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1.
Chin J Integr Med ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418174

RESUMO

OBJECTIVE: To explore the clinical effect and adverse reactions of Strychnos nux-vomica in bortezomib-induced peripheral neuropathy (BIPN) of patients with multiple myeloma (MM). METHODS: A total of 19 MM patients with BIPN were enrolled and Nux Vomica Capsule (NVC, 0.4 g, thrice daily) were orally administrated for 30 days. Comparative analysis on parameters between pre- and post-therapy, including peripheral neuropathy (PN) grade, neurotoxicity score, Chinese medicine (CM) syndrome score, total neuropathy score (TNS), coagulation function, and serum nerve growth factor (NGF) levels were conducted. The adverse events were monitored. RESULTS: In BIPN of MM patients who received NVC, PN grade was lowered, neurotoxicity score was obviously decreased (P⩽0.01), and both CM syndrome score and TNS were remarkably decreased (P<0.01). After the therapy, activated partial thromboplastin time was prolonged (P<0.01) and fibrinogen was declined (P<0.05), showing improvement in the hypercoagulable state of patients. No significant difference of NGF recovery degrees was detected between pre- and post-therapy (P>0.05). No evident adverse reactions were observed during the course of treatment. CONCLUSION: Strychnos nux-vomica L. has significantly effect with a good safety in treatment of BIPN in MM patients.

2.
BMC Biol ; 18(1): 33, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213189

RESUMO

BACKGROUND: Current therapies for multiple myeloma (MM) are associated with toxicity and resistance, highlighting the need for novel effective therapeutics. Berberine (BBR), a botanical alkaloid derived from several Berberis medicinal plants, has exhibited anti-tumor effects, including against multiple myeloma (MM); however, the molecular mechanism underlying the anti-MM effect has not been previously described. This study aimed to identify the target of berberine and related mechanisms involved in its therapeutic activity against MM. RESULTS: Here, we demonstrated that BBR treatment killed MM cells in vitro and prolonged the survival of mice bearing MM xenografts in vivo. A screening approach integrating surface plasmon resonance (SPR) with liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified UHRF1 (ubiquitin-like with PHD and RING Finger domains 1) as a potential target of BBR. Combining molecular docking and SPR analysis, we confirmed UHRF1 as a BBR-binding protein and discovered that BBR binds UHRF1 in the tandem tudor domain and plant homeodomain (TTD-PHD domain). BBR treatment induced UHRF1 degradation via the ubiquitin-dependent proteasome system and reactivated p16INK4A and p73 in MM cells. Overexpression of UHRF1 promoted the MM cell proliferation and rendered MM cells more resistant to BBR, while silencing of UHRF1 with siRNA attenuated BBR-induced cytotoxicity. CONCLUSIONS: In summary, our study has identified UHRF1 as a direct target of BBR and uncovered molecular mechanisms involved in the anti-MM activity of BBR. Targeting UHRF1 through BBR may be a novel therapeutic strategy against MM.

3.
Hematology ; 25(1): 85-90, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32063160

RESUMO

Objective: This meta-analysis was designed to investigate the association between interferon-gamma (IFN-γ) polymorphisms and occurrence risk of aplastic anemia.Methods: Literature search was conducted in PubMed, Embase and Cochrane Library up to April 2018. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by R 3.12.Results: Total five studies with 304 aplastic anemia patients and 588 controls were included. The statistically significant results were found in the following models: allele genetic model (T vs A: OR = 2.1749, 95% CI = 1.6825-2.8114, P < 0.01), additive genetic model (TA vs AA: OR = 2.1071, 95% CI = 1.3962-3.1799, P < 0.01; TT vs AA: OR = 4.5788, 95% CI = 2.6606-7.8797, P < 0.01), recessive genetic model (TT vs AA + TA: OR = 2.5579, 95% = 1.6680-3.9226, P < 0.01), dominant genetic model (TT + TA vs AA: OR = 2.5599, 95% = 1.7424-3.7611, P < 0.01), the results suggested that the increased occurrence risk of aplastic anemia is significantly associated with the IFN-γ polymorphism.Conclusions: Patients with IFN-γ genotype carrying allele T have higher occurrence risk of aplastic anemia.

