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1.
JCI Insight ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34990406

RESUMO

Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Several investigators have reported that adaptive NKG2C+ NK cells persistently expand during CMV reactivation. In our study, two cohorts were enrolled to explored the relationships among the NKG2C genotype, NKG2C+ NK cell reconstitution, and CMV infection. Multivariate analysis showed that donor NKG2C gene deletion was an independent prognostic factor for CMV reactivation and refractory CMV reactivation. Furthermore, the quantitative, qualitative reconstitution and anti-CMV function of adaptive NKG2C+ NK cells after transplantation was significantly lower in patients grafted with NKG2Cwt/del donor cells than in those grafted with NKG2Cwt/wt donor cells. The quantitative reconstitution of NKG2C+ NK cells at day 30 after transplantation was significantly lower in patients with treatment-refractory CMV reactivation than in those in the no-CMV-reactivation and CMV-reactivation groups. In humanized CMV-infected mice, we found that compared with those from NKG2Cwt/del donors, adaptive NKG2C+ NK cells from NKG2Cwt/wt donors induced earlier and stronger expansion of NKG2C+ NK cells and earlier and stronger CMV clearance in vivo. In conclusion, donor NKG2C homozygosity contributes to CMV clearance by promoting the quantitative and qualitative reconstruction of adaptive NKG2C+ NK cells after haploidentical allo-HSCT.

2.
Br J Haematol ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741461

RESUMO

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.

3.
Huan Jing Ke Xue ; 42(11): 5210-5219, 2021 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-34708960

RESUMO

Real-time BTEX(including benzene, toluene, ethylbenzene, m-, p-, and o-xylenes) were measured continuously in Tianjin urban site in July 2019 and January 2020 using a Syntech Spectras GC955 analyzer. The BTEX concentration levels, composition, and evolutionary mechanisms during typical pollution episodes were investigated. The potential sources of BTEX were analyzed qualitatively using the diagnostic ratios method. Finally, the BTEX health risk was evaluated by using the human exposure analysis and evaluation method according to US EPA. The averaged total mixing ratio of BTEX were 1.32×10-9 and 4.83×10-9 during ozone pollution and haze episodes, respectively. Benzene was the most abundant species, followed by toluene. The mixing ratio of BTEX was largely affected by short southwestern distance transportation in January, while local emissions in July. In addition, the BTEX mixing ratio depended on the influence of temperature and relative humidity(RH) in July, while the concentration was more sensitive to changes in RH when the temperature was low in January. Diagnostic ratios and source implications suggested that the BTEX was affected mainly by biomass/biofuel/coal burning during haze episodes. The traffic related emissions also had an impact except for the influence of biomass/biofuel/coal burning in July. The averaged hazard quotient(HQ) values were 0.072 and 0.29 during ozone pollution and haze episodes, respectively, which were in the upper safety range limit recommended by the US EPA. The carcinogenic risk posed by benzene in both cleaning and pollution processes was higher than the safety threshold set by the US EPA, which should be monitored carefully.


Assuntos
Poluentes Atmosféricos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Benzeno/análise , Benzeno/toxicidade , Derivados de Benzeno/análise , Derivados de Benzeno/toxicidade , Monitoramento Ambiental , Humanos , Medição de Risco , Tolueno/análise , Tolueno/toxicidade , Xilenos
5.
Huan Jing Ke Xue ; 42(10): 4660-4668, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581108

