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1.
J Clin Transl Hepatol ; 8(3): 277-284, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083250

RESUMO

Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377.

2.
Antiviral Res ; 184: 104953, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33065138

RESUMO

BACKGROUND & AIMS: Normal/mildly elevated ALT (<2 × ULN) CHB patients are potentially at risk of progression to cirrhosis and/or hepatocellular carcinoma (HCC). We aimed to assess the outcomes of anti-viral therapy for normal/mild elevation of ALT CHB patients. METHODS: CHB patients (n = 432) who have had liver biopsied were determined. It was determined that the outcomes of anti-viral therapy in CHB patients with normal/mild elevation of ALT, in response to nucleoside/nucleotide analogues (NAs) (n = 190) and pegylated interferon (PEG-IFN) (n = 30) treatment for up to 72 weeks. Non-anti-viral treated patients were used as control (n = 40). RESULTS: There was about 50% of the CHB patients showed hepatic inflammatory necrosis ≥ G2 and/or fibrosis ≥ S2 among >30-years-old. The rate of undetectable HBV DNA in NAs and PEG-IFN groups was ~50%, ~80% or ~90% at week 24, 48 or 72, respectively. HBeAg clearance rate was lower in NAs treated than that in PEG-IFN group at week 48 (6% vs 20%, P < 0.05). ALT normalization rate was increased by 1.18-fold at week 72. HBsAg decline in HBeAg+ patients treated with NAs or PEG-IFN was 0.418 or 1.217 log IU/mL (P < 0.0001) at week 48; whereas HBsAg decline was 0.176 or 0.816 log IU/mL (P < 0.001) in HBeAg- patients. HBsAg at baseline and week 24 were strong predictors of "low HBsAg at week 48". CONCLUSION: Long term anti-viral therapy inhibits HBV replication effectively in ALT<2 × ULN CHB patients. PEG-IFN therapy is recommended for HBeAg+ patients with baseline HBsAg<4.37 log IU/ml and HBeAg- patients with baseline HBsAg<2.66 log IU/ml to achieve "low HBsAg at week 48".

3.
Front Public Health ; 8: 555550, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042952

RESUMO

The COVID-19 outbreak has become a pandemic. The outbreak was able to be controlled in China by mid-April through the implementation of critical measures; however, significant reverse transmission has resulted in hot spots perturbing prevention and control. To date, there have only been a total of 92 indigenous COVID-19 cases confirmed in the Gansu Province, which is considered to be a consequence of the strict screening approach applied during the outbreak. The emergency response level to COVID-19 were able to be decreased from high to low, despite some relatively minor reverse transmission cases from other countries in March 2020. The stringent preparative measures undertaken by the Gansu authorities, involving high-level, streamlined cooperation between the transportation, quarantine, and medical resource departments, have underpinned this success. There has been an emergence of clusters of freshly infected COVID-19 patients in the Jilin Province in northeast China. The single largest cluster has been in Shulan of the Jilin Province, involving 43 confirmed infections. A strict lockdown was implemented immediately. The source of the current outbreak of COVID-19 is suggested to be travelers returning from Russia. The current strategy from the Chinese authorities is aimed at preventing reverse transmission via international importation to avert a rebound of COVID-19 in China. These data highlight the need for an exceptionally high level of vigilance and for a pre-emptive response that is informative for the development of policy to prevent a second and further waves of infections in general.

