以重水为氘源的钴催化脱卤氘代反应

自2017年氘代丁苯那嗪获得美国食品药品监督管理局批准以来,氘代化合物在药物开发领域的潜力受到越来越多的重视.开发高效实用的有机分子选择性氘化方法成为有机和药物化学家的研究热点.有机卤化物是性质稳定且来源广泛的化学品,其脱卤氘代反应已经发展成为构建氘代化合物的有效策略.然而,已报道的制备方法普遍存在氘代试剂昂贵、底物适用范围较窄或需要使用特殊的反应设备(光催化或电化学)等诸多问题.因此,开发简单普适的廉价金属催化体系,实现以廉价重水为氘源的脱卤氘代反应,具有重要的研究意义.相较于钯、铑等贵金属,储量丰富且毒性较低的钴金属催化剂对水分敏感度较低,且对C(sp2)-X和C(sp3)-X键活化都表现出较好的反应活性.基于此,本文开发了制备简单、普适性较好的钴催化体系,实现了位点选择性氘代化合物的构建.反应以锰金属为还原剂,重水为氘源,对各种类有机卤化物或类卤化合物,如芳基、烯基、苄基、烯丙基或烷基卤化物,均获得较好的收率和氘代率.值得注意的是,对于炔丙基乙酸酯类化合物,该催化体系也展现出较好的适用性,可以专一的选择性得到氘代联烯类化合物.在此基础上,成功将该方法应用于一系列药物类似物的选择性脱卤氘代.利用简单的C-O偶联和脱溴氘代反应,即可实现氘代的N-甲基度洛西汀的合成.鉴于药物分子直接进行氢-氘同位素交换时位点选择性控制的挑战,本文发展了卤代-氘代的两步策略.该策略成功应用于生育酚、萘普生、黄毒素、萘丁美酮等多个药物分子的位点选择性氢-氘同位素交换,充分展现出该催化合成方法在药物开发领域的应用潜力.为了验证反应机理,开展了一系列对照实验.结果表明,反应可能是由一价钴物种催化启动的.此外,自由捕获和抑制实验结果表明,反应并非通过自由基反应过程进行.基于以上实验结果提出了一个反应机理,它涉及Co(I)到Co(III)再回到Co(I)的催化循环.具体来说,首先,一价钴络合物与底物发生氧化加成生成三价钴络合物;随后,三价钴物种与重水络合,并通过还原消除的方式生成氘代化合物和一价钴物种.最后,为了验证这一机理,还利用密度泛函理论进行了计算,结果进一步证明了该机理的合理性.综上,本文利用钴催化体系,以廉价重水为氘源,实现芳基、烯基、苄基、烯丙基或烷基等卤化物,以及炔丙基乙酸酯类类卤化合物的选择性氘代反应.该反应表现出较好的底物适用性,为相关氘代有机化合物的制备提供了新思路.

生物标记物及探针在胃癌分子影像诊断中的研究进展

胃癌在世界范围内仍然是一种发病率和死亡率较高的恶性肿瘤,其发病较为隐匿,发现时已经处于晚期,缺乏有效的个体化治疗方法,预后也较差.如果胃癌能够实现早期诊断,可以极大程度提高患者的生存率,然而目前传统的成像方式缺乏特异性与敏感性.近年来,分子成像技术蓬勃发展,可以在细胞和分子水平对胃癌进行非侵入性地动态监测,为临床选择治疗方案、评估疗效和预后提供更多的参考信息.本文就胃癌的生物标志物以及在各种成像模式下的分子探针做一综述.

