RESUMEN
OBJECTIVE: To explore the clinical efficacy and safety of flumatinib mesylate produced in China in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). METHODS: 32 newly diagnosed CML-CP patients admitted to the Hematology Department of the Affiliated Hospital of Southwest Medical University from March 1, 2020 to March 31, 2022, who had never received any tyrosine kinase inhibitor (TKI) were included in the study. The patients were treated by flumatinib mesylate 600mg once daily. The hematologic, cytogenetic and molecular responses were assessed at 3-, 6- and 12-month, and adverse effects of the drug were evaluated. RESULTS: 31 patients were treated with flumatinib for≥3 months, of which 24 patients were treated for ≥6 months and 14 patients were treated for≥12 months. At 3rd month of treatment, 30 out of 31 patients achieved complete hematologic response (CHR); 24 patients underwent cytogenetic testing and 22 cases achieved major cytogenetic response(MCyR), of which 21 cases achieved complete cytogenetic response (CCyR); Among 25 patients who underwent molecular testing, 22 patients had BCR-ABLIS≤10%, including 10 patients with BCR-ABLIS≤0.1%, and 6 patients with BCR-ABLIS≤0.01%. At 6th month of treatment, 23 out of 24 patients achieved CHR; 17 patients underwent cytogenetic testing and all achieved CCyR; Among 23 patients who underwent molecular testing, 20 patients had BCR-ABLIS≤1%, including 16 patients with BCR-ABLIS≤0.1% and 12 patients with BCR-ABLIS≤0.01%. At 12nd month of treatment, all 14 patients achieved CHR and CCyR; Among them, 10 patients had BCR-ABLIS≤0.1%, including 9 patients with BCR-ABLIS≤0.01%. The grade â ¢/â £ leukopenia, thrombocytopenia and anemia rates in the patients were 13.3%, 20.0% and 3.3%, respectively. One patient stopped flumatinib therapy due to severe and persistent hematologic toxicity. The major non-hematologic adverse events were abnormal liver function (20%), diarrhea (10%), bone/joint pain (10%), muscle spasm (10%), rash (6.7%), acute kidney injury (6.7%) and nausea(3.3%), most of which were grade I-II. No patient experienced grade â £ non-hematologic adverse events. No drug toxicity-related death occurred. CONCLUSION: Flumatinib mesglate, as the first-line treatment for newly diagnosed CML-CP, can enable the patients to achieve early and deep molecular and cytogenetic responses, and shows good safety.
Asunto(s)
Anemia , Antineoplásicos , Leucemia Mielógena Crónica BCR-ABL Positiva , Trombocitopenia , Humanos , Mesilato de Imatinib/uso terapéutico , Pirimidinas/farmacología , Proteínas de Fusión bcr-abl , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Benzamidas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del Tratamiento , Respuesta Patológica Completa , Mesilatos/uso terapéutico , Antineoplásicos/uso terapéuticoRESUMEN
OBJECTIVE: To observe the efficacy of veneclax combined with azacitidine in acute myeloid leukemia(AML) patients and explore the predictors of treatment response and recurrence. METHODS: The clinical data of 30 AML patients who received venetecla combined with azacitidine in the Affiliated Hospital of Southwest Medical University from January 2021 to September 2022 were retrospectively analyzed, composite complete remission (CRc) rate, overall response rate(ORR), and disease free survival(DFS) of patients were observed. RESULTS: After one course of trea- tment, CRc was 16 cases and ORR was 23/30. Patients with TP53 mutation had poor treatment response (P=0.009). After 1-2 courses, 25 patients reached CR/CRi. Finally, 24 patients who obtained CR/CRi were included to observe the duration of remission. 17 patients had relapse, with a median recurrence time of 3.9 (0.6-15.9) months. The Kaplan-Meier curve showed that MRD negative was a favorable factor for maintaining DFS status (HR=0.5647,95%CI:0.2179-1.464,P=0.007), while NRAS mutation was an adverse factor for maintaining DFS (HR=2.036,95%CI:0.6639-6.245,P=0.0003). Univariate combined multivariate cox regression analysis showed that NRAS mutation was an independent risk factor affecting DFS in patients (HR=5.569, P<0.05). In addition, the cases number of early recurrence in MRD negative group (n=8) and MRD non-negative group (n=9) was 0 and 5, respectively, the difference was statistically significant (P=0.012). There were 3 cases of early recurrence in the NRAS mutant group (n=4) and 2 cases in the NRAS wild-type group (n=13), the difference was statistically significant (P=0.022). CONCLUSION: TP53 mutation is a predictor of poor response to veneclax in combination with azacitidine. With the conti-nuation of the combination chemotherapy regimen described above, NRAS mutation is an independent risk factor for DFS in patients. Moreover, the patients with non-negative MRD and NRAS mutations are at high risk of early recurrence.
