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1.
Injury ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34625240

RESUMO

BACKGROUND: Chest trauma was the third most common cause of death in polytrauma patients, accounting for 25% of all deaths from traumatic injury. Chest trauma involves in injury to the bony thorax, intrathoracic organs and thoracic medulla. This study aimed to investigate the incidence, clinical characteristics, and outcome of polytrauma patients with pulmonary contusion, flail chest and upper thoracic spinal injury. METHODS: Patients who met inclusion criteria were divided into groups: Pulmonary contusion group (PC); Pulmonary contusion and flail chest group (PC + FC); Pulmonary contusion and upper thoracic spinal cord injury group (PC + UTSCI); Thoracic trauma triad group (TTT): included patients with flail chest, pulmonary contusion and the upper thoracic spinal cord injury coexisted. Outcomes were determined, including 30-day mortality and 6-month mortality. RESULTS: A total 84 patients (2.0%) with TTT out of 4176 polytrauma patients presented to Tongji trauma center. There was no difference in mean ISS among PC + FC group, PC + UTSCI group and TTT group. Patients with TTT had a longer ICU stay (21.4 days vs. 7.5 and 6.2; p<0.01), relatively higher 30-day mortality (40.5% vs. 6.0% and 4.3%; p<0.01), and especially higher 6-month mortality (71.4% vs. 6.5%, 13.0%; p<0.01), compared to patients with PC + FC or with PC + UTSCI. The leading causes of death for patients with TTT were ARDS (44.1%) and pulmonary infection (26.5%) during first 30 days after admission. For those patients who died later than 30 days during the 6 months, the predominant underlying cause of death was MOF (53.8%). CONCLUSIONS: Lethal triad of thoracic trauma (LTTT) were described in this study, which consisting of pulmonary contusion,flail chest and the upper thoracic spine cord injury. Like the classic "lethal triad", there was a synergy between the factors when they coexist, resulting in especially high mortality rates. Polytrauma patients with LTTT were presented relatively high 30-day mortality and 6 months mortality. We should pay much more attention to the patients with LTTT for further minimizing complications and mortality.

2.
J Immunother Cancer ; 9(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34599021

RESUMO

BACKGROUND: Triple negative breast cancer (TNBC) is a subtype of breast cancers with poor prognosis and targeted drug therapies are limited. To develop novel and efficacious therapies for TNBC, we developed a bispecific antibody F7AK3 that recognizes both trophoblast cell surface antigen 2 (TROP2) and CD3 and evaluated its antitumor activities both in vitro and in vivo. METHODS: The binding affinities of F7AK3 to the two targets, TROP2 and CD3, were evaluated by surface plasmon resonance. Binding of F7AK3 to TNBC cells and T cells were evaluated by flow cytometry. Immunofluorescent staining was performed to demonstrate the interactions between T cells with TNBC cells. The cytotoxicity of T cells against TNBC cell lines and primary tumor cells mediated by F7AK3 were determined in vitro. In vivo antitumor activity of F7AK3 was investigated in a xenograft TNBC tumor model, using immunodeficient mice that were reconstituted with human peripheral blood mononuclear cells. RESULTS: We demonstrated that F7AK3 binds specifically to human TROP2 and CD3 antigens, as well as TNBC cell lines and primary tumor cells. Human T cells can only be activated by F7AK3 in the presence of target tumor cells. F7AK3 recruits T cells to TROP2+ tumor cells in vitro and into tumor tissues in vivo. Antitumor growth activity of F7AK3 is observed in a xenograft TNBC tumor model. CONCLUSION: This study showed the antitumor potential of an anti-TROP2xCD3 bispecific antibody F7AK3 to TNBC tumor cells both in vitro and in vivo. These data demonstrate that F7AK3 has the potential to treat TNBC patients, which warrants further preclinical and clinical evaluation of the F7AK3 in advanced or metastatic TNBC patients.

