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1.
BMC Cancer ; 22(1): 9, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980000

RESUMO

PURPOSE: We sought to understand the clinical course and molecular phenotype of patients who showed disease progression after programmed cell death ligand 1 (PD-L1) inhibitor treatment but subsequently responded to PD-1 inhibitor treatment. We also explored the response to PD-1-axis targeted therapy of classical Hodgkin lymphoma (cHL) according to genetically driven PD-L1 and programmed cell death ligand 2 (PD-L2) expression. METHODS: Five patients in a phase II clinical trial of CS1001 (PD-L1 inhibitor) for relapsed or refractory (R/R) cHL were retrospectively reviewed. Formalin-fixed, paraffin-embedded whole tissues from the five patients were evaluated for 9p24.1 genetic alterations based on FISH and the expression of PD-L1, PD-L2, PD-1, major histocompatibility complex (MHC) class I-II, and the tumor microenvironment factorsCD163 and FOXP3 in the microenvironmental niche, as revealed by multiplex immunofluorescence. RESULTS: All five patients showed primary refractory disease during first-line treatment. Four patients received PD-1 inhibitor after dropping out of the clinical trial, and all demonstrated at least a partial response. The progression-free survival ranged from 7 to 28 months (median = 18 months), and 9p24.1 amplification was observed in all five patients at the PD-L1/PD-L2 locus. PD-L1 and PD-L2 were colocalized on Hodgkin Reed-Sternberg (HRS) cells in four of the five (80%) patients. There was differential expression of PD-L1 and PD-L2 in cells in the tumor microenvironment in cHL, especially in HRS cells, background cells and tumor-associated macrophages. CONCLUSIONS: PD-L1 monotherapy may not be sufficient to block the PD-1 pathway; PD-L2 was expressed in HRS and background cells in cHL. The immunologic function of the PD-L2 pathway in anti-tumor activity may be underestimated in R/R cHL. Further study is needed to elucidate the anti-tumor mechanism of PD-1 inhibitor and PD-L1 inhibitor treatment.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 264: 120207, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34419829

RESUMO

Lysozyme (Lyz) is an important antibacterial protein that exists widely in nature. In recent years, the application of graphene oxide (GO) in the field of biotechnology electronics, optics, chemistry and energy storage has been extensively studied. However, due to the unique properties of GO, the mechanism of its interaction with biomacromolecule proteins is very complex. To further explore the interaction between GO and proteins we explore the influence of different pH and heat treatment conditions on the interaction between GO and Lyz, the GO (0-20 µg/mL) was added at a fixed Lyz concentration (0.143 mg/mL) under different pHs. The structure and surface charge changes of Lyz were measured by spectroscopic analysis and zeta potential. The results showed that the interaction between GO and Lyz depends on temperature and pH, significant changes have taken place in its tertiary and secondary structures. By analyzing the UV absorption spectrum, it was found that lysozyme and GO formed a stable complex, and the conformation of the enzyme was changed. In acidic pH conditions (i.e., pH < pI), a high density of Lyz were found to adsorb on the GO surface, whereas an increase in pH resulted in a progressive decrease in the density of the adsorbed Lyz. This pH-dependent adsorption is ascribed to the electrostatic interactions between the negatively charged GO surface and the tunable ionization of the Lyz molecules. The secondary structure of Lyz adsorbed on GO was also found to be highly dependent on the pH. In this paper, we investigated the exact mechanism of pH-influenced GO binding to lysozyme, which has important guidance significance for the potential toxicity of GO biology and its applications in biomedical fields such as structure-based drug design.


