Patient-derived xenograft model in colorectal cancer basic and translational research

Colorectal cancer(CRC)is one of the most popular malignancies globally,with 930000 deaths in 2020.The evaluation of CRC-related pathogenesis and the discovery of po-tential therapeutic targets will be meaningful and helpful for improving CRC treat-ment.With huge efforts made in past decades,the systematic treatment regimens have been applied to improve the prognosis of CRC patients.However,the sensitivity of CRC to chemotherapy and targeted therapy is different from person to person,which is an important cause of treatment failure.The emergence of patient-derived xenograft(PDX)models shows great potential to alleviate the straits.PDX models possess similar genetic and pathological characteristics as the features of primary tu-mors.Moreover,PDX has the ability to mimic the tumor microenvironment of the original tumor.Thus,the PDX model is an important tool to screen precise drugs for individualized treatment,seek predictive biomarkers for prognosis supervision,and evaluate the unknown mechanism in basic research.This paper reviews the recent advances in constructed methods and applications of the CRC PDX model,aiming to provide new knowledge for CRC basic research and therapeutics.

Predicting potential invasion risks of Leucaena leucocephala(Lam.)de Wit in the arid area of Saudi Arabia

The presence of invasive plant species poses a substantial ecological impact,thus comprehensive evaluation of their potential range and risk under the influence of climate change is necessary.This study uses maximum entropy(MaxEnt)modeling to forecast the likelihood of Leucaena leucocephala(Lam.)de Wit invasion in Saudi Arabia under present and future climate change scenarios.Utilizing the MaxEnt modeling,we integrated climatic and soil data to predict habitat suitability for the invasive species.We conducted a detailed analysis of the distribution patterns of the species,using climate variables and ecological factors.We focused on the important influence of temperature seasonality,temperature annual range,and precipitation seasonality.The distribution modeling used robust measures of area under the curve(AUC)and receiver-operator characteristic(ROC)curves,to map the invasion extent,which has a high level of accuracy in identifying appropriate habitats.The complex interaction that influenced the invasion of L.leucocephala was highlighted by the environmental parameters using Jackknife test.Presently,the actual geographic area where L.leucocephala was found in Saudi Arabia was considerably smaller than the theoretical maximum range,suggesting that it had the capacity to expand further.The MaxEnt model exhibited excellent prediction accuracy and produced reliable results based on the data from the ROC curve.Precipitation and temperature were the primary factors influencing the potential distribution of L.leucocephala.Currently,an estimated area of 216,342 km^(2)in Saudi Arabia was at a high probability of invasion by L.leucocephala.We investigated the potential for increased invasion hazards in the future due to climate change scenarios(Shared Socioeconomic Pathways(SSPs)245 and 585).The analysis of key climatic variables,including temperature seasonality and annual range,along with soil properties such as clay composition and nitrogen content,unveiled their substantial influence on the distribution dynamic of L.leucocephala.Our findings indicated a significant expansion of high risk zones.High-risk zones for L.leucocephala invasion in the current climate conditions had notable expansions projected under future climate scenarios,particularly evident in southern Makkah,Al Bahah,Madina,and Asir areas.The results,backed by thorough spatial studies,emphasize the need to reduce the possible ecological impacts of climate change on the spread of L.leucocephala.Moreover,the study provides valuable strategic insights for the management of invasion,highlighting the intricate relationship between climate change,habitat appropriateness,and the risks associated with invasive species.Proactive techniques are suggested to avoid and manage the spread of L.leucocephala,considering its high potential for future spread.This study enhances the overall comprehension of the dynamics of invasive species by combining modeling techniques with ecological knowledge.It also provides valuable information for decision-making to implement efficient conservation and management strategies in response to changing environmental conditions.

