Objective:To compare the inhibitory effect of neferine and isoliensinine on 5α-reductase to provide reference for the development of 5α-reductase inhibitors. Methods: Different reaction tubes and control tubes were prepared, liver was homogenated, and reducing coenzyme II ( NADPH) , testosterone, pending test sample, the positive drug and buffer was respectively added into 96-well plates. The change in the absorbance of NADPH at 340nm in 1h was determined by a microplate reader. Compared the experimen-tal group with the blank control group, the inhibition rate ( I%) of the test drugs against 5α-reductase was calculated. Results:As for the six concentration gradients (2-40 mg·ml-1 ) in the experiments, the best inhibitory concentration of neferine and isoliensinine was 10 mg·ml-1(I% =25.00 ±1.030% and 29.90 ±2.410%, respectively). Compared with the control group, neferine and isoliensi-nine showed significant inhibition against 5α-reductase (P<0. 05). Compared with the positive group at the same concentration (10 mg ·ml-1), the inhibition of neferine and isoliensinine was significantly lower (P<0. 05). The inhibition effect of isoliensinine was rel-atively better than that of neferine (P<0. 05). Conclusion:Neferine and isoliensininein have notable inhibitory effect on 5α-reduc-tase, which show certain application prospect in the treatment of prostatic hyperplasia in clinics.

Objective:To explore the clinical efficacy and risk factors of umbilical cord mesenchymal stem cells (UCMSCs) infusion at an early stage (i.e.gross hematuria) for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The relevant clinical data were retrospectively reviewed for 300 patients undergoing allo-HSCT from January 2016 to July 2021.According to the presence or absence of HC, they were assigned into two groups of HC (n=89) and non-HC (control, n=211). According to whether or not receiving an infusion of UCMSCs, 51 patients of HC degree Ⅱ-Ⅳ were divided into two groups of UCMSC infusion and non-infusion.The risk factors of HC after allo-HSCT were analyzed by χ2 test.Logistic regression was employed for multivariate analysis of P<0.05.Mann-Whitney U test was utilized for statistically analyzing the duration of gross hematuria and urinary tract irritation symptoms and evaluating the clinical efficacy of UCMSCs infusion for HC. Results:Among them, 89 (29.67%) developed HC post-allo-HSCT.Clinical grades were Ⅰ (n=38, 42.70%), Ⅱ (n=36, 40.45%), Ⅲ (n=13, 14.61%) and Ⅳ (n=2, 2.25%). The median occurrence time was 29 (21.5-35.0) days post-allo-HSCT.In univariate analysis, age ≤30 years, haploid transplantation, antithymocyte globulin (ATG), acute graft-versus-host disease (aGVHD), CMV-DNA positive pretreatment significantly boosted the risk of HC ( P<0.05). In multivariate analysis, aGVHD was an independent risk factor for HC ( OR=10.281, 95% CI: 1.606-65.813, P=0.014). Among 89 HC patients, 38 grade Ⅰ patients were complete remission(CR). Among 51 patients of grade Ⅱ-Ⅳ HC, the outcomes were CR (n=48) and non-remission(NR)(n=3). And 24/51 of them received UCMSCs plus conventional treatment.The duration of gross hematuria was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [12(9-17) vs 17(12.0-26.5) day] and the difference was statistically significant ( P=0.045). And the duration of urinary tract irritation symptoms was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [18(11-30) vs 27(18.0-35.5) days] and the difference was statistically significant ( P=0.048). Conclusions:Indicated for post-ALLO-HSCT HC, infusion of UCMSCs may significantly shorten the course of disease.Age ≤30 years, haploid transplantation and preconditioning with positive ATG, aGVHD and CMV-DNA may boost the risks of HC post-allo-HSCT.And aGVHD is an independent risk factor for HC after allo-HSCT.

Objective:To evaluate the safety and efficacy of bortezomib plus highdose melphalan (L-phenylalanine nitrogen mustard) (Bor-HDM) pretreatment regimen for multiple myeloma (MM) with autologous hematopoietic stem cell transplantation (ASCT).Methods:From August 2008 to December 2021, the relevant clinical data were retrospectively reviewed for 58 MM patients undergoing MM transplantation.The conditioning regimens were Bor-HDM (n=36) and HDM (n=22). Non-hematopoietic adverse reactions, hematopoietic reconstruction time, remission rate post-ASCT and minimal negative rate of residual disease (MRD) on flow cytometry within 3 months post-ASCT and survivals were analyzed.Results:In Bor-HDM and HDM groups, median time of neutrophil engraftment was 12(8-30) and 11(8-29) day and median time of platelet reconstitution 16(8-33) and 16(7-32) day respectively.There was no significant inter-group difference ( P=0.890, P=0.638). In Bor-HDM group, the most common non-hematological adverse reactions were nausea (n=21, 58.0%) and diarrhea (n=11, 30.6%). There was no transplant-related death.Complete remission (CR) rate was (25/36, 69.4%) versus (9/22, 40.9%). The inter-group difference was statistically significant ( P=0.032). Median follow-up period was 29.0(2.0-91.0) vs. 20.5(5.0-114.0) month, 3-year progression-free survival(PFS)62.1% vs. 39.7% and 3-year overall survival(OS) 83.8% vs. 62.5%.There were relapse (n=10 vs.10) and death (n=6 vs. 7). Median PFS in Bor-HDM and HDM groups was non-attained and 27 months( P=0.047) and median OS time non-attained and 40 months respectively ( P=0.282). Multivariate analysis revealed that CR was an independent risk factor for PFS ( HR=28.896, 95% CI: 6.130-136.198, P<0.001). Non-CR was an independent risk factor for OS ( HR=3.843, 95% CI: 1.334-11.071, P=0.013; HR=28.595, 95% CI: 6.273-130.355, P<0.001). Conclusions:Bor-HDM pretreatment regimen of ASCT is both safe and efficacious for MM patients.

Objective:To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis.Methods:The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group ( n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group ( n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results:The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group ( P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group ( P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively ( P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively ( P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively ( P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% ( P=0.565), 34.0% and 35.7% ( P=0.859), 43.4% and 33.3% ( P=0.318), and 20.8% and 50.0% ( P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group ( P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively ( P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively ( P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively ( P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation ( HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant ( HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion:allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

Case 1: A 27-year-old female with ALK-positive anaplastic large cell lymphoma/leukemia; Case 2: A 27-year-old male with acute myeloid leukemia; Case 3: A 56-year-old male with myelodysplastic syndrome. These three patients underwent haploid hematopoietic stem cell transplantation and experienced severe oral mucosal inflammation, nausea, vomiting, diarrhea, and other symptoms over a long period, which significantly restricted eating. Neurological and psychiatric symptoms appeared at 50, 38, and 50 days following transplantation, respectively. The diagnosis of Wernicke encephalopathy was made by head magnetic resonance imaging, whereas the condition improved significantly after intravenous infusion of vitamin B 1.

OBJECTIVETo evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer.

METHODSA total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation.

RESULTSOf the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome (LFS) and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% (2/17) of all very young (≤30 years) breast cancer patients in our study.

CONCLUSIONThe TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; DNA Mutational Analysis ; Exons ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome ; ethnology ; genetics ; Male ; Middle Aged ; Pedigree ; Risk Factors ; Tumor Suppressor Protein p53 ; genetics ; Young Adult