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Objective@# To establish a comprehensive health evaluation index system for HIV-infected pregnant women in floating populations, so as to support the elimination of mother-to-child transmission of HIV. @*Methods@# The preliminary framework of the comprehensive health evaluation indicators was constructed based on literature review and focus group discussion. Experts from maternal and child healthcare, clinical medicine and public health were invited to participate in two-round Delphi consultations. The indicators were scored and weighed according to the importance, priority and measurability, and determined according to means and coefficients of variation of scores. The effectiveness of the consultation was evaluated by positive coefficient, authority coefficient and coordination coefficient.@*Results@# Twenty-six experts participated in this study, including 19 women. There were 5 experts aged 30-40 years, 14 experts aged 41-50 years, and 7 experts aged 51 years and over. There were 17 experts with a master degree and above. All experts had vice senior professional titles and above. The positive coefficients in the two rounds of consultations were 96.30% and 100.00%, the authority coefficients were 0.84 and 0.89, respectively. Finally, 4 primary indicators (individuals and families, disease factors, social environment, health service utilization) and 50 secondary indicators were identified, with the coefficients of variation ranging from 0.084 to 0.236 and the coordination coefficients ranging from 0.282 to 0.405 (all P<0.001). Among the secondary indicators, getting antiviral drugs at the place of residence was restricted to floating populations or not (0.780), HIV viral load during pregnancy (0.750), the registration of maternal and childbirth care manuals at the place of residence was restricted to floating populations or not (0.749), and first-trimester registration or not (0.738) had a high weight. @*Conclusion @#This index system can provide the reference for evaluating the health equity of HIV-infected pregnant and lying-in women in floating populations.
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Objective:To investigate the application value of Metagenomic Next-Generation sequencing (mNGS) in infectious patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Patients suspected with local or systemic infections were retrospectively included after allo-HSCT in our department from April 2019 to November 2020. Pathogenic microorganisms were tested by mNGS in samples from peripheral blood, cerebrospinal fluid, alveolar lavage Liquid, abscess, etc. Other diagnostic methods such as bacterial/fungal culture, viral PCR detection were simultaneously explored comparing with mNGS results.Results:A total of 112 samples in 83 patients were detected by mNGS, and 34 pathogenic microorganisms were determined. Among these positive samples, 11 strains of bacteria (17 times) with the most common Escherichia coli (4/17) were reported. There were 7 strains of fungi (10 times) detected with primary Candida albicans (7/29). Although arvovirus 30.2% (39/129) were predominantly detected, its diagnostic relevance with infections was not definite. Other pathogenic viruses including cytomegalovirus (CMV) 25.6% (33/129) and Epstein Barr virus (EBV) 14.0% (18/129)were of significance. Comparing with golden diagnostic criteria, the sensitivity of mNGS was 86.5%, and specificity was 45.0%. Regarding single pathogen infection, the consistency of mNGS and conventional methods was 82.9% (29/35), while it was 16/17 in combination infections.Conclusion:mNGS could be a potential method to determine pathogens in patients suspected with infections after allo-HSCT.
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Objective:To compare the efficacy of medial patellofemoral ligament (MPFL) reconstruction using single half tunnel, double half curved tunnel and suture anchor fixation in the treatment of patellar dislocation.Methods:A retrospective cohort study was used to analyze the clinical data of 58 patients with patellar dislocation treated in Second Hospital of Lanzhou University from June 2018 to February 2021, including 22 males and 36 females, aged 12-34 years [(19.6±5.5)years]. MPFL reconstruction was performed arthroscopically using single half tunnel fixation in 20 patients (single half tunnel group), double half curved tunnel fixation in 18 (double half curved tunnel group) and suture anchor fixation in 20 (suture anchor group). The Lysholm score, International Knee Documentation Committee (IKDC) score and Tegner activity score were compared among groups before operation, at 3 months after operation and at the last follow-up. The knee range of motion was compared among the three groups at 3 months after operation and at the last follow-up. The postoperative complications of the three groups were observed at the last follow-up.Results:All patients were followed up for 9-39 months [(26.5±9.1)months]. In single half tunnel group, double half curved tunnel group and suture anchor group, the Lysholm score was (78.4±12.0)points, (88.7±7.5)points and (81.1±9.8)points at 3 months after operation, and (80.4±14.2)points, (90.9±9.0)points and (83.3±9.1)points at the last follow-up. The postoperative Lysholm score in all groups was significantly increased from that preoperatively (all P<0.01). The Lysholm score in double half curved tunnel group was significantly higher than that in other two groups at 3 months after operation and at last follow-up (all P<0.05), but there was no significant difference between other groups (all P>0.05). In single half tunnel group, double half curved tunnel group and suture anchor group, the IKDC score was (76.7±12.2)points, (78.4±8.9)points and (81.0±8.1)points at 3 months after operation, and (77.6±15.8)points, (83.2±7.8)points and (82.4±12.4)points at the last follow-up. The postoperative IKDC score in all groups was significantly increased from that preoperatively (all P<0.01), but there was no significant difference among the three groups (all P>0.05). In single half tunnel group, double half curved tunnel group and suture anchor group, the Tegner score was (4.0±1.2)points, (5.4±1.7)points and (5.3±1.7)points at 3 months after operation, and (4.1±1.4)points, (5.8±1.8)points and (5.3±2.2)points at the last follow-up. The postoperative Tegner score in all groups was significantly improved from that preoperatively (all P<0.01). The Tegner score in single half tunnel group was significantly lower than that in other two groups at 3 months after operation and at last follow-up (all P<0.05), but there was no significant difference between other groups (all P>0.05). In single half tunnel group, double half curved tunnel group and suture anchor group, the knee range of motion was (122.3±6.4)°, (121.7±7.1)° and (123.3±5.7)° at the last follow-up, which were significantly increased from (117.3±8.0)°, (115.3±7.9)° and (116.8±8.3)° at 3 months after operation (all P<0.05), with no significant difference among the three groups (all P>0.05). The postoperative complication rate was 10.0% (2/20) in single half tunnel group, 5.6% (1/18) in double half curved tunnel group, and 25.0% (5/20) in suture anchor group ( P>0.05). Conclusions:For patellar dislocation, MPFL reconstruction using single half tunnel, double half curve tunnel and suture anchor fixation have achieved satisfactory improvement of knee range of motion, but knee functional recovery is much better after double half curved tunnel fixation.
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Objective:To investigate early neonatal deaths born to pregnant women with syphilis and the risk factors.Methods:Data were obtained from the maternal syphilis surveillance system in Zhejiang Province. Pregnant women with syphilis who delivered ≥28 weeks during January 2014 to December 2020 were included. Demographic characteristics (age, education level, occupation, gravidity, parity, adverse pregnancy history, etc.), maternal and perinatal health records, syphilis laboratory test results, syphilis treatment regimen, delivery information, and infant information were collected. Trend chi-square analysis was conducted to track the early neonatal mortality over years. Pearson correlation coefficient was used to estimate the relationship between maternal syphilis treatment and early neonatal mortality. Logistic analysis was conducted to investigate the risk factors for early neonatal death.Results:Among the 71 cases with early neonatal death, 49 cases (69.01%) were aged from 21 to 34 years old, 52 cases (73.24%) had middle school education, 39 cases (54.93%) had no fixed occupation, 39 cases (54.93%) had more than three gravidities, 48 cases (67.61%) were multiparas. There were eight cases (11.27%) of stillbirth abortion. Forty-nine cases (69.01%) with rapid plasma reagin circle card test (RPR) or tolulized red unheated serum test (TRUST) titer ≥1∶4. Among the 72 early neonatal deaths, 40 were males and 32 were females. The leading cause of death was preterm birth/low birth weight (56 cases, 77.78%). From 2014 to 2020, the early neonatal mortality rate of pregnant women with syphilis in Zhejiang Province decreased from 10.37‰ (24/2 314) to 1.49‰(3/2 007) (trend χ2=20.05, P<0.001). The rate of maternal antisyphilitic treatment was negatively correlated with early neonatal mortality ( r=-0.895, P=0.006). Multivariate analysis showed that standard treatment reduced the risk of early neonatal death (Wald=24.845, P<0.001, odds ratio ( OR)=0.181). However, RPR or TRUST titer ≥1∶4 in the last trimester (Wald=72.026, P<0.001, OR=10.112) increased the risk of early neonatal death. Conclusions:Preterm birth and low birth weight are the leading causes of early neonatal death in pregnant women with syphilis. Strengthening the treatment of syphilis in pregnancy women, especially the standard treatment, is beneficial to reduce the risk of early neonatal death.
