[Diagnostic and prognostic values of flow cytometry in diffuse large B-cell lymphoma with bone marrow involvement].

Objective: To analyze the diagnostic and prognostic values of flow cytometry (FC) in diffuse large B cell lymphoma (DLBCL) with bone marrow involvement (BMI). Methods: The clinical data of 412 patients with newly diagnosed DLBCL, including 243 males and 169 females, aged 64 (28-92) years old, in the Department of Hematology at Peking University Third Hospital from December 2012 to June 2022 were retrospectively analyzed. All patients underwent bone marrow biopsy (BMB) and bone marrow FC. The patients with BMI by FC were further detected by fluorescence in situ hybridization (FISH) for gene analysis. The positive rates and consistency of BMI detected by BMB and FC were evaluated. According to the results of BMB and FC examinations, all patients were divided into four groups: the BMB+FC+group (115 cases), the BMB-FC+group (50 cases), the BMB+FC-group (8 cases, the results did not include in statistical analysis because of small sample size), and the BMB-FC-group (239 cases). The clinical features, treatment response rates, 5-year survival rates, and immunophenotype characteristics by FC in different groups were analyzed. Results: Among the 412 patients with DLBCL, the positivity rates of BMB and FC for BMI detection were 29.9% (123/412) and 40.0% (165/412), respectively. Good consistency between BMB and FC was found (Kappa=0.841, P=0.001). The numbers of extranodal involvement≥2, splenomegaly, huge mass, higher Ki-67 score, higher international prognostic index (IPI) score, thrombocytopenia, and elevated lactate dehydrogenase level were more prevalent in the BMB+FC+group than those in the BMB-FC+group and the BMB-FC-group (all P<0.05). The treatment response rate in BMB+FC+group was 63.5% (73/115), which was lower than those in BMB-FC+group (88.0%, 44/50, P=0.048) and BMB-FC-group (90.0%, 215/239, P=0.032), respectively. The 5-year overall survival rates in three groups were (53.6±9.7) %, (72.5±8.6) %, and (75.2±7.6) %, respectively, with a statistically significant difference (P=0.037). According to the FISH results of bone marrow, 102 cases were diagnosed as not otherwise specified (NOS), 48 cases were diagnosed as double hit lymphoma (DHL), and 15 cases were diagnosed as triple hit lymphoma (THL). Compared with NOS subtypes, the tumor cells in DHL or THL subtypes had higher proportion of increased side scatter (SSC), higher positive rates of CD10 expression, CD38 strong expression and CD56 expression, and lower proportion of surface immunoglobulin light chain restriction (all P<0.05). Conclusions: FC is well consistent with BMB in diagnosing DLBCL with BMI. Combined with FISH detection, FC can contribute to the auxiliary diagnosis and risk stratification for DHL and THL, and provide reference for the prognostic evaluation in DLBCL with BMI.

[Psychological and behavioral functioning of children and adolescents during long-term home-schooling].

Objective: To study the characteristics and risk factors of psychological and behavioral problems of children and adolescents of different ages and genders in long-term home-schooling during the coronavirus disease-2019 pandemic. Further, to provide scientific basis for more targeted psychological intervention and coping strategies in the future. Methods: A cross-sectional survey using an online questionnaire was conducted on students aged 6-16 years old in five representative cities of North (Beijing), East (Shanghai), West (Chongqing), South (Guangzhou) and Middle (Wuhan) in China. In this study, the social behavior and psychological abnormalities which was defined as the positive of any dimension were investigated in multiple dimensions during long-term home-schooling. The influencing factors of psycho-behavioral problems were analyzed by Logistic regression, and the confounding factors were corrected with graded multivariable adjustment. Results: A total of 6 906 valid questionnaires were collected including 3 592 boys and 3 314 girls, of whom 3 626 were children (6-11 years old) and 3 280 were adolescents (12-16 years old). The positive detection rate of psychosocial-behavioral problems were 13.0% (900/6 906) totally, 9.6% (344/3 592) in boys and 16.8% (556/3 314) in girls respectively, and 7.3%(142/1 946) in boys aged 6-11, 14.0%(235/1 680) in girls aged 6-11, 12.3%(202/1 646) in boys aged 12-16, 19.6%(321/1 634) in girls aged 12-16 respectively. There were significant differences between the psychological problems group and the non-psychological problems group in gender, parent-offspring conflict, number of close friends, family income change, sedentary time, homework time, screen exposure time, physical activity, dietary problems (χ²=78.851, 285.264, 52.839, 26.284, 22.778, 11.024, 10.688, 36.814, 70.982, all P<0.01). The most common symptoms in boys aged 6-11 years were compulsive activity, schizoid and depression, in girls aged 6-11 years were schizoid/compulsive activity, hyperactivity and social withdrawal, in boys aged 12-16 years were hyperactivity, compulsive activity and aggressive behavior, and in girls aged 12-16 years were schizoid, anxiety/compulsive activity and depression/withdrawal, respectively. After graded multivariable adjustment, besides the common risk factors, homework time and online study time were the risk factors of 6-11 years old groups [boys OR(95%CI): 1.750 (1.32-2.32), 1.214(1.00-1.47), girls: 1.579(1.25-1.99), 1.222(1.05-1.42), all P<0.05], videogames time were the risk factors of 12-16 years old groups [ boys: 2.237 (1.60-3.13), girls: 1.272 (1.00-1.61), all P<0.05]. Conclusions: Some children and adolescents may have psychological and behavioral problems during long-term home-schooling. The psychological and behavioral manifestations differed in age and gender subgroups, which deserve special attention in each subgroups. Schools, families and specialists should actively provide precise psychological support and comprehensive intervention strategies according to special features and risk factors.

