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1.
Leukemia ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824464

RESUMO

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.

2.
Transplant Cell Ther ; 27(3): 253.e1-253.e9, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33781524

RESUMO

Acute cholecystitis (AC) is a potentially fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, only limited information is available on its clinical features, outcomes, and risk management strategies. This retrospective, nested, case-control study included 6701 patients undergoing allo-HSCT at our center from January 2004 to June 2019. In total, 72 patients (1.1%) were diagnosed with AC; among these, acute acalculous cholecystitis had a slightly higher prevalence (42 patients, 58.3%). Patients with moderate and severe AC exhibited remarkably worse overall survival (P = .001) and non-relapse mortality (P = .011) than others. Survival of haploidentical HSCT recipients with AC was comparable to that for patients with human leukocyte antigen (HLA)-identical donors. Age ≥ 18 years, antecedent stage II to IV acute graft-versus-host disease, and total parenteral nutrition were identified as potential risk factors for AC following allo-HSCT, while haploidentical transplantations were not more susceptible to AC than HLA-identical HSCT. Based on these criteria, a risk score model was developed and validated to estimate the probability of AC following allo-HSCT. The model separates all patients into low-, intermediate-, and high-risk groups and thereby provides a basis for early detection of this complication in the management of allo-HSCT.

3.
Life Sci ; 274: 119324, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33711382

RESUMO

AIMS: Intervertebral Disc Degeneration (IDD) is a key factor involved in low back pain (LBP) which affects approximately 540 million individuals worldwide. Chlorogenic Acid (CGA), a natural compound, exerts anti-inflammatory property in several diseases. Here, we aim to investigate the biological effect of CGA on IDD and explore the underlying mechanism. MATERIALS AND METHODS: Lumbar spine instability (LSI) model in mice was utilized to mimic process of IDD. The effects of CGA in response to LSI were evaluated by luminescent imaging, micro-CT, histomorphology, and immunohistochemistry in vivo. Besides, the cytotoxicity of CGA on chondrocytes was detected by cell counting kit-8 (CCK-8) and the biological effects were assessed by polymerase chain reaction (PCR) in vitro. KEY FINDINGS: We found that CGA treatment dramatically suppressed the NF-κB activity in LSI mice. Moreover, administration of CGA mitigated cartilaginous endplate degeneration and postponed IDD development accompanying a decrease of inflammatory and catabolic mediators. Specifically, CGA ameliorated endplate degeneration might be related to its protective effects against endplate chondrocytes apoptosis and trans-differentiation. We further elucidated that CGA exerted these biological effects mainly by repressing NF-κB signaling in cartilage endplate. SIGNIFICANCE: Our study has illustrated, for the first time, the curative effects as well as the latent mechanism of CGA in IDD and our results suggested that CGA administration might be used as an alternative therapy for IDD.

4.
Carbohydr Polym ; 260: 117827, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33712167

RESUMO

Alginates, a kind of naturally occurring polysaccharides, have been exploited for functional materials owing to their versatility, sustainability, nontoxicity, and relatively low cost. Inherent flame retardancy is one of the most attractive features of alginates, as it enables the high-value-added utilization of alginates for eco-friendly flame-retardant materials. Now, the influence of metal ions on the flame retardancy and pyrolysis behaviors of alginates has been systematically studied; besides, the applications of alginates for flame-retardant materials have been greatly developed, such as for preparing flame-retardant fibers, fabrics, aerogel composites, and foams, as well as serving as a component or modifier of functional coatings, hybrids, and additives. This review will give an overview of the recent progress and the prospects of using alginates in flame-retardant fields, which can guide the design of bio-based flame retardants and benefit the further development of more diverse applications of alginates.

5.
Chin Med J (Engl) ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33734137

RESUMO

BACKGROUND: For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. METHODS: A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. RESULTS: All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. CONCLUSION: This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