4.
Front Public Health ; 8: 477, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32923422

RESUMO

Background: As an emerging infectious disease, COVID-19 has garnered great research interest. We aimed to explore the differences between English language and Chinese language Medical/Scientific journals publications, particularly aiming to explore the efficacy/contents of the literature published in English and Chinese in relation to the outcomes of management and characterization of COVID-19 during the early stage of COVID-19 pandemic. Methods: Publications on COVID-19 research were retrieved from both English and Chinese databases. Bibliometric analyses were performed using VOSviewer 1.6.14, and CiteSpace V software. Network maps were generated to evaluate the collaborations between different authors, countries/provinces, and institutions. Results: A total of 143 English and 721 Chinese original research articles and reviews on COVID-19 were included in our study. Most of the authors and institutions of the papers were from China before March 1st, 2020, however, the distribution of authors and institutions were mainly in developed countries or more wealthy areas of China. The range of the keywords in English publications was more extensive than those in Chinese. Traditional Chinese Medicine was seen more frequently in Chinese papers than in English. Of the 143 articles published in English, 54 articles were published by Chinese authors only and 21 articles were published jointly by Chinese and other overseas authors. Conclusions: The publications in English have enabled medical practitioners and scientists to share/exchange information, while on the other hand, the publications in the Chinese language have provided complementary educational approaches for the local medical practitioners to understand the essential and key information to manage COVID-19 in the relatively remote regions of China, for the general population with a general level of education.

5.
Cell Biosci ; 10: 94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765828

RESUMO

Background: Gastric cancer (GC) is a malignancy with high morbidity/mortality, partly due to a lack of reliable biomarkers for early diagnosis. It is important to develop reliable biomarker(s) with specificity, sensitivity and convenience for early diagnosis. The role of tumour-associated macrophages (TAMs) and survival of GC patients are controversial. Macrophage colony stimulating factor (MCSF) regulates monocytes/macrophages. Elevated MCSF is correlated with invasion, metastasis and poor survival of tumour patients. IL-34, a ligand of the M-CSF receptor, acts as a "twin" to M-CSF, demonstrating overlapping and complimentary actions. IL-34 involvement in tumours is controversial, possibly due to the levels of M-CSF receptors. While the IL-34/M-CSF/M-CSFR axis is very important for regulating macrophage differentiation, the specific interplay between these cytokines, macrophages and tumour development is unclear. Methods: A multi-factorial evaluation could provide more objective utility, particularly for either prediction and/or prognosis of gastric cancer. Precision medicine requires molecular diagnosis to determine the specifically mutant function of tumours, and is becoming popular in the treatment of malignancy. Therefore, elucidating specific molecular signalling pathways in specific cancers facilitates the success of a precision medicine approach. Gastric cancer tissue arrays were generated from stomach samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, M-CSF, IL-34 and macrophages were determined. Results: We found that IL-34 may serve as a predictive biomarker, but not as an independent, prognostic factor in GC; M-CSF inversely correlated with survival of GC in TNM III-IV subtypes. Increased CD68+ TAMs were a good prognostic factor in some cases and could be used as an independent prognostic factor in male T3 stage GC. Conclusion: Our data support the potency of IL-34, M-CSF, TAMs and the combination of IL-34/TAMs as novel biological markers for GC, and may provide new insight for both diagnosis and cellular therapy of GC.

6.
Front Physiol ; 11: 526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655398

RESUMO

Background and Aims: Necroptosis is a newly identified type of cell death with programmed pathways. The current study was performed to investigate necroptosis by measuring its key regulators; receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL) in patients with Hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF). Methods: HBV-related ACLF (HBV-ACLF) patients (n = 90), non-ACLF patients without cirrhosis (N = 70), patients with cirrhosis (N = 40), and healthy controls (HCs; n = 70) were enrolled in the study. All patients were subject to serum RIPK3 measurement. Hepatic RIPK3 and MLKL were also determined in the livers of 18 patients and five donors, using immunohistochemistry. Results: Serum RIPK3 was significantly elevated in HBV-ACLF patients compared to that of non-ACLF patients and the HCs. Serum RIPK3 in ACLF patients at recruitment was significantly higher in non-survivors than those in survivors at the 90-day follow-up. The predictive accuracy of serum RIPK3 at the 90-day outcome was relatively good with an area under the receiver operating curve (AUROC) of 0.72 (p < 0.001), similar to that of the model of end-staged liver disease (MELD) score (0.76, p < 0.001). The combined use of RIPK3 and MELD score further increased the AUROC to 0.80. The hepatic RIPK3 and MLKL measured by immunohistochemistry, significantly increased in the patients with HBV-ACLF than in the patients without ACLF and the HCs. Conclusion: Circulating RIPK3 was significantly increased in patients with HBV-ACLF and was associated with a clinical outcome. The improved combined objective scores could offer additional prognostic value in ACLF patients, for physicians with more accurate expectations.