[Analysis of the correlation between lymphocyte subsets and severity of corona virus disease 19].

OBJECTIVE: To understand the differences in lymphocyte subsets in patients with different clinical classifications of corona virus disease 19 (COVID-19). METHODS: Eighty-one patients with COVID-19 who were admitted to the isolation ward under the responsibility of three medical aid teams in the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from February 8, 2020 to March 28, 2020, were selected to collect clinical data. According to the relevant diagnostic criteria, the disease status of the patients was classified into moderate cases (n=35), severe cases (n=39) and critical cases (n=7) when lymphocyte subset testing was performed. Their blood routine tests, lymphocyte subsets and other indicators were tested to compare whether there were differences in each indicator between the patients of different clinical classification groups. RESULTS: The differences in the absolute count of total lymphocytes, T-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and natural killer (NK) cells among the three groups of patients were all statistically significant (P < 0.05), and the critical cases were significantly lower than the moderate and severe cases in the above indicators, and the indicators showed a decreasing trend with the severity of the disease. In 22 patients, the six indicators of the absolute count of T-lymphocytes, B-lymphocytes, CD4+T-lymphocytes, CD8+T-lymphocytes and NK cells, CD4+/CD8+ ratio were all within the normal reference range in the first test, and 59 patients had abnormalities of the above indicators, with the absolute count of NK cells and CD8+ T lymphocytes decreasing most frequently (61%, 56%). The patients with the absolute count of NK cells and CD8+ T lymphocytes below the normal reference range were one group, and the remaining abnormal patients were the other group. There were more critical cases in the former group (moderate : severe : critical cases were 4 : 8 : 7 vs. 19 : 21 : 0, respectively, P=0.001), and all the deaths were in this group (6 cases vs. 0 case, P=0.001). The absolute B lymphocyte count was below the normal reference range in 15 patients, and the remaining 64 cases were within the normal range. The ratio of moderate, severe and critical cases in the reduced group was 4 : 7 : 4, and the ratio of critical cases was more in normal group which was 30 : 31 : 3, and the difference between the two groups was statistically significant (P=0.043). CONCLUSION: The more critical the clinical subtype of patients with COVID-19, the lower the absolute count of each subset of lymphocytes.

[Analysis of survival and treatment outcome of patients with primary diffuse large B cell lymphoma in reproductive system].

Objective: To analyze clinical feature and treatment outcome of patients with primary diffuse large B cell lymphoma(DLBCL) in reproductive system. Methods: A total of 26 patients with DLBCL in reproductive system were retrospectively analyzed, and the clinical features, laboratory data were included in Kaplan-Meier and prognostic analysis. Results: In our center, the incidence of primary diffuse large B cell lymphoma in reproductive system was 3.5% in all DLBCL patients, and the median age was 62.0 years. Male are more common with unilateral testicular involvement, and 38.5% patients belong to Ⅲ and Ⅳstage while 84.6% patients belong to non-germinal center B cell-like subgroup. The overall response rate(ORR) for the whole group was 88.5%. The complete response rate was 76.9%. The 3, 5-year progression free survival rate was 70.5% and 62.7% , and the 3, 5-year overall survival rate was 83.5% and 69.6%, respectively. The most common recurrent sites were contralateral testis and central nervous system. Rituximab can improve the survival of patients and combined with contralateral irradiation can furtherly improve progression free survival of patients(P=0.047). Clinical stage, B symptom, IPI, the level of LDH, and CRP, age>60 years, and initial treatment outcome were predictive of overall survival. Conclusion: Primary diffuse large B cell lymphoma in reproductive system is a rare type of extranodal DLBCL which occurs in older men with aggressive features. The most common sites of recurrence were contralateral testis and central nervous system. Surgery, rituximab , radiotherapy and prophylactic intrathecal injection can improve the survival of patients and may be the first-line treatment.