Assuntos
Grafite , Muramidase , Adsorção , Muramidase/metabolismo , Estrutura Secundária de Proteína
3.
Sci Total Environ ; 806(Pt 3): 150685, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600986

RESUMO

Livestock farms are recognized as the main sources of antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) with potential implications for human health. In this study, we systematically analyzed microbiome composition, distribution of ARGs and mobile genetic elements (MGEs) in the oropharynx and gut of workers in cattle farms and surrounding villagers, cattle feces and farm air, and the relationship of microbial communities among farm air, cattle feces and farmworkers (oropharynx and gut). Exposure to the farm environment may have remodeled farmworkers' oropharynx and gut microbiota, with reduced microbial diversity (P < 0.05) and enrichment of some opportunistic pathogenic bacteria like Shigella, Streptococcus, and Neisseria in the oropharynx. Meanwhile, compared with villagers, ARG abundance in oropharynx of farmworkers increased significantly (P < 0.05), but, no significant difference in gut (P > 0.05). Microbial composition and ARG profile in farmworkers might be influenced by working time and work type, ARG abundance in farmworkers' gut was positively correlated with working time (P < 0.01), and higher ARG abundance was found in the oropharynx of drovers. The network analysis revealed that 4 MGEs (tnpA-01, tnpA-04, Tp614, and IS613), 5 phyla (e.g. Bacteroidetes, Fusobacteria, and TM7), and 6 genera were significantly associated with 37 ARGs (ρ > 0.6, P < 0.01). Overall, our results indicated that farm exposure may have affected the microbial composition and increased ARG abundance of farmworkers. Transmission of some ARGs may have occurred among the environment, animals and humans via host bacteria, which might pose a potential threat to human health.


Assuntos
Antibacterianos , Microbiota , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Animais , Antibacterianos/farmacologia , Bovinos , Resistência Microbiana a Medicamentos , Fazendas , Genes Bacterianos , Orofaringe
4.
Bioresour Technol ; 344(Pt A): 126162, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34678451

RESUMO

Bamboo biomass was widely considered as a promising substitute for lignocellulose to produce fermentable sugars and biofuels in the south of China. When P. amarus were treated using hydrogen peroxide and acetic Acid pretreatment in the presence of sulphuric acid at 60 ℃ for 2 h, 82.63% lignin was removed from the bamboo residue, and enzymatic saccharification yield of 79.3% and ethanol content of 13.31 g/L were obtained. Analysis indicated that HPAC pretreatment increased the hydrophilic and porous nature of substrate, which can improve the enzyme accessibility to cellulose. When HPAC-pretreated D. sinicus, B. lapidea, N. affinis, andD. giganteus were used as the substrates of enzymatic saccharification, glucose yields of 71-84% at 72 h were achieved. HPAC pretreatment was a highly efficient and environmentally friendly method for bamboo biorefinery in the south of China.


Assuntos
Ácido Acético , Peróxido de Hidrogênio , Biocombustíveis , Biomassa , Celulose , Hidrólise , Lignina
5.
Front Microbiol ; 12: 779749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880847

RESUMO

Salmonella contamination of eggs and egg shells has been identified as a public health problem worldwide. Here, we reported an outbreak of severe gastrointestinal symptoms caused by Salmonella enterica serovar Enteritidis (S. enteritidis) in China. We evaluated the outbreak by using epidemiological surveys, routine laboratory testing methods, and whole genome sequencing (WGS). This outbreak occurred in a canteen in Beijing, during March 9-11, 2021, 225 of the 324 diners who have eaten at the canteen showed gastrointestinal symptoms. The outbreak had characteristical epidemiological and clinical features. It caused a very high attack rate (69.4%) in a short incubation time. All patients developed diarrhea and high fever, accompanied by abdominal pain (62.3%), nausea (50.4%), and vomiting (62.7%). The average frequency of diarrhea was 12.4 times/day, and the highest frequency of diarrhea was as high as 50 times/day. The average fever temperature was 39.4°C, and the highest fever temperature was 42°C. Twenty strains of S. enteritidis were recovered, including 19 from the patients samples, and one from remained egg fried rice. Antibiotic susceptibility test showed that the 20 outbreak strains all had the same resistance pattern. PFGE results demonstrated that all 20 strains bore completely identical bands. Phylogenetic analysis based on WGS revealed that all 20 outbreak strains were tightly clustered together. So the pathogenic source of this food poisoning incident may was contaminated egg fried rice. Resistance gene analysis showed that the outbreak strains are all multi-drug resistant strains. Virulence gene analysis indicated that these outbreak strains carried a large number of virulence genes, including 2 types of Salmonella pathogenicity islands (SPI-1 and SPI-2). Other important virulence genes were also carried by the outbreak strains, such as pefABCD, rck and shdA. And the shdA gene was not in other strains located in the same evolutionary branch as the outbreak strain. We speculated that this is a significant reason for the serious symptoms of gastroenteritis in this outbreak. This outbreak caused by S. enteritidis suggested government should strengthen monitoring of the prevalence of outbreak clone strains, and take measures to mitigate the public health threat posed by contaminated eggs.

