RESUMO
A 56-year-old male patient sought medical attention due to a gradual decline in bilateral visual acuity, which had been ongoing for a year and had rapidly worsened over the past three months. He received an initial diagnosis of bilateral concurrent cataracts and bilateral anterior megalophthalmos. Subsequently, cataract removal surgery was performed. During the surgery, it was observed that the patient had lax and fragile zonules of the crystalline lens. To address this issue, the surgical team employed reverse optic capture technique for the implantation of a three-piece intraocular lens. Following the surgery, the patient experienced a substantial improvement in uncorrected visual acuity. Remarkably, the patient remained free from adverse reactions, such as elevated intraocular pressure, during a follow-up period extending to 11 years.
Assuntos
Extração de Catarata , Catarata , Lentes Intraoculares , Masculino , Humanos , Pessoa de Meia-Idade , Implante de Lente Intraocular/métodos , Catarata/complicações , Catarata/terapia , Extração de Catarata/métodos , Olho , Complicações Pós-Operatórias , SeguimentosRESUMO
Objective: To compare the effects of two administration time strategies for rabbit antihuman thymocyte immunoglobulin (rATG) of 5mg/kg total dose in matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) . Methods: This study retrospectively analyzed the clinical data of 32 patients who received MSD-HSCT with 5 mg/kg rATG conditioning regimen at the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from October 2020 to April 2022. The patients were classified into two groups: the 4d-rATG group (16 cases), who received antithymocyte globulin (ATG) from day -5 to day -2, and the 2d-rATG group (16 cases), who received ATG from day -5 to day -4. Between the two groups, the transplantation outcomes, serum concentrations of active antithymocyte globulin (ATG) in patients from -4 days to 28 days after graft infusion (+28 days), and the reconstitution of lymphocyte subsets on days +30, +60, and +90 were compared. Results: The cumulative incidences of acute graft-versus-host disease at 100 days after graft infusion were 25.0% (95% CI 7.8% -47.2% ) and 18.8% (95% CI 4.6% -40.2% ) (P=0.605) in the 4d-rATG group and 2d-rATG group, respectively. The 1-year cumulative incidences of chronic graft-versus-host disease were 25.9% (95% CI 8.0% -48.6% ) and 21.8% (95% CI 5.2% -45.7% ) (P=0.896). The 1-year cumulative incidence of relapse was 37.5% (95% CI 18.9% -65.1% ) and 14.6% (95% CI 3.6% -46.0% ) (P=0.135), and the 1-year probabilities of overall survival were 75.0% (95% CI 46.3% -89.8% ) and 100% (P=0.062). The total area under the curve (AUC) of serum active ATG was 36.11 UE/ml·d and 35.89 UE/ml·d in the 4d-rATG and 2d-rATG groups, respectively (P=0.984). The AUC was higher in the 4d-rATG group than that in the 2d-rATG group (20.76 UE/ml·d vs 15.95 UE/ml·d, P=0.047). Three months after graft infusion, the average absolute count of CD8(+) T lymphocytes in the 4d-rATG group was lower than that in the 2d-rATG group (623 cells/µl vs 852 cells/µl, P=0.037) . Conclusion: The efficiencies of GVHD prophylaxis in MSD-PBSCT receiving 4d-ATG regimen and the 2d-rATG regimen were found to be similar. The reconstruction of CD8(+)T lymphocytes in the 2d-rATG group was better than that in the 4d-rATG group, which is related to the lower AUC of active ATG after transplantation.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Coelhos , Humanos , Soro Antilinfocitário/uso terapêutico , Irmãos , Estudos Retrospectivos , Doadores de Tecidos , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Condicionamento Pré-TransplanteRESUMO
OBJECTIVE: To compare the differences in pathogenicity and gene expression profiles between adult Schistosoma japonicum isolated from hilly and marshland and lake regions of Anhui Province, so as to provide the scientific evidence for formulating the precise schistosomiasis control strategy in different endemic foci. METHODS: C57BL/6 mice were infected with cercariae of S. japonicum isolates from Shitai County (hilly regions) and Susong County (marshland and lake regions) of Anhui Province in 2021, and all mice were sacrificed 44 days post-infection and dissected. The worm burdens, number of S. japonicum eggs deposited in the liver, and the area of egg granulomas in the liver were measured to compare the difference in the pathogenicity between the two isolates. In addition, female and male adult S. japonicum worms were collected and subjected to transcriptome sequencing, and the gene expression profiles were compared between Shitai and Susong isolates of S. japonicum. The differentially expressed