RESUMO
Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% vs. (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunodeficiência Combinada Severa , Transplante Homólogo , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Retrospectivos , Masculino , Feminino , Lactente , Prognóstico , Imunodeficiência Combinada Severa/terapia , Imunodeficiência Combinada Severa/mortalidade , Pré-Escolar , Criança , Fatores de Risco , Taxa de Sobrevida , Doadores não Relacionados , Resultado do Tratamento , Irmãos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Estimativa de Kaplan-Meier , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodosRESUMO
Objective: To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment. Methods: A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples. Results: The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor's surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34ßE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC (P=0.002), TP63 (P=0.002), CDKN1C (P=0.002) and NFE2L2 (P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway (P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway (P=0.013) and PI3K pathway (P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion: Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Neoplasias Esofágicas/genética , Fosfatidilinositol 3-Quinases , Diferenciação Celular , Carcinoma de Células Escamosas/genéticaRESUMO
OBJECTIVE: Triple-negative breast cancer (TNBC) is a heterogeneous disease with aggressive behavior and poor prognosis. Here, we used gene expression profiling to define new subtypes of TNBC, which may improve prevention and treatment through personalized medicine. MATERIALS AND METHODS: Gene expression profiles from the public datasets GSE76250, GSE61724, GSE61723, and GES76275 were subjected to co-expression analysis to identify differentially expressed genes (DEGs) between TNBC and non-TNBC tissues. Consistency clustering was used to define TNBC subtypes, whose correlation with gene modules was analyzed. Enrichment analysis was used to identify module genes' biological functions and pathways. Single-sample gene set enrichment analysis was used to assess immune cell infiltration in the different TNBC subtypes, and the ChAMP package was used to examine methylation sites in TNBC. RESULTS: A total of 4,958 DEGs in TNBC were identified, which showed the same expression differences across all datasets as in the dataset GSE76250 and clustered into 9 co-expression modules. TNBC samples clustered into two subtypes based on nine hub genes from the modules. Class I showed the most significant correlation with module 1, whose genes were related mainly to interleukin-1 response, while class II showed the most significant correlation with module 6, whose genes were related mainly to the transforming growth factor-ß pathway. Class I was significantly enriched in cell cycle and DNA replication, and tumors of this subtype showed lower immune cell infiltration than class II tumors. Tumor infiltration by Th2 cells correlated positively with the expression of MCM10 and negatively with the expression of PREX2. A greater methylation of CIDEC, DLC1, EDNRB, EGR2 and SRPK1 correlated with better prognosis. CONCLUSIONS: Class I TNBC, for which a useful biomarker is MCM10, may be associated with a worse prognosis than class II TNBC, for which PREX2 may serve as a biomarker.
Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Perfilação da Expressão Gênica , Transcriptoma , Biomarcadores , Análise em Microsséries , Proteínas Serina-Treonina Quinases/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Objective: To investigate the risk factors and outcomes of cytomegalovirus (CMV) infection post umbilical cord blood stem cell transplantation (UCBT) in children with primary immunodeficiency diseases (PID). Methods: Clinical data of 143 PID children who received UCBT in the Children's Hospital of Fudan University from January 2015 to June 2020 were collected retrospectively. CMV-DNA in the plasma was surveilled once or twice a week within 100 days post-UCBT. According to the CMV-DNA test results, children were divided into the CMV-infected group and the CMV-uninfected group. The incidence and risk factors of CMV infection were analyzed. At 1-month post-UCBT, the absolute lymphocyte count, ratio of lymphocyte subsets and immunoglobulin levels were compared