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Objective To observe the effects of the intercellular gap junction (GJIC) composed of connexin 43(Cx43) in mesenchymal stem cells (MSCs) from different sources and their signals on the biological behavior of multiple myeloma (MM) lateral population cells (SP cells), and to explore its possible mechanism. Methods Mesenchymal stem cells (MSCs) from different sources were isolated and cultured. SP cells of MM cell line RPMI 8266 were sorted by flow cytometry. RT-PCR and Western blot were used to detect the expression of Cx43 gene and protein in MSCs, RPMI 8266 and SP cells from different sources. The effects of MSCs from different sources on SP cell cycle, Cx43 protein expression, colony formation ability in vitro, stem cell related gene expression, cytokine secretion and drug resistance were observed. Results There was no significant difference in morphology and phenotype between MM-MSCs and ND-MSCs. Both MM-MSCs and RPMI 8266 cells expressed a higher level of Cx43. Co-culture with MM-MSCs induced more SP cells to enter G0 phase (P<0.001). The expressions of c-myc, Kif4 and Sox2 genes in SP cells were significantly up-regulated, while the expression of Oct-4 gene was down-regulated. After adding α-GA, c-myc, Kif4 and Sox2 were down-regulated in varying degrees, but there was no significant difference. The expression of Cx43 was up-regulated by (31.00±2)% and (39.00±2)%, respectively. The colony formation ability in vitro was up-regulated, and the addition of α-GA could partially inhibit this effect. A small amount of c-myc, Kif4, Sox2 and Oct-4 genes were expressed in RPMI 8266. These genes were significantly up-regulated in SP cell subpopulation. MM-MSCs secreted high levels of interleukin (IL)-6. After co-culture with SP cells, the expressions of IL-6, IL-10 and TGF-β in the supernatant of MM-MSCs were up-regulated (P=0.0072, P=0.037). bFGF and IL-17 had no significant change. After adding α-GA, the levels of IL-6, IL-10 and TGF-β in the supernatant decreased. MM cells were sensitive to bortezomib (BTZ) induced apoptosis, but SP cells were less sensitive. Co-culture with MM-MSCs significantly reduced BTZ-mediated apoptosis. The addition of α-GA partially restored the sensitivity of MM cells to bortezomib. Conclusion MM-MSCs and multiple myeloma SP cells up-regulate the expression of Cx43 protein, form more GJIC, and promote the proliferation and drug resistance of SP cells by changing the cytokine secretion profile of MSCs, which may be one of the reasons for the recurrence of MM.
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Objective:To investigate the optimal monochromatic level for evaluation of in-stent lumen after transjugular intrahepatic portosystemic shunt (TIPS) by dual-layer detector CT.Methods:Twenty-nine patients after TIPS were retrospectively enrolled who underwent abdomen enhanced examinations with portal venous phases by a dual-layer detector CT between December 2019 and July 2021. The mixed iterative image (conventional group) and monochromatic images (40 keV group, 50 keV group, 60 keV group and 70 keV group) were obtained by reconstruction. Circular regions of interest were placed in the in-stent of the cross-sectional reconstructed image and in the vertical spinal muscle on the same plane to obtain the corresponding average CT value and noise. The contrast to noise ratio (CNR) and signal to noise ratio (SNR) were calculated. Then 4-point scale was performed to evaluate image quality subjectively by 2 physicians blindly and separately. One-way ANOVA or Kruskal Wallis H rank-sum test was used for the overall analysis between groups, and LSD test or Dunn′s Bonforoni test was used for pairwise comparison within groups. Results:There was no significant difference in noise values among the 5 groups ( P>0.05). The difference of CNR and SNR between the 5 groups was statistically significant ( F=72.28, 56.45, P<0.001). The CNR and SNR in the 40 keV group were the highest, which were 50.4±15.7 and 59.3±18.4 respectively, and the difference was statistically significant ( P<0.001). Subjective scores showed statistically significant differences among the 5 groups (χ2=101.61, P<0.001). The score of the 40 keV group was higher than that of the 60 keV group, 70 keV group, and conventional group ( P<0.001), and there was no significant difference when compared with the subjective score of the 50 keV group ( P>0.05). Conclusions:The 40 keV monochromatic image of dual detector spectral CT is the best image to observe the lumen of the stent after TIPS.