genes (DEGs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. RESULTS: The total worm burdens [(14.50 ± 3.96) worms/mouse vs. (16.10 ± 3.78) worms/mouse; t = 0.877, P = 0.392], number of female and male paired worms [(4.50 ± 0.67) worms/mouse vs. (5.10 ± 1.45) worms/mouse; t = 1.129, P = 0.280], number of unpaired male worms [(5.50 ± 4.01) worms/mouse vs. (5.60 ± 1.69) worms/mouse; t = 0.069, P = 0.946], number of eggs deposited in per gram liver [(12 116.70 ± 6 508.83) eggs vs. (16 696.70 ± 4 571.56) eggs; t = 1.821, P = 0.085], and area of a single egg granuloma in the liver [(74 359.40 ± 11 766.34) µm2 vs. (74 836.90 ± 13 086.12) µm2; t = 0.081, P = 0.936] were comparable between Shitai and Susong isolates of S. japonicum. Transcriptome sequencing identified 584 DEGs between adult female worms and 1 598 DEGs between adult male worms of Shitai and Susong isolates of S. japonicum. GO enrichment analysis showed that the DEGs between female adults were predominantly enriched in biological processes of stimulus response, cytotoxicity, multiple cell biological processes, metabolic processes, cellular processes and signaling pathways, cellular components of cell, organelles and cell membranes and molecular functions of binding and catalytic ability, and KEGG enrichment analysis showed that these DEGs were significantly enriched in pathways of vascular endothelial growth factor signaling, glutathione metabolism, arginine and proline metabolism. In addition, the DEGs between male adults were predominantly enriched in biological processes of signaling transduction, multiple cell biological processes, regulation of biological processes, metabolic processes, development processes and stimulus responses, cellular components of extracellular matrix and cell junction and molecular functions of binding and catalytic ability, and these DEGs were significantly enriched in pathways of Wnt signaling, Ras signaling, natural killer cells-mediated cytotoxicity, extracellular matrix-receptor interactions and arginine biosynthesis. CONCLUSIONS: There is no significant difference in the pathogenicity between S. japonicum isolates from hilly and marshland and lake regions of Anhui Province; however, the gene expression profiles vary significantly between S. japonicum isolates.
Assuntos
Schistosoma japonicum , Esquistossomose Japônica , Animais , Feminino , Masculino , Camundongos , Lagos , Camundongos Endogâmicos C57BL , Schistosoma japonicum/patogenicidade , Esquistossomose Japônica/epidemiologia , Transcriptoma , Fator A de Crescimento do Endotélio Vascular/genética , Virulência , China , Meio AmbienteRESUMO
Objective: To observe the effect of ruxolitinib combined with glucocorticoid on cytomegalovirus (CMV) activation in patients with acute graft-versus-host disease (aGVHD) . Methods: The clinical data of 195 patients who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology of the First Medical Center of the People's Liberation Army General Hospital from August 2018 to September 2020 were retrospectively analyzed. According to the severity of aGVHD, the patients were divided into the non-GVHD group, aGVHD grade â group, aGVHD grade â ¡-â £ group, and aGVHD grade â ¢/â £ group. In addition, they were classified into two subgroups according to the first-line treatment regimen for aGVHD: combined regimen group (ruxolitinib combined with glucocorticoid) and classical regimen group (glucocorticoid alone) . The cumulative incidence of CMV activation, the duration of CMV activation, and the duration of CMV negativity in each subgroup at 90 and 180 days after transplantation were analyzed. The overall survival and disease-free survival rates of patients in both regimens were compared. Results: Sixty-four (32.8%) patients in the group did not develop aGVHD. The numbers of patients with grade â , â ¡-â £, and â ¢/â £ aGVHD were 30 (15.4%) , 101 (51.8%) , and 14 (7.2%) , respectively. Compared with patients in the classical regimen, no significant difference was observed in the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity in patients with grade â -â £ aGVHD in the combined regimen at 90 and 180 days after transplantation (P>0.05) . Further analysis of patients with grade â ¡-â £ and â ¢/â £ aGVHD showed that the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity did not show significant difference between the two treatment regimens (P>0.05) . In addition, there was no significant difference in the overall survival and disease-free survival rates of patients in both regimens (P>0.05) . Conclusion: Ruxolitinib combined with glucocorticoid as the first-line therapy for aGVHD did not increase the risk of CMV activation.
Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Citomegalovirus/fisiologia , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença AgudaRESUMO
Objective: To explore the pathogenic variants of a family with syndromic deafness by high-throughput sequencing. Methods: The family was from Puyang City, Henan Province, and had four members, including two with syndromic deafness. The proband and his sister had congenital deafness, and their parents had normal phenotypes. The clinical phenotype of the family was characterized using clinical examinations and pedigree analysis. The clinical examinations included imaging examination, audiometry (pure tone audiometry, acoustic immittance, brainstem auditory evoked potential, and otoacoustic emission), vestibular function test, and ophthalmic examination (visual acuity test, visual field test, fundus examination, visual evoked potential, and electroretinogram). Target exome sequencing of 129 known deafness genes and bioinformatics analysis were used to screen suspected pathogenic variants. Sanger sequencing and minigene assay were used to verify and functionally investigate the mutation detected, respectively. According to the standards and guidelines for interpreting genetic variants proposed by the American College of Medical Genetics and Genomics, the variants c.6049G>A and c.8699A>G were classified as pathogenic/likely pathogenic, and the variant c.9856C>G was classified as variants of uncertain significance. Results: The probands and his sister had severe sensorineural hearing loss with decreased binocular vision, night blindness, decreased peripheral visual field sensitivity and partial visual field defect, and normal vestibular function. Both of them had three CDH23 mutations, including CDH23 (NM_022124.5) c.6049G>A (p.Gly2017Ser),c.9856C>G (p.His3286Asp), and c.8699A>G (p. Asp2900Gly), The first two were inherited from the father, and the last one was from the mother. The missense variants c.9856C>G and c.8699A>G were not included in the gnomad database. The missense mutation c.6049G>A was located in the last position of exon 46 and was predicted to affect splicing by bioinformatics software. The minigene experiment showed that the mutation cause exon skipping of exon 46, resulting in an abnormal protein. Conclusions: Compound heterozygous variations of the CDH23 are the leading cause of USH1D in the family. This study confirms that the compound heterozygosity of splicing and missense variants of the CDH23 gene could lead to USH1D.
Assuntos
Caderinas , Surdez , Perda Auditiva Neurossensorial , Síndromes de Usher , Proteínas Relacionadas a Caderinas , Caderinas/genética , Surdez/genética , Potenciais Evocados Visuais , Éxons , Perda Auditiva Neurossensorial/genética , Humanos , Mutação , Linhagem , Fenótipo , Síndromes de Usher/genéticaRESUMO
OBJECTIVE: The competing endogenous RNA (ceRNA) presents a comprehensive regulatory network among lncRNAs, miRNAs and mRNA. The ceRNA provides significant information in understanding the pathology of cancer. This study aimed to explore a lncRNA-associated ceRNA network for predicting the overall survival of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In this study, RNA-sequencing data of HCC were downloaded from The Cancer Genomes Atlas (TCGA) database. The module-trait relationship was analyzed with Weighted gene co-expression network analysis (WGCNA). The key module associated with tumor was identified, as well as the involved lncRNAs, mRNAs and miRNAs. The preliminary ceRNA network was constructed with Cytoscape. The survival analysis was further performed to screen survival-relevant lncRNAs, mRNAs and miRNAs, and then the survival-associated ceRNA network was reconstructed. RESULTS: Eventually, 5 lncRNAs, 10 miRNAs, and 25 mRNAs were included in the reconstructed ceRNA network. CONCLUSIONS: The identified lncRNAs were promising candidate biomarkers in HCC diagnosis and therapeutics. This analysis process was effective to construct ceRNA network. The result will be conductive to explore the significant lncRNAs and regulatory mechanism.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Transcriptoma , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. METHODS: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. RESULTS: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients. CONCLUSIONS: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.
