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1.
BMC Musculoskelet Disord ; 21(1): 315, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434505

RESUMO

BACKGROUND: The need for a transfusion is one of the adverse events following total knee arthroplasty (TKA), and accurately predicting this need remains challenging for arthroplasty surgeons. The purpose of the present research is to study the preoperative predictors of transfusion risk in patients following TKA and develop a nomogram. METHODS: The nomogram was developed based on a training set of 5402 patients who underwent TKA at the Affiliated Hospital of Qingdao University between September 2013 and November 2018. The independent predictors of transfusion were identified by univariate, LASSO, and binary logistic regression analyses. Then, a nomogram was established based on these independent predictors. The area under the curve (AUC), calibration curve, and decision curve analysis (DCA) were selected to evaluate the nomogram. The results were validated using an independent set of 1116 patients who underwent TKA between December 2018 and September 2019. In addition, we also carried out subgroup analyses in the training and testing sets based on the independent predictors. RESULTS: Five independent predictors were identified by multivariate analysis and were used to establish the nomogram. The AUCs of the nomogram were 0.884 (95% CI: 0.865-0.903) and 0.839 (95% CI, 0.773-0.905) in the training and testing sets, respectively. In both the training and testing sets, the calibration curve indicated that the prediction by the nomogram was highly consistent with the actual observation, and the DCA indicated that the nomogram had a favorable level of clinical usefulness. In addition, the AUC of the nomogram was significantly higher than the AUC of any independent predictor for predicting transfusion risk following TKA, and the subgroup analysis showed good performance in 20 subgroups. CONCLUSION: Lower preoperative Hb levels, simultaneous bilateral TKA, lower BMI, older age, and coronary heart disease were identified as independent predictors of postoperative transfusion in patients following TKA. A nomogram incorporating the above five predictors could accurately predict the transfusion risk.

2.
ACS Chem Biol ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32401486

RESUMO

The development of a tumor-targeted immunotherapy is highly required. The most advanced application is the use of CD19 chimeric antigen receptor (CAR)T (CAR-T) cells to B cell malignancies, but there are still side effects including potential carcinogenicity of lentiviral or retroviral insertion into the host cell genome. Here, we developed a nonviral aptamer-T cell targeted strategy for tumor therapy. Tumor cells surface-specific ssDNA aptamers were conjugated to CD3+T cells (aptamer-T cells) using N-azidomannosamine (ManNAz) sugar metabolic cell labeling and click chemistry. We found that the aptamer-T cells could specifically target and bind to tumor cells (such as SGC-7901 gastric cancer cell and CT26 colon carcinoma cell) in vitro and in mice after adoptively transfer in. Aptamer-T cells led to significant regression in tumor volume due to being enriched at tumor microenvironment and producing strong cytotoxicity activities of CD3+T cells with enhanced perforin, granzyme B, CD107a, CD69, and FasL expression. Moreover, aptamer-T displayed even stronger antitumor effects than an anti-PD1 immune-checkpoint monoclonal antibody (mAb) treatment in mice and combination with anti-PD1 yielded synergic antitumor effects. This study uncovers the strong potential of the adoptive nonviral aptamer-T cell strategy as a feasible and efficacious approach for tumor-targeted immunotherapy application.

4.
Int J Biol Macromol ; 156: 40-50, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32275992

RESUMO

Alzheimer's disease is the most common form of neurodegenerative disease and the formation of Aß amyloid aggregates has been widely demonstrated to be the principal cause of Alzheimer's disease. Our previous study and other studies suggested that the gallate moiety played an obligatory role in the inhibition process of naturally occurring polyphenols on Aß amyloid fibrils formation. However, the detailed mechanisms were still unknown. Thus, in the present study, the gallic acid (GA) was specially selected and the molecular recognition mechanisms between GA molecules and Aß1-40 monomer were examined and analyzed by molecular dynamics simulation. The in silico experiments revealed that GA significantly prevented the conformational changes of Aß1-40 monomer with no ß-sheet structure during the whole 100 ns. By analyzing the binding sites of GA molecules to Aß1-40 monomer, we found that both hydrophilic and hydrophobic amino acid residues were participated in the binding of GA molecules to Aß1-40 monomer. Moreover, results from the binding free energy analysis further demonstrated that the strength of polar interactions was significantly stronger than that of nonpolar interactions. We believed that our results could help to elucidate the underlying mechanisms of gallate moiety on the anti-amyloidogenic effects of polyphenols at the atomic level.