between those whose CMV infection developed 1-month later post-UCBT and those not. Mann-Whitney U test and chi-squared test were used for comparision between groups. Kaplan-Meier survival analysis was used to analyze the impact of CMV infection on survival. Results: Among 143 patients, there were 113 males and 30 females, with a age of 14 (8, 27) months at UCBT. Chronic granulomatosis disease (n=49), very-early-onset inflammatory bowel disease (n=43) and severe combined immunodefiency (n=29) were the three main kinds of PID. The rate of CMV infection was 21.7% (31/143), and the time of infection occurring was 44 (31, 49) days post-UCBT. The incidence of recurrent CMV infection was 4.2% (6/143) and refractory CMV infection was 4.9% (7/143).There was no significant difference in the first time CMV-DNA copy and peak CMV-DNA copy during treatment between the recurrent CMV infection group and the non-recurrent CMV infection group (32.8 (18.3, 63.1)×106 vs. 22.5 (13.2, 31.9)×106 copies/L, Z=-0.95, P=0.340;35.2 (20.2, 54.6)×106 vs. 28.4 (24.1, 53.5)×106copies/L, Z=-0.10, P=0.920), so were those between the refractory CMV infection group and non-refractory CMV infection group (21.8 (13.1, 32.2)×106 vs. 25.9 (14.2, 12.2)×106copies/L, Z=-1.04, P=0.299; 47.7 (27.9, 77.6)×106 vs. 27.7 (19.7,51.8)×106copies/L, Z=-1.49, P=0.137). The CMV-infected group accepted more reduced-intensity conditioning (RIC) regimen than the CMV-uninfected group (45.2% (14/31) vs. 25.0% (28/112), χ2=4.76, P<0.05). The rate of CMV-seropositive recipients and â ¡-â £ acute graft versus host diseases (aGVHD) are significantly higher in the CMV-infected group than the CMV-uninfected group (100% (31/31) vs. 78.6% (88/112), 64.5% (20/31) vs. 26.8% (30/112), χ2=7.98,15.20, both P<0.05). The follow-up time was 31.6 (13.2, 45.9) months, CMV infection had no effect on overall survival (OS) rate (χ2=0.02, P=0.843). There was significant difference in the survival rate among three groups of refractory CMV infection, non-refractory CMV infection and the CMV-uninfected (4/7 vs.95.8% (23/24) vs. 86.6% (97/112), χ2=5.91, P=0.037), while there was no significant difference in the survival rate among three groups of recurrent CMV infection, non-recurrent CMV infection and the CMV-uninfected (5/6 vs. 88.0% (22/25) vs. 86.6% (97/112), χ2=0.43, P=0.896). Children who developed CMV infection after 30 days post-UCBT had lower absolute count and rate of CD4+ T cells and immunoglobulin G (IgG) level than those in the CMV-uninfected group (124.1 (81.5, 167.6) ×106 vs. 175.5 (108.3, 257.2) ×106/L, 0.240 (0.164, 0.404) vs. 0.376 (0.222, 0.469), 9.3 (6.2, 14.7) vs. 13.6 (10.7, 16.4) g/L, Z=-2.48, -2.12,-2.47, all P<0.05), but have higher rate of CD8+T cells than those in CMV-uninfected group (0.418 (0.281, 0.624) vs. 0.249 (0.154, 0.434), Z=-2.56, P=0.010). Conclusions: RIC regimen, grade â ¡-â £ aGVHD and CMV-seropositive recipients are the main risk factors associated with CMV infection in PID patients post-UCBT. Survival rate of children with refractory CMV infection after UCBT is reduced. Immune reconstitution in children after UCBT should be regularly monitored, and frequency of CMV-DNA monitoring should be increased for children with delayed immune reconstitution.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças da Imunodeficiência Primária , Criança , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Citomegalovirus , Infecções por Citomegalovirus/etiologia , DNA , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunoglobulina G , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Objective: To evaluate the efficacy and safety of unrelated umbilical cord blood stem cell transplantation (UCBT) with reduced-intensity conditioning regimens in the treatment of hyper-IgM syndrome (HIGM) caused by CD40 ligand gene (CD40LG) mutation. Methods: Clinical features, laboratory data and treatment prognosis of 3 patients with HIGM caused by CD40LG mutation treated with UCBT in Children's Hospital of Fudan University from May 2018 to August 2019 were analyzed retrospectively. The literature search was conducted with "CD40 ligand deficiency" and "hematopoietic stem cell transplantation" as keywords at China National Knowledge Infrastructure, Wanfang, Weipu and Pubmed databases (up to February 2021) to summarize donor selection, stem cell source, conditioning regimen and prognostic factors of