Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Local Responses to Macro Development Policies and Their Effects on Rural System in China's Mountainous Regions:The Case of Shuanghe Village in Sichuan Province

China has promulgated a series of policies including the Western Development Program, the Grain for Green Project, agricultural support policies and building a new countryside strategy to eliminate east-west differences and urban-rural disparities since the late 1990s. This paper gives a holistic examination on local responses to the four typical macro socio-economic development policies and their effects on rural system based on a case study of a mountainous village in southern Sichuan Province. The results showed that the policies have not moved the case study village from its historically marginal status. To some extent, its socio-economic situation might have been worsened by accelerated out- migration of the youth, loss of agricultural land due to afforestation and industrial plants, increased fire hazard due to afforestation and reforestation, increased environmental pollution due to industrial enterprises attracted to the village and a steep decline in agricultural production due to loss of and inefficient use of cultivated land. Factors causing local villages' dilemmas include the nonuniformity of actors' objectives, finiteness of villagers' abilities, and the imperfect incentive and restraint mechanism for local government's activities under existing policy framework composed of uncoordinated one-size-fits- all policies. We suggest that China's rural policy in the new period should gradually shift from a sectoral to a place-based one, from top-down incentives to the development of bottom-up projects, and fully recognize the diversity of rural space, so as to lift localcapacities and make good use of the knowledge shared by different actors. Moreover, it is also necessary to integrate the various sectoral policies, and improve the interministerial and interdepartmental coordination of rural policies at regional and local levels.

Shock-induced energy localization and reaction growth considering chemical-inclusions effects for crystalline explosives

Chemical inclusions significantly alter shock responses of crystalline explosives in macroscale gap experiments but their microscale dynamics origin remains unclear.Herein shock-induced energy localization,overall physical responses,and reactions in a-1,3,5-trinitro-1,3,5-triazinane(a-RDX)crystal entrained various chemical inclusions were investigated by the multi-scale shock technique implemented in the reactive molecular dynamics method.Results indicated that energy localization and shock reaction were affected by the intrinsic factors within chemical inclusions,i.e.,phase states,chemical compositions,and concentrations.The atomic origin of chemical-inclusions effects on energy localization is dependent on the dynamics mechanism of interfacial molecules with free space volume,which includes homogeneous intermolecular compression,interfacial impact and shear,and void collapse and jet.As introducing various chemical inclusions,the initiation of those dynamics mechanisms triggers diverse decay rates of bulk RDX molecules and hereby impacts on growth speeds of final reactions.Adding chemical inclusions can reduce the effectiveness of the void during the shock impacting.Under the shockwave velocity of 9 km/s,the parent RDX decay rate in RDX entrained amorphous carbon decreases the most and is about one fourth of that in RDX with a vacuum void,and solid HMX and TATB inclusions are more reactive than amorphous carbon but less reactive than dry air or acetone inclusions.The lessdense shocking system denotes the greater increases in local temperature and stress,the faster energy liberation,and the earlier final reaction into equilibrium,revealing more pronounced responses to the present intense shockwave.The quantitative models associated with the relative system density(RD_(sys))were proposed for indicating energy-localization mechanisms and evaluating initiation safety in the shocked crystalline explosive.RD_(sys)is defined by the density ratio of defective RDX to perfect crystal after dynamics relaxation and reveals the global density characteristic in shocked systems filled with chemical inclusions.When RD_(sys)is below 0.9,local hydrodynamic jet initiated by void collapse dominates upon energy localization instead of interfacial impact.This study sheds light on novel insights for understanding the shock chemistry and physical-based atomic origin in crystalline explosives considering chemical-inclusions effects.

Controlling optical responses through local dielectric resonance in nanometre metallic clusters

Optical responses in dilute composites are controlled through the local dielectric resonance of metallic clusters. We consider two located metallic clusters close to each other with admittances ε1 and ε2. Through varying the difference admittance ratio η[= （ε2 - ε0）/（ε1 - ε0）], we find that their optical responses are determined by the local resonance. There is a blueshift of absorption peaks with the increase of η- Simultaneously, it is known that the absorption peaks will be redshifted by enlarging the cluster size. By adjusting the nano-metallic cluster geometry, size and admittances, we can control the positions and intensities of absorption peaks effectively. We have also deduced the effective linear optical responses of three-component composites εe=ε0 （1＋∑^n n=1[（γn1＋ηγn2）/（ε0（s-sn））]） and the sum rule of cross sections：∑^n n=1（γn1＋ηγn2）=Nh1＋Nh2,, where Nh1and Nh2 are the numbers of εl and ε2 bonds along the electric field, respectively. These results may be beneficial to the study of surface plasmon resonances on a nanometre scale.