4.
J Diabetes ; 12(1): 25-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31141300

RESUMO

BACKGROUND: It is clear that aerobic training (AT) can delay pancreatic exhaustion and slow the progression from prediabetes to type 2 diabetes (T2D), but there is little information regarding the effects of resistance training (RT) in people with prediabetes. This study compared the effectiveness of RT and AT in improving metabolic control and protecting ß-cell function in people with prediabetes. METHODS: Chinese subjects (n = 248) with prediabetes were randomized to three groups: AT (n = 83), RT (n = 82) and control (n = 83). Subjects in the RT group performed 13 different resistance exercises per session using an elastic string. Those in the AT group performed aerobic exercises at 60%-70% of maximum heart rate. In both cases, exercises were performed three times per week for a period of 6 months. The primary outcome was improvement in metabolic control. Longitudinal changes between groups were tested using repeated-measures analysis of variance. RESULTS: Of the initial 248 participants, 217 finished the study, but all participants were included in the intention-to-treat analyses. There were no significant differences in demographic characteristics among the RT, AT, and control groups (P > 0.05). Changes in HbA1c were not significantly greater in RT than AT cohort (P = 0.059), but the decrease in HbA1c in both exercise groups was higher than in the control group (P < 0.05). CONCLUSIONS: In subjects with prediabetes, RT appears to improve metabolic control and preserve ß-cell function comparable to AT.

5.
J Ethnopharmacol ; 248: 112317, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31629862

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arnebiae Radix, a common herbal medicine in China, is often utilized to treat blood-heat syndrome and has been reported to exert an effect on the heart. AIM OF THE STUDY: The combination of acetylcholine (Ach) and CaCl2 has been widely used to induce atrial fibrillation (AF) in animals. However, whether Arnebiae Radix displays any preventive action on Ach-CaCl2 induced AF in rats remains uncertain. In our study, we attempted to investigate the protective effects of Arnebiae Radix on Ach-CaCl2 induced AF compared to amiodarone, which was employed as the positive control. MATERIALS AND METHODS: To establish the AF model, SD rats were treated with a mixture of 0.1 mL/100 g Ach-CaCl2 (60 µg/mL Ach and 10 mg/mL CaCl2) by tail vein injection for 7 days. Rats were also given a gavage of Arnebiae Radix (0.18 g/mL) one week before or concurrently with the establishment of the AF model. At the end of the experimental period, the induction, duration and timing of AF were monitored using electrocardiogram recordings. Left atrial tissues were stained to observe the level of fibrosis. Electrophysiological measurements were used to examine atrial size and function. RESULTS: In Ach-CaCl2-induced AF rats, Arnebiae Radix decreased AF induction, duration and susceptibility to AF. In addition, Arnebiae Radix significantly reduced atrial fibrosis and inhibited atrial enlargement induced by Ach-CaCl2. Moreover, there was an apparent improvement in cardiac function in the Arnebiae Radix-treated group. CONCLUSIONS: Our findings indicate that Arnebiae Radix treatment can attenuate Ach-CaCl2-induced atrial injury and serve as an effective therapeutic strategy for the treatment of AF in the future.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1925-1932, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839061

RESUMO

OBJECTIVE: To evaluate the regulation of VEGF-Notch signaling pathway on proliferation and apoptosis of mesenchymal stem cells (MSC) in the patients with aplastic anemia (AA). METHODS: The bone marrow specimens of AA patients were collected for isolation and identification of BM MSC. Westen blot was used to detect the expression of VEGF-Notch signaling pathway-related proteins (VEGF, VEGFR, Notch 1, Jagged 1, Delta-like 1 and Hes1). The VEGF (100 ng/ml) and DAPT (γ-secretase inhibitor, 10 µmol/L) were respectively added into MSC culture system in oder to activate and inhibit the signaling transduction of VEGF-Notch in BM MSC. The proliferation, apoptosis and cell cycle of MSC in AA patients were detected by CCK8 assay and flow cyfometry. The adipogenic differentiation of BM MSC was detected by oil red O staining. RESULTS: The VEGF-Notch signaling pathway was significantly inhibited in AA BM tissues and AA MSC (P<0.05) detected by Western blot. The intervention of VEGF and DAPT significantly activated and inhibited VEGF-Notch signaling in AA MSC, respectively. CCK8 assay showed that VEGF intervention significantly promoted the proliferation of MSC in AA patients (P<0.05). Flow cytometry showed that VEGF significantly inhibited apoptosis of MSCs by blocking S phase cells (P<0.05). CONCLUSION: The activation of VEGF-Notch can restore the proliferation function of MSC in AA patients.