this disease. Results: Three boys with recurrent respiratory tract infection were diagnosed as HIGM with CD40LG mutation. The age of UCBT was 1.0, 1.4 and 0.5 years respectively. Reduced-intensity conditioning regimen including busulifan, fludarabine and cyclophosphamide were used in all patients. Human leucocyte antigen matching of patients and umbilical cord blood was 8/10, 10/10 and 9/10 respectively. All patients achieved complete donor chimerism 14 days after UCBT. All patient suffered grade â acute skin graft-versus-host disease without other severe complications. Up to the last follow-up, their disease-free survival time were 33, 18, 18 months after transplantation respectively. No reports were found in Chinese journals, while 24 publications were found in English journals. According to the literature, 258 HIGM patients with CD40LG mutation were treated with hematopoietic stem cell transplantation (HSCT). Matched sibling donors (30.6%(79/258)) and unrelated donors (40.3% (104/258)) were main donor types. Bone marrow (50.8%(131/258)) was the main source of grafts, myeloablative conditioning (66.7% (172/258)) was the main conditioning regimen, and the overall survival rate after transplantation was 70.9% (183/258). Lung injury and liver complications before transplantation were adverse factors affecting prognosis. Among the 14 patients who received UCBT, 2 patients suffered from engraftment failure, 2 patients had mixed chimerism and 3 patients died after transplantation. Conclusions: UCBT is safe and effective in the treatment of HIGM caused by CD40LG mutation. Reduced-intensity conditioning regimen is worthy of further study.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndrome de Imunodeficiência com Hiper-IgM , Ligante de CD40/genética , Humanos , Masculino , Mutação , Estudos Retrospectivos , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
Objective: To construct the competitive endogenous RNA (ceRNA) network related to gastric cancer and explore the molecular mechanism. Methods: The expression profiles of lncRNA, miRNA and mRNA in gastric cancer and paracancer tissues were analyzed by biochip technology, edgeR package in R software was used to filtrate differential expression genes (multiple change of >1.5 times, P<0.05) and volcano map was drawn. Based on the online miRNA-lncRNA prediction tool lncBase database and the miRNA Target gene prediction database (miRTarBase, target-scan, miRDB, starBase), the relationship between miRNA, lncRNA and mRNA was predicted. Cytoscape software was used to construct lncRNA-miRNA-mRNA ceRNA network and key genes (hub genes) were identified based on cytohubba calculation of degree score of each node. Then Hub genes related to the prognosis of gastric cancer were verified in the TCGA database. The GO and KEGG enrichment analysis of differentially expressed mRNA was performed using the online biological information annotation database DAVID, P<0.05 and false discovery rate (FDR)<0.05 were used as cut-off criteria. R software was used to download the RNA sequencing data and mirna-seq data of gastric cancer and adjacent tissues in TCGA database, edgeR package was used to screen out differentially expressed mRNA, miRNA and lncRNA, and some differentially expressed genes in our data were verified. In OncoLnc database, STAD project of TCGA data was selected and hub gene was input. Patients were divided into two groups based on the median value for hub genes and Kaplan-meier analysis was performed. Results: The differentially expressed 766 mRNA, 110 lncRNA and 10 miRNA were screened out, among them 90 mRNA, 4 lncRNA and 6 miRNA were used to construct the ceRNA network, and 2 of the 20 hub genes were related to the prognosis of patients. MLK7-AS1, SPP1, SULF1, hsa-miR-1307-3p were upregulated in gastric cancer tissues from our biochip, while MT2A, MT1X were downregulated, which were consistent with the results of TCGA gastric cancer database. The differentially expressed mRNAs were significantly enriched in the biological process (BP) and the mineral absorption pathway. CHST1 was negatively correlated while miR-183-5p was positively corelated with the survival of patients. Conclusion: The establishment of ceRNA network for gastric cancer is conducive to further understanding of the molecular biological mechanism. CHST1 and miR-183-5p can be used as prognostic factors of gastric cancer.
