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Objective@#To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports.@*Methods@#Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated.@*Results@#A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated.@*Conclusions@#The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.
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Objective:To evaluate the effects of different irradiation ranges in definitive intensity-modulated radiotherapy (IMRT) combined with chemotherapy on the survival of esophageal cancer patients.Methods:Clinical data of 360 esophageal cancer patients who received definitive chemoradiotherapy in the Fourth Hospital of Hebei Medical University from 2006 to 2015 were retrospectively analyzed. Among them, 131 patients received elective nodal irradiation (ENI) and 229 patients underwent involved-field irradiation (IFI). Platinum-based chemotherapy was adopted. The overall survival (OS) rate was analyzed by Kaplan- Meier method and Logrank test. Results:Until the final follow-up at the end of December 2018, the follow-up rate was 96%. The median follow-up time was 64 months (95% CI: 53-76). The median survival time was 24 months (95% CI: 20-28). The 1-, 3-, 5-year OS rates were 76.1%, 38.7% and 21.0%, respectively. After propensity score matching, the 1-, 3-, 5-year OS rates were 83.9%, 48.6%, 26.8% vs. 74.0%, 33.8%, 17.5% between the ENI ( n=131) and IFI groups ( n=131)( P=0.011), respectively. Subgroup analysis showed that patients with male, aged≤66 years, cervical and upper-thoracic location, tumor length≤7 cm, tumor volume≤50 cm 3, T 1-3 stage, dosage>60 Gy and concurrent chemoradiotherapy obtained better OS rates in the ENI group than their counterparts in the IFI group (all P<0.05). In the ENI group, the total failure rate, locoregional failure rate and distant metastasis rate were significantly lower, whereas the incidence of ≥Grade Ⅲ myelosuppression was remarkably higher than those in the IFI group (all P<0.05). Conclusion:Compared with IFI, ENI can significantly improve the survival for patients with early-stage and cervical and upper-thoracic esophageal cancer receiving definitive IMRT combined with chemotherapy.
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Objective:To evaluate the recurrence patterns of esophageal squamous cell carcinoma (ESCC) after radical surgery and analyze the predictors of post-recurrence survival (PRS).Methods:A total of 382 ESCC patients who developed recurrence after radical surgery were retrospectively reviewed from January 2007 to December 2011. All of them received salvage treatment after recurrence. The Univariate analysis was determined using the Kaplan-Meier method and log-rank test. Multivariate prognostic analysis was determined using the Cox proportional hazard model.Results:The 1-, 3-, 5-year overall survival (OS) rates were 80.9%, 35.6% and 20.4%, respectively. The median survival time and recurrence time were 29.2 months and 15.0 months. The 1-, 3-, 5-year PRS rates were 37.7%, 14.6% and 11.9%, respectively. The median PRS time was 10.2 months. Locoregional recurrence was noted at 462 sites among 382 patients including 20.5% (95/462) of sites in supraclavicular LN (lymph node), 10.0% (46/462) in anastomosis, 56.1% (259/462) in mediastinal regional LN and 13.4% (62/462) in upper abdominal LN. There were 156, 43, 82 and 101 patients treated with salvage radiotherapy, chemotherapy, chemoradiotherapy and palliative care after recurrence, respectively. The univariate analysis showed that T stage, N stage, TNM stage, recurrence site, number of recurrent regions and treatment regimen after recurrence were significantly correlated with PRS ( χ2=5.336, 4.292, 8.067, 7.482, 4.093, 76.426, P<0.05). Patients receiving salvage radiotherapy with the median dose of 60 Gy, were divided into <60 Gy group and ≥ 60 Gy group. The ≥60 Gy group had a better PRS than <60 Gy group ( χ2=8.320, P<0.05). Multivariate analysis showed that number of recurrent regions and treatment regimen were independent prognostic factors of PRS. Conclusions:Mediastinal and supraclavicular regions were the most common sites of recurrence in ESCC patients after radical surgery. Salvage radiotherapy and chemoradiotherapy could significantly improve PRS in recurrent ESCC patients.