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Objective:To explore the application value of CT pulmonary function imaging in patients with Coronavirus Disease 2019 (COVID-19) in the convalescent phase.Methods:The COVID-19 patients who were clinically cured and discharged from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were prospectively collected from January to April 2020. Clinical pulmonary function tests (PFTs) and CT pulmonary function imaging were performed 3 months after discharge. The Philips IntelliSpace Portal image post-processing workstation was used to obtain the paired inspiratory-expiratory CT quantitative indexes of the whole lung, left lung, right lung and five lobes. The patients were divided into two groups according to whether residual lesions remain in inspiratory CT images: non-residual lesion group and residual lesion group. The chi-square test was used to compare the differences in the PFT results between groups; the Mann-Whitney U test was used to compare the differences in PFT indexes [forced expiratory volume in the first second as percentage of predicted value (FEV 1%), FEV 1/forced vital capacity (FEV 1/FVC), total lung capacity as percentage of predicted value (TLC%), FVC%] and the differences in quantitative CT indexes [lung volume (LV), mean lung density (MLD), volume change in inspiratory phase and expiratory phase (?LV)] between groups. Multiple linear regression was used to analyze the relationship between CT pulmonary function imaging and PFT indexes of convalescent COVID-19 patients. Results:Of the 90 patients with COVID-19, 35 were males and 55 were females; 45 were included in the non-residual lesion group and 45 were included in the residual lesion group. Fifty-three patients had clinical pulmonary dysfunction 3 months after discharge, including 22 patients in the non-residual lesion group and 31 patients in the residual lesion group. In patients with residual disease, left lower lobe and right lower lobe LV, left lower lobe and right lower lobe ?LV in the inspiratory and expiratory phase were smaller than those without residual disease; whole lung, left lung, right lung, left upper lobe, left lower lobe and right lower lobe MLD in the inspiratory phase and left lower lobe and right lower lobe MLD in the expiratory phase were greater than those without residual disease ( P<0.05). Since there was no significant difference in FEV 1/FVC and FVC% between residual and non-residual lesion groups ( P>0.05), FEV 1/FVC and FVC% of two groups were combined. Multiple linear regression analysis showed FEV 1/FVC=91.765-0.016×LV in-right middle lobe+0.014×MLD ex-left lower lobe ( R2=0.200, P<0.001), FVC%=-184.122-0.358×MLD in-right lung-0.024×?LV left upper lobe ( R2=0.261, P<0.001). There was significant difference in TLC% between residual and non-residual lesion groups ( P<0.05), so multiple linear regression analysis was performed both in the two groups. In the non-residual lesion group, TLC%=80.645+0.031×LV ex-right lower lobe ( R2=0.132, P<0.001); In the residual lesion group, TLC%=-110.237-0.163×MLD in-right upper lobe-0.098×MLD ex-left upper lobe -0.025×LV ex-right lower lobe ( R2=0.473, P<0.001). Conclusion:CT pulmonary function imaging can quantitatively analyze the whole lung, unilateral lung and lobulated lung, thus reflecting the regional pulmonary function, providing more valuable diagnostic information for the assessment of pulmonary function in convalescent patients with COVID-19.
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Objective@#To investigate the current status of syphilis treatment and its influencing factors among pregnant and lying-in women in Zhejiang Province, so as to promote the standardized treatment for pregnant and lying-in women with syphilis.@*Methods @#The sociodemographic characteristics ( age, educational level, ethnicity, marital status, occupation ), fertility ( gravidity, parity, number of children, and adverse pregnancy history ), gestational week at the first antenatal care visit and syphilis treatment ( treatment or not, standardized treatment or not, and antibody titer ) were collected from the pregnant and lying-in women with syphilis infections delivered in Zhejiang Province in 2018, based on the Zhejiang Provincial Information Management System for Prevention of Mother-to-Child Transmission of AIDS, Syphilis and Hepatitis B. Factors affecting the treatment of syphilis infections were identified using a structural-equation model.@*Results@#A total of 2 061 pregnant and lying-in women with syphilis infections were included, with a median age of 29 years and a mean gestational week at the first antenatal care visit of ( 14.33±11.85 ) weeks, and there were 844 women ( 40.95% ) diagnosed in early pregnancy ( <13 weeks of gestational age ). There were 1 978 cases ( 95.97% ) receiving syphilis treatment, and 1 616 cases ( 78.41% ) received standardized treatment. The structural-equation modeling analysis showed that the gestational age at the first antenatal care visit and fertility had direct impacts on the treatment of syphilis infections among pregnant and lying-in women, with standardized path coefficients of -0.187 and -0.157 (both P<0.05 ), respectively, and the sociodemographic characteristics affected the treatment of syphilis through the mediating role of fertility, with a standardized path coefficient of 0.070 ( P<0.05 ).@*Conclusions@#The proportion of syphilis treatment is more than 95% among pregnant and lying-in women in Zhejiang Province, which achieves the required process criteria for validation of elimination of mother-to-child transmission of HIV and syphilis. Gestational week at the first antenatal care visit, fertility status, and sociodemographic characteristics are factors affecting the treatment syphilis infections during pregnancy.