Evaluation of oxaliplatin and tigio combination therapy in locally advanced gastric cancer

BACKGROUND Locally advanced gastric cancer(LAGC)is a common malignant tumor.In recent years,neoadjuvant chemotherapy has gradually become popular for the treatment of LAGC.AIM To investigate the efficacy of oxaliplatin combined with a tigio neoadjuvant chemotherapy regimen vs a conventional chemotherapy regimen for LAGC.METHODS Ninety patients with LAGC were selected and randomly divided into control and study groups with 45 patients in each group,according to the numerical table method.The control group was treated with conventional chemotherapy,and the study group was treated with oxaliplatin combined with tigio-neoadjuvant che-motherapy.The primary outcome measures were the clinical objective response rate(ORR)and surgical resection rate(SRR),whereas the secondary outcome measures were safety and Karnofsky Performance Status score.RESULTS The ORR in the study group was 80.00%,which was significantly higher than that of the control group(57.78%).In the study group,SRR was 75.56%,which was significantly higher than that of the control group(57.78%).There were 15.56%adverse reactions in the study group and 35.56%in the control group.These differences were statistically significant between the two groups.CONCLUSION The combination of oxaliplatin and tigio before surgery as neoadjuvant chemotherapy for patients with LAGC can effectively improve the ORR and SRR and is safe.

Subcellular Localization of Large Yellow Croaker(Larimichthys crocea) TLR21 and Expression Profiling of Its Gene in Immune Response

Toll-like receptor 21(TLR21) is a non-mammalian type TLR, and plays an important role in innate immune response in fish. In this paper, the full-length cDNA sequence of TLR21 gene was identified and characterized from large yellow croaker, Larimichthys crocea and was termed as LcTLR21. It consists of 3365 bp, including a 5'-terminal untranslated region(UTR) of 97 bp, a 3'-terminal UTR of 331 bp, and an open reading frame(ORF) of 2937 bp encoding a polypeptide of 978 amino acid residues. The deduced LcTLR21 contains a signal peptide domain at N-terminal, 12 leucine-rich repeats(LRRs) at the extracellular region, a transmembrane domain and a cytoplasmic toll-interleukin-1 receptor(TIR) domain at the C-terminal. Subcellular localization analysis revealed that the LcTLR21-GFP was constitutively expressed in cytoplasm. Tissue expression analysis indicated that LcTLR21 gene broadly expressed in most of the examined tissues, with the most predominant abundance in spleen, followed by head-kidney and liver, while the weakest expression was detected in brain. The expression level of LcTLR21 after LPS, poly I:C and Vibrio parahaemolyticus challenges was investigated in spleen, head-kidney and liver. LcTLR21 gene transcripts increased significantly in all examined tissues after the challenges, and the highest expression level was detected in liver at 24 h after poly I:C stimulation(P <0.05), suggesting that LcTLR21 might play a crucial role in fish resistance to viral and bacterial infections.

Responses of Tree Species to Climate Warming at Different Spatial Scales

Tree species respond to climate change at multiple scales,such as species physiological response at fine scale and species distribution (quantified by percent area) at broader spatial scale.At a given spatial scale,species physiological response and distribution can be correlated positively or negatively.The consistency of such correlation relationships at different spatial scales determines whether species responses derived from local scales can be extrapo-lated to broader spatial scales.In this study,we used a coupled modeling approach that coupled a plot-level ecosystem process model (LINKAGES) with a spatially explicit landscape model (LANDIS).We investigated species physio-logical responses and distribution responses to climate warming at the local,zonal and landscape scales respectively,and examined how species physiological response and distribution correlated at each corresponding scale and whether the correlations were consistent among these scales.The results indicate that for zonal and warming-sensitive species,the correlations between species physiological response and distribution are consistent at these spatial scales,and therefore the research results of vegetation response to climate warming at the local scale can be extrapolated to the zonal and landscape scales.By contrast,for zonal and warming-insensitive species the correlations among different spatial scales are consistent at some spatial scales but at other scales.The results also suggest that the results of azonal species at the local scale near their distribution boundaries can not be extrapolated simply to broader scales due to stronger responses to climate warming in those boundary regions.

