Objective To evaluate the clinical value of 3D reconstruction in preoperative assessment of laparoscopic partial nephrectomy(LPN),and to help improve the safety of surgical treatment and promote individualized treatment in clinical practice.Methods A retrospective study was conducted on 120 patients with T1 renal cell carcinoma who underwent LPN at Fudan University Shanghai Cancer Center during Dec.2019 and Dec.2023.The patients were divided into a 3D group(n=60)and a 2D group(.n=60).Surgical parameters and vascular variation data were compared between the two groups.Results Baseline characteristics were comparable between the two groups(P＞0.05).The 3D group had significantly shorter operation time[129.5(110.3,154.0)min vs.145.0(125.0,173.8)min,P=0.016],less blood loss[50.0(10.0,50.0)mL vs.200(100.0,200.0)mL,P＜0.001],and shorter warm ischemia time[22.0(18.0,27.0)min vs.29.0(26.0,32.0)min,P＜0.001].The operation time,intraoperative blood loss and warm ischemia time were significantly longer or more in patients with vascular variations than in those without(P＜0.05).Conclusion 3D reconstruction can enhance the accuracy of preoperative assessment of tumors and the surrounding anatomical structures as well as vascular variations in LPN,optimize surgical planning,reduce intraoperative trauma,and demonstrate greater advantages in cases with complex vascular anatomy.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Objective To investigate the suitable habitats of Phlebotomus chinensis in Gansu Province, so as provide insights into effective management of mountain-type zoonotic visceral leishmaniasis (MT-ZVL). Methods The geographical coordinates of locations where MT-ZVL cases were reported were retrieved in Gansu Province from 2015 to 2023, and data pertaining to 26 environmental variables were captured, including 19 climatic variables (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter), five geographical variables (elevation, annual normalized difference vegetation index, vegetation type, landform type and land use type), and two population and economic variables (population distribution and gross domestic product). Twelve species distribution models were built using the biomod2 package in R project, including surface range envelope (SRE) model, generalized linear model (GLM), generalized additive model (GAM), multivariate adaptive regression splines (MARS) model, generalized boosted model (GBM), classification tree analysis (CTA) model, flexible discriminant analysis (FDA) model, maximum entropy (MaxEnt) model, optimized maximum entropy (MAXNET) model, artificial neural network (ANN) model, random forest (RF) model, and extreme gradient boosting (XGBOOST) model. The performance of 12 models was evaluated using the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS), and Kappa coefficient, and single models with high performance was selected to build the optimal ensemble models. Factors affecting the survival of Ph. chinensis were identified based on climatic, geographical, population and economic variables. In addition, the suitable distribution areas of Ph. chinensis were predicted in Gansu Province under shared socioeconomic pathway 126 (SSP126), SSP370 and SSP585 scenarios based on climatic data during the period from 1991 to 2020, from 2041 to 2060 (2050s), and from 2081 to 2100 (2090s) . Results A total of 11 species distribution models were successfully built for prediction of potential distribution areas of Ph. chinensis in Gansu Province, and the RF model had the highest predictive accuracy (AUC = 0.998). The ensemble model built based on the RF model, XGBOOST model, GLM, and MARS model had an increased predictive accuracy (AUC = 0.999) relative to single models. Among the 26 environmental factors, precipitation of the wettest quarter (12.00%), maximum temperature of the warmest month (11.58%), and annual normalized difference vegetation index (11.29%) had the greatest contributions to suitable habitats distribution of Ph. sinensis. Under the climatic conditions from 1991 to 2020, the potential suitable habitat area for Ph. chinensis in Gansu Province was approximately 5.80 × 10⁴ km², of which the highly suitable area was 1.42 × 10⁴ km², and primarily concentrated in the southernmost region of Gansu Province. By the 2050s, the unsuitable and lowly suitable areas for Ph. chinensis in Gansu Province had decreased by varying degrees compared to that of 1991 to 2020 period, while the moderately and highly suitable areas exhibited expansion and migration. By the 2090s, under the SSP126 scenario, the suitable habitat area for Ph. chinensis increased significantly, and under the SSP585 scenario, the highly suitable areas transformed into extremely suitable areas, also showing substantial growth. Future global warming is conducive to the survival and reproduction of Ph. chinensis. From the 2050s to the 2090s, the highly suitable areas for Ph. chinensis in Gansu Province will be projected to expand northward. Under the SSP126 scenario, the suitable habitat area for Ph. chinensis in Gansu Province is expected to increase by 194.75% and 204.79% in the 2050s and 2090s, respectively, compared to that of the 1991 to 2020 period. Under the SSP370 scenario, the moderately and highly suitable areas will be projected to increase by 164.40% and 209.03% in the 2050s and 2090s, respectively, while under the SSP585 scenario, they are expected to increase by 195.98% and 211.66%, respectively. Conclusions The distribution of potential suitable habitats of Ph. sinensis gradually shifts with climatic changes. Intensified surveillance and management of Ph. sinensis is recommended in central and eastern parts of Gansu Province to support early warning of MT-ZVL.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

