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1.
J Trace Elem Med Biol ; 66: 126755, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33838565

RESUMO

OBJECTIVE: We aimed to evaluate the association between baseline plasma zinc and the development of proteinuria as well as possible effect modifiers in hypertensive patients. METHODS: This is a subset of the China Stroke Primary Prevention Trial (CSPPT) Renal Sub-Study. In the CSPPT, participants were randomized to receive a daily oral dose of 1 tablet containing 10 mg enalapril and 0.8 mg folic acid or 1 tablet containing 10 mg enalapril only. A total of 783 participants with plasma zinc measurements and without proteinuria at baseline were included in the current study. The study outcome was the development of proteinuria during the follow-up, defined as a urine dipstick reading of trace or ≥1+ at the exit visit. RESULTS: During a median follow-up duration of 4.4 years, the development of proteinuria occurred in 93 (11.9 %) participants. There was an inverse relation of baseline plasma zinc with the development of proteinuria (per SD increment; OR, 0.74, 95 % CI: 0.55-0.99), p for trend of quartiles = 0.005. CONCLUSIONS: In Chinese hypertensive patients, there was a significant inverse association between baseline plasma zinc and the development of proteinuria, although plasma zinc remained in the reference range.

2.
Cancer ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826754

RESUMO

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

3.
Eat Weight Disord ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844178

RESUMO

PURPOSE: Visceral adiposity index (VAI) is a reliable indicator for the distribution and function of adipose tissue in the body. The relation of VAI with new-onset type 2 diabetes and new-onset impaired fasting glucose (IFG) remains uncertain. We aimed to investigate the prospective relation of VAI with new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive adults. METHODS: A total of 14,838 hypertensive adults free of type 2 diabetes at baseline were included from the China Stroke Primary Prevention Trial. The primary outcome was new-onset type 2 diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary outcome was new-onset IFG, defined as fasting glucose < 6.1 mmol/L at baseline, while fasting glucose ≥ 6.1 mmol/L and < 7.0 mmol/L at the exit visit. RESULTS: Over a median of 4.5 years' follow-up, 1612 (10.9%) participants developed type 2 diabetes. When VAI was categorized into quartiles, compared with participants in quartile 1-3 (< 2.80), significantly higher risk of new-onset type 2 diabetes (OR 1.30; 95% CI 1.08-1.56) and new-onset IFG (OR 1.28; 95% CI 1.08-1.52) was found in those in quartile 4 (≥ 2.80). Moreover, the positive associations were consistent in participants with or without single abnormal VAI components, including general obesity, abdominal obesity, elevated triglycerides and low high-density lipoprotein cholesterol (HDL-C) levels; or with different numbers of abnormal VAI components (all P interactions > 0.05). CONCLUSION: Our study suggested a positive relation of VAI with the risk of new-onset type 2 diabetes and new-onset IFG in Chinese hypertensive patients, independent of its components. LEVEL OF EVIDENCE: Level III, a well-designed cohort.

4.
BMC Public Health ; 21(1): 696, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836720

RESUMO

BACKGROUND: According to the Global Burden of Disease Study 2017, smoking is one of the leading four risk factors contributing to deaths in China. We aimed to evaluate the associations of smoking with all-cause mortality in a Chinese rural population. METHODS: Male participants over age 45 (n = 5367) from a large familial aggregation study in rural China, were included in the current analyses. A total of 528 former smokers and 3849 current smokers accounted for 10 and 71.7% of the cohort, respectively. Generalized Estimating Equations were used to evaluate the association between baseline smoking status and mortality, adjusting for pertinent covariates. RESULTS: There were 579 recorded deaths during the 15-year follow-up. Current smokers (odds ratio [OR],1.60; 95% CI,1.23-2.08) had higher all-cause mortality risks than nonsmokers. Relative to nonsmokers, current smokers of more than 40 pack-years ([OR],1.85; 95% CI,1.33-2.56) had a higher all-cause mortality risk. Compared to nonsmokers, current smokers who started smoking before age 20 ([OR],1.91; 95% CI,1.43-2.54) had a higher all-cause mortality risk, and former smokers in the lower pack-year group who quit after age 41 (median) ([OR],3.19; 95% CI,1.83-5.56) also had a higher risk of death after adjustment. Furthermore, former smokers who were also former drinkers had the highest significant risk of mortality than never smokers or drinkers. (P for interaction = 0.034). CONCLUSIONS: This study provides evidence that current smokers and former smokers have a higher mortality risk than nonsmokers and would benefit from cessation at a younger age.

