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1.
Adv Healthc Mater ; : e2002202, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33943037

RESUMO

The topographic features at the cell-material biointerface are critical for cellular sensing of the extracellular environment (ECM) and have gradually been recognized as key factors that regulate cell adhesion behavior. Herein, a well-defined nanostructured biointerface is fabricated via a new generation of mussel-inspired polymer coating to mimic the native ECM structures. Upon the bioinert background presence and biospecific ligands conjugation, the affinity of cancer cells to the resulting biofunctional surfaces, which integrate topographic features and biochemical cues, is greatly strengthened. Both the conjugated bioligand density, filopodia formation, and focal adhesion expression are significantly enhanced by the surficial nano-features with an optimized size-scale. Thus, this nanostructured biointerface exhibits high capture efficiency for circulating tumor cells (CTCs) with high sensitivity, high biospecificity, and high purity. Benefiting from the unique bioligands conjugation chemistry herein, the captured cancer cells can be responsively detached from the biointerfaces without damage for downstream analysis. The present biofunctional nanostructured interfaces offer a good solution to address current challenges to efficiently isolate rare CTCs from blood samples for earlier cancer diagnosis.

2.
Arthritis Res Ther ; 23(1): 122, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33882993

RESUMO

BACKGROUND: The esophagus involvement in systemic sclerosis (SSc) is very common yet underestimated due to the lack of suitable screening tools. This study aims to explore the usefulness of ultrasound (US) in the assessment of esophagus involvement and to identify its relationship with clinical and CT manifestations. METHODS: We performed transabdominal esophageal US in 38 SSc patients and 38 controls. US parameters including the abdominal esophagus length, esophagus wall thickness, shear-wave elastography, gastro-esophageal (His) angle, and reflux were compared. Relationships between distinguishable US parameters and clinical/CT parameters, such as gastro-esophageal reflux disease questionnaire (GERDQ), modified Rodnan skin score (mRSS), interstitial lung disease (ILD) score, the largest esophagus diameter (Dmax), and esophagus dilation percentage (%Eop), were evaluated. RESULTS: Abdominal esophagus length was shorter in the SSc group than the control group (2.69 cm vs 3.06 cm, P = 0.018), whereas His angle and the angle change before and after drinking water were larger in the SSc group than the control group (121° vs 108°, P < 0.001; 7.97° vs 2.92°, P = 0.025). Reflux was more frequently seen in the SSc group than the control group (7/38 vs 0/38; P = 0.017). As for correlation with clinical and CT parameters, His angle was higher in patients with GERDQ ≥ 8 than GERDQ < 8 (116.5° vs 125.6°, P = 0.035). Patients with reflux showed higher ILD score than patients without (15.8 vs 9.6, P = 0.043). Furthermore, abdominal esophagus length was negatively correlated with %Eop and Dmax (r = - 0.573, P < 0.001; r = - 0.476, P = 0.003). CONCLUSION: US parameters of the esophagus can distinguish SSc patients from controls, as well as have correlations with clinical and CT characteristics. Our pilot study first shows that US can be used as a noninvasive and convenient method to evaluate the esophagus involvement in SSc.

3.
Environ Sci Technol ; 55(8): 4440-4451, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33793238

RESUMO

Pig production contributes considerably to land use and greenhouse gas (GHG) and reactive nitrogen (Nr) emissions. Land use strategies were widely proposed, but the spillover effects on biological flow are rarely explored. Here, we simultaneously assessed the carbon (C), nitrogen (N), and cropland footprints of China's pig production at the provincial scale in 2017. The environmental impacts of land use strategies were further evaluated. Results show that one kg live-weight pig production generated an average of 1.9 kg CO2-equiv and 59 g Nr emissions, occupying 3.5 m2 cropland, with large regional variations. A large reduction in GHG (58-64%) and Nr (12-14%) losses and occupied cropland (10-11%) could be achieved simultaneously if combined strategies of intensive crop production, improved feed-protein utilization efficiency, and feeding co-products were implemented. However, adopting a single strategy may have environmental side-effects. Reallocating cropland that pigs used for feed to plant food alternatives would enhance human-edible energy (3-20 times) and protein delivery (1-5 times) and reduce C and N footprints, except for rice and vegetables. Reallocating cropland to beef and milk production would decrease energy and protein supply. Therefore, a proper combination of land use strategies is essential to alleviate land use changes and nutrient emissions without sacrificing food supply.