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model

Objective： To develop and validate a radiomics prediction model for individualized prediction of perineural invasion（PNI） in colorectal cancer（CRC）.Methods： After computed tomography（CT） radiomics features extraction, a radiomics signature was constructed in derivation cohort（346 CRC patients）. A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen（CEA） level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation（separate from the cohort used to build the model） was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram.Results： The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell＇s concordance index（c-index）： 0.817; 95% confidence interval（95% CI）： 0.811–0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination（c-index： 0.803; 95% CI： 0.794–0.812）.Conclusions： Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

Spontaneous xenogeneic GvHD in Wilms'tumor Patient-Derived xenograft models and potential solutions

Severely immunocompromised NOD.Cg-PrkdcIl2rg(NOG)mice are among the ideal animal recipients for generation of human cancer models.Transplantation of human solid tumors having abundant tumor-i nfiltrating lymphocytes(TILs)can induce xenogeneic graft-versus-host disease(xGvHD)following engraftment and expansion of the TILs inside the animal body.Wilms’tumor(WT)has not been recognized as a lymphocyte-predominant tumor.However,3 consecutive generations of NOG mice bearing WT patient-derived xenografts(PDX)xenotransplanted from a single donor showed different degrees of inflammatory symptoms after transplantation before any therapeutic intervention.In the initial generation,dermatitis,auto-amputation of digits,weight loss,lymphadenopathy,hepatitis,and interstitial pneumonitis were observed.Despite antibiotic treatment,no response was noticed,and thus the animals were prematurely euthanized(day 47 posttransplantation).Laboratory and histopathologic evaluations revealed lymphoid infiltrates positively immunostained with anti-human CD3 and CD8 antibodies in the xenografts and primary tumor,whereas no microbial infection or lymphoproliferative disorder was found.Mice of the next generation that lived longer(91 days)developed sclerotic skin changes and more severe pneumonitis.Cutaneous symptoms were milder in the last generation.The xenografts of the last 2 generations also contained TILs,and lacked lymphoproliferative transformation.The systemic immunoinflammatory syndrome in the absence of microbial infection and posttransplant lymphoproliferative disorder was suggestive of xGvHD.While there are few reports of xGvHD in severely immunodeficient mice xenotransplanted from lymphodominant tumor xenografts,this report for the first time documented serial xGvHD in consecutive passages of WT PDX-bearing models and discussed potential solutions to prevent such an undesired complication.

Global Existence of Classical Solutions to a Cancer Invasion Model

This paper deals with a chemotaxis-haptotaxis model of cancer invasion of tissue. The model consists of three reaction- diffusion- taxis partial differential equations describing interactions between cancer cells, matrix degrading enzymes, and the host tissue. The equation for cell density includes two bounded nonlinear density-dependent chemotactic and haptotactic sensitivity functions. In the absence of logistic damping, we prove the global existence of a unique classical solution to this model by some delicate a priori estimate

Numerical Solution of Model of Cancer Invasion with Tissue

Chemotaxis-haptotaxis model of cancer invasion with tissue remodeling is one of the important PDE’s systems in medicine, mathematics and biomathematics. In this paper we find the solution of chemotaxis-haptotaxis model of cancer invasion using the new homotopy perturbation method (NHPM). Then by comparing some estimated numerical result with simulation laboratory result, it shows that NHPM is an efficient and exact way for solving cancer PDE’s system.

A multi-scale modelling framework to guide management of plant invasions in a transboundary context

Background：Attention has recently been drawn to the issue of transboundary invasions,where species introduced and naturalized in one country cross international borders and become problematic in neighbouring countries.Robust modelling frameworks,able to identify the environmental drivers of invasion and forecast the current and future potential distribution of invasive species,are needed to study and manage invasions.Limitations due to the lack of species distribution and environmental data,or assumptions of modelling tools,often constrain the reliability of model predictions.Methods：We present a multiscale spatial modelling framework for transboundary invasions,incorporating robust modelling frameworks（Multimodel Inference and Ensemble Modelling） to overcome some of the limitations.The framework is illustrated using Hakea sericea Schrad.（Proteaceae）,a shrub or small tree native to Australia and invasive in several regions of the world,including the Iberian Peninsula.Two study scales were considered：regional scale（western Iberia,including mainland Portugal and Galicia） and local scale（northwest Portugal）.At the regional scale,the relative importance of environmental predictors sets was evaluated and ranked to determine the main general drivers for the species distribution,while the importance of each environmental predictor was assessed at the local scale.The potential distribution of H.sericea was spatially projected for both scale areas.Results：Model projections for western Iberia suggest that a large area is environmentally suitable in both Portugal and Spain.Climate and landscape composition sets were the most important determinants of this regional distribution of the species.Conversely,a geological predictor（schist lithology） was more important in explaining its local-scale distribution.Conclusions：After being introduced to Portugal,H.sericea has become a transboundary invader by expanding in parts of Galicia（Spain）.The fact that a larger area is predicted as environmentally suitable in Spain raises concerns regarding its potential continued expansion.This highlights the importance of transboundary cooperation in the early management of invasions.By reliably identifying drivers and providing spatial projections of invasion at multiple scales,this framework provides insights for the study and management of biological invasions,including the assessment of transboundary invasion risk.

