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1.
Magn Reson Med ; 87(1): 302-311, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34617626

RESUMO

PURPOSE: Previous cardiac imaging studies using hyperpolarized (HP) [1-13 C]pyruvate were acquired at end-diastole (ED). Little is known about the interaction between cardiac cycle and metabolite content in the myocardium. In this study, we compared images of HP pyruvate and products at end-systole (ES) and ED. METHODS: A dual-phase 13 C MRI sequence was implemented to acquire two sequential HP images within a single cardiac cycle at ES and ED during successive R-R intervals in an interleaved manner. Each healthy volunteer (N = 3) received two injections of HP [1-13 C]pyruvate for the dual-phase imaging on the short-axis and the vertical long-axis planes. Spatial distribution of HP 13 C metabolites at each cardiac phase was correlated to multiphase 1 H MRI to confirm the mechanical changes. Ratios of myocardial HP metabolites were compared between ES and ED. Segmental analysis was performed on the midcavity short-axis plane. RESULTS: In addition to mechanical changes, metabolic profiles of the heart detected by HP [1-13 C]pyruvate differed between ES and ED. The myocardial signal of [13 C]bicarbonate relative to [1-13 C]lactate was significantly smaller at ED than the ratio at ES (p < .05), particularly in mid-anterior and mid-inferoseptal segments. The distinct metabolic profiles in the myocardium likely reflect the technical aspects of the imaging approach such as the coronary flow in addition to the cyclical changes in metabolism. CONCLUSION: The study demonstrates that metabolic profiles of the heart, measured by HP [1-13 C]pyruvate, are affected by the cardiac cycle in which that the data are acquired.

2.
Chin J Integr Med ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731433

RESUMO

Due to its complex pathogenesis and lack of effective therapeutic methods, Alzheimer's disease (AD) has become a severe public health problem worldwide. Recent studies have discovered the function of central nervous system lymphatic drainage, which provides a new strategy for the treatment of AD. Chinese herbal medicine (CHM) has been considered as a cure for AD for hundreds of years in China, and its effect on scavenging ß-amyloid protein in the brain of AD patients has been confirmed. In this review, the mechanism of central nervous system lymphatic drainage and the regulatory functions of CHM on correlation factors were briefly summarized. The advances in our understanding regarding the treatment of AD via regulating the central lymphatic system with CHM will promote the clinical application of CHM in AD patients and the discovery of new therapeutic drugs.

4.
Eur J Med Chem ; : 113998, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34839997

RESUMO

Development of small molecule PD-1/PD-L1 inhibitors as a novel immunotherapy strategy exhibits great promise. Herein, a novel series of quinazoline derivatives were designed, synthesized and their inhibitory activity against the PD-1/PD-L1 interaction was evaluated through a homogenous time-resolved fluorescence (HTRF) assay. Among them, the compound 39 exhibited the most potent inhibitory activity with an IC50 value of 1.57 nM. Furthermore, the cellular level assays revealed that 39 could inhibit the PD-1/PD-L1 interaction and restore T-cell function, and showed low toxicity on the PBMCs. In addition, the structure-activity relationships (SARs) of the novel quinazoline derivatives were explored and the binding mode of 39 with dimeric PD-L1 was analyzed by molecular docking. This work demonstrates that incorporation of pyrimidine group between the 2 and 3-positions of the biphenyl structure is an effective strategy for designing novel and more potent small molecule PD-1/PD-L1 inhibitors, and 39 can be regarded as a promising lead compound for further investigation.

5.
Transl Androl Urol ; 10(9): 3620-3627, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34733657

RESUMO

Background: To investigate the significance of simultaneous urography of the upper and lower urinary tract of transplanted kidneys combined with computed tomography urography (CTU), computed tomography arteriography (CTA), and computed tomography venography imaging in the planning of open surgery performed to treat any ureteral complications of a transplanted kidney. Methods: In all, 24 patients with ureteral complications after renal transplantation were admitted, 12 of whom had renal graft ostomy during open surgery. Simultaneous antegrade urography of the upper urinary tract and retrograde cystography of the transplanted kidneys were performed on the patients. With the use of computed tomography imaging results, surgical planning was carried out. Results: All surgeries were successfully completed according to preoperative planning. Three patients underwent end-to-end anastomosis of the ureter and bladder muscle flap, 8 patients underwent ureterocystostomy, and 1 patient underwent an end-to-end ureteral anastomosis. After the follow-up up to now, all the patients had stable renal function, and no complications such as ureteral stenosis or urine leakage have thus far reoccurred in the transplanted kidneys. Conclusions: When open surgery is required to treat any ureteral complications following renal transplantation, preoperative multiangle imaging can be used to better understand the condition of the transplanted urinary tract and thus aid considerably in surgical planning.