Asunto(s)
Leucemia Mieloide Aguda , Humanos , Inducción de Remisión , Pronóstico , Estudios Retrospectivos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Recurrencia , Azacitidina/uso terapéutico , Enfermedad Crónica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
PURPOSE: The renewal and iteration of chemotherapy drugs have resulted in more frequent long-term remissions for patients with multiple myeloma (MM). MM has transformed into a chronic illness for many patients, but the cancer-related fatigue (CRF) of many MM convalescent patients experience is frequently overlooked. We investigated whether the accompanying treatment of family members would affect MM patients' CRF and explore their serum metabolomics, so as to provide clinicians with new ideas for identifying and treating CRF of MM patients. METHODS: This was a single-center study, and a total of 30 MM patients were included in the study. Patients were divided into two groups based on whether they have close family members accompanying them through the whole hospitalization treatment. These patients received regular chemotherapy by hematology specialists, and long-term follow-up was done by general practitioners. Patients' CRF assessment for several factors used the Chinese version of the Brief Fatigue Inventory (BFI-C). Face-to-face questionnaires were administered at a time jointly determined by the patient and the investigator. All questionnaires were conducted by a general practitioner. The LC-MS-based metabolomics analysis determined whether the patients' serum metabolites were related to their fatigue severity. A correlation analysis investigated the relationship between serum metabolites and clinical laboratory indicators. RESULTS: The fatigue severity of MM patients whose family members participated in the treatment process (group A) was significantly lower than patients whose family members did not participate in the treatment process (group B). There was a statistically significant difference (fatigue severity composite score: t = - 2.729, p = 0.011; fatigue interference composite score: t = - 3.595, p = 0.001). There were no differences between the two groups of patients' gender, age, regarding clinical staging, tumor burden, blood routine, biochemical, or coagulation indexes. There were 11 metabolites, including guanidine acetic acid (GAA), 1-(Methylthio)-1-hexanethiol, isoeucyl-asparagine, L-agaritine, tryptophyl-tyrosine, and betaine, which significantly distinguished the two groups of MM patients. GAA had the strongest correlation with patient fatigue, and the difference was statistically significant (fatigue severity composite score: r = 0.505, p = 0.0044; fatigue interference composite score: r = 0.576, p = 0.0009). The results showed that GAA negatively correlated with albumin (r = - 0.4151, p = 0.0226) and GGT (r = - 0.3766, p = 0.0402). Meanwhile, GAA positively correlated with PT (r = 0.385, p = 0.0473), and the difference was statistically significant. CONCLUSION: The study is the first to report that family presence throughout the whole hospitalization may alleviate CRF in MM patients. Moreover, the study evaluated serum metabolites linked to CRF in MM patients and found that CRF has a significant positive correlation with GAA. GAA may be a more sensitive biomarker than liver enzymes, PT, and serum albumin in predicting patient fatigue. While our sample may not represent all MM patients, it proposes a new entry point to help clinicians better identify and treat CRF in MM patients.