6.
Front Immunol ; 12: 761354, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880859

RESUMO

Objective: To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children. Methods: Children hospitalized in the Department of Neurology, Hunan Children's Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestations and imaging characteristics, five children who were only positive for GFAP-IgG antibodies in serum were excluded, and the remaining 35 children were diagnosed with autoimmune GFAP-A. The clinical data derived from the 35 children were retrospectively analyzed. Results: A total of 35 children, including 23 males and 12 females with a mean age of 6.3 ± 0.6 years, manifested clinical symptoms of fever (62.9%), headache (42.9%), convulsions (42.9%), abnormal mental behavior (51.4%), disorders of consciousness (54.3%), visual disturbance (22.9%), ataxia (11.4%), paralysis (40%), and autonomic dysfunction (25.7%). One child exhibited only the clinical symptom of peripheral facial nerve palsy. Eleven out of 35 children were also positive for other antibodies. In addition to the common overlapping autoimmune syndromes, one case of autoimmune GFAP-A also manifested as Bickerstaff's brainstem encephalitis. Linear periventricular enhancement upon MRI was significantly less frequent in children (8.5%) than in adults. In pediatric patients, MRI contrast enhancement was principally seen in the meninges and brain lobes. Although repeated relapse (17.1%) and sequelae symptoms (20%) occurred in some cases, most children showed a favorable prognosis. Spearman's rank correlation showed that the antibody titer was not significantly associated with the severity of the initial disease conditions. Conclusions: The disease diagnosis in children seropositive for GFAP antibodies only should receive a comprehensive diagnosis based on their clinical symptoms, imaging, electroencephalographic characteristics, and treatment responses. Some patients with relapses should receive repeated gamma globulin and corticosteroid therapy or the addition of immunosuppressants to their therapeutic regimen, and slow-dose tapering of corticosteroids and extended treatment are recommended for patients with overlapping autoimmune syndromes.

7.
Front Pharmacol ; 12: 727102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34867332

RESUMO

Background: Bevacizumab was demonstrated to have efficacy in patients with NSCLC. However, application of different doses of bevacizumab in different clinical trials was overlooked. This study aims to investigate the effects and safety of different doses of bevacizumab in the treatment. Methods: From January 2016 to March 2020, 79 patients with NSCLC received first-line combination treatment with chemotherapy (pemetrexed + platinum) and bevacizumab for four cycles; patients without progression after four cycles were randomly assigned to maintenance therapy with bevacizumab combined with pemetrexed, of which 57 patients received bevacizumab at a dose of 7.5 mg/kg and 22 patients at a dose of 15 mg/kg. The primary endpoint was progression-free survival, and secondary endpoints were overall response rate, disease control rate, and adverse events. Results: There was no significant difference between two groups in effectiveness; Median PFS in 7.5 mg/kg group and in 15 mg/kg group were 8.0 and 8.7 months, respectively (p = 0.663), reaching the primary endpoint. The ORR and DCR in the bevacizumab 7.5 and 15 mg/kg group were 45.46 and 86.0% vs. 50 and 90.9% showing no statistical significance (p = 0.804 and 0.717). Most of side effects were tolerable. The incidences of overall toxicities were higher in 15 mg/kg group (p = 0.001). No new safety signals were observed. Conclusion: We did not detect significant difference of efficacy and safety between 7.5 mg/kg group and 15 mg/kg group for bevacizumab administration, the cost-effectiveness of the 7.5 mg/kg group was significantly better than that of the 15 mg/kg group.

