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1.
Artigo em Inglês | MEDLINE | ID: mdl-34774324

RESUMO

Burn wounds are susceptible to bacterial infections and are usually accompanied by a large amount of exudate, making the treatment of burn wounds a challenge in the clinic. Here, we developed a biodegradable cryogel with high water absorption and good antibacterial and antibiofilm activity based on gelatin (GT) and silver nanoparticles (Ag NPs) to promote burn wound healing. The porous GT/Ag cryogel had a swelling ratio of up to 4000%, effectively absorbing wound exudate and allowing for gas exchange. Moreover, the GT/Ag cryogel had an excellent killing effect on methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA), which burn wounds are susceptible to, and can effectively remove mature biofilms. In the rat liver defect noncompressible hemorrhage model, GT/Ag cryogels with shape memory performance showed better hemostatic ability than commercial gelatin sponges. Most importantly, the GT/Ag cryogel was more effective than the TegadermTM dressing and GT cryogel in promoting wound contraction, collagen deposition, and angiogenesis and reducing inflammation in a PA-infected burn wound model. In addition, GT/Ag cryogels degraded in the body within 4 weeks, which alleviated the pain of peeling the dressing from the wound. Therefore, GT/Ag cryogels with outstanding antibacterial properties and effective absorption of wound exudates are excellent candidates for wound dressings to promote burn wound repair.

3.
BMC Infect Dis ; 21(1): 912, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488678

RESUMO

BACKGROUND: Entecavir (ETV) is recommended as a first-line anti-HBV treatment. However, many chronic hepatitis B patients initiate anti-HBV treatment such as lamivudine and telbivudine with low genetic barriers in China, which leads to compensatory mutations and increases the rate of ETV resistance. The management of ETV resistance in China is an essential clinical issue. METHODS: Patients from 2011 to 2017 with nucleos(t)ide analog resistance were screened and 72 patients with ETV resistance were included. These patients received different rescue therapies including an ETV and adefovir (ADV) combination therapy group (n = 25), a tenofovir (TDF) monotherapy group (n = 27), and an ETV and TDF combination therapy group (n = 20). Virologic, biochemical, and serologic responses were compared among the three groups. RESULTS: The rate of ETV resistance among all HBV-resistant variants increased from 6.04% in 2011 to 15.02% in 2017. TDF monotherapy and TDF combination groups showed similar rates of negative HBV DNA at 48 weeks (74.07% vs 70.00%, P > 0.05), while the ETV and ADV group showed the worst virologic response (28.00%). Also, TDF monotherapy and TDF combination therapy showed similar decline of HBV DNA at weeks 12, 24, and 48. There was no significant difference in the rates of HBeAg clearance, ALT normalization, and abnormal renal function among the three groups. CONCLUSIONS: TDF monotherapy showed a comparable virologic response to TDF and ETV combination therapy and a better virologic response than ETV and ADV combination therapy. Thus, TDF monotherapy is the preferred rescue therapy for ETV resistance.


Assuntos
Hepatite B Crônica , Antivirais/uso terapêutico , DNA Viral , Farmacorresistência Viral/genética , Quimioterapia Combinada , Guanina/análogos & derivados , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Lamivudina/uso terapêutico , Resultado do Tratamento , Carga Viral
4.
Int J Endocrinol ; 2021: 1264707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497643

RESUMO

Aim: This study is aimed at the characteristics of glucose metabolism and islet ß cell function evaluated by the homeostasis model assessment of ß cell function (HOMA-ß) value and its risk factors in chronic hepatitis B (CHB) patients. Method: This cross-sectional study recruited 110 CHB patients (CHB group) and 110 patients without hepatitis B virus (non-HBV group); the groups were matched according to sex, age, and body mass index under the same glucose metabolism status. The risk factors, characteristics, and differences in glucose metabolism and HOMA-ß values between the two groups were analyzed. Results: The abnormal glucose metabolism rate was higher in CHB patients with liver cirrhosis (LC) or hepatitis B envelope antigen (HBeAg) (-) status. In addition, under the same glucose metabolism status, the fasting plasma glucose (FPG) levels and 2-hour postprandial plasma glucose (2h-PG) levels in the CHB group were higher, while the HOMA-ß values were significantly lower and the homeostasis model assessment of insulin resistance (HOMA-IR) value was not higher than that in the non-HBV group (all P < 0.0001). Further analyses revealed that the main risk factors for abnormal glucose metabolism were HBeAg (-) status and hepatitis B envelope antibody levels. But HBV serological and virological indicators had no effects on the HOMA-ß values. Conclusion: Islet ß cell function in patients with CHB was compromised, which is closely associated with fasting and postprandial hyperglycemia in chronic hepatitis B patients. Further research should be done to verify the compromised islet ß cell function and then to investigate the mechanisms behind the effect of hepatitis B virus infection on islet ß cell function in CHB patients.

