OBJECTIVE To explore the clinical efficacy and safety of Ruyi jinhuang powder for external application combined with immune checkpoint inhibitors （ICIs） in the treatment of patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder. METHODS All patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder were admitted to our hospital from January 2018 to June 2022 and assigned into observation group and control group according to random number table method. Patients in the control group （n＝56） were treated with ICIs （Navulizumab injection/Sintilimab injection/Camrelizumab for injection） 200 mg， ivgtt， 21 days as a treatment cycle. Patients in the observation group （n＝56） were additionally treated with Ruyi jinhuang powder for external application， once a day， on the basis of control group. The therapeutic effects of 2 groups were compared after a treatment cycle. The levels of interleukin-6 （IL- 6）， matrix metalloproteinase-9 （MMP-9）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， carbohydrate antigen 199 （CA199）， alpha-fetoprotein （AFP） and vascular endothelial growth factor （VEGF） in serum were compared between 2 groups before and after treatment. Karnofsky functional status （KPS） score， digital rating scale （NRS） score， total symptom score of traditional Chinese medicine， and the occurrence of adverse reactions were recorded for both groups of patients. RESULTS After treatment， the levels of IL-6， MMP-9， COX-2， PGE2， CA199， AFP， VEGF， NRS score and total symptom score of traditional Chinese medicine in observation group were significantly lower than control group （P＜0.05）， KPS score was significantly higher than the control group （P＜0.05）. The zypp-04） total effective rate and remission rate of the observation group were 64.29% and 80.36%， those of control group were 60.71% and 73.21%. There was no statistical significance between two groups （P＞0.05）. The adverse drug reactions of both groups were mainly nausea and vomiting， liver function injury， fever hlshli@yeah.net and so on； the incidence of adverse reaction in observation group was significantly lower than that of control group （P＜0.05）. CONCLUSIONS In patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder， the combination of Ruyi jinhuang powder for external application and ICIs can help inhibit the secretion of pain mediators， regulate vascular endothelial function， reduce the inflammatory response， promote the recovery of cardiopulmonary function， improve clinical efficacy and has good safety.

Objective:To investigate the changes of various cytokines and coagulation function in B cell acute lymphoblastic leukemia(ALL) patients with different CRS scores during CD19-CAR-T cell immunotherapy.Methods:87 patients with B-ALL hospitalized in the First Affiliated Hospital of Soochow University and 30 normal controls were enrolled into this study from July 2018 to October 2020. The age of the patients was 32(20, 56) years old and 36(41.4%) were female. All these coagulation indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, fibrinogen (Fg) were analyzed by automatic blood coagulation in B-ALL patients before and after treated with CAR-T cell. The ratio of CD19-CAR-T cells and the expression of IL-6, IL-10, IFN-γ, TFN-α, IL-2, IL-4, and IL-17A were analyzed using flow cytometry. The patients′ clinical parameters were detected, and the CRS classification of severity was made according to the standard of consensus.Results:Patients with CRS>3 had prolonged PT and APTT, increased D-dimer, and decreased fibrinogen ( P<0.05). The levels of cytokines of IFN-γ, IL-6, and IL-10 were significantly higher in patients with CRS>3 than that in controls ( P<0.05).The D-dimer level is positively correlated with IL-10. Conclusion:Patients with severe CRS grading have significant coagulation dysfunction in CD19-CAR-T cell immunotherapy. Cytokines IFN-γ, IL-6, and IL-10 may affect coagulation function and CRS grading during CD19-CAR-T cell immunotherapy.

AIM: To construct and identify the mammary gland cell-specific conditional knockout of SENP7 by the Cre-loxP system. METHODS: The homozygous SENP7