7.
Biophys Rev ; 12(4): 757-759, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32661901

RESUMO

As a non-English-speaking PhD student without previous scientific skills, I have been so lucky to be supervised and mentored by Professor Cristobal dos Remedios. In this commentary, I have commented my experience in dos Remedios laboratory. Finally, I would like to express my greatest appreciation to Professor dos Remedios for his kindness and mentorship over the last 31 years. His continuous support, which continues to the present, has been instrumental for the achievement of my current position.

8.
Biophys Rev ; 12(4): 925-930, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32638330

RESUMO

Colorectal cancer (CRC) is still a big killer nowadays, but the precise underlying mechanism remains to be explored. It is believed that imbalance of host immunity in the local microenvironment plays a critical role in the tumorigenesis of CRC. IL-34 is inversely correlated with overall survival in CRC patients, perhaps via regulating terminal differentiation of a subset of macrophages (M2). It is believed that the recruitment/differentiation of M2 macrophages within the cancer simply represents an increase in number, but the function of these M2 macrophages may be compromised. IL-36s (IL-36α, ß and γ) are constitutively expressed in non-cancer colon tissue, but colonic IL-36α, IL-36ß and IL-36γ are substantially reduced in the CRC tissues (~ 80%). IL-36α is an independent factor affecting the survival of CRC patients. The level of IL-36α and/or IL-36γ in CRC tissue could potentially be used as biomarkers for predicting the prognosis of CRC at both the later or early stages of CRC. IL-38 is also an anti-inflammatory cytokine. Colonic IL-38 is ~ 95% lower in CRC compared to non-CRC colonic tissue, consistent with the positive correlation between differentiation of CRC, and colonic tumour expression of IL-38. IL-38 is a reliable/sensitive biomarker for distinguishing between CRC and non-cancer colonic tissue. There is a positive correlation between colonic IL-38 in CRC and prognosis and/or overall survival, particularly in advanced CRC, supporting IL-38 probably being a reliable and consistent independent factor in predicting the prognosis of CRC. The findings above may be useful in exploring therapeutic targeting for precision medicine.

9.
Oncol Lett ; 20(1): 465-473, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32565971

RESUMO

Circular RNAs (circRNAs) are highly conserved and stable closed-loop non-coding RNAs. They are involved in numerous biological functions, including regulating gene transcription or protein translation by interacting with proteins and regulating expression of microRNAs. The aberrant expression of circRNAs has been reported in many cancers, including gastric cancer. By regulating gene expression, circRNAs are able to affect the proliferation, invasion and metastasis of gastric cancer. The current review focused on the characteristics and biological functions of circRNAs, the carcinogenic potential and the possible implications of circRNAs on the diagnosis and treatment of gastric cancer. In conclusion, circRNAs may serve as potential biomarkers for diagnosis, as well as therapeutic targets.

10.
Aust J Gen Pract ; 49(6): 364-368, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32464736

RESUMO

BACKGROUND AND OBJECTIVES: As a result of the pandemic, family physicians face the additional challenge of navigating COVID-19. The aim of this study was to provide simulated training for best-practice management of COVID-19 presentations for residency program trainees in Shanghai, China. METHOD: A simulated suspected COVID-19 case was designed on the basis of a real patient. The simulation included: pre­ and post-simulation surveys, a PowerPoint presentation, simulation practice, debriefing and reflection. Improvement in survey outcomes was assessed using a paired t-test. RESULTS: A total of 25 trainees participated in the simulation, consisting of first-, second- and third-year family medicine residents. Significant improvement was observed in their knowledge of COVID-19, and sub-analysis showed that all three grades of residents improved their knowledge significantly. Ninety-six per cent of participants believed the simulation was very helpful. DISCUSSION: The simulation scenario improves crisis management skills for family physicians managing the high risk of transmission of respiratory infectious diseases. Higher-order learning outcomes will be explored in future training programs.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Medicina de Família e Comunidade/educação , Internato e Residência/métodos , Pneumonia Viral/terapia , Treinamento por Simulação/métodos , Adulto , China , Competência Clínica , Feminino , Humanos , Masculino , Pandemias
11.
Travel Med Infect Dis ; 37: 101741, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407893