5.
Mol Biol Rep ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33866496

RESUMO

This study investigated the differentiation of transplanted transplanted mesenchymal stem cells MSCs into neuron-like cells, repair of erectile dysfunction (ED), and synergy of MSCs seeded to nanofibrous scaffolds with after transplantation around the injured cavernous nerve (CN) of rats. The synthesized polymer was electrospun in a rotating drum to prepare nanofiber meshes (NMs). Human MSCs were prepared and confirmed. Eight-week-old male Sprague-Dawley rats were divided into five groups of six each: group 1-sham operation; group 2-CN injury; group 3-MSCs treatment after CN injury; group 4-nanofibrous scaffold treatment after CN injury; and group 5-post-CN injury treatment combining a nanofibrous scaffold and MSCs (nano-MSCs). In the latter group, the damaged CN was instantly surrounded by an MSC-containing a nanofibrous scaffold in the aftermath of injury. Morphological analysis and immuno-histochemical staining in relation to nerves (Tuj1, NF, MAP2, MBP and peripherin), endothelium (vWF), smooth muscle (SMA), neurofilament (NF), and apoptosis (TUNEL) were performed. We evaluated the mean proportion expressed as a percentage of the ratio of muscle to collagen of penile cavernous smooth-muscle cells as well as the expression of cavernous SMA, NF, vWF, and TUNEL makers. Compared to the group free of CN injury, erectile function was markedly reduced in the group with CN injury at 2 and 4 weeks (p < 0.05). By contrast, compared to the sham operation group, erectile function was better in the group with MSC transplantation (p < 0.05). Similarly, by comparison to the group solely with hMSCs, erectile function was better in the group with nano-MSC transplantation (p < 0.05). Transplantation of MSCs demonstrated the neuronal differentiation. By contrast to MSCs on their own, neuronal differentiation was more significantly expressed in nano-MSCs. The mean proportion expressed as a percentage of the ratio of muscle to collagen of penile cavernous smooth-muscle cells, the expression of cavernous SMA, NF, vWF, and apoptosis improved in the cavernosum after transplantation. NMs showed synergy with MSCs for the repair of erectile dysfunction. Transplanted MSCs differentiated into neuron-like cells and repaired erectile dysfunction in the rats with CN injury. Transplanted MSCs increased the mean percentage of the collagen area of the caversnosum as well as the expression levels of cavernous neuronal, endothelial, smooth-muscle markers, and apoptosis.

6.
Am J Surg ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33867048

RESUMO

BACKGROUND: Localized gastrointestinal stromal tumors (GISTs) are rare tumors typically managed with surgery, but outcomes among octogenarians remain less studied. METHODS: Octogenarian patients with stage I-III gastric GISTs were identified from the National Cancer Database and classified by resection status. Cox regression and Kaplan-Meier survival analyses analyzed 5-year overall survival (OS). Ninety-day mortality was analyzed following 1:1 propensity score matching. RESULTS: Identified octogenarians (N = 949) who underwent resection (N = 632) had improved adjusted OS (71% vs 59.6%, HR 0.75, p 0.049) as compared to non-resected patients. Following matching, 90-day mortality was 5.7% and 11% in resected and non-resected patients (p 0.052), respectively. After exclusion of patients with 90-day mortality, resected patients maintained an OS advantage (77.3% vs 71.1%, HR 0.64, p 0.028). CONCLUSIONS: The majority of octogenarians with localized gastric GIST are treated with surgery portending improved survival but an appreciable mortality, suggesting a necessity for careful selection of older patients for surgery.

