Objective:To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL).Methods:This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children′s Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors.Results:Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×10 9/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively ( χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant ( χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively ( χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%, χ2=4.13, P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%, χ2=4.06, P=0.044;(58.3±18.6)% vs. (85.7±3.2)%, χ2=9.44, P=0.002). Multivariate analysis showed that age ( OR=0.58, 95% CI 0.35-0.97) and white blood cell count at first diagnosis ( OR=0.43, 95% CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 ( OR=0.55,95% CI 0.31-0.97), ETV6-RUNX1 fusion gene ( OR=0.13,95% CI 0.03-0.54), MLL gene rearrangement ( OR=2.55,95% CI 1.18-5.53) and white blood cell count at initial diagnosis ( OR=0.52,95% CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions:The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

In order to obtain polyclonal antibodies against the fibrillar(Fiber)protein of fowl ade-novirus serotype 11(FAdV-11)and investigate its cross-reactivity to different serotypes of FAdV Fiber,the gene encoding the FAdV-11 Fiber protein was cloned into a prokaryotic expression vec-tor pET-32a by homologous recombination technology,then the plasmid was transformed into BL21(DE3)receptor cells,and the purified recombinant protein was used as an immunogen to im-munize rabbits to prepare polyclonal antibody after induced expression,and the cross-reactivity of the polyclonal antibody against different serotypes of FAdV Fiber proteins was identified by West-ern blot and indirect immunofluorescence(IFA).The results showed that the His-FAdV-11-Fiber recombinant protein was mainly expressed as inclusion bodies and was well expressed.Western blot and IFA showed that the prepared polyclonal antibody reacted with the Fiber proteins of FAdV-8a,FAdV-8b,and FAdV-11,but did not with the 2 Fiber of FAdV-4(Fiber 1 and Fiber 2)proteins.In conclusion,in this study,we successfully prepared rabbit polyclonal antibodies against FAdV-11 Fiber and showed that it specifically recognized the Fiber proteins of FAdV-8a,FAdV-8b and FAdV-11,which lays the foundation for further establishment of serological differential diag-nosis of FAdV-11.

Organ transplantation is the most effective treatment for various types of end-stage diseases. To resolve the problem of donor shortage in organ transplantation, the possibility of xenotransplantation has been gradually explored by surgeons. Pig is one of the common donor sources for xenotransplantation. As a bridge between two species, the viruses carried by pig organs may be transmitted between species and cause the risk of zoonosis. Porcine endogenous retrovirus (PERV) is integrated into the genome, which is a category of retrovirus featuring cross-species transmission. In this article, the influencing factors of transmission characteristics of PERV, the transmission risk of PERV and its recombinant virus, and the detection and transmission risk assessment of PERV in xenotransplantation test were reviewed, aiming to provide reference for alleviating severe shortage of donor organs and driving the advancement of xenotransplantation technologies.

Objective:To explore the risk factors affecting the incidence of acute kidney injury(AKI)after liver transplantation(LT).Methods:From November 2019 to November 2022, clinical data were retrospectively reviewed for 105 recipients of classic orthotopic LT.There are 89 males and 16 females with an age range of(50.52±10.35)years.They are assigned into two groups of AKI(66 cases)and non-AKI(39 cases)according to the AKI diagnostic and staging criteria of Global Kidney Disease Prognosis Organization in 2012.General profiles and clinical data(e.g.previous medical history, MELD score, total bilirubin, albumin, serum creatinine level, coagulation function, anhepatic phase and time to surgery)of two groups of recipients are compared.The factors with statistically significant differences are included into multivariate Logistic regression analysis for obtaining independent risk factors for early AKI post-LT.Results:Among them, 66 patients developed AKI within 7 days post-operation with an incidence rate of 62.86%(66/105).The clinical stages of AKI are Ⅰ(46 cases, 69.70%), Ⅱ(10 cases, 15.15%)and Ⅲ(10 cases, 15.15%).Statistically significant inter-group differences exists in age, abdominal surgery history, preoperative serum level of creatinine, operative duration, anhepatic phase and intraoperative plasma transfusion(all P<0.05).Multivariate Logistic regression analysis indicated that abdominal surgery history( OR=5.803, 95% CI: 1.008~33.401, P=0.049), anhepatic phase( OR=1.054, 95% CI: 1.008~1.101, P=0.020)and preoperative serum level of creatinine( OR=0.968, 95% CI: 0.943~0.994, P=0.016)are independent risk factors for early AKI after classical orthotopic LT recipients. Conclusions:Abdominal surgery history, anhepatic phase, and preoperative serum level of creatinine are independent risk factors for early AKI in classic orthotopic LT recipients.