RESUMO

Background: The transmission of COVID-19 is about to come under control within China, however, an emerging challenge to the Chinese authorities is reverse transmission due to COVID-19 patients/carriers evacuating from overseas to China. Methods: We analysed the epidemiological characteristics of 311 Chinese citizens evacuated from Iran. All confirmed COVID-19 cases amongst the returnees were displayed by the spatial distribution pattern of the extent of COVID-19 infection. Results: Characteristics that differed significantly amongst these returnees compared to the original infected cohorts in Gansu were mean age, occupation and sex. Differences observed between infected patients and non-patients amongst returnees were age, sex, race, occupation, the use of facemasks, and residential situation in Iran. The clinical features that were significantly related to infection were chill, shortness of breath, chest pain and nausea. Spatial distribution pattern analysis indicated that infected returnees had resided within Iranian provinces that had experienced high levels of COVID-19. The spatial distribution of the original homes of these returnees before departure for Iran demonstrated that returnees will largely return to northwest China, to regions that have only experienced low levels of infection within China. Conclusion: Blocking the reverse transmission of COVID-19 is critical in preventing a secondary outbreak of COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Betacoronavirus , Pré-Escolar , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Lactente , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Quarentena , Fatores de Risco , Estudantes , Viagem
12.
Emerg Infect Dis ; 26(6): 1257-1265, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32168465

RESUMO

To determine the epidemiology of coronavirus disease (COVID-19) in a remote region of China, far from Wuhan, we analyzed the epidemiology of COVID-19 in Gansu Province. From January 23 through February 3, 2020, a total of 35 (64.8%) of 54 reported cases were imported from COVID-19-epidemic areas. Characteristics that differed significantly during the first and second waves of illness in Gansu Province were mean patient age, occupation, having visited epidemic areas, and mode of transportation. Time from infection to illness onset for family clusters was shorter in Gansu Province than in Wuhan, consistent with shortened durations from onset to first medical visit or hospitalization. Spatial distribution pattern analysis indicated hot spots and spatial outliers in Gansu Province. As a result of adequate interventions, transmission of the COVID-19 virus in Gansu Province is decreasing.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Criança , Pré-Escolar , China/epidemiologia , Feminino , Sistemas de Informação Geográfica , Hospitalização , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Análise Espacial , Fatores de Tempo , Adulto Jovem
13.
Cancer Med ; 9(9): 3057-3069, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32150664