7.
Aesthetic Plast Surg ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649929

RESUMO

BACKGROUND: The Motiva Ergonomix™ Round SilkSurface (Establishment Labs Holdings Inc., Alajuela, Costa Rica) is the fifth generation of a silicone gel-filled breast implant that is commercially available in Korea. OBJECTIVES: In this study, we describe 4-year interim results of the safety of augmentation mammaplasty using the Motiva Ergonomix™ Round SilkSurface in Korean women. METHODS: In the current multicenter, retrospective study, we performed a retrospective review of medical records of a total of 1314 patients who received augmentation mammaplasty using the Motiva Ergonomix™ Round SilkSurface at our hospitals between September 1, 2016, and August 31, 2020. For safety assessment, we analyzed incidences of postoperative complications and Kaplan-Meier complication-free survival of the patients. RESULTS: We included a total of 873 patients (1746 breasts, mean age = 32.18 ± 6.88 years) in the current study. There were a total of 111 cases (12.70%) of postoperative complications; these include 24 cases (2.70%) of early seroma, 18 cases (2.10%) of hematoma, 18 cases (2.10%) of capsular contracture, 17 cases (1.95%) of dissatisfaction with shape, 16 cases (1.83%) of dissatisfaction with size, 9 cases (1.03%) of asymmetry, 6 cases (0.70%) of infection and 3 cases (0.34%) of rippling. Moreover, time-to-events were estimated at 918.34 ± 36.22 days (95% CI 845.44-988.52). CONCLUSIONS: Here, we describe 4-year interim results of the safety of augmentation mammaplasty using the Motiva Ergonomix™ Round SilkSurface in Korean women in a non-manufacturer-sponsored study. But further large-scale, prospective, multicenter studies with a long period of follow-up are warranted to establish our results. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

8.
Artigo em Inglês | MEDLINE | ID: mdl-33787223

RESUMO

Enhancement in weak-light detection and other photodetection properties was observed for organic-inorganic halide perovskite photodetectors as a result of benzylammonium iodide (BzAI) treatment at the methylammonium lead triiodide (MAPbI3) and hole-transport layer (HTL) interface. After treatment, growth of the two-dimensional Ruddlesden-Popper perovskite phase was observed at the MAPbI3 surface, which shifted the overall surface work function upwards and thus effectively facilitated charge transfer across the MAPbI3/HTL interface. As a result, the fully fabricated device with 10 mg/mL (BzAI/isopropanol) treatment exhibited shorter rise time (trise) and decay time (tdecay) of 53 and 38 µs, respectively, compared to trise and tdecay of 214 and 120 µs, respectively, for the pristine MAPbI3 sample. In addition, the BzAI-treated device exhibited larger linearity compared to the pristine MAPbI3 sample, demonstrating a high and stable specific detectivity of 1.49 × 1013 to 2.14 × 1013 Jones under incident light intensity of 10-3 to 100 mW/cm2, respectively.

9.
Huan Jing Ke Xue ; 42(3): 1123-1130, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742908

RESUMO

A life cycle conceptual site model (LC-CSM) can represent the actual spatial distribution and migration of pollution of a site very accurately and be beneficial in supporting decisions for accurate site remediation or risk management. A volatile chlorinated hydrocarbon contaminated site in the Beijing-Tianjin-Hebei region was chosen as the study case. LC-CSMs were established following the site assessment, preliminary investigation, detailed investigation, and supplementary investigation of each stage. The application of field screening tests such as a membrane interface probe and the multi-electrode resistivity method assisted in identifying potential pollution sources and hot points. Concurrently, a large amount of vinyl chloride, the end product of chlorinated hydrocarbon degradation, was detected in some boreholes, indicating that pollutant biodegradation had occurred at this site. Some typical boreholes and cross-sections were chosen to analyze the biodegradation indicators and chemical fingerprints, combining the results of the comprehensive score of chlorinated hydrocarbon anaerobic biodegradability in groundwater reaching 22. It is judged that the site has strong anaerobic biodegradability. This step-by-step optimization forms an LC-CSM for site investigation, which provides scientific support for accurate site characterization.

10.
Respir Res ; 22(1): 91, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757521

RESUMO

BACKGROUND: Airway remodelling is the major pathological feature of chronic obstructive pulmonary disease (COPD), and leads to poorly reversible airway obstruction. Current pharmacological interventions are ineffective in controlling airway remodelling. In the present study, we investigated the potential role of artesunate in preventing and treating airway remodelling and the underlying molecular mechanisms in vitro and in vivo. METHODS: A COPD rat model was established by cigarette smoke (CS) exposure. After 12 weeks of artesunate treatment, pathological changes in the lung tissues of COPD rats were examined by ELISA and histochemical and immunohistochemical staining. A lung functional experiment was also carried out to elucidate the effects of artesunate. Human bronchial smooth muscle (HBSM) cells were used to clarify the underlying molecular mechanisms. RESULTS: Artesunate treatment inhibited CS-induced airway inflammation and oxidative stress in a dose-dependent manner and significantly reduced airway remodelling by inhibiting α-smooth muscle actin (α-SMA) and cyclin D1 expression. PPAR-γ was upregulated and TGF-ß1/Smad2/3 signalling was inactivated by artesunate treatment in vivo and in vitro. Furthermore, PPAR-γ knockdown by siRNA transfection abolished artesunate-mediated inhibition of HBSM cell proliferation by activiting the TGF-ß1/Smad2/3 signalling pathway and downregulating the expression of α-SMA and cyclin D1 in HBSM cells. CONCLUSIONS: These findings suggest that artesunate could be used to treat airway remodelling by regulating PPAR-γ/TGF-ß1/Smad signalling in the context of COPD.