Asunto(s)
Mieloma Múltiple , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Fatiga/etiología , Fatiga/terapia , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To investigate the regulatory effect of miRNA-29a-3p (miR-29a-3p ) on hepatoma-derived growth factor (HDGF), and its influences on the proliferation and apoptosis of acute lymphoblastic leukemia (ALL) cell line E6-1. METHODS: Thirty-five patients with ALL treated in our hospital from January 2017 to January 2019 were selected as research objects, and 35 adults who underwent physical examination in the same period were selected as healthy control group. The miR-29a-3p overexpression vector, miR-29a-3p inhibitory expression vector, and miR-29a-3p and HDGF co-overexpression vector were transfected into E6-1 cells. The expression levels of miR-29a-3p and HDGF mRNA were detected by RT-qPCR. The expression of protein was detected by Western blot. The targeting relationship between miR-29a-3p and HDGF was detected by dual luciferase reporter assay. The cell proliferation was detected by CCK-8 method, while apoptosis detected by flow cytometry. RESULTS: Compared with healthy control group, HDGF was highly expressed in serum of patients with ALL and leukemia cells HuT 78, E6-1, CCRF-CEM, while miR-29a-3p was low expressed (P<0.05). After overexpression of miR-29a-3p , the expression levels of CyclinD1 and Bcl-2 in leukemia cells E6-1 were significantly reduced, while the expression levels of p21 and Bax were significantly increased (P<0.05). The activity of E6-1 cells was also significantly reduced, while the apoptosis rate of E6-1 cells was significantly increased (P<0.05). miR-29a-3p could target and regulate the expression of HDGF, while overexpression of HDGF reversed the inhibitory effect of miR-29a-3p overexpression on the proliferation and promotion effect on the apoptosis of leukemia cells E6-1. CONCLUSION: Overexpression of miR-29a-3p can inhibit the proliferation and promote the apoptosis of ALL cells E6-1, and its mechanism may be related to the regulation of HDGF expression.
Asunto(s)
Leucemia , MicroARNs , Humanos , Apoptosis , Proliferación Celular , MicroARNs/genéticaRESUMEN
Metabolic abnormality has been considered to be the seventh characteristic in cancer cells. The potential prospect of using serum biomarkers metabolites to differentiate ALL from AML remains unclear. The purpose of our study is to probe whether the differences in metabolomics are related to clinical laboratory-related indicators. We used LC-MS-based metabolomics analysis to study 50 peripheral blood samples of leukemia patients from a single center. Then Chi-square test and T test were used to analyze the clinical characteristics, laboratory indicators and cytokines of 50 patients with leukemia. Correlation analysis was used to explore the relationship between them and the differential metabolites of different types of leukemia. Our study shows that it is feasible to better identify serum metabolic differences in different types and states of leukemia by metabolomic analysis on existing clinical diagnostic techniques. The metabolism of choline and betaine may also be significantly related to the patient's blood lipid profile. The main enrichment pathways for distinguishing differential metabolites in different types of leukemia are amino acid metabolism and fatty acid metabolism. All these findings suggested that differential metabolites and lipid profiles might identify different types of leukemia based on existing clinical diagnostic techniques, and their rich metabolic pathways help us to better understand the physiological characteristics of leukemia.
RESUMEN
OBJECTIVE: To investigate the potential therapeutic role of porous SiO2 -coated ultrasmall selenium particles nanospheres (Se@SiO2 nanospheres) pretreatment in acute pancreatitis (AP) and to investigate the related mechanism. METHODS: C57BL/6 mice were randomized to the normal control (CON) group, the AP (induced by cerulein injection) (CAE) group, and AP pretreated with Se@SiO2 nanocomposites at 1 and 2 mg/kg (CAE + 1 or 2 mg/kg Se@SiO2 ) groups, respectively. Serum levels of amylase and lipase, inflammatory cytokines (interleukin [IL]-6, IL-1ß and tumor necrosis factor [TNF]-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were measured, and histopathology was performed to examine the tissue samples of the pancreas, lungs, kidneys and liver. Immunofluorescence assay of reactive oxygen species (ROS), myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were conducted, and levels of MPO, malondialdehyde, superoxide dismutase and glutathione were evaluated. Finally, Western blot analysis was used to evaluate protein expressions of Nrf2, HO-1, NQO1, TLR4, MyD88 and p-p65 in pancreatic tissue. RESULTS: Se@SiO2 nanospheres alleviated pathological damage to the pancreas, and reduced pancreatic enzymes and inflammatory cytokines. Injury to other organs such as the liver, lungs and kidneys was also alleviated, as indicated by decreased ALT, AST, BUN, and Cr levels as well as improved histopathology. Moreover, Se@SiO2 nanospheres reduced oxidative stress, and ultimately inhibited TLR4/ MyD88/p-p65 pathway and increased the protein expressions of NQO1, Nrf2, and HO-1. CONCLUSION: Se@SiO2 nanospheres may alleviate AP by relieving oxidative stress and targeting the TLR4/Myd88/p-p65 and NQO1/Nrf2/HO-1 pathways.