RESUMO

BACKGROUND: Alpha-fetoprotein (AFP), routinely used for diagnosis of hepatocellular carcinoma (HCC), is limited with relatively low sensitivity and high false positivity in HBV-related HCC (HBV-HCC). Thus, an alternative approach was explored to improve specificity/sensitivity for diagnosis of HBV-HCC, using the combination of AFP, inflammatory score, and liver function. METHODS: Chronic hepatitis B (CHB) (n = 510) and HBV-HCC (n = 473) patients were identified retrospectively for this study. The diagnostic value of single vs combined biomarkers for HBV-HCC was analyzed, using ROC curve. RESULTS: It was observed that elderliness, male sex, cirrhosis, HBeAg+ or no-antiviral therapy, and elevation of ALT, AST, neutrophil-lymphocyte ratio (NLR), and AFP were associated with developing HBV-HCC. However, the cut-off ALT defined by Chinese standard, but not by AASLD, was a risk factor. Interestingly, AFP of HBeAg- HBV-HCC patients without cirrhosis was significantly higher than that of the HBeAg+ patients. AUC values for AFP, ALT, AST, or NLR were 0.84 (95% CI: 0.815-0.862), 0.533 (95% CI: 0.501-0.565), 0.696 (95% CI: 0.666-0.725), or 0.684 (95% CI: 0.654-0.713) with optimal cut-off at 7.21 ng/mL, 43 IU/mL, 38 IU/mL, or 2.61, respectively. Combination of AFP with ALT, AST, and NLR improved the diagnostic performance for HBV-HCC, compared to any of the single biomarkers or any other combinations among these patients (except no-cirrhosis). CONCLUSIONS: Elderliness, male sex, elevated ALT, AST, NLR, AFP, cirrhosis, HBeAg+ , and no-antiviral treatment were independent risk factors for HBV-HCC. AASLD standard of ALT cut-off value may not be suitable for the Chinese population. Regular monitoring of HCC among HBeAg- patients with abnormal AFP may improve the management of HBV-HCC. The diagnostic performance of AFP combined with ALT, AST, and NLR for HBV-HCC was superior to single biomarker or any other combinations among these patients, and its diagnostic equation can be used as useful tool for differentiation of HBV-HCC from CHB.

14.
BMC Cancer ; 20(1): 92, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013927

RESUMO

BACKGROUND AND AIMS: Colorectal cancer (CRC) is a major killer. Host immunity is important in tumorigenesis. Direct comparison among IL-36α, IL-36ß and IL-36γ in the prognosis of CRC is unclear. METHODS: CRC tissue arrays were generated from colorectostomy samples with TNM stage, invasion depth and the demography of these patients (n = 185). Using immunohistochemistry/histopathology, IL-36α, IL-36ß and IL-36γ were determined, in comparison to non-cancer tissues. RESULTS: A significant association was observed between colonic IL-36α, IL-36ß or IL-36γ and the presence of cancer (with all P < 0.0001). Using ROC curve analysis, specificity and sensitivity of IL-36α, IL-36ß or IL-36γ were confirmed, with area under the curve (AUC) values of 0.68, 0.73 and 0.65, respectively. Significant differences in survival were observed between IL-36αhigh and IL-36αlow (P = 0.003) or IL-36γhigh and IL-36γlow (P = 0.03). Survival curves varied significantly when further stratification into sub-groups, on the basis of combined levels of expression of two isotypes of IL-36 was undertaken. A significant difference was observed when levels of IL-36α and IL-36ß were combined (P = 0.01), or a combination of IL-36α plus IL-36γ (P = 0.002). The sub-groups with a combination of IL-36αhigh plus IL-36ßhigh, or IL-36αhigh plus IL-36γlow exhibited the longest survival time among CRC patients. In contrast, the sub-groups of IL-36αlow plus IL-36ßhigh or IL-36αlow plus IL-36γhigh had the shortest overall survival. Using the log-rank test, IL-36αhigh expression significantly improved survival in patients with an invasion depth of T4 (P < 0.0001), lymph node metastasis (P = 0.04), TNM III-IV (P = 0.03) or with a right-sided colon tumour (P = 0.02). Similarly, IL-36γlow expression was significantly associated with improved survival in patients with no lymph node metastasis (P = 0.008), TNM I-II (P = 0.03) or with a left-sided colon tumour (P = 0.05). Multivariate analysis demonstrated that among IL-36α, IL-36ß and IL-36γ, only IL-36α (HR, 0.37; 95% CI, 0.16-0.87; P = 0.02) was an independent factor in survival, using Cox proportional hazards regression analysis. CONCLUSION: IL-36α or IL-36γ are reliable biomarkers in predicting the prognosis of CRC during the later or early stages of the disease, respectively. Combining IL-36α plus IL-36γ appears to more accurately predict the postoperative prognosis of CRC patients. Our data may be useful in the management of CRC.