3.
J Leukoc Biol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34612525

RESUMO

Iron plays a critical role in immune responses. However, its role in T helper cell differentiation and function remains poorly understood. In this study, it is shown that the restraint of iron availability through blocking CD71-mediated iron endocytosis impaired the differentiation and pathogenicity of TH 17 cells. Administrations of anti-CD71 mAb could relieve the development of experimental autoimmune encephalomyelitis (EAE). Mechanistically, the iron deficiency due to the blocking of CD71 enhanced IL-2 expression, which further restrained the differentiation of TH 17 cells. Meanwhile, CD71 blockade impaired histone modifications of Il17 gene and reduced the recruitment of RORγt to Il17a locus. In sum, the findings reveal that iron plays a pivotal role in regulating TH 17 cell differentiation and function in autoimmune diseases.

4.
RNA Biol ; : 1-12, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586036

RESUMO

RNA-seq has been widely used to reveal the molecular mechanism of variants of life process. We have developed an alternative method, MustSeq, which generates multiple second strands along a single 1st strand cDNA by random-priming initiation, immediately after reverse transcription for each RNA extract using sample-barcoded poly-dT primers, then 3' ends-enriching PCR is applied to construct the library. Unlike the conventional RNA seq, MustSeq avoids procedures such as mRNA isolation, fragmentation and RNA 5'-end capture, enables early pooling of multiple samples, and requires only one twentieth of sequencing reads of full-length sequencing. We demonstrate the power and features of MustSeq comparing with TruSeq and NEBNext RNA-seq, two conventional full-length methods and QuantSeq, an industrial 3' end method. In cancer cell lines, the reads distribution of CDS-exon as well as genes, lncRNAs and GO terms detected by MustSeq are closer than QuantSeq to TruSeq. In mouse hepatocarcinoma and healthy livers, MustSeq enriches the same pathways as by NEBNext, and reveals the molecular profile of carcinogenesis. Overall MustSeq is a robust and accurate RNA-seq method allowing efficient library construction, sequencing and analysis, particularly valuable for analysis of differentially expressed genes with a large number of samples. MustSeq will greatly accelerate the application of bulk RNA-seq on different fields, and potentially applicable for single cell RNA-seq.

5.
BMC Infect Dis ; 21(1): 951, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521370

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable mortality. The risk factors, clinical treatments, especially comprehensive risk models for COVID-19 death are urgently warranted. METHODS: In this retrospective study, 281 non-survivors and 712 survivors with propensity score matching by age, sex, and comorbidities were enrolled from January 13, 2020 to March 31, 2020. RESULTS: Higher SOFA, qSOFA, APACHE II and SIRS scores, hypoxia, elevated inflammatory cytokines, multi-organ dysfunction, decreased immune cell subsets, and complications were significantly associated with the higher COVID-19 death risk. In addition to traditional predictors for death risk, including APACHE II (AUC = 0.83), SIRS (AUC = 0.75), SOFA (AUC = 0.70) and qSOFA scores (AUC = 0.61), another four prediction models that included immune cells subsets (AUC = 0.90), multiple organ damage biomarkers (AUC = 0.89), complications (AUC = 0.88) and inflammatory-related indexes (AUC = 0.75) were established. Additionally, the predictive accuracy of combining these risk factors (AUC = 0.950) was also significantly higher than that of each risk group alone, which was significant for early clinical management for COVID-19. CONCLUSIONS: The potential risk factors could help to predict the clinical prognosis of COVID-19 patients at an early stage. The combined model might be more suitable for the death risk evaluation of COVID-19.