9.
BMC Endocr Disord ; 21(1): 240, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34856980

RESUMO

BACKGROUND: Pentraxin 3 (PTX3) - a crucial humoral innate immunity component - is related to obesity and cardiovascular complications in women who suffer from polycystic ovary syndrome (PCOS). However, the circulating PTX3 level in PCOS is still debated. In this study, we aimed to evaluate PTX3 plasma levels in PCOS women of childbearing age, and find possible endocrine/metabolic factors that could affect this level. METHODS: A total of 360 women were enrolled: 120 PCOS women and 240 body mass index (BMI) matched normally ovulating women. Blood samples were collected on the third day of natural menstrual cycle or from the bleeding after progesterone withdrawal. The PTX3 concentration was measured by immunoassay. RESULTS: The PTX3 plasma level was significantly higher in PCOS women compared to controls. There was a positive correlation between PTX3 plasma level and PCOS diagnosis, overweight, cycle length, serum LH to FSH ratio, estradiol, total testosterone (TT) on the third day of menstrual cycle, antral follicle count (AFC), as well as uric acid. Multivariant linear regression analysis indicated that participants' serum PTX3 levels were proportional to the circulating TT level, existence of PCOS, basal estradiol level and AFC. CONCLUSIONS: Overall, the circulating PTX3 level was elevated in PCOS women and significantly associated with the presence of hyperandrogenism. This study provided the basis for further in-depth researches regarding PTX3 role in PCOS pathophysiology.

10.
Bioresour Technol ; 346: 126639, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34971777

RESUMO

A three-constituent deep eutectic solvent (3c-DES) pretreatment with choline chloride-oxalic acid-ethylene glycol was applied to examine its effectiveness on bamboo residues. The 3c-DES pretreatment can remove 91.09% xylan and significantly improved the 72 h hydrolysis yield of D. sinicus by 6.3 and 1.7 times as compared with the liquid hot water and two-constituent deep eutectic solvent (2c-DES) pretreatment. The introduction of ethylene glycol (EG) into choline chloride (ChCl)/ oxalic acid (OA) decreased the content of surface lignin and the condensation of lignin, which contributed to the increase of hydrophilic nature and cellulose accessibility in substrates. Moreover, higher glucose (85.72%) and xylose (91.05%) yields of 3c-DES pretreated bamboo were achieved with the addition of Tween 80. The 3c-DES system provides an alternative approach for the development of efficient bamboo pretreatment, and had broad space for bamboo biorefinery in southern China.

11.
Reprod Biol Endocrinol ; 19(1): 187, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34906165

RESUMO

BACKGROUND: Recurrent implantation failure (RIF) is a major limitation of assisted reproductive technology, which is associated with impaired endometrial receptivity. Although N6-methyladenosine (m6A) has been demonstrated to be involved in various biological processes, its potential role in the endometrium of women with RIF has been poorly studied. METHODS: Global m6A levels and major m6A methyltransferases/demethylases mRNA levels in mid-secretory endometrium from normal and RIF women were examined by colorimetric m6A quantification strategy and quantitative real-time PCR, respectively. The effects of METTL3-mediated m6A modification on embryo attachment were evaluated by an vitro model of a confluent monolayer of Ishikawa cells co-cultured with BeWo spheroids, and the expression levels of homeo box A10 (HOXA10, a well-characterized marker of endometrial receptivity) and its downstream targets were evaluated by quantitative real-time PCR and Western blotting in METTL3-overexpressing Ishikawa cells. The molecular mechanism for METTL3 regulating HOXA10 expression was determined by methylated RNA immunoprecipitation assay and transcription inhibition assay. RESULTS: Global m6A methylation and METTL3 expression were significantly increased in the endometrial tissues from women with RIF compared with the controls. Overexpression of METTL3 in Ishikawa cells significantly decreased the ration of BeWo spheroid attachment, and inhibited HOXA10 expression with downstream decreased ß3-integrin and increased empty spiracles homeobox 2 expression. METTL3 catalyzed the m6A methylation of HOXA10 mRNA and contributed to its decay with shortened half-life. Enforced expression of HOXA10 in Ishikawa cells effectively rescued the impairment of METTL3 on the embryo attachment in vitro. CONCLUSION: Increased METTL3-mediated m6A modification represents an adverse impact on embryo implantation by inhibiting HOXA10 expression, contributing to the pathogenesis of RIF.