Assuntos
Efeito Estufa , Gases de Efeito Estufa , Animais , Pegada de Carbono , Bovinos , China , Gases de Efeito Estufa/análise , Nitrogênio/análise , Suínos
4.
Aging Cell ; 20(3): e13323, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657282

RESUMO

There is growing interest in studying the genetic contributions to longevity, but limited relevant genes have been identified. In this study, we performed a genetic association study of longevity in a total of 15,651 Chinese individuals. Novel longevity loci, BMPER (rs17169634; p = 7.91 × 10-15 ) and TMEM43/XPC (rs1043943; p = 3.59 × 10-8 ), were identified in a case-control analysis of 11,045 individuals. BRAF (rs1267601; p = 8.33 × 10-15 ) and BMPER (rs17169634; p = 1.45 × 10-10 ) were significantly associated with life expectancy in 12,664 individuals who had survival status records. Additional sex-stratified analyses identified sex-specific longevity genes. Notably, sex-differential associations were identified in two linkage disequilibrium blocks in the TOMM40/APOE region, indicating potential differences during meiosis between males and females. Moreover, polygenic risk scores and Mendelian randomization analyses revealed that longevity was genetically causally correlated with reduced risks of multiple diseases, such as type 2 diabetes, cardiovascular diseases, and arthritis. Finally, we incorporated genetic markers, disease status, and lifestyles to classify longevity or not-longevity groups and predict life span. Our predictive models showed good performance (AUC = 0.86 for longevity classification and explained 19.8% variance of life span) and presented a greater predictive efficiency in females than in males. Taken together, our findings not only shed light on the genetic contributions to longevity but also elucidate correlations between diseases and longevity.

5.
Phys Rev Lett ; 126(7): 075701, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33666443

RESUMO

Shock reverberation compression experiments on dense gaseous deuterium-helium mixtures are carried out to provide thermodynamic parameters relevant to the conditions in planetary interiors. The multishock pressures are determined up to 120 GPa and reshock temperatures to 7400 K. Furthermore, the unique compression path from shock-adiabatic to quasi-isentropic compressions enables a direct estimation of the high-pressure sound velocities in the unexplored range of 50-120 GPa. The equation of state and sound velocity provide particular dual perspectives to validate the theoretical models. Our experimental data are found to agree with several equation of state models widely used in astrophysics within the probed pressure range. The current data improve the experimental constraints on sound velocities in the Jovian insulating-to-metallic transition layer.

6.
EBioMedicine ; 65: 103242, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33684886

RESUMO

BACKGROUND: Type 2 diabetes (T2D) increases the risk of many types of cancer. Dysregulation of proteasome-related protein degradation leads to tumorigenesis, while Exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist, possesses anti-cancer effects. METHODS: We explored the co-expression of proteasome alpha 2 subunit (PSMA2) and GLP-1R in the Cancer Genome Atlas (TCGA) database and human cervical cancer specimens, supplemented by in vivo and in vitro studies using multiple cervical cancer cell lines. FINDINGS: PSMA2 expression was increased in 12 cancer types in TCGA database and cervical cancer specimens from patients with T2D (T2D vs non-T2D: 3.22 (95% confidence interval CI: 1.38, 5.05) vs 1.00 (0.66, 1.34) fold change, P = 0.01). psma2-shRNA decreased cell proliferation in vitro, and tumour volume and Ki67 expression in vivo. Exendin-4 decreased psma2 expression, tumour volume and Ki67 expression in vivo. There was no change in GLP-1R expression in 12 cancer types in TCGA database. However, GLP-1R expression (T2D vs non-T2D: 5.49 (3.0, 8.1) vs 1.00 (0.5, 1.5) fold change, P < 0.001) was increased and positively correlated with PSMA2 expression in T2D-related (r = 0.68)  but not in non-T2D-related cervical cancer specimens. This correlation was corroborated by in vitro experiments where silencing glp-1r decreased psma2 expression. Exendin-4 attenuated phospho-p65 and -IκB expression in the NF-κB pathway. INTERPRETATION: PSMA2 and GLP-1R expression in T2D-related cervical cancer specimens was increased and positively correlated, suggesting hyperglycaemia might promote cancer growth by increasing PSMA2 expression which could be attenuated by Exendin-4. FUNDING: This project was supported by Postdoctoral Fellowship Scheme, Direct Grant, Diabetes Research and Education Fund from the Chinese University of Hong Kong (CUHK).