Assuntos
COVID-19 , Sepse , Humanos , Unidades de Terapia Intensiva , Escores de Disfunção Orgânica , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
6.
J Card Surg ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499370

RESUMO

OBJECTIVE: Postinfarction ventricular septal defect (PIVSD) is a severe complication of acute myocardial infarction (AMI). Transcatheter closure (TCC) is an alternative option to surgical repair. This study was undertaken to examine the published literature to provide objective evidence for TCC using a meta-analysis. METHODS: We searched for significant medical and publisher databases. Two reviewers checked the quality of the studies and extracted data. Eligible studies included single-arm studies and comparative studies. Weighted means, pooled event rates, efficacy outcomes and odds ratios (ORs) for immediate shunt reduction (ISR), presence of cardiogenic shock (CS), New York Heart Association (NYHA) class IV, time from AMI to ventricular septal defect (VSD), and time to VSD closure was estimated. RESULTS: A total of 27 single-arm articles (462 patients) were included. The pooled event rate was 89.7% (95% confidence interval [CI]: 0.772-1.021) for successful device implantation, 80.9% (95% CI: 0.645-0.972) for ISR, 31.5% (95% CI: 0.149-0.482) for 30-day mortality, and 25.3% (95% CI: 0.072-0.434) for 30-day mortality of primary closure at the acute phase. CS (OR = 3.607, 95% CI: 2.301-5.653), NYHA class IV (OR = 6.491, 95% CI: 1.444-29.188) and time to VSD closure were risk predictors for TCC. There was no correlation between defect size (OR = 2.592, 95% CI: 0.380-17.661) and mortality. CONCLUSION: TCC should be a relatively safe and minimally invasive method for PIVSD, with an excellent successful device implantation rate and acceptable low 30-day mortality. The procedure appears promising, but its safety and efficacy could only be demonstrated by randomized controlled trials. Therefore, the mortality of data comparing surgery to TCC compels the need for future comparative trials.

7.
Signal Transduct Target Ther ; 6(1): 328, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471088

RESUMO

Understanding the pathological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in an animal model is crucial for the treatment of coronavirus disease 2019 (COVID-19). Here, we compared immunopathological changes in young and old rhesus macaques (RMs) before and after SARS-CoV-2 infection at the tissue level. Quantitative analysis of multiplex immunofluorescence staining images of formalin-fixed paraffin-embedded (FFPE) sections showed that SARS-CoV-2 infection specifically induced elevated levels of apoptosis, autophagy, and nuclear factor kappa-B (NF-κB) activation of angiotensin-converting enzyme 2 (ACE2)+ cells, and increased interferon α (IFN-α)- and interleukin 6 (IL-6)-secreting cells and C-X-C motif chemokine receptor 3 (CXCR3)+ cells in lung tissue of old RMs. This pathological pattern, which may be related to the age-related pro-inflammatory microenvironment in both lungs and spleens, was significantly correlated with the systemic accumulation of CXCR3+ cells in lungs, spleens, and peripheral blood. Furthermore, the ratio of CXCR3+ to T-box protein expression in T cell (T-bet)+ (CXCR3+/T-bet+ ratio) in CD8+ cells may be used as a predictor of severe COVID-19. These findings uncovered the impact of aging on the immunopathology of early SARS-CoV-2 infection and demonstrated the potential application of CXCR3+ cells in predicting severe COVID-19.


Assuntos
Linfócitos T CD8-Positivos/imunologia , COVID-19/imunologia , Microambiente Celular/imunologia , Pulmão/imunologia , Receptores CXCR3/imunologia , SARS-CoV-2/imunologia , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Linfócitos T CD8-Positivos/patologia , COVID-19/patologia , Modelos Animais de Doenças , Inflamação/imunologia , Inflamação/patologia , Interferon-alfa/imunologia , Interleucina-6/imunologia , Pulmão/patologia , Pulmão/virologia , Macaca mulatta , Masculino
8.
Small ; : e2103140, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510739

RESUMO

The miniaturization of lasers holds promise in ultradense data storage and biosensing, but greater pump power is required to reach the lasing thresholds to overcome increased optical losses with reduced resonant cavity sizes. Here, the whispering galley mode (WGM) of Yb3+ /Tm3+ doped upconversion nanoparticles (UCNPs) coupled with microcavities (≈5 µm) is used to achieve ultralow threshold upconverted lasing at 800 nm with excitation fluences as low as 4 W cm-2 . The continuous-wave (CW) upconverted lasing, with a Q factor on the order of 103 , can remain stable for more than 6 h. In addition, ultralow threshold upconverted microlasers spanning the full visible spectrum from Yb3+ /Er3+ , Yb3+ /Ho3+ , and Yb3+ /Tm3+ doped UCNPs are obtained with the same WGM cavity design. These upconverted microlasers working under low power CW 980 nm laser will enable promising applications in biosensing and imaging.