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Three-amino acid loop extension (TALE) transcription factors play important roles in plant growth and cell differentiation. There are plenty of studies on TALE transcription factors in several model plants, but not in radish (Raphanus sativas). A genome-wide bioinformatics analysis identified 33 TALE family genes in the Xiang-Ya-Bai (XYB) radish, These genes, are distributed on nine chromosomes and all contain 4-6 exons. The 33 TALE genes in radish showed a co-linearity relationship with the 17 homologous genes in Arabidopsis thaliana. Moreover, a large number of stress response cis-elements were found in the promoter regions of these genes. Expression analysis showed that four genes in the BELL subfamily were highly expressed in roots, and two genes in the KNOX subfamily were highly expressed in shoots of bolting plants and callus. All radish TALE genes contain sequences encoding the conserved HOX domain, except for the gene RSA10037940, which is homologous to Arabidopsis KNATM. The deduced 3D structures of the TALE proteins irrespective of subtypes are highly similar. All the encoded proteins were weakly acidic and hydrophilic. The radish TALE gene family is relatively evolutionarily conserved, which was consistent with results from Arabidopsis, but quite different from that of rice. This study provides important clues for studying the biological functions of TALE transcription factors in radish.
Subject(s)
Amino Acids , Arabidopsis/metabolism , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins/metabolism , Raphanus/metabolism , Transcription Factors/metabolismABSTRACT
The capacity for neurogenesis in the adult mammalian brain is extremely limited and highly restricted to a few regions, which greatly hampers neuronal regeneration and functional restoration after neuronal loss caused by injury or disease. Meanwhile, transplantation of exogenous neuronal stem cells into the brain encounters several serious issues including immune rejection and the risk of tumorigenesis. Recent discoveries of direct reprogramming of endogenous glial cells into functional neurons have provided new opportunities for adult neuro-regeneration. Here, we extensively review the experimental findings of the direct conversion of glial cells to neurons in vitro and in vivo and discuss the remaining issues and challenges related to the glial subtypes and the specificity and efficiency of direct cell-reprograming, as well as the influence of the microenvironment. Although in situ glial cell reprogramming offers great potential for neuronal repair in the injured or diseased brain, it still needs a large amount of research to pave the way to therapeutic application.
Subject(s)
Animals , Cellular Reprogramming , Nerve Regeneration , Neurogenesis , Neuroglia , NeuronsABSTRACT
Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo + m-DLI in our center. With a median follow-up of 918 (457-1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1% ± 4.9% and 25.0% ± 8.4%. The cumulative incidences of relapse were 50.0% ± 9.8% and 53.5% ± 9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo + m-DLI.
Subject(s)
Humans , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Lymphocytes , Recurrence , Retrospective Studies , Transplantation, HomologousABSTRACT
Objective:To investigate the value of minimal residual disease (MRD) in prediction of prognosis in acute lymphoblastic leukemia (ALL) patients with or above complete remission 2 (CR2) underwent.Methods:A retrospective analysis was performed on 201 ALL patients who received allogeneic stem cell transplantation (allo-SCT) and pretransplant disease status ≥CR2 in Peking University People′s Hospital from January 2009 to December 2018. MRD was measured by multi-parameter flow cytometry at 1 month before transplantation and 1 month, 2 months, 3 months, 4 months, 6 months, 9 months or 12 months after transplantation. To investigate the influence of dynamic changes of MRD before and after transplantation on prognosis.Results:201 ALL patients, including 126 males and 75 females, with a median age of 18 years. The 3-year cumulative incidence of relapse (CIR), non-relapse mortality (NRM), leukemia-free survival (LFS) and overall survival (OS) of all cases were 34%, 16%, 50%, and 56%, respectively. Positive pre-SCT MRD patients with higher 3-year CIR (47% vs 26%, P=0.003), lower 3-year LFS (40% vs 55%, P=0.047) and OS (42% vs 60%, P=0.065) than those with negative one. Subjects with positive post-MRD had higher 3-year CIR (73% vs 22%, P<0.001) and lower 3-year LFS (28% vs 56%, P=0.005) and OS (32% vs 60%, P=0.040) compared with those with negative one. Multivariate analysis showed that both pre-MRD and post-MRD were associated with higher CIR ( HR=1.823, P=0.018; HR=3.474, P<0.001), lower LFS ( HR=1.779, P=0.007; HR=2.185, P=0.001) and OS ( HR=1.609, P=0.034; HR=1.970, P=0.001). Negative pre-and post-SCT MRD group had lower 3-year CIR (17%, 42%, 82%; P<0.001) and higher 3-year LFS (61%, 44%, 18%; P<0.001) and OS (63%, 47%, 27%; P<0.001) compared with those unrisen post-SCT MRD group, and increased post-SCT MRD group. Multivariate analysis showed that pre-and post-SCT MRD dynamics were associated with CIR, LFS and OS ( P<0.01 for all) independently. The pre-and post-SCT MRD dynamics could better distinguish CIR (C=0.669) from that of pre-SCT MRD (C=0.587) and post-SCT MRD (C=0.629). Conclusion:Our data suggest that pre-SCT MRD, post-SCT MRD and the dynamic peri-SCT MRD could be used to predict transplant outcome of ALLpatients with or above CR2 who underwent allo-SCT.