6.
PLoS Pathog ; 16(4): e1008481, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32298394

RESUMO

Reactive oxygen species (ROS) production is one of the earliest responses when plants percept pathogens and acts as antimicrobials to block pathogen entry. However, whether and how pathogens tolerate ROS stress remains elusive. Here, we report the chromatin remodeling in Verticillium dahliae, a soil-borne pathogenic fungus that causes vascular wilts of a wide range of plants, facilitates the DNA damage repair in response to plant ROS stress. We identified VdDpb4, encoding a histone-fold protein of the ISW2 chromatin remodeling complex in V. dahliae, is a virulence gene. The reduced virulence in wild type Arabidopsis plants arising from VdDpb4 deletion was impaired in the rbohd mutant plants that did not produce ROS. Further characterization of VdDpb4 and its interacting protein, VdIsw2, an ATP-dependent chromatin-remodeling factor, we show that while the depletion of VdIsw2 led to the decondensing of chromatin, the depletion of VdDpb4 resulted in a more compact chromatin structure and affected the VdIsw2-dependent transcriptional effect on gene expression, including genes involved in DNA damage repair. A knockout mutant of either VdDpb4 or VdIsw2 reduced the efficiency of DNA repair in the presence of DNA-damaging agents and virulence during plant infection. Together, our data demonstrate that VdDpb4 and VdIsw2 play roles in maintaining chromatin structure for positioning nucleosomes and transcription regulation, including genes involved in DNA repair in response to ROS stress during development and plant infection.

7.
Med Care ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32265354

RESUMO

OBJECTIVES: We can learn something about how Veterans value the Veterans Health Administration (VHA) versus community providers by observing Veterans' choices between VHA and Medicare providers after they turn 65. For a cohort of Veterans who were newly age-eligible for Medicare, we estimated the change in VHA reliance (VHA outpatient visits divided by total VHA and Medicare visits) associated with specific events: receiving a life-threatening diagnosis, having a Medicare-paid hospitalization, or moving further from the VHA. RESEARCH DESIGN: A longitudinal cohort study of VHA and Medicare administrative data. SUBJECTS: A total of 5932 VHA users who completed a health survey in 1999 and became age-eligible for Medicare from 1998 to 2000 were followed through 2016. PRINCIPAL FINDINGS: More Veterans chose to rely on the VHA than Medicare (64% vs. 36.%). For a VHA-reliant Veteran, a Medicare-paid hospital stay was associated with a decrease of 7.8 percentage points (pps) (P<0.001) in VHA reliance in the subsequent 12 months, but by 36 months reliance increased to near prehospitalization levels (-1.5 pps; P=0.138). Moving further from the VHA, or receiving a diagnosis of cancer, heart failure, or renal failure had no significant association with subsequent VHA reliance; however, a diagnosis of dementia was associated with a decrease in VHA reliance (-8.6 pps; P=0.026). CONCLUSIONS: A significant majority of newly Medicare-eligible VHA users voted with their feet in favor of sustaining the VHA as a provider of comprehensive medical care for Veterans. These VHA-reliant Veterans maintained their reliance even after receiving a life-threatening diagnosis, and after experiencing Medicare-provided hospital care.

8.
Dig Dis Sci ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323072

RESUMO

BACKGROUND/AIMS: Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here, we prepare an active targeting drug carrier of low immunogenicity and toxicity for targeted therapy. METHODS: Immature dendritic cells (imDCs) from BALB/c mice were used as donor cells of exosomes (Exos) that were transfected with the plasmids expressing fusion proteins of a tumor-targeting peptide known as internalizing RGD (iRGD) to construct a type of tumor-targeting iRGD-Exos and observe the interaction between these iRGD-Exos. Also, recombinant methioninase (rMETase) was loaded into the iRGD-Exos by electroporation to construct iRGD-Exos-rMETase and to assess the tumor-targeting function of the iRGD-Exos-rMETase. Finally, 30 BALB/c were randomly divided into five groups (n = 6), to observe tumor growth in vivo. RESULTS: The iRGD-Exos-rMETase was 99.58 nm in diameter and presented a unique "goblet" structure under transmission electron microscopy (TEM), with the encapsulation efficiency (EE) of 19.05%. iRGD-Exos-rMETase group has the strongest tumor suppressive effect. Compared to the iRGD-Exos-rMETase group, rMETase group and the blank-Exos-rMETase group were less effective, while the PBS group and the iRGD-Exos group showed no inhibitory effect on tumor growth. After treatment, the iRGD-Exos-rMETase group had gastric tumors significantly smaller and lighter than the other groups (P < 0.05). CONCLUSION: The iRGD-Exos-rMETase is an effective antitumor therapy that delivers rMETase to tumor tissue using the iRGD-Exos. With its favorable inhibitory effect and tumor-targeting function, the iRGD-Exos-rMETase shows excellent potential value and exciting prospects in clinical applications.