9.
Toxicology ; 460: 152884, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34358620

RESUMO

Perfluorodecanoic acid (PFDA) is a member of the perfluoroalkyl substances, which are toxic to organic functions. Recently, it has been found in follicular fluid, seriously interfering with reproduction. Follicular fluid provides the oocyte with necessary resources during the process of oocytes maturation. However, the effects of PFDA on the oocyte need investigation. Our study evaluated the impacts of PFDA on the meiosis and development potential of mouse oocytes by exposing oocytes to PFDA in vitro at 350, 400, and 450 µM concentrations. The results showed that exposure to PFDA resulted in the first meiotic prophase arrest by obstructing the function of the maturation-promoting factor. It also induced the dysfunction of the spindle assembly checkpoint, expedited the progression of the first meiotic process, and increased the risk of aneuploidy. The oocytes treated with PFDA had a broken cytoskeleton which also contributed to meiotic maturation failure. Besides, PFDA exposure caused mitochondria defections, increased the reactive oxygen species level in oocytes, and consequently induced oocyte apoptosis. Moreover, PFDA produced epigenetic modifications in oocytes and increased the frequency of mature oocytes with declined development potential. In summary, our data indicated that PFDA disturbs the meiotic process and induces oocyte quality deterioration.


Assuntos
Ácidos Decanoicos/toxicidade , Fluorcarbonetos/toxicidade , Meiose/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Relação Dose-Resposta a Droga , Feminino , Humanos , Fator Promotor de Maturação/metabolismo , Meiose/fisiologia , Camundongos , Camundongos Endogâmicos ICR
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 380-384, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374257

RESUMO

Objective: To investigate the effects of Shaosha-7 in rats with myocardial ischemia-reperfusion injury and its mechanisms. Methods: male SD rats were divided into sham operation group (n=10), myocardial ischemia-reperfusion injury group (n=10), low, medium and high dose of Shaosha-7 groups (n=10), and positive drug group (n=10). The rats of Shaosha-7 (low, medium and high dose) groups were treated with Shaosha-7 at the doses of 0.4, 0.8 and 1.6 g/kg respectively, once a day for 15 days. The rats of positive drug group were treated with 0.3 g/kg Danshen, once a day for 15 days. The rats of the sham operation group and myocardial ischemia-reperfusion injury were treated with 2 ml/100 g distilled water, once a day for 15 days. After 15 days, the rats of the model group and the treatment group underwent thoracotomy and ligation of coronary artery for 30 minutes, then thoracic cavity was closed after reperfusion. Rats in six groups were executed electrocardiographic examination and their hearts were taken for Hematoxylin-Eosin (HE) staining and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining to observe infarct area and myocardial pathological changes. The contents of cTnI, CK-MB, LDH, MDA, SOD, GSH-Px, TNF-α, IL-18, IL-6 and IL-1 ß in serum were detected by ELISA. The expression of NF-кB was detected by immunohistochemistry. Results: Compared with the sham operation group, the infarct size, the levels of cTnI, CK-MB, CK-MB, LDH, MDA, GSH-Px, TNF-α, IL-18, IL-6, IL-1ß and NF-кB were increased and the content of SOD were decreased in rats with myocardial ischemia-reperfusion injury. Compared with the rats with myocardial ischemia-reperfusion injury, Shaosha-7 improved the arrhythmia and pathological changes, reduced the infarct area, decreased the contents of cTnI, CK-MB, LDH, MDA, GSH-Px, TNF-α, IL-18, IL-6, IL-1 ß, increased the content of SOD, decreased the expression of NF-кB. Conclusion: Mongolian medicine Shaosha-7 can effectively alleviate myocardial ischemia-reperfusion injury in rats. This study provides a theoretical basis for the treatment of myocardial ischemia-reperfusion (I/R) injury with Shaosha-7.