[B7-H3 silencing inhibits human hematological malignancy xenograft tumor tumorigenesis and metastasis in nude mice].

OBJECTIVE: To investigate the effect and mechanism of targeted B7-H3 gene silencing on the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. METHODS: Real-time fluorogentic quantitative PCR (qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13 strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which expressed high level of B7-H3 were screened out. Targeted B7-H3 knockdown in U937, Maver and Z138 was performed by lentivirus transduction and the effect of B7-H3 silencing in stable cell lines was tested by qPCR and FCM. Injecting the nine groups subcutaneously into the nude mice to establish xenograft models after dividing the U937, Maver and Z138 into non-infected control group (CON), B7-H3 knockdown group (KD) and negative non-targeted control infected group (NC),respectively, for detecting the tumorigenicity and metastasis in vivo. Furthermore, the expression of Ki-67 in xenograft tumors was detected by immunohistochemistry (IHC). The expression of metalloproteinase 2 (MMP-2) was detected by western blot. RESULTS: The stable B7-H3 silencing cell lines of U937, Maver and Z138 were successfully established. Compared with the NC group, the KD groups of U937, Maver and Z138 had an obviously slower tumor growth. The average tumor inhibition rates at the end of observation period were 61.83% (F=43.78, P<0.05), 59.12% (F=36.51, P<0.05) and 67.37% (F=40.29, P<0.05); there was no significant difference in tumor volume growth between the NC group and the CON group (P>0.05). The liver distant metastasis of all the xenograft tumor models in nude mice was the most common and the rates of distant metastasis in KD groups were significantly lower than that of the corresponding NC groups. The Ki-67 indexes of the KD groups were significantly lower than those of the relative NC groups in three cell lines (U937: 40.3%±5.2% vs. 79.1%±6.3%, q=30.31, P<0.05, Maver: 35.2%±6.4% vs. 69.6%±5.1%, q=24.82, P<0.05; Z138: 38.4%±7.1% vs. 75.7%±4.8%, q=28.07, P<0.05); there was no significant difference in the expression of Ki-67 between the NC group and the CON group (P>0.05). The expressions of MMP-2 were also significantly lower in the KD groups than in the NC groups (U937: q=14.59, P<0.05; Maver: q=9.25, P<0.05; Z138: q=11.04, P<0.05); there was no significant difference in the expression of MMP-2 between the NC group and the CON group (P>0.05). CONCLUSION: Targeted B7-H3 gene silencing could inhibit the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. The mechanism may be related to the down-regulation of Ki-67 and MMP-2.

[Analysis of survival and treatment outcome of young patients with high-risk diffuse large B cell lymphoma].

Objective: To analyze clinical feature and treatment outcome of young patients with high-risk diffuse large B cell lymphoma. Methods: A total of 122 young patients with high-risk diffuse large B cell lymphoma who were treated in Third Hospital of Peking University during the period from January 2000 to April 2015 were retrospectively analyzed, and the clinical features, laboratory data were included in Kaplan-Meier and prognostic analysis. Results: In our center, the incidence of young high-risk DLBCL was 27.1% in all DLBCL patients, median age was 44.0 years, 99.2% patients belong to Ⅲ and Ⅳstage, 50% patients had more than two extranodal organs involvement, and the higher proliferation index(Ki-67≥80%) was present in 63.1% of patients, Immunohistochemistry showed that 36.7% patients in 30 cases were double-expressed DLBCL. The overall response rate(ORR) for the whole group was 79.4%, the complete response rate was 39.7% , the 3, 5-year progression free survival rate was 59.8% and 57.0%, the 3, 5-year overall survival rate was 63.5% and 57.8%, respectively. 44.3% patients were refractory-relapsed DLBCL. Rituximab can improve the survival of patients and 3-year overall survival rate was 75.2% vs 46.1%(P=0.001). High-dose chemotherapy was superior to CHOP regimen which 3-year overall survival rate was 84.6% vs 54.1%(P=0.006). Compared with chemotherapy group , auto-hematopoietic stem cell transplantation can improve prognosis of patients and 3-year overall survival rate was 93.4% vs 48.3%(P<0.001). The level of Ki-67, B symptom, ECOG score, the level of LDH, WBC and albumin, ESR level, anemia, rituximab therapy, initial regimens, ASCT, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated that albumin level(RR=5.462, P=0.019), initial treatment outcome(RR=34.863, P<0.001) and refractory-relapsed (RR=24.374, P<0.001)were independent prognostic risk factors. Conclusions: Young patients with high-risk DLBCL were highly aggressive in clinical and pathological features . Rituximab and high-dose regimens can improve the survival of patients.