Assuntos
Povo Asiático/estatística & dados numéricos , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Esofágicas/patologia , Mucina-1/metabolismo , Neoplasias Gástricas/patologia , População Branca/estatística & dados numéricos , Idoso , Carcinoma de Células em Anel de Sinete/etnologia , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/terapia , Estudos de Coortes , Terapia Combinada , Neoplasias Esofágicas/etnologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/etnologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
Objective: To evaluate the medium-and long-term outcomes of cardiac assist devices after coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction. Methods: From January 2012 to May 2018, a total of 127 patients with low left ventricular ejection fraction (LVEF) value (≤40%) undergoing CABG in the Department of Cardiovascular Surgery of the First Affiliated Hospital of Zhengzhou University were selected. Meanwhile, another 2 454 cases with LVEF>55% were also enrolled as controls. Clinical data of intra-aortic balloon pump (IABP) and extracorporeal membrane oxygenation (ECMO) application were compared and analyzed. All patients were followed up at the Outpatient Clinic at different time points (3 and 6 months after surgery, then every year). Results: Compared to the control group, IABP usage (10.2% vs 0.8%), ECMO usage (6.3% vs 0.3%) and the mortality (4.7% vs 0.7%) were higher (all P<0.05) in the left ventricular dysfunction group. Additionally, Intensive Care Unit stay [(50±12) h vs (33±10) h] and the hospital stay after surgery [(15±3) d vs (11±4) d] was longer in the left ventricular dysfunction group (all P<0.05). In the left ventricular dysfunction group, LVEF at 3, 6 month and 1 year was (48±8)%, (51±9)%, and (55±9)%, respectively, and then maintained stable. Conclusions: Patients with left ventricular dysfunction who received coronary artery bypass grafting had a high rate of cardiac assist devicesuse, however, optimal perioperative management can save the lives of some patients, whose medium-and long-term outcome are good. Therefore, it is worthy of being recommended in clinical practice.
Assuntos
Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Ponte de Artéria Coronária , Humanos , Balão Intra-Aórtico , Estudos Retrospectivos , Volume Sistólico , Resultado do TratamentoRESUMO
PURPOSE: The purpose of this study was to retrospectively compare the imaging features of hepatic epithelioid angiomyolipoma (HEAML) to those of hepatocellular carcinoma negative for hepatitis B surface antigen and hepatitis C antibody (NBNC-HCC) on contrast-enhanced ultrasound (CEUS) with sulphur hexafluoride microbubbles. MATERIAL AND METHODS: Twenty-two patients (4 men, 18 women) with a mean age of 42.6±10.2 (SD) years (range: 22-63 years) with histopathologically confirmed HEMAL were included in the study. Forty-four patients (30 men, 14 women) with a mean age of 57.3±15.9 years (range: 19-85 years) with histopathologically confirmed NBNC-HCC were randomly selected from our institution's database as a control group. The CEUS characteristics of the two groups were compared. RESULTS: On conventional ultrasound, significant differences in tumor diameter were found between HEAML (4.0±2.0 [SD] cm; range: 1.3-8.9cm) and NBNC-HCC (8.4±4.4 [SD] cm; range: 1.6-18cm) (P<0.001) as well as in degrees of enhancement during the portal (P=0.001) and late phases (P=0.003), contrast distribution (P<0.001) and absence of pseudocaspule (P<0.001). On CEUS, hyperenhancement during the arterial phase was observed in 21/22 (95.5%) HEAMLs and in 43/44 (97.7%) NBNC-HCCs (P>0.999). Homogeneous enhancement was more frequent in HEAMLs (20/22; 90.9%) than in NBNC-HCCs (13/44; 29.6%) (P<0.001). Pseudocapsule was observed in 0/22 HEAMLs (0.0%) and in 36/44 NBNC-HCCs (81.8%) (P=0.017). A prolonged enhancement was observed in 5/22 HEAMLs (22.7%) and in 0/44 NBNC-HCCs (0.0%) (P<0.001) during the late phase. CONCLUSION: CEUS with sulphur hexafluoride microbubbles is helpful in discriminating between HEAML and NBNC-HCC. Homogeneous enhancement and lack of pseudocapsule are suggestive features for the diagnosis of HEAML.
