RESUMO
Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide ß(ß-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5bãß-CTXãPINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, ß-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) µg/L vs (15.6±5.5) µg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and ß-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, ß-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.
Assuntos
Doenças Ósseas , Mieloma Múltiplo , Fosfatase Ácida , Biomarcadores , Humanos , Inibidores de Proteassoma , Fosfatase Ácida Resistente a TartaratoRESUMO
Objective: To investigate the effects and mechanisms of miR-144 on proliferation, apoptosis and cisplatin (DDP) resistance of neuroblastoma cells. Methods: Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the mRNA expressions of miR-144 and MYCN in neuroblastoma cell lines, including SH-SY5Y and SK-N-SH, and human umbilical vein endothelial cells HUVEC. The miR-negative control, miR-144 mimics, si-negative control, si-MYCN, miR-144 mimics and pcDNA, miR-144 mimics and pcDNA-MYCN co-transfected SH-SY5Y cells were described as miR-NC, miR-144, si-NC, si-MYCN, miR-144+ pcDNA and miR-144+ pcDNA-MYCN group, respectively. The half maximal inhibitory concentration (IC(50)) and cell proliferation were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The protein expressions of MYCN, p21, cyclin D1, Bax, Bcl-2 were analyzed by western blot. Cell apoptosis was detected by flow cytometry. The cell fluorescence activity was detected by double luciferase reporter gene assay. Results: Compared with HUVEC cells, the expressions of miR-144 in neuroblastoma cells SH-SY5Y and SK-N-SH significantly decreased, while the mRNA and protein expression of MYCN significantly increased. The IC(50) of DDP was 9.16 µg/ml in SH-SY5Y cells. The absorbance value in 490nm (A(490) value) of miR-144 group was 0.30±0.03, significantly lower than 0.46±0.03 of miR-NC group. The cell apoptotic rate of miR-144 group was 26.94%±2.01%, significantly higher than 9.68%±0.52% of miR-NC group. The IC(50) value of DDP in miR-144 group was 2.95±0.26, significantly lower than 9.23±0.61 of miR-NC group. The expressions of p21, cyclin D1, Bax, Bcl-2 in miR-NC and miR-144 group were 2.67±0.19, 0.41±0.04, 2.12±0.21, 0.18±0.01 and 1.01±0.07, 1.00±0.06, 1.00±0.05, 1.00±0.06, respectively, with statistical significance (all P<0.05). Knockdown of MYCN showed the similar effects with those of miR-144 overexpression in SH-SYSY cells. MiR-144 significantly inhibited the fluorescence activity of ectopic MYCN expressing cells and negatively regulated the expression of MYCN. Overexpression of MYCN can reverse the effects of miR-144 on proliferation inhibition, apoptosis promotion and sensitization of SH-SY5Y cells to DDP. Conclusion: MiR-144 inhibits proliferation, promotes apoptosis and enhances the sensitivity of neuroblastoma cells to DDP through targeting MYCN, which provides a potential treatment for neuroblastoma.