[Retrospective analyses of CHOPE plus L-asparaginase regimen in treatment of T-cell lymphoma].

OBJECTIVE: To investigate prognostic factors of the T-cell non-Hodgkin's lymphoma (T-NHL), and to study the clinical efficacy of CHOPE plus L-asparaginase(L-ASP) regimen for T-NHL. METHODS: Retrospective analyses were made of 61 T-NHL patients who were treated from July 2007 to August 2013. Randomly divided into two groups CHOPE and CHOPE+L group(Based on CHOPE, added with L-ASP on the 1st, 3rd, 5th, 7th, 9th and 11th day). RESULTS: Of the 61 patients evaluatd with the median survival was 22 (3-65) months,the complete remission rate was 52.50%, the partial remission rate 29.51%, and the response rate 80.01%. The complete remission rate was 57.89%, and the patial remission rate 84.21% in CHOPE+L and the complete remission rate 43.48%, the response rate 78.26% in CHOPE, respectively (both P>0.05). The 1-, 2-, and 5-year overall survival rates were 91.0%, 87.6% and 65.7% respectively (P>0.05). But the overall survival rate in CHOPE+L was significantly higher than that in CHOPE group in extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (P<0.05). The analysis of the prognostic factors indicated that ENKTCL, the outside junction lesions, and the CR rate were poor factors with statistic significance in T-NHL. CONCLUSION: CHOPE+L regimen has better efficacy for ENKTCL, but whether CHOPE+L regimen is used in the treatment of T-NHL, large prospective clinical trials are worth for further investigation.

[Early immune reconstitution after hematopoietic stem cell transplantation].

OBJECTIVE: To search for differences in early immune reconstitution after allogenic or autologous hematopoietic stem cell transplantation (HSCT). METHODS: The peripheral blood (PB) from 31 adult patients undergoing allogenic HSCT (allo-HSCT, 15 patients) or autologous HSCT (auto-HSCT, 16 patients) for the treatment of hematological malignancies and from 20 related healthy controls (HC) from December 2011 to August 2014 was used to analyze the kinetic recovery of lymphocyte subsets by means of flow cytometry during 12 months after HSCT. The T cell receptor rearrangement excision circle (TREC) levels among CD3(+) T cells were measured in the patients and HC to evaluate the thymic-dependent T cell reconstitution. RESULTS: The allo- and auto-HSCT recipients did not differ significantly in CD4(+) T cells, CD8 naive T cells, effecter memory T cells (TEM), CD4 central memory T cells (TCM), mid-activated T cells and dendritic cells (DC)during the follow-up (P>0.05). But they both differed significantly from HC (P<0.05). CD8(+) T cells and NK cells reconstructed rapidly. There was no significant difference in the numbers of B cells between the allo- and auto-HSCT groups from M1 to M3 (P>0.05). B cells in both the groups were lower than those in HC (P<0.05). The recovery of B cells in auto-HSCT group was faster than in allo-HSCT group at M6 and M12 (P<0.05). The frequencies of CD4 naive T cells and later activated T cells in allo-HSCT group were significantly higher than in auto-HSCT group at M6 and M12 (P<0.05). The frequencies of CD8 TCM in auto-HSCT group were significantly higher than in allo-HSCT group at M6 and M12 (P<0.05). The TREC levels were significantly lower than in both the groups compared with the age-matched HC during the follow-up (P<0.05). No significant difference was observed between allo-HSCT and auto-HSCT groups (P>0.05). CONCLUSION: The differences of the nature and the speed of lymphocyte reconstitution observed between the two patents groups were minor. This leads us to conclude that in allografted patients, immune reconstitution and subpopulations of peripheral blood lymphocytes are probably not related to the allogenicity of the graft, but due to the impaired thymus functions and slow differentiation of T lymphocytes in thymus.

[Levels of dichlorodiphenyltrichloroethane internal exposure levels in pregnant women of Xiamen and influencing factors].