Assuntos
Anemia Aplástica , Células-Tronco Mesenquimais , Apoptose , Medula Óssea , Proliferação de Células , Humanos , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 33(11): 1384-1388, 2019 Nov 15.
Artigo em Chinês | MEDLINE | ID: mdl-31650753

RESUMO

Objective: To investigate evaluation and treatment of osteochondral injury of knee joint and its effectiveness. Methods: Between January 2010 and January 2016, 17 patients with osteochondral injury of knee joint were admitted. There were 2 males and 15 females, with an average age of 19.3 years (range, 15-33 years). The causes of injury included the sprain in 14 cases and knee hyper-extension and varus due to violence in 3 cases. The osteochondral injury located at patella in 8 cases, lateral femoral condyle in 4 cases, medial femoral condyle in 1 case, and tibial plateau in 4 cases. There were 15 cases of fresh fractures and 2 cases of old fractures. The Lysholm score of the knee joint was 31.6±2.3. After open reduction of osteochondral fractures of 14 cases, the absorbable rods (9 cases), absorbable cartilage nail (3 cases), or absorbable sutures (2 cases) were selected for fixation. The osteochondral fractures at the medial tibial plateau margin (non-weight-bearing area) in 3 cases were removed. Results: The incision fat liquefaction occurred in 1 case after operation and healed after debridement. The other incisions had primary healing. All 17 patients were followed up 6 months to 2 years (mean, 13 months). Thirteen of 14 patients with internal fixation had good fractures healing without traumatic arthritis; 1 case of patella osteochondral fracture did not heal. Three patients with non-weight-bearing osteochondral removal had no narrowing of the medial joint space and traumatic arthritis during the follow-up. The Lysholm score of knee joint at 1 year after operation was 91.3±1.1, which significantly improved when compared with preoperative score ( t=7.136, P=0.001). Conclusion: For the osteochondral injury of the knee joint, the osteochondral block with full-layer cancellous bone can be treated with open reduction and internal fixation; while osteochondral block with punctate cancellous bone can be directly remove.


Assuntos
Articulação do Joelho , Adolescente , Adulto , Feminino , Fixação Interna de Fraturas , Humanos , Traumatismos do Joelho , Masculino , Patela , Tíbia , Fraturas da Tíbia , Resultado do Tratamento , Adulto Jovem
8.
Transl Oncol ; 12(6): 801-809, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30953928

RESUMO

As a heterogeneous group of clonal disorders, acute myeloid leukemia with internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD) mutation usually shows an inferior prognosis. In the present study, we found that homoharringtonine (HHT), a protein translation inhibitor of plant alkaloid in China, exhibited potent cytotoxic effect against FLT3-ITD (+) cell lines and primary leukemia cells, and a remarkable synergistic anti-leukemia action was demonstrated in vitro and in vivo in xenograft mouse models when co-treated with the heat shock protein 90 inhibitor IPI504. Mechanistically, HHT combined with IPI504 synergistically inhibited the growth of leukemia cells by inducing apoptosis and G1 phase arrest. This synergistic action resulted in a prominent reduction of total and phosphorylated FLT3 (p-FLT3) as well as inhibition of its downstream signaling molecules such as STAT5, AKT, ERK and 4E-BP1. Furthermore, co-treatment of HHT and IPI504 led to a synergistic or additive effect on 55.56%(10/18) of acute myeloid leukemia cases tested, including three relapsed/refractory patients. In conclusion, our findings indicate that the combination of HHT and HSP90 inhibitor provides an alternative way for the treatment of FLT3-ITD positive acute myeloid leukemia, especially for relapsed/refractory AML.

