Numerical Study of the High-Frequency Wave Loads and Ringing Response of A Bottom-Hinged Vertical Cylinder in Focused Waves

This paper presents a numerical study on the high-frequency wave loads and ringing response of offshore wind turbine foundations exposed to moderately steep transient water waves.Input wave groups are generated by the technique of frequency-focusing,and the numerical simulation of focused waves is based on the NewWave model and a Fourier time-stepping procedure.The proposed model is validated by comparison with the published laboratory data.In respect of both the wave elevations and the underlying water particle kinematics,the numerical results are in excellent agreement with the experimental data.Furthermore,the local evolution of power spectra and the transfer of energy into higher frequencies can be clearly identified.Then the generalized FNV theory and Rainey’s model are applied respectively to calculate the nonlinear wave loads on a bottom-hinged vertical cylinder in focused waves.Resonant ringing response excited by the nonlinear high-frequency wave loads is found in the numerical simulation when frequency ratios(natural frequency of the structure to peak frequency of wave spectra)are equal to 3–5.Dynamic amplification factor of ringing response is also investigated for different dynamic properties(natural frequency and damping ratio)of the structure.

The Effect of Corporate Social Responsibility on Employees＇ Organizational Commitment in High-tech Enterprises of Jiangsu Province--Based on the Mediating Role of Regulatory Focus

With China＇s rapid economic development, corporate social responsibility （CSR） plays greater impact on its direct stakeholder employees＇ organizational commitment （EOC）. A questionnaire survey was conducted on 426 employees of high-tech enterprises within Jiangsu Province. Multiple regression method was used to test the hypothesis based on the questionnaire reliability and validity analysis. The results show that the four dimensions of CSR including employees responsibility, products responsibility, environment responsibility and charitable responsibility have positive effect on the affective commitment;while the continuance commitment might be more influenced by the environment and charitable responsibility. The regulatory focus plays a moderate effect between CSR and EOC. Promote regulatory focus have positive impact on affective commitment and negative impact on continuance commitment. Defense regulatory focus is just on the opposite.

参仙升脉口服液化学成分的UHPLC-Q Exactive Focus MS/MS快速分析

目的探究参仙升脉口服液的化学物质基础。方法利用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UHPLC-Q Exactive Focus MS/MS)对参仙升脉口服液的化学成分进行整体、系统辨识。采用Thermo Accucore aQ C_(18)色谱柱(150 mm×2.1 mm,2.6μm),流动相0.1%甲酸水溶液(A)-甲醇(B)梯度洗脱,洗脱程序为0-13 min,5%-60%B;13-27 min,60%-95%B;27-30 min,95%B,流速0.3 mL·min^(-1),柱温30°C;质谱分析离子化方式为加热电喷雾离子化(H-ESI),扫描模式为正、负离子切换,扫描范围m/z 120-1800,碰撞能量30 eV、50 eV、70 eV。结果共鉴定出160个化学成分,包括29个黄酮类成分,24个有机酸类成分,21个生物碱类成分,19个萜类成分,15个苯丙素类成分,12个皂苷类成分和40个其他类成分;其中6个化学成分(芦丁、补骨脂苷、异补骨脂苷、补骨脂素、异补骨脂素和补骨脂酚)经对照品比对确认。结论该研究借助UHPLC-Q Exactive Focus MS/MS技术实现了参仙升脉口服液化学成分准确、快速、系统的分析和鉴定,为其化学物质基础的阐明和质量控制提供了重要依据。

Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized with HIFU-generated vaccine,tumor-generated vaccine,and saline,respectively.In addition,20 mice bearing H22 tumors were successfully treated with HIFU ablation. The protective immunity of the vaccinated mice was investigated before and after a subsequent H22 tumor challenge.Using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide assay,the cytotoxicity of splenic lymphocytes co-cultured with H22 cells wasdetermined in vitro before the tumor challenge,and tumor volume and survival were measured in vivo after the challenge in each group.The mechanism was also explored by loading the vaccines with bone marrowderived dendritic cells(DCs). RESULTS:Compared to the control,HIFU therapy, tumor-generated and HIFU-generated vaccines significantly increased cytolytic activity against H22 cells in the splenocytes of the vaccinated mice(P<0.001). The tumor volume was significantly smaller in the HIFU vaccine group than in the tumor vaccine group(P <0.05)and control group(P<0.01).However,there was no tumor growth after H22 rechallenge in the HIFU therapy group.Forty-eight-day survival rate was 100%in mice in the HIFU therapy group,30%in both the HIFU vaccine and tumor vaccine groups,and 20% in the control group,indicating that the HIFU-treated mice displayed significantly longer survival than the vaccinated mice in the remaining three groups(P< 0.001).After bone marrow-derived DCs were incubated with HIFU-generated and tumor-generated vaccines, the number of mature DCs expressing MHC-Ⅱ + ,CD80 + and CD86 + molecules was significantly increased,and interleukin-12 and interferon-γlevels were significantly higher in the supernatants when compared with immature DCs incubated with mouse serum(P<0.001). However,no differences of the number of mature DCs and cytokine levels were observed between the HIFU- generated and tumor-generated vaccines(P>0.05). CONCLUSION:Tumor debris remaining after HIFU can improve tumor immunogenicity.This debris releases tumor antigens as an effective vaccine to develop host antitumor immune response after HIFU ablation.

Effect of high-intensity focused ultrasound (HIFU) combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and evaluation of side effects

Objective:To study the effect of high-intensity focused ultrasound (HIFU) combined with radiotherapy on tumor malignancy in patients with advanced pancreatic cancer and the corresponding side effects.Methods:A total of 84 patients with advanced pancreatic cancer treated in our hospital between May 2013 and March 2016 were selected and randomly divided into HIFU group and IGRT group, HIFU group accepted high-intensity focused ultrasound combined with radiotherapy and IGRT group received radiotherapy alone. 4 weeks after treatment, the levels of tumor markers, liver and kidney function indexes, perineural invasion-related molecules and cytokines in serum as well as the levels of immune cells in peripheral blood were determined.Results:4 weeks after treatment, serum CA199, CA242, OPN, NGAL, RBP4, NGF, TrkA, p75, BDNF and TrkB levels of HIFU group were significantly lower than those of IGRT group, serum IL-2, TNF-α, IFN-γ and IL-13 levels as well as peripheral blood NKT cell and CD4+T cell levels were significantly higher than those of IGRT group, and serum ALT, AST, Cr and BUN levels were not significantly different from those of IGRT group.Conclusion:HIFU combined with radiotherapy treatment of advanced pancreatic cancer can more effectively kill cancer cells, inhibit pancreatic cancer cell invasion to the peripheral nerve and enhance the antitumor immune response mediated by NKT cells and CD4+T cells.

Vitamin D improves viral response in hepatitis C genotype 2-3 nave patients

AIM: To examine whether vitamin D improved viral response and predicted treatment outcome in patients with hepatitis C virus (HCV) genotype 2-3. METHODS: Fifty patients with chronic HCV genotype 2-3 were randomized consecutively into two groups: Treatment group [20 subjects, age 48 ± 14 years, body mass index (BMI) 30 ± 6, 65% male], who received 180 μg pegylated α-interferon-2a plus oral ribavirin 800 mg/d (Peg/RBV), together with oral vitamin D3 (Vitamidyne D drops; 2000 IU/d, 10 drops/d, normal serum level > 32 ng/mL) for 24 wk; and control group (30 subjects, age 45 ± 10 years, BMI 26 ± 3, 60% male), who received identical therapy without vitamin D. HCV RNA was assessed by reverse transcription polymerase chain reaction. Undetectable HCV RNA at 4, 12 and 24 wk after treatment was considered as rapid virological response, complete early virological response, and sustained virological response (SVR), respectively. Biomarkers of in? ammation were measured. RESULTS: The treatment group with vitamin D hadhigher BMI (30 ± 6 vs 26 ± 3, P < 0.02), and high viral load (> 400 000 IU/mL, 65% vs 40%, P < 0.01) than controls. Ninety-fi ve percent of treated patients were HCV RNA negative at week 4 and 12. At 24 wk after treatment (SVR), 19/20 (95%) treated patients and 23/30 (77%) controls were HCV RNA negative (P < 0.001). Baseline serum vitamin D levels were lower at baseline (20 ± 8 ng/mL) and increased after 12 wk vitamin D treatment, to a mean level of (34 ± 11 ng/ mL). Logistic regression analysis identifi ed vitamin D supplement [odds ratio (OR) 3.0, 95% CI 2.0-4.9, P < 0.001], serum vitamin D levels (< 15 or > 15 ng/mL, OR 2.2, P < 0.01), and BMI (< 30 or > 30, OR 2.6, P < 0.01) as independent predictors of viral response. Adverse events were mild and typical of Peg/RBV. CONCLUSION: Low vitamin D levels predicts negative treatment outcome, and adding vitamin D to conventional Peg/RBV therapy for patients with HCV genotype 2-3 signifi cantly improves viral response.