Assuntos
Redes Reguladoras de Genes/genética , Neoplasias Gástricas/genética , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética , RNA Mensageiro/genética , SoftwareRESUMO
Objective: To explore the application, advantages and disadvantages of minimally invasive surgery for lumbar schwannoma. Methods: this study was a prospective, non-randomized controlled study with a trial group (minimally invasive surgery group) and a control group (traditional laminectomy group).For the patients with lumbar schwannoma hospitalized in the neurosurgical spinal ward of Beijing Tian Tan hospital, the surgeon communicated with them one-on-one to inform the patients of the advantages and disadvantages of minimally invasive surgery through channels and traditional laminectomy. After the surgical risks and their respective advantages and disadvantages were identified, patients who underwent minimally invasive surgery to remove tumors through the channel were admitted to the channel surgery group according to the wishes of the patients; otherwise, patients who underwent traditional laminectomy were included in the control group. From December 2017 to March 2019, a total of 15 patients (experimental group) were treated with minimally invasive surgery. A total of 15 patients with tumors similar in size and location to those in the experimental group were selected from the control group who were hospitalized during the same period for traditional laminectomy. Relevant clinical data of the two groups of patients were collected and analyzed, including preoperative lesion imaging characteristics, intraoperative blood loss, operation time, postoperative hospital stay, postoperative complications, symptom improvement, etc. Results: the operating time of the experimental group and the control group was (157±27) min and (158±29) min, respectively (P=0.897). Intraoperative blood loss was (66±27) ml and (110±43) ml, respectively (P=0.020). The mean hospital stay was (7.60±1.29) days and (11.67±1.23) days, respectively (P=0.000). Postoperative JOA scores were 26.73±2.84 and 26.60±2.41, respectively (P=0.891). Postoperative VAS scores were 0.40±1.12 and 0.27±0.71, respectively (P=0.699).The mean blood loss and hospital stay in the experimental group were significantly lower than those in the control group, the difference in operation time between the two groups was not significant, and there was no difference in neurological function results. Conclusion: In certain types of lumbar schwannoma tumors (non-giant tumors), minimally invasive resection through channels has the advantages of less surgical trauma, less bleeding, faster recovery and definite curative effect, which is a safe and effective surgical treatment.
Assuntos
Neurilemoma , Fusão Vertebral , Humanos , Laminectomia , Vértebras Lombares , Procedimentos Cirúrgicos Minimamente Invasivos , Neurilemoma/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The efficacy and safety of transvenous embolization for brain arteriovenous malformations remains unclear, given the very limited number of cases reported. This prospective study was performed to assess this technique in ruptured AVMs. MATERIALS AND METHODS: Twenty-one consecutive patients with ruptured brain AVMs who underwent transvenous embolization were prospectively followed between November 2016 and November 2018. The Spetzler-Martin grade was I in 3 AVMs (14.3%), II in four (19.0%), III in eleven (52.4%), and IV in three (14.3%). The complete AVM occlusion rate was calculated from 6-month follow-up DSA images. Occurrence of hemorrhage and infarction after embolization was evaluated using CT and MR imaging within 1 month after the operation. The mRS was used to assess the functional outcomes. RESULTS: Complete AVM nidus obliteration was shown in 16 (84%) of 19 patients with technically feasible AVMs immediately after embolization. One (5%) patient with a small residual nidus after treatment showed complete obliteration at 13-month follow-up. There were 5 hemorrhages and 1 infarction; 4 patients' symptoms improved gradually. The percentage of cases with mRS ≤ 2 rose from 57.1% (12/21) before embolization to 66.7% (14/21) at 1-month follow-up. Both the morbidity and mortality rates were 4.8% (1/21). CONCLUSIONS: Transvenous embolization can be performed only in highly selected hemorrhagic brain AVMs with high complete obliteration rates, improved functional outcomes, and acceptable morbidity and mortality rates, but it should not be considered as a first-line treatment.
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Fístula Arteriovenosa/cirurgia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Malformações Arteriovenosas Intracranianas/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Hemorragias Intracranianas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Holliday junction-recognizing protein (HJURP) was found to be upregulated in several tumors, including non-small cell lung cancer (NSCLC), and the effect of HJURP on NSCLC remains unknown. The objective of the present study was to explore the clinical significance of HJURP and its function in regulating the progression of NSCLC. PATIENTS AND METHODS: Reverse Transcriptions-Polymerase Chain Reaction (RT-PC) and Western blot were performed to detect the expression levels of HJURP in NSCLC tissues and cell lines. The association of HJURP expression level with various important clinicopathological parameters was evaluated. Then, the effects of HJURP expression on tumor cell behavior in vitro were analyzed by the Cell Counting Kit-8 (CCK-8), EdU assays, colony formation, flow cytometry, and transwell assays. The protein levels of related proteins of the Wnt/ß-catenin pathway were determined using the Western blot assay. RESULTS: Our study showed that HJURP was significantly upregulated in both NSCLC tissues and cell lines. The higher expression of HJURP was associated with advanced TNM stage, distant metastasis, and poor prognosis. Our data from in vitro assays confirmed that the knockdown of HJURP suppressed NSCLC cells proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) progress, and induced cells apoptosis. Notably, through Western blot analysis, we found that HJURP suppression remarkably decreased ß-catenin, cyclin D1 and c-myc expression level in NSCLC cell lines. CONCLUSIONS: Our findings provide clues regarding the role of HJURP as a tumor promoter in NSCLC via the activation of the Wnt/ß-catenin pathway, indicating HJURP may be a promising therapeutic target for NSCLC.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Neoplasias Pulmonares/patologia , Apoptose , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/genética , Bases de Dados Genéticas , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Regulação para Cima , Via de Sinalização WntRESUMO