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D₃ of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Objective:To discuss the value of real-time three-dimensional speckle tracking imaging(RT3D-STI) in the evaluation of the left atrial (LA) volume and function in end-stage renal disease (ESRD) patients with different dialysis methods.Methods:Eighty-three ESRD patients who were treated in the Affiliated Hospital of Qingdao University from February to August 2019 were enrolled and divided into non-dialysis group ( n=25), hemodialysis group (HD group, n=31) and peritoneal dialysis group (PD group, n=27). And 30 healthy volunteers were enrolled as control group. Subsequently, the LA volume indexs including LA maximal volume index (LAVImax), LA minimal volume index (LAVImin) and LA presystolic volume index (LAVIpre), the LA function parameters including LA ejection fraction (LAEF), LA passive ejection fraction(LApEF) and LA active ejection fraction (LAaEF) and the LA global strain parameters including global longitudinal strain(GLS), global radial strain(GRS) and global circumferential strain(GCS) were obtained by RT3D-STI. The differences of the parameters among these groups were compared and the correlations between the myocardial strain parameters and dialysis time were analyzed. Results:①The LAVImax, LAVImin and LAVIpre of the non-dialysis group, PD group and HD group were higher than those in the control group, while the LAEF, LApEF, GLS, GRS and GCS were lower than those in the control group(all P<0.05); the LAVImin of the PD group as well as the LAVImin, LAVIpre and LAVImax of HD group were higher than those of non-dialysis group, while the LAEF, LApEF, GLS, GCS of the PD group and the LAEF, LApEF, GLS, GRS, GCS of HD group were lower than those of non-dialysis group (all P<0.05). The LAVImax, LAVImin, LAVIpre of HD group were higher than those of PD group, while the LAEF, LApEF, GLS, GRS and GCS of HD group were lower than those of PD group (all P<0.05). ②The GLS and GCS in PD group were negatively correlated with the dialysis time( r=-0.670, -0.596, all P<0.05), and the GLS, GCS and GRS in HD group were negatively correlated with the dialysis time( r=-0.624, -0.631, -0.551, all P<0.05). Conclusions:RT3D-STI can assess the LA volume and function of ESRD patients with different dialysis methods effectively and can further evaluate the prognosis of patients and guide timely clinical intervention.

Collaboration of c-KIT mutations with AML1-ETO (AE) has been demonstrated to induce t(8; 21) acute myeloid leukemia (AML). Targeted therapies designed to eliminate AE and c-KIT oncoproteins may facilitate effective treatment of t(8; 21) AML. Homoharringtonine (HHT) features activity against tumor cells harboring c-KIT mutations, whereas oridonin can induce t(8; 21) AML cell apoptosis and AE cleavage. Therefore, studies should explore the efficacy of combination therapy with oridonin and HHT in t(8; 21) AML. In this study, we investigated the synergistic effects and mechanism of oridonin combined with HHT in t(8; 21) AML cell line and mouse model. The two drugs synergistically inhibited cell viability and induced significant mitochondrial membrane potential loss and apoptosis. Oridonin and HHT induced significant downregulation of c-KIT and its downstream signaling pathways and promoted AE cleavage. HHT increased intracellular oridonin concentration by modulating the expressions of MRP1 and MDR1, thus enhancing the effects of oridonin. The combination of oridonin and HHT prolonged t(8; 21) leukemia mouse survival. In conclusion, oridonin and HHTexert synergistic effects against t(8; 21) leukemia in vivo and in vitro, thereby indicating that their combination may be an effective therapy for t(8; 21) leukemia.