Assuntos
Angiomiolipoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiomiolipoma/diagnóstico por imagem , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Feminino , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ultrassonografia , Adulto JovemRESUMO
Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade â ¡~â £ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Resistencia a Medicamentos Antineoplásicos , Humanos , Linfoma de Células T Periférico/tratamento farmacológico , Recidiva Local de Neoplasia , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the role of dexmedetomidine (DEX) in myocardial ischemia-reperfusion (I/R) injury model and investigate its specific molecular mechanism. MATERIALS AND METHODS: The I/R rat model was established by ligating the anterior descending coronary artery for 30 min and reperfusion for 120 min. In this experiment, all rats were divided into sham operation (SH) group, I/R group, DEX group and I/R + rapamycin (RAP) group. After 120 min of I/R treatment, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal rates of rise and fall of left ventricular pressure (±dp/dtmax) and ischemic area were detected. Serum samples of rats in each group were collected. The levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), superoxide dismutase (SOD), creatine kinase (CK), CK-muscle/brain (CK-MB), tumor necrosis factor (TNF) and interleukin-6 (IL-6) were detected using enzyme-linked immunosorbent assay (ELISA). The apoptosis of myocardium in each group was detected according to the instructions of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expressions of mammalian target of rapamycin (mTOR), phosphorylated-mTOR (p-mTOR), protein kinase B (Akt) and p-Akt in myocardial tissues were detected via Western blotting. Moreover, the messenger ribonucleic acid (mRNA) expression level of mTOR in each group was detected using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Compared with SH group, LVSP and ±dp/dtmax in I/R group were significantly decreased, whereas LVEDP was remarkably increased in I/R group (p<0.01). After DEX administration, LVSP and ±dp/dtmax were remarkably increased, while LVEDP and infarction area were markedly decreased (p<0.01). After treatment with mTOR inhibitor rapamycin (RAP), LVSP and ±dp/dtmax were evidently decreased, while LVEDP and infarction area were increased when compared with those of DEX group (p<0.01). Compared with SH group, the levels of CK, CK-MB, TNF-α and IL-6 in I/R group were significantly increased. However, the levels of these molecules were significantly decreased after DEX treatment in I/R rats. After the combination of DEX and RAP, the expression levels of these indexes were significantly increased. No significant differences were found between DEX + RAP group and model group, and between I/R + RAP group and model group. MDA level in I/R group was significantly higher than that of SH group, while the levels of SOD, CAT and GSH-PX were notably lower (p<0.01). Compared with I/R group, the level of MDA in DEX group was significantly reduced, but the levels of SOD, CAT and GSH-PX were markedly increased (p<0.05, p<0.01). Meanwhile, compared with DEX group, MDA level in I/R group was significantly increased. However, the levels of SOD, CAT and GSH-PX were remarkably decreased after the application of combined DEX and mTOR inhibitor (p<0.01). After the addition of RAP, no significant changes were found in each index compared with I/R group. DEX could alleviate myocardial cell apoptosis caused by I/R treatment (p<0.01). The levels of p-mTOR and p-Akt in I/R group were significantly increased when compared with those of SH group. However, the levels of these indexes in DEX group were evidently higher than those of I/R group after DEX administration based on myocardial I/R model (p<0.01). After combination of DEX and RAP, the latter canceled the effect of the former on enhancing the expression of p-mTOR and the phosphorylation level of mTOR. Furthermore, there was no significant change in mTOR and its mRNA expression in each group. CONCLUSIONS: DEX can play a protective role in myocardial I/R rats, improve the cardiac function of I/R rats, eliminate oxygen free radicals, relieve oxidative stress injury, inhibit inflammatory responses and reduce the release of CK and other substances. The myocardial protection effects of DEX are mainly achieved through the phosphatidylin-ositol-3-kinase (PI3K)-Akt-mTOR pathway.
Assuntos
Cardiotônicos/administração & dosagem , Dexmedetomidina/administração & dosagem , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Creatina Quinase/metabolismo , Modelos Animais de Doenças , Radicais Livres/metabolismo , Humanos , Masculino , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismoRESUMO
Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion: Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.
