Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P＜0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P＜0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Objective:To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy.Methods:The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed,the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed.Results:Among 180 patients with multiple myeloma,23 cases developed herpes zoster(12.8％).The incidence of herpes zoster was 19.1％in patients with renal dysfunction and 23.5％after autologous hematopoietic stem cell transplantation(ASCT).The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens(21/137,15.3％)than that in those without bortezomib(2/43,4.7％),but there was no statistical difference(P=0.067).Antiviral prophylaxis was associated with fewer zoster infections,8/111(7.2％)developed herpes zoster in patients who received antiviral prophylaxis,and 15/69(21.7％)in those receiving no prophylaxis(P=0.005).65.2％of patients with herpes zoster did not receive antiviral prophylaxis.Multivariate analysis showed that bortezomib treatment,AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster,while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster.Herpes zoster had no effect on OS in patients with multiple myeloma.Conclusion:The risk of herpes zoster in multiple myeloma patients was increased.Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.

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.

Objective:To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed,and they were divided into rituximab± DHAX(R±DHAX)regimen group(18 cases)and rituximab±CHOP(R-CHOP)regimen group(18 cases)according to the treatment plan,and clinical features,efficacy and survival of the patients were observed.Results:Compared with R-CHOP group,patients of the R±DHAX group were older,and had worse performance status and higher IPI score,the differences between two groups in age,ECOG score and IPI score were statistically significant(P=0.005,P=0.018,P=0.035),but there were no significant differences be ween two groups in gender,whether there were B symptoms,whether LDH was elevated,whether there was extranodal involvement,cell origin,bone marrow infiltration,and whether rituximab was combined(P=0.738,P=1,P=0.315,P=0.305,P=0.413,P=0.177,P=0.711,P=0.229).The efficacy could be evaluated in 36 cases,including CR 14(38.9％),PR 17(47.2％),PD 5(13.9％),and ORR of 86.1％(31/36).There were no statistically significant differences in CR[(27.8％(5/18)vs 50.0％(9/18);P＞0.05]and PR[44.4％(8/18)vs 50.0％(9/18);P＞0.05]of R±DHAX group and R-CHOP group,there was statistically significant difference in ORR[72.2％(13/18)vs 100.0％(18/18);P=0.045]between two groups.The 1-year OS of R±DHAX group and R-CHOP group was(38.9+11.5％)％and(94.4±7.4％)％,respectively,2-year OS was(16.7±8.8)％and(72.2±10.6)％,respectively,and the differences between two groups were statistically significant(P=0.001,P=0.002).The median survival time in the R±DHAX group was 11 months(95％CI;8.9-13.1),and the median survival time in the R-CHOP group was not reached,and there was a statistically significant difference between the groups(P＜0.001).Conclusion:For elderly DLBCL patients,R± DHAX may not be superior to R-CHOP in OS,and ECOG score,IPI score and age may affect the survival of elderly DLBCL patients.However,R±DHAX regimen is safe,tolerable and has a certain efficacy,which can be used as one of the clinical treatment options for elderly DLBCL.

Objective:To investigate the effect of CD8+CD28-T cells on acute graft-versus-host disease(aGVHD)after haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Methods:The relationship between absolute count of CD8+CD28-T cells and aGVHD in 60 patients with malignant hematological diseases was retrospectively analyzed after haplo-HSCT,and the differences in the incidence rate of chronic graft-versus host disease(cGVHD),infection and prognosis between different CD8+CD28-T absolute cells count groups were compared.Results:aGVHD occurred in 40 of 60 patients after haplo-HSCT,with an incidence rate of 66.67％.The median occurrence time of aGVHD was 32.5(20-100)days.At 30 days after the transplantation,the absolute count of CD8+CD28-T cells of aGVHD group was significantly lower than that of non-aGVHD group(P=0.03).Thus the absolute count of CD8+CD28-T cells at 30 days after transplantation can be used to predict the occurrence of aGVHD to some extent.At 30 days after transplantation,the incidence rate of aGVHD in the low cell count group(CD8+CD28-T cells absolute count＜0.06/μl)was significantly higher than that in the high cell count group(CD8+CD28-T cells absolute count ≥0.06/μl,P=0.011).Multivariate Cox regression analysis further confirmed that the absolute count of CD8+CD28-T cells at 30 days after transplantation was an independent risk factor for aGVHD,and the risk of aGVHD in the low cell count group was 2.222 times higher than that in the high cell count group(P=0.015).The incidence of cGVHD,fungal infection,EBV infection and CMV infection were not significantly different between the two groups with different CD8+CD28-T cells absolute count.The overall survival,non-recurrent mortality and relapse rates were not significantly different between different CD8+CD28-T cells absolute count groups.Conclusion:Patients with delayed CD8+CD28-T cells reconstitution after haplo-HSCT are more likely to develop aGVHD,and the absolute count of CD8+CD28-T cells can be used to predict the incidence of aGVHD to some extent.The absolute count of CD8+CD28-T cells after haplo-HSCT was not associated with cGVHD,fungal infection,EBV infection,and CMV infection,and was also not significantly associated with the prognosis after transplantation.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.