The number of H7N9 bird flu cases was high and the situation was grim in guizhou province in 2017. To understand the molecular characteristics of the hemagglutinin gene (HA) and the risk of human infection with avian influenza virus A(H7N9) in Guizhou Province, 2017. Homology, genetic evolution and pivotal sites related to receptor binding regions, pathogenicity and potential glycosylation of 14 avian influenza viruses A(H7N9) were analyzed by a series of bioinformation softwares. It was cleared that there was 95.9%-100% similarity among 14 strains in nucleotide of the HA gene, and there were 96.8%-97.8% and 96.8%-97.9% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Phylogenetic analysis showed that 14 HA genes were directly evolved in the Yangtze River Delta evolution branch, but they could be derived from five diffenrent strains. Then 13 of 14 strains cleavage site sequences of HA protein revealed they were low pathogenic avian influenza viruses, while A/Guizhou-Weining/CSY01/2017 was high pathogenic avian influenza virus. Mutation G186V at the receptor binding sites in the HA was found in all 14 strains, and mutation Q226L in 13 strains besides A/Guizhou-Weining/CSY01/2017. All five potential glycosylation motifs in the HA were conservative.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Aviária/virologia , Influenza Humana/virologia , Animais , Aves , China/epidemiologia , Humanos , Influenza Aviária/epidemiologia , Influenza Humana/epidemiologia , FilogeniaRESUMO
Objective: To understand the molecular characteristics of hemagglutinin (HA) and neuraminidase (NA) as well as the disease risk of influenza virus A H7N9 in Guizhou province. Methods: RNAs were extracted and sequenced from HA and NA genes of H7N9 virus strains obtained from 18 cases of human infection with H7N9 virus and 6 environmental swabs in Guizhou province during 2014-2017. Then the variation and the genetic evolution of the virus were analyzed by using a series of bioinformatics software package. Results: Homology analysis of HA and NA genes revealed that 2 strains detected during 2014-2015 shared 98.8%-99.2% and 99.2% similarities with vaccine strains A/Shanghai/2/2013 and A/Anhui/1/2013 recommended by WHO, respectively. Two strains detected in 2016 and 14 strains detected in 2017 shared 98.2%-99.3% and 97.6%-98.8% similarities with vaccine strain A/Hunan/02650/2016, respectively. Other 6 stains detected in 2017 shared 99.1%-99.4% and 98.9%-99.3% similarities with strain A/Guangdong/17SF003/2016, respectively. Phylogenetic analysis showed that all the strains were directly evolved in the Yangtze River Delta evolution branch, but they were derived from different small branch. PEVPKRKRTAR↓GLF was found in 6 of 24 strains cleavage site sequences of HA protein, indicating the characteristic of highly pathogenic avian influenza virus. Mutations A134V, G186V and Q226L at the receptor binding sites were found in the HA. All the strains had a stalk deletion of 5 amino acid residue "QISNT" in NA protein, and drug resistance mutation R294K occurred in strain A/Guizhou-Danzhai/18980/2017. In addition, potential glycosylation motifs mutations NCS42NCT were found in the NA of 9 of 24 strains. Conclusions: HA and NA genes of avian influenza A (H7N9) virus showed genetic divergence in Guizhou province during 2014-2017. The mutations of key sites might enhance the virulence of the virus, human beings are more susceptible to it. Hence, the risk of infection is increasing.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hemaglutininas/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Influenza Humana/virologia , Neuraminidase/genética , Animais , Sequência de Bases , Aves , China/epidemiologia , Genoma Viral , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Humanos , Subtipo H7N9 do Vírus da Influenza A/enzimologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Aviária , Influenza Humana/epidemiologia , Filogenia , RNA Viral/genética , Análise de Sequência de DNARESUMO
Objective: To evaluate the relationship of dosimetry parameters and efficacy of (125)I seeds implantation for pelvic recurrent cervical cancer (PRCC) after external beam radiotherapy(EBRT) under CT guidance. Methods: A retrospective analysis was made on 30 PRCC patients after EBRT in Peking University Third Hospital with (125)I seeds implantation under CT guidance. Postoperative plans were made to evaluate the dosimetric parameters. Kaplan-Meier method was used to calculate local progression free survival (LPFS) rate and overall survival (OS) rate, and Log-rank test and Cox regression were used for univariate and multivariate analysis. Results: The 1-year and 2-year LPFS rate was 39.4% and 22.5%, respectively. The 1-year and 2-year OS rate was 57.3% and 27.4%, respectively. On postoperative plan, D(90) was (132±47) Gy, D(100) was (51±24) Gy, V(100) was 88%±10%, V(150)was 69%±15%, V(200) was 51%±18%.LPFS time would be longer while D(90) ≥105 Gy or D(100) ≥ 55 Gy or V(100) ≥ 91% (all P<0.05). D(100) was significantly related to LPFS (P<0.05). But these dosimetry parameters got no effect on OS. Conclusions: LPFS time of (125)I seeds implantation for PRCC after EBRT under CT guidance would be longer when D(90)≥105 Gy or D(100)≥ 55 Gy, or V(100)≥ 91%. D(100) is an independent factor related to LPFS.
