BACKGROUND:Autologous bone marrow mesenchymal stem cel transplantation for the treatment of cardiovascular disease has become one of the hotspots, but it is unclear whether the proliferation and directional differentiation of autologous bone marrow mesenchymal stem cels varies changes with age. OBJECTIVE: To explore the proliferation and differentiation changes of rat bone mesenchymal stem cels in different ages. METHODS:The bone marrow mesenchymal stem cels from Sprague-Dawley rats in different age groups were purified and cultured, and then examined by flow cytometry in terms of cel cycle. Meanwhile, neonatal rat cardiomyocytes were co-cultured with bone marrow mesenchymal stem cels. The morphologic changes of bone marrow mesenchymal stem cels and the protein expression of troponin T were detected with immunofluorescence technique. RESULTS AND CONCLUSION: The percentage of bone marrow mesenchymal stem cels in G0/G1 phase was increased with age; while the percentage of expression of troponin T proteins-positive bone marrow mesenchymal stem cels were decreased with age. These findings indicate that the proliferation and differentiation abilities of rat bone marrow mesenchymal stem cels descend with age.

Objective:To investigate the expression levels of PPARα/γin RAW264. 7 cells in the early stages of co-cultivation with Echinococcus granulosus in vitro. Methods:RAW264. 7 cells were co-cultured with E. granulosus and collected at 12,24,36,48, 72 h. The mRNA levels of PPAR-γ,PPAR-α,M1 macrophages-associated cytokines including TNF-α,MCP-1 and IL-1β,and M2 mac-rophages-associated cytokines including Arg-1,TGF-β and Fizz-1 were detected by qRT-PCR. The protein levels of Arg-1 and MR were analyzed by ELISA. Results:The expression levels of PPAR-γ, PPAR-αand the M2 macrophages-associated cytokines including Arg-1,TGF-β,Fizz-1 and MR were significantly increased,especially at 72 h (P<0. 05). M1 macrophages-associated cytokines including TNF-α,MCP-1 and IL-1β were decreased at 72h although increased at first. Conclusion:During the early stages of co-cultivation with Echinococcus granulosus in vitro, the levels of PPAR-γ/α are up-regulated in RAW264. 7 cells, which may drive macrophage polarization and play a role in the immune escape.

BACKGROUND:Nanocomposite hydrogel has great research prospects and application potential in the treatment of osteoarthritis. OBJECTIVE:To review the research progress of nanocomposite hydrogel in osteoarthritis and cartilage repair. METHODS:Databases such as CNKI and PubMed were searched.The English key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,electrostatic interaction,covalent crosslinking",and the Chinese key words were"nanocomposite hydrogel,nanogel,osteoarthritis,cartage,physical encapsulation,physical encapsulation,electrostatic effect,covalent cross-linking".After an initial screening of all articles based on inclusion and exclusion criteria,71 articles with high correlation were retained for review. RESULTS AND CONCLUSION:In cell or animal experiments,nanocomposite hydrogel has the effect of improving osteoarthritis.Nanocomposite hydrogel can promote cartilage repair,improve the internal environment of osteoarthritis,and achieve the therapeutic purpose of osteoarthritis by improving the mechanical environment between joints,carrying targeted drugs,and promoting the chondrogenesis of seed cells.At present,the research of nanocomposite hydrogel in osteoarthritis disease still has a huge space to play.It is expected to open up a new way for the clinical treatment of osteoarthritis by continuing to deepen the research of material preparation and actively carrying out cell and animal experiments.

Objective To explore the genetic mutation spectrum of patients with hypertrophic cardiomyopathy (HCM) and analysis the correlation of genotype phenotype.Methods Collect peripheral venous blood of the 51 cases unrelated HCM patients(35 male and 16 female) in the Beijing Anzhen Hospital of Capital Medical University from 2013 to 2016.Sequence whole exons of human and analysis seven major mutations of HCM including:MYBPC3、MYH7 、TNNT2、TNNI3 、MYL2 、TPM1 and ACTC1.Then compare the results with clinical characteristics.Results 24 patients(47.1％) had 22 kinds of pathogenicity or possibly pathogenicity mutations.The 90.9％ (20/22) of mutations only occurred one time,except MYH7 gene's 663 amino acid and the TNND gene's 157 amino acid which had twice.The mutations of MYBPC3,MYH7,TNNT2,TNNI3,MYL2,TPM1 and ACTC1 accounted for 45.8％ (11/24),20.8％ (5/24),12.5％ (3/24),8.3％ (2/24),8.3％ (2/24),4.2％ (1/24),and 0 respectively.No amphimutation had been found that causes illness or possibly.Through the comparison of clinical features between Genotype positive(24 cases) and negative(27 cases) patients:the incidence of syncope(19.6％ vs.7.8％,P ＜ 0.05),the largest left ventricular wall thickness[(22.8 ± 2.6) mm vs.(20.0 ± 3.4) mm,P ＜ 0.05],family history of HCM(20.8％ vs.0,P ＜0.05),percentage of apical hypertrophy(25.5％ vs.11.8％,P ＜ 0.05);The ratio of left ventricular outflow tract obstruction in MYH7 group was higher than MYBPC3 group (80.0％ vs.18.2％,P ＜ 0.05).Conclusion MYBPC3 is the most common mutation gene in HCM patients.Phenotype is more severe in geuotype positive patients than in genotype negative patients.Relationship between specific gene mutations and clinical phenotype requires further study.