9.
Chem Res Toxicol ; 33(3): 789-799, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32122129

RESUMO

Around 10 million people in the United States and 3 million people in the United Kingdom are estimated to use vaping category products. There are some estimates that there will be 75-80 million vapers worldwide by 2020. Most of these products are based on coil-and-wick technology. Because the heating and aerosol formation are separate processes, the system can lead to dry-wicking and elevated emission of carbonyls if designed and/or manufactured poorly. Low-nicotine and low-power coil-and-wick devices have also been linked to increased exposure to formaldehyde due to compensatory behavior by users. We characterized the emissions of a vaping product which uses a fabric-free stainless-steel mesh distiller plate technology that heats and aerosolizes the e-liquid in a single process. The plate has a microporous structure for capillary-induced liquid transformation (wicking) and aerosolization that is optimized to avoid fluid starvation and overheating and improved control. Compared with emissions previously reported for a coil-and-wick nicotine vaping product (e-cigarette), most classes of harmful and potentially harmful constituents (HPHCs) from this vaping product were below the level of detection or quantification. For those that were quantifiable, this vaping product generally had lower levels of emissions than the e-cigarette, including carbonyls. Formaldehyde and methyl glyoxal levels did not differ significantly between vaping products. In this system, the single mode of liquid transfer and vapor formation permits high aerosol mass delivery but further reduces emissions of HPHCs that may be present in conventional e-cigarette aerosol, by lessening the risk of thermal breakdown of the aerosol-generating solvent mixture.

10.
Sci Rep ; 10(1): 5414, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214168

RESUMO

Previous investigations have indicated that environmental and genetic factors collectively contribute to the development of acute mountain sickness (AMS), but whether the EDN1 gene is involved in AMS remains to be elucidated. A total of 356 healthy male soldiers who had not traveled to high altitudes in the previous 12 months were enrolled in our study. All participants were taken by plane from 500 m (Chengdu in Sichuan Province) to a 3700 m highland (Lhasa) within 2 hours. Clinical data were collected within 24 hours, and pulmonary function parameters were completed simultaneously. Genotypes were obtained by using iMLDR genotyping assays. A total of 237 soldiers (66.57%) presented AMS symptoms, including headache, dizziness, gastrointestinal upset and fatigue. Soldiers with AMS showed an increase in heart rate (HR), plasma tryptophan and serotonin, and a decrease in SaO2, FEV1, PEF, FVC, V75, V50, V25 and MMF (all P < 0.01). Notably, allele T in single nucleotide polymorphism (SNP) rs2070699 showed a positive correlation with the occurrence of AMS. A general linear regression analysis showed that rs2060799, Mean Arterial Pressure (MAP), SaO2, FVC, tryptophan and serotonin were independent predictors for the occurrence of AMS. Importantly, the area under the curve (AUC) values for tryptophan (0.998), serotonin (0.912) and FVC (0.86) had diagnostic specificity and sensitivity. Our results demonstrated that AMS is accompanied by changes in lung function parameters, increased plasma tryptophan and serotonin levels, and that the EDN1 polymorphism is a potential risk factor for AMS.