Predictive value of CA-153,CA-125 and Apo A for ocular metastasis in menopausal female patients with breast cancer

AIM:To establish a meaningful standard for diagnosing ocular metastasis(OM)in menopausal breast cancer(BC)women,and explore the relationship between CA-153,CA-125,apolipoprotein A,and OM.METHODS:A total of 1362 menopausal female BC patients with OM volunteered to take part in this study between July 2012 and July 2022.Women with BC who are menopausal were found to have an OM incidence of 1.6%.Furthermore,CA-153,CA-125,and apolipoprotein A(Apo A)all contributed to OM in women with BC who are postmenopausal according to binary logistic regression.Receiver operating curve(ROC)analysis was used to assess the diagnostic value of OM in patients with BC.RESULTS:Both CA-153 and CA-153+CA-125 showed a higher sensitivity of 95.45%,whereas CA-153+Apo A illustrated the highest specificity of 99.02%.Moreover,CA-153 and CA-153+CA-125 had higher areas under the curve(AUC)of 0.973.CONCLUSION:The data indicate that the serum concentrations of CA-153 exhibited the most significant predictors of the diagnosis of OM in menopausal women with BC.The current study researches the utility of risk factors in predicting of OM in menopausal BC women and put forward the latest suggestions on their clinical application.

Lipid-lowering effects of gefarnate in statin-treated patients with residual hypertriglyceridemia:a randomized controlled study

BACKGROUND The prevention of coronary artery disease(CAD)faces dual challenges:the aspirin-induced gastrointestinal injury,and the residual cardiovascular risk after statin treatment.Geraniol acetate(Gefarnate)is an anti-ulcer drug.It was reported that geraniol might participate in lipid metabolism through a variety of pathways.The aim of this study was to assess the lipid-lowering effects of gefarnate in statin-treated CAD patients with residual hypertriglyceridemia.METHODS In this prospective,open-label,randomized,controlled trial,69 statin-treated CAD patients with residual hypertriglyceridemia were randomly assigned to gefarnate group and control group,received gefarnate(100 mg/3 times a day)combined with statin and statin alone,respectively.At baseline and after one-month treatment,the levels of plasma triglyceride,high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)and total cholesterol were tested.RESULTS After one-month gefarnate treatment,triglyceride level was significantly lowered from 2.64 mmol/L to 2.12 mmol/L(P=0.0018),LDL-C level lowered from 2.7 mmol/L to 2.37 mmol/L(P=0.0004),HDL-C level increased from 0.97 mmol/L to 1.17mmol/L(P=0.0228).Based on statin therapy,gefarnate could significantly reduce the plasma triglyceride level(P=0.0148)and increase the plasma HDL-C level(P=0.0307).Although the LDL-C and total cholesterol levels tended to decrease,there was no statistically significant difference.CONCLUSIONS The addition of gefarnate to statin reduced triglyceride level and increased HDL-C level to a significant extent compared to statin alone in CAD patients with residual hypertriglyceridemia.This suggested that gefarnate might provide the dual benefits of preventing gastrointestinal injury and lipid lowering in CAD patients.

Mediating role of social support in dysphoria,despondency,and quality of life in patients undergoing maintenance hemodialysis

BACKGROUND Dysphoria and despondency are prevalent psychological issues in patients undergoing Maintenance Hemodialysis(MHD)that significantly affect their quality of life(QOL).High levels of social support can significantly improve the physical and mental well-being of patients undergoing MHD.Currently,there is limited research on how social support mediates the relationship between dysphoria,despondency,and overall QOL in patients undergoing MHD.It is imperative to investigate this mediating effect to mitigate dysphoria and despondency in patients undergoing MHD,ultimately enhancing their overall QOL.AIM To investigate the mediating role of social support in relationships between dysphoria,despondency,and QOL among patients undergoing MHD.METHODS Participants comprised 289 patients undergoing MHD,who were selected using a random sampling approach.The Social Support Rating Scale,Self-Rating Anxiety Scale,Self-Rating Depression Scale,and QOL Scale were administered.Correlation analysis was performed to examine the associations between social support,dysphoria,despondency,and QOL in patients undergoing MHD.To assess the mediating impact of social support on dysphoria,despondency,and QOL in patients undergoing MHD,a bootstrap method was applied.RESULTS Significant correlations among social support,dysphoria,despondency,and quality in patients undergoing MHD were observed(all P<0.01).Dysphoria and despondency negatively correlated with social support and QOL(P<0.01).Dysphoria and despondency had negative predictive impacts on the QOL of patients undergoing MHD(P<0.05).The direct effect of dysphoria on QOL was statistically significant(P<0.05).Social support mediated the relationship between dysphoria and QOL,and this mediating effect was significant(P<0.05).Similarly,the direct effect of despondency on QOL was significant(P<0.05).Moreover,social support played a mediating role between despondency and QOL,with a significant mediating effect(P<0.05).CONCLUSION These findings suggest that social support plays a significant mediating role in the relationship between dysphoria,despondency,and QOL in patients undergoing MHD.