Objective: To investigate the level of and factors influencing internal exposure to dichlorodiphenyltrichloroethane (DDT) in pregnant women. Methods: In all, 1 064 pregnant women were recruited in a hospital of Xiamen. Participants were asked to complete a questionnaire to obtain data on sociodemographic characteristics and lifestyle. Peripheral venous blood and cord blood samples were collected. Of the 1 064 pregnant women, 600 were enrolled in this study after completing the questionnaire and providing peripheral venous blood and cord blood. Among those women, 150 were selected randomly using a systematic sampling method. A gas chromatography coupled electron capture detector was used to determine the concentration of six DDT homologues: p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT), p,p'-dichlorodiphenyldichloroethane (p,p'-DDD), o,p'-dichlorodiphenyldichloroethane (o,p'-DDD), p,p'-dichlorodiphenylethylene (p,p'-DDE), and o,p'-dichlorodiphenylethylene (o,p'-DDE) . Pregnant women were divided into two groups according to DDT concentration: a low concentration group (detection value≤P50) and a high concentration group (detection value>P50). multivariate logistic regression was used to analyze the association between the DDT levels and potential influencing factors which investigated in the questionnaire. Results: The detection rates of p,p'-DDT, o,p'-DDT, p,p'-DDD, o,p'-DDD, p,p'-DDE and o,p'-DDE in the peripheral venous blood samples from the 150 pregnant women were 83.3% (125), 29.3% (44), 58.0% (87), 24.0% (36), 82.0% (123), and 34.7% (52), respectively. The median concentrations were 1.56, 0.03, 0.07, 0.03, 0.93 and 0.03 µg/ml, respectively. The detection rates of p,p'-DDT, o,p'-DDT, p,p'-DDD, o,p'-DDD, p,p'-DDE and o,p'-DDE in the cord blood samples were 69.3% (104), 10.7% (16), 29.3% (44), 20.7% (31), 81.3% (122) and 45.3% (68), and the median concentrations were 0.41, 0.03, 0.03, 0.03, 0.42 and 0.03 µg/ml, respectively. The concentration ranges in the low and high DDT concentration groups which contained 75 respondents respectively were 0-3.69 and 3.74-82.09 µg/ml, respectively. In the single-factor analysis, the number (percentage) of those who consumed seafood " rarely" , "less than twice a week" , and " twice a week or more" was 15 (20.3%), 22 (29.7%), and 37 (50.0%), respectively, in the low concentration group, and 4(5.3%), 20(26.7% ), and 51(68.0% ) in the high concentration group (χ2=8.69, P=0.013). The results of the multivariate logistic regression analysis indicate that pregnant women who consume seafood less than twice a week, twice a week or more have higher peripheral blood DDT concentrations compared with those who rarely consume seafood. The OR (95% CI) values were 1.14 (1.08-1.21), 2.11 (1.55-2.85), respectively. Conclusion: The exposure level of pregnant women to DDTs in the Xiamen area is higher than that of women in other regions. High seafood intake is a risk factor for internal exposure to DDTs.

[A survey on the current situation of serum vitamin A and vitamin D levels among children aged 2-<7 years of 20 cities in China].

Objective: To investigate serum vitamin A and vitamin D status in children aged 2-<7 years in 20 cities in China. Methods: A cross-sectional study was conducted. A total of 2 924 healthy children aged 2-<7 years were recruited from September 2018 to September 2019 from 20 cities in China, categorized by age groups of 2-<3 years, 3-<5 years, and 5-<7 years. The demographic and economic characteristics and health-related information of the enrolled children were investigated. Body weight and height were measured by professional staff members. The serum vitamin A and vitamin D levels were detected by high-performance liquid chromatography-tandem mass spectrometry. Chi-square test and Logistic regression were applied to analyze the association between vitamin A and vitamin D deficiency and insufficiency as well as their underlying impact factors. Results: The age of the 2 924 enrolled children was 4.33 (3.42, 5.17) years. There were 1 726 males (59.03%) and 1 198 females (40.97%). The prevalences of vitamin A and vitamin D deficiency in enrolled children were 2.19% (64/2 924) and 3.52% (103/2 924), respectively, and the insufficiency rates were 29.27% (856/2 924) and 22.20% (649/2 924), respectively. Children with both vitamin A and vitamin D deficiencies or insufficiencies were found in 10.50% (307/2 924) of cases. Both vitamin A (χ2=7.91 and 8.06, both P=0.005) and vitamin D (χ2=71.35 and 115.10, both P<0.001) insufficiency rates were higher in children aged 3-<5 and 5-<7 years than those in children aged 2-<3 years. Vitamin A and vitamin D supplementation in the last 3 months was a protective factor for vitamin A and D deficiency and insufficiency, respectively (OR=0.68 and 0.22, 95%CI 0.49-0.95 and 0.13-0.40, both P<0.05). The rates of vitamin A and D insufficiency was higher in children with annual household incomes <60 000 RMB than in those with annual household incomes ≥60 000 RMB (χ2=34.11 and 10.43, both P<0.01). Northwest and Southwest had the highest rates of vitamin A and vitamin D insufficiency in children aged 2-<7 yeas, respectively (χ2=93.22 and 202.54, both P<0.001). Conclusions: Among 20 cities in China, children aged 2-<7 years experience high rates of vitamin A and vitamin D insufficiency, which are affected by age, family economic level, vitamin A and vitamin D supplementation, and regional economic level. The current results suggest that high level of attention should be paid to vitamin A and vitamin D nutritional status of preschool children.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation treatment for T lymphoblastic leukemia/lymphoma].