Assuntos
Neoplasias Colorretais/patologia , Interleucina-1/metabolismo , Idoso , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Análise Serial de Tecidos
15.
World J Gastroenterol ; 26(6): 645-656, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103873

RESUMO

BACKGROUND: Reports on bacterial infection (BI) in decompensated cirrhosis (DC) is mainly from alcoholic cirrhosis. The role of BI as a trigger or complication of acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus decompensated cirrhosis (HBV-DC) remains to be investigated. AIM: To investigate the impact of BI on the outcomes of the patients with HBV-DC admitted into the hospital with or without ACLF. METHODS: This retrospective study included patients with HBV-DC admitted to two tertiary centers in China. In-hospital overall survival, 90-d transplant-free survival, 5-year post-discharge survival, and cumulative incidence of ACLF were evaluated. Risk factors for death were analyzed considering liver transplantation as a competing event. RESULTS: A total of 1281 hospitalized HBV-DC patients were included; 284 had ACLF at admission. The overall prevalence of BI was 28.1%. The patients with BI had a significantly lower in-hospital survival and transplant-free 90-d survival than those without, in both the patients admitted with and without ACLF. The presence of BI significantly increased the risk of developing ACLF [sub-distribution hazard ratio (sHR) = 2.52, 95%CI: 1.75-3.61, P < 0.001] in the patients without ACLF. In the patients discharged alive, those who had an episode of BI had a significantly lower 5-year transplant-free survival. BI was an independent risk factor for death in the patients admitted without ACLF (sHR = 3.28, 95%CI: 1.93-5.57), while in ACLF admissions, the presence of pneumonia, but not other type of BI, independently increased the risk of death (sHR = 1.87, 95%CI: 1.24-2.82). CONCLUSION: BI triggers ACLF in patients with HBV-DC and significantly impairs short-term survival. HBV-DC patients should be monitored carefully for the development of BI, especially pneumonia, to avoid an adverse outcome.

16.
Cancer Immunol Immunother ; 69(1): 69-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31786620

RESUMO

Colorectal cancer (CRC) is a leading cause of cancer-related death, partly due to a lack of reliable biomarkers for early diagnosis. To improve the outcome of CRC, it is critical to provide diagnosis at an early stage using promising sensitive/specific marker(s). Using immunohistochemistry and histopathology, IL-38 expression was determined in tissue arrays of CRC with different TNM status and depth of tumour invasion. Data were compared to IL-38 in adjacent non-cancer tissue and correlated with demographic information, including survival. A substantial reduction of IL-38 was detected in the CRC tissue compared to adjacent non-cancer colonic tissue. IL-38 correlated with the extent of tumour differentiation (P < 0.0001); CRC location in the left side of the colon (P < 0.05), and smaller tumour size (≤ 5 cm; P < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated both high specificity and high sensitivity of IL-38 for the diagnosis of CRC [area under the curve (AUC) = 0.89)]. By sub-group analysis, AUC of IL-38 for the diagnosis of CRC was higher in poorly differentiated, right-sided CRC or tumour size > 5 cm (all AUC > 0.9). Significantly, longer survival was observed for the IL-38high versus the IL-38low groups in CRC patients (P = 0.04). Survival was also longer for IL-38high patients with lymph node metastasis (P = 0.01) and TNM stage III-IV (P = 0.02). Multivariate analysis demonstrated that IL-38 (P = 0.05) and tumour invasion depth (P = 0.04) were independent factors for survival. High IL38 in CRC is an independent prognostic factor for the longer survival of CRC patients. IL-38 signalling may constitute a therapeutic target in CRC.