Assuntos
Linfoma de Células T Periférico , Transplante de Células-Tronco de Sangue Periférico , Adolescente , Adulto , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma de Células T Periférico/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Transplante Autólogo , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Silibinin, a natural polyphenolic flavonoid, possesses anti-oxidant, anti-inflammation and anti-cancer properties. The present study was designed to investigate the effects of silibinin on rheumatoid arthritis (RA) pathogenesis-related cells and collagen-induced arthritis (CIA) and further explore the potential underlying mechanisms. Our results showed that silibinin suppressed cell viability and increased the percentage of apoptotic RA-fibroblast-like synoviocytes (FLS). Furthermore, the production of inflammatory cytokines in RA-FLS and a CIA rat model was effectively inhibited by silibinin. Silibinin also induced macrophage M2 polarization in RAW264.7 cells. We further demonstrated that silibinin inhibits Th17 cell differentiation in vitro. The nuclear factor kappa B (NF-κB) pathway was suppressed in RA-FLS. In addition, Sirtuin1 (SIRT1) was decreased after silibinin treatment, and RA-FLS transfection with a short hairpin RNA (shRNA) of SIRT1 enhanced silibinin-induced apoptosis. Autophagy was markedly decreased in a dose-dependent manner following silibinin treatment. These findings indicate that silibinin inhibited inflammation by inhibiting the NF-κB pathway, and SIRT1 may participate in silibinin-induced apoptosis. Silibinin also inhibited autophagy in RA-FLS. Thus, silibinin may be a potential therapeutic agent for the treatment of RA.
Assuntos
Anti-Inflamatórios/administração & dosagem , Apoptose/efeitos dos fármacos , Artrite/tratamento farmacológico , Artrite/patologia , Silibina/administração & dosagem , Sinoviócitos/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Autofagia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Modelos Biológicos , Ratos , Silibina/farmacologia , Sinoviócitos/fisiologia , Células Th17/efeitos dos fármacos , Células Th17/fisiologia , Usos TerapêuticosRESUMO
Hematopoietic cell transplantation (HCT) activity in China was surveyed to assess its current status. A record number of HCTs (21 884: 16 631 allogeneic (76%) and 5253 autologous (24%)) were reported by 76 centers in China between 1 January 2008 and 30 June 2016. HCT trends included continued growth in transplant activity, a continued rapid increase in haploidentical donors (HID), and slower growth for unrelated donors, matched-related donors (MRD) and cord blood transplantation (CBT). The proportion of HID HCT among allogeneic HCTs increased from 29.6% (313/1062) in 2008 to 48.8% (1939/3975) in 2015, even 51.7% (1157/2237) in the first half of 2016. During this time frame, the proportion of MRD HCTs among allogeneic HCTs decreased from 48.1% (511/1062) to 33.0% (332/3975). The proportion of unrelated donor HCTs among allogeneic HCTs decreased from 20.4 (216/1062) to 13.6% (540/3975). The proportion of CBTs among allogeneic HCTs was increased from 2.1% (22/1062) to 4.2% (184/3975). HCTs have been increasing continuously for all indications except chronic myelogenous leukemia. Severe aplastic anemia is a common HCT indication among non-malignant diseases in China. The number of cases of allogeneic HCT for this disorder has increased annually, from 59 (5.6%) in 2008 to 569 (14.3%) in 2015, even 334 (14.9%) in the first half year in 2016. This survey clearly shows recent trends for HCTs in China.
Assuntos
Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/tendências , Anemia Aplástica/terapia , China , Humanos , Inquéritos e Questionários , Doadores de Tecidos/estatística & dados numéricosRESUMO
Objective: To establish a method for rapid determination of 47 volatile organic compounds in the air of workplace using portable gas chromatography-mass spectrometer(GC-MS). Methods: The mixed standard gas with different concentration levels was made by using the static gas distribution method with the high purity nitrogen as dilution gas. The samples were injected into the GC-MS by a hand-held probe. Retention time and characteristic ion were used for qualitative analysis,and the internal standard method was usd for quantitation. Results: The 47 poisonous substances were separated and determined well. The linear range of this method was 0.2-16.0 mg/m(3),and the relative standard deviation of 45 volatile ovganic compounds was 3.8%-15.8%. The average recovery was 79.3%-119.0%. Conclusion: The method is simple,accurate,sensitive,has good separation effect,short analysis period, can be used for qualitative and quantitative analysis of volatile organic compounds in the workplace, and also supports the rapid identification and detection of occupational hazards.