Assuntos
Apoptose/genética , Proliferação de Células/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Proteína Proto-Oncogênica N-Myc/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/genética , Antineoplásicos/farmacologia , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Criança , Regulação Neoplásica da Expressão Gênica , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Objective: To investigate the inhibitory effect of programmed cell death factor 4 (PDCD4) on arsenic trioxide (As(2)O(3))-induced cell growth and nuclear factor kappa B (NF-κB) signaling pathway in neuroblastoma. Methods: The PDCD4 overexpression vector was transfected into neuroblastoma cells and detected by fluorescence quantitative PCR and Western blot. As(2)O(3) was used to treat PDCD4 overexpressing neuroblastoma cells. MTT assay was used to measure the proliferation. Colony formation assay was used to determine the cell clone forming ability. Apoptosis was measured by flow cytometry. Western blot was used to detect the expression of NF-κB p65 and cleaved caspase-3 protein in cells. Results: The transfection of PDCD4 overexpression vector significantly increased the expression level of PDCD4 in neuroblastoma cells. The cell survival rates of the control group, PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were 100%, (72.14±5.20)%, (62.58±3.14)% and (40.87±2.47)%, respectively. The colony formation rates in these four groups were (91.25±8.36)%, (65.32±7.14)%, (57.23±5.28)% and (37.14±3.64)%, respectively. In addition, the cell apoptotic rates of these four groups were (3.57±0.24)%, (28.64±3.20)%, (36.41±4.58)% and (49.65±5.27)%, respectively. Therefore, overexpression of PDCD4 in the absence or presence of As(2)O(3) inhibited cell proliferation and clone formation ability, while promoted apoptosis. Furthermore, the expression levels of cleaved caspase-3 in the control group, PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were 0.21±0.03, 0.30±0.02, 0.43±0.05 and 0.57±0.06, respectively. And the expression levels of NF-κB p65 protein were 0.68±0.04, 0.52±0.03, 0.43±0.04, and 0.32±0.02, respectively. Compared with the control group, the expression levels of NF-κB p65 protein in PDCD4 group, As(2)O(3) group and As(2)O(3)+ PDCD4 group were significantly decreased (P<0.05), whereas the expression level of cleaved Caspase-3 protein was significantly increased (P<0.05). The changes in As(2)O(3)+ PDCD4 group were more significant than those in PDCD4 group and As(2)O(3) groups (both P<0.05). Conclusion: PDCD4 enhances the inhibitory effect of As(2)O(3) on the growth and NF-κB signaling pathway in neuroblastoma cells.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Apoptose/efeitos dos fármacos , Trióxido de Arsênio/farmacologia , NF-kappa B/fisiologia , Neuroblastoma/tratamento farmacológico , Proteínas de Ligação a RNA/genética , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos , Proteínas Reguladoras de Apoptose/metabolismo , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Objective: To explore the clinical significance of serum bone metabolites ß C-termianl telopeptide of type â collagen(ß-CTX), Procollagen type â N-terminal peptide(PINP) concentration and ratio of beta -CTX/PINP in multiple myeloma bone disease (MMBD) and bone metastases. Methods: A total of 31 cases of MM, 46 cases of bone metastases and 12 healthy controls were enrolled in the department of hematology, oncology and physical examination center of Henan Provincial People's Hospital respectively from October 2016 to October 2017. According to the imaging findings, MMBD was divided into 0-4 grades, group A included the patitents with grade 0-2 of osteopathy (n=8), and group B included the grade 3-4 (n=23). After two courses of chemotherapy, the curative effect was evaluated. MM group were divided into effective group (above partial remission , n=22) and uneffective group (unreached partial remission, n=9). ELISA method was used to detect the concentration of serum beta -CTX and PINP, and the ratio of beta -CTX/PINP was calculated. Results: The serum beta -CTX concentration in newly diagnosed MM, bone metastases and healthy control were (3 563 ± 544)ng/L, (6 690±343)ng/L, (2 726±1 026)ng/L (χ2=22.207, P<0.001), PINP concentration were (72 ± 14) ng/L, (112 ± 62) ng/L, (171 ± 62) ng/L (χ2=7.418, P=0.024) , and beta -CTX/PINP ratio were 93±19, 141±21, 17±8 (χ2=20.192, P<0.001), the differences were statistically significant. The ratio of initial MM beta -CTX/PINP was higher than that of healthy control (P=0.001). The concentration of beta -CTX (P=0.003) and the ratio of beta -CTX/PINP(P<0.001) in bone metastases were higher than those in healthy controls. The serum concentration of beta-CTX in newly diagnosed MM was lower than that in bone metastases (P<0.001). Before chemotherapy, the serum levels of beta -CTX and PINP in A and B groups were not statistically significant, but the ratio of serum beta -CTX/PINP in A group was lower than that in group B, and the difference was statistically significant. After two courses chemotherapy, the concentration of serum beta -CTX (P=0.023) and the ratio of beta -CTX/PINP (P<0.001) were decreased in MM group. There were no significant difference of serum beta -CTX, PINP concentration, and beta-CTX/PINP ratio before and after treatment in Group A. Patients in the group B, there was no significant difference in the changes of serum PINP concentration, but both serum beta -CTX concentration and beta-CTX/PINP ratio decreased after two courses[(4 027 ± 648)ng/L vs (2 370± 460) ng/L, P=0.043; 111± 23 vs 30± 6, P=0.002]. The ratio of serum beta-CTX/PINP decreased in the effective group, and the difference was statistically significant. There was no significant difference in serum beta-CTX, PINP concentration and beta-CTX/PINP ratio before and after treatment in the uneffective group. Conclusions: There is a difference between newly diagnosed MMBD and bone metastases in serum beta-CTX, which might be helpful for differential diagnosis, and the ratio of beta-CTX/PINP is positively correlated with the severity of MMBD, which might be used to evaluate the severity of bone disease and have a certain monitoring significance for the treatment of MM.