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Dosagem Radioterapêutica , Neoplasias do Colo do Útero , Braquiterapia , Feminino , Humanos , Isótopos de Iodo , Recidiva Local de Neoplasia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/radioterapiaRESUMO
Objective: To assess the feasibility and safety of interventional treatment of symptomatic intracranial in-stent restenosis (SISR). Methods: Clinical data of 21 patients with SISR who underwent interventional treatment in the General Hospital of the PLA Rocket Force from January 2012 to May 2018 were retrospectively analyzed. Perioperative complications, angiographic and clinical follow-up results were recorded. Results: The success rate of treatment was 100%, including 21 lesions of SISR (7 at the V4 segment of the vertebral artery, 7 at the basilar artery, 5 at the M1 segment of middle cerebral artery, 2 at the internal carotid artery). The residual stenosis rate was preoperative 84±7, postoperative 30±14 respectively. Balloon angioplasty and stent implantation were performed in 10 patients (48.6%) and 11 patients (52.4%), respectively. After treatment, 1 patient experienced perforating event without neurological sequelae. Of the 11 patients (52.4%) completed angiography follow-up, 3 (3/11, 27.3%) ocurred restenosis and 1 was retreated. During clinical follow-up, 1 patients received intravenous thrombolysis for the symptom of acute cerebral infarction in territory of stenting artery, in-stent restenosis or occlusion was not demonstrated by emergency cerebral angiography. Conclusion: Interventional treatment of SISR is feasible and safe, however, further studies need to warrant the long-term effects.
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Reestenose Coronária , Arteriosclerose Intracraniana , Constrição Patológica , Seguimentos , Humanos , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
Objective: To compare the clinical effects of stent-assisted embolization and surgical clipping in the treatment of middle cerebral artery bifurcation wide-necked aneurysms. Methods: From July 2014 to March 2017, the clinical and imaging data of 45 patients with Hunt-Hess 0-â ¢ grade middle cerebral artery bifurcation wide-necked aneurysms were divided into stent-assisted embolization group (20 patients from PLA Rocktet Army Hospital) and surgical clipping group (25 patients from Peking University International Hospital). The total occlusion rates of aneurysm, operation-related adverse events, clinical outcomes, and results of follow-up imaging from the two groups were compared. Results: The total occlusion rates in the stent-assisted embolization group and surgical clipping group were 90.0% (18/20) and 92.0% (23/25), respectively, and the difference was not statistically significant (P=0.815). The favorable six-month postoperative outcomes defined as the modified Rankin Scale ≤2 were 94.7% (18/19) in the stent-assisted embolization group and 91.3% (21/23) in the surgical clipping group (P=0.667). Fewer patients experienced the operation-related adverse events in the stent-assisted embolization group (15.0%, 3/20), as compared to that of the surgical clipping group (24.0%, 6/25), but the difference were not significant (P=0.453). After 2-24 months (median 7 months) of the operation, the follow-up imaging indicated that in the stent-assisted embolization group, 2 out of the 19 patients had residual or recurrent aneurysms.While in the surgical clipping group, residual or recurrent aneurysms were identified in 2 out of the 23 patients 2-14 months (median 3 months) after the surgery; the frequency was not statistically different between the two groups (P=0.841). Conclusion: Stent assisted embolization is a safe and effective treatment for the low grade middle cerebral artery bifurcation wide-necked aneurysms.