6.
Magn Reson Med ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34687086

RESUMO

PURPOSE: This study is to investigate time-resolved 13 C MR spectroscopy (MRS) as an alternative to imaging for assessing pyruvate metabolism using hyperpolarized (HP) [1-13 C]pyruvate in the human brain. METHODS: Time-resolved 13 C spectra were acquired from four axial brain slices of healthy human participants (n = 4) after a bolus injection of HP [1-13 C]pyruvate. 13 C MRS with low flip-angle excitations and a multichannel 13 C/1 H dual-frequency radiofrequency (RF) coil were exploited for reliable and unperturbed assessment of HP pyruvate metabolism. Slice-wise areas under the curve (AUCs) of 13 C-metabolites were measured and kinetic analysis was performed to estimate the production rates of lactate and HCO 3 - . Linear regression analysis between brain volumes and HP signals was performed. Region-focused pyruvate metabolism was estimated using coil-wise 13 C reconstruction. Reproducibility of HP pyruvate exams was presented by performing two consecutive injections with a 45-minutes interval. RESULTS: [1-13 C]Lactate relative to the total 13 C signal (tC) was 0.21-0.24 in all slices. [13 C] HCO 3 - /tC was 0.065-0.091. Apparent conversion rate constants from pyruvate to lactate and HCO 3 - were calculated as 0.014-0.018 s-1 and 0.0043-0.0056 s-1 , respectively. Pyruvate/tC and lactate/tC were in moderate linear relationships with fractional gray matter volume within each slice. White matter presented poor linear regression fit with HP signals, and moderate correlations of the fractional cerebrospinal fluid volume with pyruvate/tC and lactate/tC were measured. Measured HP signals were comparable between two consecutive exams with HP [1-13 C]pyruvate. CONCLUSIONS: Dynamic MRS in combination with multichannel RF coils is an affordable and reliable alternative to imaging methods in investigating cerebral metabolism using HP [1-13 C]pyruvate.

7.
Adv Sci (Weinh) ; 8(21): e2101936, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34605226

RESUMO

The neurokinin-1 receptor (NK-1R) antagonists are approved as treatment for chemotherapy-associated nausea and vomiting in cancer patients. The emerging role of the substance P-NK-1R system in oncogenesis raises the possibility of repurposing well-tolerated NK-1R antagonists for cancer treatment. This study reports that human colorectal cancer (CRC) patients with high NK-1R expression have poor survival, and NK-1R antagonists SR140333 and aprepitant induce apoptotic cell death in CRC cells and inhibit CRC xenograft growth. This cytotoxicity induced by treatment with NK-1R antagonists is mediated by induction of endoplasmic reticulum (ER) stress. ER stress triggers calcium release, resulting in the suppression of prosurvival extracellular signal-regulated kinase (ERK)-c-Myc signaling. Along with ER calcium release, one ER stress pathway mediated by protein kinase RNA-like ER kinase (PERK) is specifically activated, leading to increased expression of proapoptotic C/EBP-homologous protein (CHOP). Moreover, NK-1R antagonists enhance the efficacy of chemotherapy by increasing the sensitivity and overcoming resistance to 5-fluorouracil in CRC cells through the induction of sustained ER stress and the consequent suppression of ERK-c-Myc signaling both in vitro and in vivo. Collectively, the findings provide novel mechanistic insights into the efficacy of NK-1R antagonists either as a single agent or in combination with chemotherapy for cancer treatment.