Assuntos
Poluentes Ocupacionais do Ar/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos Orgânicos Voláteis/análise , Local de Trabalho , Humanos , NitrogênioRESUMO
Emerging data demonstrate promising results of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) for the treatment of hematologic malignancies. Data about G-CSF primed PBSC as reliable source of graft with myeloablative conditioning are lacking. We updated the outcomes in 130 adult patients with high-risk hematologic malignancies who received haplo-PBSC transplantation consecutively under busulfan-based conditioning. PBSC were freshly isolated and infused without ex vivo T-cell depletion into the recipients. Myeloid recovery was achieved in 99.2% patients with full donor chimerism. The cumulative incidence of acute grade 3-4 GvHD, overall and extensive chronic GvHD was 14.9%, 38.6% and 16.5%, respectively. The 3-year non-relapse mortality rate was 24.1%. Non-remission prior to transplant was associated with higher incidence of relapse (P=0.006), inferior overall survival (P=0.017) and leukemia-free survival (P=0.024). These data suggest that PBSC is a reliable graft source in haploidentical, unmanipulated transplant settings under myeloablative conditioning in patients with high-risk hematologic malignancies.
Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico/métodos , Transplante Haploidêntico/métodos , Adolescente , Adulto , Bussulfano/uso terapêutico , Criança , Quimerismo , Feminino , Doença Enxerto-Hospedeiro , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Transplante de Células-Tronco de Sangue Periférico/mortalidade , Medição de Risco , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/mortalidade , Resultado do Tratamento , Adulto JovemRESUMO
Encouraging results from a small sample of patients with myelodysplastic syndrome (MDS) undergoing haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) must be extended. Furthermore, an algorithm derived from a comparison of the outcomes of HID and identical-sibling donor (ISD) HSCT must be established. Therefore, the outcomes of 454 MDS patients who underwent HSCT from HIDs (n=226) or ISDs (n=228) between 2003 and 2013 that were reported to the Chinese Bone Marrow Transplantation Registry were analyzed. Among the 3/6 HID (n=136), 4-5/6 HID (n=90) and ISD patient groups, the 4-year adjusted cumulative incidences of non-relapse mortality were 34, 29 and 16%, respectively (overall P=0.004), and of relapse were 6, 7 and 10%, respectively (overall P=0.36). The 4-year adjusted probabilities of overall survival were 58, 63 and 73%, respectively (overall P=0.07), and of relapse-free-survival were 58, 63 and 71%, respectively (overall P=0.14); pairwise comparison showed that the difference was only statistically significant in the 3/6 HID vs ISD pair. The data suggest that ISDs remain the best donor source for MDS patients while HIDs (perhaps 4-5/6 HID in particular) could be a valid alternative when an ISD is not available; human leukocyte antigen disparity had no effect on survival among the HID patients.
Assuntos
Haplótipos , Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Irmãos , Doadores de Tecidos , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Antígenos HLA/farmacologia , Histocompatibilidade/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Recidiva , Sistema de Registros , Taxa de Sobrevida , Adulto JovemRESUMO
The classic renin-angiotensin system (RAS) is a complex system in which angiotensin II (Ang II) has been identified as an important endogenous regulator that influences both smooth muscle contraction and cell growth. Although a local RAS is known to exist in the gastrointestinal tract, it is unclear whether Ang II is involved in the loss of gastric interstitial cells of Cajal (ICC) in diabetic mice. The present study was designed to investigate the effect of Ang II on ICC survival in streptozotocin (STZ)-induced diabetic mice. Western blot, immunofluorescence, isometric muscle recording, enzyme-linked immunosorbent assay (ELISA) and a cell counting kit-8 were used in this research. Our results demonstrate that the c-Kit and membrane-bound stem cell factor (mSCF) protein expression levels in gastric smooth muscle were decreased in STZ-induced diabetic mice. However, the angiotensin receptor type 1 (AT1R) expression levels in gastric smooth muscle and angiotensin-converting enzyme (ACE) expression levels in gastric mucosa were increased. The effect of Ang II on the tonic contraction of gastric smooth muscle was potentiated in diabetic mice, and the plasma Ang II level was enhanced. Ang II increased mSCF expression, cell proliferation, and Akt-Ser473 phosphorylation in cultured gastric smooth muscle cells (GSMCs). These effects were reduced by specific inhibitors ZD7155 (an AT1R antagonist) and LY294002 (a PI3-kinase inhibitor). Our results suggest that Ang II increases mSCF expression and cell proliferation in cultured GSMCs in a PI3K/Akt signaling-dependent manner. ACE and AT1R up-regulation in the stomach may help compensate for ICC loss in STZ-induced diabetic mice.