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Aneurisma Intracraniano , Artéria Cerebral Média , Embolização Terapêutica , Humanos , Período Pós-Operatório , Stents , Instrumentos Cirúrgicos , Resultado do Tratamento , Doenças VascularesRESUMO
Objective: To summarize the safety and efficacy of Pipeline embolization device in the treatment of large and giant intracranial aneurysms (maximum diameter ≥ 10 mm). Methods: The clinical and imaging data of 22 patients with intracranial aneurysms treated by Pipeline Embolization Device (PED) from February 2015 to July 2016 in the Zhengzhou University People's Hospital were retrospectively analyzed. The results about postoperative clinical and imaging follow-up and complications were evaluated. Results: The PED were successfully implanted in 22 patients with 22 intracranial aneurysms. Two aneurysms were treated with PED alone, and 20 aneurysms were treated with PED assisted coil embolization. Perioperative complications occurred in 3 patients (13.6%), and 1 patient died because aneurysm ruptured 3 days after operation. Nineteen patients (19 aneurysms) obtain imaging follow-up visit 3-17 months after operation, 13 of the 19 aneurysms (68.4%) received complete and subtotal occlusion, with no aneurysm recurrence. Eighteen patients obtain clinical follow-up visit 16-32 months after operation, with mRS (modified Rankin scale) score 1 in 5 patients, mRS score 0 in 13 patients, none developed new neurologic symptoms. Conclusions: PED has showed the high rate of obliteration for the treatment of large and giant intracranial aneurysms. But the complications needs to be further studied.
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Aneurisma Intracraniano , Prótese Vascular , Embolização Terapêutica , Humanos , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
We investigate the current-induced switching of the Néel order in NiO(001)/Pt heterostructures, which is manifested electrically via the spin Hall magnetoresistance. Significant reversible changes in the longitudinal and transverse resistances are found at room temperature for a current threshold lying in the range of 10^{7} A/cm^{2}. The order-parameter switching is ascribed to the antiferromagnetic dynamics triggered by the (current-induced) antidamping torque, which orients the Néel order towards the direction of the writing current. This is in stark contrast to the case of antiferromagnets such as Mn_{2}Au and CuMnAs, where fieldlike torques induced by the Edelstein effect drive the Néel switching, therefore resulting in an orthogonal alignment between the Néel order and the writing current. Our findings can be readily generalized to other biaxial antiferromagnets, providing broad opportunities for all-electrical writing and readout in antiferromagnetic spintronics.
RESUMO
OBJECTIVE: To compare the dosimetric differences between volumetric modulated arc therapy and intensity modulated radiotherapy for breast cancer patients after breast-conserving surgery. METHODS: Ten patients who received radiotherapy after breast-conserving surgery were selected. Eclipse planning system was used to design volumetric rotating intensity-modulated (2F-RapidArc) and two field intensity-modulated radiation therapy (2F-IMRT) planning for each patient. 2F-RapidArc plans were made using two partial arcs with gantry rotation from 287°-293° to 152°-162°, and 0° to 90 ° was avoidance sector. The gantry angle of 2F-IMRT were 301°-311° and 125°-135°. The prescription dose was 46 Gy/23 fractions. All plans required 95% of the target volume receiving the prescription dose. The dose distribution of the target, organs at risk, machine unit (MU) and treatment time were compared. RESULTS: 2F-RapidArc and 2F-IMRT plans' uniformity index was 1.12±0.02 and 1.11±0.03 (P=0.282), respectively; conformal index was 0.80±0.03 and 0.65±0.04 (P<0.001), respectively. V110 of plan target volume was 20.98%±14.47% and 10.43%±10.49% (P=0.030), respectively. Compared with the 2F-IMRT, 2F-RapidArc plans had a higher dosimetric parameters for left lung: V5 (48.06%±17.32% vs. 24.23%±6.56%,P=0.001), V10 (28.89±9.28 vs.17.07±4.78%,P=0.004), Dmean [(9.70±2.14) Gy vs. (6.86±1.77) Gy, P=0.002], increased the double lung: V5 (22.85%±7.55% vs. 11.01%± 2.95%,P=0.001), V10 (13.16%±4.33% vs. 7.76%± 2.16%, P=0.006), Dmean [(4.66±0.95) Gy