Asunto(s)
Ceruletida , Nanosferas , Pancreatitis , Selenio , Enfermedad Aguda , Animales , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Estrés Oxidativo , PorosidadRESUMEN
Severe acute pancreatitis (SAP) is a severe acute abdominal disease. Recent evidence shows that intestinal homeostasis is essential for the management of acute pancreatitis. Chitosan oligosaccharides (COS) possess antioxidant activity that are effective in treating various inflammatory diseases. In this study we explored the potential therapeutic effects of COS on SAP and underlying mechanisms. Mice were treated with COS (200 mg·kg-1·d-1, po) for 4 weeks, then SAP was induced in the mice by intraperitoneal injection of caerulein. We found that COS administration significantly alleviated the severity of SAP: the serum amylase and lipase levels as well as pancreatic myeloperoxidase activity were significantly reduced. COS administration suppressed the production of proinflammatory cytokines (TNF-α, IL-1ß, CXCL2 and MCP1) in the pancreas and ileums. Moreover, COS administration decreased pancreatic inflammatory infiltration and oxidative stress in SAP mice, accompanied by activated Nrf2/HO-1 and inhibited TLR4/NF-κB and MAPK pathways. We further demonstrated that COS administration restored SAP-associated ileal damage and barrier dysfunction. In addition, gut microbiome analyses revealed that the beneficial effect of COS administration was associated with its ability to improve the pancreatitis-associated gut microbiota dysbiosis; in particular, probiotics Akkermansia were markedly increased, while pathogenic bacteria Escherichia-Shigella and Enterococcus were almost eliminated. The study demonstrates that COS administration remarkably attenuates SAP by reducing oxidative stress and restoring intestinal homeostasis, suggesting that COS might be a promising prebiotic agent for the treatment of SAP.
Asunto(s)
Quitosano/uso terapéutico , Homeostasis/efectos de los fármacos , Intestinos/efectos de los fármacos , Oligosacáridos/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Pancreatitis/tratamiento farmacológico , Enfermedad Aguda , Animales , Apoptosis/efectos de los fármacos , Quitina/análogos & derivados , Quitina/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Páncreas/efectos de los fármacos , Páncreas/patología , Pancreatitis/patología , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate the expressions of stromal cell-derived factor (CXCL12), stromal cell-derived factor receptor (CXCR4), vascular endothelial growth factor (VEGF) and microvessel density (MVD) in bone marrow microsputum of patients with multiple myeloma (MM) and their correlation with the prognosis. METHODS: The expressions of CXCL12, CXCR4, VEGF and MVD in bone marrow microtubules of 57 newly diagnosed MM patients and 26 normal bone marrow samples were detected by immunohistochemistry. The rank sum test was used to compare the differences between the two groups. The clinical data of the patients were collected to analyze the correlation between the indicators of the MM group and the prognosis. RESULTS: The expressions of CXCL12, CXCR4, VEGF and MVD in the bone marrow biopsy of the patients in MM group were significantly higher than those in the normal control group (Pï¼0.05). The expressions levels of CXCL12, CXCR4, VEGF and MVD were in the bone marrow of the patients in MM group were correlated with the ISS stage, risk stratification and the proportion of plasma cells in the bone marrow (Pï¼0.05). Univariate analysis showed that age, ISS stage, risk stratification, plasma cell ratio, expressions of CXCL12, CXCR4, VEGF, and MVD associated with the prognosis of patients with MM (Pï¼0.05). Multivariate analysis found that expressions of CXCR4, VEGF, MVD, age, and plasma cell ratio were independent prognostic factors. CONCLUSION: The expressions of CXCL12, CXCR4, VEGF and MVD are increase in the bone marrow of patients with multiple myeloma, and their expressions levels are associate with the occurrence and development of multiple myeloma, and their high expression may indicate a poor prognosis.