RESUMO

Under certain terrain and weather conditions, mountain-valley circulation is one of the main meteorological factors affecting aerosol pollution in plain-mountain area. Based on environmental monitoring data and multi-source meteorological data for the Beijing-Tianjin-Hebei region between 2015 and 2019, the characteristics, similarities, and differences of mountain-valley winds in the Beijing Plain and Yanhuai Basin regions were compared. The results show that the mountain-valley winds recorded at the Beijing Observatory are from southwest to northeast compared to from the southeast to northeast at Yanqing station. With the aggravation of pollution levels, the mountain-valley wind intensity decreased by 17.7%-32.4%. When the wind speed at Beijing Observatory was 2-6 m·s-1, the maximum PM2.5 concentration in southeast was 83 µg·m-3, which was higher than in the southwest. When the wind speed at the Yanqing station was 2-6 m·s-1, the PM2.5 concentrations in SE-SSE area was 20-40 µg·m-3 higher than in other directions, and the concentrations in the valley winds were 10-12 µg·m-3 higher than the average value for the last five years. Taking the typical heavy pollution event on March 5-8, 2015, as an example, the influence of mountain-valley winds is mainly reflected in the high humidity and regional transmission of southeast winds during the valley wind stage. The PM2.5 concentrations at the Yanqing station increased by 100-130 µg·m-3 during the valley wind stage on March 6 and 7, 2015. The inversion temperature developed to 1000 m during the mountain wind stage, the local dew point at the Beijing Observatory and the Yanqing station rose by approximately 18℃. The peak dew point at the Yanqing station occurring 2 hours after the Beijing Observatory, and the concentrations of PM2.5 rose slightly under high humidity conditions. Meanwhile, the thermal gradient between the 400-m-high Yanqing Station and Yudu Mountain gradually decreased, and the mountain-valley wind decreased by 8% and 6%, respectively. The weakening of local circulation may be related to the bidirectional feedback mechanism of the boundary layer and high concentrations of aerosols.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano , Tempo (Meteorologia) , Vento
6.
Huan Jing Ke Xue ; 42(7): 3118-3126, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212637

RESUMO

Ozone pollution has recently become a severe air quality issue in the Beijing-Tianjin-Hebei region. Due to the lack of a precursor emission inventory and complexity of physical and chemical mechanism of ozone generation, numerical modeling still exhibits significant deviations in ozone forecasting. Owing to its simplicity and low calculation costs, the time series analysis model can be effectively applied for ozone pollution forecasting. We conducted a time series analysis of ozone concentration at Shangdianzi, Baoding, and Tianjin sites. Both seasonal and dynamic ARIMA models were established to perform mid- and long-term ozone forecasting. The correlation coefficient R between the predicted and observed value can reach 0.951, and the RMSE is only 10.2 µg·m-3 for the monthly average ozone prediction by the seasonal ARIMA model. The correlation coefficient R between the predicted and observed value increased from 0.296-0.455 to 0.670-0.748, and RMSE was effectively reduced for the 8-hour ozone average predicted by the dynamic ARIMA model.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Pequim , China , Monitoramento Ambiental , Previsões , Modelos Estatísticos , Ozônio/análise
7.
Transplant Cell Ther ; 27(10): 870.e1-870.e7, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34229053

RESUMO

Late-onset severe pneumonia (LOSP) is defined as severe pneumonia developing during the late phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because of the high mortality in patients with LOSP, it is important to identify prognostic factors. In this study, we aimed to develop a risk score system with broad applicability that can help predict the risk of LOSP-associated mortality. We retrospectively analyzed 100 patients with LOSP after allo-HSCT between June 2009 and July 2017. The assessment variables included immune, nutritional, and metabolic parameters at the onset of LOSP. Of these 100 patients, 45 (45%) eventually died, and 55 (55%) were positive for organisms, most commonly viruses. In the multivariate analysis, higher monocyte count (≥0.20 × 109/L versus <0.20 × 109/L; P = .001), higher albumin level (≥30.5 g/L versus <30.5 g/L; P = .044), lower lactic dehydrogenase level (<250 U/L versus ≥250 U/L; P = .008) and lower blood urea nitrogen concentration (<7.2 mmol/L versus ≥7.2 mmol/L; P = .026) at the onset of LOSP were significantly associated with better 60-day survival. A risk score system based on the foregoing results showed that the probability of 60-day survival decreased with increasing risk factors, from 96.3% in the low-risk group to 49.1% in the intermediate-risk group and 12.5% in the high-risk group. Our results indicate that this scoring system using 4 variables can stratify patients with different probabilities of survival after LOSP, which suggests that patients' immune, nutritional, and metabolic status are crucial factors in determining outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumonia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumonia/diagnóstico , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
8.
Front Med (Lausanne) ; 8: 604085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34150785