AIM: To investigate the mechanism of the involvement of SUMO-ylated Androgen receptor (AR) in tamoxifen resistance and the role of SUMO inhibitor ginkgolic acid in resistance. METHODS: Real-Time PCR was used to detect AR mRNA levels in parental cells MCF-7W and drug-resistant cells MCF-7R, AR protein levels and SUMO levels in MCF-7W and MCF-7R cells was performed by western blot, and CB/IP was applied to detect AR interacts with SUMOE3 ligase PIAS1 and HSP27 in MCF-7R cell chromatin, the transcriptional activity of SUMO AR was also evaluated by the fluorescent reporter gene experiment, the CCK-8 method and the trypan blue exclusion method were used to detect cell viability and cell viability respectively. RESULTS: The mRNA and protein expression levels of AR in MCF-7R cells were significantly higher than those in MCF-7W cells (P<0.05), and there was highly SUMOylated AR in MCF-7R cells. Further research found that there had an obvious interaction between AR and SUMO E3 ligase PIAS1 and HSP27, that was, the SUMOylated AR was modified by E3 ligase. Moreover, androgen R1881 could enhance the transcriptional activity of the SUMOylated AR in a concentration-dependent manner. Compared with ginkgo acid alone, 10 μmol/L of ginkgolic acid combined with 10 μmol/L of enzalutamide treated MCF-7R cells for 3 days, the cell number was significantly reduced, and the number of cell death increased significantly (P<0.05). CONCLUSION: The resistance mechanism of tamoxifen may be due to the enhanced AR transcription and activity increased by the hyperactive SUMOylated AR, SUMO inhibitor ginkgolic acid combined with AR antagonist enzalutamide can be a new strategy for the treatment of tamoxifen resistance.

OBJECTIVE: To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS: Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS: A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).

OBJECTIVE: To investigate the down-regulation effect of let-7b-5p on the expression of FTO in acute myeloid leukemia cell line THP-1 and inhibitory effect on THP-1 proliferation via m METHODS: The acute myeloid leukemia cell line THP-1 and the normal human peripheral blood mononuclear cells (PBMNC) were selected as subjects. The expression of let-7b-5p and FTO mRNA in those cells was detected by qPCR, further the expression of FTO protein in those cells was detected by Western blot. And, the luciferase reporter gene assay was used to verify the targeting effect of let-7b-5p on FTO. Finally, THP-1 cells were transfected respectively with let-7b-5p mimic, and PBMNC with let-7b-5p inhibitor, there after the C-MYC mRNA m RESULTS: Compared with PBMNC, the expression of let-7b-5p in THP-1 significantly decreased, while the expression of FTO was significantly increased (P<0.05). After transfection with let-7b-5p mimic combined with FTO 3'-UTR, the luciferase activity of transfected THP-1 cells significantly decreased, but the luciferase activity significantly increased after transfection with mutant 3'-UTR, which was significantly different from the negative control group(blank vector) (P<0.05). Let-7b-5p inhibitor down-regulated c-MYC mRNA m CONCLUSION Human acute myeloid leukemia cell line THP-1 low expresses the let-7b-5p, which regulates c-MYC expression through let-7b-5p-/FTO-/m
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Leukemia ; Leukocytes, Mononuclear ; MicroRNAs/genetics* ; Signal Transduction ; THP-1 Cells

Objective To explore the influencing factors of the onset of autism spectrum disorder in male children.Methods Totally 151 male children with autism spectrum disorder were selected as case group and 119 healthy male children matched with the age of the case group in the same administrative region were taken as the control group.All children were assessed with the questionnaire for children's autism etiology and risk factors.Results (1) The differences in children having anorexia and partial eclipse (x2 =50.763,P＜0.01),father's age during pregnancy (x2 =11.441,P=0.043),place of pregnancy (x2 =50.763,P＜0.01),hypertension of pregnancy (x2 =5.693,P=0.026),intrauterine hypoxia (x2 =9.332,P=0.002),umbilical cord around the neck(x2 =18.483,P＜0.01),parents smoking and drinking history during pregnancy (x2 =13.660,P=0.008),parental smoking (x2 =12.901,P=0.005) and alcohol consumption (x2 =8.386,P=0.039) during pregnancy,birth height of child (x2 =8.870,P=0.031),amniotic fluid pollution (x2 =4.561,P=0.043),participation time of artificial feeding,major caregivers,delayed development indicators in infants and young children and whether or not the harmonious parent-child relationship were statistically significant(P＜0.05).(2) Children with anorexia and partial diet (OR =12.284,95％ CI =2.768-54.507),living in rural areas during pregnancy (OR =17.251,95％ CI =1.899-1 56.745),parents' history of smoking and drinking (OR =6.191,95％ CI =1.678-22.838),and intrauterine hypoxia during pregnancy (OR=38.859,95％CI=2.944-512.930) may be risk factors for male autism spectrum disorder.Conclusion To correct children's anorexia bias,improve the living environment in pregnancy,reduce pregnancy complications and avoid exposure to tobacco and alcohol pollution during maternal pregnancy can be an effective entry point for the prevention and control of autism spectrum disorders in male children.