vs. (3.17±0.82) Gy, P=0.001], reduced the left lung: V40 (3.58%±1.46% vs. 6.19%±3.04%, P=0.006), reduced the double lung: V40 (1.61%±0.64% vs. 2.81%± 1.39%,P=0.005), increased cardiac: V5 (39.3%±17.19% vs. 8.79%±4.24%, P<0.001), V10 (21.31%±13.8% vs. 5.73%±3.42%, P=0.002), V20 (7.80%±6.08% vs. 4.05%±2.85%,P=0.018), Dmean [(0.64±0.25) Gy vs. (0.29±1.39) Gy,P<0.001],reduced the heart: V40(0.50%±0.40% vs. 1.86%±1.94%,P=0.037),increased the contralateral breast Dmean [(1.63±1.26) Gy vs. (0.09±0.05) Gy, P=0.004]. Compared with 2F-IMRTplan, 2F-RapidArc increased the treatment time [(132.9±7.2) s vs. (140.3±11.6) s, P=0.030]. Both the machine units were almost the same [(467.0±30.4) MU vs. (494.7±44.9) MU, P=0.094]. CONCLUSION: Both 2F-RapidArc and 2F-IMRT plans could reach the clinical requirements. 2F-RapidArc had a better conformal index, reduced the high dose area, but increased the low dose regions of the lung, heart, body area, and increased the average dose of the contralateral breast. The treatment time of 2F-RapidArc was longer than that of 2F-IMRT, and the MU of 2F-RapidArc and 2F-IMRT plans were almost the same.
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Neoplasias da Mama , Mastectomia Segmentar , Radioterapia de Intensidade Modulada , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por ComputadorRESUMO
Objective: To investigate the discharge outcome of external ventricular drainage(EVD) and conservative treatment in patients with severe intraventricular hemorrhage (SeIVH). Methods: From January 2011 to December 2016, patients with SeIVH admitted to the General Hospital of the PLA Rocket Force and the Army General Hospital received EVD treatment and were classified as the treatment group. According to intraventricular hemorrhage volume and age, patients received conservative treatment were pair matched and classified as control group. Then we compared the clinical outcome of moderate disability or less degree of discharge (mRS ≤3) and death incidence (mRS 6) between two groups. Results: A total of 361 patients with IVH were treated during these six years. Among them, 75 cases were chosen as treatment group. Another 75 cases were pair matched as control group from 286 cases. At the time of admission, the ventricular hemorrhage volume of two groups were (55.8±22.7) ml and (53.7±23.3) ml (P=0.569) respectively. Cerebral hemorrhage volume were (23.6±5.3) ml and (24.0±5.4) ml (P=0.631). And the median Glasgow coma score (GCS) were 4[IQR(3, 7)] and 5[IQR(4, 7)](P=0.131). At the discharge time, there were 16% (12/75) patients scored mRS≤3 in treatment group, while 2.7% (2/75) in control group (P<0.005). The absolute risk reduction (ARR) was 13.3%, and the number needed to treat (NNT) was 7.5. The mortality rate of treatment group was 13.3% (10/75), much lower than that of the control group 41.1% (31/75, P<0.001). ARR was 27.8% and NNT was 3.6. Conclusion: Although the prognosis of SeIVH was poor, compared with conservative treatment, EVD treatment significantly improved the outcome of these patients. Randomized controlled trials are needed to validate the efficacy of EVD.
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Hemorragia Cerebral , Ventrículos Cerebrais , Tratamento Conservador , Drenagem , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: To explore the efficacy of hybrid management of complex symptomatic intracranial fistulas in neurovascular hybrid operating room. Methods: From March 2014 to January 2015, 2 complex dural arteriovenous fistulas and 1 carotid cavernous fistulas were managed by hybrid surgeries in the PLA Rocket Force General Hospital.With first attempts with endovascular treatment failed, all cases were finally managed by hybrid surgery.Dural arteriovenous fistulas were approached via meningeal artery followed craniotomy.The carotid cavernous fistulas were treated by direct puncture into the left cavernous sinus after craniotomy. Results: Post-operative angiography demonstrated complete occlusion for 2 cases and nearly complete occlusion for 1 case.All 3 cases had no complications.On discharge 2 patients presented no symptoms and 1 greatly improved.Within the follow-up (1-33 months), 1 patient had recurrence after 21 months and received re-embolization with complete occlusion. Conclusion: Hybrid surgery is a promising method to manage complex intracranial fistulas.