Source localization with minimum variance distortionless response for spherical microphone arrays

To improve localization accuracy, the spherical microphone arrays are used to capture high-order wavefield in- formation. For the far field sound sources, the array signal model is constructed based on plane wave decomposition. The spatial spectrum function is calculated by minimum variance distortionless response （MVDR） to scan the three-dimensional space. The peak values of the spectrum function correspond to the directions of multiple sound sources. A diagonal loading method is adopted to solve the ill-conditioned cross spectrum matrix of the received signals. The loading level depends on the alleviation of the ill-condition of the matrix and the accuracy of the inverse calculation. Compared with plane wave decomposition method, our proposed localization algorithm can acquire high spatial resolution and better estimation for multiple sound source directions, especially in low signal to noise ratio （SNR）.

A Numerical Stress-strain Response Model of All Grades of Concretes under Uniaxial Compression

An important problem facing stress-strain response modeling of concrete is the complexity of the compressive strength grades. 21 groups of speeimens with different cubic compressive strength （56.3- 164.9 MPa ） hate beets numerically analyzed. Using only the compressive strength, a stress-strain response model of different concrete grade was established. The numerical simulation model not only qualitatively reproduces the relationship of uniaxial compressive strength, peak value stress and cubic compressive strength, but realizes the consistence of the ascending branch of stress-strain cunts with different strength grades by introducing the correction coefficient k. The results indicate k increases gradually from 0 to approximate 1 with the increase of the compressive strength, corresponding to the transition from the paracurve to straight line branch in stress-strain curves. When k is 0, the madel is identical to the Hognestad equation. A good agreement with the experiment data was obtained.

Electric field distribution and effective nonlinear AC and DC responses of graded cylindrical composites

The perturbation method is used to study the localization of electric field distribution and the effective nonlinear response of graded composites under an external alternating-current（AC） and direct-current（DC） electric field E app = E 0（1 ＋ sin ωt）.The dielectric profile of the cylindrical inclusions is modeled by function ε i（r） = C k r k（r ≤ a）,where r is the radius of the cylindrical inclusion,and C k,k,a are parameters.In the dilute limit,the local potentials and the effective nonlinear responses at all harmonics are derived.Meanwhile,the general effective nonlinear responses are also derived and compared with the effective nonlinear responses at harmonics under the AC and DC external field.It is found that the effective nonlinear AC and DC responses at harmonics can be calculated by those of the general effective nonlinear of the graded composites under the external DC electric field.Moreover,the obtained local electrical fields show that the electrical field distribution in the cylindrical inclusions is controllable,and the maximum of the electric field inside the cylinder is at its center.

Entrepreneurship corporate social responsibility and flexible innovation networks： On the interaction between TNCs＇ R＆D activities and local development

Entrepreneurship corporate social responsibility is concerned with obligations that should be undertaken by an enterprise or ＂enterprise citizen＂ to the society including interrelationship between enterprise and some related interest dependents. And it is a sense of value, discipline and respect to the people, community and environment-related policies of the enterprise. Obviously, the core of the notion refers to a commitment of the enterprise in order to improve living standard of related interest counterparts. Nowadays, entrepreneurship corporate social responsibility has been not only an ethical call, but also an institutional constraint. The consensus is that in operation process an enterprise should take into account of its economic, social and ethical effects on consumers, staffs, shareholders, communities, local governments and environment and make a better prospect to them. Based on this point of view, by field work and questionnaire method, this paper discusses specifically the interaction between TNCs＇ R＆D activities and local development of the Pudong New Area, a China＇s largest special economic zone in Shanghai to explore dynamics of the TNCs＇ R＆D activities, growth of the local economy and their roles in promoting flexible innovation networks for sustainable futures. This involves： a. notion of the entrepreneurship corporate social responsibility; b. current state and trend of TNCs＇ R＆D activities; c. mode and linkage tightness between TNCs＇ R＆D activities and the local economy; d. main problems of the TNCs＇ R＆D activities in Pudong; e. the context of flexible innovation networks; and f. manner and ways in creation of flexible innovation networks.