Focus on laboratory tests related to the pathological types of lupus nephritis to implement renal biopsy as early as possible:clinical and pathological analysis of 217 cases of single center lupus nephritis

Objective:To analyze the clinical and laboratory indices of patients with lupus nephritis(LN)of different pathological types and explore the related factors of LN pathological classification,it is helpful to grasp the timing of renal biopsy.Methods:The clinical manifestations,laboratory parameters and renal pathological types of LN patients in recent 20 years were analyzed retrospectively by SPSS 26.0 software.Results:In this study,the first three pathological types were V,IV,V+IV;latent nephritis was common in type II and V;nephritic syndrome was common in type V;nephrotic syndrome was common in type V+IV;chronic renal insufficiency group was mostly type IV;pathological types were correlated with serum creatinine,C3,albumin and erythrocyte sedimentation rate(r=0.315,P<0.001),and serum creatinine was moderately correlated(r=0.315,P<0.001);AI,CI and SLEDAI scores were significantly different among LN patients of different pathological types.Conclusion:LN is closely related to clinical pathology,clinical manifestations,comprehensive analysis of laboratory indicators and SLEDAI score to make a preliminary prediction of LN pathological type,help to initially assess the severity of pathology,improve the timing of renal biopsy implementation,optimize the timing of treatment.

玻璃体腔注射康柏西普与阿柏西普治疗厚脉络膜新生血管病变的疗效比较

目的:观察比较玻璃体腔注射康柏西普与阿柏西普治疗厚脉络膜新生血管病变(PNV)的临床疗效及安全性。方法:回顾性病例对照研究。收集2018-02/2022-10于我院确诊为PNV的患者33例35眼,根据玻璃体腔注射药物分为康柏西普组14例14眼,阿柏西普组19例21眼,比较两组患者治疗前,治疗后1、3、6mo的最佳矫正视力(BCVA)、黄斑中心凹下脉络膜厚度(SFCT)、黄斑中心凹视网膜厚度(CMT)、注药次数及临床并发症的情况。结果:治疗后1、3、6mo,两组患者的BCVA、CMT、SFCT较治疗前均明显改善(均P<0.05);在整个随访期间,两组患者玻璃体腔注射次数分别为2(2,3)、2(1.5,2)次,未见明显差异(P=0.423);在应用康柏西普及阿柏西普的治疗过程中,均未发生严重的并发症。结论:玻璃体腔注射康柏西普及阿柏西普均能治疗PNV,在提高视力的同时改善解剖结构,两种药物疗效相似,均能达到较为理想的临床效果。

Chx10+V2a interneurons in spinal motor regulation and spinal cord injury

Chx10-expressing V2 a(Chx10+V2 a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2 a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2 a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2 a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2 a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2 a interneurons also play an important role in rhythmic patterning maintenance, leftright alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2 a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2 a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2 a interneurons transplanted in spinal cord injury foci.