9.
Onco Targets Ther ; 12: 2335-2342, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30992670

RESUMO

Objective: To compare cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and CHOP plus etoposide (CHOPE) with regard to outcomes including efficacy and safety for patients with peripheral T-cell lymphoma (PTCL). Methods: Relevant literature was searched using PubMed, Embase, Wanfang, and CNKI for eligible trials comparing CHOP with CHOPE for treatment of PTCL. The following outcomes of PTCL patients were considered: complete response (CR), partial response (PR), overall response rate (ORR), and adverse events (AEs; grade >3). Risk ratios (RRs) were appropriately derived from fixed-effects or random-effects models. Results: A total of five prospective or retrospective articles with 1,560 patients were elected for the meta-analysis. There were no significant differences in CR (RR =1.11, 95% CI: 0.73-1.67, P=0.632), PR (RR =1.40, 95% CI: 0.52-3.76, P=0.504), and ORR (RR =1.25, 95% CI: 0.93-1.69, P=0.146) between the CHOP and CHOPE groups. However, AEs including anemia (RR =1.69, 95% CI: 1.33-2.16, P<0.001) and thrombocytopenia (RR =1.43, 95% CI: 1.15-1.77, P=0.001) were significantly increased in CHOPE group compared to that in CHOP group. Conclusion: Meta-analysis suggested that there were no differences in therapeutic effect for patients with PTCL between CHOP and CHOPE groups with regards to CR, PR, and ORR, whereas the CHOPE group had significantly increased AEs (anemia and thrombocytopenia) compared to CHOP group.

10.
Medicine (Baltimore) ; 98(8): e14519, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813154

RESUMO

To understand the risks associated with aplastic anemia (AA) in 4 cities of Zhejiang Province, China, with special focus on the joint contributions of multiple risks.Based on an Electronic Data Capture (EDC), a case control study was carried out. Data regarding socio-demographic, diseases history, living habits, and exposures to toxic substances, etc., were collected through survey questionnaires. t Test, chi-square test, or non-parametric rank sum test, and univariate and multivariate Logistic regression analysis were conducted to analyze data.The univariate logistic regression analysis results indicated that among all study participants (n = 1802), AA was associated with over 30 risks, in terms of their individual behaviors, daily and environmental exposures, diseases history, and family history. Multivariate logistic regression analysis further confirmed that the independent risks related to AA included presence of chemical factory within 3 km of living residence (odds ratio [OR] = 8.73, 95% CI: 1.42-53.74, P = .019), living in a newly decorated house/apartment (OR = 25.37, 95% CI: 4.44-144.81, P < .001), vegetarian diet (OR = 131.60, 95% CI: 3.45-5020.16, P = .009), preference of sugar (OR = 89.38, 95% CI: 7.22-1106.44, P < .001), preference of oily food (OR = 55.68, 95% CI: 5.12-605.26, P = .001), drinking lake water or pond water (OR = 58.05, 95% CI: 3.21-1049.81, P < .001), habit of staying up late (OR = 11.87, 95% CI: 3.43-41.02, P < .001), infection history (OR = 10.08, 95% CI: 2.75-36.93, P < .001). Result of receiver operating characteristic curve (ROC) analysis on the joint contribution of multiple risks indicated that AA was 13.835 times likely to occur when exposed to ≥1 risks than those exposed to 0 risks (95% CI: 9.995-19.149).Our study results demonstrated a comprehensive epidemiological pattern, in which the joint contributions of individual inherited health status, environment exposure, and individual behaviors lead to the occurrence of AA.


Assuntos
Anemia Aplástica/etiologia , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Anemia Aplástica/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Exposição Ambiental/efeitos adversos , Feminino , Comportamentos Relacionados com a Saúde/etnologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
11.
Eval Program Plann ; 74: 69-75, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30861395

RESUMO

Portfolio evaluation is the evaluation of multiple projects with a common purpose. While logic models have been used in many ways to support evaluation, and data visualization has been used widely to present and communicate evaluation findings, adopting logic models for portfolio evaluation and using data visualization to share findings simultaneously is surprisingly limited in the literature. With the data from a sample portfolio of 209 projects which aims to improve the system of early care and education (ECE), this study illustrated how to use logic model and data visualization techniques to conduct a portfolio evaluation by answering two evaluation questions: "To what extent are the elements of a logic model (strategies, sub-strategies, activities, outcomes, and impacts) reflected in the sample portfolio?" and "Which dominant paths through the logic model were illuminated by the data visualization technique?" For the first question, the visualization technique illuminated several dominant strategies, sub-strategies, activities, and outcomes. For the second question, our visualization techniques made it convenient to identify critical paths through the logic model. Implications for both program evaluation and program planning were discussed.