5.
Cardiol Res Pract ; 2021: 5537275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34306746

RESUMO

In this study, we investigated the association between the plasma NT-proBNP level at admission and the severity of COVID-19 pneumonia. For this retrospective, single-centre cohort study, we enrolled consecutive patients from February 9 to March 4, 2020, in a COVID-19 ward of Hubei General Hospital (East Branch) in Wuhan, which is a government-assigned centre for COVID-19 treatment. Diagnosis was confirmed by microbiological and radiographic findings following the interim guidance of the World Health Organization (WHO). A total of 91 (92.9%) patients were finally included in this study. The median age of the patients was 61 years (IQR, 47-69), and 39 (43.0%) of them were male. Two cases of death were reported (2.3%). Twenty-three patients (25.3%) had NT-proBNP levels above 300 pg/ml. Higher NT-proBNP levels were associated with worse PSI and CT scores. The natural logarithm of the NT-proBNP level was positively correlated with the PSI and CT scores (PSI score: r S = 0.396, P=0.001; CT score: r S = 0.440, P < 0.001). Patients with NT-proBNP ≥300 pg/ml showed a potential risk for higher mortality than patients with NT-proBNP <300 pg/ml (mortality rate, 8.7% vs. 0%; P=0.062). The plasma NT-proBNP level of COVID-19 patients was significantly related to the severity of pneumonia.

6.
Sci Rep ; 11(1): 11636, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34079027

RESUMO

The elevated level of D-dimer and its relationship with poor outcomes in SARS-COV-2 pneumonia patients have been demonstrated. In addition to a hypercoagulable state, D-dimer is also a biomarker of inflammation. We investigated the relationship between D-dimer level and chest computed tomography (CT) severity score, which could reflect the severity of inflammation in SARS-COV-2 pneumonia patients. We retrospectively enrolled 86 consecutive SARS-COV-2 pneumonia patients. CT severity scores were computed to quantify the overall lung involvement. The D-dimer level among CT score tertiles and the association of the D-dimer level with CT score were analyzed. Our results showed that the median D-dimer level was 0.70 mg/L (IQR 0.35-1.76). 42 patients (48.8%) had D-dimer levels above the median level. The D-dimer levels were significantly different across CT score tertiles (0.37 mg/l [IQR 0.31-0.87], 0.66 mg/l [IQR 0.39-1.43], 1.83 mg/l [IQR 0.85-4.41], P < 0.001). The natural logarithm of the D-dimer level was significantly associated with the CT score (rs = 0.586, P < 0.001). In conclusion, the D-dimer level may be associated with the severity of inflammation of SARS-COV-2 pneumonia prior to coagulopathy/thrombosis. This could be an additional explanation for the mechanism of the relationship between elevated D-dimer level and higher mortality.


Assuntos
COVID-19/diagnóstico por imagem , COVID-19/etiologia , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Adulto , Idoso , COVID-19/sangue , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/virologia , Respiração Artificial , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
7.
Sci Rep ; 11(1): 11301, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-34050222

RESUMO

People living with HIV (PLWH) bear higher prevalence of HCV coinfection. An accessible directly acting antivirals regimen with less drug-drug interaction with antiretroviral therapy (ART) is urgently needed in source limited regions. We aimed to assess the efficacy and safety of SOF + RBV for 24 weeks regimen in HIV-HCV coinfected patients in Liangshan Prefecture, China. PLWH under ART from China's national free antiretroviral treatment project (CNFATP) and diagnosed with treatment-naïve HCV infection were enrolled. SOF + RBV was administrated for 24 weeks and patients were followed for ≥ 12 weeks. The efficacy and safety were analyzed and related factors were explored. 58 patients completed 24 weeks of SOF + RBV and had all tests done. Genotype prevalence in this population was G3 44.8% (n = 26), G6 31.0% (n = 18) and G1 17.2% (n = 10) respectively. 52/58 (89.7%) patients achieved SVR12 while 10.3% experienced therapeutic failure. However, SVR12 was neither significantly different between groups of different gender, age, transmission routines, CD4+ cell count, HIV infection duration, ART duration and HBsAg prevalence nor influenced by HCV viral load, genotypes and hepatic stiffness. The regimen was well-tolerated without any serious AEs or AEs leading to treatment adjustment or discontinuation reported. PLWH in Liangshan showed a high prevalence of HCV coinfection with GT3 and GT6 as the most frequent genotypes. SOF + RBV for 24 weeks could achieve good SVR12 in this population and was well-tolerated. It has great potential to be generalized in coinfected population in source-limited regions.


