[Research progress of biomaterials with ordered micro-nano structure in wound repair].

Many injury-causing factors, including burns and surgery, etc., can lead to the destruction of structure and function of skin. Suitable wound dressing or implant is the material basis to promote wound healing and regeneration. Biomaterials with micro-nano structure can affect cell behavior, promote orderly growth of cell in accordance with the structure. Their application in wound healing can promote angiogenesis, regulate immune response, and reduce scar area. In recent years, the application of biomaterials with ordered micro-nano structure in tissue engineering has attracted extensive attention. This paper introduces the structure and preparation methods of several biomaterials with ordered micro-nano structure, and focuses on how the surface microstructure of biomaterials affects the process of wound healing and its molecular mechanism, in order to find and develop medical biomaterials that are closer to the skin tissue structure for clinical wound treatment.

Effects of platelet-rich plasma on angiogenesis and osteogenesis-associated factors in rabbits with avascular necrosis of the femoral head.

OBJECTIVE: Platelet-rich plasma (PRP) contains various growth factors and cytokines that can enhance the recovery of the damaged tissues. The present study aimed to examine the effects of PRP on the recovery of avascular necrosis of the femoral head (ANFH), and to provide novel insights into the clinical treatment of this disease. MATERIALS AND METHODS: A total of 24 New Zealand white rabbits were randomly divided into the normal control group, ANFH model and PRP-treated groups (n =1 2 each). Blood samples were extracted from the auricular vein at 4, 8 and 12 weeks after establishing the model to determine the hemorheological indexes, as well as the content of serum osteocalcin bone Gla-protein (BGP) and vascular endothelial growth factor (VEGF). In addition, femoral head tissue was collected, with part of it used for hematoxylin and eosin (HE) staining to observe the histological changes. The remaining was used to detect the mRNA expression levels of alkaline phosphatase (AKP), basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1), bone morphogenetic protein 2 (BMP-2) and platelet-derived growth factor B (PDGF-B) by reverse transcription-polymerase chain reaction. RESULTS: Compared with the model group, PRP treatment significantly improved the hemorheological indexes, as well as significantly increased the contents of BGP and VEGF. In the PRP group, the expression levels of TGF-ß1, bFGF, BMP-2 and PDGF-B were significantly upregulated, while AKP expression was downregulated compared with the model group. Furthermore, PRP evidently improved the histological structure of the ANFH tissue. CONCLUSIONS: PRP was able to improve the hemorheological indexes following femoral neck fracture, repair the local blood vessels, and promote the expression of osteoblast-associated and angiogenesis-associated factors, which suggested a high efficiency in repairing ANFH.

A diagnostic algorithm for assessment of liver fibrosis by liver stiffness measurement in patients with chronic hepatitis B.

Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)-infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV-infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut-offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut-off for severe steatosis (≥30%) was 287 dB/m. Among patients with low-grade fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low-grade fibrosis, a higher rate of false-positive rate was observed in patients with severe steatosis than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0-F2: 23.7% vs 9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by γ-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of 0.17. In patients with GPR<0.17, similar results were observed. The presence of steatosis may lead to overestimation of fibrosis assessed by liver stiffness measurement in patient with chronic hepatitis B. A diagnostic algorithm for assessing fibrosis using liver stiffness was developed by combining both controlled attenuation parameter and GPR values.

A nomogram for predicting prognostic value of inflammatory response biomarkers in decompensated cirrhotic patients without acute-on-chronic liver failure.