Assuntos
Adenocarcinoma/diagnóstico , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Interleucinas/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Interleucinas/análise , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Sensibilidade e Especificidade , Taxa de Sobrevida , Adulto Jovem
17.
ACS Biomater Sci Eng ; 6(2): 995-1007, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33464851

RESUMO

The functionality and durability of implanted biomaterials are often compromised by an exaggerated foreign body reaction (FBR). M1/M2 polarization of macrophages is a critical regulator of scaffold-induced FBR. Macrophage colony-stimulating factor (M-CSF), a hematopoietic growth factor, induces macrophages into an M2-like polarized state, leading to immunoregulation and promoting tissue repair. In the present study, we explored the immunomodulatory effects of surface bound M-CSF on poly-l-lactic acid (PLLA)-induced FBR. M-CSF was immobilized on the surface of PLLA via plasma immersion ion implantation (PIII). M-CSF functionalized PLLA, PLLA-only, and PLLA+PIII were assessed in an IL-1ß luciferase reporter mouse to detect real-time levels of IL-1ß expression, reflecting acute inflammation in vivo. Additionally, these different treated scaffolds were implanted subcutaneously into wild-type mice to explore the effect of M-CSF in polarization of M2-like macrophages (CD68+/CD206+), related cytokines (pro-inflammatory: IL-1ß, TNF and MCP-1; anti-inflammatory: IL-10 and TGF-ß), and angiogenesis (CD31) by immunofluorescent staining. Our data demonstrated that IL-1ß activity in M-CSF functionalized scaffolds was ∼50% reduced compared to PLLA-only at day 1 (p < 0.01) and day 2 (p < 0.05) post-implantation. There were >2.6-fold more CD206+ macrophages in M-CSF functionalized PLLA compared to PLLA-only at day 7 (p < 0.001), along with higher levels of IL-10 at both day 7 (p < 0.05) and day 14 (p < 0.01), and TGF-ß at day 3 (p < 0.05), day 7 (p < 0.05), and day 14 (p < 0.001). Lower levels of pro-inflammatory cytokines were also detected in M-CSF functionalized PLLA in the early phase of the immune response compared to PLLA-only: a ∼58% decrease at day 3 in IL-1ß; a ∼91% decrease at day 3 and a ∼66% decrease at day 7 in TNF; and a ∼60% decrease at day 7 in MCP-1. Moreover, enhanced angiogenesis inside and on/near the scaffold was observed in M-CSF functionalized PLLA compared to PLLA-only at day 3 (p < 0.05) and day 7 (p < 0.05), respectively. Overall, M-CSF functionalized PLLA enhanced CD206+ macrophage polarization and angiogenesis, consistent with lower levels of pro-inflammatory cytokines and higher levels of anti-inflammatory cytokines in early stages of the host response, indicating potential immunoregulatory functions on the local environment.

18.
J Mech Behav Biomed Mater ; 100: 103372, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31369958

RESUMO

Shape memory polyurethanes (SMPU) have been of great interest in biomedical applications because of their unique ability to recover a primary shape by external actuation. This advantage can allow for easy suture and minimum tissue damage caused by surgery. Since SMPU suffer from low stiffness and low strength, carbon fibres have been widely used to reinforce SMPU, and their shape memory properties have been investigated using thermomechanical tensile tests. In reality, however, bending situations are more common than tensile situations, such as human skulls. In this study, carbon fibre reinforced SMPU (CF/SMPU) composites were studied as promising cranial implants that can offer shape memory properties, shape flexibility and high strength. First, the basic properties of pristine SMPU and CF/SMPU composites were characterised, including glass transition temperature (Tg), the viscosity of SMPU, the morphology of CF/SMPU, and their tensile and flexural mechanical properties. Then, a new method using rheometer was developed to study the shape memory behaviours of SMPU and CF/SMPU with three-point bending under relatively small deformations (≤1%), including flexural stress during programming and cooling, and bending recovery force during shape recovery. Finally, due to the invisibility of recovery process that was conducted in an enclosed temperature-controlling chamber of rheometer, the finite element method (FEM) was used to simulate the bending recovery test. The results showed carbon fibres significantly enhanced the mechanical properties (Young's modulus and flexural modulus) of SMPU. In terms of bending shape recovery, compared to pristine SMPU, CF/SMPU composites obtained substantially higher flexural stress during programming and cooling processes, and larger, more stable recovery force during recovery. The FEM results consolidated the peak recovery force of SMPU and the continuously growing recovery force of CF/SMPU as the temperature increased. Our findings on the improved mechanical and shape memory properties can provide a solid foundation for the potential applications of CF/SMPU composites as cranial implants.