Assuntos
Lógica , Modelos Teóricos , Avaliação de Programas e Projetos de Saúde/métodos , Humanos , Objetivos Organizacionais , Desenvolvimento de Programas
12.
JAMA Dermatol ; 155(6): 666-672, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30916737

RESUMO

Importance: Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. Objective: To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. Design, Setting, and Participants: A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. Exposures: Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. Main Outcomes and Measures: The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. Results: Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10-5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. Conclusions and Relevance: Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.


Assuntos
Dapsona/efeitos adversos , Síndrome de Hipersensibilidade a Medicamentos/prevenção & controle , Antígeno HLA-B13/genética , Hansenostáticos/efeitos adversos , Hanseníase/tratamento farmacológico , Adulto , Alelos , China , Clofazimina/administração & dosagem , Estudos de Coortes , Dapsona/administração & dosagem , Síndrome de Hipersensibilidade a Medicamentos/epidemiologia , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Quimioterapia Combinada , Feminino , Humanos , Incidência , Hansenostáticos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Rifampina/administração & dosagem
13.
Medicine (Baltimore) ; 98(3): e14119, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30653138

RESUMO

RATIONALE: Acquired hemophilia A is a rare hemorrhagic disease in which the body produces specific antibodies that attack factor VIII, resulting in bleeding that is mainly mucocutaneous and associated with soft tissue and the gastrointestinal system. Approximately 50% of this disease derives from basic diseases, such as autoimmune diseases, cancer, and pregnancy. PATIENT CONCERNS: We report a 35-year-old postpartum female with acquired hemophilia A who initially presented with pleural hemorrhage. DIAGNOSES: In this patient activated prothrombin time (PT) and activated partial thromboplastin time (APTT) were found, and the factor VIII activity was 12.6%, furthermore Bethesda assay showed a FVIII antibody titer of 7.4 Bethesda units (BUs). INTERVENTIONS: The treatment requires a 2-pronged approach: treatment of the bleeding and elimination of the inhibitor. OUTCOMES: After hemostatic agents were used and inhibitors were eradicated, the patient achieved complete remission without relapse. LESSONS: It is essential to recognize the development of disease earlier in pregnant woman.


Assuntos
Hemofilia A/complicações , Hemotórax/etiologia , Complicações Hematológicas na Gravidez/etiologia , Adulto , Feminino , Humanos , Gravidez
14.
Medicine (Baltimore) ; 98(1): e14018, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608452

RESUMO

RATIONALE: Acute lymphoblastic leukemia (ALL) secondary to multiple myeloma (MM) is rare. Here we report a rare case of secondary ALL transformed from MM. PATIENT CONCERNS: A 64-year-old woman was diagnosed as MM IgG light chain type in 2001. She achieved complete remission after 2 cycles of therapy, and received maintenance therapy with thalidomide. The patient suffered from MM relapse in September 2011. Bone marrow examination showed that the percentage of primary lymphocytes was 59%, indicating ALL-L2 (Pre-B-ALL). The patient reached complete remission after 1 cycle of chemotherapy, and has been maintained for more than 6 years. DIAGNOSES: Immunophenotyping analysis revealed that the abnormal cell population accounted for approximately 66% which expressed HLA-DR, CD4, CD22, CD33, CD34, and cCD79a. These results indicated acute B lymphoblastic leukemia. Chromosome presented 47, XX, +5, -7, +19. Leukemia fusion gene analysis demonstrated positive EVI1 and negative IgH and TCR gene rearrangement. INTERVENTIONS: The patient accepted 1 cycle of VDCLP chemotherapy and reached complete remission, followed with consolidation therapies with VDCLP, MA, CAG and other chemotherapy regimens. OUTCOMES: This patient has maintained CR1 of ALL for more than 6 years. LESSONS: Even secondary lymphoblastic leukemia has been rarely reported in patients with MM, we still need perform bone marrow examination, flow cytology, and gene tests, especially during maintenance therapy.