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Objective:To investigate the dynamic change and clinical impact of DEK-NUP214 fusion gene in patients with acute myeloid leukemia (AML) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:Real-time quantitative polymerase chain reaction (RQ-PCR) and multicolor flow cytometry (FCM) were used to detect DEK-NUP214 gene expression and leukemia-associated immunophenotype (LAIP) in 15 newly diagnosed patients with positive DEK-NUP214 and receiving allo-HSCT from September 2012 to September 2017 at Peking University People′s Hospital. The clinical outcome was analyzed using Kaplan-Meier survival curves. The impact of DEK-NUP214 expression was analyzed by log-rank test.Results:The subjects were followed-up with a median period of 657 (62-2 212) days. The median DEK-NUP214 expression level at diagnosis was 488% (274%-1 692%). Thirteen patients achieved complete remission before allo-HSCT. Thirteen patients had a residual DEK-NUP214 expression of 0.38% (0.029%-738.9%) before allo-HSCT. After allo-HSCT, DEK-NUP214 expression in 9/13 patients remained positive, which dropped by around 500 folds (5.7-5 663.0 folds) within a month post-transplant. Five patients died and 2 patients relapsed. The 3-year cumulative incidence of relapse in patients with positive DEK-NUP214 before transplant was 17.5%±11.3% and the 3-year overall survival was 60.5%±13.8%. After allo-HSCT, DEK-NUP214-negative patients had a better outcome.Conclusion:Quantitative monitor of DEK-NUP214 fusion gene could be a sensitive indicator of MRD status after allo-HSCT.
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Objective:To investigate the role of short-term use of mycophenolate mofetil (MMF) in EB viral infection and acute graft-versus host disease (GVHD) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT) .Method:Adult patients (≥14 years) who were diagnosed with hematological malignancies received haplo-HSCT in Peking University Institute of Hematology from May 2016 to December 2017 were retrospectively reviewed. The median age was 30 (14-60) years old. A total of 498 patients including 277 males and 221 females were enrolled. Donors' median age was 38 (8-66) years old. All patients were classified into long-term use of MMF ( n=199), which was defined as 500 mg every 12 hours from day 9 pre-transplant to 250 mg every 12 hours from day 30 after transplant then withdrawal on day 45 to 60 after transplant, and short-term use of MMF ( n=299), which was defined as 500 mg every 12 hour from day 9 pre-transplant then withdrawal till neutrophil engraftment. Kaplan-Meier model was used to analyze the cumulative incidence of EBV infection, and the Cox proportional regression model for multivariate analysis. Result:Characteristics including sex, age, disease types, mismatched HLA loci, donor-recipient relationship, donor-recipient blood type, donor age, and donor sex were comparable between two groups (all P＞0.05). According to once, the incidence of EBV viremia, defined as EBV＞10 3 copies/ml at least once, in short-term group and long-term group was 19.4% (58/299) and 27.6% (55/199) respectively ( P=0.046).Donor age and the duration of MMF prophylaxis (short-term group as reference) were associated with EBV viremia according to multivariate analysis [ HR=1.022(95% CI 1.006-1.038),1.600(95% CI 1.059-2.418); P=0.006 and 0.026, respectively]. The incidence of grade Ⅱ-Ⅳ and Ⅲ/Ⅳ acute GVHD in long-term and short-term group was 32.2% (64/199) versus 20.7% (62/299)( P=0.005) and 10.1% (20/199) versus 8.0% (24/299) ( P=0.427), respectively. Donor sex (female as reference) and duration of MMF prophylaxis (short-term group as reference) were associated with grade Ⅱ-Ⅳ acute GVHD [ HR=1.908(95% CI 1.079-3.373),1.752(95% CI 1.161-2.643); P=0.026 and 0.008, respectively].There were no statistical differences in the incidence of CMV viremia, refractory CMV viremia and hemorrhagic cystitis (all P＞0.05) between the two groups. Conclusion:Short-term use of MMF can reduce EBV viremia without increasing the development of acute GVHD in haplo-HSCT patients.