Assuntos
Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Animais , Masculino , Medicina Tradicional da Mongólia , Isquemia Miocárdica/tratamento farmacológico , Miocárdio , NF-kappa B , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3180-3187, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396735

RESUMO

The soaking and fermentation of Baphicacanthus cusia( Nees),the important intermediate link of Indigo Naturalis processing,facilitates the synthesis of indigo and indirubin precursors and the dissolution of endogenous enzymes and other effective components,while the role of microorganisms in the fermentation is ignored. The present study investigated the changes of microbial community structure in Indigo Naturalis processing based on 16 S amplicon sequencing and bioinformatics. Meanwhile,the contents of indigo,indirubin,isatin,tryptanthrin,indole glycoside,etc. were determined to explore the correlation between the microorganisms and the alterations of the main components. As demonstrated by the results,the microbial diversity decreased gradually with the fermentation,which bottomed out after the addition of lime. Proteobacteria,Bacteroidetes,and Firmicutes were the main dominant communities in the fermentation. The relative abundance of Proteobacteria declined gradually with the prolongation of fermentation time,and to the lowest level after the addition of lime. The relative abundance of Firmicutes increased,and that of Bacteroidetes decreased first and then increased. The contents of effective substances in Indigo Naturalis also showed different variation tendencies. As fermentation went on,indole glycoside decreased gradually; indigo first increased and then decreased; indirubin and isatin first decreased and then increased; tryptanthrin gradually increased. Those changes were presumedly related to the roles of microorganisms in the synthesis of different components. This study preliminarily clarified the important role of microorganisms in the soaking and fermentation and provided a scientific basis for the control of Indigo Naturalis processing and the preparation of high-quality Indigo Naturalis.


Assuntos
Indigofera , Microbiota , Fermentação , Índigo Carmim , Indóis
12.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3205-3212, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396738

RESUMO

As an effective antipyretic medicine,Indigo Naturalis has a long history of application in the field of Chinese medicine.The content of organics,mainly indigo and indirubin,is about 10%. However,the active ingredients and mechanism of its antipyretic effect have not yet been fully elucidated. In view of this,they were investigated in this study with the rectal temperature change as an indicator and 2,4-dinitrophenol-induced fever rats as subjects. The content of PGE2 and c AMP in the hypothalamus and the serum levels of TNF-α,IL-1ß and IL-6 were determined by ELISA. Moreover,the plasma samples of fever rats were analyzed by metabonomics in combination with UPLC-Q-TOF-MS for the exploration of potential biomarkers and the discussion on the antipyretic mechanism of Indigo Naturalis and its active ingredients. The results showed that the rising trend of rectal temperature in rats was suppressed 0. 5 h after the treatment with Indigo Naturalis,organic matter,indigo or indirubin as compared with the rats of model group( P < 0. 05),among which Indigo Naturalis and organic matter had better antipyretic effect. ELISA results showed that organic matter and indigo can inhibit the expression of PGE2 and c AMP( P<0. 01),while Indigo Naturalis and organic matter were effective in curbing the increase in TNF-α( P<0. 05). A total of 21 endogenous metabolites were identified from the plasma samples of the Indigo Naturalis,organic matter,indigo and indirubin groups,which were mainly involved in glycerophospholipid metabolism.