12.
Medicine (Baltimore) ; 100(47): e27907, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34964760

RESUMO

RATIONALE: Early-onset facioscapulohumeral muscular dystrophy (FSHD) is defined as facial weakness before the age of 5 and shoulder weakness before the age of 10. Early-onset facioscapulohumeral muscular dystrophy is relatively rare in the clinic. This onset is relatively early, the symptoms are serious, and it is likely to be accompanied by retinal vascular disease, sensorineural deafness, epilepsy and other extramuscular multisystem diseases. We report the clinical characteristics of 2 patients with early-onset facial and shoulder brachial muscular dystrophy to improve clinicians' understanding of this particular condition. PATIENT CONCERNS: We report 2 pediatric patients with FSHD type 1. Patient 1 is an 11-year-old boy with reduced facial expression for 9 years and proximal muscle weakness for 6 years. Patient 2 is a 4-year and 6-month-old girl with developmental delay for 3 years and facial weakness for 1 year. DIAGNOSIS: According to the clinical manifestations and molecular genetic testing (such as Southern blot analysis), the patients were diagnosed with early-onset FSHD1. INTERVENTIONS: The patients received cocktail therapy (vitamin B1 tablets, vitamin B2 tablets, vitamin B6 tablets, vitamin C tablets, vitamin E tablets, idebenone tablets, etc.) to improve their muscle metabolism. OUTCOMES: Both patients' condition did not improve after being given cocktail treatment. According to a recent follow-up, the symptoms of facial weakness and proximal muscle weakness were aggravated. LESSONS: Early-onset FSHD presents early and has frequent systemic features, and it is a severe subtype of FSHD. Early identification and genetic diagnosis should be performed to improve patient prognosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34911084

RESUMO

PURPOSE: To develop a simple and clinically useful assessment tool for osteoporosis in older women with type 2 diabetes mellitus (T2DM). METHODS: A total of 601 women over 60 years of age with T2DM were enrolled in this study. The levels of serum sex hormones and bone metabolism markers were compared between the osteoporosis and non-osteoporosis groups. The least absolute shrinkage and selection operator regularization (LASSO) model was applied to generate a risk assessment tool. The risk score formula was evaluated using receiver operating characteristic analysis and the relationship between the risk score and the bone mineral density (BMD) and T-value were investigated. RESULTS: Serum sex hormone-binding globulin (SHBG), cross-linked C-telopeptide of type 1 collagen (CTX), and osteocalcin (OC) were significantly higher in the osteoporosis group. After adjustment for age and body mass index (BMI), SHBG was found to be correlated with the T-value or BMD. Then, a risk score was specifically generated with age, BMI, SHBG, and CTX using the LASSO model. The risk score was significantly negatively correlated with the T-value and BMD of the lumbar spine, femoral neck, and total hip (all P<0.05). CONCLUSION: A risk score using age, BMI, SHBG, and CTX performs well for identifying osteoporosis in older women with T2DM.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34896340

RESUMO

OBJECTIVE: The purpose of the present study was to clarify the expression of thyroid-stimulating hormone receptor (TSHR) in microglial cells, and to explore its function. MATERIALS AND METHODS: Expression of TSHR in microglia was determined by Western blot, immunocytofluorescence and double immunohistofluorescence. Cyclic adenosine 3',5'-monophosphate (cAMP) production was measured after thyrotropin receptor stimulating antibody (TSAb) treatment. RESULTS: Results showed that TSHR protein was expressed and mainly located in the mouse microglia membrane. Moreover, TSAb stimulated cAMP production in mouse microglia (p<0.05). CONCLUSIONS: This study demonstrated the presence of TSHR in microglial cells. Brain TSHR was able to respond specifically to TSAb stimulation, suggesting that TSHR expression is functional. As microglia are innate immune cells that maintain environmental stability in the central nervous system and play a key role in many neuroimmune diseases, expression of functional TSHR in microglia has important pathophysiological implications.