Objective: To analyze the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treating T lymphoblastic leukemia/lymphoma (T-ALL/LBL) . Methods: This study retrospectively evaluated 119 adolescent and adult patients with T-ALL/LBL from January 2006 to January 2020 at Peking University Third Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Patients were divided into chemotherapy-only, chemotherapy followed by allo-HSCT, and chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) groups according to the consolidation regimen, and the 5-year overall survival (OS) and progression-free survival (PFS) rates of each group were compared. Results: Among 113 patients with effective follow-up, 96 (84.9%) patients achieved overall response (ORR), with 79 (69.9%) having complete response (CR) and 17 (15.0%) having partial response (PR), until July 2022. The analysis of the 96 ORR population revealed that patients without transplantation demonstrated poorer outcomes compared with the allo-HSCT group (5-year OS: 11.4% vs 55.6%, P=0.001; 5-year PFS: 8.9% vs 54.2%, P<0.001). No difference was found in 5-year OS and 5-year PFS between the allo-HSCT and auto-HSCT groups (P=0.271, P=0.197). The same results were achieved in the CR population. Allo-HSCT got better 5-year OS (37.5% vs 0) for the 17 PR cases (P=0.064). Different donor sources did not affect 5-year OS, with sibling of 61.1% vs hap-haploidentical of 63.6% vs unrelated donor of 50.0% (P>0.05). No significant difference was found in the treatment response in the early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP) and non-ETP populations. The ETP group demonstrated lower 5-year OS compared with the non-ETP group in the chemotherapy alone group (0 vs 12.6%, P=0.045), whereas no significant difference was found between the ETP and non-ETP groups in the allo-HSCT group (75.0% vs 62.9%, P=0.852). Multivariate analysis revealed that high serum lactate dehydrogenase level, without transplantation, and no CR after chemotherapy induction were independently associated with inferior outcomes (P<0.05) . Conclusion: Allo-HSCT could be an effective consolidation therapy for adult and adolescent patients with T-ALL/LBL. Different donor sources did not affect survival. Allo-HSCT may overcome the adverse influence of ETP-ALL/LBL on OS.

[Clinical features and prognosis of 166 cases of MYC/BCL2 double-expression diffuse large B-cell lymphoma].

Objective: To investigate the clinical features and prognosis of MYC/BCL2 double-expression diffuse large B-cell lymphoma (DEL) . Methods: The clinical data, including clinical characteristics, survival, and prognostic factors, of 166 patients with DEL treated at Peking University Third Hospital from January 2016 to December 2020 were retrospectively analyzed. Results: A total of 410 patients with diffuse large B-cell lymphoma were collected, including 166 cases (40.5%) of DEL. There were 82 males and 84 females with a median age of 63.5 (21-95) years at diagnosis. A total of 110 patients (66.3%) were aged over 60 years at initial diagnosis, 106 patients (106/163, 65.0%) had elevated lactate dehydrogenase (LDH) at diagnosis, 74 patients (74/160, 46.2%) had ß(2) microglobulin level over 3 mg/L at diagnosis, and 107 patients (107/163, 65.6%) had≥2 extranodal involvement. Sixty-five patients (65/166, 39.2%) had B symptoms, 131 patients (131/165, 79.4%) had stage Ⅲ and Ⅳ disease at initial diagnosis, 41 patients (41/161, 25.5%) had an International Prognostic Index (IPI) score of 0-2 at initial diagnosis, and 38 patients (38/161, 23.6%) had an IPI score of 3 at initial diagnosis. Eighty-two patients (82/161, 50.9%) had an IPI score of 4-5 at initial diagnosis. Nine (9/56, 16.1%) patients with DEL had MYD88 and CD79B mutations. Univariate analysis showed that age over 60 years (P=0.004) , increased ß(2) microglobulin level (P=0.002) , and high IPI score (P=0.003) were associated with poor overall survival (OS) . Increased ß(2) microglobulin level (P=0.031) , LDH level (P=0.017) , stage Ⅲ-Ⅳ (P=0.001) , high IPI score (P=0.013) , immunohistochemical p53 mutation (P=0.049) , and PIM1 mutation (P=0.039) were associated with poor progression-free survival (PFS) . Multivariate analysis showed that IPI score of 4-5 was an independent risk factor for the prognosis of DEL (HR=2.622, 95% CI 1.398-4.917, P=0.003) . Survival analysis showed that there was a significant difference in the PFS between patients with DEL and those without DEL (65.6% vs 75.1%, P=0.002) . However, there was no significant difference in the OS (81.8% vs 83.6%, P=0.226) . In patients with DEL, the overall response rate of R-EPOCH regimen was higher than that of RCHOP or RCHOP-like regimen (81.5% vs 63.4%, P=0.004) . Conclusion: DEL is a group of aggressive lymphomas with relatively poor PFS. The R-EPOCH regimen may improve the overall prognosis of patients.