Assuntos
Mieloma Múltiplo , Biomarcadores , Neoplasias Ósseas , Colágeno , Humanos , Fragmentos de Peptídeos , PeptídeosRESUMO
Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F â § inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.
Assuntos
Fator VIII/uso terapêutico , Hemofilia A , Criança , Hemartrose , Hemofilia A/tratamento farmacológico , Hemorragia , Humanos , Estudos RetrospectivosRESUMO
Objective: To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase. Methods: From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (â³HtSDS) were used to explore the change in height with imatinib therapy. Results: The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) (P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy (P<0.001) and longer duration of imatinib therapy (P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions: Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.
Assuntos
Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva , Adolescente , Adulto , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Objective: To explore the expression of CD45 in newly diagnosed multiple myeloma (MM) and its relationship with clinical efficacy and prognosis. Methods: This study retrospectively analyzed expression and distribution of CD45 in 130 cases of newly diagnosed MM, comparing clinical efficacy and prognosis in CD45(+)/CD45(-) groups. Results: â The CD45(+) group was 33 cases (25.38%) , and CD45(-) group was 97 cases (74.62%) . â¡The objective remission rate (ORR) of CD45(+) and CD45(-)group was 33.33% and 64.95%, respectively. The difference was statistically significant (P=0.002) . For patients in Bortezomib regimen, the ORR of CD45(+) and CD45(-) group was 35.71% and 66.25%, respectively. The difference was statistically significant (P=0.005) . â¢The median progress free survival (PFS) of CD45(+) group and CD45(-) group was 29.8 (95%CI 10.0-59.0) months vs 34.5 (95%CI 6.0-69.0) months (χ(2)=14.59, P<0.001) and the median overall survival (OS) was 32.5 (95%CI 10.0-68.0) months vs 37.6 (95%CI 6.0-78.0) months (χ(2)=11.42, P=0.001) , respectively. Among the patients in bortezomib regimen, The median PFS and median OS of CD45 (+) group and CD45(-) group were 30.3 (95%CI 10.0-59.0) months vs 36.3 (95%CI 6.0-69.0) months (χ(2)=14.75, P=0.001) and 34.0 (95%CI 10.0-68.0) months vs 39.5 (95%CI 6.0-78.0) months (χ(2)=10.62, P=0.001) . â£Cox risk regression model analysis showed that serum creatinine≥176.8 µmol/L (HR=5.078, 95%CI 1.744-14.723, P=0.001) , CD45 positive (HR=14.504, 95%CI 0.168-0.42, P=0.001) , LDH≥220 IU/L (HR=1.308, 95%CI 1.16-2.417, P=0.015) were independent risk prognostic factors. Conclusion: CD45 expression is a risk prognostic factor of MM patients. Bortezomib did not improve the poor prognosis of CD45(+) MM patients.