RESUMO

Graft failure (GF) is a fatal complication of allogeneic stem cell transplantation, especially after haploidentical transplantation. The mortality of GF is nearly 100% without an effective salvage method. A second transplantation is usually necessary to save the patient's life. However, there is no standardized regimen, and the outcome is usually disappointing. We report on a prospective single-center study using a reduced-intensity conditioning regimen with different haploidentical donors (HIDs). Patients with GF after the first transplantation were enrolled in a prospective single-arm clinical trial (ClinicalTrials.Gov ID: NCT03717545) at the Peking University Institute of Hematology. The conditioning regimen consisted of fludarabine (30 mg/m2) (days-6 to-2) and cyclophosphamide (1,000 mg/m2/day) (days-5 to-4). Patients underwent a second transplant from a different HID using a granulocyte colony-stimulating factor primed bone marrow and peripheral blood stem cells. The primary outcome was neutrophil engraftment at day 28. The secondary outcomes included platelet engraftment at day 100, transplant-related mortality (TRM) at day 30, TRM at day 100, and overall survival (OS) at 1 year. From March 2018 to June 2020, 13 patients were enrolled in this clinical trial. Of the 13 patients, five had acute myeloid leukemia, five had acute lymphoblastic leukemia, two had myelodysplastic syndromes, and one had a non-Hodgkin lymphoma. The median age at first transplantation was 38 years (range, 8-55 years). As for the first transplantation, 11 patients underwent haploidentical transplantations and two underwent unrelated donor transplantations. At the time of GF, three patients had complete donor chimerism, five had mixed chimerism, and five had complete recipient chimerism. The median time from the first transplantation to the second transplantation was 49 (range 35-120) days. The medians of infused cell doses were as follows: mononuclear cells 7.93 (5.95-12.51) × 108/kg and CD34 + cells 2.28 (0.75-5.57) × 106/kg. All 13 patients achieved neutrophil engraftment after the second transplantation, with a median engraftment time of 11 (range 10-20) days after transplantation. The platelet engraftment rate on day 100 after transplantation was 76.9%. The TRMs at day 30, day 100, and 1-year were 0, 0, and 23.1%, respectively. The OS and disease-free survival at 1-year were 56.6 and 48.4%, respectively. For patients with GF after first transplantation, a second transplantation using a fludarabine/cyclophosphamide regimen from a different HID was a promising salvage option. Further investigation is needed to confirm the suitability of this method.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(3): 271-278, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33691921

RESUMO

OBJECTIVE: To study the clinical features and prognosis of childhood acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). METHODS: A retrospective analysis was performed on the medical data of 14 children who were diagnosed with AML-MRC from June 2014 to March 2020, including clinical features, laboratory examination results, and prognosis. RESULTS: Among the 14 children with AML-MRC, there were 9 boys and 5 girls, with a median age of 11 years (range: 1-17 years), a median leukocyte count of 8.3×109/L [range: (2.0-191.0)×109/L], a median hemoglobin level of 73 g/L (range: 44-86 g/L), and a median platelet count of 75×109/L [range: (4-213)×109/L] at diagnosis. According to the FAB classification, the children with AML-M5 accounted for 71% (10/14). Among the 14 children, 4 had multi-lineage dysplasia (MLD), 2 had a history of myelodysplastic syndrome (MDS), 5 had MDS-related cytogenetic changes, 2 had MLD with MDS-related cytogenetic changes, and 1 had a history of MDS with MLD. The median follow-up time was 10.6 months (range: 0.4-54.4 months) for 14 children, among whom 2 gave up treatment immediately after diagnosis and 12 had an evaluable treatment outcome. The 2-year overall survival (OS) rate was 50%±15%, and the 2-year disease-free survival (DFS) rate was 33%±13%. Of the 12 children, 7 underwent haploidentical hematopoietic stem cell transplantation (HSCT), among whom 5 achieved DFS and 2 died, with a 2-year OS rate of 71%±17% and a 2-year DFS rate of 43%±19%; 5 children underwent chemotherapy alone, among whom 1 achieved DFS, 3 died, and 1 was lost to follow-up, with a 2-year OS rate of 40%±30% and a 2-year DFS rate of 30%±24%. There was no significant difference in the survival condition between the transplantation and chemotherapy groups (P > 0.05). CONCLUSIONS: Childhood AML-MRC is often observed in boys, and AML-M5 is the most common type based on FAB classification. Such children tend to have a poor prognosis. HSCT is expected to improve the poor prognosis of children with AML-MRC. However due to the small number of cases, it is necessary to increase the number of cases for further observation.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Masculino , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Prognóstico , Estudos Retrospectivos
10.
Front Oncol ; 11: 639502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718234