Asunto(s)
Mieloma Múltiple , Factor A de Crecimiento Endotelial Vascular , Quimiocina CXCL12 , Humanos , Microcirculación , Neovascularización Patológica , Pronóstico , Receptores CXCR4 , Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVE: To investigate the pathological features, clinical characteristics, treatment outcomes and prognosis influcing factors in patients with extranodal NK/T cell lymphoma(ENKTL). METHODS: Clinical data of 61 patients with ENKTL treated in oncology and hematology department of Southwest Medical University Affiliated Hospital from April 2013 to August 2018 were restrospectively analyzied, the pathological features, clinical characteristics, therapeutic strategy and prognosis-related factors were explored. RESULTS: The median follow-up was 20 monthsï¼range 3 to 81 monthsï¼and median age was 48 years oldï¼range 15 to 70 years oldï¼, the proportion of male and female patients was 1.5â¶1. The overall survival(OS) rate of 1,3 years was 67.2%,26.2% respectively and progression-free survival(PFS) rate was 63.9%,24.5% respectively. Univariate analysis showed that the percentage of Ki-67 affected efficacy of initial treatment; Ann Arbor stage, LDH level, EBER test, anemia, IPI score, B-symptoms, bone marrow involvement, lymphnodes involvement, monotherapy, initial treatment effect were factors associated with prognosis. According to multivariate analysis, the initial coure remission was the independent factors for prognosis. More survival benefit could be obtained by receiving radiotherapy especially for early stage patients. CONCLUSION: Initial course remission is independent factors influencing prognosis. For patients in early stage(IE to IIE), radiotherapy or combined radiotherapy with chemotherapy is superior to chemotherapy alone; The patients diagnosed with IIIE or IVE show rapid progression of disease and poor outcome, whether they are treated with combined treatment or monotherapy. New methods such as hematopoietic stem cell infusion and CAR-T can be considered.
Asunto(s)
Linfoma Extranodal de Células NK-T , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Combinada , Femenino , Humanos , Linfoma Extranodal de Células NK-T/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To investigate the effect of microvascular endothelial cells (MEC) on the proliferation of hematopoictic stem cells (HSC) under different culture conditions in vitro. METHODS: The MEC from lung tissue of C57BL/6 mice and the HSC from bone marrow of GFP mice were used for non-contact co-culture, 2 D contact co-culture, at same time the single MEC and single HSC culture were seted up and were used as control group. The cell counting and CCK-8 method were used to detect and compare the proliferation levels of suspension cells in different groups on day 1, 3, 5 and 7. RESULTS: MEC presented adherent growth. In process of cell culture in vitro, the number of suspension cells in MEC and HSC co-culture group and single HSC culture group increased, the suspension cells in 2D contact and non-contact co-culture groups more early gated into logarithmic growth phase as compared with suspension cells in control group, the proliferation level of suspention cells in 2D contact culture group was higher than that in non-contact co-culture group and single HSC culture group (P<0.05), the proliferation level of suspension cells in non-contact co-culture group was higher than that in single HSC culture group (P<0.05). CONCLUSION: The culture of HSC in vitro can proliferate HSC, MEC can promote the proliferation of HSC, MEC also can promote the HSC proliferation by non-contact co-culture in vitro, which relates with the effect of cytokines secreted from MEC; the effect of MEC and HSC contact co-culture on the proliferation of HSC is stronger than that of non-contact co-culture, which relates with the regulation of cell-cell contact.
Asunto(s)
Médula Ósea , Células Madre Hematopoyéticas , Animales , Células de la Médula Ósea , Proliferación Celular , Células Endoteliales , Ratones , Ratones Endogámicos C57BLRESUMEN
OBJECTIVE: To study the effect and mechanism of shh and mesenchymal stem cellï¼MSCï¼synergism on the proliferation of hematopoietic stem cells in noninvasive co-culture system in vitro. METHODS: The mesenchymal stem cells were cultured in vitroï¼CD34+ cells were sorted by mini MACS magnetic bead separatorï¼flow cytometry was used to identify the purity of 2 cells. CD34+ cells and MSCs were seeded to upper and low of transwell respecibely for non-contact cocultureï¼and add exogenous shh protein for intervenece. The number of MSCs and HSCsï¼the total amount of RNAï¼the expression of ki67 and Tie-2 mRNA of HSCï¼the expression of VEGF and Ang-1 mRNA of MSC were detected for investigating the condition of cell proliferation and the expression of angiogenic factors. RESULTS: The total number of cellsï¼the total amount of RNA and the relative expression of ki67, Tie-2, VEGF and Ang-1 in non-contact co-culture group increased and showed the following trends on the 7th dayï¼the above-mentioned indexes in group MSC + HSC, group shh + HSC were higher than those in group HSC, while those in MSC + shh + HSC Group was higher than those in MSC + HSC and shh + HSC group. CONCLUSION: Angiogenic factors help MSC to proliferate HSC and amplify the CD34+ hematopoietic stem/progenitor cells by shh and MSC synergism in vitro coculture system which may be related with angiogenic factors.