Assuntos
Antígenos Comuns de Leucócito/análise , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Humanos , Antígenos Comuns de Leucócito/metabolismo , Mieloma Múltiplo/diagnóstico , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To explore the clinical characteristics and prognostic factors of the patients with non-Hodgkin's Lymphoma (NHL) complicated with HBV infection, so as to provide a basis for clinical accurate diagnosis and prognosis evaluation. Methods: The data of 313 newly diagnosed NHL patients from August 2012 to July 2016 were collected. The HBV serological markers were detected by ELISA, and HBV DNA was quantified by full automatic microparticle chemiluminescence immunoassay (≥1×10(5) copies/ml as high copy group, 1×10(3)-<1×10(5) copies/ml as low copy group). The relationship between HBV infection and prognosis was analyzed combined with the clinical features of the patients, and the HBV detection rate was compared with that of the common population (from the national HBV sero epidemiological data). Results: â The positive rate of HBsAg in NHL patients was 12.5% (39/313), which was higher than 7.2% in the general population (χ(2)=14.596, P<0.001). HBV infection in the past (HBsAg negative but HBcAb positive) in 114 cases (36.4%), the incidence was slightly higher than that in the general population (34.1%). â¡Compared HBsAg positive group with the negative group, the proportion of B cell type (87.2% vs 70.3%, P=0.027), Ann Arbor stage â ¢-â £(69.2% vs 34.6%, P<0.001), IPI score 3-5 (74.4% vs 50%, P=0.004), LDH level (79.5% vs 47.8%, P<0.001) and liver involvement (45.5% vs 31.7%, P=0.006) were all higher. The difference was statistically significant. â¢Compared the HBV infected group (114 cases) with the non-infected group (160 cases), the difference had statistical significance in the proportion of Ann Arbor stage â ¢-â £ (P=0.023) and IPI score 3-5 scores P=0.035). â£Compared HBV DNA positive group (30 cases) with negative group (71 cases), Ann Arbor stage â ¢-â £ (P=0.011), IPI score 3-5 score (P=0.030), LDH level (P=0.025) and liver involvement (P<0.001) in the proportion of patients had statistical significance. The positive patients were divided into HBV DNA high and low copy groups with 1×10(5) copies of /ml as the boundary. The results showed that there was no statistical difference between the two groups (P>0.05). Conclusions: The HBV infection rate of NHL patients is significantly higher than that of the general population, and HBV infection is more closely related to B cell type NHL. Patients with HBV infection and HBV DNA positive had late Ann Arbor stage, high IPI score, high LDH level and liver involvement, and the prognosis is poor.
Assuntos
Hepatite B , Linfoma não Hodgkin , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Humanos , PrognósticoRESUMO
Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade â ¢/â £ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Adolescente , Anemia Aplástica/terapia , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Doadores não RelacionadosRESUMO
Objective: To observe the therapeutic response of radiosynovectomy with p-32 colloid on hemophilic arthropathy, and to assess the effects of radiosynovectomy with Denver Score on hemophilic arthritis staging. Methods: Radiosynovectomy with p-32 colloid was performed on 326 hemophilic arthritis patients (405 joints) , and recorded bleeding before and after treatment. The MRI performance of 102 joints was evaluated by using Denver scoring system, then was divided into 0-6 and 7-10 groups. Finally, the differences between 2 groups were analyzed. Results: Average pain score of all hemophilic arthritis patients at 6 months, 1, 2 and 3 years post treatment decreased from 3.2±2.4 (n=326) to 1.2±0.6 (n=285, P=0.021) , 1.7±0.5 (n=242, P=0.032) , 2.1±1.1 (n=212, P=0.030) and 2.2±1.6 (n=176, P=0.037) , respectively. The frequency of bleeding in 405 joints at 1, 2 and 3 years post treatment decreased from 15.1±3.6 to 2.1±0.7, 4.3±0.6, and 4.8±0.8 times per year (P<0.01) , respectively; Meanwhile, the proportions of significantly ameliorated joints' activities were observed as of 68.50% (248/362) , 58.39% (181/310) , 55.67% (162/239) and 42.61% (75/176) , respectively. The frequencies of haemarthrosis at 1 and 2 years post treatment in patients with 0-6 Denver Score (45 target joints) reduced from 13.0±1.9 to 1.3±0.6 (P=0.002) and 3.1±0.9 (P=0.009) times per year, respectively, which also decreased in 7-10 group (57 target joints) from 16.6±2.1 to 3.1±0.9 (P=0.008) and 5.7±1.1 (P=0.004) times per year, respectively. There was no statistical difference between 0-6 and 7-10 groups before treatment in the terms of haemarthrosis frequency (P=0.773) . However, 7-10 group had higher haemarthrosis frequency at 1 and 2 years post treatment compare with 0-6 group (P=0.028 and 0.042, respectively) . Synovial volumes in 29 joints reduced after 6 month when compared with baseline [ (2 362.15±32.41) mm(3) vs (3 012.40±39.78) mm(3), t=7.621, P<0.001]. Conclusion: Radiosynovectomy with p-32 colloid on haemophilic synovitis was a safe and effective procedure. The patients with Denver Score of 0-7 had lower frequency of haemarthrosis.