7.
Int J Immunopathol Pharmacol ; 35: 20587384211000547, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33752456

RESUMO

The relapsing polychondritis (RP) patients with central nervous system (CNS) involvement were rare. We aimed to determine the clinical characteristics of RP patients with CNS involvement. The clinical data of 181 RP patients, hospitalized at Peking Union Medical College Hospital between December 2005 and February 2019, were collected. The patients were categorized into two subgroups: 25 RP patients with CNS involvement, and 156 RP patients without CNS involvement. The involvement of the ear was more frequent in RP patients with CNS involvement, compared with those of RP patients without CNS involvement (P < 0.01). After controlling sex and the admission age, logistic regression analysis revealed hypertension (odds ratio = 4.308, P = 0.006) and involvement of eye (odds ratio = 5.158, P = 0.001) and heart (odds ratio = 3.216, P = 0.025) were correlated with RP patients with CNS involvement, respectively. In addition, pulmonary infection (odds ratio = 0.170, P = 0.020), tracheal involvement (odds ratio = 0.073, P < 0.01), and involvement of laryngeal (odds ratio = 0.034, P = 0.001), costochondral joint (odds ratio = 0.311, P = 0.013), sternoclavicular joint (odds ratio = 0.163, P = 0.017) and manubriosternal joint (odds ratio = 0.171, P = 0.021) were associated with RP patients without CNS involvement, respectively. In contrast to RP patients without CNS involvement, the incidence of ear involvement was higher in RP patients with CNS involvement. After controlling the potential confounding factor sex and the admission age, hypertension and involvement of eye and heart were related with RP patients with CNS involvement, respectively.

8.
J Diabetes Res ; 2021: 3170190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553435

RESUMO

Methods: In this multicenter retrospective study, patients with COVID-19 in China were included and classified into two groups according to whether they were complicated with diabetes or not. Demographic symptoms and laboratory data were extracted from medical records. Univariable and multivariable logistic regression methods were used to explore the risk factors. Results: 538 COVID-19 patients were finally included in this study, of whom 492 were nondiabetes and 46 were diabetes. The median age was 47 years (IQR 35.0-56.0). And the elderly patients with diabetes were more likely to have dry cough, and the alanine aminotransferase, lactate dehydrogenase, Ca, and mean hemoglobin recovery rate were higher than the other groups. Furthermore, we also found the liver and kidney function of male patients was worse than that of female patients, while female cases should be paid more attention to the occurrence of bleeding and electrolyte disorders. Moreover, advance age, blood glucose, gender, prothrombin time, and total cholesterol could be considered as risk factors for COVID-19 patients with diabetes through the multivariable logistic regression model in our study. Conclusion: The potential risk factors found in our study showed a major piece of the complex puzzle linking diabetes and COVID-19 infection. Meanwhile, focusing on gender and age factors in COVID-19 patients with or without diabetes, specific clinical characteristics, and risk factors should be paid more attention by clinicians to figure out a targeted intervention to improve clinical efficacy worldwide.


Assuntos
/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Hospitalização , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
9.
Gigascience ; 10(1)2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33438729

RESUMO

BACKGROUND: The main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. RESULTS: The genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population. CONCLUSIONS: Our results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.

10.
Clin Transl Med ; 11(1): e253, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33463049

RESUMO

The tumor microenvironment is a complex ecosystem formed by distinct and interacting cell populations, and its composition is related to cancer prognosis and response to clinical treatment. In this study, we have taken the advantage of two single-cell RNA sequencing technologies (Smart-seq2 and DNBelab C4) to generate an atlas of 15,115 immune and nonimmune cells from primary tumors and hepatic metastases of 18 colorectal cancer (CRC) patients. We observed extensive changes in the proportions and functional states of T cells and B cells in tumor tissues, compared to those of paired non-tumor tissues. Importantly, we found that B cells from early CRC tumor were identified to be pre-B like expressing tumor suppressors, whereas B cells from advanced CRC tumors tended to be developed into plasma cells. We also identified the association of IgA+ IGLC2+ plasma cells with poor CRC prognosis, and demonstrated a significant interaction between B-cell and myeloid-cell signaling, and found CCL8+ cycling B cells/CCR5+ T-cell interactions as a potential antitumoral mechanism in advanced CRC tumors. Our results provide deeper insights into the immune infiltration within CRC, and a new perspective for the future research in immunotherapies for CRC.