RESUMO

Objective: Haploidentical stem cell transplantation (haplo-SCT) has demonstrated encouraging results in younger patients. There is also an increasing need for haplo-SCT in older patients. However, the high risk of treatment-related mortality (TRM) in older patients is still a major concern. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-SCT in older patients. Method: This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia or MDS; (2) without MSD and MUD, and with HID available; and (3) age ≥55 years. The Bu/Flu/Cy/ATG regimen consisted of the following agents: Ara-C (2 g/m2/day, injected i.v.) on days-10 and-9; BU (9.6 mg/kg, injected i.v. in 12 doses) on days-8,-7, and-6; Flu (30 mg/m2/day, injected i.v.) from day-6 to day-2; Cy (1 g/m2/day, injected i.v.) on days-5 and-4; semustine (250 mg/m2, orally) on day-3 and antithymocyte globulin (ATG) [2.5 mg/kg/day, rabbit, SangStat (Lyon, France)] on days-5,-4,-3, and-2. The primary endpoint was 1-year TRM. Results: From April 1, 2018 to April 10, 2020, a total of 50 patients were enrolled. All patients achieved neutrophil engraftment with complete donor chimerism. The cumulative incidence of grade 2-4 aGVHD at day-100 was 22.0%. The cumulative incidences of CMV viremia and EBV viremia on day 100 were 68.0 and 20.0%, respectively. The cumulative incidence of TRM at 1-year was 23.3%. and the cumulative incidence of relapse (CIR) at 1 year after transplantation was 16.5%. The overall survival (OS) and leukemia-free survival (LFS) at 1 year were 63.5 and 60.2%, respectively. The outcomes were also comparable with patients who received Bu/Cy/ATG regimen using a propensity score matching method. Conclusions: In conclusion, this study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for older patients. The study was registered as a clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03412409.

11.
Ann Hematol ; 100(3): 799-808, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33416901

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as a potential strategy for myeloid sarcoma (MS). The previous reports focused mainly on matched sibling donor (MSD) or matched unrelated donor (MUD) transplantation. There are no reports on haploidentical HSCT (haplo-HSCT) in MS. We retrospectively reviewed 14 MS patients who underwent haplo-HSCT. All patients achieved complete donor engraftment. The median time for neutrophil engraftment and platelet engraftment were 10 (12-21) days and 18 (8-31) days. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) and 3-year cumulative incidence of chronic GVHD were 37.7% (95%CI, 23.2-52.1%) and 35.7% (95%CI, 22.2-49.2%). Cytomegalovirus (CMV) reactivation was documented in 86% patients, and only one patient developed CMV pneumonia. Treatment-related mortality occurred in one (7%) patient. The 1- and 3-year cumulative incidence of relapse was 21.4% (95%CI, 11.8-31.1%) and 35.7% (95%CI, 22.4-49.0%). The probability of overall survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 64.3% (95%CI, 43.5-95.0%), respectively. The probability of disease-free survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 57.1% (95%CI, 36.3-89.9%), respectively. In conclusion, haplo-HSCT is a feasible method for patients with MS who have no MSD or MUD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Sarcoma Mieloide/terapia , Transplante Haploidêntico , Adolescente , Adulto , Quimioprevenção , Criança , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/epidemiologia , Sarcoma Mieloide/mortalidade , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
12.
Reprod Toxicol ; 100: 1-6, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33338580