Assuntos
Antipiréticos , Medicamentos de Ervas Chinesas , Indigofera , 2,4-Dinitrofenol , Animais , Índigo Carmim , Ratos
13.
Nucleic Acids Res ; 49(17): 10106-10119, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34390350

RESUMO

AaRSs (aminoacyl-tRNA synthetases) group into two ten-member classes throughout evolution, with unique active site architectures defining each class. Most are monomers or homodimers but, for no apparent reason, many bacterial GlyRSs are heterotetramers consisting of two catalytic α-subunits and two tRNA-binding ß-subunits. The heterotetrameric GlyRS from Escherichia coli (EcGlyRS) was historically tested whether its α- and ß-polypeptides, which are encoded by a single mRNA with a gap of three in-frame codons, are replaceable by a single chain. Here, an unprecedented X-shaped structure of EcGlyRS shows wide separation of the abutting chain termini seen in the coding sequences, suggesting strong pressure to avoid a single polypeptide format. The structure of the five-domain ß-subunit is unique across all aaRSs in current databases, and structural analyses suggest these domains play different functions on α-subunit binding, ATP coordination and tRNA recognition. Moreover, the X-shaped architecture of EcGlyRS largely fits with a model for how two classes of tRNA synthetases arose, according to whether enzymes from opposite classes can simultaneously co-dock onto separate faces of the same tRNA acceptor stem. While heterotetrameric GlyRS remains the last structurally uncharacterized member of aaRSs, our study contributes to a better understanding of this ancient and essential enzyme family.

14.
Chemosphere ; 286(Pt 2): 131722, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34352547

RESUMO

The rapid development of global logistics has led to the overuse of packaging cartons, causing problems for municipal solid waste disposal. Diverse methods of exploiting the potential value of waste cartons are needed. Herein, we fabricated a magnetic composite (MC) from waste cartons via a one-step hydrothermal treatment and characterized. Using methylene blue (MB) as a model organic pollutant, tests of the activation of persulfate (PS) via the MC for the removal of MB were performed. Meanwhile, a comparison with activation with pre-magnetized zero-valent iron (Pre-ZVI/PS) was made. The comparative results show that the removal of MB was successfully accomplished with both Pre-ZVI/PS and MC/PS. Specifically, MC/PS could remove almost 100 % of MB, with the COD removal efficiency reaching over 70 % when the MB concentration was 50 mg/L at 80 min under different pH conditions. Even when reused twice, the MC still displayed robust activation performance. Additionally, we evaluated the lifetime of magnetic memory for Pre-ZVI, and first found its consecutive loss of pre-magnetization over 30 days, corresponding to the incremental attenuation of reaction rate constants in the Pre-ZVI-activated PS process. Overall, activating PS using the MC is a promising advanced oxidation technology and also provides a valuable reference on the valorization of lignocellulosic biomass.

15.
Front Med ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387851

RESUMO

The Coronavirus disease 2019 (COVID-19) has spread globally. Although mixed liver impairment has been reported in COVID-19 patients, the association of liver injury caused by specific subtype especially chronic hepatitis B (CHB) with COVID-19 has not been elucidated. In this multi-center, retrospective, and observational cohort study, 109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age, sex, and comorbidities. Demographic characteristics, laboratory examinations, disease severity, and clinical outcomes were compared. Furthermore, univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality, respectively. A higher proportion of CHB patients (30 of 109 (27.52%)) developed into severe status than non-CHB patients (17 of 327 (5.20%)). In addition to previously reported liver impairment markers, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin, we identified several novel risk factors including elevated lactate dehydrogenase (⩾ 245 U/L, hazard ratio (HR) = 8.639, 95% confidence interval (CI) = 2.528-29.523; P < 0.001) and coagulation-related biomarker D-dimer (⩾ 0.5 µg/mL, HR = 4.321, 95% CI = 1.443-12.939; P = 0.009) and decreased albumin (< 35 g/L, HR = 0.131, 95% CI = 0.048-0.361; P < 0.001) and albumin/globulin ratio (< 1.5, HR = 0.123, 95% CI = 0.017-0.918; P = 0.041). In conclusion, COVID-19 patients with CHB were more likely to develop into severe illness and die. The risk factors that we identified may be helpful for early clinical surveillance of critical progression.