11.
Biotechnol Lett ; 42(6): 1061-1070, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32130565

RESUMO

In interstitial fibrosis, alveolar epithelial type II (AE2) cells fail to repair damaged epithelium. However, whether this dysfunction is related to fibroblast growth factor (FGF) signal pathway and how it affects the fibrotic process remains unclear. In our study, the medium of the human foetal lung fibroblast cell line MRC-5 (Med) can induce epithelial-to-mesenchymal transition (EMT) in AE2 cells, we also found that TGF-ß in Med can induce FGF-2 and CTGF expression in AE2 cells. TGF-ß or CTGF exposure trigger a FGFR2 subtype b to c transition which can be supressed by siRNA-CTGF. All together, since FGFR2IIIc have the highest affinity with FGF-2 in all of the FGFRs, we indicate the activation of FGF2 signal pathway was induced by TGF-ß, which is the key component of Med Here, we also find the inhibitory effect of msFGFR2c (S252W mutant of soluble FGFR2IIIc extracellular domain) on EMT of mouse primary AE2 cells in pulmonary fibrotic process. In a bleomycin-induced mouse pulmonary fibrosis model, msFGFR2c alleviate pulmonary fibrosis and suppress the decrease in pro-SPC levels. Thus, msFGFR2c can inhibit EMT-induced fibrosis of AE2 cells via FGF-2 signal and AE2 cells is suggested to play an important role in the lung fibrotic process.

12.
Biomed Res Int ; 2020: 1593068, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185192

RESUMO

Background: High-altitude headache (HAH) is the most common complication after high-altitude exposure. Hypoxia-inducible factor- (HIF-) related genes have been confirmed to contribute to high-altitude acclimatization. We aim to investigate a possible association between HIF-related genes and HAH in the Chinese Han population. Methods: In total, 580 healthy Chinese Han volunteers were recruited in Chengdu (500 m) and carried to Lhasa (3700 m) by plane in 2 hours. HAH scores and basic physiological parameters were collected within 18-24 hours after the arrival. Thirty-five single nucleotide polymorphisms (SNPs) in HIF-related genes were genotyped, and linkage disequilibrium (LD) was evaluated by Haploview software. The functions of SNPs/haplotypes for HAH were developed by using logistic regression analysis. Results: In comparison with wild types, the rs4953354 "G" allele (P=0.013), rs6756667 "A" allele (P=0.013), rs6756667 "A" allele (EPAS1, and rs6520015 "C" allele in PPARA (P=0.013), rs6756667 "A" allele (PPARA (P=0.013), rs6756667 "A" allele (EPAS1, and rs6520015 "C" allele in PPARA (P=0.013), rs6756667 "A" allele (. Conclusions: EPAS1 and PPARA polymorphisms were associated with HAH in the Chinese Han population. Our findings pointed out potentially predictive gene markers, provided new insights into understanding pathogenesis, and may further provide prophylaxis and treatment strategies for HAH.EPAS1, and rs6520015 "C" allele in PPARA (.

13.
Biotechnol Bioeng ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32175589

RESUMO

Beyond their widespread application as genome-editing and regulatory tools, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems also play a critical role in nucleic acid detection due to their high sensitivity and specificity. Recently developed Cas family effectors have opened the door to the development of new strategies for detecting different types of nucleic acids for a variety of purposes. Precise and efficient nucleic acid detection using CRISPR-Cas systems has the potential to advance both basic and applied biological research. In this review, we summarize the CRISPR-Cas systems used for the recognition and detection of specific nucleic acids for different purposes, including the detection of genomic DNA, nongenomic DNA, RNA, and pathogenic microbe genomes. Current challenges and further applications of CRISPR-based detection methods will be discussed according to the most recent developments.

14.
J Phys Chem Lett ; 11(7): 2765-2771, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32191479

RESUMO

In developing low-power electronics, low-voltage transistors have been intensively investigated. One of the most important findings is that some high-k oxide gate dielectrics can lead to remarkable enhancement of apparent mobility in thin-film transistors (TFTs), which is not clearly understood. Here, we investigate InOx TFTs with solution-processed AlOx dielectrics. At very low frequencies (<1 Hz), the AlOx films feature strong voltage-dependent capacitance. Also, cyclic voltammograms show clear features of surface-controlled Faradaic charge transfer. The two independent experiments both point to the formation of pseudocapacitance, which is similar to the mechanism behind some supercapacitors. A physical model including charge transfer is established to describe ion distribution. The charge transfer is probably related to residual hydrogens, as revealed by secondary-ion mass spectroscopy. The results provide direct evidence of the formation of pseudocapacitance in TFTs with high apparent mobilities and advance the understanding of mechanisms, measurements, and applications of such TFTs for low-power electronics.

