The incidence of knee osteoarthritis(KOA)is in-creasing year by year,seriously affecting patients'health.Mes-enchymal stem cells are multipotent cells with multiple differen-tiation functions.The extracellular vesicles released by these cells can carry various"cargo"to corresponding cells and tis-sues,exerting biological functions.They have shown great clini-cal potential in the treatment of KOA.This study reviews the therapeutic effects and mechanisms of extracellular vesicles se-creted by mesenchymal stem cells from different tissues such as bone marrow,adipose tissue,and synovium in KOA.It is found that miRNA is an important biological component in exerting therapeutic effects.The study also discusses the research pro-gress of engineered extracellular vesicles in KOA,pointing out the current challenges in clinical application,such as standard-ized acquisition of extracellular vesicles and difficulties in targe-ted action,aiming to provide a certain reference for the basic re-search and clinical application of extracellular vesicle therapy for KOA.

Objective To compare the efficacies of acellular dermal matrix(ADM)and pedicle buccal fat pad flap(PBFPF)in repairing buccal soft tissue defect.Methods A total of 84 patients undergoing repair of buccal mucosa defect in our hospital were selected and randomly divided into the ADM group and PBFPF group,with 42 cases in each group.Patients of the ADM group were repaired tby ADM,while patients of the the PBFPF group were repaired by PBFPF.The repair time,oral feeding time,hospital stay were compared between the two groups.The maximum opening degree of patients before surgery,and 1 week,1 month and 6 months after surgery was measured and compared.The effective rate of repair and the occurrence of complications of patients were recorded.The improvement of oral and maxillofa-cial function(including swallowing function,language function and masticatory function)after surgery of patients were observed.Results There was no significant difference in the repair time,oral feeding time,hospital stay,total incidence of complications,postoperative swallowing function or postoperative language function between the two groups(P＞0.05).The maximum opening degree had no significant difference between the ADM group and PBFPF group or in the interaction effect between groups and time points(P＞0.05),but had signifi-cant difference in the comparison of time points(P＜0.05).The effective rate of repair for patients with defect area of＞13～20 cm2 in the PBFPF group was higher than that in the ADM group(P＜0.05).The masticatory function of patients in the PBFPF group was better than that in the ADM group(P＜0.05).Conclusion Both PBFPF and ADM have advantages in the repair of oral mucosal tissue defects,and PBFPF has better repair effect in patients with larger mucosal defect area(＞13～20 cm2).

Heart failure(HF)is the end stage of almost all cardiovascular diseases,including coronary heart disease and structural heart disease.For end-stage HF,medications and cardiac assist devices have limited therapeutic effects,and heart transplantation is associated with donor shortage and immune rejection.Alginate hydrogel has the ability to mechanically support and induce cardiac tissue regeneration and repair.In March 2021,we conducted the world's first transcatheter endocardial alginate-hydrogel implantation in patients with end-stage heart failure,and explored the safety and feasibility of the treatment.Given that patients with heart failure who had undergone cardiac resynchronization therapy defibrillator(CRT-D)were excluded from previous studies,this paper is the first to report a case of transcatheter endocardial alginate-hydrogel implantation in a patient with heart failure who did not respond to CRT-D,with a significant reduction in the number of visits to the doctor and a significant improvement in the quality of life during the post-procedure follow-up,which may expand the indications for the use of this technology.

Objective To evaluate the efficacy of extracorporeal membrane oxygenation(ECMO)in patients with reduced left ventricular ejection fraction(LVEF)undergoing transcatheter aortic valve implantation(TAVR).Methods This was a single-center,retrospective study enrolling a total of 30 patients with reduced LVEF undergoing TAVR from January 2020 to January 2024.Of these,12 patients underwent TAVR with ECMO.Baseline clinical characteristics,preprocedural echocardiographic and computed tomographic(CT)measurements,TAVR procedural details,and follow-up data at 60-day and 6-month were collected.Results Among the 30 patients,there were 20 males with an average age of(67.0±10.4)years,an average STS score of(8.2±1.8)points,and an average LVEF of(21.2±5.3)％.This study included 11 AR patients,all of whom were in the group without ECMO implantation,and the difference between the two groups was statistically significant(P=0.027).During the operation,there were 0 cases of circulatory collapse in the ECMO group,and 5 cases(5/18)of circulatory collapse in the non ECMO group.All 5 patients underwent emergency ECMO placement.There were statistically significant differences(P＜0.05)in the comparison of two groups with circulatory collapse and salvage ECMO implantation.The technical success rate of 30 patients was 76.7％(23/30),and the instrument success rate was 60.0％(18/30).Among them,the technical success rate and instrument success rate of the ECMO group were higher than those of the non ECMO group,but the differences were not statistically significant(both P＞0.05).During a 30 day follow-up,there were 0 all-cause deaths in the ECMO group and 9 all-cause deaths(9/18)in the non ECMO group.Among them,7 cases(7/18)died from cardiovascular causes.The differences in all-cause and cardiovascular cause deaths between the two groups were statistically significant(both P＜0.05).During a 6-month follow-up,one patient with ECMO died due to extensive cerebral infarction.The all-cause mortality rate during the 6-month follow-up was 1/12(8.3％),while the all-cause mortality rate without ECMO was 9/18(5.0％).The difference between the two groups was statistically significant(P=0.024).The incidence of stroke with ECMO was 1/12(8.3％),while without ECMO it was 0.There was no statistically significant difference between the two groups(P=0.978).Conclusions In patients with reduced LVEF undergoing TAVR,periprocedural ECMO support does seem to improve patient outcome.

