1. Study on mechanism of Hippo/YAP pathway inhibition by salvianolic acid B in HuH-7 cells
Xin-Mei YU ; Li-Li LI ; Yan YANG ; Ao ZHANG ; Jie DENG
Chinese Pharmacological Bulletin 2024;40(1):106-113
Aim To investigate whether salvianolic acid B ( Sal B) has inhibitory effect on hepatoma HuH- 7 cells and explore whether it works via Hippo/YAP signaling pathway. Methods HuH-7 cells were induced by TGF-β1 (9 pmol · L
2.Research progress on the mechanism of circular RNA involved in platinum resistance in ovarian cancer
Bin-Xin LIU ; Ya-Dan FAN ; Chun-Yan LYU ; Zi-Man MEI ; Qing-Chun DENG
Journal of Regional Anatomy and Operative Surgery 2024;33(2):179-182
Ovarian cancer has become the most lethal gynecological tumor due to the difficulty in early diagnosis,the late stage when diagnosed and the high recurrence rate.Resistance to platinum-based anti-tumor chemotherapy drugs is an important reason for the poor prognosis of ovarian cancer.circular RNA(circRNA)is more stable than mRNA in cells due to its special structure,and it is involved in the regulation of the occurrence,development and chemotherapy resistance of a variety of tumors.circRNA can be used as a competing endogenous RNA(ceRNA)of miRNA to bind to proteins,and regulates the phenotypic polarization of macrophages,it can also be used as an exosomal circRNA to regulate the sensitivity of platinum resistance in ovarian cancer.circRNA is expected to be a new marker of platinum resistance and a new target for the treatment of platinum resistance.In order to further explore the relationship between circRNA and platinum resistance in ovarian cancer,this article summarizes the recent literature related to circRNA and platinum resistance in ovarian cancer.
3.Clinical trial of olaparib maintenance therapy combined with GP chemotherapy regimen and thermal therapy in the treatment of patients with advanced ovarian cancer
Yan-Mei DENG ; Ling-Ling LIU ; Yong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(12):1709-1713
Objective To observe the clinical efficacy of olaparib maintenance therapy combined with gemcitabine+cisplatin(GP)chemotherapy regimen and thermal therapy in the treatment of advanced ovarian cancer and analyze the prognosis.Methods Patients with advanced ovarian cancer were divided into control group and treatment group according to the random number table method.The control group was treated with GP chemotherapy regimen and thermal therapy,and given intravenous infusion of 1 250 mg·in-2 of gemcitabine on the 1st day and 8th day and 40 mg·m-2of cisplatin on the 1st day and 3rd day,and given 60 min of local deep thermal therapy(qod)with temperature at 42 ℃ on the 1st day of chemotherapy,and the patients were treated for 4 courses with 21 days as a course.The treatment group was additionally given olaparib maintenance therapy on the basis of the control group,and given continuously oral administration of olaparib 200 mg(bid)during chemotherapy,and the patients were treated for 4 courses with 21 days as a course of treatment.The clinical efficacy,peritoneal carcinomatosis index(PCI),peripheral blood lymphocyte subsets,serum tumor markers[carcinoembryonic antigen(CEA),carbohydrate antigen 125(CA125),carbohydrate antigen 72-4(CA72-4),human epididymal protein 4(HE4)],progressive-free survival time(PFS),overall survival(OS)and occurrence of adverse drug reactions were compared between both groups of patients.Results There were 37 cases in treatment group and 36 cases in control group.After treatment,the total effective rates in treatment group and control group were 54.05%(20 cases/37 cases)and 30.56%(11 cases/36 cases);the PCI scores were(10.79±2.56)and(12.54±3.17)scores,with significant difference(all P<0.05).After treatment,the proportions of peripheral blood CD4+cell in treatment group and control group were(33.63±3.17)%and(30.06±3.24)%;the ratios of CD4+/CD8+were 0.78±0.16 and 0.67±0.13;serum CEA levels were(33.17±6.82)and(39.35±7.51)ng·mL-1;CA125 levels were(47.64±8.56)and(55.84±10.02)U·mL-1;CA72-4 levels were(6.35±1.27)and(8.59±1.64)U·mL-1;HE4 levels were(124.62±20.14)and(141.62±21.43)pmol·mL-1,all with significant difference(all P<0.05).PFS values in treatment group and control group were 9.00 months(95%CI:7.79-10.21)and 8.00 months(95%CI:7.20-8.80),and OS values were 13.00 months(95%CI:12.35-13.65)and 11.00 months(95%CI:10.46-11.54),all with significant difference(all P<0.05).The adverse drug reactions in treatment group mainly included nausea and vomiting,hypertension and constipation,the adverse drug reactions in control group mainly included nausea and vomiting and stomatitis.The total incidence rates of adverse drug reactions in treatment group and control group were 32.43%and 22.22%,with no significant difference(P>0.05).Conclusion Olaparib maintenance therapy combined with GP chemotherapy regimen and thermal therapy has a significant effect in the treatment of patients with advanced ovarian cancer,and it can prolong the survival time of patients without increasing adverse drug reactions.