[The Autism Spectrum Disorder Cohort-the sub-cohort of China National Birth Cohort].

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

Study on the epigenetic methylation modification of bipolar disorder major genes.

OBJECTIVE: We aimed to study changes and possible roles of epigenetic modification of candidate genes in the pathogenesis of bipolar disorder, and provide the basis for clinical diagnosis and analysis. PATIENTS AND METHODS: A total of 150 patients with bipolar disorder were enrolled in this study from January 2014 to June 2015; also, 50 healthy subjects were enrolled as control group. The patients were followed up for 18 months and followed up once every 3 months to review the methylation status. The methylation status was examined before and after treatment, and the patients were followed up every 3 months after treatment, and the follow-up period was 18 months. RESULTS: Compared with the healthy control group, there were 2075 CpG island aberrant methylation points in patients with bipolar disorder, which can be divided into 24 categories. Log-Ratio > 0.5 was used as the positive criteria, and COMT and PPIEL were identified as the genes associated with bipolar disorder. Compared with the control group, the levels of COMT and PPIEL gene methylation in the observation group were significantly higher (p < 0.05). There was no significant difference in the methylation level of COMT and PPIEL gene between the two groups (p > 0.05) after 12 months of treatment. CONCLUSIONS: The methylation level of COMT and PPIEL gene is closely related to bipolar disorder.

[Structural change of the corpus callosum fibers in toddlers with autism spectrum disorder: two-year follow-up].