Objective:To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway.Methods:The expression levels of LMP1 protein,CD38 and the phosphorylation levels of p70S6K in EBV+and EBV-DLBCL cell lines were detected by Western blot.Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi.The expression of LMP1 gene was verified by RT-qPCR.The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot.Results:Compared with EBV-DLBCL cells,the expression of LMP1 was detected on EBV+DLBCL cells(P=0.0008),EBV+DLBCL cells had higher phosphorylation levels of p70S6K(P=0.0072)and expression levels of CD38(P=0.0091).Compared with vector group,the cells of LMP1OE group had higher expression levels of LMP1 and CD38(P=0.0353;P＜0.0001),meanwhile molecular p70S6K was phosphorylated much more(P=0.0065);expression of LMP1 mRNA was verified(P＜0.0001).Compared with si-NC group,expression level of LMP1 protein(P=0.0129)was not detected and phosphorylated p70S6K disappeared of LMP1KO group(P=0.0228);meanwhile,expression of CD38 decreased,although there was no significant difference(P=0.2377).Conclusion:LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.

Objective:To summarize the clinical characteristics,therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma(HL).Methods:A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled,and their clinical data,including sex,age,pathological type,Ann Arbor stage,ECOG score,blood test,β2-microglobulin,lactate dehydrogenase level,albumin level were collected.The clinical characteristics,therapeutic effect and long-term prognosis of the patients were summarized and analyzed.Results:In classical HL,nodular sclerosis HL accounted for the highest proportion of 51.6％,followed by mixed cellularity HL(36.5％),lymphocyte-rich classical HL(3.2％),and lymphocyte depletion HL(0.7％),while nodular lymphocyte predominant HL accounted for 4.8％.The 3-year overall survival(OS)rate of HL patients was 89.8％,and 5-year OS was 85.0％.The 3-year progression-free survival(PFS)rate was 73.4％,and 5-year PFS was 63.1％.Multivariate regression analysis indicated that IPI score was an independent negative factor,while hemoglobin(Hb)level was an independent positive factor for OS in HL patients.When the mediastinal mass size was 9.2 cm,it was most significant to judge the survival status of HL patients.5-year OS and 5-year PFS were 97.4％and 76.0％in early-stage HL patients without large mass,respectively,while in patients with advanced-stage HL was 83.4％and 55.9％(both P＜0.05).After 2-4 courses of treatment,the overall response rate(ORR)of patients who received chemotherapy combined with radiotherapy was 95.0％,while that was 89.6％in those with chemotherapy alone.Conclusions:The overall prognosis of patients with HL is satisfactory,especially those in early-stage without large mass.IPI score and Hb level are independent risk factors for the prognosis of HL patients.A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

AIM To observe the effects of Yiqi Fumai Lyophilized Injection on a mouse model of chronic heart failure after acute myocardial infarction and H9C2 cells with injury induced by oxygen and glucose deprivation.METHODS Thirty C57BL/6J mice were randomly divided into the sham-operation group,the model group,and the Yiqi Fumai group,among which the chronic heart failure model was made by ligation of anterior descending coronary artery and given 4 weeks corresponding drug administration.The H9C2 cells were divided into the normal group,the OGD model group,the low-dose,medium-dose and high-dose Yiqi Fumai groups,and the JQ1(BRD4 inhibitor)group.The following detections were conducted:heart ultrasound among the mice;the HE staining of the myocardial tissue for the observation of the morphological changes,spectrophotometry of cellular ATP level,JC-1 method for the determination of the mitochondrial membrane potential,RT-qPCR for the assessment of the mRNA expressions of ANP、BNP and BRD4,TUNEL method for the determination of level of cardiomyocytes apoptosis,and Western blot for the determination of the protein expressions of BRD4,AMPK and p-AMPK in both the mice and H9C2 cells.RESULTS Compared with the sham-operation group,the model group displayed decreased heart function(P＜0.01);obviously more hypertrophic or morphologically irregular cardiomyocytes;up-regulated mRNA expressions of ANP,BNP and BRD4(P＜0.01);increased cardiomyocyte apoptosis rate(P＜0.01);decreased p-AMPK/AMPK protein expression(P＜0.01);and increased BRD4 protein expression(P＜0.01).Compared with the model group,the Yiqi Fumai groups shared improvement in terms of all the aforementioned indices levels(P＜0.05,P＜0.01).Compared with the H9C2 cells of the normal group,those of the OGD model group displayed up-regulated mRNA expressions of ANP,BNP and BRD4(P＜0.01);increased apoptosis rate(P＜0.01);decreased p-AMPK/AMPK protein expression(P＜0.01);increased BRD4 protein expression(P＜0.01),and decreased mitochondrial membrane potential and ATP levels(P＜0.01).Compared with the OGD model group,the groups treated with either Yiqi Fumai or JQ1 demonstrated improvement in terms of the aforementioned indices levels(P＜0.05,P＜0.01).CONCLUSION Yiqi Fumai Lyophilized Injection exhibits its efficacy in improving cardiac function,myocardial energy metabolism,intracellular mitochondria dysfunction and biogenesis in a mouse model of chronic heart failure after myocardial infarction.The effects may be mediated by regulation of BRD4/AMPK signaling pathway.