Pattern changes and early risk warning of Spartina alterniflora invasion:a study of mangrove-dominated wetlands in northeastern Fujian,China

The exotic saltmarsh cordgrass,Spartina alterniflora(Loisel)Peterson&Saarela,is one of the important causes for the extensive destruction of mangroves in China due to its invasive nature.The species has rapidly spread wildly across coastal wetlands,challenging resource managers for control of its further spread.An investigation of S.alterniflora invasion and associated ecological risk is urgent in China's coastal wetlands.In this study,an ecological risk invasive index system was developed based on the Driving Force-Pressure-State-Impact-Response framework.Predictions were made of'warning degrees':zero warning and light,moderate,strong,and extreme warning,by developing a back propagation(BP)artificial neural network model for coastal wetlands in eastern Fujian Province.Our results suggest that S.alterniflora mainly has invaded Kandelia candel beaches and farmlands with clustered distributions.An early warning indicator system assessed the ecological risk of the invasion and showed a ladder-like distribution from high to low extending from the urban area in the central inland region with changes spread to adjacent areas.Areas of light warning and extreme warning accounted for43%and 7%,respectively,suggesting the BP neural network model is reliable prediction of the ecological risk of S.alterniflora invasion.The model predicts that distribution pattern of this invasive species will change little in the next 10 years.However,the invaded patches will become relatively more concentrated without warning predicted.We suggest that human factors such as land use activities may partially determine changes in warning degree.Our results emphasize that an early warning system for S.alterniflora invasion in China's eastern coastal wetlands is significant,and comprehensive control measures are needed,particularly for K.candel beach.

Translational pancreatic cancer research:a comparative study on patient-derived xenograft models

AIM To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice.METHODS This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations(intraperitoneal, subcutaneous and pancreatic). Histological analysis(haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis(TUNEL), proliferation(Ki-67), angiogenesis(CD31) and fibrogenesis(α-SMA) were performed. When a tumour xenograft reached the target size, it was reimplanted in a new nude mouse. Three sequential tumour xenograft generations were generated(F1, F2 and F3).RESULTS The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth(69.9%), followed by intraperitoneal(57.6%) and pancreatic(55%) models. Tumour development was faster in the subcutaneous model(17.7 ± 2.6 wk) compared with the pancreatic(23.1 ± 2.3 wk) and intraperitoneal(25.0 ± 2.7 wk) models(P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models(F1 28.1% vs F2 71.4% vs F3 80.9%, P < 0.001). There were no significant differences in tumour xenograft differentiation and cell proliferation between human samples and the three experimental models among the sequential generations of tumour xenografts. However, a progressive decrease in fibrosis, fibrogenesis, tumour vascularisation and apoptosis was observed in the three experimental models compared with the human samples. All three pancreatic patient-derived xenograft models presented similar histological and immunohistochemical characteristics.CONCLUSION In our experience, the faster development andgreatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer.