Objective: To investigate the dynamic changes of antibodies induced by leptospiral vaccines. Methods: Antigens for antibody detection were screened out. ELISA was used to analyze antibody responses induced at different time points after immunizing guinea pigs with different batches of leptospiral vaccines from different manufacturers. To investigate the relationship between antibody responses induced by leptospiral vaccines and their protective effects in animal model, guinea pigs were challenged with Leptospira after immunization. Results: There was no significant antigen-antibody reaction between the LigA protein or Patoc Ⅰ antigen and the serum samples of guinea pigs immunized with leptospiral vaccines. Notable IgG and IgM antibody reactions were observed in all vaccination groups when using bacterial proteins from seven Leptospira reference strains which were used for the preparation of leptospiral vaccines as envelope antigens. Antigen-specific IgG antibodies peaked at 35 d after the last immunization, and the highest peak of antigen-specific IgM antibodies was reached 11 d after the last immunization. Results of the challenge test showed that non-diluted leptospiral vaccines induced significant IgG and IgM antibody reactions in guinea pigs as compared with those diluted three or nine times, showing good protective effects. Conclusions Analysis of the dynamic changes of antibodies induced by leptospiral vaccines revealed that there was correlation between the induced serum antibody responses and the protective effects. This study provided reference for further study on alternative methods for evaluating leptospiral vaccine potency.

Objective : To explore the effects of“radiotherapy assistant”application on lung cancer patients who receive radiotherapy. Methods : A total of 120 patients with lung cancer who received radiotherapy in Hangzhou Cancer Hospital from March to September 2017 were recruited and randomly divided into a control group and an experimental group. The patients in the control group received the routine health education,while the ones in the experimental group performed the“radiotherapy assistant”application focused on interactive guidance. Before and after the intervention,the scores of treatment-nursing compliance and self-management efficacy between the two groups were compared. Results : After the intervention,the compliance scores of radiotherapy treatment,health behaviors,regular review,moderate exercise,medication and diets in the experimental group were 2.77±0.43,2.67±0.51,2.68±0.50,2.45±0.75,2.77±0.43 and 2.65±0.55;the ones in the control group were 2.62±0.49,2.42±0.59,2.55±0.50,2.37±0.64,2.67±0.48 and 2.37±0.69. The scores of the six items of compliance in the two groups were all improved compared to the ones before the intervention,but the interaction between the groups and intervention time was not statistically significant（P>0.05）. The scores of positive attitude,self-decompression,self-decision and total self- management efficacy in the experimental group were 52.48±7.69,10.51±3.31,36.88±6.15 and 97.62±12.87,respectively;the ones in the control group were 37.38±10.44,5.70±1.51,27.58±9.41,and 92.17±11.19. The scores of the two groups were all improved compared to the ones before the intervention,and the ranges of the scores improved in the experimental group were wider than those in the control group. Conclusion The“radiotherapy assistant”application can significantly improve the self-management efficacy of patients who receive the lung cancer radiotherapy,but its effect on the improvement of treatment compliance requires long-term intervention to verify.

Objective Lab color mode can be used to digitize the color.This study explores the possibility of using Lab model to measure facial pigmentations.Methods Lab color model was used to measure the normal skin and three common clinical pigmentations (Ota nevus,freckles and melasma).We also analyzed the characteristics and assessed the data changes after the treatment.Results Average L,a and b values were 54.4,13.8 and 19.0 in normal skin,34.6,5.17 and 6.9 in Ota nevus,43.25,16.15 and 23.05 in freckles and 40.5,16.8 and 23.35 in melasma,respectively.The Lab values of freckles and melasma were close.The order of L value was:normal skin ＞ freckle ＞ melasma ＞Ota nevus;the order of value of a and b was:melasma ＞ freckle ＞ normal skin ＞ Ota nevus.After treatment,the Lab values gradually tended to be the values of normal skin.Conclusions The Lab color mode can be used as a digital description method for skin color and facial pigmentation,which provides an objective measure for clinical research.