4.Design of automatic urine volume detection and collection device
Yan CHEN ; De-Zhao ZHAI ; Xiao-Quan ZHANG ; Fu-Long LIU ; Xiao-Tao ZHANG ; Yong-Mei ZHANG ; Wei CEHN ; Fang ZHANG ; Guo-Hui WU ; Jun DENG ; Dan LI
Chinese Medical Equipment Journal 2024;45(4):66-69
Objective To develop an automatic urine volume detection and collection device to solve the problems of routine urine test.Methods An automatic urine volume detection and collection device was developed with the components of a main control system,a detection system,a prompting system and a grasping and moving system.The main control system consisted of two STM32 microcontrollers and a reset switch;the detection system was made up of a weighing module,an infrared module and indicator lights,which had its urine volume automatic detection algorithm developed based on the Keil5 platform;the prompting system realized voice broadcasting through the voice module fixed on the back panel of the box;the grasping and moving system was composed of a rail drive motor(86CM stepper motor),a photoelectric switch and a motorized gripper.Results The device developed tested urine samples with an accuracy of 99.44%,and could collect qualified samples automatically and quickly.Conclusion The device developed detects urine volume and collects samples automatically,and enhances the accuracy and efficiency of urine examination.[Chinese Medical Equipment Journal,2024,45(4):66-69]
5.Porcine SIRT5 promotes replication of foot and mouth disease virus type O in PK-15 cells
Guo-Hui CHEN ; Xi-Juan SHI ; Xin-Tian BIE ; Xing YANG ; Si-Yue ZHAO ; Da-Jun ZHANG ; Deng-Shuai ZHAO ; Wen-Qian YAN ; Ling-Ling CHEN ; Mei-Yu ZHAO ; Lu HE ; Hai-Xue ZHENG ; Xia LIU ; Ke-Shan ZHANG
Chinese Journal of Zoonoses 2024;40(5):421-429
The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.
6.The Polymorphism Analysis of HLA Class Ⅱ Alleles Based on Next-Generation Sequencing and Prevention Strategy for Allele Dropout
Su-Qing GAO ; Zhan-Rou QUAN ; Yan-Ping ZHONG ; Hao CHEN ; Liu-Mei HE ; Hong-Yan ZOU ; Zhi-Hui DENG
Journal of Experimental Hematology 2024;32(2):603-609
Objective:To investigate the accuracy of next-generation sequencing technology(NGS)in detecting the polymorphisms of HLA-DRB1,DQB1,DQA1,DRB3,DRB4,DRB5,DPA1 and DPB1 alleles in randomly-selected unrelated healthy individuals from Shenzhen Han population,investigate the potential reason for HLA-DRB1 allele dropout in routine NGS,and establish an internal quality control system.Methods:NGS-based HLA class Ⅱ genotyping was performed on 1 012 samples using the MiSeqDxTM platform.The suspected missed alleles indicated by the quality control software and HLA-DRB1 homozygotes were confirmed by PCR-SSOP or PCR-SBT methods.Results:A total of 139 alleles were detected,including HLA-DRB1(45),DRB3(7),DRB4(5),DRB5(7),DQA1(17),DQB1(21),DPA1(10)and DPB1(27).HLA-DRB 1*09:01(17.09%),15:01(10.72%);DRB3*02:02(25.99%),03:01(10.18%);DRB4*01:03(36.46%);DRB5*01:01(15.42%);DQA1*01:02(20.01%),03:02(17.19%);DQB1*03:01(19.47%),03:03(17.98%),05:02(11.66%),06:01(10.67%);DPA1*02:02(54.45%),01:03(31.18%)and DPB1*05:01(39.13%),02:01(16.90%)alleles were the most common alleles in Shenzhen Han population(frequencies>10%).There was no statistical difference between the gene frequencies of HLA-DRB1 and DQB1 loci in our study.The HLA Common and Well-Documented Alleles in China(CWD2.4)(x2=12.68,P>0.05).94 cases of HLA-DRB1 homozygous samples detected by NGS were retested by PCR-SSOP or SBT method,and one case of allele dropout at HLA-DRB1 locus was found.SBT method confirmed that the allele of DRB1*04:03 was missed.The laboratory internal quality control system was established.Two cases of new alleles were detected and named by WHO Nomenclature Committee for Factors of the HLA System.Conclusion:The HLA genotyping results based on NGS showed a significantly lower ambiguity rate.The HLA class Ⅱ alleles exhibit genetic polymorphism in the Han population of unrelated healthy individuals in Shenzhen.The independent method based on NGS in clinical histocompatibility testing has limitations and requires internal quality control strategies to avoid allele-dropout events.