15.
Front Microbiol ; 12: 736565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34751223

RESUMO

Staphylococcus aureus (S. aureus), which is one of the most important species of Staphylococci, poses a great threat to public health. Clustered regularly interspaced short palindromic repeats (CRISPR) and their CRISPR-associated proteins (Cas) are an adaptive immune platform to combat foreign mobile genetic elements (MGEs) such as plasmids and phages. The aim of this study is to describe the distribution and structure of CRISPR-Cas system in S. aureus, and to explore the relationship between CRISPR and horizontal gene transfer (HGT). Here, we analyzed 67 confirmed CRISPR loci and 15 companion Cas proteins in 52 strains of Staphylococci with bioinformatics methods. Comparing with the orphan CRISPR loci in Staphylococci, the strains harboring complete CRISPR-Cas systems contained multiple CRISPR loci, direct repeat sequences (DR) forming stable RNA secondary structures with lower minimum free energy (MFE), and variable spacers with detectable protospacers. In S. aureus, unlike the orphan CRISPRs away from Staphylococcal cassette chromosome mec (SCCmec), the complete CRISPR-Cas systems were in J1 region of SCCmec. In addition, we found a conserved motif 5'-TTCTCGT-3' that may protect their downstream sequences from DNA interference. In general, orphan CRISPR locus in S. aureus differed greatly from the structural characteristics of the CRISPR-Cas system. Collectively, our results provided new insight into the diversity and characterization of the CRISPR-Cas system in S. aureus.

16.
Front Microbiol ; 12: 770935, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34819926

RESUMO

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic since March 2020 and led to significant challenges to over 200 countries and regions all over the world. The establishment of highly pathogenic coronavirus animal model is beneficial for the study of vaccines and pathogenic mechanism of the virus. Laboratory mice, Syrian hamsters, Non-human primates and Ferrets have been used to establish animal models of emerging coronavirus infection. Different animal models can reproduce clinical infection symptoms at different levels. Appropriate animal models are of great significance for the pathogenesis of COVID-19 and the research progress related to vaccines. This review aims to introduce the current progress about experimental animal models for SARS-CoV-2, and collectively generalize critical aspects of disease manifestation in humans and increase their usefulness in research into COVID-19 pathogenesis and developing new preventions and treatments.

17.
Int Immunopharmacol ; : 108390, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34844871

RESUMO

OBJECTIVE: The aim of this study was to investigate the impact of asthma on the risk for mortality among coronavirus disease 2019 (COVID-19) patients in the United States by a quantitative meta-analysis. METHODS: A random-effects model was used to estimate the pooled odds ratio (OR) with corresponding 95% confidence interval (CI). I2 statistic, sensitivity analysis, Begg's test, meta-regression and subgroup analyses were also performed. RESULTS: The data based on 56 studies with 426,261 COVID-19 patients showed that there was a statistically significant association between pre-existing asthma and the reduced risk for COVID-19 mortality in the United States (OR: 0.82, 95% CI: 0.74-0.91). Subgroup analyses by age, male proportion, sample size, study design and setting demonstrated that pre-existing asthma was associated with a significantly reduced risk for COVID-19 mortality among studies with age ≥ 60 years old (OR: 0.79, 95% CI: 0.72-0.87), male proportion ≥ 55% (OR: 0.79, 95% CI: 0.72-0.87), male proportion < 55% (OR: 0.81, 95% CI: 0.69-0.95), sample sizes ≥ 700 cases (OR: 0.80, 95% CI: 0.71-0.91), retrospective study/case series (OR: 0.82, 95% CI: 0.75-0.89), prospective study (OR: 0.83, 95% CI: 0.70-0.98) and hospitalized patients (OR: 0.82, 95% CI: 0.74-0.91). Meta-regression did reveal none of factors mentioned above were possible reasons of heterogeneity. Sensitivity analysis indicated the robustness of our findings. No publication bias was detected in Begg's test (P = 0.4538). CONCLUSION: Our findings demonstrated pre-existing asthma was significantly associated with a reduced risk for COVID-19 mortality in the United States.