Predicting the Potential Invasion Hotspots of Chromolaena odorata under Current and Future Climate Change Scenarios in Heterogeneous Ecological Landscapes of Mizoram,India

Recent trends in globalization,human mobility surge and global trade aggravated the expansion of alien species introduction leading to invasion by alien plants compounded by climate change.The ability to predict the spread of invasive species within the context of climate change holds significance for accurately identifying vulnerable regions and formulating strategies to contain their wide proliferation and invasion.Anthropogenic activities and recent climate change scenarios increased the risk of Chromolaena odorata invasion and habitat expansion in Mizoram.To forecast its current distribution and habitat suitability amidst climatic alterations in Mizoram,a MaxEnt-driven habitat suitability model was deployed using the default parameters.The resultant model exhibited that the current spatial range of C.odorata occupies 15.37%of geographical areas deemed suitable for varying degrees of invasion.Projections for 2050 and 2070 anticipated an expansion of suitable habitats up to 34.37%of the geographical area of Mizoram,specifically under RCP 2.6 in 2070 in comparison with its present distribution.Currently,the distributional range of C.odorata in Mizoram spans from lower(450 m)to mid elevational ranges up to 1700 meters,with limited presence at higher altitudes.However,the habitat suitability model extrapolates that climate changes will elevate the invasion risk posed by C.odorata across Mizoram,particularly in the North-Western and Central regions.The projection of further territorial expansion and an upward shift in altitudinal range in the future underscores the urgency of instating robust management measures to pre-empt the impact of C.odorata invasion.This study recommends the imperative nature of effective C.odorata management,particularly during the initial stages of invasion.

Monitoring the little fire ant,Wasmannia auropunctata(Roger 1863),in the early stage of its invasion in China:Predicting its geographical distribution pattern under climate change

Invasive alien ants(IAAs)are among the most aggressive,competitive,and widespread invasive alien species(IAS)worldwide.Wasmannia auropunctata,the greatest IAAs threat in the Pacific region and listed in“100 of the world’s worst IAS”,has established itself in many countries and on islands worldwide.Wild populations of W.auropunctata were recently reported in southeastern China,representing a tremendous potential threat to China’s agricultural,economic,environmental,public health,and social well-being.Estimating the potential geographical distribution(PGD)of W.auropunctata in China can illustrate areas that may potentially face invasion risk.Therefore,based on the global distribution records of W.auropunctata and bioclimatic variables,we predicted the geographical distribution pattern of W.auropunctata in China under the effects of climate change using an ensemble model(EM).Our findings showed that artificial neural network(ANN),flexible discriminant analysis(FDA),gradient boosting model(GBM),Random Forest(RF)were more accurate than categorical regression tree analysis(CTA),generalized linear model(GLM),maximum entropy model(MaxEnt)and surface distance envelope(SRE).The mean TSS values of ANN,FDA,GBM,and RF were 0.820,0.810,0.843,and 0.857,respectively,and the mean AUC values were 0.946,0.954,0.968,and 0.979,respectively.The mean TSS and AUC values of EM were 0.882 and 0.972,respectively,indicating that the prediction results with EM were more reliable than those with the single model.The PGD of W.auropunctata in China is mainly located in southern China under current and future climate change.Under climate change,the PGD of W.auropunctata in China will expand to higher-latitude areas.The annual temperature range(bio7)and mean temperature of the warmest quarter(bio10)were the most significant variables affecting the PGD of W.auropunctata in China.The PGD of W.auropunctata in China was mainly attributed to temperature variables,such as the annual temperature range(bio7)and the mean temperature of the warmest quarter(bio10).The populations of W.auropunctata in southern China have broad potential invasion areas.Developing strategies for the early warning,monitoring,prevention,and control of W.auropunctata in southern China requires more attention.

Combination Therapy of Capecitabine with Cyclophosphamide as a Second-Line Treatment after Failure of Paclitaxel plus Bevacizumab Treatment in a Human Triple Negative Breast Cancer Xenograft Model

