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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed millions of lives worldwide, not to mention innumerable losses in the global economy and disruptions in social relationships. Unfortunately, state-of-the-art treatments still lag behind the fast emergence of new variants of concern. The key to resolve this issue is to develop broad-spectrum antivirals with innovative antiviral mechanisms in which coronaviruses are deactivated regardless of their variant development. Herein, we report a new antiviral strategy involving extracellular disintegration of viral proteins that are indispensable for viral infection with hyperanion-grafted enediyne molecules. The sulfate groups ensure low cellular permeability and rather low cytotoxicity of the molecules, while the core enediyne generates reactive radical species and causes significant damage to the spike (S) protein of coronavirus. The enediyne compounds exhibit antiviral activity at micromolar to nanomolar concentrations, and the selectivity index of up to 20,000 against four kinds of human coronaviruses, including the SARS-CoV-2 omicron variant, suggesting the high potential of this new strategy in combating the COVID-19 pandemic.
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The citations of original foreign language books in doctorial dissertations of Suzhou University in 2013 were analyzed,which showed that the number of cited original foreign language books on humanities and social sciences was greater than that on other science, the cited books were not limited to those that were recently published, the number of cited original foreign language books published by university press was greater than that published by other publishers. Suggestions were put forward for improving the acquisition of original foreign language books.
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<p><b>BACKGROUND</b>The postremission therapies for adult patients generally contain consolidation chemotherapy, allogeneic hematopoietic stem cell transplantation and autologous hematopoietic stem cell transplantation (auto-HSCT). Because of the various results from different centers, the optimal therapy for adult acute lymphoblastic leukemia (ALL) patients is still uncertain. This study aimed to better understand predictive factors and role of auto-HSCT in the postremission therapy for adult ALL patients.</p><p><b>METHODS</b>The outcomes of 135 adult patients with ALL, who received the first auto-HSCT in Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 1994 to February 28, 2014, were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method and simultaneous effects of multiple covariates were estimated with the Cox model.</p><p><b>RESULTS</b>Overall survival (OS) and disease-free survival (DFS) at 5 years for the whole cohort were 59.1 ± 4.5% and 59.0 ± 4.4%, respectively. The cumulative nonrelapse mortality and relapse rate at 5 years were 4.5 ± 0.03% and 36.6 ± 0.19%. For both OS and DFS, acute T-cell lymphoblastic leukemia, high lactate dehydrogenase (LDH) at diagnosis, blast cell proportion ≥5% on the 15 th day of induction therapy, and extramedullary infiltration before HSCT were the poor prognosis factors. In addition, age ≥35 years predicted poor DFS. Only T-ALL and high LDH were the independent undesirable factors associated with OS and DFS in Cox regression model. For 44 patients who had results of pretransplantation minimal residual disease (MRD), positive MRD (MRD ≥0.01%) indicated poor OS (P = 0.044) and DFS (P = 0.008). Furthermore, for the standard risk group, the patients with negative MRD (MRD <0.01%) had better results (OS at 18 months was 90.0 ± 9.5%, while for the patients with positive MRD OS was 50.0 ± 35.4%, P = 0.003; DFS at 18 months was 90.0 ± 9.5%, while for the positive MRD group DFS was 0%, P < 0.001).</p><p><b>CONCLUSIONS</b>This study confirmed that auto-HSCT combined with posttransplantation maintenance chemotherapy could be an option for adult ALL patients and pretransplantation MRD may play a significant role in the direction of therapy for adult ALL patients.</p>
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , China , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Estimativa de Kaplan-Meier , Neoplasia Residual , Mortalidade , Terapêutica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Mortalidade , Terapêutica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Transplante HomólogoRESUMO