11.
Huan Jing Ke Xue ; 42(4): 2003-2015, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742835

RESUMO

In order to evaluate the potential ecological risk of heavy metals in the soil-crop system in the Xiong'an New District, the heavy metal contents and forms in wheat seed and root soil samples are analyzed, and the comprehensive pollution index (IPIN), potential ecological risk index (RI), bio-enrichment coefficient (BFC), risk assessment code (RAC), principal component analysis, and correlation analysis are used to assess the potential ecological risk of heavy metals and analyze their sources. The results indicate that the average content of Cd, Cu, Pb, and Zn in the root soil is significantly higher than the soil background value in Hebei province. The IPIN ranges from 0.2 to 5.18, 94.83% of the soil samples are in the safe and pollution-free grade, and the potential ecological risks of heavy metal are slight and moderate, accounting for 64.66% and 30.17%, respectively. Cd has the greatest potential ecological harm, followed by Hg, Cr, Ni, and Zn. All the heavy metal elements besides Cd in the root soil are dominated by the residual form, which accounts for 60%, and the bioactive form (ion-exchange and water-soluble state) of Cd accounts for 33.43%, indicating relatively high bio-availability. The risk assessment code can be ranked as Cd > Ni > Hg > As > Cu > Cr > Zn > Pb, and the risk of Cd is moderate, while other elements are of low or no risk. The leading potential source of heavy metals is human activity combined with the geological background. The migration and enrichment capability of the wheat seeds is in order from strong to weak of Zn > Cu > Cd > Hg > As > Ni > Pb > Cr, and the biological effective components of As, Cd, Pb, and Zn plays an substantial role in promoting the absorption of heavy metals. The content of heavy metals in the wheat seeds has a negative correlation with the soil pH, and the physical and chemical indices, such as OM and CEC, has bi-directional influence on the biological effective state of the heavy metals.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
12.
Bioorg Chem ; 110: 104783, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33714021

RESUMO

Paeonone A (1), a unique nonanortriterpenoid, and a new octanortriterpenoid, paeonone B (2), were isolated from the roots of Paeonia lactiflora, together with a known analogue, palbinone (3). Paeonone A (1) is the first example of naturally occurring nonanortriterpenoid with a diketo acid group. Extensive NMR and HRESIMS experiments were applied to identify the structures of 1 and 2, and their absolute configurations were solved by single-crystal X-ray diffraction and ECD data. Biological properties of 1-3 were explored against pancreatic lipase and cancer cell lines.

13.
Exp Neurobiol ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33707347

RESUMO

Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3+ double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10+Foxp3+ regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10+Foxp3+ regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

14.
Eur J Cancer Care (Engl) ; : e13443, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764597

RESUMO

OBJECTIVE: To investigate factors associated with influenza vaccination in cancer survivors. METHODS: Study subjects were 1,945 Korean adult cancer survivors. Through medical record review and self-administered questionnaires, social and medical information was collected. Influenza vaccination was defined as ever having received a flu vaccine between one year before cancer diagnosis and the survey date. Multiple logistic regression analysis was used to evaluate factors associated with influenza vaccination. RESULTS: Overall, 60.8% of study subjects had received an influenza vaccination. Younger survivors had a significantly lower vaccination rate than did the elderly survivors (80.22% vs. 54.73%). In younger survivors, longer time elapsed since cancer diagnosis, lifestyle modification counselling during cancer treatment, adequate physical exercise (≥150 min/week) and complementary medication use were positively associated with vaccination, whereas extra-pulmonary cancers, multimodality (≥3) cancer treatment and higher educational achievement were inversely associated. In elderly survivors, fewer factors had a positive (adequate physical exercise) or inverse (multimodality cancer treatment and current smoking) association with influenza vaccination. CONCLUSION: Influenza vaccination rate was suboptimal, especially among younger cancer survivors. Targeted strategies are necessary to improve influenza vaccination in cancer survivors with consideration of individual characteristics such as age, lifestyle, cancer treatment modality, cancer type and education level.