We examined the antitumor efficacy of the capecitabine (CAPE) plus cyclophosphamide (CPA) combination as a 2nd-line therapy after paclitaxel (PTX) plus bevacizumab (BEV) treatment in a xenograft model of human triple negative breast cancer (TNBC) cell line, MX-1. After tumor growth was confirmed, PTX (20 mg/kg;i.v.) + BEV (5 mg/kg;i.p.) treatment was started (Day 1). Each agent was administered once a week for 5 weeks and tumor regression was observed for at least the first 3 weeks. For 2nd-line treatment, we selected mice in which the tumor volume had increased from day 29 to day 36 and was within 130 - 250 mm3 on day 36. After randomization of mice selected on day 36, CPA (10 mg/kg;p.o.) and CAPE (539 mg/kg;p.o.) were administered daily for 14 days (days 36 - 49), followed by cessation of the drugs for 1 week. The tumor growth on day 57 was significantly suppressed in the CPA, CAPE and CAPE + CPA groups as compared with the control group (p < 0.05). Furthermore, the antitumor activity on day 57 of CAPE + CPA was significantly stronger than that of CPA or CAPE alone (p < 0.05). The thymidine phosphorylase (TP) level in tumor tissue was evaluated by immunohistochemistry on day 50, and was significantly higher in the CPA group than those in the control group (p < 0.05). Upregulation of TP in tumor tissues by CPA treatment would increase the 5-FU level in tumor tissues treated with CAPE. This would explain the possible mechanism that made CAPE + CPA superior to CAPE alone in the 2nd-line treatment. Our preclinical results suggest that the CAPE + CPA combination therapy may be effective as 2nd-line therapy after disease progression in PTX + BEV 1st-line treatment for TNBC patients.

Establishment of various biliary tract carcinoma cell lines and xenograft models for appropriate preclinical studies

We recently reported several driver genes of biliary tract carcinoma(BTC) that are known to play important roles in oncogenesis and disease progression. Although the need for developing novel therapeutic strategies is increasing, there are very few BTC cell lines and xenograft models currently available for conducting preclinical studies. Using a total of 88 surgical BTC specimens and 536 immunodeficient mice, 28 xenograft models and 13 new BTC cell lines, including subtypes, were established. Some of our cell lines were found to be resistant to gemcitabine, which is currently the first choice of treatment, thereby allowing highly practical preclinical studies to be conducted. Using the aforementioned cell lines and xenograft models and a clinical pathological database of patients undergoing BTC resection, we can establish a preclinical study system and appropriate parameters for drug efficacy studies to explore new biomarkers for practical applications in the future studies.

Radiomics for predicting perineural invasion status in rectal cancer

BACKGROUND Perineural invasion(PNI),as a key pathological feature of tumor spread,has emerged as an independent prognostic factor in patients with rectal cancer(RC).The preoperative stratification of RC patients according to PNI status is beneficial for individualized treatment and improved prognosis.However,the preoperative evaluation of PNI status is still challenging.AIM To establish a radiomics model for evaluating PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 303 RC patients in a single institution from March 2018 to October 2019.These patients were classified as the training cohort(n=242)and validation cohort(n=61)at a ratio of 8:2.A large number of intraand peritumoral radiomics features were extracted from portal venous phase images of computed tomography(CT).After deleting redundant features,we tested different feature selection(n=6)and machine-learning(n=14)methods to form 84 classifiers.The best performing classifier was then selected to establish Rad-score.Finally,the clinicoradiological model(combined model)was developed by combining Rad-score with clinical factors.These models for predicting PNI were compared using receiver operating characteristic curve(ROC)analysis and area under the ROC curve(AUC).RESULTS One hundred and forty-four of the 303 patients were eventually found to be PNIpositive.Clinical factors including CT-reported T stage(cT),N stage(cN),and carcinoembryonic antigen(CEA)level were independent risk factors for predicting PNI preoperatively.We established Rad-score by logistic regression analysis after selecting features with the L1-based method.The combined model was developed by combining Rad-score with cT,cN,and CEA.The combined model showed good performance to predict PNI status,with an AUC of 0.828[95%confidence interval(CI):0.774-0.873]in the training cohort and 0.801(95%CI:0.679-0.892)in the validation cohort.For comparison of the models,the combined model achieved a higher AUC than the clinical model(cT+cN+CEA)achieved(P<0.001 in the training cohort,and P=0.045 in the validation cohort).CONCLUSION The combined model incorporating Rad-score and clinical factors can provide an individualized evaluation of PNI status and help clinicians guide individualized treatment of RC patients.