Assuntos
Infecções por HIV/virologia , Hepatite C/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Adulto , Antivirais/uso terapêutico , China/epidemiologia , Coinfecção/tratamento farmacológico , Quimioterapia Combinada/métodos , Feminino , Genótipo , Infecções por HIV/complicações , HIV-1/genética , HIV-1/patogenicidade , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/complicações , Hepatite C/virologia , Humanos , Masculino , População Rural , Resposta Viral Sustentada
8.
Drug Discov Today ; 26(9): 2190-2197, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34048895

RESUMO

The Clp protease is an AAA+ protease that executes abnormally folded or malfunctioning proteins, and has an important role in producing virulence factors, forming biofilms or persisters and developing methicillin-resistant Staphylococcus aureus (MRSA). Recent studies showed that Clp protease controls virulence via agr signaling and degrades antitoxins of the toxin-antitoxin system to modulate the formation of persisters and biofilms. In this review, we focus on recent developments concerning the virulence and persistence regulatory pathways and resistance-related mechanism of Clp protease in S. aureus, with an overview of the Clp modulators developed to treat MRSA infection.

9.
Comput Struct Biotechnol J ; 19: 2460-2467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025936

RESUMO

Bacterial Mip-like FK506-binding proteins (FKBPs) mostly exhibit peptidyl-prolyl-cis/trans-isomerase (PPIase) and chaperone activities. These activities are associated with various intracellular functions with diverse molecular mechanisms. Herein, we report the PA3262 gene-encoded crystal structure of the Pseudomonas aeruginosa PAO1's Mip-like protein PaFkbA. Biochemical characterization of PaFkbA demonstrated PaFkbA's chaperone activity for periplasmic protein MucD, a negative regulator of alginate biosynthesis. Furthermore, structural analysis of PaFkbA was used to describe the key features of PaFkbA chaperone activity. The outcomes of this analysis showed that the hinge region in the connecting helix of PaFbkA leads to the crucial conformational state transition for PaFkbA activity. Besides, the N-terminal domains participated in dimerization, and revealed its potential connection with FKBP domain and substrate binding. Mutagenesis and chaperone activity assay supported the theory that inter-domain motions are essential for PaFkbA function. These results provide biochemical and structural insights into the mechanism for FKBP's chaperone activity and establish a plausible correlation between PaFkbA and P. aeruginosa MucD.

10.
PLoS One ; 16(5): e0251359, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33961683

RESUMO

Acute lung injury (ALI) is a serious inflammation disease usually arises alveolar epithelial membrane dysfunction and even causes death. Therefore, the aims of this study are to screen the differentially expressed lncRNAs, circRNAs, miRNAs, and mRNAs in ALI based on the high-throughput sequencing. The lipopolysaccharide (LPS)-induced ALI mouse model was established, the injury of ALI mouse model was evaluated through histological analysis with hemotoxylin and eosin (H & E) staining assay, dry/wet ratio, infiltrated-immune cells, ET-1 mRNA expression and released-proinflammation factors. Then, expression data of lncRNAs, circRNAs, miRNAs and mRNAs in ALI were acquired using whole-transcriptome sequencing. The differential expression of lncRNAs (DE lncRNAs), circRNAs (DE circRNAs), miRNAs (DE miRNAs) and mRNAs (DE mRNAs) were identified, and the lncRNA-miRNA-mRNA network and circRNA-miRNA-mRNA network were constructed, and the biological function of target genes were annotated based on bioinformatics analysis. In the present study, the LPS-induced ALI mouse model was successfully established. The biological analysis results showed that total 201 DE lncRNAs, 172 DE circRNAs, 62 DE miRNAs, and 3081 DE mRNAs were identified in ALI. The 182 lncRNA-miRNA-mRNA networks and 32 circRNA-miRNA-mRNA networks were constructed were constructed based on the correlation between lncRNAs/circRNAs, miRNAs, mRNAs. The biological function analysis indicated that TNF signaling pathway, chemokine signaling pathway and so on involved in ALI. In the present study, the differential expression coding and non-coding RNAs (ncRNAs) in ALI were identified, and their regulatory networks were constructed. There might provide the potential biomarkers and underlying mechanism for ALI diagnosis and treatment.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Transcriptoma , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Animais , Biologia Computacional , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Lipopolissacarídeos , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
11.
Theranostics ; 11(12): 5911-5925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897889

RESUMO

Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.