15.
J Cell Mol Med ; 24(8): 4687-4697, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32166857

RESUMO

Increasing number of circular RNAs (circRNAs) have been reported to play important role in gene regulation, carcinogenesis and pathogenesis in various cancers. However, the biological functions and underlying molecular mechanisms of circRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain elusive. Thus, secondary circRNA-seq profiling was performed to identify the differentially expressed circRNAs between HSCC tissues and adjacent normal tissues, and the expression level of circMATR3 (derived from human gene matrin3 (MATR3), has_circRNA_0008922) was confirmed by qRT-PCR. Proliferation of HSCC cells was detected by cell counting kit-8 (CCK8) assay, apoptosis and the cell cycle were analysed by flow cytometry, and the migration and invasion of HSCC cells was determined by transwell assay. Bioinformatics analysis was conducted to predict possible pathways and potential miRNA targets of circMATR3. We found that circMATR3 was up-regulated in HSCC tissues, and abundant circMATR3 expression was markedly correlated with late T classification, advanced clinical stage, greater lymph node metastasis, and poor prognosis. Furthermore, knock-down of circMATR3 significantly inhibited proliferation, migration and invasion of HSCC cells, whereas silencing of circMATR3 induced cell apoptosis. Our analysis predicted that circMATR3 may participate in cancer-related pathways by serving as miRNA sponges. In conclusion, our findings first identified the oncogenic roles of circMATR3 in promoting the progression of HSCC and demonstrated that circMATR3 may be a novel prognostic marker and therapeutic target for HSCC.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32205218

RESUMO

BACKGROUND & AIMS: Non-invasive and accurate methods are needed to identify patients with clinically significant portal hypertension (CSPH). We investigated the ability of deep convolutional neural network (CNN) analysis of computed tomography (CT) or magnetic resonance (MR) to identify patients with CSPH. METHODS: We collected liver and spleen image from patients who underwent contrast-enhanced CT or MR analysis within 14 days of transjugular catheterization for hepatic venous pressure gradient measurement. The CT cohort comprised participants with cirrhosis in the CHESS1701 study, performed at 4 university hospitals in China from August 2016 through September 2017. The MR cohort comprised participants with cirrhosis in the CHESS1802 study, performed at 8 university hospitals in China and 1 in Turkey from December 2018 through April 2019. Patients with CSPH were identified as those with a hepatic venous pressure gradient ≥10 mmHg. In total, we analyzed 10014 liver images and 899 spleen images collected from 679 participants who underwent CT analysis, and 45554 liver and spleen images from 271 participants who underwent MR analysis. For each cohort, participants were shuffled and then randomly and equiprobably sampled for 6 times into training, validation, and test datasets (ratio of 3:1:1). Therefore, a total of 6 deep CNN models for each cohort were developed for identification of CSPH. RESULTS: The CT-based CNN analysis identified patients with CSPH with the area under receiver operating characteristic curve (AUC) value of 0.998 in the training set (95% CI, 0.996-1.000), an AUC of 0.912 in the validation set (95% CI, 0.854-0.971), and an AUC of 0.933 (95% CI, 0.883-0.984) in the test datasets. The MR-based CNN analysis identified patients with CSPH with an AUC of 1.000 in the training set (95% CI, 0.999-1.000), and AUC of 0.924 in the validation set (95% CI, 0.833-1.000), and an AUC of 0.940 in the test dataset (95% CI, 0.880-0.999). When the model development procedures were repeated 6 times, and AUCs for all CNN analyses were 0.888 or greater, with no significant differences between rounds (P>.05). CONCLUSIONS: We developed a deep CNN to analyze CT or MR images of liver and spleen from patients with cirrhosis that identifies patients with CSPH with an AUC value of 0.9. This provides a non-invasive and rapid method for detection of CSPH (ClincialTrials.gov number, NCT03138915; NCT03766880).