BACKGROUND: Inflammation plays a vital role in liver cirrhosis progression and prognosis. AIM: To investigate the prognostic significance of inflammatory response markers in decompensated cirrhotic patients without acute-on-chronic liver failure (ACLF). METHODS: Independent predictors were identified using multivariate Cox model and then assembled into a nomogram to predict survival. Concordance index (C-index) and time-dependent receiver operating characteristics (td-ROC) analysis were adopted to evaluate and compare the performance of nomogram, model for end-stage liver disease (MELD) scores, MELD-Na and Chronic Liver Failure-consortium score for acute decompensated (CLIF-C ADs). RESULTS: A total of 902 decompensated cirrhotic patients with different aetiologies were enrolled, with 6-month, 1-year and 3-year mortality of 18.6%, 24.4% and 34.8%, respectively. The cut-off values for neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) determined by X-tile program were 5.7 and 1.1 respectively. Patients with NLR>5.7 or LMR≤1.1 had significantly higher mortality (P < 0.001). Independent factors derived from multivariable Cox analysis of development cohort to predict mortality were age, NLR and LMR (hazard ratio (HR): 1.064, 95% confidence interval (CI): 1.045-1.084, P < 0.001; HR: 1.124, 95%CI: 1.091-1.158, P < 0.001; HR: 0.794, 95%CI: 0.702-0.898, P < 0.001, respectively). The C-indexes of nomogram were higher than that of MELD score, MELD-Na and CLIF-C ADs for predicting survival. The tdROC and decision curves showed that nomogram was superior to MELD score, MELD-Na and CLIF-C ADs. Similar results were observed in validation cohort. CONCLUSION: The proposed nomogram with neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio resulted in accurate prognostic prediction for decompensated cirrhotic patients without ACLF.

Classification and regression tree analysis of acute-on-chronic hepatitis B liver failure: Seeing the forest for the trees.

At present, there is no ideal model for predicting the short-term outcome of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBLF were screened in the study, which were recognized as derivation cohort and validation cohort, respectively. CART analysis was applied to predict the 3-month mortality of patients with ACHBLF. The accuracy of the CART model was tested using the area under the receiver operating characteristic curve, which was compared with the model for end-stage liver disease (MELD) score and a new logistic regression model. CART analysis identified four variables as prognostic factors of ACHBLF: total bilirubin, age, serum sodium and INR, and three distinct risk groups: low risk (4.2%), intermediate risk (30.2%-53.2%) and high risk (81.4%-96.9%). The new logistic regression model was constructed with four independent factors, including age, total bilirubin, serum sodium and prothrombin activity by multivariate logistic regression analysis. The performances of the CART model (0.896), similar to the logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667, P<.001). The results were confirmed in the validation cohort. We have developed and validated a novel CART model superior to MELD for predicting three-month mortality of patients with ACHBLF. Thus, the CART model could facilitate medical decision-making and provide clinicians with a validated practical bedside tool for ACHBLF risk stratification.

[Efficacy and safety of IA regimen containing different doses of idarubicin in de-novo acute myeloid leukemia for adult patients].

Objective: To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m(2), 10 mg/m(2) or 12 mg/m(2) as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) . Methods: A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m(2)) as induction chemotherapy in newly diagnosed patients of adult AML. Results: Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m(2) group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m(2) was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m(2) when compared with the IDA 8 mg/m(2) was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×10(9)/L in IDA 8 mg/m(2) group, IDA 10 mg/m(2) group and IDA 12 mg/m(2) group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×10(9)/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) . Conclusions: For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m(2) is clinically superior to IDA 8 mg/m(2) and IDA 12 mg/m(2) in favorable intermediate AML subgroup. However, idarubicin 12 mg/m(2) is more suitable to adverse AML subgroup.

Usefulness of albumin-bilirubin grade for evaluation of long-term prognosis for hepatitis B-related cirrhosis.

Long-term prognosis varies widely among patients with hepatitis B virus (HBV)-related liver cirrhosis. Our study aimed to investigate the applicability of albumin-bilirubin (ALBI), Child-Pugh and model for end-stage liver disease (MELD) scores to the long-term prognosis prediction of HBV-related cirrhosis. Patients diagnosed with HBV-associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long-term outcome prediction for HBV-related cirrhosis was compared with Child-Pugh and MELD scores using time-dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow-up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child-Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1-year, 2-year and 3-year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child-Pugh class. Thus, ALBI score was effective in predicting the long-term prognosis for patients with HBV-related cirrhosis and more accurate than Child-Pugh and MELD scores.