11.
Arthritis Res Ther ; 23(1): 21, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430962

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is an acquired autoimmune disorder characterized by excessive accumulation of collagen and progressive tissue fibrosis. Although interstitial lung disease (ILD) complicates the majority of SSc patients and is the leading cause of death, its pathogenesis remains largely unclear. In the current study, we aimed to evaluate the role of microRNAs in SSc-ILD. METHODS: miRNA expression patterns were assessed by miRNA array and real-time PCR from serum and PBMCs of SSc-ILD patients and healthy controls. Bleomycin-induced SSc-ILD mouse model was used to verify the miRNA expression in the lung tissue. The function of miRNAs in pulmonary fibroblasts was assessed using miRNA inhibitors, and mimics. RESULTS: miR-320a was significantly downregulated in both SSc-ILD patients and mouse models. The inhibition or overexpression of miR-320a in human pulmonary fibroblasts significantly affected the protein expression of type I collagen. Luciferase reporter assay, RT-PCR, and western blot analysis identified TGFBR2 and IGF1R as direct targets of miR-320a. Upon TGF-ß stimulation, the expression of miR-320a and collagen genes were significantly upregulated. CONCLUSION: miR-320a, together with its target genes, TGFBR2 and IGF1R, constituted a complex regulatory network, and played an important role in the fibrotic process of SSc-ILD. Investigation of more detailed mechanisms of miR-320a-mediated regulation of collagen expression may provide new therapeutic strategies for SSc-ILD.

12.
J Exp Med ; 218(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33136155

RESUMO

Both somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by activation-induced cytidine deaminase (AID). Dysregulation of these processes has been linked to B cell lymphomagenesis. Here we performed an in-depth analysis of diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL) genomes. We characterized seven genomic mutational signatures, including two B cell tumor-specific signatures, one of which is novel and associated with aberrant SHM. We further identified two major mutational signatures (K1 and K2) of clustered mutations (kataegis) resulting from the activities of AID or error-prone DNA polymerase η, respectively. K1 was associated with the immunoglobulin (Ig) switch region mutations/translocations and the ABC subtype of DLBCL, whereas K2 was related to the Ig variable region mutations and the GCB subtype of DLBCL and FL. Similar patterns were also observed in chronic lymphocytic leukemia subtypes. Thus, alterations associated with aberrant CSR and SHM activities can be linked to distinct developmental paths for different subtypes of B cell lymphomas.

13.
Cell ; 184(2): 404-421.e16, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33357445

RESUMO

Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.

14.
Carbohydr Polym ; 254: 117481, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357932

RESUMO

The intrinsic intermittence of solar energy raises the necessity for thermal energy storage (TES) systems to balance the contradiction between energy supply and demand energy. This work experimentally provides solid-liquid phase change materials (PCMs) with sufficient storage capacity and discharging rate to offer heating for agriculture products by enhancing heat transfer in phase change fiber composites (PCF). To achieve this, we prepared dipole responsive magnetic/solar-driven PCF composites reinforced with magnetic cellulose nanocrystals hybrids (MCNC). The obtained PCF/MCNC-5% showed excellent magnetic property with a saturation magnetization (MS) value of 1.3 emu/g and effective latent heat phase change enthalpies of 69.2 ± 3.5 J/g - 83.1 ± 4.2 J/g. More importantly, PCF/MCNC-5% showed robust high magnetic to thermal energy storage efficiency of 32.5 % and solar light accelerated energy storage efficiency of 58.5 %. These advantages make the PCF composites promising and more desirable for drying and preservation of the fruits and other agriculture products.

15.
Biomaterials ; 268: 120543, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33260094

RESUMO

Hydrogels with tunable mechanical properties have provided a tremendous opportunity to regulate stem cell differentiation. Hydrogels with osteoid (about 30-40 kPa) or higher stiffness are usually required to induce the osteogenic differentiation of mesenchymal stem cells (MSCs). It is yet difficult to achieve the same differentiation on very soft hydrogels, because of low environmental mechanical stimuli and restricted cellular mechanotransduction. Here, we modulate cellular spatial sensing of integrin-adhesive ligands via quasi-hexagonally arranged nanopatterns to promote cell mechanosensing on hydrogels having low stiffness (about 3 kPa). The increased interligand spacing has been shown to regulate actomyosin force loading to recruit extra integrins on soft hydrogels. It therefore activates mechanotransduction and promotes the osteogenic differentiation of MSCs on soft hydrogels to the level comparable with the one observed on osteoid stiffness. Our work opens up new possibilities for the design of biomaterials and tissue scaffolds for regenerative therapeutics.

