEUS-guided CNB have certain advantages, especially for larger lymph nodes.

17.
JAMA Psychiatry ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33263727

RESUMO

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

18.
Ann Palliat Med ; 9(6): 3966-3975, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33302659

RESUMO

BACKGROUND: Venous thromboembolism (VTE) is a serious health problem for which pharmacological prophylaxis has been proven to be effective. However, there are significant gaps between the guidelines and clinical practice. This study is to evaluate the effect of physician educational intervention (PEI) on VTE pharmacological prophylaxis in medical inpatients from the respiratory department. METHODS: Medical inpatients from the respiratory department between February 2014 and December 2016 were recruited in this retrospective cohort study. They were assigned to the PEI group or the control group according to whether their physicians undertook a quality improvement (QI) project carried out in hospital to raise physician awareness of pharmacological thromboprophylaxis by educational intervention. Any and appropriate pharmacological VTE prophylaxis rates, the use of appropriate anticoagulants, and the occurrence of VTE events in the two groups were calculated and compared using a chi-square test and continuity correction. Poisson regression analysis was used to evaluate the relative risk (RR) of PEI on the occurrence of VTE events. RESULTS: The any pharmacological VTE prophylaxis rate (11.3% vs. 5.9%, P=0.048) and appropriate pharmacological VTE prophylaxis rate (9.3% vs. 5.5%, P=0.036) in high-risk patients without high major bleeding risk were both significantly higher than the control group. Compared with the control group, appropriate anticoagulants in the PEI group took up a larger proportion of all used anticoagulants (90.3% vs. 78.7%, P=0.007). In anticoagulants used for high-risk patients without high major bleeding, appropriate anticoagulants show no statistical difference between the two groups (93.8% vs. 77.8%, P=0.153). There was no difference in the occurrence of VTE events between the two study groups in overall patients (0.5% vs. 0.6%, P=0.913), and among those with high VTE risk (1.7% vs. 1.0%, P=0.554). PEI had no association with the probability of VTE event occurrence (RR, 1.246; 95% CI, 0.478-2.188, P=0.954). CONCLUSIONS: Educational intervention effectively increased physician awareness of VTE prophylaxis in the respiratory department. Further interventions are still necessary since the guidelines were implemented to a relatively low degree.

19.
J Infect Dev Ctries ; 14(11): 1264-1273, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33296339

RESUMO

INTRODUCTION: To date, the relationship between the causative pathogens and the changes of hematological parameters was rarely referred and deserves further investigation. METHODOLOGY: A total of 825 adult patients, including 134 negative blood cultures patients and 691 bloodstream infection (BSI) patients, were screened for eligibility in this study. Receiver operating characteristic curves and binary logistic regression models were used to assess the power of hematological parameters to distinguish patients with BSI caused by different pathogens. RESULTS: Except for platelet-to-lymphocyte ratio (PLR) and platelet larger cell count (P-LCC), the other hematological parameters investigated in the study were significantly different in patients with BSI caused by different pathogens, including Candida. The specific combinations of lymphocyte count (LYM), platelet count (PLT), neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), MPV-to-PLT ratio (MPV/PLT), platelet larger cell ratio (P-LCR), and C-reactive protein (CRP) can improve the ability to distinguish various BSI from negative blood cultures. The highest area under the curve of was 0.753 (95% CI 0.709-0.797) for positive blood cultures, 0.715 (95% CI 0.658-0.771) for Gram-positive pathogens BSI, 0.777 (95% CI 0.730-0.824) for Gram-negative pathogens BSI, 0.797 (95% CI 0.747-0.846) for Escherichia coli BSI, 0.943 (95% CI 0.899-0.987) for Enterobacter aerogenes BSI, 0.830 (95% CI 0.740-0.921) for Pseudomonas aeruginosa BSI, and 0.767 (95% CI 0.695-0.839) for Staphylococcus aureus BSI. CONCLUSIONS: The specific combinations of hematological parameters can improve the power to distinguish patients with BSI caused by different pathogens. Attention to these parameters can be easily integrated into daily medical activities, without extra costs.

20.
J Org Chem ; 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33290070

RESUMO

A novel diterpenoid, sinueretone A (1), featuring an unprecedented tricyclo[12.1.0.05,9]pentadecane carbon framework, along with two new (2 and 3) and one known (4) casbane diterpenoids were isolated from the South China Sea soft coral Sinularia erecta. The structures of the new compounds, especially their absolute stereochemistry, were established by extensive spectroscopic analysis, various quantum chemical calculations, and/or X-ray diffraction analyses. A plausible biogenetic relationship of 1-4 was proposed, which gave an insight for future biomimetic synthesis of the novel compounds. In a bioassay, compounds 1 and 2 displayed interesting anti-inflammatory activity by the inhibition of lipopolysaccharide-induced tumor necrosis factor-α protein release.

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