15.
Medicine (Baltimore) ; 100(10): e24941, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33725856

RESUMO

INTRODUCTION: Total knee replacement (TKR) is a surgical procedure that is being increasingly performed as a result of population aging and the increased average human life expectancy in South Korea. Consistent with the growing number of TKR procedures, the number of patients seeking acupuncture for relief from adverse effects, effective pain management, and the enhancement of rehabilitative therapy effects and bodily function after TKR has also been increasing. Thus, an objective examination of the evidence regarding the safety and efficacy of acupuncture treatments is essential. The aim of this study is to verify the hypothesis that the concurrent use of acupuncture treatment and usual care after TKR is more effective, safe, and cost-effective for the relief of TKR symptoms than usual care therapy alone. METHODS/DESIGN: This is an open-label, parallel, assessor-blinded randomized controlled trial that includes 50 patients with TKR. After screening the patients and receiving informed consent, the patients are divided into two groups (usual care + acupuncture group and usual care group); the patients will then undergo TKR surgery and will be hospitalized for 2 weeks. The patients will receive a total of 8 acupuncture treatments over 2 weeks after surgery and will be followed up at 3, 4, and 12 weeks after the end of the intervention. The primary outcome is assessed using the Korean version of the Western Ontario and McMaster Universities Arthritis Index (K-WOMAC), and the secondary outcome is measured using the Numerical Rating Scale (NRS), Risk of Fall, and Range of Motion (ROM). Moreover, the cost per quality-adjusted life years (QALYs) is adopted as a primary economic outcome for economic evaluation, and the cost per NRS is adopted as a secondary economic outcome. ETHICS AND DISSEMINATION: This trial has received complete ethical approval from the Ethics Committee of Catholic Kwandong University International St. Mary's Hospital (IS17ENSS0063). We intend to submit the results to a peer-reviewed journal and/or conferences. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03633097.


Assuntos
Terapia por Acupuntura/efeitos adversos , Artroplastia do Joelho/reabilitação , Osteoartrite do Joelho/cirurgia , Manejo da Dor/métodos , Dor Pós-Operatória/diagnóstico , Terapia por Acupuntura/economia , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/economia , Terapia Combinada/efeitos adversos , Terapia Combinada/economia , Terapia Combinada/métodos , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/economia , Manejo da Dor/efeitos adversos , Manejo da Dor/economia , Medição da Dor/estatística & dados numéricos , Dor Pós-Operatória/economia , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/reabilitação , Projetos Piloto , Anos de Vida Ajustados por Qualidade de Vida , República da Coreia , Resultado do Tratamento
16.
Cell ; 184(8): 2183-2200.e22, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33756110

RESUMO

Antibodies are crucial to immune protection against SARS-CoV-2, with some in emergency use as therapeutics. Here, we identify 377 human monoclonal antibodies (mAbs) recognizing the virus spike and focus mainly on 80 that bind the receptor binding domain (RBD). We devise a competition data-driven method to map RBD binding sites. We find that although antibody binding sites are widely dispersed, neutralizing antibody binding is focused, with nearly all highly inhibitory mAbs (IC50 < 0.1 µg/mL) blocking receptor interaction, except for one that binds a unique epitope in the N-terminal domain. Many of these neutralizing mAbs use public V-genes and are close to germline. We dissect the structural basis of recognition for this large panel of antibodies through X-ray crystallography and cryoelectron microscopy of 19 Fab-antigen structures. We find novel binding modes for some potently inhibitory antibodies and demonstrate that strongly neutralizing mAbs protect, prophylactically or therapeutically, in animal models.

17.
Zhongguo Zhong Yao Za Zhi ; 46(3): 638-644, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645031

RESUMO

According to human carboxylesterase 2(hCE2) inhibitors reported in the literature, the pharmacophore model of hCE2 inhibitors was developed using HipHop module in Discovery Studio 2016. The optimized pharmacophore model, which was validated by test set, contained two hydrophobic, one hydrogen bond acceptor, and one aromatic ring features. Using the pharmacophore model established, 5 potential hCE2 inhibitors(CS-1,CS-2,CS-3,CS-6 and CS-8) were screened from 20 compounds isolated from the roots of Paeonia lactiflora, which were further confirmed in vitro, with the IC_(50) values of 5.04, 5.21, 5.95, 6.64 and 7.94 µmol·L~(-1), respectively. The results demonstrated that the pharmacophore model exerted excellent forecasting ability with high precision, which could be applied to screen novel hCE2 inhibitors from Chinese medicinal materials.