A FAST SEARCH METHOD OF STEERED RESPONSE POWER WITH SMALL-APERTURE MICROPHONE ARRAY FOR SOUND SOURCE LOCALIZATION

The Steered Response Power(SRP)method works well for sound source localization in noisy and reverberant environment.However,the large computation complexity limits its practical application.In this paper,a fast SRP search method is proposed to reduce the computational complexity using small-aperture microphone array.The proposed method inspired by the SRP spatial spectrum includes two steps:first,the proposed method estimates the azimuth of the sound source roughly and determines whether the sound source is in far field or near field;then,different fine searching operations are performed according to the sound source being in far field or near field.Experiments both in simulation environments and real environments have been performed to compare the localization accuracy and computation complexity of the proposed method with those of the conventional SRP-PHAT algorithm.The results show that,the proposed method has a comparative accuracy with the conventional SRP algorithm,and achieves a reduction of 93.62%in computation complexity compared to the conventional SRP algorithm.

The role of soil in structure response of a building damaged by the 26 December 2018 earthquake in Italy

Local soil conditions can significantly modify the seismic motion expected on the soil surface.In most cases,the indications concerning the influence of the underlying soil provided by the in-force European and Italian Building Codes underestimate the real seismic amplification effects.For this reason,numerical analyses of the local seismic response(LSR)have been encouraged to estimate the soil filtering effects.These analyses are generally performed in free-field conditions,ignoring the presence of superstructures and,therefore,the effects of dynamic soil-structure interaction(DSSI).Moreover,many studies on DSSI are characterised by a sophisticated modelling of the structure and an approximate modelling of the soil(using springs and dashpots at the foundation level);while others are characterised by a sophisticated modelling of the soil and an approximate modelling of the structure(considered as a simple linear elastic structure or a single degree of freedom system).This paper presents a set of finite element method(FEM)analyses on a fully-coupled soil-structure system for a reinforced concrete building located in Fleri(Catania,Italy).The building,designed for gravity loads only,was severely damaged during the 26 December 2018 earthquake.The soil was modelled considering an equivalent visco-elastic behaviour,while the structure was modelled assuming both the visco-elastic and visco-inelastic behaviours.The comparison made between the results of the FEM analyses and the observed damage is valuable.

Local Shear Stresses Elicit Different Mechanical Response and Gene Expression from Complex Stresses

It is well established that living cells and tissues respond to mechanical forces such as flow-related shear stresses in blood or interstitial space and complex tractional stresses at cell-matrix contacts and cell-cell contacts.However,how different modes of forces impact mechanical and biological responses is elusive.Here we describe a strategy of using the three-dimensional magnetic twisting cytometry(3D MTC)technology to apply forces in any desired directions to the same living cell.We reveal that for a fixed stress amplitude and frequency,a live cell exhibits mechanical anisotropy and responds to a local shear stress differently from responding to a local complex stress by stretching chromatin and upregulating gene transcription to different levels,extending our previous finding on force-induced direct gene activation.This finding highlights the importance of force modes in impacting cellular mechanical and biological responses in living cells and tissues and may have implications in tissue patterning and embryonic development.

Therapeutic response and safety of different treatments for cutaneous leishmaniasis in patients: A retrospective cross-sectional study

Objective:To analyze the therapeutic response and safety of different treatments for cutaneous leishmaniasis,received by patients in the Program for the Study and Control of Tropical Diseases-PECET-Medellín-Colombia.Methods:This is a retrospective cross-sectional study of patients attended at PECET Research Center during 2016-2021.Relevant information regarding sociodemographic characteristics,history of leishmaniasis,characterization of current infection,treatment received,follow-up of therapeutic response and safety was collected from the medical records.Data were analyzed with Pearson's Chi-square association tests and Mann-Whitney U test using statistical software.Results:A total of 486 clinical records of patients were analyzed,and 356 received treatment.Eight different therapeutic alternatives(systemic,local and in combination)were analyzed.The therapeutic response of the different alternatives used(except thermotherapy)was higher than 50%.Most frequent adverse events were myalgias,arthralgias and headache,and vesicles for systemic and local treatment,respectively.Conclusions:Safety profile and performance of local therapeutic alternatives and combined schemes for the treatment of uncomplicated cutaneous leishmaniasis are an interesting option for the management of the disease.