Assuntos
Hemartrose , Doenças Hematológicas , Adolescente , Artrite , Coloides , Hemofilia A , Humanos , SinoviteRESUMO
Objective: To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL). Methods: Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m(-2)·d(-1), d(1-28)) + ATO (0.16 mg·kg(-1)·d(-1), d(1-28)) + Idarubicin (8 mg·m(-2)·d(-1), d(3-5)) /daunorubicin (40 mg·m(-2)·d(-1), d(3-5)) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above. Of 184 cases, 69 cases accompanied with WBC counts>10×10(9)/L, 115 cases with WBC counts≤10×10(9)/L at onset. Results: â Short-term efficacy: After one cycle induction therapy, the rates of hematologic remission, genetic remission, molecular remission and induced differentiation syndrome (DS) in three-drug regimen group were 98.3%, 87.9%, 72.4% and 0 respectively, while those in two-drug regimen group were 87.3%, 65.9%, 51.6% and 12.7% respectively. In patients with WBC >10×10(9)/L, DS rate and early mortality in three-drug regimen group were lower than in two-drug regimen group (0 vs 15.6%, 4.2% vs 15.6%, respectively). In patients with WBC≤10×10(9)/L, DS rate in three-drug regimen group was also lower than in two-drug regimen group (0 vs 12.3%) , but there were no statistical differences in terms of relapse and early mortality. â¡ Long-term efficacy: The relapse rate, overall survival (OS) and disease free survival (DFS) in three-drug regimen group were 0, 98.5%, 96.6% respectively, while those in two-drug regimen group were 8.6%, 86.5% and 84.1% respectively; the advantages of three-drug over two-drug regimen, especially in cases of WBC >10×10(9)/L were observed. ⢠Side effects: the incidences of gastrointestinal reaction, liver dysfunction, myocardial damage and headache in three-drug regimen group hardly increased. Conclusion: The efficacies of three-drug induction therapy were superior to two-drug one.
Assuntos
Leucemia Promielocítica Aguda , Antraciclinas , Protocolos de Quimioterapia Combinada Antineoplásica , Daunorrubicina , Intervalo Livre de Doença , Humanos , Idarubicina , Terapia Neoadjuvante , Recidiva , Indução de Remissão , TretinoínaRESUMO
Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People's Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored. Results: â Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . â¡At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ(2)=8.462, P=0.004; 16.1% vs 4.3%, χ(2)=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ(2)=5.610, P=0.018; 16.7% vs 4.4%, χ(2)=4.833, P=0.028, respectively) . â¢The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34(+), CD56(+) or FLT3-ITD mutation were worse (P<0.05) . Conclusions: Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.
Assuntos
Leucemia Promielocítica Aguda , Adulto , Intervalo Livre de Doença , Humanos , Mutação , Prognóstico , Tirosina Quinase 3 Semelhante a fmsRESUMO
Ichthyosis hystrix (IH) is characterized by spiny hyperkeratotic scale, and includes Brocq type, Lambert type, Curth-Macklin type, Rheydt type and Bäfverstedt type. The first documented cases of familial IH were of Lambert type. However, the ultrastructural features of IH Lambert type have not been reported. Three patients in two generations of a family from north China were observed. The patients showed widespread verrucose lesions without blister formation. The face, palms and soles were unaffected. This presentation strongly resembled IH Lambert type. The lesions faded dramatically in summer, without treatment. Light microscopic examinations showed binuclear cells and shell formation in the granular and upper spinous layers in all specimens, with similar findings in winter, when lesions were prominent, and in summer, when lesions had subsided. Electron microscopic examination revealed binuclear keratinocytes and concentric, thin to thick, unbroken shells of tonofilaments surrounding the nuclei, and segregation of cytoplasmic components. This family is the first with familial IH strongly resembling Lambert type to be reported in China. Binuclear cells and tonofilaments shells surrounding the nucleus in upper keratinocytes were characteristic features, which were similar to those reported in IH Curth-Macklin type. The basic histopathological defects were not changed despite significant clinical improvement of the lesion.