Objective: To conduct a follow-up investigation of structural changes of the corpus callosum fibers of toddlers (2 to 5 years of age) with autism spectrum disorder(ASD) and to explore the associations with clinical symptoms. Method: In this prospective randomized controlled study, ASD children who were diagnosed in the Child Mental Health Research Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University from May 2011 to November 2012 were included in the ASD group, and developmentally delayed children were included in the control group (DD group). Diffusion tensor imaging (DTI) data from the two groups were obtained at two age levels: 2-3 years of age, and 4-5 years of age. Region of interest analysis was applied to assess characteristic values of total area and sub-regions of corpus callosum: the fraction anisotropy (FA), the mean diffusivity (MD), the radial diffusivity (RD) and the axial diffusivity (AD). All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Treatment Evaluation Checklist (ATEC). The characteristic values of total area and sub-regions of corpus callosum of ASD group at two age levels were analyzed by paired sample t test; the characteristic values of total area and sub-regions of corpus callosum of ASD group and DD group were analyzed by independent-sample t test; the correlations between FA values of the total area and sub-regions of corpus callosum and ADI-R or ATEC scores were analyzed by Pearson correlation analysis. Result: Forty cases meeting inclusion criteria were enrolled in ASD group, and 31 eligible cases were enrolled in the control group. Four children in the ASD group were lost to follow-up, and 5 children in the control group were lost to follow-up. Longitudinal comparison between the two age subgroups of ASD patients showed that the FA values of the total corpus callosum increased (0.499 55±0.027 59 vs. 0.505 83±0.086 64, t=4.88, P<0.05), but MD values, RD values and AD values of the total corpus callosum area decreased (0.000 89±0.000 03 vs. 0.000 81±0.000 14, 0.000 61±0.000 04 vs. 0.000 55±0.000 09, 0.001 43±0.000 03 vs. 0.001 38±0.000 03, t=9.31, 7.90, 8.66, P<0.05 for all comparisons). In the area of corpus callosum genu, FA and AD values increased (t=5.59, 8.48, P<0.05 for both comparisons), but MD and RD values decreased (t=12.67, 11.28, P<0.05 for both comparisns). In the area of corpus callosum body, FA and RD values increased(t=5.46, 8.48, P<0.05 for both comparisons), but MD and AD values decreased (t=8.08, 6.22, P<0.05 for both comparisons). In the area of corpus callosum splenium, MD, RD and AD values decreased (t=6.81, 4.44, 5.51, P < 0.05 for all comparisons). Among the participants 2 to 3 years of age, there were no significantly differences in FA values of total area and sub-regions of corpus callosum between ASD group and the DD group (P > 0.05 for all comparisons); as compared with the DD group, ASD group had higher AD values of total area and splenium of corpus callosum (0.001 43±0.000 03 vs. 0.001 40±0.000 04, 0.001 34±0.000 03 vs. 0.001 32±0.000 04, t=1.56, 1.14, P < 0.05 for both comparisons); ASD group had lower AD values but higher RD and MD values of corpus callosum genu (t=0.07, 0.55, 0.07, P < 0.05 for all comparisons); ASD group had lower RD values of corpus callosum body (t=0.07, P < 0.05). Among the participants 4 to 5 years of age, as compared with the DD group, ASD group had higher FA value of total corpus callosum area(0.505 83±0.086 64 vs. 0.483 77±0.099 30, t=8.56, P < 0.05), lower RD value of total corpus callosum(0.000 55±0.000 09 vs. 0.000 56±0.000 12, t=14.44, P < 0.05), lower RD values of corpus callosum body (t=2.20, P < 0.05), higher FA values (t=3.35, P < 0.05) but lower AD values of corpus callosum splenium (t=2.20, P < 0.05). A correlation analysis between FA values of total area and sub-regions of corpus callosum and clinical variables showed that the FA values of total area and splenium of corpus callosum in ASD group at 2 to 3 years of age were negatively correlated with the scores of language skills in ATEC (r=-0.35,-0.36, P < 0.05 for both comparisons). And after two years, FA values of total corpus callosum were positively correlated with the scores of social communication in ATEC (r=0.34, P < 0.05). There was no significant correlation between FA values of sub-regions of corpus callosum and the scores of ATEC (P > 0.05 for all comparisons). There was no significant correlation between FA values of total area and sub-regions of corpus callosum and the scores of ADI-R (P > 0.05 for all comparisons). Conclusion: The fiber structure of corpus callosum was still in the process of maturing during the age of 2 to 5 years; however, compared with DD group, ASD group had more extensive structural abnormalities of the corpus callosum fibers as age increased, and the structural abnormalities had correlation with the core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.

Structural and functional design of WWTP operation decision support system with a case study.

This paper developes the WWTP operation decision support system (ODSS) to simulate the dynamic behavior of the WWTP treatment process based on ASMs (activated sludge models) and WWTP experiential knowledge. The novel structure and functions of ODSS can offer more flexible and general instructions to the WWTP operations. The three independent sub-systems, namely expert system, simulation system and training system, can cooperate to achieve many more functions such as operation alert, fault diagnosis, process simulation and so forth. The expert system based on the dynamic simulation, an essential part of WWTP ODSS, has been proved to be feasible and effective by the implementation at Fang Zhuang WWTP. Our results indicated that the WWTP ODSS has significant potential for improving plant performance and reducing treatment costs by assisting the operators at the decision-making level.

Structure-function relationship of trichosanthin.

Trichosanthin (TCS), a 27 kDa ribosome inactivating protein extracted from the root tuber of Trichosanthes plant, was subjected to limited chymotrypsin digestion and three peptide fragments designated TCS-F1 72-247, TCS-F2 100-247, and TCS-F3 133-247 were generated. The RNA-N-glycosidase and cytotoxic activities of the TCS fragments were compared with that of inact TCS. TCS-F1 and TCS-F2 were biologically active, while TCS-F3 was completely inactive. Dose-dependent studies showed that TCS-F1 and TCS-F2 were less potent in their trophoblast cytotoxicity than intact TCS, however, full biological effect could still be obtained with a higher dosage. Based on the known three-dimensional structure of TCS, we postulate that the putative active site of TCS is located at amino acid residues 110 to 174.

Preventive and therapeutic effects of lithium carbonate on acute radiation injury of hemopoietic system in mice.

The administration of Li2CO3 to female LACA mice for three consecutive days before or after 4Gy whole body gamma-irradiation appeared to have both preventive and therapeutic effects on radiation-induced leucopenia, especially on the depression of CFU-GM. It is effective in small dosage, short course, and even when given 24 hours after irradiation.