ANALYSIS OF THE LOCALIZATION OF DAMAGE AND THE COMPLETE (STRESS-STRAIN) RELATION FOR MESOSCOPIC HETEROGENEOUS ROCK UNDER UNIAXIAL TENSILE LOADING

The mechanical behavior of rock under uniaxial tensile loading is different from that of rock under compressive loads. A micromechanics-based model was proposed for mesoscopic heterogeneous brittle rock undergoing irreversible changes of their microscopic structures due to microcrack growth. The complete stress-strain relation including linear elasticity, nonlinear hardening,rapid stress drop and strain softening was obtained. The influence of all microcracks with different sizes and orientations were introduced into the constitutive relation by using the probability density function describing the distribution of orientations and the probability density function describing the distribution of sizes. The influence of Weibull distribution describing the distribution of orientations and Rayleigh function describing the distribution of sizes on the constitutive relation were researched. Theoretical predictions have shown to be consistent with the experimental results.

ANALYSIS OF THE LOCALIZATION OF DAMAGE AND THE COMPLETE STRESS-STRAIN RELATION FOR MESOSCOPIC HETEROGENEOUS BRITTLE ROCK SUBJECTED TO COMPRESSIVE LOADS

A micromechanics-based model is established. The model takes the interaction among sliding cracks into account, and it is able to quantify the effect of various parameters on the localization condition of damage and deformation for brittle rock subjected to compressive loads. The closed-form explicit expression for the complete stress-strain relation of rock containing microcracks subjected to compressive loads was obtained. It is showed that the complete stress-strain relation includes linear elasticity,nonlinear hardening,rapid stress drop and strain softening.The behavior of rapid stress drop and strain softening is due to localization of deformation and damage. Theoretical predictions have shown to be consistent with the experimental results.

Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

CEA levels predict tumor response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Objective The aim of this study was to evaluate the impact of serum carcinoembryonic antigen(CEA)in the prediction of pathological complete response(pCR)in locally advanced rectal cancer(LARC)patients treated with neoadjuvant chemoradiotherapy(nCRT).Methods A total of 925 LARC patients who underwent nCRT followed by TME between March 2006 and February 2018 were enrolled at Fudan University Shanghai Cancer Center.Using logistic regression models,we investigated the associations between serum CEA levels and pathological complete remission(pCR).Further stratified analyses were performed according to different CEA thresholds.Results We found that pre-nCRT CEA and post-nCRT CEA were negatively correlated with pCR(P<0.001).Stratified analyses revealed that when the CEA cutoff value was set to 5 ng/mL,10.6%of patients with post-nCRT CEA levels>5 ng/mL achieved pCR.Meanwhile,when the CEA cutoff value was set to 10 ng/mL,only 6.8%of the patients with post-nCRT CEA levels>10 ng/mL achieved pCR.Conclusion In summary,pre and post-nCRT CEA levels≤5 ng/mL were favorable predictors of pCR in LACR patients,and the“watch and wait”strategy is not recommended for patients with post-nCRT CEA levels>10 ng/mL.

Effect of ropivacaine combined with dexamethasone local infiltration on the pain level and inflammatory stress response after pediatric tonsillectomy

Objective:To study the effect of ropivacaine combined with dexamethasone local infiltration on the pain level and inflammatory stress response after pediatric tonsillectomy.Methods:A total of 84 children who received selective tonsillectomy in Mianyang Central Hospital between June 2014 and April 2017 were selected as the research subjects and divided into two groups by random number table method, combined group received ropivacaine combined with dexamethasone local infiltration, and control group accepted ropivacaine local infiltration anesthesia. Serum levels of pain mediators, inflammatory mediators and stress mediators were detected 6 h, 12 h and 24 h after surgery.Results: 6 h after surgery, serumβ-EP, SP, BK, TNF-α, MCP-1, IL-4, IL-10, F-Cor, NE, AT-II and GH levels were not significantly different between the two groups;12 h and 24 h after surgery, serumβ-EP, SP, BK levels of control group were significantly higher than those 6 h after surgery, serumβ-EP, SP, BK levels of combined group were not significantly different from those 6 h after surgery. Serum TNF-α, MCP-1, IL-4, IL-10, F-Cor, NE, AT-II and GH levels of two groups were significantly higher than those 6 h after surgery, and Serum TNF-α, MCP-1, IL-4, IL-10, F-Cor, NE, AT-II and GH levels of combined group were significantly lower than control group.Conclusion:Ropivacaine combined with dexamethasone local infiltration is with more durable and exact effect than ropivacaine local infiltration alone on relieving the pain and inflammatory stress response after pediatric tonsillectomy.