6.
Sci Rep ; 11(1): 4839, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649485

RESUMO

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

7.
Zhongguo Gu Shang ; 34(2): 101-7, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33665994

RESUMO

OBJECTIVE: To compare therapeutic effects of internal fixation with volar locking plate in treating extension and flexion type of distal radius fracture (DRF). METHODS: From January 2015 to June 2018, 103 patients with DRF were retrospectively analyzed. According to original fracture displacement direction, patients were divided into extension fracture(Colles) group and flexion fracture (Smith) group. In Colles fracture group, there were 24 males and 44 females aged from 20 to 79 years old with an average of (59.0±13.4) years old;according to AO classification, 9 patients of type A2, 13 patients of type A3, 16 patientsof type C1, 17 patients of type C2 and 13 patients of type C3;the time from injury to operation ranged from 2 to 9 days with an average of (3.9±0.8) days. In Smith fracture group, there were 15 males and 20 females, aged from 27 to 87 years old with an average of (60.1±15.3) years old;according to AO classification, 4 patienst of A2, 7 patients of A3, 14 patients of C1, 5 patients of C2 and 5 patients of C3;the time from injury to operation ranged from 2 to 6 days with an average of (4.1±0.9) days. Operation time, fracture healing time and postoperative complications were recorded between two groups. Disabilities of arm, shoulder and hand (DASH) score at 6 and 8 weeks, 6 and 8 months were used to evaluate functional recovery of affected limbs during each follow up. Volar tilt, radial inclination and radius height were measured at 8 months after operation. Mayo score was measured at 8 months after operation to evaluate recovery of limb function. RESULTS: All patients were followed up for 8 to 30 months with an average of (14.8±4.3) months, and no difference in follow up between two groups (P> 0.05). There were no statistical differences in operation time, fracture healing time and postoperative complications between two groups(P>0.05). DASH score at 6 and 12 weeks in Colles fracture group were (37.24±5.08) and (19.68±4.55), while in Smith fracture group were (39.05±4.79) and (23.44±4.21);Colles fracture group was better than that of Smith fracture group (P<0.001);while there were no differences in DASH score at 6 and 8 months between two groups (P>0.05). Volar tilt of Smith fracture group (11.1±3.1)° was better than that of Colles fracture group (8.6±4.1) °, and there were no significant difference in radial inclination and radius height between two groups(P>0.05). Also there was no significant difference in Mayo score between two group(P>0.05). CONCLUSION: Patients with Colles fracture and Smith fracture could receive good reduction and fixation through volar locking plate. The radiographic parameters of both groups recovered satisfactorily after operation. Recovery of volar tilt of Smith fracture group is better than that of Colles fracture group, and early recovery function of Colles fracture group is better than that of Smith group, but there is no significant difference in long-term wrist joint function and incidence of postoperative complications between two groups.


Assuntos
Fraturas do Rádio , Adulto , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas , Feminino , Fixação Interna de Fraturas , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Articulação do Punho , Adulto Jovem
8.
Zhongguo Gu Shang ; 34(3): 265-8, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787173

RESUMO

Osteoporosis is one of the common clinical orthopedic diseases, which can lead to a variety of complications. There are many pathogenic factors in this disease. The latest research found that ATP6V1H is a new gene leading to the occurrence of osteoporosis, and it is likely to become a new target for the future drug treatment of osteoporosis.This paper introduces the biological structure and characteristics of H subunit, summed up the human body caused by loss of ATP6V1H and animal models such as zebrafish, mice bone loss and osteoporosis symptom such as related research reports of the loss, from osteoclast, osteoblast and marrow stromal cell level and the connection between the various subunits further expounds the H subunit regulate bone dynamic balance of mechanism, to explore ATP6V1H in bone developmentand bone related diseases has laid a solid foundation, also provide new ideas for clinical treatment of osteoporosis.


Assuntos
Osteoporose , Peixe-Zebra , Animais , Osso e Ossos , Camundongos , Osteoblastos , Osteoclastos , Osteoporose/genética
10.
Am J Hematol ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606900

RESUMO

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

11.
J Cell Physiol ; 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33611789

RESUMO

Thrombocytopenia is a common complication of human cytomegalovirus (HCMV) infection in immunocompromised hosts, which contributes to poor prognosis even in patients receiving antiviral treatment. Here, we investigated the megakaryo/thrombopoiesis process, including the involvement of the c-Mpl/IEX-1 pathway, after HCMV infection, identified receptors mediating the interaction between megakaryocytes (MKs) and HCMV, and explored novel therapeutic targets. Our data shows that HCMV directly infects megakaryocytes in patients with HCMV DNAemia and influences megakaryopoiesis via the c-Mpl/IEX-1 pathway throughout megakaryocyte maturation, apoptosis, and platelet generation in vivo and in vitro. After treatment with inhibitors of PDGFRα and αvß3, the HCMV infection rate in MKs was significantly reduced, suggesting that IMC-3G3 and anti-αvß3 are potential therapeutic alternatives for viral infection. In summary, our study proposes a possible mechanism and potential treatments for thrombocytopenia caused by HCMV infection and other viral diseases associated with abnormal hemostasis.