Asunto(s)
Células Madre Mesenquimatosas , Médula Ósea , Células de la Médula Ósea , Proliferación Celular , Técnicas de Cocultivo , Sangre Fetal , Células Madre HematopoyéticasRESUMEN
BACKGROUND: Tissue sampling for biliary stricture is important for differential diagnosis and further treatment. The aim of this study was to assess a novel dilation catheter-guided mini-forceps biopsy (DCMB) method in the diagnosis of malignant biliary strictures. METHODS: 42 patients with malignant biliary stricture who underwent both brush cytology and DCMB during endoscopic retrograde cholangiopancreatography between October 2014 and November 2015 were retrospectively included. During DCMB, the mini biopsy forceps was introduced into the biliary stricture through the dilation catheter, and then the position and direction of the forceps were adjusted to obtain tissue samples. RESULTS: The positive rate of DCMB was significantly higher than that of brush cytology (81.0â% [34/42] vs. 38.1â% [16/42]; Pâ<â0.001). No severe complications occurred; three patients (7.1â%) experienced mild procedure-related acute pancreatitis. CONCLUSIONS: The novel DCMB technique was a practical, safe, efficient, and low-costing method for diagnosing malignant biliary stricture with a high accuracy rate.
Asunto(s)
Carcinoma/diagnóstico , Colestasis/etiología , Neoplasias del Sistema Digestivo/diagnóstico , Biopsia Guiada por Imagen/métodos , Anciano , Carcinoma/complicaciones , Carcinoma/patología , Catéteres , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Neoplasias del Sistema Digestivo/complicaciones , Neoplasias del Sistema Digestivo/patología , Femenino , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/instrumentación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Instrumentos QuirúrgicosRESUMEN
An increasing number of reports have demonstrated that there is an association between the presence of pathogenic microorganisms and pancreatic cancer. However, the role of the duodenal microbiota in pancreatic carcinogenesis remains unknown. In this study, duodenal mucosal microbiota was analyzed in 14 patients with pancreatic head cancer and 14 healthy controls using 16S rRNA gene pyrosequencing methods. Plasma endotoxin activity and the concentrations of the proinflammatory cytokine IL-6 and C-reactive protein (CRP) were measured in blood samples. The urea breath test was used to detect Helicobacter pylori infections. Endoscopic duodenal mucosal biopsies were evaluated by histological examinations. Statistical comparisons of inflammatory factors revealed significantly higher levels of CRP and IL-6 in the pancreatic cancer group as compared to healthy controls. Patients with pancreatic cancer also had a higher incidence of H. pylori infections and showed mucosal changes, including villous abnormalities and diffuse inflammatory cell infiltration in the lamina propria. The sequences analysis showed that based on linear discriminant analysis effect size (LEfSe) analysis at the genus level, Acinetobacter, Aquabacterium, Oceanobacillus, Rahnella, Massilia, Delftia, Deinococcus, and Sphingobium were more abundant in the duodenal mucosa of pancreatic cancer patients, whereas the duodenal microbiotas of healthy controls were enriched with Porphyromonas, Paenibacillus, Enhydrobacter, Escherichia, Shigella, and Pseudomonas. These results reveal a picture of duodenal microbiota in pancreatic head cancer patients that could be useful in future trials investigating the role of gut microbiota in pancreatic cancer.