16.
PLoS One ; 15(12): e0244125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33332437

RESUMO

BACKGROUND: A worldwide outbreak of coronavirus disease (COVID-19), since 2019, has brought a disaster to people all over the world. Many researchers carried out clinical epidemiological studies on patients with COVID-19 previously, but risk factors for patients with different levels of severity are still unclear. METHODS: 562 patients with laboratory-confirmed COVID-19 from 12 hospitals in China were included in this retrospective study. Related clinical information, therapies, and imaging data were extracted from electronic medical records and compared between patients with severe and non-severe status. We explored the risk factors associated with different severity of COVID-19 patients by logistic regression methods. RESULTS: Based on the guideline we cited, 509 patients were classified as non-severe and 53 were severe. The age range of whom was 5-87 years, with a median age of 47 (IQR 35.0-57.0). And the elderly patients (older than 60 years old) in non-severe group were more likely to suffer from fever and asthma, accompanied by higher level of D-dimer, red blood cell distribution width and low-density lipoprotein. Furthermore, we found that the liver and kidney function of male patients was worse than that of female patients in both severe and non-severe groups with different age levels, while the severe females had faster ESR and lower inflammatory markers. Of major laboratory markers in non-severe cases, baseline albumin and the lymphocyte percentage were higher, while the white blood cell and the neutrophil count were lower. In addition, severe patients were more likely to be accompanied by an increase in cystatin C, mean hemoglobin level and a decrease in oxygen saturation. Besides that, advanced age and indicators such as count of white blood cell, glucose were proved to be the most common risk factors preventing COVID-19 patients from aggravating. CONCLUSION: The potential risk factors found in our study have shown great significance to prevent COVID-19 patients from aggravating and turning to critical cases during treatment. Meanwhile, focusing on gender and age factors in groups with different severity of COVID-19, and paying more attention to specific clinical symptoms and characteristics, could improve efficacy of personalized intervention to treat COVID-19 effectively.


Assuntos
/metabolismo , Índice de Gravidade de Doença , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , /epidemiologia , Criança , Pré-Escolar , China/epidemiologia , Surtos de Doenças , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
17.
Artigo em Inglês | MEDLINE | ID: mdl-33188425

RESUMO

OBJECTIVES: To analyse the effectiveness of tofacitinib for the treatment of refractory skin thickening in dcSSc. METHODS: Data from 10 patients with dcSSc treated with tofacitinib (5 mg twice daily) were analysed. A total of 12 dcSSc patients treated with intensive conventional immunosuppressants were selected as the historical comparator group. A clinically relevant response was defined as a decrease in the modified Rodnan skin score (mRSS) of >5 points and ≥25% from baseline. Clinical indicators were compared between the two groups to evaluate the effect of tofacitinib. RESULTS: The mRSS significantly improved the first month after tofacitinib treatment, with a mean change in the mRSS of -3.7 (95% CI -5.52, -1.88; P = 0.001) and greater than the comparators at 6 months [-10.0 (95% CI -14.74, -5.26) vs -4.1 (95% CI -7.49, -0.73), P = 0.026]. Tofacitinib-treated patients had a significantly shorter response time than the comparators (P = 0.015 by log-rank test), with overall response rates of 20% (2/10) vs 0% (0/12) and 60% (6/10) vs 16.7% (2/12) at 1 and 3 months, respectively. CONCLUSION: Our results indicate that tofacitinib may be as effective as or even better than intensive conventional immunosuppressants, with a quicker and higher response rate in refractory dcSSc patients with progressive skin thickness.