8.
Adv Mater ; : e2106822, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34676930

RESUMO

In recent years, two-dimensional Ruddlesden-Popper (2DRP) perovskite materials have been explored as emerging semiconductor materials in solar cells owing to their excellent stability and structural diversity. Although 2DRP perovskites have achieved photovoltaic efficiencies exceeding 19%, their widespread use is hindered by their inferior charge-carrier transport properties in the presence of diverse organic spacer cations, compared to that of traditional 3D perovskites. Hence, a systematic understanding of the 2D perovskite's carrier transport mechanism is critical for the development of high-performance 2D perovskite solar cells (PSCs). In this review, we summarize the recent advances in the carrier behavior of 2DRP PSCs and provide guidelines for successfully enhancing carrier transport. First, we discuss the composition and crystal structure of 2DRP perovskite materials that affect carrier transport. Then, we evaluate the features of 2DRP perovskite films (phase separation, grain orientation, crystallinity kinetics, etc.), which are closely related to carrier transport. Next, we reveal the principal direction of carrier transport guiding the selection of the transport layer. Finally, we propose an outlook and rationalize strategies for enhancing carrier transport in high-performance PSCs. This article is protected by copyright. All rights reserved.

9.
Ren Fail ; 43(1): 1266-1275, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34493167

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs)-based therapy has shown promising results for renal injury. In this study, the efficacy and safety of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in treating nonspecific interstitial fibrosis and tubular atrophy (IFTA) were evaluated. METHODS: From March 2011 to January 2013, 11 renal transplanted patients with IFTA were recruited. At baseline, patients were given one intra-arterial infusion of BM-MSCs; 7 days and 1 month later, another two intravenous infusions of cells were followed. Serum creatinine, creatinine clearance rate, and serum cystatin-C at baseline and 7 days, 1 month, 3 months, 6 months, and 12 months after the intra-arterial infusion of BM-MSCs were used to assess renal function. At baseline and 6 months, histological examination based on hematoxylin-eosin, Masson's trichrome and periodic acid-Schiff staining and immunohistochemistry for transforming growth factor ß1 (TGF-ß1) and connective tissue growth factor (CTGF) was performed. Adverse events were recorded to evaluate the safety of BM-MSCs treatment. RESULTS: At 12 months, the renal function of 6 patients (54.5%) was improved, 3 (27.3%) were stable and 2 (18.2%) were worsened. At 6 months, the mean IFTA scores of all participators were similar with the baseline (1.73 ± 0.41 vs.1.50 ± 0.0.77, p = 0.242); however, it was significantly decreased when only 6 patients with improved renal function were analyzed (1.67 ± 0.41 vs. 1.08 ± 0.20, p = 0.013). Besides, decreased expression of TGF-ß1 and CTGF were also observed at 6 months. During 1 year follow-up period, only two minor complications including infection and allergy were observed. CONCLUSION: Our results demonstrated that autologous BM-MSCs are safe and beneficial for IFTA patients. Abbreviations: MSCs: mesenchymal stem cells; BM-MSCs: marrow-derived mesenchymal stem cells; IFTA: interstitial fibrosis and tubular atrophy; CAN: chronic allograft nephropathy; CNIs: calcineurin inhibitors; Scr: serum creatinine; CCr: creatinine clearance rate; Cys-C: cystatin-C; TGF-ß1: transforming growth factor ß1; CTGF: connective tissue growth factor.

10.
Zhen Ci Yan Jiu ; 46(9): 769-74, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34558243

RESUMO

OBJECTIVE: To observe the effect of moxibustion at myofascial trigger points on microglia activation and the expression of brain-derived neurotrophic factor (BDNF) in the spinal cord of rats with myofascial pain syndrome (MPS), so as to explore the central mechanism of the analgesic effect of moxibustion. METHODS: Twenty-four male SD rats were randomly divi-ded into control, model and moxibustion groups (n=8 in each group). The MPS model was established by strinking on fascia musculares and eccentric exercise. Rats in the moxibustion group were treated with mild moxibustion at myofascial trigger point for 15 min, once daily for 7 days. The thermal withdrawal latency (TWL) of rats was measured with a hot stabbing instrument. The pathological changes of the rat medial femoris muscle were observed after H.E. staining. The expressions of microglia marker (OX-42) and BDNF in the spinal dorsal horn were detected by immunohistochemistry and Western blot, separately. RESULTS: After modeling, the TWL of both the model and the moxibustion groups were significantly down-regulated (P<0.01),and were significantly decreased in contrast to that of the control group (P<0.01). After treatment and compared with the model group, the TWL of the moxibustion group was significantly increased (P<0.01) in the moxibustion group. Rat's muscle fibers of the control group were uniform in thickness and arranged tightly and regularly. While in the model group, some fractures and connective structure tissue renewal, irregular arrangement, and inflammatory cell infiltration were seen. The morphology of muscle fibers in the moxibustion group was close to normal, and the arrangement was neat and orderly, with a small amount of inflammatory cell infiltration. Compared with the control group, the expression of OX-42 and BDNF in the spinal dorsal horn of rats in the model group was increased(P<0.01). Following the treatment, and in comparison with the model group, the expression of OX-42 and BDNF of moxibustion group was down-regulated(P<0.05). CONCLUSION: Moxibustion can significantly improve the injury of the medial femoral muscle and the TWL in MPS rats,which may be related to its effects in inhibiting the activation of spinal dorsal horn microglia and reducing the expression of BDNF.