Objective To analyze the echocardiographic findings , associated anomalies and chromosomal characteristics in fetuses with pulmonary atresia with ventricular septal defect ( PA/VSD ) . Methods T he echocardiographic data and follow‐up materials were retrospectively reviewed in 30 256 fetuses from December 2012 to M arch 2018 in the consultation center of fetal heart disease in maternal‐fetal medicine in Anzhen hospital . Of all the fetuses ,59 cases ( 0 .19% ) had PA/VSD . T he echocardiographic findings ,associated anomalies and chromosomal characteristics were retrospectively analyzed in all the 59 fetuses with PA/VSD . Based on w hether the presence of the native pulmonary arteries and the major aortopulmonary collateral arteries ( M APCAs) or not ,the PA‐VSD was classified into type A ,type B ,and type C . Results A large ventricular defect was demonstrated in five‐chamber view with 61 .7% of the mean ratio of the aortic overriding . O ther fetal echocardiographic features of all the 59 fetuses with PA/VSD included :the right aortic arch ( n ＝19 ) ,reversal flow in the ductus arteriosus ( n ＝40 ) ,M APCAs ( n ＝24) . T he classification of the PA/VSD included :type A ( n ＝35) ,type B ( n ＝5) and type C ( n ＝19) . Associated anomalies :persistent left superior vena cava ( n ＝ 13 ) ,anomalous pulmonary vein connection ( n＝5 ) ,complete atrioventricular septal defect ( n ＝ 5 ) ; single umbilical artery ( n ＝ 3 ) ,right atrial isomerism ( n ＝3) . Of all the 30 cases performed chromosomal test ,3 cases had aneuploidy and 7 cases had microdeletion of chromosome . Conclusions The fetal echocardiographic findings of the PA/VSD are characteristic . For prenatal diagnosis of PA/VSD ,the type of PA/VSD should be defined and chromosomal test should be performed ,w hich can be helpful for prenatal consulting .

Objective According investigate the expression of NLRP3 in liver tissues of mice with hepatic ischemia-reperfusion injury (HIRI),to determin the role of NLRP3 in the process of HIRI.Methods Established mice model of partial HIRI.Forty-two male C57BL/6 mice (aged 7 to 8 weeks,weight 20 to 25 g) were respectively divided into 7 groups:no-treatment control group,sham operation group,HIRI groups (2、6、12、24 h) and CY-09 group,6 mice in each group.The injury of the hepatic tissues in the 7 groups was analyzed based on detecting the levels of alanine transaminase (ALT),aspartate transaminase (AST),interleukin-1β (IL-1β),interleukin-18 (IL-18),tumor necrosis factor-α (TNF-α) by ELISA.HE and TUNEL staining were used to observe the pathological changes of liver tissues after HIRI.Western blotting assay were carried out to detect the expressions of NLRP3 and Caspase-1.Measurement data were expressed as mean ± standard deviation (Mean ± SD),and one-way variance analysis was used for comparison between groups.If the variance was not uniform,Dunnett C test was used.Results Serum ALT,AST,IL-1 β,IL-18 and TNF-α of mice detected in HIRI groups were higher than no-treatment control group and sham operation group at all endpoints (P ＜ 0.05).The relative expression of NLRP3 and Caspase-1 in the liver tissues of mice in the HIRI groups were significantly higher than that in the no-treatment control group and sham operation group.Serum ALT,AST,IL-1β,IL-18 and TNF-α of mice detected in CY-09 group were lower than HIRI groups at all endpoints (P ＜ 0.05).Less hepatocellular necrosis were exhibited in CY-09 group,comparing to HIRI groups.The hepatocyte apoptosis rate of mice in the CY-09 group was significantly lower than that in the 12 h HIRI group (P ＜ 0.05).The relative expression of NLRP3 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups.The relative expression of Caspase-1 in the liver tissues of mice in the CY-09 group was significantly lower than that in other groups except the no-treatment control group and sham operation group.Conclusions HIRI cause an increase in NLRP3 expression.The inhibition of NLRP3 can reduce HIRI.

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.