18.
Front Oncol ; 11: 750323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804937

RESUMO

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1-2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

19.
Oncol Lett ; 22(6): 849, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34733367

RESUMO

Due to the high incidence of colorectal cancer worldwide, the underlying molecular mechanisms have been extensively investigated. The Wnt/ß-catenin signaling pathway plays a key role in the carcinogenesis of colorectal adenoma. In addition, the high mobility group AT-hook 2 (HMGA2) protein, which is involved in several biological processes, such as proliferation, differentiation, transformation and metastasis, is expressed at significantly high levels in colorectal cancer tissues compared with adjacent normal tissues. Currently, the role of HMGA2 in the carcinogenesis of sporadic colorectal tubular adenoma remains unclear. The downstream Wnt/ß-catenin signaling molecule, T-cell factor/lymphoid enhancing factor (TCF/LEF), shares a similar domain with HMGA2, which enhances ß-catenin transcriptional activity and TCF/LEF binding. Thus, the present study investigated the association between HMGA2 and the Wnt/ß-catenin signaling pathway, and their role in the carcinogenesis of sporadic colorectal tubular adenoma via immunohistochemistry, siRNA, quantitative PCR and western blot analyses. The results demonstrated that the positive rate of HMGA2 expression gradually increased during tumor progression. Furthermore, HMGA2 expression was positively correlated with Wnt/ß-catenin signaling protein expression [Wnt, ß-catenin, cyclin-dependent kinase 4 (CDK4) and cyclin D1], suggesting its involvement in the carcinogenesis of sporadic colorectal tubular adenoma and its potential to synergistically interact with the Wnt/ß-catenin signaling pathway. HMGA2 knockdown in the human colorectal cancer cell line, HCT 116 decreased ß-catenin expression and its downstream targets, CDK4 and cyclin D1. Furthermore, silencing of Wnt or ß-catenin decreased HMGA2 expression. Taken together, the results of the present study suggest the coordinated regulation of HMGA2 and the Wnt/ß-catenin signaling pathway in the carcinogenesis of sporadic colorectal tubular adenoma.

20.
Clin Cancer Res ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716199

RESUMO

PURPOSE: Tislelizumab is an anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody specifically designed to minimize binding to Fcγ receptors (FcγR). EXPERIMENTAL DESIGN: Here, we present the extended 3-year follow-up of a phase II study of tislelizumab in 70 patients with relapsed/refractory classical Hodgkin lymphoma (cHL) who failed or were ineligible for autologous stem cell transplantation. RESULTS: With a median follow-up of 33.8 months, the overall response rate by the independent review committee was 87.1%, and the complete response (CR) rate was 67.1%. Responses were durable as shown by a median duration of response of 31.3 months, and median progression-free survival (PFS) of 31.5 months. The 3-year PFS and overall survival rates were 40.8% and 84.8%, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 97.1% of patients; the grade {greater than or equal to}3 TRAE rate was low (31.4%), and only 8.6% of patients experienced adverse events leading to treatment discontinuation. Correlative biomarker analysis showed that FcγRΙ-expressing macrophages had no observed impact on either the CR rate or PFS achieved with tislelizumab, which may be potentially related to its engineered Fc region. CONCLUSIONS: With extended follow-up, tislelizumab yielded long-term benefits and demonstrated a favorable safety profile for patients with relapsed/refractory cHL. This trial was registered at clinicaltrials.gov as NCT03209973.

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