Assuntos
Moxibustão , Síndromes da Dor Miofascial , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Masculino , Microglia , Ratos , Ratos Sprague-Dawley , Medula Espinal
11.
Inorg Chem ; 60(19): 14810-14819, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34546744

RESUMO

Three tris-heteroleptic mononuclear Ru(II) complexes with dual fluorescence and phosphorescence-[Ru(dpma)(bpy)(phen)]2+ (12+), [Ru(dpma)(bpy)(dppz)]2+ (22+), and [Ru(dpma)(phen)(dppz)]2+ (32+)-have been designed and used as ratiometric light-response probes for DNA, where dpma is di(pyrid-2-yl)(methyl)-amine, bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline, and dppz is dipyridophenazine, respectively. Single crystals of complex 2(PF6)2 have been obtained and studied by X-ray analysis. The interactions of these complexes with different DNAs are investigated by means of spectroscopic methods, viscosity measurements, and molecular modeling. In the presence of calf thymus DNA, complexes 2(PF6)2 and 3(PF6)2 show the emergence of a new lower-energy phosphorescence emission band; meanwhile, the higher-energy fluorescence emission band is essentially unchanged, functioning as an intrinsic internal reference. These two complexes exhibit stronger preference for calf thymus DNA over single-strand DNA (d(A)16 and d(C)16). In contrast, no binding interaction between 1(PF6)2 and calf thymus DNA is observed. The intrinsic binding constants (Kb) of 2(PF6)2 and 3(PF6)2 with calf thymus DNA are determined to be (1.4 ± 0.4) × 105 and (9.5 ± 0.15) × 104 M-1, respectively. In addition, these spectroscopic results are compared with those of the prototype complex [Ru(bpy)2(dppz)]2+ (42+), and density functional theory and time-dependent density functional theory calculations are employed to elucidate these experimental findings.


Assuntos
Complexos de Coordenação/química , DNA/química , Rutênio/química , Animais , Bovinos , Estrutura Molecular
12.
J Agric Food Chem ; 69(40): 11992-12001, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34498855

RESUMO

Food allergies (FAs) are a crucial public health problem and a severe food safety issue, resulting in an urgent need for an accurate method to detect all of the hidden allergens that exist in food systems. Current methods for detecting allergens typically utilize ELISA, PCR, or LC-MS, which are suitable for the confirmatory analysis of allergens from ingredients rather than unintended contaminants. In this study, we demonstrate a hybridization probe cluster-targeted next-generation sequencing (HPC-NGS) platform for high-throughput screening of potential allergens in food systems. The HPC-NGS successfully captured target DNA fragments and identified 19 allergenic ingredients in a complex food system. Additionally, the HPC-NGS provided expected allergenic species matching rates of 94.24-100% in single food materials and 99.87-99.98% in processed food products. Thus, HPC-NGS enables the accurate characterization of allergenic ingredients and unintended allergenic contaminants in foods. Our results provide new perspectives on the use of HPC-NGS in the accuracy of high-throughput detection technologies for allergens imposed by the complex matrix effect.


Assuntos
Alérgenos , Hipersensibilidade Alimentar , Alérgenos/análise , Cromatografia Líquida , Análise de Alimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Espectrometria de Massas
13.
Cancer Med ; 10(21): 7665-7672, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34590788

RESUMO

BACKGROUND: Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real-world benefit of first-line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. METHODS: This study included HR-positive, HER2-negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression-free survival (PFS) was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time-dependent variable. RESULTS: In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93-NR). Median PFS for patients with bone-only metastases (n = 54) was not reached (95% CI 18.21-NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33-33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71-0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97-1.18, p = 0.203). CONCLUSION: The effectiveness of palbociclib and endocrine therapy in the treatment of HR-positive, HER2-negative mBC in the real-world setting is similar to the efficacy reported in the PALOMA-2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.