Objective To investigate the heterogeneous lineage of cancer-associated fibroblast(CAF)in clear cell renal cell carcinoma(ccRCC),and explore the relationship between antigen-presentation carcinoma-associated fibroblast(apCAF)and the spatial distribution and formation potential of tertiary lymphoid structure(TLS).Methods Seven single-cell transcriptomic cohorts(n=88)were integrated,and batch effects were corrected using the Harmony algorithm to identify consistent CAF subpopulations across samples.The spatial transcriptomics(GSE175540,n=24)were combined to analyze the spatial interactions between CAF and TLS.Functional annotation was performed using AUCell,and Wilcoxon test was employed to compare the differences in CAF abundance between the immune-sensitive group and the resistant group.The co-localization of TLS with different chemokines was assessed.Results Nine conserved CAF clusters were defined,which were reproducible across different cohorts.Among them,Fibro 4 served as an antigen-presenting type of apCAF,characterized by high expression of HLA-DRA/CD74,and abundance in the immune-sensitive group;its functions were enriched in T cell activation pathways;it was strongly correlated with TLS,and positioned at the periphery of TLS.Cell co-localization analysis revealed that apCAF could recruit lymphocytes to aggregate and form TLS structures via the CXCL13-CXCR5 and CCL19-CCR7 axes.Conclusion This study first reveals that apCAF drives the formation of TLS in ccRCC through a chemokine network,thereby correlating with the response to immunotherapy.The apCAF-TLS axis provides a new strategy for targeting stromal remodeling in the immune microenvironment,and its combined scoring is expected to serve as a biomarker for predicting the efficacy of immune checkpoint blockade therapy.

In recent years,the combined application of targeted-immunotherapy has become a recommended treatment option for advanced renal cell carcinoma in various guidelines.However,although this strategy has significant therapeutic effects and survival advantages,it is associated with a variety of adverse reactions that cannot be ignored.Therefore,how to effectively manage adverse reactions and ensure the treatment safety has become one of the core issues.This article systematically reviews the adverse effects and management strategies,discusses the early identification of adverse reactions,monitoring methods,the design of individualized treatment plans and future development,aiming to provide practical safety management guidance and explore the direction of future development.

Objective To evaluate the clinical value of 3D reconstruction in preoperative assessment of laparoscopic partial nephrectomy(LPN),and to help improve the safety of surgical treatment and promote individualized treatment in clinical practice.Methods A retrospective study was conducted on 120 patients with T1 renal cell carcinoma who underwent LPN at Fudan University Shanghai Cancer Center during Dec.2019 and Dec.2023.The patients were divided into a 3D group(n=60)and a 2D group(.n=60).Surgical parameters and vascular variation data were compared between the two groups.Results Baseline characteristics were comparable between the two groups(P＞0.05).The 3D group had significantly shorter operation time[129.5(110.3,154.0)min vs.145.0(125.0,173.8)min,P=0.016],less blood loss[50.0(10.0,50.0)mL vs.200(100.0,200.0)mL,P＜0.001],and shorter warm ischemia time[22.0(18.0,27.0)min vs.29.0(26.0,32.0)min,P＜0.001].The operation time,intraoperative blood loss and warm ischemia time were significantly longer or more in patients with vascular variations than in those without(P＜0.05).Conclusion 3D reconstruction can enhance the accuracy of preoperative assessment of tumors and the surrounding anatomical structures as well as vascular variations in LPN,optimize surgical planning,reduce intraoperative trauma,and demonstrate greater advantages in cases with complex vascular anatomy.

Objective To investigate the heterogeneous lineage of cancer-associated fibroblast(CAF)in clear cell renal cell carcinoma(ccRCC),and explore the relationship between antigen-presentation carcinoma-associated fibroblast(apCAF)and the spatial distribution and formation potential of tertiary lymphoid structure(TLS).Methods Seven single-cell transcriptomic cohorts(n=88)were integrated,and batch effects were corrected using the Harmony algorithm to identify consistent CAF subpopulations across samples.The spatial transcriptomics(GSE175540,n=24)were combined to analyze the spatial interactions between CAF and TLS.Functional annotation was performed using AUCell,and Wilcoxon test was employed to compare the differences in CAF abundance between the immune-sensitive group and the resistant group.The co-localization of TLS with different chemokines was assessed.Results Nine conserved CAF clusters were defined,which were reproducible across different cohorts.Among them,Fibro 4 served as an antigen-presenting type of apCAF,characterized by high expression of HLA-DRA/CD74,and abundance in the immune-sensitive group;its functions were enriched in T cell activation pathways;it was strongly correlated with TLS,and positioned at the periphery of TLS.Cell co-localization analysis revealed that apCAF could recruit lymphocytes to aggregate and form TLS structures via the CXCL13-CXCR5 and CCL19-CCR7 axes.Conclusion This study first reveals that apCAF drives the formation of TLS in ccRCC through a chemokine network,thereby correlating with the response to immunotherapy.The apCAF-TLS axis provides a new strategy for targeting stromal remodeling in the immune microenvironment,and its combined scoring is expected to serve as a biomarker for predicting the efficacy of immune checkpoint blockade therapy.

In recent years,the combined application of targeted-immunotherapy has become a recommended treatment option for advanced renal cell carcinoma in various guidelines.However,although this strategy has significant therapeutic effects and survival advantages,it is associated with a variety of adverse reactions that cannot be ignored.Therefore,how to effectively manage adverse reactions and ensure the treatment safety has become one of the core issues.This article systematically reviews the adverse effects and management strategies,discusses the early identification of adverse reactions,monitoring methods,the design of individualized treatment plans and future development,aiming to provide practical safety management guidance and explore the direction of future development.

Large language models (LLMs), represented by ChatGPT, have garnered significant attention due to their powerful capabilities in understanding and generating human language. Research on the application of LLMs across various medical tasks has shown a vigorous development trend. This review aims to outline the development and clinical applications of LLMs, with a focus on the primary tasks of medical intelligent assistants, including their associated opportunities and challenges. At the technical level, we provide a detailed explanation of the architecture and training processes of existing medical LLMs, and summarize the general technical steps for adapting large models to the healthcare domain. At the application level, we introduce the main tasks of medical intelligent assistants from both healthcare provider- and patient-oriented perspectives, andcompare the performance of different LLMs across various medical tasks to illustrate their unique advantages and limitations in medical applications.