Systematic review with network meta-analysis: the comparative effectiveness and safety of interventions in patients with overt hepatic encephalopathy.

BACKGROUND: Interventional treatment for overt hepatic encephalopathy (OHE), includes non-absorbable disaccharides, neomycin, rifaximin, L-ornithine-L-aspartate and branched chain amino acids (BCAA). However, the optimum regimen remains inconclusive. AIM: To compare interventions in terms of patients' adverse events and major clinical outcomes. METHODS: Literature search of PubMed, Embase, Scopus, and Cochrane Library studies published up to July 31 2014. RCTs of above interventions in OHE patients were included. Network meta-analysis combined direct and indirect evidence to estimate odds ratios (ORs) and mean difference (MD) between treatments and the probabilities of ranking for treatment based on clinical outcomes. RESULTS: Twenty eligible RCTs were included. When compared with observation, only L-ornithine-L-aspartate (OR 3.71, P < 0.001) and BCAA (OR 3.37, P < 0.001) improved clinical efficacy significantly. However, when L-ornithine-L-aspartate was compared with BCAA, non-absorbable disaccharides and neomycin, there was a trend suggesting that L-ornithine-L-aspartate may be the most effective intervention with respect to clinical improvement (OR 1.10), rifaximin (OR 1.31), non-absorbable disaccharides (OR 2.75), neomycin (OR 2.22). In addition, L-ornithine-L-aspartate (MD -20.18, 95% CI -40.12 to -0.27) provided a significant reduction in blood ammonia concentration compared with observation. Neomycin appeared to be associated with more adverse events in comparison with non-absorbable disaccharides (OR 10.15), rifaximin (OR 17.31), L-ornithine-L-aspartate (OR 3.16) or BCAA (OR 7.69). CONCLUSIONS: L-ornithine-L-aspartate treatment may show a trend in superiority for clinical efficacy among standard interventions for OHE. Rifaximin shows the greatest reduction in blood ammonia concentration, and treatment with neomycin demonstrates a higher probability in causing adverse effects among the five compared interventions.

Systematic review with network meta-analysis: adjuvant therapy for resected biliary tract cancer.

BACKGROUND: Major adjuvant therapies for biliary tract cancer (BTC) include fluorouracil, gemcitabine and chemoradiation (CRT), but the optimum regimen remains inconclusive. AIM: To compare these therapies in terms of patient survival rates after resection and toxic effects. METHODS: We searched PubMed for controlled trials comparing the above three therapies with each other or observation alone until 31 January 2014. We estimated the hazard ratios (HRs) for death and odds ratios (ORs) for toxic effects among different therapies. Subgroup analyses based on positive lymph node or resection margin were also performed. RESULTS: Twelve eligible articles were included. Gemcitabine improved 5-year survival (HR 2.12, 95% CI, confidence interval 1.23-4.02, P = 0.01), whereas fluorouracil (HR 1.61, 95% CI 0.74-3.67) and CRT (HR 1.55, 95% CI 0.82-3.32) provided a poorer survival outcome compared with gemcitabine after 1 year. Similarly, for 5-year survival rates, although differing, CRT did not provide a significant improvement in survival (HR 0.46, 95% CI 0.20-0.97) compared with gemcitabine. Fluorouracil did not appear to provide benefit over gemcitabine (HR 1.56, 95% CI 0.77-3.35). CRT was ranked highest for toxic effects including haematological (OR 5.45, 95% CI 0.01-483.85) and nonhaematological (OR 5.77, 95% CI 0.01-3807.40). CONCLUSIONS: Chemotherapy with gemcitabine is the optimum adjuvant treatment with a balanced benefit-toxicity ratio for resected biliary tract cancer. Chemoradiation was more likely to cause toxic effects.

Relationship between IL-10 gene -1082A/G and -592C/A polymorphisms and the risk of hepatitis C infection: a meta-analysis.