<p><b>OBJECTIVE</b>To better understand predictive factors and role of autologous hematopoietic stem cell transplantation (auto-HSCT)in the post-remission therapy for adult Ph-negative B-cell acute lymphoblastic leukemia (B-ALL)patients.</p><p><b>METHODS</b>Outcomes of 86 adult patients with B-ALL who received auto-HSCT in our center from January 1996 to February 2014 were retrospectively analyzed.</p><p><b>RESULTS</b>Overall survival (OS)and disease free survival (DFS)at 5 years for the cohort were (63.8 ± 5.6)% and (60.9 ± 5.6)%, respectively. The cumulative non-relapse mortality (NRM)and relapse at 5 years were (4.70 ± 0.05)% and (34.40 ± 0.31)%. For DFS, age ≥ 35 years, high lactate dehydrogenase at diagnosis, high initial WBC count, blast cell proportion ≥ 5% on 15th day of the first induction therapy, complete remession (CR)1 to HSCT interval >6 months and CD34⁺ cells in graft ≥ 3.8 × 10⁶/kg were the poor prognostic factors. CR1 to HSCT interval >6 months was the independently undesirable factors in COX regression model. For 34 patients who had results of minimal residual disease (MRD), positive pretransplantation MRD (MRD≥0.01%), positive post-induction MRD or MRD positive again during the chemotherapy indicated poor prognosis, and the last one was the independent adverse prognostic factor.</p><p><b>CONCLUSION</b>Auto-HSCT combined with post-transplantation maintenance chemotherapy could be an optional approach for adult B-ALL patients. MRD plays a significant role in the treatment choice for adult Ph-negative B-ALL patients.</p>
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Adulto , Humanos , Doença Aguda , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas , Quimioterapia de Manutenção , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Terapêutica , Recidiva , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
ObjectiveTo investigate the efficacy and toxicity of postoperative radiochemotherapy compared with chemotherapy alone in the treatment of locally advanced gastric cancer.MethodsA total of 83 patients with resected adenocarcinoma of the stomach were randomly assigned to postoperative radiochemotherapy group (RCT) ( n =43 ) or chemotherapy alone group (CT) ( n =40 ).Patients in RCT group received radiotherapy concurrent with capecitabine chemotherapy then followed by 4 - 6 cycles of FOLFOX4 chemotherapy.The total dose of radiation was 45 Gy.The dose of capecitabine was 1600 mg/m2per day.In the CT group,patients received 6 - 8 cycles FOLFOX4 chemotherapy.Survival was analyzed using Kaplan-Meier method and Logrank test. Results The follow-up rate was 96%. The number of patients who had a minimum of 2-,3-year follow-up time were 37,12 in the RCT group and 31,10 in the CT group.The 1-,2-,3-year local control rates for RCT and CT groups were 100%,97%,94% and 95%,87%,73% (x2 =4.54,P =0.033),respectively.The 1-,2-,3-year survival rates were 98%,86%,81% in the RCT group,with 93%,80%,64% in the CT group ( x2 =3.96,P =0.047 ).The incidence of grade 3hematological toxicity in the RCT and CT group was 23% vs 15% ( x2 =0.93,P =0.630 ),and grade 3gastrointestinal toxicity was 16% vs 10% ( x2 =0.95,P =0.624 ). Conclusions Compared with chemotherapy alone,postoperative radiochemotherapy can improve survival of locally advanced gastric cancer patients with acceptable toxicities.
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Objective To evaluate the ability of 3-AB to sensitize the human esophageal carcinoma cell strain (CaEs-17) to radiation in v/tro and its mechanisms. Methods CaEs-17 cells were treated with 3-AB at 0, 2.5, 7.5 mmol/L and given irradiation O, 3, 6, 9, 12 Gy. 3-AB concentration in each group was made dose-survival curve using multi-target single-hit maiths model by clonogenie assay. MTT assay was performed to observe the survival of irradiated cells.comet assay and metaphase chromosome analysis were used to measure the DNA damage degree and chromosome aberration of CaEs-17 cell after 3-AB treatment and irradiation. Results Cell survival experiments showed SER of 1.21, 1.52 for 2.5 mmol/L, 7.5 mmol/L 3-AB respectively using multi-target single-hit maths model. The survival fraction of irradiated CaEs-17 cell was decreased after 3-AB treatment. DNA damage and the chromatid breakage number of irradiated CaEs-17 cells were increased after 3-AB treatment. Conclusions 3-AB, a PARP inhibitor, can enhance the radiosensitivity of human esophageal carcinoma cell strain (CaEs-17). DNA damage repair inhibition by 3-AB might be one of the mechanisms.
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Objective To evaluate the clinical application of GlideScope~ video laryngoscope in anesthetic endotracheal intubation.Methods Two hundred patients who received surgery under general anesthesia with ASA I or II were involved in this study.One hundred patients were assigned to be intubated with GlideScope~(GS group) and the other 100 with size 3 Macintosh laryngoscope(ML group).The following data were recorded and analyzed: noninvasive blood pressure(NBP),heart rate(HR) at the different time points of intubation process,glottic exposure time,CormarkLehane grade,tracheal intubation time and total intubation attempts. Results The rise of NBP and HR in ML group were significantly higher than those in GS group(P