14.
Support Care Cancer ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34510238

RESUMO

BACKGROUND: Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL). METHODS: Caregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses. RESULTS: The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions. CONCLUSION: This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.

15.
Mil Med Res ; 8(1): 48, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34496967

RESUMO

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Proteínas Citotóxicas Formadoras de Poros/farmacologia , Proteínas Citotóxicas Formadoras de Poros/farmacocinética , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Humanos
16.
EClinicalMedicine ; 38: 101026, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34337366

RESUMO

Background: Beginning March 2020, the COVID-19 pandemic has disrupted different aspects of life. The impact on children's rate of weight gain has not been analysed. Methods: In this retrospective cohort study, we used United States (US) Electronic Health Record (EHR) data from Optum® to calculate the age- and sex- adjusted change in BMI (∆BMIadj) in individual 6-to-17-year-old children between two well child checks (WCCs). The mean of individual ∆BMIadj during 2017-2020 was calculated by month. For September-December WCCs, the mean of individual ∆BMIadj (overall and by subgroup) was reported for 2020 and 2017-2019, and the impact of 2020 vs 2017-2019 was tested by multivariable linear regression. Findings: The mean [95% Confidence Interval - CI] ∆BMIadj in September-December of 2020 was 0·62 [0·59,0·64] kg/m2, compared to 0·31 [0·29, 0·32] kg/m2 in previous years. The increase was most prominent in children with pre-existing obesity (1·16 [1·07,1·24] kg/m2 in 2020 versus 0·56 [0·52,0·61] kg/m2 in previous years), Hispanic children (0·93 [0·84,1·02] kg/m2 in 2020 versus 0·41 [0·36,0·46] kg/m2 in previous years), and children who lack commercial insurance (0·88 [0·81,0·95] kg/m2 in 2020 compared to 0·43 [0·39,0·47] kg/m2 in previous years). ∆BMIadj accelerated most in ages 8-12 and least in ages 15-17. Interpretation: Children's rate of unhealthy weight gain increased notably during the COVID-19 pandemic across demographic groups, and most prominently in children already vulnerable to unhealthy weight gain. This data can inform policy decisions critical to child development and health as the pandemic continues to unfold. Funding: Amgen, Inc.

17.
BMJ Open ; 11(8): e051588, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362806

RESUMO

OBJECTIVE: To examine age, gender, and temporal differences in baseline characteristics and clinical outcomes of adult patients hospitalised with COVID-19. DESIGN: A cohort study using deidentified electronic medical records from a Global Research Network. SETTING/PARTICIPANTS: 67 456 adult patients hospitalised with COVID-19 from the USA; 7306 from Europe, Latin America and Asia-Pacific between February 2020 and January 2021. RESULTS: In the US cohort, compared with patients 18-34 years old, patients ≥65 had a greater risk of intensive care unit (ICU) admission (adjusted HR (aHR) 1.73, 95% CI 1.58 to 1.90), acute respiratory distress syndrome(ARDS)/respiratory failure (aHR 1.86, 95% CI 1.76 to 1.96), invasive mechanical ventilation (IMV, aHR 1.93, 95% CI, 1.73 to 2.15), and all-cause mortality (aHR 5.6, 95% CI 4.36 to 7.18). Men appeared to be at a greater risk for ICU admission (aHR 1.34, 95% CI 1.29 to 1.39), ARDS/respiratory failure (aHR 1.24, 95% CI1.21 to 1.27), IMV (aHR 1.38, 95% CI 1.32 to 1.45), and all-cause mortality (aHR 1.16, 95% CI 1.08 to 1.24) compared with women. Moreover, we observed a greater risk of adverse outcomes during the early pandemic (ie, February-April 2020) compared with later periods. In the ex-US cohort, the age and gender trends were similar; for the temporal trend, the highest proportion of patients with all-cause mortality were also in February-April 2020; however, the highest percentages of patients with IMV and ARDS/respiratory failure were in August-October 2020 followed by February-April 2020. CONCLUSIONS: This study provided valuable information on the temporal trends of characteristics and outcomes of hospitalised adult COVID-19 patients in both USA and ex-USA. It also described the population at a potentially greater risk for worse clinical outcomes by identifying the age and gender differences. Together, the information could inform the prevention and treatment strategies of COVID-19. Furthermore, it can be used to raise public awareness of COVID-19's impact on vulnerable populations.