Asunto(s)
Duodeno/microbiología , Microbioma Gastrointestinal , Neoplasias Pancreáticas/microbiología , Anciano , Proteína C-Reactiva/análisis , Endotoxinas/sangre , Enteritis/epidemiología , Enteritis/etiología , Enteritis/microbiología , Femenino , Voluntarios Sanos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori , Humanos , Incidencia , Interleucina-6/análisis , Masculino , Persona de Mediana Edad , Páncreas/patología , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , ARN Ribosómico 16S/análisisRESUMEN
Steroid-induced avascular necrosis of femoral head (SANFH) occurs frequently in patients receiving high-dose steroid treatment for these underlying diseases. The target of this study is to investigate the effect of microRNA-320 (miR-320) on SANFH by targeting CYP1A2. CYP1A2 expression was detected using immunohistochemistry. Specimens were collected from patients with SANFH and femoral neck fracture. Seventy rats were assigned into seven groups. The targeting relationship between miR-320 and CYP1A2 was verified by bioinformatics website and dual luciferase reporter gene assay. RT-qPCR and Western blot analysis were used to detect miR-320 and CYP1A2 expressions. The enzymatic activity of CYP1A2 was detected by fluorescence spectrophotometry. Hemorheology and microcirculation were measured in rats. MiR-320 expression decreased and CYP1A2 expression and enzymatic activity increased in SANFH patients compared to those with femoral neck fracture. CYP1A2 was the target gene of miR-320. Hemorheology and microcirculation results showed that up-regulated expression of CYP1A2 promoted the development of SANFH while increased expression of miR-320 inhibited the development of SANFH. Compared with the SANFH group, the SANFHâ¯+â¯miR-320 mimic group showed increased miRNA-320 expression, and decreased CYP1A2 expression and enzymatic activity. Opposite results were found in the SANFHâ¯+â¯miR-320 inhibitor group. The SANFHâ¯+â¯miR-320 inhibitorâ¯+â¯pCR-CYP1A2_KO group showed decreased miRNA-320 expression and the SANFHâ¯+â¯pCR-CYP1A2_KO group showed decreased CYP1A2 expression and enzymatic activity. Our findings provide evidences that miR-320 might inhibit the development of SANFH by targeting CYP1A2.
Asunto(s)
Citocromo P-450 CYP1A2/metabolismo , Fracturas del Cuello Femoral/metabolismo , Necrosis de la Cabeza Femoral/metabolismo , MicroARNs/biosíntesis , Regulación hacia Arriba , Animales , Citocromo P-450 CYP1A2/genética , Femenino , Fracturas del Cuello Femoral/genética , Fracturas del Cuello Femoral/patología , Necrosis de la Cabeza Femoral/genética , Necrosis de la Cabeza Femoral/patología , Necrosis de la Cabeza Femoral/prevención & control , Humanos , Masculino , MicroARNs/genética , Ratas , Ratas Sprague-DawleyRESUMEN
Cutaneous scars (particularly hypertrophic and keloid scars), not only can cause adverse cosmetic problems, but also can be associated with emotional distress such as anxiety and depression. Comparing with other surgical treatments, patients who do not opt for or cannot opt for invasion therapies are more eligible for using the topical anti-scarring agents. In this mini-review, we have researched for and collected the data between October 2005 and October 2015, in PubMed and Web of Science, and identified those agents including silicone-based products, imiquimod, corticosteroids, 5-fluorouracil, bleomycin, mitomycin, and plant extracts such as onion extract, asiaticoside, aloe vera, vitamin E, and so on. Besides, we have listed these popular products in commercial market with their useful information. We have also described the combined process according to our clinical experience. However, to establish the more effective treatment among different types of topical agents or their combined process, large, well-designed head-to-head comparisons between individual and combined preparations in relevant patient populations are urgently needed.
Asunto(s)
Cicatriz/tratamiento farmacológico , Cicatriz/prevención & control , Piel/efectos de los fármacos , Administración Tópica , Alantoína/uso terapéutico , Cicatriz/patología , Combinación de Medicamentos , Heparina/uso terapéutico , Pomadas/uso terapéutico , Extractos Vegetales/uso terapéutico , Piel/patología , Triterpenos/uso terapéuticoRESUMEN
BACKGROUND: Liposuction-curettage (LC) is a popular and effective surgical method for the treatment of axillary bromhidrosis (AB). However, residual malodour and skin necrosis often appear after this type of surgery. We investigated the efficacy and complications of 4 methods of LC. METHODS: A total of 280 patients with AB comprised the study cohort, of which 228 were followed up. We carried out 4 methods of modified tumescent LC through mini-incisions and provided a questionnaire for evaluation of surgical outcome. Evaluations were malodour elimination, scarring, reduced growth of hair, and complications. Mean follow-up was 15 months. RESULTS: The study involved 449 axillae. In patients with LC in the final phase of improvement (programmed and well-organized LC, skin pinching to wrap up the cannula, LC to the skin around 2 surgical incisions, and cotton balls packed in gauze and an elastic set for post-operative management), excellent elimination of malodor was observed in 141 (89.81%) of 157 axillae. Only 4 (2.55%) cases encountered a small area of skin necrosis, and 28 (17.83%) had local damage to the epidermis. CONCLUSION: These data suggest that LC with a final phase of improvement through mini-incisions is effective for AB treatment.