Increasing evidence suggests that interleukin-10 (IL-10) gene promoter polymorphisms may be associated with chronic hepatitis C virus (HCV) infection and HCV clearance. To more precisely estimate the association between these variants and the risk of HCV infection, we performed a meta-analysis of 26 studies describing the IL-10-1082A/G, -819C/T, -592C/A genotypes, including 4039 chronic HCV infection cases and 2902 controls. When compared with a healthy population, the -1082GG allele had a 43% increased risk of chronic HCV infection in combined populations (GG vs GA + AA: odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.052-1.952, P = 0.023). In subgroup analysis by ethnicity, a significant increased risk was associated with the -1082GG genotype in the Caucasian population (GG vs AA: OR = 1.390, 95% CI: 1.108-1.744, P = 0.004; GG vs GA + AA: OR = 1.621, 95% CI: 1.267-2.075, P = 0.000). However, no significant association was found in Asian, African or Chinese populations. Moreover, a higher distribution of -592A was found in the spontaneously recovered population (AA vs CC: OR = 0.585, 95% CI = 0.387-0.884, P = 0.011; AA + AC vs CC: OR = 0.738, 95% CI = 0.551-0.988, P = 0.041; AA vs AC + CC: OR = 0.788, 95% CI = 0.664-0.935, P = 0.006) than that in the chronic HCV infection population. In conclusion, the IL-10-1082GG allele may increase the risk of chronic HCV infection in Caucasian population, and people carrying the IL-10-592A allele are more likely to clear HCV spontaneously.

A model to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure using artificial neural network.

Model for end-stage liver disease (MELD) scoring was initiated using traditional statistical technique by assuming a linear relationship between clinical features, but most phenomena in a clinical situation are not linearly related. The aim of this study was to predict 3-month mortality risk of acute-on-chronic hepatitis B liver failure (ACHBLF) on an individual patient level using an artificial neural network (ANN) system. The ANN model was built using data from 402 consecutive patients with ACHBLF. It was trained to predict 3-month mortality by the data of 280 patients and validated by the remaining 122 patients. The area under the curve of receiver operating characteristic (AUROC) was calculated for ANN and MELD-based scoring systems. The following variables age (P < 0.001), prothrombin activity (P < 0.001), serum sodium (P < 0.001), total bilirubin (P = 0.015), hepatitis B e antigen positivity rate (P < 0.001) and haemoglobin (P < 0.001) were significantly related to the prognosis of ACHBLF and were selected to build the ANN. The ANN performed significantly better than MELD-based scoring systems both in the training cohort (AUROC = 0.869 vs 0.667, 0.591, 0.643, 0.571 and 0.577; P < 0.001, respectively) and in the validation cohort (AUROC = 0.765 vs 0.599, 0.563, 0.601, 0.521 and 0.540; P ≤ 0.006, respectively). Thus, the ANN model was shown to be more accurate in predicting 3-month mortality of ACHBLF than MELD-based scoring systems.

The tumour necrosis factor-α-238A allele increases the risk of chronic HBV infection in European populations.

Tumour necrosis factor-α (TNF-α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF-α genes. However, there have been conflicting results reported in previous studies on TNF-α-238 and TNF-α-863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966-August, 2010) and China Biological Medicine Database (January, 1978-August, 2010) and carried out a meta-analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta-analysis did not suggest significant associations of TNF-α-238 and TNF-α-863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF-α-238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07-4.58, P = 0.032; OR = 4.46, 95% CI: 1.75-11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF-α-238A allele may increase the risk of chronic HBV infection in European populations.

Tumour necrosis factor-α-857T allele reduces the risk of hepatitis B virus infection in an Asian population.

Tumour necrosis factor-α (TNF-α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF-α-857 polymorphism and chronic HBV infection have reported conflicting results. So a meta-analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966-March, 2011) and the China Biological Medicine Database (January, 1978-March, 2011) were searched using the keywords TNF-α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta-analysis. All fourteen studies focussed on an Asian population. The overall meta-analysis suggested that TNF-α-857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71-0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy-Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68-0.98, P = 0.043; OR = 0.77, 95% CI: 0.68-0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70-0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF-α-857T allele reduces the risk of chronic HBV infection in this Asian population.