Objective: To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph⁺ ALL) treated by hematopoietic stem cell transplantation (HSCT). Methods: Clinical features and prognoses of 63 newly diagnosed Ph⁺ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed. Results: Of 63 Ph⁺ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ²=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ²=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ²=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ²=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS. Conclusions First-line administration of generic dasatinib could improve EFS for Ph⁺ALL patients treated by HSCT when compered with imatinib.

Objective To investigate the effect of recipient's pre-transplant triglyceride (TG) abnormalities on early graft function (EGF) after kidney transplantation.Methods According to the inclusion and exclusion criteria,154 identified living-kidney transplant recipients in the 309 Hospital of Chinese PLA from Jan.2011 to Dec.2014 were enrolled in present study,including 124 males and 30 females,and aged of 31.9 ± 8.4 years.The cohort was divided into two groups:TG normal group (0.40＜TG≤1.70mmol/L,n=107) and TG abnormalities group (TG＞l.70mmol/L or require lipid lowering therapy,n=47).The incidences of poor early graft renal function (PEGF),slow graft function (SGF) and delayed graft function (DGF) were compared between the two groups,and then the serum creatinine (Scr) levels were compared among the patients showing immediate graft function (IGF) at 3rd,7th and 30th day after transplantation.The ROC curve was drawn up taking TG as diagnosis index to explore the optimal cut-offvalue for predicting PEGF,SGF and DGF after transplantation.Results Compared with the TG normal group,the TG abnormalities group showed significantly higher incidence of PEGF and DGF (P＜0.05).Among the IGF patients,the TG abnormalities group showed higher Scr level at the 7th and 30th day after transplantation (P＜0.05).The area under ROC curve (AUC) reflected TG levels for PEGF,SGF and DGF were 0.774,0.704 and 0.818,respectively (P＜0.05).The optimal cut-offvalues were all 1.37mmol/L.Conclusions Recipients with abnormal pre-transplant TG level may have worse EGF after renal transplantation.The risk of developing PEGF,S GF and D GF tends to emerge when pre-transplant TG level is higher than 1.37mmol/L.

OBJECTIVETo investigate the changes of thrombospondin 1(TSP1) level and von Willebrand factor cleaving protease(ADAMTS13) activity in the patients with hematologic malignancies before and after treatment and to evaluate their clinical significance.

METHODSEighty-two patients with hematologic malignancies were enrolled in this study, among them 20 patients were with acute leukemia, 48 patients were with lymphoma and 14 patients were with multiple myeloma. The plasma samples of 82 patients with hematologic malignancies and 45 healthy controls were collected. The activities of ADAMTS13 were evaluated by residue collagen binding assay(R-CBA), the levels of TSP1 and vWF antigen were measured by enzyme-linked immunosorbent assay(ELISA).

RESULTSThe activity of plasma ADAMTS13 in patients with hematologic malignancies was lower than that of normal controls(P<0.05). The levels of vWF antigen and TSP1 in the patients with hematologic malignancies were higher than those in normal controls(P<0.05). After standard induction chemotherapy, the ADAMTS13 activity of the patients with hematologic malignancies at the complete remission was higher than that before therapy(P<0.05); the vWF antigen level was significantly lower than that in the patients with hematologic malignancies before therapy(P<0.05), but still higher than that in controls(P<0.05). There were 25 infection patients in 82 cases of hematologic malignancies, and the ADAMTS13 activity in the patients with newly diagnosed hematologic malignancies complicated with infection before therapy was obviously lower than that in the patients with hematologic malignancies without infection(P<0.05), the levels of vWF antigen and TSP1 were significantly lower than that in patients without infection (P<0.05). In the process of treatment, 8 patients have been speculated to suffer from thrombus, and the ADAMTS13 activity in the patients with thrombus was obviously lower than that in the patients without thrombus(P<0.05).

CONCLUSIONLow ADAMTS13 activity and high TSP1 level may participate in the progress of hematologic malignancies, the infection and thrombotic events may lead to further reduction of the ADAMTS13 activity. Assaying the level of ADAMTS13 activity in the patients with malignant tumor may be helpful to prevent the infection and thrombosis in the patients with hematologic malignancies.