7.Comparison of the Prognostic Value of C-Reactive Protein to Albu-min Ratio and Glasgow Prognostic Score in Patients with Diffuse Large B-Cell Lymphoma
Hong-Yan WANG ; Hong DENG ; Mei-Jiao HUANG ; Liang ZHANG ; Tai-Ran CHEN ; Yu LIU ; Xing-Li ZOU
Journal of Experimental Hematology 2024;32(3):742-749
Objective:To compare the prognostic value of two predictive models based on C-reactive protein(CRP)and albumin(ALB),namely the CRP to ALB ratio(CAR)and the Glasgow prognostic score(GPS),in newly diagnosed patients with diffuse large B-cell lymphoma(DLBCL).Methods:The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed.A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical,laboratory data and follow-up information were included.The receiver operating characteristic(ROC)curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival.Furthermore,the association between CAR and baseline clinical,laboratory characteristics of patients was evaluated,and progression-free survival(PFS)and overall survival(OS)were compared between different CAR and GPS subgroups.Finally,the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes.Results:ROC curve showed that the area under the curve(AUC)of CAR predicting PFS and OS in DLBCL patients was 0.687(P=0.002)and 0.695(P=0.005),respectively,with the optimal cut-off value of 0.11 for both predicting PFS and OS.Compared with the lower CAR(<0.11)group,the higher CAR(≥0.11)group had more clinical risk factors,including age>60 years(P=0.025),ECOG score ≥2(P=0.004),Lugano stage Ⅲ-Ⅳ(P<0.001),non-germinal center B-cell-like(non-GCB)subtype(P=0.035),elevated lactate dehydrogenase(LDH)(P<0.001),extranodal involved site>1(P=0.004)and IPI score>2(P<0.001).The interim response evaluation of patients showed that the overall response rate(ORR)and complete response rate(CRR)in the lower CAR group were both significantly better than those in the higher CAR group(ORR:96.9%vs 80.0%,P=0.035;CRR:63.6%vs 32.5%,P=0.008).With a median follow-up of 24 months,patients with lower CAR had significantly longer median PFS and OS than those with higher CAR(median PFS:not reached vs 67 months,P=0.0026;median OS:not reached vs 67 months,P=0.002),while there was no statistical difference in PFS(P=0.11)and OS(P=0.11)in patients with GPS of 0,1,and 2.Multivariate Cox regression analysis indicated that only sex(male)and IPI score>2 were independent risk factors for both PFS and OS.Conclusion:CAR is significantly correlated with disease progression and survival in DLBCL patients;And compared with GPS,CAR has more advantages in predicting disease outcomes in DLBCL patients.