Neutronics analysis of a subcritical blanket system driven by a gas dynamic trap-based fusion neutron source for ^(99)Mo production

Gamma-emitting radionuclide ^(99m)Tc is globally used for the diagnosis of various pathological conditions owing to its ideal single-photon emission computed tomography (SPECT) characteristics.However,the short half-life of ^(99m)Tc (T_(1/2)=6 h)makes it difficult to store or transport.Thus,the production of ^(99m)Tc is tied to its parent radionuclide ^(99)Mo (T_(1/2)=66 h).The major production paths are based on accelerators and research reactors.The reactor process presents the potential for nuclear proliferation owing to its use of highly enriched uranium (HEU).Accelerator-based methods tend to use deuterium–tritium(D–T) neutron sources but are hindered by the high cost of tritium and its challenging operation.In this study,a new ^(99)Mo production design was developed based on a deuterium–deuterium (D–D) gas dynamic trap fusion neutron source (GDT-FNS) and a subcritical blanket system (SBS) assembly with a low-enriched uranium (LEU) solution.GDT-FNS can provide a relatively high-neutron intensity,which is one of the advantages of ^(99)Mo production.We provide a Monte Carlo-based neutronics analysis covering the calculation of the subcritical multiplication factor (k_(s)) of the SBS,optimization design for the reflector,shielding layer,and ^(99)Mo production capacity.Other calculations,including the neutron flux and nuclear heating distributions,are also provided for an overall evaluation of the production system.The results demonstrated that the SBS meets the nuclear critical safety design requirement (k_(s)<0.97) and maintained a high ^(99)Mo production capacity.The proposed system can generate approximately 157 Ci ^(99)Mo for a stable 24 h operation with a neutron intensity of 1×10^(14) n/s,which can meet 50%of China’s demand in 2025.

Retinal microvascular and microstructural alterations in the diagnosis of meibomian gland dysfunction in severely obese population:a new approach

AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with severely obese population(PAT group;24 eyes)and 12 healthy controls(HC group;24 eyes)were recruited.OCTA images were segmented into five[superior(S),nasal(N),inferior(I),temporal(T),and central foveal(C)]or nine[inner superior(IS),outer superior(OS),inner nasal(IN),outer nasal(ON),inner inferior(II),outer inferior(OI),inner temporal(IT),outer temporal(OT),and C]subregions.The superficial vessel density(SVD),retinal thickness(RT),foveal avascular zone(FAZ)parameters,and retinal volume were measured.RESULTS:Visual acuity was significantly different between two groups(0.8±0.17 in PAT group vs 0.2±0.06 in HC group).SVD was significantly lower in PATs in N,T,OS,IN,OT,and ON.The area under the receiver operating characteristic curve(AUC)for T was 0.961[95% confidence interval(CI):0.908 to 1.000],for OS was 0.962(95%CI:0.915 to 1.000).RT was significantly lower in PATs in IS,OS,OI,OT,ON,IT,IN,and II.AUC for OT was 0.935(95%CI:0.870 to 0.999),for IS was 0.915(95%CI:0.838 to 0.992).Angiography results showed significantly lower area and perimeter of FAZ,SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group.CONCLUSION:Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures.These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

Evaluation of polygenic risk score for risk prediction of gastric cancer

Genetic variations are associated with individual susceptibility to gastric cancer.Recently,polygenic risk score(PRS)models have been established based on genetic variants to predict the risk of gastric cancer.To assess the accuracy of current PRS models in the risk prediction,a systematic review was conducted.A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models.The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823.Incorporation of epidemiological factors or Helicobacter pylori(H.pylori)status increased the accuracy for risk prediction,while selection of single nucleotide polymorphism(SNP)and number of SNPs appeared to have little impact on the model performance.To further improve the accuracy of PRS models for risk prediction of gastric cancer,we summarized the association between gastric cancer risk and H.pylori genomic variations,cancer associated bacteria members in the gastric microbiome,discussed the potentials for performance improvement of PRS models with these microbial factors.Future studies on comprehensive PRS models established with human SNPs,epidemiological factors and microbial factors are indicated.