RESUMO

Human sperm nucleus contains diverse RNA populations. This study aimed to screen and identify host microRNAs (miRs) that regulate gene expression of hepatitis B virus (HBV) during transmission from patients' sperm to sperm-derived embryos. Using microarrays, 336 miRs were found to be differentially expressed. After validation using real-time quantitative RT-PCR (RT-qPCR), four miRs were selected as targets. Using RT-qPCR and enzyme-linked immunosorbent assays, when patients' sperm were treated with mimics (or inhibitors) specific for hsa-miR-19a-3p and hsa-miR-29c-3p, the S gene transcription in sperm and translation in sperm-derived embryos was downregulated (or upregulated). There were significant differences in transcriptional and translational levels of the S gene between the test and control groups. These findings suggest that hsa-miR-19a-3p and hsa-miR-29c-3p significantly suppressed expression of the S gene, offering potential therapeutic targets for treating patients with HBV infection, and further reducing the negative impact of HBV infection on sperm fertilizing capacity.


Assuntos
Embrião de Mamíferos/virologia , Regulação Viral da Expressão Gênica/genética , Vírus da Hepatite B/genética , Hepatite B/transmissão , MicroRNAs/genética , Espermatozoides/virologia , Adulto , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , MicroRNAs/fisiologia , Reprodutibilidade dos Testes
13.
Transpl Infect Dis ; 23(3): e13544, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33326670

RESUMO

BACKGROUND: Human herpesvirus 6 (HHV-6) reactivation is relatively common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the incidence of HHV-6 reactivation and the clinical outcomes following unmanipulated haploidentical HSCT (haplo-HSCT) remain unknown. METHOD: We prospectively monitored blood HHV-6 DNA using real-time quantitative polymerase chain reaction weekly until day 100 post unmanipulated haplo-HSCT in patients with hematological malignancies. RESULTS: From November 2016 to March 2017, 102 patients (58 male and 44 female, median age 25(2-58) years old) were enrolled. Within 100 days post-transplantation, 27 patients (27/136, 19.9%) developed HHV-6 viremia with a median onset time of 14 (7-98) days. The cumulative incidence of HHV-6 reactivation on day 100 post-HSCT was 25.5 ± 4.3% in haplo-HSCT. The median HHV-6 copy number was 1.45 × 103 (5.48 × 102 -2.00 × 104 ) copies/ml. The HHV-6 viremia duration time was 7 days in 23 patients, 14 days in one patient and 21 days in one patient. In multivariate analysis, prior HHV-6 reactivation was an independent risk factor for grade 2-4 graft-versus-host disease (GVHD). But it did not influence the overall survival (OS)(HR 1.624, 95%CI 0.768-3.432, P = .204), disease-free survival (DFS) (HR 1.640, 95%CI 0.799-3.367, P = .177) and non-relapse mortality (NRM) (HR 1.644, 95%CI 0.670-4.038, P = .278). CONCLUSION: The reactivation of HHV-6 after unmanipulated haploidentical transplantation predicts the occurrence of grade 2-4 a-GVHD, but it may not influence the overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM).


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Infecções por Roseolovirus , Ativação Viral , Adulto Jovem
14.
Andrology ; 9(3): 944-955, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33382193