12.
Am J Ind Med ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33616226

RESUMO

BACKGROUND: Healthcare workers (nurses and nursing aides) often have different exposures and injury risk factors depending on their occupational subsector and location (hospital, long-term care, or home health care). METHODS: A total of 5234 compensation claims for nurses and nursing aides who suffered injuries to their lower back, knee, and/or shoulder over a 5-year period were obtained from the Ohio Bureau of Workers' Compensation and analyzed. Injury causation data was also collected for each claim. The outcome variables included indemnity costs, medical costs, total costs, and the number of lost work days. The highest prescribed morphine equivalent dose for opioid medications was also calculated for each claim. RESULTS: Home healthcare nurses and nursing aides had the highest average total costs per claim. Hospital nurses and nursing aides had the highest total claim costs, of $5 million/year. Shoulder injuries for home healthcare nursing aides (HHNAs) had the highest average total claim costs ($20,600/injury) for all occupation, setting, and body area combinations. Opioids were most frequently prescribed for home healthcare nurses (HHNs) and nursing aides (18.9% and 17.7% having been prescribed opioids, respectively). Overexertion was the most common cause for HHN and nursing aide claims. CONCLUSIONS: With the rapidly expanding workforce in the home healthcare sector, there is a potential health crisis from the continued expansion of home healthcare worker injuries and their associated costs. In addition, the potential for opioid drug usage places these workers at risk for future dependence, overdose, and prolonged disability. Future research is needed to investigate the specific and ideally reversible causes of injury in claims categorized as caused by overexertion.

13.
Glob Health Res Policy ; 6(1): 7, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597021

RESUMO

BACKGROUND: The Regional Network for Asian Schistosomiasis and Other Helminth Zoonoses (RNAS+) was established in 1998, which has developed close partnerships with Asian countries endemic for schistosomiasis and other helminthiasis in Asia. RNAS+ has provided an ideal regional platform for policy-makers, practitioners and researchers on the prevention, control and research of parasitic diseases in Asian countries. China, one of the initiating countries, has provided significant technical and financial support to the regional network. However, its roles and contributions have not been explored so far. The purpose of this study was to assess China's contributions on the supporting of RNAS+ development. METHODS: An assessment research framework was developed to evaluate China's contributions to RNAS+ in four aspects, including capacity building, funding support, coordination, and cooperation. An anonymous web-based questionnaire was designed to acquire respondents' basic information, and information on China's contributions, challenges and recommendations for RNAS+development. Each participant scored from 0 to 10 to assess China's contribution: "0" represents no contribution, and "10" represents 100% contribution. Participants who included their e-mail address in the 2017-2019 RNAS+ annual workshops were invited to participate in the assessment. RESULTS: Of 71 participants enrolled, 41 responded to the survey. 37 (37/41, 90.24%) of them were from RNAS+ member countries, while the other 4 (4/41, 9.76%) were international observers. Most of the respondents (38/41, 92.68%) were familiar with RNAS+. Respondents reported that China's contributions mainly focused on improving capacity building, providing funding support, coordination responsibility, and joint application of cooperation programs on RNAS+ development. The average scores of China's contributions in the above four fields were 8.92, 8.64, 8.75, and 8.67, respectively, with an overall assessment score of 8.81 (10 for a maximum score). The challenge of RNAS+ included the lack of sustainable funding, skills, etc. and most participants expressed their continual need of China's support. CONCLUSIONS: This survey showed that China has played an important role in the development of RNAS+ since its establishment. This network-type organization for disease control and research can yet be regarded as a great potential pattern for China to enhance regional cooperation. These findings can be used to promote future cooperation between China and other RNAS+ member countries.