Elastic responses of underground circular arches considering dynamic soil-structure interaction:A theoretical analysis

Due to the wide applications of arches in underground protective structures, dynamic analysis of circular arches including soil-structure interactions is important. In this paper, an exact solution of the forced vibration of circular arches subjected to subsurface denotation forces is obtained. The dynamic soil-structure interaction is considered with the introduction of an interfacial damping between the structure element and the surrounding soil into the equa- tion of motion. By neglecting the influences of shear, rotary inertia and tangential forces and assuming the arch incompressible, the equations of motion of the buried arches were set up. Analytical solutions of the dynamic responses of the protective arches were deduced by means of modal super- position. Arches with different opening angles, acoustic impedances and rise-span ratios were analyzed to discuss their influences on an arch. The theoretical analysis suggests blast loads for elastic designs and predicts the potential failure modes for buried protective arches.

Study on Technologies for Information Monitoring and Quick Response of Agricultural Focuses and Significant Events

This article analyzed the importance of information monitoring and quick response on agricultural focuses and significant events, proposed the workflow and technical framework for information monitoring and quick response based on modern information technologies, and explained key technologies during implementation and the functional structure for prototype system of the technical support platform.

The radiation response of androgen-refractory prostate cancer cell line C4-2 derived from androgen-sensitive cell line LNCaP

Radiation therapy is a relatively effective therapeutic method for localized prostate cancer （PCa） patients. However, radioresistance occurs in nearly 30% of patients treated with potentially curative doses. Therapeutic synergy between radiotherapy and androgen ablation treatment provides a promising strategy for improving the clinical outcome. Accordingly, the androgen deprivation-induced signaling pathway may also mediate radiosensitivity in PCa cells. The C4-2 cell line was derived from the androgen-sensitive LNCaP parent line under androgen-depleted condition and had acquired androgen-refractory characteristics. In our study, the response to radiation was evaluated in both LNCaP and C4-2. Results showed that C4-2 cells were more likely to survive from irradiation and appeared more aggressive in their resistance to radiation treatment compared with LNCaP, as measured by clonogenic assays and cell viability and cell cycle analyses. Gene expression analyses revealed that a set of genes involved in cell cycle arrest and DNA repair were differentially regulated in LNCaP and C4-2 in response to radiation, which was also consistent with the radiation-resistant property observed in C4-2 cells. These results strongly suggested that the radiation-resistant property may develop with progression of PCa to androgen- independent status. Not only can the LNCaP and C4-2 PCa progression model be applied for investigating androgen-refractory progression, but it can also be used to explore the development of radiation resistance in PCa.

Factors associated with early virological response to peginterferon-α-2a/ribavirin in chronic hepatitis C

AIM: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to pegin-terferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. METHODS: We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d).RESULTS: A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventyeight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CONCLUSION: CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.

Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p

BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Z α-1 antitrypsin deficiency and the endoplasmic reticulum stress response

The serine proteinase inhibitor α-1 antitrypsin(AAT) is produced principally by the liver at the rate of 2 g/d.It is secreted into the circulation and provides an antiprotease protective screen throughout the body but most importantly in the lung,where it can neutralise the activity of the serine protease neutrophil elastase.Mutations leading to def iciency in AAT are associated with liver and lung disease.The most notable is the Z AAT mutation,which encodes a misfolded variant of the AAT protein in which the glutamic acid at position 342 is replaced by a lysine.More than 95% of all individuals with AAT def iciency carry at least one Z allele.ZAAT protein is not secreted effectively and accumulates intracellularly in the endoplasmic reticulum(ER) of hepatocytes and other AAT-producing cells.This results in a loss of function associated with decreased circulating and intrapulmonary levels of AAT.However,the misfolded protein acquires a toxic gain of function that impacts on the ER.A major function of the ER is to ensure correct protein folding.ZAAT interferes with this function and promotes ER stress responses and inflammation.Here the signalling pathways activated during ER stress in response to accumulation of ZAAT are described and therapeutic strategies that can potentially relieve ER stress are discussed.