Assuntos
Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Medula Óssea/patologia , Feminino , Rearranjo Gênico/genética , Humanos , Imunofenotipagem/métodos , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Indução de Remissão , Resultado do Tratamento
15.
Eval Program Plann ; 72: 88-96, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30321687

RESUMO

Outcome evaluation is very important for program evaluation and has been becoming increasingly so in the age of accountability. Typically, outcome evaluation is conducted for a single program from a single perspective. However, in a real-life situation, many programs exist in a system, and the effects could be viewed from various perspectives. The authors illustrate a typology of program effects in a system. It moves from the paradigm of a single program's single effect to that of a set of programs' multiple effects. Methodological implications are discussed.


Assuntos
Pesquisa Comportamental/organização & administração , Educação/organização & administração , Avaliação de Programas e Projetos de Saúde/métodos , Pesquisa Comportamental/normas , Criança , Pré-Escolar , Educação/normas , Feminino , Humanos , Avaliação de Programas e Projetos de Saúde/normas , Melhoria de Qualidade/organização & administração , Reprodutibilidade dos Testes , Fatores Socioeconômicos
16.
Exp Clin Transplant ; 17(3): 425-428, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29251580

RESUMO

A 24-year-old man was diagnosed with myelodysplastic syndrome and received a haploidentical hematopoietic stem cell transplant. The patient experienced graft failure posttransplant. Analysis of specific antibodies revealed that the patient had strongly positive donor-specific antibodies; therefore, we changed the donor to the patient's mother and added a single unit of cord blood to perform the second transplant. Corresponding treatments targeting donor-specific antibodies were administered to reverse the graft rejection and to reduce the antibody load. The grafts were implanted successfully, but the patient developed an invasive fungal infection. A lung biopsy was performed, and the pathogen was confirmed to be Aspergillus terreus via gene sequencing and analysis. The combined treatment of micafungin and posaconazole had good efficacy in this case, and this patient now receives close follow-up and receives oral posaconazole for antifungal maintenance treatment.

17.
J Cell Biochem ; 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30230583

RESUMO

OBJECTIVE: Vascular endothelial growth factor (VEGF)-Notch signaling pathway plays an important role in aplastic anemia (AA). This study aimed to evaluate the regulatory roles of VEGF-Notch signaling pathway on mesenchymal stem cells (MSCs) isolated from AA patients with kidney deficiency and blood stasis (KB) (AA MSCs). METHODS: Expression of VEGF-Notch signaling related factors, including VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was detected in bone marrow (BM) tissues and AA MSCs by Western blot analysis. VEGF (100 ng/mL) and γ-secretase inhibitor (DAPT) (10 µM) was used to active and inhibit VEGF-Notch signaling in AA MSCs, respectively. After treatment, the proliferation, apoptosis, and adipogenic differentiation of AA MSCs was detected by Cell Counting Kit-8, flow cytometry, and Oil red O staining, respectively. Lentivirus short hairpin RNA (shRNA) were constructed to downregulate Notch-1 and VEGF in normal bone marrow mesenchymal stem cells (BMSCs), and the effects of VEGF/Notch-1 shRNA transfected BMSCs on the proliferation, migration, and angiogenesis of human umbilical vein endothelial cells (HUVECs) were evaluated. RESULTS: Significantly lower expression of VEGF, VEGFR, Notch-1, Jagged1, Delta-like1, and hes1 was revealed in AA BM tissues and AA MSCs when compared with the normal control (P < 0.05). The intervention of DAPT significantly inhibited the proliferation, and promoted the apoptosis and adipogenic differentiation of AA MSCs, while VEGF intervention exhibited opposite results (P < 0.05). Meanwhile, the proliferation, migration, and angiogenesis of HUVECs were significantly promoted by normal BMSCs, while inhibited by VEGF/Notch-1 shRNA transfected BMSCs (P < 0.05). CONCLUSION: The activation of VEGF-Notch signaling pathway may be a potential therapeutic target for AA with KB.