16.
J Immunol Res ; 2021: 1891519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34423050

RESUMO

The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.

17.
Signal Transduct Target Ther ; 6(1): 303, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400610

RESUMO

Abnormally enhanced de novo lipid biosynthesis has been increasingly realized to play crucial roles in the initiation and progression of varieties of cancers including breast cancer. However, the mechanisms underlying the dysregulation of lipid biosynthesis in breast cancer remain largely unknown. Here, we reported that seryl tRNA synthetase (SerRS), a key enzyme for protein biosynthesis, could translocate into the nucleus in a glucose-dependent manner to suppress key genes involved in the de novo lipid biosynthesis. In normal mammary gland epithelial cells glucose can promote the nuclear translocation of SerRS by increasing the acetylation of SerRS at lysine 323. In SerRS knock-in mice bearing acetylation-defective lysine to arginine mutation, we observed increased body weight and adipose tissue mass. In breast cancer cells the acetylation and nuclear translocation of SerRS are greatly inhibited. Overexpression of SerRS, in particularly the acetylation-mimetic lysine to glutamine mutant, dramatically inhibits the de novo lipid synthesis and hence greatly suppresses the proliferation of breast cancer cells and the growth of breast cancer xenografts in mice. We further identified that HDAC4 and HDAC5 regulated the acetylation and nuclear translocation of SerRS. Thus, we identified a SerRS-meditated inhibitory pathway in glucose-induced lipid biosynthesis, which is dysregulated in breast cancer.

19.
Spinal Cord ; 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34326463

RESUMO

STUDY DESIGN: A retrospective study of incomplete cervical spinal cord injury (SCI) treated with and without hyperbaric oxygen (HBO) therapy after operation. OBJECTIVE: To investigate the effects of hyperbaric oxygen therapy on patients' postoperative recovery after incomplete cervical spinal cord injury. SETTING: Shulan Hangzhou Hospital, Hangzhou, China. METHODS: We analyzed the clinical data of 78 patients admitted in the Orthopedic Department of our hospital from June 2014 to June 2016, due to trauma-induced incomplete cervical spinal cord injury. All study subjects underwent nerve decompression and internal fixation procedures within 2 weeks of injury. The patients were divided into hyperbaric oxygen therapy (HBO) group (n = 40) and non-hyperbaric oxygen therapy (NHBO) group (n = 38) according to the chosen treatment option. The NHBO group only receive the conventional treatment regimen while the HBO group received a combination of conventional treatment and hyperbaric oxygen therapy. The subsequent changes in spinal functions and activities of daily living (ADL) were assessed by The American Spinal Injury Association (ASIA) scale and the Barthel Index at different time points (pretreatment, 1 month and 3 months of treatment, as well as 6 months, 1 year, 2 years, and 3 years after the surgical procedure). RESULTS: There were no significant differences in age, gender, injury site, and disease condition between patients (p > 0.05). The results showed a significant difference in treatment total effectiveness rate between the HBO and NHBO groups (p < 0.05) (90% and 78.9%, respectively). Analyses of the ASIA scores and Barthel indices between the two groups indicated significant differences at 1 month and 3 months treatment time points, as well as 6 months and 1 year after the initial operation (p < 0.05). It showed that subjects in the HBO group had a better recovery than their NHBO counterparts, with the 1-month treatment time point being the most significant. In addition, the results indicated significant improvements in Barthel Index scores as well as ASIA sensory and motor function scores in both groups after a 1-month treatment, with the HBO group faring significantly better than the NHBO group (p < 0.01). CONCLUSIONS: Our results not only showed that hyperbaric oxygen therapy is safe and effective for the treatment of incomplete cervical spinal cord injury but also indicated that the longer the treatment lasts (therapy initiation within 3 months after the surgical operation), the better the effects. In addition, a correct hyperbaric oxygen therapy leads to a peak in recovery within the first postoperative 3 months and can effectively promote spinal cord functions, reduce the disabilities, and improve patients' quality of life.

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