The sensitivity of the array resistivity log to mud filtrate invasion and its primary five-parameter inversion for improved oil water recognition

In order to improve reservoir fluid recognition, the sensitivity of array resistivity response to the difference of the invasion properties in both oil-bearing layers and water layers is analyzed. Then the primary inversion is carried out based on the array resistivity log. The mud invasion process is numerically simulated based on the oil-water flow equation and water convection diffusion equation. The results show that the radial resistivity of a fresh mud-invaded oil-bearing layer presents complex distribution characteristics, such as nonlinear increase, increasing to decreasing and low resistivity annulus, and the resistive invasion profile of a water layer is monotonic. Under specific conditions, array resistivity log can reflect these changes and the array induction log is more sensitive. Nevertheless, due to the effect of factors like large invasion depth, reservoir physical and oil-bearing properties, the measured apparent resistivity may differ greatly from the actual mud filtrate invasion profile in an oil-bearing layer. We proposed a five-parameter formation model to simulate the complex resistivity distribution of fresh mud-invaded formation. Then, based on the principle of non-linear least squares, the measured array resistivity log is used for inversion with the Marquardt method. It is demonstrated that the inverted resistivity is typically non-monotonic in oil-bearing layers and is monotonic in water layers. Processing of some field data shows that this is helpful in achieving efficient reservoir fluid recognition.

Lymph node metastasis in early gastric cancer with submucosal invasion:Feasibility of minimally invasive surgery

AIM:To explore the feasibility of pertorming minimally invasive surgery(MIS)on subsets of submucosal gastric cancers that are unlikely to have regional lymph node metastasis. METHODS:A total of 105 patients underwent radical gastrectomy with lymph node dissection for submucosal gastric cancer at our hospital from January 1995 to December 1995.Besides investigating many clinicopathological features such as tumor size,gross appearance,and differentiation, we measured the depth of invasion into submucosa minutely and analyzed the clinicopathologic features of these patients regarding lymph node metastasis. RESULTS:The rate of lymph node metastasis in cases where the depth of invasion was<500 μm,500-2 000 μm,or >2 000 μm was 9%(2/23),19%(7136),and 33%(15/46), respectively(P<0.05).In univariate analysis,no significant correlation was found between lymph node metastasis and clinicopathological characteristics such as age,sex,tumor location,gross appearance,tumor differentiation,Lauren's classification,and lymphatic invasion.In multivariate analysis, tumor size(>4 cm vs≤2 cm,odds ratio=4.80, P=0.04)and depth of invasion(>2 000 μm vs ≤500 μm, odds ratio=6.81,P=0.02)were significantly correlated with lymph node metastasis.Combining the depth and size in cases where the depth of invasion was less than 500 μm, we found that lymph node metastasis occurred where the tumor size was greater than 4 cm.In cases where the tumor size was less than 2 cm,lymph node metastasis was found only where the depth of tumor invasion was more than 2 000 μm. CONCLUSION:MIS can be applied to submucosal gastric cancer that is less than 2 cm in size and 500 μm in depth.

Salmonella invasion

Salmonella enterica serovar Typhimurium encodes two type Ⅲ protein secretion/translocation systems within the pathogenicity island 1(SPI-1)and island 2(SPI-2).These translocation systems inject a panel of bacterial effector proteins into host cells to promote bacterial entry into the host cells via the "trigger" mechanism.The translocated effectors exploit the host actin cytoskeleton leading to macropinocytosis and bacteria entry.In this review,we present a working model based on recent advances in understanding contributions from individual Salmonella effectors.First,activation of the type Ⅲ secretion system and the delivery of bacterial effector proteins(Ⅰ).Injection of the exchange factor SopE and the inositol polyphosphatase SopB results in the activation of CDC42 and Rac1(Ⅱ),leading to the recruitment of ruffling-associated molecules.SipA and SipC function to lower the critical concentration of actin,stimulating the bundling activity of plastin and stabilizing fibrous actin(F-actin),and nucleating the actin assembly(Ⅲ).SopB promotes membrane fission process by decreasing the local concentration of PIP2 at the base of the membrane ruffles and by recruiting VAMP8(Ⅳ).The combined activities of these effectors result in a localized and pronounced outward extension of the membrane ruffles,resulting in the engulfment of Salmonella in an enclosed membrane compartment.Salmonella delivers another effector protein,SptP,which reverses the activation of these small G proteins by stimulating their intrinsic GTPase activity and therefore facilitating cell recovery(Ⅴ).