Anesthetic effect of dexmedetomidine in high intensity focused ultrasound treatment of uterine fibroids

Objective: To study the effect of dexmedetomidine in high intensity focused ultrasound treatment of uterine fibroids on pain degree, pain mediator and stress mediator secretion as well as stress signal molecule expression. Methods: 78 patients with uterine fibroids who received high intensity focused ultrasound treatment in Shaanxi Second Provincial People's Hospital between February 2015 and February 2018 were selected as the research subjects and randomly divided into the Dex group who accepted dexmedetomidine + fentanyl + midazolam anesthesia and the control group who accepted fentanyl + midazolam anesthesia. The pain degree was assessed 1 day and 3 d after surgery;the secretion of pain mediators and stress mediators in serum as well as the expression levels of stress signaling molecules in peripheral blood were measured before surgery and 3 d after surgery. Results: 1 d and 3 d after surgery, the NRS pain scores of Dex group were significantly lower than those of control group;3 d after surgery, serum SP, BK, 5-HT, IL-6, IL-8, NE, COR, ACTH and MDA contents as well as peripheral blood NF-κB, p38MAPK, NOX4 and Nrf2 expression of both groups of patients were higher than those before surgery whereas serum SOD and HO-1 contents as well as peripheral blood Keap1 expression were lower than those before surgery, and serum SP, BK, 5-HT, IL-6, IL-8, NE, COR, ACTH and MDA contents as well as peripheral blood NF-κB, p38MAPK, NOX4 and Nrf2 expression of Dex group 3 d after surgery were lower than those of control group whereas serum SOD and HO-1 contents as well as peripheral blood Keap1 expression were higher than those of control group. Conclusion: The application of dexmedetomidine in high intensity focused ultrasound treatment of uterine fibroids can reduce the degree of postoperative pain and stress response.

CYFRA 21-1 as an early predictor of first line chemotherapy response in advanced non small cell lung cancer

Objective： In an era of ever evolving, promising new therapies for advanced non small cell lung cancer （NSCLC）, early predictors of response to therapy, are needed. We evaluated early variations in CYFRA 21-1 serum levels of patients with advanced NSCLC receiving first line chemotherapy and correlated the results with objective tumor response. Methods： 29 consecutive, previously untreated, patients of advanced non small cell lung cancer, with measurable disease on CT scan were evaluated. All patients were treated with conventional systemic chemotherapy, although the choice of chemotherapy was left to the discretion of the treating physicians. Serum samples were obtained immediately before the start of 1st and 2nd cycles of chemotherapy. CYFRA 21-1 was measured with an electrochemiluminescense immunoassay on an automatic analyzer （Elecsys 2000; Roche Diagnostics）. Response was evaluated using Response evaluation criteria in solid tumors （RECIST） criteria. Results： 10 patients had partial response, 9 patients had stable disease and 9 had progressive disease. None of the patients had complete response. 21/29 （72%） patients had an elevated baseline value of CYFRA 21-1.62% patients （18/29） had a decrease in CYFRA 21-1 after 1 cycle of chemotherapy. The average reduction in the 2nd reading was irrespective of whether baseline value was normal or not. The average reduction was statistically significant （P = 0.002; 95% CI, from 0.8369 to 3.49464; t test）. 8 out of 10 （80%） patients with partial response had a reduction in their 2nd reading of. CYFRA （P = 0.019; 95% CI, from 0.81965 to 7.20035; t test） which was significant. We also observed that 6/9 （66%） patients whose disease remains stable also had a decrease in their subsequent reading （P = 0.0106; 95% CI, from -0.44942 to 3.82720; t test）, though it was not significant statistically. Although 5 out of 9 （55%） patients, who had an increase in their CYFRA 21-1 level, had progressive disease, but it was not statistically significant （P = 0.537; 95% CI, from -1.20021 to 2.13354; ttest）. 14 out of 19 （73%） who either had partial response or had stable disease, had a reduction in their 2nd value of CYFRA 21-1 and was significant statistically （P = 0.004; 95% CI, from 0.74792 to 3.50208; t test）. We also observed that except for 1 patient, all patients who had a decrease of 42% or more in their subsequent CYFRA 21-1 level, were those who had either responded to chemotherapy or had stable disease （P = 0.001）, which was statistically significant. Conclusion： We can conclude that monitoring of serum marker CYFRA 21-1, early dudng first-line chemotherapy may be a useful prognostic tool for evaluation of early tumor response in patients with advanced NSCLC.