8.Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35,TGF-β and IL-10 in Hemophilia A Patients with FⅧ Inhibitor
Hong-Xia HE ; Yan-Yan XIE ; Qing-Yun SUN ; Lin-Hong WANG ; Yi-Wen ZHU ; JIE LI ; Xin WANG ; Zhao-Ling DENG ; Mei-Rong YANG ; Zhen-Yu YAN
Journal of Experimental Hematology 2024;32(4):1197-1200
Objective:To explore the levels of regulatory T cells(Tregs)and cytokines IL-35,TGF-β and IL-10 in peripheral blood of hemophilia A(HA)patients with F Ⅷ inhibitor and their clinical significance.Methods:43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected,including 6 cases with F Ⅷ inhibitor and 37 cases without FⅧ inhibitor.In addition,20 healthy males who underwent physical examinations were selected as healthy controls.Flow cytometry was used to detect the levels of CD4+CD25+CD127-Tregs in peripheral blood of the HA patients and healthy controls,and ELISA assay was used to detect the expression levels of IL-35,TGF-β and IL-10 in serum,and their differences between different groups were compared.Results:Compared with the healthy control group,the level of Tregs in HA patients was decreased,and the level of Tregs in the FⅧ inhibitor positive group was the lowest,the difference was statistically significant(P<0.05).There was no significant difference in the expression level of Tregs in HA patients of different severity levels.The serum IL-35,TGF-β,and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group,and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group(all P<0.05).Conclusion:The decrease of Tregs,IL-35,TGF-β,and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.
9.Efficacy and Safety of Flumatinib and Imatinib as First-line Treatments for Newly-diagnosed Chronic Myeloid Leukemia in Chronic Phase:A Real-world Study
Liang ZHANG ; Hong DENG ; Yu LIU ; Tai-Ran CHEN ; Mei-Jiao HUANG ; Hong-Yan WANG ; Xing-Li ZOU
Journal of Experimental Hematology 2024;32(6):1676-1681
Objective:To compare the efficacy and safety of flumatinib (FM)and imatinib (IM)as first-line treatment in newly-diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP ) in real world. Methods:A total of 84 newly-diagnosed CP-CML patients in our center from December 2019 to December 2022 were retrospectively analyzed.Among them,32 cases received FM as first-line treatment,and 52 cases received IM. Molecular response (MR),disease progression,survival and incidence of adverse events (AEs)were compared between the two groups.Results:At 3 months of treatment,the incidences of early molecular response (EMR ),MR2.0 and MR3.0 were 96.7%,70.0% and 20.0% in FM group,respectively,which were significantly higher than 77.1%,29. 2% and 0 in IM group (all P<0.05 ).At 6,9 and 12 months of treatment,the incidences of major molecular response (MMR)in FM group were 68.2%,85.7% and 90.0%,respectively,which were significantly higher than 22.9%,34.0% and 51.1% in IM group (all P<0.01).The median time to achieve MMR in FM group was 6(6-9)months,which was significantly shorter than 18(12-22)months in IM group (P<0.001 ).The 3-year progression-free survival rate and 3-year event-free survival rate in FM group were 100% and 68.8%,respectively,while in IM group were 98.1% and 55.8%.There were no significant differences between the two groups (P>0.05). The incidence of grade 3-4 hematologic AEs in FM group was 21 .9%,which was slightly lower than 25.0% in IM group,but the difference was not significant (P>0.05 ).Conclusion:In real clinical practice,FM as first-line treatment achieves MMR earlier than IM,and exhibits good safety profile in newly-diagnosed CML-CP patients,which potentially leads to improved long-term survival and treatment-free remission.
10.The protective effect of licorice on cisplatin-induced liver injury in rats based on untargeted metabolomics study
Ting-Mei YIN ; Bi-Qian YANG ; Guang-Miao GAO ; Xiao-Yan FU ; Xiao-Long LIAN ; Ling-Ling YANG ; Jie LI ; Yi DENG
Chinese Pharmacological Bulletin 2024;40(12):2246-2255
Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and lico-rice administration groups(450,900 and 1 800 mg·kg-1).After 5 days of prophylactic administration,8 mg·kg-1 of cisplatin was injected intraperitoneally in-to the model,positive control,and licorice administra-tion groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to ana-lyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Re-sults PLS-DA score plots showed significant separa-tion of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were signifi-cantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabo-lism;parathyroid hormone synthesis,secretion,and ac-tion;tyrosine metabolism;biosynthesis of phenylala-nine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Con-clusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced he-patic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of a-mino acid metabolism and other related pathways.

Result Analysis
Print
Save
E-mail