Assuntos
Anti-Inflamatórios/farmacologia , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Curcumina/farmacologia , Preparações de Ação Retardada/farmacologia , Hidrogéis/farmacologia , Magnésio/farmacologia , Tendões/efeitos dos fármacos , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Manguito Rotador/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Cicatrização/efeitos dos fármacos
12.
Sci Rep ; 11(1): 7510, 2021 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-33820919

RESUMO

The prognosis of Artificial liver support system (ALSS) for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is hard to be expected, which results in multiple operations of ALSS and excessive consumption of plasma, increase in clinical cost. A total of 375 HBV-ACLF patients receiving ALSS treatment were randomly divided a train set and an independent test set. Logistic regression analysis was conducted and a decision tree was built based on 3-month survival as outcome. The ratio of total bilirubin before and after the first time of ALSS treatment was the most significant prognostic factor, we named it RPTB. Further, a decision tree based on the multivariate logistic regression model using CTP score and the RPTB was built, dividing patients into 3 main groups such as favorable prognosis group, moderate prognosis group and poor prognosis group. A clearly-presented and easily-understood decision tree was built with a good predictive value of prognosis in HBV-related ACLF patients after first-time ALSS treatment. It will help maximal the therapeutic value of ALSS treatment and may play an important role in organ allocation for liver transplantation in the future.


Assuntos
Fígado Artificial , Modelos Teóricos , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Área Sob a Curva , Árvores de Decisões , Feminino , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Prognóstico , Curva ROC
13.
Int J Infect Dis ; 105: 626-631, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722684

RESUMO

BACKGROUND: Limited data exist regarding the efficacy and long-term safety of nucleos(t)ide analogue therapy throughout pregnancy for women with chronic hepatitis B and their children. METHODS: This retrospective cohort study included 165 women in total: 91 women received telbivudine (LDT) and 74 women received tenofovir (TDF) throughout pregnancy. The virological response and safety in women were recorded, and the physical development and bone mineral density in children were evaluated up to 5 years of age. RESULTS: The rate of virological breakthrough in women was 4.24% overall (7.70% in LDT group and 0% in TDF group; P < 0.05). No cases of renal injury or other obstetric adverse events occurred in either group of women. Among the children, only one child had a significantly low Z score for weight for age (<-2), and no children had a significantly low Z score for height for age or bone mineral density. No significant difference was found between the children in the two groups. CONCLUSIONS: Nucleos(t)ide analogue therapy with TDF or LDT throughout pregnancy had no effect on the long-term physical development and bone development of children. In addition, the use of TDF throughout pregnancy had better long-term antiviral efficacy than LDT in women, with no evidence of renal toxicity.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/fisiologia , Hepatite B Crônica/tratamento farmacológico , Nucleosídeos/uso terapêutico , Telbivudina/uso terapêutico , Tenofovir/uso terapêutico , Adulto , Densidade Óssea , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Gravidez , Estudos Retrospectivos
14.
J Gastroenterol Hepatol ; 36(7): 1754-1768, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33569851

RESUMO

BACKGROUND AND AIM: There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease). METHODS: The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data. RESULTS: A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05-1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62-53.31), 3.19 (7 studies, 95% CI 1.14-8.93), 6.02 (6 studies, 95% CI 4.69-7.74), and 11.46 (4 studies, 95% CI 5.33-24.63), respectively. CONCLUSION: Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.

15.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33576464

RESUMO

Recently, severe acute respiratory syndrome (SARS) coronavirus (CoV) 2 (SARS­CoV­2)­causing CoV disease 2019 (COVID­19) emerged in China and has become a global pandemic. SARS­CoV­2 is a novel CoV originating from ß­CoVs. Major distinctions in the gene sequences between SARS­CoV and SARS­CoV­2 include the spike gene, open reading frame (ORF) 3b and ORF 8. SARS­CoV­2 infection is initiated when the virus interacts with angiotensin­converting enzyme 2 (ACE2) receptors on host cells. Through this mechanism, the virus infects the alveolar, esophageal epithelial, ileum, colon and other cells on which ACE2 is highly expressed, causing damage to target organs. To date, host innate immunity may be the only identified direct factor associated with viral replication. However, increased ACE2 expression may upregulate the viral load indirectly by increasing the baseline level of infectious virus particles. The peak viral load of SARS­CoV­2 is estimated to occur ~10 days following fever onset, causing patients in the acute stage to be the primary infection source. However, patients in the recovery stage or with occult infections can also be contagious. The host immune response in patients with COVID­19 remains to be elucidated. By studying other SARS and Middle East respiratory syndrome coronaviruses, it is hypothesized that patients with COVID­19 may lack sufficient antiviral T­cell responses, which consequently present with innate immune response disorders. This may to a certain degree explain why this type of CoV triggers severe inflammatory responses and immune damage and its associated complications.