RESUMO

BACKGROUND: Hepatitis B virus (HBV) was found to exist in semen and male germ cells of patients with chronic HBV infection. Our previous studies demonstrated that HBV surface protein (HBs) could induce sperm dysfunction by activating a calcium signaling cascade and triggering caspase-dependent apoptosis. However, the relationship between sperm dysfunction caused by HBs and caspase-independent apoptosis has not been investigated. OBJECTIVES: To evaluate the effects of HBs exposure on sperm dysfunction by activating caspase-independent apoptosis. MATERIALS AND METHODS: Spermatozoa were exposed to HBs at concentrations of 0, 25, 50, and 100 µg/mL for 3 h. Flow cytometry, qRT-PCR, immunofluorescence assay, ELISA, and zona-free hamster oocyte penetration assays were performed. RESULTS: With increasing concentrations of HBs, various parameters of the spermatozoa changed. The number of Bcl2-positive cells declined and that of both Bax-positive cells and Apaf-1-positive cells increased. The transcription level of Bcl2 increased and that of both Bax and Apaf-1 declined. The average levels of AIF and Endo G declined in mitochondria and increased in the cytoplasm and nucleus. The sperm DNA fragmentation index increased. The mean percentages of live spermatozoa declined and that of both injured and dead spermatozoa increased; and the sperm penetration rate declined. For the aforementioned parameters, the differences between the test and the control groups were statistically significant. CONCLUSION: HBs exposure can activate the Bax/Bcl2 signaling cascade that triggers AIF/Endo G-mediated apoptosis, resulting in sperm DNA fragmentation, sperm injury, and death, and a decrease in the sperm fertilizing capacity. This new knowledge will help to evaluate the negative impact of HBV on male fertility in HBV-infected patients.

15.
Clin Transplant ; 35(2): e14160, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33222318

RESUMO

OBJECTIVES: The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. METHODS: A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. RESULTS: Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort. CONCLUSIONS: Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.


Assuntos
Anemia Aplástica , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Quimerismo , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Fatores de Proteção , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do Tratamento
16.
Ying Yong Sheng Tai Xue Bao ; 31(11): 3814-3822, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33300732

RESUMO

During atmospheric precipitation, the evaporation of raindrops falling from the bottom of cloud layer to the ground and passing through unsaturated air, a process was called sub-cloud secondary evaporation, which will change the isotopic composition of precipitation. Using the hydrogen and oxygen stable isotope method to understand the temporal and spatial variation of secondary evaporation effect under clouds and its causes is important to understand regional water cycle process. Based on hourly meteorological data of 187 meteorological stations in Shaanxi-Gansu-Ningxia region from March 2018 to February 2019, the spatial and temporal variations of evaporation surplus ratio (f) and precipitation excess deuterium variation (Δd) were analyzed using the improved Ste-wart model, and the relationships between f and meteorological elements and Δd were examined. The results showed that, at the hourly scale, the minimum values of f and Δd in all provinces of the region appeared in the daytime, and the maximum values appeared in the night, indicating that the secondary evaporation effect under the cloud was more obvious in the daytime. At the monthly scale, the monthly variation trend of f and Δd in each province was relatively consistent, with the minimum value appearing in the summer half year, and the maximum value appearing in the winter half year, indicating that the second evaporation effect under cloud was more significant in the summer half year. From the spatial perspective, the spatial variation of f and Δd values in the region was consistent with that at the seasonal scale. In spring, the eastern and western regions were larger while the central part was smaller. In summer, the northwest region was smaller, and other regions were larger. In autumn, it decreased from south to north. In winter, the central and southern regions were smaller, and the western and northeast regions were larger. The spatial differences of secondary evaporation effects under clouds in different seasons was significant. The slopes of the linear relationship between f and Δd in Shaanxi, Gansu and Ningxia provinces were all less than 1‰·%-1, which may be caused by the arid and semi-arid climate in this area. When air temperature was higher and the relative humidity, vapor pressure, precipitation and raindrop diameter were smaller, the value of Δd was smaller, and the secondary evaporation effect under the cloud was more obvious.


Assuntos
Monitoramento Ambiental , Chuva , China , Isótopos de Oxigênio/análise , Estações do Ano
17.
Huan Jing Ke Xue ; 41(9): 3993-4002, 2020 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-33124279