14.
Phytochemistry ; 184: 112656, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33524854

RESUMO

Three previously undescribed pyridyl-steroidal glycoalkaloids, solanindiosides A‒C, one rare 23S,26R-hydroxylated spirostanoid saponin, and two steroidal alkaloid aglycones, solanindins A and B, derived from the acid hydrolysis of solanindiosides A‒C, were isolated from the fruits of Solanum violaceum, together with five known analogues, including two rare steroidal glycosides, two lignans and a diterpene. Structurally, they comprise a 16ß-methoxy-23-deoxy-22,26-epimino-cholest-type skeleton moiety, and a 16ß-methoxy-3,23-dideoxy-22,26-epimino-cholest-3,5-dien derivative. The hitherto undescribed structures were established on the basis of extensive spectroscopic analyses. Configurations of sugar moieties were resolved by chemical derivations. Solanindiosides A‒C, (22R,23S,25R,26R)-spirost-5-ene-3ß,23,26-triol3-O-ß-d-xylopyranosyl-(1→3)-ß-d-glucopyranoside, solanindins A and B, and (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol were evaluated for their cytotoxic and antibacterial activities. (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol showed the most potent cytotoxic activity against MCF-7 cells (IC50 = 4.386 ± 0.098 µM), while solanindin B displayed some inhibitory effects against Staphylococcus aureus Rosenbach with MIC50 value of 37.32 ± 0.793 µM. In addition, (1S,2S)-1-(4-hydroxy-3-methoxyphenyl)-2-[2-methoxy-4-[(2S,3R,4R)-tetrahydro-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)-2-furanyl]phenoxy]-1,3-propanediol induced dose dependent apoptosis effect in MCF-7 cells.


Assuntos
Saponinas , Solanum , Frutas , Glicosídeos , Saponinas/farmacologia , Esteroides
15.
J Cell Mol Med ; 25(2): 1128-1139, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33459528

RESUMO

Interleukin 18 (IL-18) is a pleiotropic pro-inflammatory cytokine and is associated with arrested follicle development and anovulation which are the typical pathological changes of PCOS. Theca cells (TCs) have a key role in follicular growth and atresia. But whether IL-18 can directly affect ovarian TCs function is unknown. Therefore, the objective of this study was to determine the effect of IL-18 on proliferation and steroidogenesis of bovine TCs and to explore the biological effect of IL-18 on folliculogenesis. This work revealed that at 300-1000 pg/mL, IL-18 led to a time- and dose-dependently increase in cell proliferation (P < .05). IL-18 increased 17-hydroxyprogesterone (17OHP4) and androstenedione (A2) secretion with up-regulation of key steroidogenesis-related genes CYP11A1 and CYP17A1 (P < .05). Furthermore, our data demonstrated that the IL-18R protein is predominantly expressed in small-follicle (3-6 mm) TCs than large follicles (8-22 mm) by immunohistochemistry. We also found that the stimulation effects of IL-18 on TCs can be reversed with the addition of IL-18BP as early as at 4 hours of culture and reached the peak at 16 hours. We conclude that IL-18 appears to target TCs in bovine, and suggest an important role for this cytokine in ovarian function. Present findings further validate potential effects of IL-18 in the conditions associated with follicular dysplasia and excessive growth of ovarian TCs (such as PCOS). But additional research is needed to further understand the mechanism of action of IL-18 in theca cells as well as its precise role in folliculogenesis.

16.
Cell Mol Immunol ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33408344

RESUMO

Haploidentical stem cell transplantation (haplo-SCT) achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation (MSDT) in treating hematological malignancies. To define the underlying regulatory dynamics, we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension. First, we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility (MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo. We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden. The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor-α, interferon-γ, pore-forming proteins and CD107a secreted by T cells or natural killer cells. Furthermore, we conducted a prospective clinical trial which enrolled 135 patients with t(8;21) acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT. The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT. Ex vivo experiments showed that, 1 year after transplantation, cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period. Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.

17.
J Diabetes Complications ; 35(3): 107830, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33446411

RESUMO

AIMS: To assess the effectiveness of renin-angiotensin-aldosterone system (RAAS) inhibitors, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) separately to prevent all-cause mortality, myocardial infarction (MI), stroke and heart failure (HF) in patients with diabetes considering the number needed to treat (NNT) and minimal clinical effect (MCE). METHODS: Data from 17 morbidity-mortality trials in patients with diabetes were used to calculate NNTs and evaluate MCE to prevent all-cause mortality, myocardial infarction, stroke, and heart failure. RESULTS: A total of 17 trials involving 42,037 patients were included in this meta-analysis. Mean follow-up was 3.7 years. ACEIs significantly reduced the risk of all-cause mortality, MI and HF; the corresponding mean NNTBs were 48, 62 and 78, respectively, but ARBs were only associated with a reduction in heart failure. The clinical significance assessment of the included trials indicated that most of the statistically significant trial results had no definitive clinical significance, and only some of them had possible clinical significance. CONCLUSIONS: Among patients with diabetes, ACEIs reduced all-cause mortality, MI and HF, whereas ARBs could only prevent HF. However, none of the results of these trials had clear clinical significance, and most had only possible clinical significance.