Neural stem cell transplantation inhibits glial cell proliferation and P2X receptor-mediated neuropathic pain in spinal cord injury rats

P2X4 and P2X7 receptors play an important role in neuropathic pain after spinal cord injury. Regulation of P2X4 and P2X7 receptors can obviously reduce pain hypersensitivity after injury. To investigate the role of neural stem cell transplantation on P2X receptor-mediated neuropathic pain and explore related mechanisms, a rat model of spinal cord injury was prepared using the free-falling heavy body method with spinal cord segment 10 as the center. Neural stem cells were injected into the injured spinal cord segment using a micro-syringe. Expression levels of P2X4 and P2X7 receptors, neurofilament protein, and glial fibrillary acidic protein were determined by immunohistochemistry and western blot assay. In addition, sensory function was quantitatively assessed by current perception threshold. The Basso-Beattie-Bresnahan locomotor rating scale was used to assess neuropathological pain. The results showed that 4 weeks after neural stem cell transplantation, expression of neurofilament protein in the injured segment was markedly increased, while expression of glial fibrillary acidic protein and P2X4 and P2X7 receptors was decreased. At this time point, motor and sensory functions of rats were obviously improved, and neuropathic pain was alleviated. These findings demonstrated that neural stem cell transplantation reduced overexpression of P2X4 and P2X7 receptors, activated locomotor and sensory function reconstruction, and played an important role in neuropathic pain regulation after spinal cord injury. Therefore, neural stem cell transplantation is one potential option for relieving neuropathic pain mediated by P2X receptors.

The ROCK pathway inhibitor Y-27632 mitigates hypoxia and oxidative stress-induced injury to retinal Müller cells

Rho kinase （ROCK） was the first downstream Rho effector found to mediate RhoA-induced actin cytoskeletal changes through effects on myosin light chain phosphorylation. There is abundant evidence that the ROCK pathway participates in the pathogenesis of retinal endothelial injury and proliferative epiretinal membrane traction. In this study, we investigated the effect of the ROCK pathway inhibitor Y-27632 on retinal Müller cells subjected to hypoxia or oxidative stress. Müller cells were subjected to hypoxia or oxidative stress by exposure to CoCl2 or H2O2. After a 24-hour treatment with Y-27632, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to assess the survival of Müller cells. Hoechst 33258 was used to detect apoptosis, while 2′,7′-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species generation. A transwell chamber system was used to examine the migration ability of Müller cells. Western blot assay was used to detect the expression levels of α-smooth muscle actin, glutamine synthetase and vimentin. After treatment with Y-27632, Müller cells subjected to hypoxia or oxidative stress exhibited a morphology similar to control cells. Y-27632 reduced apoptosis, α-smooth muscle actin expression and reactive oxygen species generation under oxidative stress, and it reduced cell migration under hypoxia. Y-27632 also upregulated glutamine synthetase expression under hypoxia but did not impact vimentin expression. These findings suggest that Y-27632 protects Müller cells against cellular injury caused by oxidative stress and hypoxia by inhibiting the ROCK pathway.

Neutronics analysis of a stacked structure for a subcritical system with LEU solution driven by a D-T neutron source for~(99)Mo production

The utilization of neutrons markedly affects the medical isotope yield of a subcritical system driven by an external D-T neutron source.The general methods to improve the utilization of neutrons include moderating multiplying,and reflecting neutrons,which ignores the use of neutrons that backscatter to the source direction.In this study,a stacked structure was formed by assembling the multiplier and the low-enriched uranium solution to enable the full use of neutrons that backscatter to the source direction and further improve the utilization of neutrons.A model based on SuperMC was used to evaluate the neutronics and safety behavior of the subcritical system,such as the neutron effective multiplication factor,neutron energy spectrum,medical isotope yield,and heat deposition.Based on the calculation results,when the intensity of the neutron source was 59×10^(13)n/s,the optimized design with a stacked structure could increase the yield of ^(99)Mo to182 Ci/day,which is approximately 16% higher than that obtained with a single-layer structure.The inlet H_(2)O coolant velocity of 1.0 m/s and initial temperature of 20℃ were also found to be sufficient to prevent boiling of the fuel solution.

