0.05).No significant difference was found in c-myc and p16 protein.CONCLUSION:Human BMSCs cultured in vitro in autologous serum meets the requirement of clinic,with enough number,well growth,without karyotype variation,and BMSCs can differentiate into cardiomyocytes.No tumorigenesis is found in body after implantation.Moreover,no significant difference is seen in telomerase activation and c-myc and p16 gene expression.

Objective To evaluate the long-term efficacy of recombinant human endostatin (rh-Endo) combined with FOLFOX4 as an adjuvant treatment for patients of stage Ⅱ and Ⅲ colorectal cancer.Methods Eligible patients were randomly assigned to receive FOLFOX4 or FOLFOX4 plus rh-Endo regimen in which patients receiving 7.5 mg/m2 Ⅳ on day 1-7,repeated every 2 weeks,to a total of 12 cycles in 6 months.Results A total of 197 eligible patients were accrued in this research with 105 patients in the control group and 92 patients in the experimental arm.Median follow-up period was 42 months.The baseline characteristics distributed were balanced by treatment.Rh-Endo combined with FOLFOX4 regimen resulted in significant improvement on DFS compared to FOLFOX4 regimen for patients with stage Ⅲ colon cancer (HR =0.19,95％ CI0.05-0.75,P =0.0124),and with a 34％ improvement on 3-year DFS and 81％ reduced recurrence.Although rh-Endo combined with FOLFOX4 regimen failed to make significant difference on DFS in the whole (HR =0.75,95％ CI 0.31-1.83,P =0.5589),it was also observed a 17％ improveiment on 3-year DFS.No statistical significant difference on DFS was observed in patients with stage Ⅱ disease.Conclusions Rh-Endo combined with FOLFOX4 regimen significantly improved the disease-free survival for patients with stage Ⅲ colorectal cancer,indicating that patients with stage Ⅲ disease,but not stage Ⅱ disease,can benefit from FOLFOX4 plus rh-Endo regimen in adjuvant treatment.

ObjectiveTo explore the possible mechanism of the Yiqi Jiedu formula （YQ） in treating ischemic stroke （IS） from the perspective of the microbial-gut-brain axis （MGBA）. MethodRats were randomly divided into five groups， with six in each group， including sham surgery group， model group， and low， medium， and high dose YQ groups （1， 5， and 25 mg·kg^-1）. Except for the sham surgery group， all other groups were established with a middle cerebral artery occlusion （MCAO） model using the thread occlusion method. The success of modeling was determined through neurobehavioral scoring， and the protective effect of YQ on IS was evaluated. Then， the changes in gut microbiota before and after MCAO modeling and YQ administration were compared using 16S rDNA sequencing technology， and the possible biological pathways related to the effect of this formula were analyzed. The expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-17A （IL-17A）， and interleukin-10 （IL-10） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression of tight junction proteins ZO-1 and Occludin in brain and intestinal tissue， and hematoxylin-eosin staining （HE） was used to observe pathological changes in the cerebral cortex and colon， so as to validate the possible mechanism of action. ResultYQ significantly improved the neurobehavioral score of MCAO rats （P<0.01） and played a good regulatory role in intestinal microbial disorders caused by enriched pathogens and opportunistic pathogens during the acute phase. Among them， significantly changed microorganisms include Morgentia， Escherichia Shigella， Adlercreutzia， and Androbacter. Bioinformatics analysis found that these bacteria may be related to the regulation of inflammation in the brain. Compared with the blank group， the detection of inflammatory factors in the serum of IS model rats showed an increase in inflammatory factors IL-6 and IL-17A （P<0.01） and a decrease in the content of anti-inflammatory factor IL-10 （P<0.01）. Compared with the model group， the content of inflammatory factors IL-6 and IL-17A in the serum of the treatment group decreased （P<0.05）， and that of anti-inflammatory factor IL-10 increased （P<0.01）. The expression results of barrier proteins ZO-1 and Occludin in brain and intestinal tissue showed that the expression levels of both decreased in IS model rats （P<0.05）， while the expression levels of both increased in the treatment group （P<0.05）. ConclusionAcute cerebral ischemia can lead to an imbalance of intestinal microbiota and damage to the intestinal barrier， and it can increase intestinal permeability. YQ can regulate intestinal microbiota imbalance caused by ischemia， inhibit systemic inflammatory response， and improve the disruption of the gut-blood brain barrier， preventing secondary cascade damage to brain tissue caused by inflammation. The MGBA may be an important mechanism against the IS.