Predicting hepatocellular carcinoma: A new non-invasive model based on shear wave elastography

BACKGROUND Integrating conventional ultrasound features with 2D shear wave elastography(2D-SWE)can potentially enhance preoperative hepatocellular carcinoma(HCC)predictions.AIM To develop a 2D-SWE-based predictive model for preoperative identification of HCC.METHODS A retrospective analysis of 884 patients who underwent liver resection and pathology evaluation from February 2021 to August 2023 was conducted at the Oriental Hepatobiliary Surgery Hospital.The patients were divided into the modeling group(n=720)and the control group(n=164).The study included conventional ultrasound,2D-SWE,and preoperative laboratory tests.Multiple logistic regression was used to identify independent predictive factors for RESULTS In the modeling group analysis,maximal elasticity(Emax)of tumors and their peripheries,platelet count,cirrhosis,and blood flow were independent risk indicators for malignancies.These factors yielded an area under the curve of 0.77(95%confidence interval:0.73-0.81)with 84%sensitivity and 61%specificity.The model demonstrated good calibration in both the construction and validation cohorts,as shown by the calibration graph and Hosmer-Lemeshow test(P=0.683 and P=0.658,respectively).Additionally,the mean elasticity(Emean)of the tumor periphery was identified as a risk factor for microvascular invasion(MVI)in malignant liver tumors(P=0.003).Patients receiving antiviral treatment differed significantly in platelet count(P=0.002),Emax of tumors(P=0.033),Emean of tumors(P=0.042),Emax at tumor periphery(P<0.001),and Emean at tumor periphery(P=0.003).CONCLUSION 2D-SWE’s hardness value serves as a valuable marker for enhancing the preoperative diagnosis of malignant liver lesions,correlating significantly with MVI and antiviral treatment efficacy.

Progress in Mechanical Modeling of Implantable Flexible Neural Probes

Implanted neural probes can detect weak discharges of neurons in the brain by piercing soft brain tissue,thus as important tools for brain science research,as well as diagnosis and treatment of brain diseases.However,the rigid neural probes,such as Utah arrays,Michigan probes,and metal microfilament electrodes,are mechanically unmatched with brain tissue and are prone to rejection and glial scarring after implantation,which leads to a significant degradation in the signal quality with the implantation time.In recent years,flexible neural electrodes are rapidly developed with less damage to biological tissues,excellent biocompatibility,and mechanical compliance to alleviate scarring.Among them,the mechanical modeling is important for the optimization of the structure and the implantation process.In this review,the theoretical calculation of the flexible neural probes is firstly summarized with the processes of buckling,insertion,and relative interaction with soft brain tissue for flexible probes from outside to inside.Then,the corresponding mechanical simulation methods are organized considering multiple impact factors to realize minimally invasive implantation.Finally,the technical difficulties and future trends of mechanical modeling are discussed for the next-generation flexible neural probes,which is critical to realize low-invasiveness and long-term coexistence in vivo.

Endoscopic diagnosis and management of gallbladder carcinoma in minimally invasive era:New needs,new models

Gallbladder cancer(GBC)is a rare and lethal malignancy;however,it represents the most common type of biliary tract cancer.Patients with GBC are often diagnosed at an advanced stage,thus,unfortunately,losing the opportunity for curative surgical intervention.This situation leads to lower quality of life and higher mortality rates.In recent years,the rapid development of endoscopic equipment and techniques has provided new avenues and possibilities for the early and minimally invasive diagnosis and treatment of GBC.This editorial comments on the article by Pavlidis et al.Building upon their work,we explore the new needs and corresponding models for managing GBC from the endoscopic diagnosis and treatment perspective.