Radiomics model for distinguishing tuberculosis and lung cancer on computed tomography scans

BACKGROUND Pulmonary tuberculosis(TB)and lung cancer(LC)are common diseases with a high incidence and similar symptoms,which may be misdiagnosed by radiologists,thus delaying the best treatment opportunity for patients.AIM To develop and validate radiomics methods for distinguishing pulmonary TB from LC based on computed tomography(CT)images.METHODS We enrolled 478 patients(January 2012 to October 2018),who underwent preoperative CT screening.Radiomics features were extracted and selected from the CT data to establish a logistic regression model.A radiomics nomogram model was constructed,with the receiver operating characteristic,decision and calibration curves plotted to evaluate the discriminative performance.RESULTS Radiomics features extracted from lesions with 4 mm radial dilation distances outside the lesion showed the best discriminative performance.The radiomics nomogram model exhibited good discrimination,with an area under the curve of 0.914(sensitivity=0.890,specificity=0.796)in the training cohort,and 0.900(sensitivity=0.788,specificity=0.907)in the validation cohort.The decision curve analysis revealed that the constructed nomogram had clinical usefulness.CONCLUSION These proposed radiomic methods can be used as a noninvasive tool for differentiation of TB and LC based on preoperative CT data.

Impact of Tobacco Smoking on Health Care Utilization and Medical Costs in Chronic Obstructive Pulmonary Disease,Coronary Heart Disease and Diabetes

Objective To determine the impact of smoking on disease-specific health care utilization and medical costs in patients with chronic non-communicable diseases(NCDs).Methods Participants were middle-aged and elderly adults with chronic NCDs from a prospective cohort in China.Logistic regressions and linear models were used to assess the relationship between tobacco smoking,health care utilization and medical costs.Results Totally,1020 patients with chronic obstructive pulmonary disease(COPD),3144 patients with coronary heart disease(CHD),and 1405 patients with diabetes were included in the analysis.Among patients with COPD,current smokers(β:0.030,95%CI:−0.032-0.092)and former smokers(β:0.072,95%CI:0.014-0.131)had 3.0%and 7.2%higher total medical costs than never smokers.Medical costs of patients who had smoked for 21-40 years(β:0.028,95%CI:−0.038-0.094)and≥41 years(β:0.053,95%CI:−0.004β0.110)were higher than those of never smokers.Patients who smoked≥21 cigarettes(β:0.145,95%CI:0.051-0.239)per day had more inpatient visits than never smokers.The association between smoking and health care utilization and medical costs in people with CHD group was similar to that in people with COPD;however,there were no significant associations in people with diabetes.Conclusion This study reveals that the impact of smoking on health care utilization and medical costs varies among patients with COPD,CHD,and diabetes.Tobacco control might be more effective at reducing the burden of disease for patients with COPD and CHD than for patients with diabetes.

Fractal sorting vector-based least significant bit chaotic permutation for image encryption

The image's least significant bit(LSB) covers lots of the details that have been commonly used in image encryption analysis. The newly proposed fractal sorting vector(FSV) and FSV-based LSB chaotic permutation(FSV-LSBCP) is a novel chaotic image encryption cryptosystem introduced in this article. The FSV-LSBCP effectively strengthens the security of the cryptographic scheme concerning the properties of the FSV. Key analysis, statistical analysis, resistance differential attack analysis, and resistance to cropping attacks and noise attacks are the focus of the suggested image encryption cryptosystem. The security experiment shows that the cryptosystem is adequate to achieve the desired degree of security.