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Objective:To evaluate the efficacy of target area of radical radiotherapy for inoperable esophageal carcinoma patients treated with intensity-modulated radiotherapy (IMRT).Methods:A retrospective analysis was performed on the clinical data of 564 Ⅰ-Ⅳ non-surgical esophageal cancer who received definitive intensity-modulated radiotherapy alone in our hospital from 2006 to 2015. Propensity score matching (PSM) was used to identify well-balanced patients for comparison. The Kaplan-Meier method was used to calculate local-regional failure-free survival (LRFFS), progression-free survival (PFS), overall survival (OS) rates and univariate analysis. The multivariate analysis of prognostic factors were tested by COX proportional hazard model.Results:The last follow-up time was December 2018, the median follow-up time was 99.7 (95% CI: 77.5-122.1) months. Follow-up rate was 95.9%. For the 564 patients, the 1-, 3-, 5- year LRFFS were 61.5%, 26.5%, 14.3%, PFS were 56.7%, 25.0%, 13.4%, OS were 73.0%, 31.1%, 16.8%. After PSM, for the elective-nodal irradiation (ENI) ( n=141) and involved-nodal irradiation (IFI) ( n=141) groups, the 1-, 3-, 5- year LRFFS were 68.8%, 34.2%, 19.1% vs. 65.2%, 32.1%, 17.9% ( P>0.05), PFS were 63.1%, 31.0%, 16.6% vs. 60.3%, 29.3%, 16.6% ( P>0.05), OS were 80.9%, 41.5%, 23.3% vs. 80.1%, 35.0%, 20.2% ( P>0.05). In multivariate analysis, tumor volume≤37 cm 3 and Ⅰ+ Ⅱ stage were independent factors for LRFFS, PFS and OS. Subgroup analysis showed that there were no significant differences in the survival rates between the ENI group and IFI group ( P>0.05). Comparing to the IFI group, ENI reduced the local-regional failure rate ( P=0.048). Conclusions:Using intensity-modulated radiation therapy alone for inoperable esophageal carcinoma, ENI can significantly reduce the local-regional failure rate, but not improve survival rates compared to the IFI.
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Objective To investigate the prognostic effects and failure patterns of different clinical target volumes of IMRT in definitive chemoradiotherapy for cervical and upper-thoracic esophageal cancer,in order to provide a reference for radiotherapy target area delineation.Methods A retrospective analysis was performed on the clinical data of 132 patients with cervical and upper-thoracic esophageal cancer who received definitive IMRT and concurrent chemotherapy in our hospital from 2010 to 2014.Seventy-one patients received elective nodal irradiation (ENI) and the other 61 patients received involvedfield irradiation (IFI).The Kaplan-Meier method was used to calculate local control (LC),progressionfree survival (PFS) and overall survival (OS) rates.The significant difference was evaluated by the logrank test.The prognostic factors were determined by Cox univariate and multivariate analyses.Results The last follow-up time was December 2017,the median follow-up time was 59.5 (14.2-95.8) months.Follow-up rate was 99.2％.For the ENI and IFI groups,the 1-,3-,5-year LC were 77.5％,58.8％,48.8％ vs.64.3％,29.1％,26.2％ (x2=9.68,P=0.002),PFS were 68.6％,37.7％,25.9％ vs.47.5％,17.2％,3.6％ (x2=11.39,P=0.001),OS were 81.7％,53.9％,31.3％ vs.70.5％,31.9％,16.3％ (x2=7.70,P =0.006),respectively.In multivariate analysis,T stage,N stage,and RT field were independent factors for LC,PFS and OS(P＜0.05).The total failure rates,local-regional recurrent rate in ENI group were lower than those in IFI group (x2 =13.23,5.24,P＜0.05).No significant differences were found in acute radiation esophagitis,pneumonitis and myelosuppression (Grades ≥ 3) between the two groups(P＞0.05).Conclusions Compared with IFI,ENI can significantly reduce local-regional recurrence and distant metastasis and improve the long-term survival for cervical and upper-thoracic esophageal cancer patients who received definitive chemoradiotherapy.
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Objective To evaluate the effect of RNF2 gene knockdown in ECA109 cells on the radiosensitivity to esophageal cancer cell xenograft in nude mice. Methods Thirty-six male BALB/c/nu nude mice were randomly divided into 6 groups: control group, control+ irradiation group, NC group, NC+irradiation group, RNF2 shRNA group and RNF2 shRNA+ irradiation group. The nude mouse models with transplanted tumors were established by subcutaneous inoculation of EAC109 cells and given with irradiation at a dose of 3 Gy for 5 times. The longest ( a) and shortest ( b) diameters of the transplanted tumor were measured every 2 to 3 day since the fourteenth day after inoculation. The time of tumor formation was recorded. The tumor volume was calculated according to the formula ( ab2/2 ) . The growth curve was delineated. Three nude mice were sacrificed in each group at 24 h after the initial irradiation. The expression of RNF2 at the mRNA and protein levels in transplanted tumor tissues was measured by qRT-PCR and immunohistochemistry, respectively. The growth and tumor volume of the other nude mice in each group were observed. The cell apoptosis of transplanted tumor tissues was detected by TUNEL assay. The expression of Bcl-2 and Bax at the mRNA and protein levels in transplantated tumor tissues was quantitatively measured by qRT-PCR and immunohistochemistry, respectively. Results The tumor growth rate was the highest in the control and NC groups. The knockdown of RNF2 reduced the growth rate of xenografts and the tumor growth rate was the slowest in the RNF2 shRNA+ irradiation group ( P<0.05) . TUNEL assay revealed that the cell apoptosis rates in all groups were significantly increased after irradiation ( all P<0.05) . Before and after irradiation, the apoptosis rate in the RNF2 shRNA group was markedly higher than those in the control and NC groups ( both P<0.05) . Prior to irradiation, the expression levels of RNF2 mRNA and protein in the RNF2 shRNA group were significantly lower compared with those in the control and NC groups ( all P<0.05) , and the tendency became more significant after irradiation. Compared with the control and NC groups, the expression levels of Bcl-2 mRNA and protein were significantly down-regulated in the RNF2 shRNA group before and after irradiation ( all P<0.05) , whereas those of Bax mRNA and protein were considerably up-regulated ( all P<0.05 ) . Conclusions In vivo experiment demonstrates that RNF2 knockdown effectively increases the radiosensitivity of esophageal carcinoma EAC109 cells in nude mouse models with transplanted tumors, which is intimately associated with inducing the cell apoptosis.