18.
Adv Mater ; : e2006986, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206452

RESUMO

The extracellular matrix (ECM) undergoes dynamic remodeling and progressive stiffening during tissue regeneration and disease progression. However, most of the artificial ECMs and in vitro disease models are mechanically static. Here, a self-strengthening polymer coating mimicking the dynamic nature of native ECM is designed to study the cellular response to dynamic biophysical cues and promote cell mechanical sensitive response. Spiropyran (SP) is utilized as dynamic anchor group to regulate the strength of cell adhesive peptide ligands. Benefiting from spontaneous thermal merocyanine-to-spiropyran (MC-SP) isomerization, the resulting self-responsive coating displays dynamic self-strengthening of interfacial interactions. Comparing with the static and all of the previous dynamic artificial ECMs, cells on this self-responsive surface remodel the weakly bonded MC-based coatings to activate α5ß1 integrin and Rac signaling in the early adhesion stage. The subsequent MC-to-SP conversion strengthens the ligand-integrin interaction to further activate αvß3 integrin and RhoA/ROCK signaling in the latter stage. This sequential process enhances cellular mechanotransduction as well as the osteogenic differentiation of mesenchymal stem cells (MSCs). It is worth emphasizing that the self-strengthening occurs spontaneously in the absence of any stimulus, making it especially useful for implanted scaffolds in regenerative medicine.

19.
Int J Clin Pract ; : e13819, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33159416

RESUMO

OBJECTIVE: To analyse clinical characteristics, risk and prognosis factors for systemic sclerosis (SSc) patients with lung cancer. METHODS: SSc patients with lung cancer admitted to Peking Union Medical College Hospital from February 1992 to December 2018 were included. Age and sex-matched controls were selected from a pool of SSc patients without lung cancer during the same period. Conditional logistic regression and Cox proportional-hazard regression were used to identify risk factors and prognosis factors. The Kaplan-Meier method was used to draw the survival curve and calculate median survival. RESULTS: Nineteen SSc patients with lung cancer and 76 controls were included. The mean age at lung cancer diagnosis was 54.4 ± 10.2 years. In all 19 cases the lung cancer had been diagnosed after SSc and the median interval between SSc onset and lung cancer onset was 10.5 years (range 2.0-36.2 years). Among SSc patients with lung cancer, the median follow-up time and median survival were 2.6 years and 1.4 years, respectively. In the sex and age-matched conditional logistic multivariable regression analysis, family history of malignancy (OR 4.930, 95%CI 1.926-12.619, P = .001), ILD (OR 7.701, 95%CI 1.009-58.767, P = .049) were independent risk factors for lung cancer among SSc patients, and considering sex and age of SSc onset, SSc patients with more advanced staging of lung cancer (HR 3.190, 95%CI 1.127-6.126, P = .06) had poorer prognosis. CONCLUSION: Lung cancer is not uncommon in SSc patients, especially those with family histories of malignancy or ILD. Early detection of lung cancer is of vital importance for better prognosis.

20.
Pharmacol Res ; : 105290, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33181320

RESUMO

The coronavirus disease 2019 (COVID-19) epidemic has been almost controlled in China under a series of policies, including "early diagnosis and early treatment". This study aimed to explore the association between early treatment with Qingfei Paidu decoction (QFPDD) and favorable clinical outcomes. In this retrospective multicenter study, we included 782 patients (males, 56 %; median age 46) with confirmed COVID-19 from 54 hospitals in nine provinces of China, who were divided into four groups according to the treatment initiation time from the first date of onset of symptoms to the date of starting treatment with QFPDD. The primary outcome was time to recovery; days of viral shedding, duration of hospital stay, and course of the disease were also analyzed. Compared with treatment initiated after 3 weeks, early treatment with QFPDD after less than 1 week, 1-2 weeks, or 2-3 weeks had a higher likelihood of recovery, with adjusted hazard ratio (HR) (95 % confidence interval [CI]) of 3.81 (2.65-5.48), 2.63 (1.86-3.73), and 1.92 (1.34-2.75), respectively. The median course of the disease decreased from 34 days to 24 days, 21 days, and 18 days when treatment was administered early by a week (P < 0.0001). Treatment within a week was related to a decrease by 1-4 days in the median duration of hospital stay compared with late treatment (P<0.0001). In conclusion, early treatment with QFPDD may serve as an effective strategy in controlling the epidemic, as early treatment with QFPDD was associated with favorable outcomes, including faster recovery, shorter time to viral shedding, and a shorter duration of hospital stay. However, further multicenter, prospective studies with a larger sample size should be conducted to confirm the benefits of early treatment with QFPDD.

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