Response Surface Methodology as an Approach for Optimization of the Synthesis of 1-(2-Aminoethyl)-2-imidazolidone

Ruthenium loaded on activated carbon pre-treated by HNO3 was used to catalyze the reaction of 1-(2-Aminoethyl)-2-imidazolidone (AEI) synthesized from ethylenediamine, ethanolamine and CO2. Response surface methodology (RSM) based on Box-Behnken design (BBD) was employed to optimize the synthesis of AEI. The statistical analysis results showed that the yield of AEI was significantly affected by the CO2 pressure, reaction temperature and reaction time. According to the results of variance analysis, the value of the determination coefficient of 0.9854 was in reasonable agreement with the “Adj R-Squared” of 0.9666, which means this model can predict the yield of AEI well and can be used to optimize reaction conditions for higher AEI yield. The optimal values of AEI yield predicted by RSM was 84.9% under temperature 206.51?C, CO2 pressure 9.35 Mpa, reaction time 10.11 h, and the verification experiment yield of AEI was 83.1%.

Extreme value of wind-excited response considering influence of bandwidth

This paper addresses the peak factors of wind- excited responses including alongwind, acrosswind tall building responses and vortex-induced vibration considering the bandwidth parameter. The influence of bandwidth parameter on the peak factor is investigated using advanced upcrossing theory taking the bandwidth influence into account. Results show that Davenport＇s formula without consideration of bandwidth parameter servers well in general. However, the advanced upcrossing theory leads to a better prediction of the peak factor of wind-induced response of very lightly damped buildings.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

The 5’-Untranslated Region of the C9orf72 mRNA Exhibits a Phylogenetic Alignment to the Cis-Aconitase Iron-Responsive Element;Novel Therapies for Amytrophic Lateral Sclerosis

The hexanucleotide repeat mutation in the intron-1 of the chromosome 9 open reading frame (C9orf72) is a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Altered RNA folding plays a role in ALS pathogenesis in two ways: non-ATG translation of the repeat can lead to aggregates of the known C9orf72 specific dipeptide polymer, whereas the repeat also can form neurotoxic RNA inclusions that dose-responsively kill motor neurons. We report the presence of a homology in the 5’untranslated region (UTR) of the messenger RNA encoding C9orf72 with the iron responsive elements (IRE) that control expression of iron-associated transcripts and predict that this RNA structure may iron-dependently regulate C9orf72 translation. We previously report altered serum ferritin levels track with severity of ALS in patients. Here, we conduct bioinformatics analyses to determine the secondary structure of the 5’UTR in C9orf72 mRNA and find it aligned with IREs in the human mitochondrial cis-aconitase and L and H-ferritin transcripts. Comparison of the role of RNA repeats in Friedriech’s ataxia and fragile X mental retardation suggests the utility of RNA based therapies for treatment of ALS. Antisense oligonucleotides (ASO) have been reported to therapeutically target these GGGGCC repeats. At the same time, because the function of C9orf72 is unknown, knockdown strategies carry some risk of inducing or compounding haploinsufficiency. We propose, for consideration, an approach that may enhance its therapeutic dynamic range by increasing the 5’UTR driven translation of C9orf72 protein to compensate for any potential ALS-specific or ASO-induced haploinsufficieny.

基于“情景-任务-能力”的长三角传染病区域协同处置能力提升

提升传染病区域协同处置能力是深化长三角卫生健康协同发展的重要抓手。卫生应急演练是检验卫生应急体系建设的重要手段。本研究将“情景-任务-能力”的方法引入长三角传染病区域协同处置领域,以构建杭州亚运会测试赛期间发现登革热等输入传染病病例后区域协查和联动处置情景为例,分析应急处置5个阶段的任务、主要责任单位及任务要点,并以“区域联合风险评估和风险管理”为例,从预案方案、组织领导、人员、设备与系统、物资、培训、演练等7个方面着手,详细分析能力评估的内容。同时,采用“任务分类”的思想,针对属于第二类任务的区域联动涉及的协查、评估和培训等任务,以“区域联合风险评估和风险管理”任务为例,提出制定区域联合风险评估和风险管理协议或方案,成立区域卫生应急专家智库,加强区域公共卫生风险评估交流和统一培训等措施建议。