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Objective To compare the clinical efficacy between simultaneous integrated boost (SIB) and sequential boost (SB) using intensity-modulated radiotherapy (IMRT),and investigate the long-term clinical efficacy and adverse events of SIB-IMRT in combination with chemotherapy in the treatment of esophageal cancer.Methods Clinical data of 330 patients diagnosed with esophageal cancer undergoing radical chemoradiotherapy in Fourth Hospital of Hebei University from January 2006 to December 2015 were respectively analyzed.All patients were assigned into the SIB-IMRT (n=135) and SB-IMRT groups (n=195).All patients received definitive radiotherapy with elective nodal irradiation (ENI).After the propensity score matching (PSM),105 patients were enrolled in each group.Kaplan-Meier method was used to survival analysis.Cox model was used to multivariate prognostic analysis.Results Prior to PSM,the 1-,3-and 5-year local control rates were 80.1％,58.3％,46.7％ and 72.1％,44.9％,40.5％ in the SIB-IMRT and SB-IMRT groups (P=0.050),and the 1-,3-and 5-year OS rates were 81.4％,51.9％,43.5％ and 80.5％,37.9％,22.3％(P=0.014),respectively.After the PSM,the 1-,3-and 5-year LC rates were 80.2％,54.2％,43.9％ and 75.5％,47.2％,41.2％ (P=0.264),and the 1-,3-and 5-year OS rates were 78.9％,49.0％,40.8％ and 83.3％,41.7％,24.8％ (P=0.265),respectively.Multivariate analysis demonstrated that TNM staging was an independent prognostic factor in the SIB-IMRT group,whereas TNM staging and chemotherapy served as the independent prognostic factors in the SB-IMRT group.Stratified analysis revealed that the LC rate in the SIB-IMRT was significantly higher than that in the SB-IMRT group when radiotherapy alone was performed (P =0.018).The OS rate in the SIB-IMRT group was equally higher compared with that in the SBIMRT group.Conclusions The LC and OS rates are almost identical after SB-IMRT and SIB-IMRT in the treatment of esophageal cancer,whereas the prognostic survival in the SIB-IMRT group is significantly longer compared with that in the SB-IMRT group during radiotherapy alone.The findings remain to be validated by multi-center investigations with a large sample size.
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Objective To evaluate the repeated dose toxicity of MNT-016 in SD rats and to provide reference for toxicity evaluation.Methods MNT-016 was administered to rats at 5, 20 and 80 mg/kg for 90 days.The toxic effects on the animals were evaluated by observing the clinical signs and measuring the body weight, hematology and blood biochemistry as well as histopathological examination.NOAEL and benchmark dose lower confidence limit(BMDL) were observed by the end point of toxicity.Results Compared with the control group, the AST, TBIL, DBIL and Crea of male rats were increased in a dose-dependent manner, while TG and CHOL decreased.The body mass(before anatomy), heart, liver, thymus, epididymis of male rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of the heart and lung was increased.The body mass (before anatomy) and thymus of female rats in 80 mg/kg group were significantly decreased (P<0.05), while absolute organ mass of lungs was increased.Vacuolation of hepatocytes was observed in groups each dose, tubule atrophy was found in the kidneys of 20 and 5 mg/kg groups, and tubule basophilia was observed in 80 mg/kg group.The incidence of the above lesions was higher in male animals than in female ones.Conclusion The NOAEL of MNT-016 is lower than 5 mg/kg in male rats and 5 mg/kg in female rats.BMDL value is 2.65 mg/kg in male animals and more accurate than NOAEL, and is 9.04 mg/kg in female animals,which is slightly larger than the corresponding NOAEL.
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The purpose of risk assessment is to evaluate the permissible exposure level under specific risk factors.To extrapolate the human acceptable daily intake (ADI) and/or reference dose (RfD), the traditional method uses the no-observed-adverse-effect level ( NOAEL ) to quantify toxicity after being divided by uncertainty factor.There are many limitations with NOAEL method in safety evaluation,for it relies too much on experimental design.Benchmark dose ( BMD) approach is a more reliable method with many advantages.BMD approach and its analysis software, the advantages of BMD over NOAEL, the application and methodological perfection in risk assessment of long-team exposure toxicity are presented in this review.