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Objective:To investigate the incidences and risk factors of poor hematopoietic reconstitution (PHR) in patients with hematological diseases who underwent haploidentical allograft and were treated with rituximab for desensitization.Methods:Eight-three donor specific anti-HLA antibody (DSA, 2000 ≤MFI<10 000) positive patients who underwent haploidentical allograft were prospectively enrolled. Rituximab (375 mg/m 2) was used for desensitization day-3 of conditioning regimen. Incidence and factors associated with PHR, including primary poor graft function and prolonged thrombocytopenia, were investigated. Results:There were 22 males and 61 females with a median age of 39(range: 1-65) years. Kaplan-Meier analysis showed that the 100 day cumulative incidences of neutrophil and platelet engraftment were 93.0% and 90.7%, respectively. The incidences of PHR were 14.7%. The 3-year relapse rate, non-relapse mortality (NRM) rate, event-free survival (EFS), leukemia-free survival (DFS) and overall survival (OS) were 6.5%, 15.1%, 70.8%, 79.4% and 79.4%, respectively. Patients with DSA MFI<5 000 (group A, n=46) experienced lower PHR (4.4% vs. 27.5%, P=0.003), and higher 3-year EFS (79.5% vs. 59.8%, P=0.020) compared to those with DSA MFI≥5 000 (group B, n=37). Multivariate analysis showed that DSA MFI≥5 000 was correlated with PHR ( HR=6.101, P=0.021). PHR was associated with higher NRM ( HR=4.110, P=0.026), lower DFS ( HR=3.656, P=0.019) and OS ( HR=3.656, P=0.019). Conclusion:Our data suggest that high pre-transplant DSA level is a risk factor for PHR in patients with hematological diseases receiving haploidentical allograft and rituximab for desensitization.
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Objective:Donor cytomegalovirus (CMV) serological negative status may have an adverse effect on the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT), while there is inadequate data for Chinese people. This study is to explore the impact of donor CMV serological status on the outcome of CMV seropositive patients receiving allo-HSCT.Methods:Our study retrospectively analyzed 16 CMV seropositive patients with hematological malignancies receiving allogeneic grafts from CMV seronegative donors (antibody IgG negative) at Peking University People′s Hospital from March 2013 to March 2020, which was defined as D -/R + group. The other 64 CMV seropositive patients receiving grafts from CMV seropositive donors at the same period of time were selected as matched controls through a propensity score with 1∶4 depending on age, disease state and donor-recipient relationship (D +/R + group). Results:Patients in D -/R + group developed CMV DNAemia later than patients in the D +/R + group (+37 days vs. +31 days after allo-HSCT, P=0.011), but the duration of CMV DNAemia in D -/R + group was longer than that of D +/R + group (99 days vs. 34 days, P=0.012). The rate of CMV reactivation 4 times or more in D -/R + group was 4/16, significantly higher than that of D +/R + group (4.7%, 3/64, P=0.01). The incidences of refractory CMV DNAemia (14/16 vs. 56.3%, P=0.021) and CMV disease (4/16 vs. 4.7%, P=0.01) in D -/R + group were both higher than those in D +/R + group. In addition, the application of CMV-CTL as the second-line antiviral treatment in D -/R + group was more than that in D +/R + group. Univariate analysis and multivariate analysis suggested that CMV serological negativity is an independent risk factor for refractory CMV DNAemia and the duration of CMV infection. The cumulative incidence of aGVHDⅡ-Ⅳ, cGVHD, 3-year probability of NRM, overall survival, and the cumulative incidence of relapse were all comparable in two groups. Conclusions:Although there is no significant effect on OS and NRM, the incidence of refractory CMV DNAemia, the frequency of virus reactivation, and the development of CMV disease in D -/R + group are higher than those in controls. Therefore, CMV seropositive donors are preferred for CMV seropositive patients.