Assuntos
Ictiose/patologia , Pele/ultraestrutura , Adolescente , China , Feminino , Humanos , Ictiose/genética , Masculino , Microscopia EletrônicaRESUMO
Defense mechanisms against Sporothrix schenckii were studied using mouse models. After an intracutaneous injection of the yeast form of S. schenckii to the dorsal skin of the congenitally athymic nude and normal heterozygote littermate mice, nodules were formed. They regressed and disappeared in 10 weeks in the case of normal mice. On the other hand, nodules and then ulceration developed progressively in nude mice until all animals expired by dissemination of microorganisms at the 11th week of inoculation. Histopathologically the migrated cells were similar in both the normal and the nude mice, particularly during the early phase (within 24 h), with infiltration by PMNs being predominant. Fragmentation of S. schenckii commenced early during the 12-24 h stage of inoculation in the normal mice, while such fragmentation was scarce in nude mice even though numerous PMNs accumulated. Microscopic observations in the early stages (within 24 h of inoculation) suggested that the lack of killing activity by PMNs in nude mice contributes more to the impaired defense than the lack of macrophage activation by T-cells.
Assuntos
Hospedeiro Imunocomprometido/imunologia , Neutrófilos/imunologia , Esporotricose/imunologia , Abscesso/microbiologia , Animais , Modelos Animais de Doenças , Granuloma/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Esporotricose/patologia , Fatores de TempoRESUMO
Sporothrix schenckii produces two extracellular proteinases, namely proteinase I and II. Proteinase I is a serine proteinase, inhibited by chymostatin, while proteinase II is an aspartic proteinase, inhibited by pepstatin. Studies on substrate specificity and the effect of proteinase inhibitors on cell growth suggest an important role for these proteinases in terms of fungal invasion and growth. There has, however, been no evidence presented demonstrating that S. schenckii produces 2 extracellular proteinases in vivo. In order to substantiate the in vivo production of proteinases and to attempt a preliminary serodiagnosis of sporotrichosis, serum antibodies against 2 proteinases were assayed using S. schenckii inoculated hairless mice. Subsequent to an intracutaneous injection of S. schenckii to the mouse skin, nodules spontaneously formed and disappeared for a period of 4 weeks. Histopathological examination results were in accordance with the microscopic observations. Micro-organisms disappeared during the fourth week. Serum antibody titers against purified proteinases I and II were measured weekly, using enzyme-linked immunosorbent assay (EIA). As a result, the time course of the antibody titers to both proteinases I and II were parallel to that of macroscopic and microscopic observations in an experimental mouse sporotrichosis model. These results suggest that S. schenckii produces both proteinases I and II in vivo. Moreover, the detection of antibodies against these proteinases can contribute to a serodiagnosis of sporotrichosis.
Assuntos
Anticorpos Antifúngicos/sangue , Endopeptidases/imunologia , Sporothrix/imunologia , Esporotricose/imunologia , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Camundongos , Camundongos Pelados , Camundongos Endogâmicos ICR , Testes Sorológicos , Testes Cutâneos , Sporothrix/enzimologia , Esporotricose/diagnóstico , Esporotricose/patologiaRESUMO
Sporothrix schenckii produces two extracellular proteinases, namely proteinase I and II. Proteinase I is a serine proteinase, inhibited by chymostatin. On the other hand, proteinase II is an aspartic proteinase, inhibited by pepstatin. The addition of either pepstatin or chymostatin to the culture medium did not inhibit cell growth, however the addition of both inhibitors strongly inhibited fungal growth. Accordingly, this suggested that extracellular proteinases play an important role in cell growth and that such cell growth may be suppressed if these proteinases are inhibited. In order to substantiate this speculation in sporotrichosis, the effects of proteinase inhibitors on the cutaneous lesions of mice were studied. Ointments containing 0.1% chymostatin, 0.1% pepstatin and 0.1% chymostatin-0.1% pepstatin were applied twice daily on the inoculation sites of hairless mouse skin, and the time courses of the lesions examined. The inhibitory effect in vivo on S. schenckii was similar to that demonstrated in our previous in vitro study. Compared to the control, the time course curve of the number of nodules present after the application of either pepstatin or chymostatin was slightly suppressed. The application of both pepstatin and chymostatin, however, strongly suppressed nodule formation. This study not only confirmed the role of 2 proteinases of S, schenckii for fungal growth in vivo, but also may lead to their use as new topical therapeutic agents.