RESUMO

To better understand the isotope variations on a short time scale, this study focused on a long-term rainfall event with light precipitation (June 26-27) and a short-term one with heavy precipitation (July 28) in Lanzhou City in the summer of 2019. Combined with HYSPLIT model, samples collected during a continuous precipitation event every 10 min and 30 min were analyzed to explore the characteristics and mechanism of stable hydrogen and oxygen isotopes in precipitation. The results indicate that the effect of sub-cloud secondary evaporation makes the slope of the sequential meteoric water line (SMWL) smaller at the beginning of the rainfall event. Most of the continuous sampling points are distributed above the global meteoric water line (GMWL) and local meteoric water line (LMWL). Moreover, the deuterium excess is larger than the local average annual deuterium (8.13), indicating that the samples have experienced moisture recycling to a certain extent. During two consecutive days (June 26-27) of rainfall, the variations in oxygen isotope δ18O did not follow the effect of precipitation amount; the precipitation δ18O of the first day was "L" shaped, and it fluctuated the next day. On July 28, δ18O steadily decreased, and the range of δ18O exceeded 9‰. On June 26, the moisture transport path was short at the height of 500 m and on June 27 local evaporation was the main pathway. On July 28, with a relatively stable air mass, the moisture source of the entire precipitation event did not change significantly, neither did the isotope value. Therefore, for a single precipitation event on a short time scale, the difference in moisture sources is one of the reasons for isotope variations.


Assuntos
Monitoramento Ambiental , Chuva , Hidrogênio/análise , Isótopos de Oxigênio/análise , Estações do Ano , Água
19.
Huan Jing Ke Xue ; 41(6): 2586-2595, 2020 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608772

RESUMO

As important precursors of near-surface ozone, secondary organic aerosols (SOAs), and volatile organic compounds (VOCs) play an important role in photochemical reactions and fine particle formation. In this study, real-time VOCs were measured continuously by Syntech Spectras GC955 analyzers at the regional background site of the North China Plain from September 1 to 27, 2017. The VOC concentration levels, compositions, spatiotemporal variations, and the ozone formation potential during the observation period were investigated. The potential sources of initial VOCs indicated from the diagnostic ratios were further studied. The averaged total mixing ratio of VOCs was 12.53×10-9. Among all measured VOC species, alkanes were the most abundant species, which accounted for 65.3% of the total concentrations, followed by alkenes (26.7%) and aromatics (6.5%). In addition, the total OH radical loss rate of VOCs (L·OH) was 5.2 s-1. In particular, the contribution of C4-C5 alkenes to L·OH was as high as 61%, followed by C2-C3 alkenes, with a 12.8% contribution of L·OH. The average ozone formation potential of VOCs was 36.5×10-9. Among all the measured VOC species, alkenes were the most abundant species, which accounted for 71.2%. Among alkenes, the contribution of C4-C5 alkenes was the most prominent. Although the concentration of alkanes in Shangdianzi was much higher than other VOC species, the ozone formation potential was lower. Diagnostic ratios and source implications suggested that Shangdianzi was affected mainly by biomass/biofuel/coal burning, with substantially elevated benzene levels during the observation period, whereas a slight influence of traffic-related emissions was observed.

20.
Bone Marrow Transplant ; 55(6): 1147-1160, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31992849

RESUMO

This study investigated the epidemiological characteristics of cytomegalovirus retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (HSCT). We studied a cohort of 1466 consecutive patients who had undergone haploidentical HSCT between 2013 and 2017. We documented 34 episodes of CMVR in 31 patients, with a median onset of 167 days after the transplant. The cumulative incidence of CMVR was 2.3% 1 year after the transplant. Multivariate analysis suggested that platelet engraft failure at 100 days, EBV DNAemia, refractory or recurrent CMV DNAemia, and acute graft-versus-host disease were related to the development of CMVR in patients with CMV DNAemia. Patients with ≥3 risk factors (high risk) had a higher 1-year incidence of CMVR than patients with ≤2 risk factors (low risk) (26.2% vs. 0.6%, P < 0.001). In patients with CMVR, visual acuity (VA) improved in 16 episodes, remained stable in 10 episodes, and worsened in 8 episodes. The variable related to the improvement of VA was VA ≥ 0.1 at time of CMVR diagnosis. Our study showed that CMVR was a rare complication after haploidentical HSCT but that the risk was greater in patients with multiple risk factors.


Assuntos
Retinite por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Retinite por Citomegalovirus/epidemiologia , Retinite por Citomegalovirus/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco
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