Assuntos
COVID-19 , Adolescente , Adulto , Estudos de Coortes , Feminino , Saúde Global , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pandemias , Respiração Artificial , SARS-CoV-2 , Adulto Jovem
18.
Sci Immunol ; 6(62)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389612

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a chronic inflammatory process often associated with comorbid asthma. In this study, we analyzed the transcriptomes of single T helper (TH) cells from nasal polyps of patients with CRSwNP and validated these findings using multiparameter flow cytometry. Polyp tissue contained suppressive T regulatory (Treg) cells, TH2 cells, type 2 innate lymphoid cells, and three transcriptionally distinct subsets of cytotoxic CD4+ T cells (CD4+ CTL). GATA3 expression was a feature of polyp Treg cells, whereas TH2 cells highly expressed TCN1, CD200R, and HPGDS and were enriched for genes involved in lipid metabolism. Only a portion of polyp TH2 cells expressed the prostaglandin D2 receptor CRTH2, whereas a subpopulation of CD109+CRTH2- TH2 cells expressed mRNA for common inhibitor receptors including LAG3 and TIM3 and produced IL-10. Together, we resolved the complexity of TH cells in patients with CRSwNP, identifying several distinct clusters of CD4+ CTL and a population of CD109+CRTH2- TH2 cells with putative regulatory potential.

19.
Am J Transl Res ; 13(6): 5956-5968, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306337

RESUMO

Urethral stricture is one of the common diseases in urology. It can lead to obstructive voiding dysfunction and may cause long-term damage to the entire urinary tract. Here, we investigated the effect of combined use of 5-fluorouracil (5-FU) and triamcinolone acetonide (TA) in improving urethral stricture. We established urethral stricture in vivo and in vitro model. The role of TA combined with 5-FU treatment in scar tissue and fibroblast cells were examined by RT-PCR, Western blot and immunohistochemical methods. The function of miRNA in improving urethral stricture by TA combined with 5-FU treatment were further investigated. We found that TA combined with 5-FU treatment obviously prevent urethral fibrosis in vivo as well as in vitro. MiR-192-5p level was downregulated in urethral stricture tissue and urethral tissue fibroblast, TA combined with 5-FU treatment rescue the expression of miR-192-5p. The improvement of urethral fibrosis by TA combined with 5-FU treatment was blocked by miR-192-5p inhibitor. miR-192-5p mediated the improvement of urethral scar by triamcinolone acetonide combined with 5-FU by directly targeting ATG7, which is marker gene of autophagy. Our data demonstrated that TA combined with 5-FU suppresses urethral scar fibroblasts autophagy and fibrosis by increasing miR-192-5p expression, thus offering a new strategies and target for Urethral stricture.

20.
Environ Sci Technol ; 55(12): 8191-8202, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34086441

RESUMO

As typical brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) and its derivative TBBPA-bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) are ubiquitous in various environmental compartments. However, the potential health risk posed by these compounds, especially at environmentally relevant levels, remains unclear. In this study, using adult male mice, we investigated the toxicity of orally administered TBBPA and TBBPA-BDBPE at an environmentally relevant dose (57 nmol/kg body weight). After a single exposure and daily exposure, we assessed lipid metabolism homeostasis, the transcriptome, and immune cell components in the liver. We found that the single exposure to TBBPA or TBBPA-BDBPE alone increased the number of hepatic macrophages, induced alterations in the levels of lipids, including triacylglycerol and free fatty acids, and caused transcriptome perturbation. The results from the daily administration groups showed that TBBPA and TBBPA-BDBPE both significantly increased the triacylglycerol content; however, the elevation of hepatic macrophages was observed only in the TBBPA-BDBPE treatment group. This study confirmed that environmentally relevant levels of TBBPA and TBBPA-BDBPE are toxic to the liver. Our findings revealed that dysfunction of the liver is a health concern, following exposure to BFRs, even at very low concentrations. The chronic effects induced by TBBPA and its derivatives should be further investigated.


Assuntos
Retardadores de Chama , Bifenil Polibromatos , Animais , Éter , Retardadores de Chama/toxicidade , Fígado , Masculino , Camundongos , Bifenil Polibromatos/toxicidade
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