Assuntos
COVID-19/patologia , SARS-CoV-2/fisiologia , Imunidade Adaptativa , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/imunologia , COVID-19/virologia , Humanos , Imunidade Inata , SARS-CoV-2/genética , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Carga Viral
16.
Sci Rep ; 11(1): 1469, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446902

RESUMO

Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng' score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p < 0.05). The PALS score had significant linear correlation with 3-month mortality (R2 = 0.970, p = 0.000). PALS score of 0-2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6-9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3-5 who received 3-5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1-2 sessions (32.8% vs. 59.2%, p < 0.05). The more severe patients with PALS score of 6-9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions.Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471 .


Assuntos
Insuficiência Hepática Crônica Agudizada/mortalidade , Previsões/métodos , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Bilirrubina/análise , Estudos de Coortes , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/terapia , Feminino , Encefalopatia Hepática , Hepatite B/complicações , Vírus da Hepatite B , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/metabolismo , Fígado Artificial/tendências , Masculino , Pessoa de Meia-Idade , Troca Plasmática/métodos , Prognóstico , Protrombina/análise , Estudos Retrospectivos , Fatores de Risco
17.
Med Res Rev ; 41(4): 1855-1889, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33501747

RESUMO

Ribosomes, which synthesize proteins, are critical organelles for the survival and growth of bacteria. About 60% of approved antibiotics discovered so far combat pathogenic bacteria by targeting ribosomes. However, several issues, such as drug resistance and toxicity, have impeded the clinical use of ribosome-targeting antibiotics. Moreover, the complexity of the bacteria ribosome structure has retarded the discovery of new ribosome-targeting agents that are considered as the key to the drug-resistance and toxicity. To deal with these challenges, efforts such as medicinal chemistry optimization, combination treatment, and new drug delivery system have been developed. But not enough, the development of structural biology and new screening methods bring powerful tools, such as cryo-electron microscopy technology, advanced computer-aided drug design, and cell-free in vitro transcription/translation systems, for the discovery of novel ribosome-targeting antibiotics. Thus, in this paper, we overview the research on different aspects of bacterial ribosomes, especially focus on discussing the challenges in the discovery of ribosome-targeting antibacterial drugs and advances made to address issues such as drug-resistance and selectivity, which, we believe, provide perspectives for the discovery of novel antibiotics.


Assuntos
Antibacterianos , Ribossomos , Antibacterianos/farmacologia , Bactérias , Microscopia Crioeletrônica , Desenho de Fármacos , Humanos
18.
J Clin Transl Hepatol ; 8(3): 255-261, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083247

RESUMO

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

20.
J Clin Lab Anal ; 34(10): e23566, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32914892

RESUMO

BACKGROUND: Declared as pandemic by WHO, the coronavirus disease 2019 (COVID-19) pneumonia has brought great damage to human health. The uncontrollable spread and poor progression of COVID-19 have attracted much attention from all over the world. We designed this study to develop a prognostic nomogram incorporating Prognostic nutritional index (PNI) in COVID-19 patients. METHODS: Patients confirmed with COVID-19 and treated in Renmin Hospital of Wuhan University from January to February 2020 were included in this study. We used logistic regression analysis to find risk factors of mortality in these patients. A prognostic nomogram was constructed and receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of PNI and this prognostic model. RESULTS: Comparison of baseline characteristics showed non-survivors had higher age (P < .001), male ratio (P = .038), neutrophil-to-lymphocyte ratio (NLR) (P < .001), platelet-to-lymphocyte ratio (PLR) (P < .001), and PNI (P < .001) than survivors. In the multivariate logistic regression analysis, independent risk factors of mortality in COVID-19 patients included white blood cell (WBC) (OR 1.285, P = .039), PNI (OR 0.790, P = .029), LDH (OR 1.011, P < .015). These three factors were combined to build the prognostic model. Area under the ROC curve (AUC) of only PNI and the prognostic model was 0.849 (95%Cl 0.811-0.888) and 0.950 (95%Cl 0.922-0.978), respectively. And calibration plot showed good stability of the prognostic model. CONCLUSION: This research indicates PNI is independently associated with the mortality of COVID-19 patients. Prognostic model incorporating PNI is beneficial for clinicians to evaluate progression and strengthen monitoring for COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Inflamação/fisiopatologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Adulto , Idoso , Betacoronavirus , COVID-19 , China , Estudos de Coortes , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prognóstico , Fatores de Risco , SARS-CoV-2 , Sensibilidade e Especificidade
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