17.
Acta Otolaryngol ; : 1-7, 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186224

RESUMO

Background: Neoadjuvant chemotherapy is important for advanced laryngeal and hypopharyngeal carcinoma (LHC).Aims/objectives: To determine the efficacy and toxicity of the combination of docetaxel, nedaplatin, and 5-fluorouracil in induction treatment of advanced LHC.Material and methods: A total of 157 cancer patients were included. The primary endpoints of this study were overall response rate, pathological complete response rate, the safety of induction treatment, progression-free survival (PFS), and overall survival (OS).Results: After two-cycle induction treatment, 17(10.8%) patients experienced complete remission, 76 (48.4%) experienced partial remission, 47 (30.0%) had stable disease, and 17 (10.8%) had progressive disease. The TNM stage decreased by two or more in 17 cases, decreased by one in 71 cases, increased in 15 cases, and did not change in 54 cases after induction treatment. Most of the adverse chemotherapy responses were alleviated by symptomatic management. After the induction treatment, 29 patients continued receiving chemotherapy followed by radiotherapy, and 112 underwent surgical management depending on tumor site followed by radiotherapy. The median PFS was 13.00 ± 2.10 months and the median OS was 14.20 ± 0.29 months.Conclusions and significance: Combination of docetaxel, nedaplatin, and 5-fluorouracil plays an important role in the comprehensive treatment of advanced LHC.

18.
Cell Rep ; 30(12): 3951-3963.e4, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32209458

RESUMO

Rationally designing drugs that last longer in the face of biological evolution is a critical objective of drug discovery. However, this goal is thwarted by the diversity and stochasticity of evolutionary trajectories that drive uncertainty in the clinic. Although biophysical models can qualitatively predict whether a mutation causes resistance, they cannot quantitatively predict the relative abundance of resistance mutations in patient populations. We present stochastic, first-principle models that are parameterized on a large in vitro dataset and that accurately predict the epidemiological abundance of resistance mutations across multiple leukemia clinical trials. The ability to forecast resistance variants requires an understanding of their underlying mutation biases. Beyond leukemia, a meta-analysis across prostate cancer, breast cancer, and gastrointestinal stromal tumors suggests that resistance evolution in the adjuvant setting is influenced by mutational bias. Our analysis establishes a principle for rational drug design: when evolution favors the most probable mutant, so should drug design.

19.
Front Immunol ; 11: 62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32153559

RESUMO

Viral infection is associated with many types of tumorigenesis, including human papillomavirus (HPV)-induced cervical cancer. The induction of a specific T-cell response against virus-infected cells is desired to develop an efficient therapeutic approach for virus-associated cancer. Chinese herbal medicine (CHM) has a long history in the treatment of cancer patients in Asian countries. Hedyotis diffusa Willd (Bai Hua She She Cao, BHSSC) is frequently used clinically and has been shown to inhibit tumor growth in vitro. However, in vivo data demonstrating the antitumor efficacy of BHSSC are still lacking. We showed that BHSSC induces murine and human antigen-presenting cell (APC) activation via the MAPK signaling pathway and enhances antigen presentation in bone marrow-derived dendritic cells (BMDCs) in vitro. Furthermore, we identified that treatment with BHSSC leads to improved specific effector and memory T-cell responses in vivo. Variant peptide-based vaccines combined with BHSSC improved antitumor activity in preventive, therapeutic, and recurrent HPV-related tumor models. Furthermore, we showed that rutin, one of the ingredients in BHSSC, induces a strong specific immune response against HPV-related tumors in vivo. In summary, we demonstrated that BHSSC extract and its active compound, rutin, can be used as adjuvants in peptide-based vaccines to increase immunogenicity and to bypass the requirement of a conditional adjuvant.

20.
J Arthroplasty ; 35(6): 1703-1707, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32046872

RESUMO

BACKGROUND: The purpose of this study is to investigate the incidence and timing of postoperative, symptomatic pulmonary embolism (PE) in patients receiving nonwarfarin treatment following primary total joint arthroplasty (TJA), to clarify the appropriate duration of postoperative VTE prophylaxis. METHODS: We retrospectively reviewed the medical records of 11,148 patients who underwent primary TJA, including total knee arthroplasty and total hip arthroplasty at our institution between January 2012 and March 2019. The median postoperative day of diagnosis of symptomatic PE and the interquartile range for day of diagnosis were determined. Multivariate Cox proportional hazards modeling was used to test the difference of timing for PE based on demographics and comorbidities. RESULTS: The overall 90-day rate of symptomatic PE was 0.71%. The median day of diagnosis for symptomatic PE was 3 days postoperatively (interquartile range, 2-7 days). Factors showed statistical significance on multivariate analysis in association with earlier timing of PE occurrence in patients with atrial fibrillation, diabetes mellitus, coronary heart disease, and history of stroke. CONCLUSION: The vast majority of symptomatic PE occurs in the early postoperative period after TJA, and atrial fibrillation, diabetes mellitus, coronary heart disease, and history of stroke were independent factors affecting the timing of symptomatic PE.

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