18.
Ann Hematol ; 100(2): 505-516, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33389025

RESUMO

We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146-15.306, p < .001) was an independent risk factor for CNS relapse after allo-HSCT for AML. The 3-year overall survival (OS) for patients with CNS relapse was 60.3 ± 8.8%, which was significantly lower than that in the controls (81.5 ± 4.5%, p = .003). The incidence of CNS relapse was 1.64% for patients who received HID-HSCT and 2.55% for those who received ISD-HSCT (p = .193). There was no significant difference in OS between the HID-HSCT and ISD-HSCT subgroups among the patients with CNS relapse. In conclusion, CNS relapse is a rare but serious complication after allo-HSCT for AML, and the incidence and outcomes of patients with CNS relapse are comparable following HID-HSCT and ISD-HSCT.


Assuntos
Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Aloenxertos , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Taxa de Sobrevida
19.
Ann Hematol ; 100(2): 555-562, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33415424

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment for acute myeloid leukemia (AML). We explored the outcome of haploidentical donor (HID) transplantation for intermediate-risk AML and compared to that of matched sibling donor (MSD) transplants. One hundred twenty-seven consecutive patients with intermediate-risk AML in the first complete remission (CR1) who underwent allo-HSCT between January 1, 2015, and August 1, 2016, were enrolled. Thirty-seven patients received MSD grafts, and 90 received HID grafts. The 2-year leukemia-free survival (LFS) of the HID group was comparable to that of the MSD group: 82.0% ± 4.1% versus 82.7% ± 6.4%, P = 0.457. The 2-year cumulative incidences of relapse and transplantation-related mortality (TRM) were comparable between the HID and MSD groups (relapse, 4.5% ± 0.1%, versus 11.5% ± 0.3%, P = 0.550; TRM, 13.4% ± 0.1% vs. 5.8% ± 0.2%, P = 0.154). The HID recipients had a trend of a lower 2-year cumulative incidence of positive posttransplant flow cytometry (FCM+) and relapse than the MSD recipients (5.6% ± 0.1% vs. 19.9% ± 0.5%, P = 0.092). These results suggest that the outcomes of allo-HSCT with HIDs are comparable to those with MSDs in terms of LFS, TRM, and relapse for intermediate-risk AML in CR1. HIDs could be an alternative to MSDs for intermediate-risk AML.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Irmãos , Doadores de Tecidos , Adolescente , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Taxa de Sobrevida
20.
Sci Total Environ ; 750: 141667, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871370

RESUMO

Stable isotopes are increasingly used to detect and understand the impacts of environmental changes on riverine ecological properties. The δ13C and δ15N signatures of fish with different feeding habits were measured in a large subtropical river to evaluate how fish isotopic niches respond to environmental gradients and human disturbance. From basal resources to fish consumers, the high values of epilithic periphyton (biofilm) δ13C and suspended particulate organic matter δ15N concurrently determined the niche ranges and space (e.g., convex hull area) of fish communities. Along a longitudinal gradient (except in the industrial zone), the number of fish trophic guilds identified by Bayesian ellipses continuously increased; meanwhile, higher trophic diversity and less redundancy were observed near the lower reaches and estuary. Variance inflation factors were estimated to detect the multicollinearity of 40 environmental variables, 14 of which were selected as indicators. Relative importance (RI) analysis was used to evaluate the explanatory power of these indicators for the spatial variation in isotopic niche metrics; the results showed that riffle habitat area, water nitrate concentration, gravel-cobble substrate, and riparian buffer width were the 4 key environmental indicators (average RI > 12%) that determined the longitudinal pattern of fish isotopic niches. These findings suggested that community-level δ13C signatures are more responsive to changes in habitats (e.g., riffle) and substrates (e.g., gravel-cobble) supporting the productivity of autochthonous diatoms while δ15N signatures respond to water quality altered by nitrogen pollution from manure-fertilized farming and poultry livestock effluent. Furthermore, δ15N may be more robust and interpretable than δ13C as an isotopic indicator of ecosystem change in rivers exposed to multiple or complex anthropogenic stressors.


Assuntos
Ecossistema , Rios , Animais , Teorema de Bayes , Isótopos de Carbono/análise , China , Indicadores Ambientais , Monitoramento Ambiental , Humanos , Isótopos de Nitrogênio/análise
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