Assuntos
Fibra de Carbono/química , Poliuretanos/química , Materiais Inteligentes/química , Varredura Diferencial de Calorimetria , Simulação por Computador , Módulo de Elasticidade , Análise de Elementos Finitos , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Modelos Teóricos , Desenho de Prótese , Reprodutibilidade dos Testes , Reologia , Crânio/patologia , Estresse Mecânico , Temperatura , Resistência à Tração , Viscosidade
19.
Biosci Trends ; 13(2): 130-135, 2019 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-30930359

RESUMO

Single nucleotide polymorphisms (SNP) influence the outcome of antiviral therapy in chronic hepatitis B patients. Interferon ß promoter stimulator 1 polymorphisms (IPS-1) regulate interferon (IFN) mediated viral clearance in hepatitis B virus (HBV) infection. In our study, HepG2 and HepG2.2.15 were transfected with different SNP genotype expression vectors of IPS-1 (wild-type, rs17857295, rs7262903 and rs7269320). The production of IPS-1 and IFN were evaluated in these transfected cells. IPS-1 in the HepG2.2.15 cells transfected with rs17857295 or rs7262903 was 37% or 31% lower than that with wild-type transfection (p < 0.001). IFN-ß in rs17857295 or rs7262903 transfected HepG2.2.15 cells was 5.4 or 3.7 fold higher than that of wild-type transfection (p < 0.0001). IPS-1 in rs7269320 SNP transfected HepG2.2.15 cells was 40% lower than that of wild-type transfection (p < 0.0001); no significantly different IFN-ß was observed between rs7269320 SNP and wild-type transfections. IFN-ß expression was > 2 fold higher in rs17857295 transfected HepG2.2.15 cells than HepG2 cells (p < 0.001). The data suggests that host HBV viral clearance is stronger in IPS-1 rs17857295 or rs7262903 SNP genotype patients than wild-type patients. Relatively weak inducible IFN-ß production in HBV infected patients with IPS-1 rs7269320 SNP or wild-type may contribute to chronic virus infection.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Hepatite B/genética , Interferon beta/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Vetores Genéticos/metabolismo , Genótipo , Células HEK293 , Células Hep G2 , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
20.
Dig Liver Dis ; 51(9): 1323-1329, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30928419

RESUMO

BACKGROUND: The aim of this study was to compare the diagnostic accuracy of the FibroTouch and FibroScan in patients with chronic liver disease (CLD) for staging fibrosis. METHODS: A prospective study was conducted in 435 CLD patients between 2014 and 2017. Index tests (FibroTouch, FibroScan, APRI, and FIB-4 score) and a reference standard (liver biopsy) were performed within one week. RESULTS: The area under the receiver operating curve (AUROC) of the FibroTouch was similar with that of the FibroScan for the diagnosis of significant fibrosis, severe fibrosis, or cirrhosis; however, the AUROC of the FibroTouch was higher than that of APRI or FIB-4 (p < 0.001). There was a significant correlation (rho = 0.85, p < 0.001) between the FibroTouch and FibroScan for liver stiffness. The overall diagnostic accuracy of FibroTouch for significant fibrosis, severe fibrosis, or cirrhosis was 73.3%, 83.2%, or 84.1%, respectively. No significant differences between the FibroTouch and FibroScan were detected regarding the sensitivity, specificity, negative predictive value, positive predictive value, and accuracy. The optimal cut-off values for each stage of fibrosis were similar between the FibroTouch and FibroScan. CONCLUSION: The FibroTouch is a valuable diagnostic tool for diagnosing liver fibrosis with good diagnostic accuracy which was comparable with that of the FibroScan, but superior to that of the APRI and FIB-4.


Assuntos
Técnicas de Imagem por Elasticidade/instrumentação , Hepatopatias/patologia , Fígado/patologia , Adulto , Doença Crônica , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC
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