Prediction of critical energy release rate for cortical bone structure under different failure modes / 中国组织工程研究

BACKGROUND:Critical energy release rate is a global fracture parameter that could be measured during the failing process,and its value may change under different failure modes even in the same structure. OBJECTIVE:To propose an approach to predict the critical energy release rate in the femoral cortical bone structure under different failure modes. METHODS:Three-point bending and axial compression experiments and the corresponding fracture simulations were performed on the rat femoral cortical bone structures.Different critical energy release rates were repeatedly assigned to the models to perform fracture simulation,and the predicted load-displacement curves in each simulation were compared with the experimental data to back-calculate the critical energy release rate.The successful fit was that the differences in the fracture parameters between the predicted and experimental results were less than 5%. RESULTS AND CONCLUSION:(1)The results showed that the cortical bone structure occurred tensile open failure under three-point bending load,and the predicted critical energy release rate was 0.16 N/mm.(2)The same cortical bone structure occurred shear open failure under axial compression load,and the predicted critical energy release rate was 0.12 N/mm,which indicates that the critical energy release rate of the same cortical bone structure under different failure modes was different.(3)A comprehensive analysis from the perspectives of material mechanical properties and damage mechanism was conducted to reveal the reasons for the differences in the critical energy release rate in the cortical bone structure under different failure modes,which provided a theoretical basis for the measurement of the energy release rate and the accurate fracture simulation.

Renshen Baidusan Regulates Autophagy to Repair Mucosa in Ulcerative Colitis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Renshen Baidusan in repairing intestinal mucosa in ulcerative colitis （UC） by regulating autophagy to scavenge peroxides. MethodThe mouse model of UC was induced by free drinking of 3.0% dextran sulphate sodium （DSS） solution. Sixty male C57BL/6J mice were randomized into normal， model， mesalazine （0.3 g·kg-1）， and high-， medium-， and low-dose （12.35， 8.22， 4.11 g·kg-1， respectively） Renshen Baidusan groups （n=10）. The mice were administrated with corresponding drugs by gavage for 7 consecutive days. The colon tissue was stained with hematoxylin-eosin （HE） to reveal the pathological changes， and Alcian blue-Periodic acid Scheff （PAS/AB） staining was employed to observe the goblet cell changes. The fluorescence expression of reactive oxygen species （ROS） in the colon tissue was detected by the immunofluorescence assay. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were measured by the biochemical methods. Western blot was employed to determine the expression levels of proliferating cell nuclear antigen （PCNA）， microtubule-associated protein 1 light chain 3 （LC3）， leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， and p62. ResultDestroyed mucosal epithelial structure， intestinal gland destruction， loss of goblet cells， and massive infiltration of inflammatory cells appeared in the model group. Compared with the normal group， the model group showed increased tissue damage injury （TDI） score of the colon tissue， decreased SOD activity and LC3Ⅱ/Ⅰ， PCNA value， and elevated levels of p62， MDA， ROS， and LGR5 （P<0.05）. Compared with the model group， different doses of Renshen Baidusan decreased the TDI score， promoted the generation of new goblet cells， elevated the levels of PCNA， LGR5， SOD， and LC3Ⅱ/Ⅰ， and lowered the levels of p62， MDA， and ROS （P<0.05）. Moreover， the low dose group showed the best performance （P<0.05）. ConclusionRenshen Baidusan can promote intestinal epithelial repair by activating intestinal autophagy， alleviating oxidative stress， and promoting intestinal stem cell proliferation and differentiation.

Regulating the structure of bacterial cellulose by altering the expression of bcsD using CRISPR/dCas9 / 生物工程学报

Gluconacetobacter xylinus is a primary strain producing bacterial cellulose (BC). In G. xylinus, BcsD is a subunit of cellulose synthase and is participated in the assembly process of BC. A series of G. xylinus with different expression levels of the bcsD gene were obtained by using the CRISPR/dCas9 technique. Analysis of the structural characteristics of BC showed that the crystallinity and porosity of BC changed with the expression of bcsD. The porosity varied from 59.95%-84.05%, and the crystallinity varied from 74.26%-93.75%, while the yield of BC did not decrease significantly upon changing the expression levels of bcsD. The results showed that the porosity of bacterial cellulose significantly increased, while the crystallinity was positively correlated with the expression of bcsD, when the expression level of bcsD was below 55.34%. By altering the expression level of the bcsD gene, obtaining BC with different structures but stable yield through a one-step fermentation of G. xylinus was achieved.

COVID-19: Why SOLIDARITY and DisCoVeRy trials may fail to bring informative and timely results

ObjectiveThe SOLIDARITY and DisCoVeRy trials were launched to facilitate the rapid worldwide comparison of the efficacy and safety of treatments against COVID-19. This study aimed to review the trial designs of SOLIDARITY and DisCoVeRy and their feasibility to generate high-quality evidence. MethodA systematic search of the European Clinical trial registry, the U.S. National Library of Medicine ClinicalTrials.gov, and the World Health Organizations (WHO) International Clinical Trials Registry Platform (ICTRP) was conducted on May 10th, 2020 to identify the study details of the SOLIDARITY and DisCoVeRy trials. A supplementary search of PubMed, WHOs website, French authorities websites, and Google search engine was conducted. A critical review was performed on the findings. ResultsThe DisCoVeRy trial design was detailed consistently in both the European and the US clinical rial registries. SOLIDARITY was registered on ICTRP, with country-specific information reported on country-level registry platforms. The DisCoVeRy trials design appears to be ideal from the methodological perspective. Both trials appear difficult to implement, impractical, and disconnected from the pandemic reality. This is consistent with the apparent failure of the trials to deliver conclusions before the end of the pandemic. ConclusionBoth trials constitute an interesting initiative yet may lack the resources to support a high-quality implementation. The authors call for a pandemic task force, with various experts on the front-line of COVID-19, to inform policy-makers to make effective decisions that may not be based on traditional, methodological state-of-the-art evidence, but rather pragmatic and revisable decisions reflecting emerging evidence for the benefit of patients and society.

Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials

PurposeThis study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. MethodA rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. ResultsA total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. ConclusionBased on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties.

A multicenter study on the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis / 中华实用儿科临床杂志

Objective To explore the clinical features and risk factors of poor prognosis in neonatal necrotizing enterocolitis(NEC).Methods A retrospective study was carried out in the infants with NEC admitted to 6 cooperative hospitals in Guangdong Province between January 2005 and December 2014.The clinical features and risk factors of poor prognosis in preterm and full-term infants diagnosed NEC,early onset and late onset NEC were analyzed.Results A total of 449 cases who met the criteria were admitted during the study time.The mortality was 23.6％ (106/449 cases),of which the preterm group was 24.6％ (58/238 cases) while the full-term group was 22.7％ (48/211 cases),the early onset group was 22.1％ (45/204 cases) while the late onset group was 24.3％ (57/235 cases).The median number of NEC onset in preterm group was 11 d after birth while the number of the full-term group was 6 d.Full-term infants who diagnosed NEC were more likely to manifest themselves as abdominal distension (52.1％ vs.42.0％,x2 =4.597,P =0.032),vomiting(36.5％ vs.17.2％,x2 =21.428,P =0.000) and bloody stool(30.3％ vs.21.4％,x2 =4.653,P =0.031);but in the onset of NEC,preterm infants more likely to have feeding intolerance (21.0％ vs.12.8％,x2=5.309,P =0.021).The early onset group of full-term NEC was much common in twins or multiplets(9.4％ vs.1.1％,x2 =6.226,P =0.013),which rate of surgical therapy was much higher (41.0％ vs.27.0％,P =0.036) and the breast-feeding rate before NEC was lower than the late onset group(14.5％ vs.32.6％,x2 =9.500,P =0.002),the differences were statistically significant.The gestational age and birth weight were bigger in the early onset group of preterm NEC[(33.8 ±2.5) weeks vs.(32.2 ±2.8) weeks,t =4.261,P =0.000;(2.1 ±0.5) kg vs.(1.7 ± 0.5) kg,t =4.735,P =0.000)],but length of stay was shorter than the late onset group (18.0 d vs.26.5 d,P =0.000).Logistic regression analysis showed that the risk factors of poor prognosis of full-term NEC were shock,peritonitis and sepsis;while risk factors of poor prognosis of preterm NEC were small for gestational age infant,pulmonary hemorrhage,shock,intestinal perforation and sepsis;the risk factors of poor prognosis of the early onset group of full-term NEC was shock;while those of the late onset group were shock and peritonitis;the risk factors of poor prognosis in the early onset group of preterm NEC were shock and sepsis,while those in the late onset group were pulmonary hemorrhage,shock,intestinal perforation and sepsis.Conclusions Compared to the preterm NEC,the onset time of full-term NEC was earlier and the clinical manifestations were more typical.Early identification and management of shock,peritonitis,intestinal perforation,sepsis and pulmonary hemorrhage can reduce the risk of poor prognosis of neonate NEC.

Current status of the establishment of acute promyelocytic leukemia in mouse models / 实用肿瘤学杂志

Acute promyelocytic leukemia(APL)is a class of malignant disease of hematopoietic tissue. Animal models are important tools for exploring human-related diseases.Many studies have beer shown that APL mouse models can be established by transgenic,retroviral-mediated and leukemia cell transplantation.These models established by these three methods can be re-transplanted.The establishment of these models lays the foundation for understanding the pathogenesis and efficacy of APL.In order to determine whether the model is successfully established,these methods can be used for blood tests,blood smear and bone marrow smear,immunol-ogy,molecular biology and pathology related to complete the examination.Successful establishment of APL animal model can provide important experimental basis and theoretical basis for the study,development and evaluation of drug efficacy in APL,which will help people to understand human APL further.

Current status of the establishment of acute promyelocytic leukemia in mouse models / 实用肿瘤学杂志

Acute promyelocytic leukemia(APL)is a class of malignant disease of hematopoietic tissue. Animal models are important tools for exploring human-related diseases.Many studies have beer shown that APL mouse models can be established by transgenic,retroviral-mediated and leukemia cell transplantation.These models established by these three methods can be re-transplanted.The establishment of these models lays the foundation for understanding the pathogenesis and efficacy of APL.In order to determine whether the model is successfully established,these methods can be used for blood tests,blood smear and bone marrow smear,immunol-ogy,molecular biology and pathology related to complete the examination.Successful establishment of APL animal model can provide important experimental basis and theoretical basis for the study,development and evaluation of drug efficacy in APL,which will help people to understand human APL further.