18.
Exp Cell Res ; 371(2): 409-416, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30179602

RESUMO

Identifying and targeting oncogenic fusion genes have revolutionized the treatment of leukemia, such as PML-RARα fusion gene in acute promyelocytic leukemia. Here we identified an intrachromosomal fusion gene located on chromosome 19q.13 between UBA2 and WTIP gene in a case of acute myeloid leukemia. The UBA2-WTIP fusion gene contains the N-terminal E1_enzyme_family, VAE_Ubl domains of UBA2, and the C-terminal LIM domains of WTIP. The UBA2-WTIP fusion was detected by reverse transcriptase polymerase chain reaction and Sanger sequencing in 19 of 56 acute myeloid leukemia samples (33.9%). Ectopic expression of the UBA2-WTIP fusion in human acute myeloid leukemia KG-1a cells showed enhanced cell proliferation both in vitro and in vivo. The UBA2-WTIP fusion induced phosphorylation of STAT3, STAT5 and ERK1/2, and abrogates WTIP-mediated mammalian processing body formation. Finally, triptolide displayed selective cytotoxicity against KG-1a cells harboring the UBA2-WTIP fusion. Collectively, our findings suggest that the UBA2-WTIP fusion is an oncogenic fusion gene, as well as a promising therapeutic target for the treatment of acute myeloid leukemia.


Assuntos
Proteínas de Transporte/genética , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/genética , Leucócitos/metabolismo , Proteínas de Fusão Oncogênica/genética , Enzimas Ativadoras de Ubiquitina/genética , Animais , Antineoplásicos Alquilantes/farmacologia , Apoptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Leucócitos/efeitos dos fármacos , Leucócitos/patologia , Camundongos , Camundongos Endogâmicos NOD , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Fenantrenos/farmacologia , Domínios Proteicos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT5/genética , Fator de Transcrição STAT5/metabolismo , Análise de Sobrevida , Enzimas Ativadoras de Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Medicine (Baltimore) ; 97(30): e11619, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30045301

RESUMO

RATIONALE: Chronic lymphocytic leukemia often results in secondary tumors, the most common being large B cell lymphoma known as Richter syndrome, followed by extranodal NK/T-cell lymphoma (nasal type) is extremely rare. PATIENT CONCERNS: A chronic lymphocytic leukemia patient presented with nasal congestion. DIAGNOSES: Nasal endoscopy identified a left nasal mass, and the pathology suggested extranodal NK/T-cell lymphoma (nasal type). INTERVENTIONS: The patient received a course of chemotherapy. OUTCOMES: Pneumonia and coagulopathy occurred after chemotherapy, and the patient died shortly thereafter. LESSONS: It is essential to recognize the transformation of disease earlier in chronic lymphoblastic leukemia patient.


Assuntos
Leucemia Linfocítica Crônica de Células B/patologia , Linfoma Extranodal de Células T-NK/patologia , Segunda Neoplasia Primária/patologia , Neoplasias Nasais/patologia , Idoso , Evolução Fatal , Humanos , Masculino
20.
Leuk Lymphoma ; 59(11): 2679-2685, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29448851

RESUMO

The purpose of this prospective, multi-center study was to examine the efficacy and safety of tigecycline as empirical treatment in neutropenic patients with hematological malignancies who failed to respond to first-line antibiotics. A total of 125 patients with persistent fever (>72 h) despite first-line antibiotics received empirical treatment with tigecycline (loading dose of 100 mg, followed by 50 mg every 12 h). The use of other antimicrobial agents was not restricted. Treatment success rate was 68.0%. Subgroup analysis revealed a success rate of 73.1% in patients with pneumonia and 35.3% in patients with bacteremia. Toxicities were moderate with gastrointestinal symptoms being the main side effects. In conclusion, tigecycline-based antibacterial regimen was a justifiable empirical treatment in febrile neutropenic patients who failed to respond to first-line antibiotics except those with bacteremia. For patients with bacteremia, trials on higher-dose of tigecycline are needed.


Assuntos
Neutropenia Febril/tratamento farmacológico , Neoplasias Hematológicas/complicações , Terapia de Salvação/métodos , Tigeciclina/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Neutropenia Febril/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , /estatística & dados numéricos , Pneumonia/complicações , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
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