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Objective:To explore the method of establishing a modified demyelination and myelination regeneration model induced by dicyclohexanone oxalyl dihydrazone (CPZ) in mice with multiple sclerosis (MS), and to analyze the image markers of demyelination and myelination regeneration in mouse MS model.Methods:After the intragastrically administered with sodium carboxymethyl cellulose (CMCNa) for one week, a total of 30 C57BL/6 male mice were randomly divided into the control group ( n=10), the demyelination group ( n=10), and the remyelination group ( n=10). The mice of the control group were immediately performed MR scanning and pathological specimen obtaining; the mice in the demyelination group were administered with intragastrical CPZ-CMCNa once a day for 6 weeks for inducing demyelination, then received MR scanning and specimen obtaining with the same protocols used in control group; the mice in the remyelination group were administered with intragastrical CPZ-CMCNa once a day for six weeks for demyelination, then CPZ was withdrawn and normal diet was given for another four weeks. Then MR scanning and specimen obtaining were performed with the same protocols used in the other two groups. Regions of interest (ROIs) were set at the rostrum of corpus callosum (rCC), the bilateral normal appearing white matters (NAWM) of the rostrum of corpus callosum, and the bilateral cerebral cortex (Cx). The normalized T 2WI (T 2-normalized), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were compared among the three groups by one-way ANOVA. Results:The demyelination and remyelination mice model of MS were successfully established. The T 2-normalized values of rCC in control group, demyelination group and remyelination group were 0.47±0.03, 0.72±0.04, 0.54±0.04, respectively, with statistically significant difference found ( F=90.511, P<0.05). Post-hoc multiple comparisons showed significant differences among those groups ( P<0.05). There was no significant difference of T 2-normalized value in NAWM and Cx among the three groups ( P>0.05). Moreover, there were significant differences in the FA values (0.36±0.04, 0.29±0.03, and 0.32±0.05), the MD values [(0.572±0.015), (0.598±0.034), and (0.626±0.043)×10 -3 mm 2/s], the AD values [(0.79±0.04), (0.77±0.06), and (0.83±0.04)×10 -3 mm 2/s], and the RD values [(0.46±0.02), (0.51±0.03), and (0.53±0.05)×10 -3 mm 2/s] of rCC of the control group, the demyelination group, and the remyelination group (all P<0.05). Significant difference was found in FA values between the demyelination group and the control group ( P<0.05), and in MD values between the remyelination group and the control group ( P<0.05), as well as in AD values between the remyelination group and the demyelination group ( P<0.05). There were also significant differences in RD values between the remyelination group and the control group, and the demyelination group and the control group (all P<0.05). However, no significant difference was found in all diffusion tensor imaging (DTI) metrics of NAWM and Cx among the three groups (all P>0.05). The LFB-eosin staining showed that the myelin sheath of rCC was lost in the demyelination group, and the rCC was partially regenerated and repaired in the remyelination group. Conclusion:The modified CPZ-CMCNa model can selectively induce demyelination and remyelination of rCC, and the changes of demyelination and remyelination of rCC in the modified CPZ-CMCNa model can be quantitatively detected by T 2WI combined with DTI, which might provide related theoretical basis for the study on dynamic changes of MS lesions.
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Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale finger-printing method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM tech-nique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.
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Objective:To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA) - associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery.Methods:Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time>183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results:Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P<0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P<0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis ( HR=5.253, 95% CI 1.757-15.702, P=0.003). Conclusions:PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.
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Objective:To evaluate the protective effect of exogenous biliverdin on ultraviolet B (UVB) -induced photodamage to keratinocytes, and to explore its mechanisms.Methods:HaCaT cells were divided into 5 groups: UVB group irradiated with 30 mJ/cm 2 UVB alone, 0.1-, 1- and 10-μmol/L UVB groups treated with 0.1, 1 and 10 μmol/L biliverdin respectively and irradiated with 30 mJ/cm 2 UVB, and control group receiving no treatment. After irradiation, cells in the above groups continued to be cultured for 24 hours. Then, the reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected in HaCaT cells, and enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of the inflammatory factors interleukin 6 (IL-6) and IL-8 in the culture supernatants of HaCaT cells. One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference (LSD) - t test was used for multiple comparisons. Results:Significant differences were observed among the UVB group, 0.1-, 1- and 10-μmol/L UVB groups and control group in the ROS levels (3 613.33 ± 206.61, 2 958.67 ± 193.87, 2 678.33 ± 178.24, 2 274.67 ± 118.81, 1 905.67 ± 250.25, respectively, F = 34.02, P < 0.05), SOD activity (24.41 ± 1.78, 28.96 ± 2.21, 29.75 ± 1.75, 30.19 ± 2.29, 37.52 ± 2.31, respectively, F = 57.36, P < 0.05), MDA contents (5.61 ± 0.32, 5.46 ± 0.55, 4.65 ± 0.22, 2.55 ± 0.93, 1.31 ± 0.05, respectively, F = 214.09, P < 0.05), and supernatant levels of IL-6 ( F = 29.73, P < 0.05) and IL-8 ( F = 11.40, P < 0.05). The UVB group showed significantly increased levels of ROS, IL-6 and IL-8, and MDA contents compared with the other 4 groups (all P < 0.05), but significantly decreased SOD activity compared with the other 4 groups ( P < 0.05) . Conclusion:Exogenous biliverdin has some protective effect on UVB-induced photodamage, likely by reducing oxidative damage to cells, attenuating inflammatory reactions and suppressing lipid peroxidation.