Predictive value of a serum tumor biomarkers scoring system for clinical stage Ⅱ/Ⅲ rectal cancer with neoadjuvant chemoradiotherapy

BACKGROUND Multiple classes of molecular biomarkers have been studied as potential predictors for rectal cancer(RC)response.Carcinoembryonic antigen(CEA)is the most widely used blood-based marker of RC and has proven to be an effective predictive marker.Cancer antigen 19-9(CA19-9)is another tumor biomarker used for RC diagnosis and postoperative monitoring,as well as monitoring of the therapeutic effect.Using a panel of tumor markers for RC outcome prediction is a practical approach.AIM To assess the predictive effect of pre-neoadjuvant chemoradiotherapy(NCRT)CEA and CA19-9 levels on the prognosis of stage II/III RC patients.METHODS CEA and CA19-9 levels were evaluated 1 wk before NCRT.According to the receiver operating characteristic curve analysis,the optimal cut-off point of CEA and CA19-9 levels for the prognosis were 3.55 and 19.01,respectively.The novel serum tumor biomarker(NSTB)scores were as follows:score 0:Pre-NCRT CEA<3.55 and CA19-9<19.01;score 2:Pre-NCRT CEA>3.55 and CA19-9>19.01;score 1:Other situations.Pathological information was recorded according to histopathological reports after the operation.RESULTS In the univariate analysis,pre-NCRT CEA<3.55[P=0.025 for overall survival(OS),P=0.019 for disease-free survival(DFS)],pre-NCRT CA19-9<19.01(P=0.014 for OS,P=0.009 for DFS),a lower NSTB score(0-1 vs 2,P=0.009 for OS,P=0.005 for DFS)could predict a better prognosis.However,in the multivariate analysis,only a lower NSTB score(0-1 vs 2;for OS,HR=0.485,95%CI:0.251-0.940,P=0.032;for DFS,HR=0.453,95%CI:0.234-0.877,P=0.019)and higher pathological grade,node and metastasis stage(0-I vs II-III;for OS,HR=0.363,95%CI:0.158-0.837,P=0.017;for DFS,HR=0.342,95%CI:0.149-0.786,P=0.012)were independent predictive factors.CONCLUSION The combination of post-NCRT CEA and CA19-9 was a predictive factor for clinical stage II/III RC patients receiving NCRT,and the combined index had a stronger predictive effect.

前缘缝翼对风电叶片翼型气动性能影响的研究

前缘缝翼作为叶片提升气动性能的部件,在减少叶片表面的流动分离、提高升力比方面发挥着重要作用。本文采用CFD数值模拟的方法对S830翼型添加前缘缝翼前后进行研究,得结论如下:添加前缘缝翼,S830翼型的升力系数与阻力系数均增加,升力系数增加的更明显,最大增幅为8.62%;随着攻角的增加,S830翼型的流动分离区逐渐增加;添加前缘缝翼可有效控制S830翼型的流动分离;缝翼的存在增大了S830压力面压力的同时减小了吸力面的压力,从而使得翼型的升力增加。

Theoretical analysis and experimental validation of radial cascaded composite ultrasonic transducer

A radial cascaded composite ultrasonic transducer is analyzed.The transducer consists of three short metal tubes and two radially polarized piezoelectric ceramic short tubes arranged alternately along the radial direction.The short metal tubes and the piezoelectric ceramic short tubes are connected in parallel electrically and in series mechanically,which can multiply the input sound power and sound intensity.Based on the theory of plane stress,the electro-mechanical equivalent circuit of radial vibration of the transducer is derived firstly.The resonance/anti-resonance frequency equation and the expression of the effective electromechanical coupling coefficient are obtained.Excellent electromechanical characteristics are determined by changing the radial geometric dimensions.Two prototypes of the transducers are designed and manufactured to support the analytical theory.It is concluded that the theoretical resonance/anti-resonance frequencies are consistent with the numerical and experimental results.When R_(2) is at certain values,both the anti-resonance frequency and effective electromechanical coupling coefficient corresponding to the second mode have maximal values.The radial cascaded composite ultrasonic transducer is expected to be used in the fields of ultrasonic water treatment and underwater acoustics.