Assuntos
Carboxilesterase , Carboxilesterase/antagonistas & inibidores , Carboxilesterase/metabolismo , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas
18.
Indian Heart J ; 73(1): 121-124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33714397

RESUMO

Myocarditis is an inflammatory disease of the myocardium with high morbidity and mortality; however, definite prognostic factors are still unclear. Therefore, we aimed to evaluate the predictor of clinical outcomes of acute myocarditis focusing on electrocardiographic findings. The overall result of the study consists of a total of 51 patients demonstrated that wide QRS duration is a meaningful factor for predicting the fulminant course of acute myocarditis. This finding may encourage timely mechanical support resulting in better clinical outcomes.

19.
Hypertens Res ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33564178

RESUMO

We aimed to investigate the association between neutrophil counts and first stroke and examine possible effect modifiers among treated hypertensive adults. This is a post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT). A total of 11,878 hypertensive adults with data on neutrophil counts at baseline were included in the current study. The primary outcome was first stroke. During a median follow-up of 4.5 years, 414 (3.5%) participants experienced a first stroke, including 358 with ischemic stroke, 55 with hemorrhagic stroke and one with uncertain type of stroke. Compared with participants in quartile 1 (<2.9 × 109/L) of neutrophil counts, those in the upper quartiles (quartile 2-4 [≥2.9 × 109/L]) had a significantly higher risk of first stroke (HR, 1.35; 95% CI: 1.02, 1.78) or first ischemic stroke (HR, 1.38; 95% CI: 1.02, 1.86). Moreover, a strong positive association between neutrophil counts and first ischemic stroke was found in participants with total homocysteine (tHcy) levels <15 µmol/L (HR, 1.74; 95% CI: 1.17, 2.58; vs. ≥15 µmol/L; HR, 0.91; 95% CI: 0.57, 1.46, P interaction = 0.042) at baseline or time-averaged mean arterial pressure (MAP) ≥102 mmHg (median) (HR, 1.92; 95% CI: 1.27, 2.89; vs. <102 mmHg; HR, 0.89; 95% CI: 0.57, 1.41, P interaction = 0.015) during the treatment period. However, no such association between neutrophil counts and first hemorrhagic stroke was found. In summary, high baseline neutrophil counts were associated with an increased risk of first ischemic stroke among hypertensive patients, especially in those with low tHcy at baseline or high time-averaged MAP during the treatment period.

20.
Ann Surg Oncol ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591480

RESUMO

INTRODUCTION: Preoperative biopsy (PBx) is often recommended for retroperitoneal sarcoma (RPS), but its utilization rate and impact on perioperative management and outcomes remains undefined. METHODS: Using the National Cancer Database, patients who underwent resection of non-metastatic RPS were identified (2006-2014). Patients who did and did not undergo PBx of the primary tumor were compared using propensity matching, and factors associated with survival were assessed by multivariable analysis. RESULTS: Of 2620 patients, 1110 (42.4%) underwent PBx. Factors significantly associated with performance of PBx included male sex [odds ratio (OR) 1.2, P = 0.035], tumor size ≤ 5 cm (OR 1.5, P = 0.012), tumor size > 5 to ≤ 10 cm (OR 1.3, P = 0.009), non-well-differentiated liposarcoma histology (OR 2.0, P ≤ 0.001), and treatment at a high-volume center (OR 1.3, P = 0.021). Receipt of PBx was significantly associated with administration of neoadjuvant radiation (OR 8.8, P < 0.001) or systemic therapy (OR 3.3, P < 0.001), radical surgical resection (OR 1.6, P < 0.001), and complete tumor resection (OR 1.5, P < 0.003). Neoadjuvant radiation [hazard ratio (HR) 0.7, P = 0.003] and complete tumor resection (HR 0.6, P < 0.001) were significantly associated with improved overall survival (OS). Performance of PBx was not associated with OS (HR 1.1, P = 0.070), and following propensity matching, 5-year OS did not differ between the two groups (56.5% PBx vs 58.4% no PBx, P = 0.247). CONCLUSIONS: A minority of patients with non-metastatic RPS undergo PBx. PBx does not negatively impact survival, but may indirectly improve outcomes in select patients by virtue of receipt of neoadjuvant therapy and attainment of complete tumor resection.

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