HISTORIQUE: La liposuccion-curetage (LC) est un mode opératoire efficace et populaire pour traiter la bromidrose axillaire (BA). Cependant, de mauvaises odeurs résiduelles et une nécrose cutanée se produisent souvent après ce type d'opération. Les auteurs ont examiné l'efficacité et les complications de quatre types de LC. MÉTHODOLOGIE: Au total, 280 patients ayant une BA ont formé la cohorte de l'étude, dont 228 ont fait l'objet d'un suivi. Les auteurs ont effectué quatre types de LC tumescente modifiée par mini-incisions et ont remis un questionnaire d'évaluation des résultats de l'opération. Les points évalués étaient l'élimination des mauvaises odeurs, la cicatrice, la réduction de la pilosité et les complications. Le suivi moyen était de 15 mois. RÉSULTATS: L'étude portait sur 449 aisselles. Chez les patients ayant subi une LC qui en étaient à la dernière phase d'amélioration (LC programmée et bien organisée, pincement de la peau pour installer la canule, LC jusqu'à la peau par deux incisions chirurgicales, tampons d'ouate emballés dans de la gaze et bandage élastique pour la prise en charge postopératoire), les auteurs ont observé une excellente élimination des mauvaises odeurs dans 141 aisselles sur 157 (89,81%). Seulement quatre cas (2,55%) ont présenté une petite région de nécrose cutanée et 28 (17,83%), une atteinte locale de l'épiderme. CONCLUSION: Selon ces données, la LC accompagnée d'une phase finale d'amélioration par mini-incisions est efficace pour traiter la BA.
RESUMEN
OBJECTIVES: To investigate the effect of miR-183 on the cell proliferation in SW1990 pancreatic cancer cell line by targeting programmed cell death factor 4(PDCD4). METHODS: The SW1990 pancreatic cancer cells were transfected with miR-183 mimics and inhibitors at different concentrations, the alteration of PDCD4 levels was observed at specific concentrations by qPCR and Western blot. The cellular proliferation of transfected cells was determined by MTT assay. The distribution of cell cycle and apoptosis was examined by flow cytometry (FCM) and Hoechst 33258 staining. The expression of B-cell lymphoma(bcl-2) was evaluated by Western blot. RESULTS: The miR-183 mimic and inhibitor (at concentrations of 50 nmol/L or 150 nmol/L) showed significantly increasing or decreasing effects on the levels ofmiR-183 respectively. The expression of PDCD4 was downregulated in the cells transfected with miR-183 mimics, while significantly upregulated in the cells treated with miR-183 inhibitors. Western blot showed that miR-183 inhibitors resulted in a marked decrease in the expression levels of bcl-2. The growth of SW1990 cells was obviously inhibited after anti-miR-183 treatment, while an increase of apoptosis cells proportion and cell cycle G0/G1 arrest were observed after miR-183 inhibitors transfection. CONCLUSIONS: The miR-183 inhibitors could restrain cell proliferation, promote cell apoptosis and increase G0/G1 arrest in SW1990 pancreatic cancer cells, which may be possibly through targeting PDCD4.
Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , MicroARNs/genética , Neoplasias Pancreáticas/patología , Proteínas de Unión al ARN/genética , Apoptosis , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , TransfecciónRESUMEN
OBJECTIVE: To determine the viability of Schistosoma japonicum cercariae by staining. METHODS: Schistosoma japonicum cercariae were stained by 0.4% trypan blue, 0.5% methylene blue-eosin-borax (M.E.B), 0.5% eosin, 0.5% methylene blue and 0.05% neutral red, respectively, for 5 min, then they were observed under a stereoscopic microscope. RESULTS: The dead cercariae were stained in the trypan blue, M.E.B, eosin and neutral red, but unstained in the methylene blue. The vital cercariae were unstained in all the five kinds of dyes. CONCLUSION: The staining methods by using 0.4% trypan blue, 0.5%M.E.B, 0.5% eosin and 0.05% neutral red can be used to determine the viability of S. japonicum cercariae.