Since 2017,twelve chimeric antigen receptor gene-modified T lymphocyte(CAR-T cell)products have been approved for the treatment of hematological malignancies,including relapsed/refractory acute B lymphoblastic leukemia(B-ALL),specific subtypes of B cell lymphoma,and multiple myeloma.However,CAR-T cell therapy faces numerous challenges in its clinical application,such as resistance,lengthy production cycles,high individuation and costs in hematological tumors,and tumor heterogeneity/antigen escape,insufficient infiltration capability,immunosuppressive microenvironments,and poor therapeutic response in solid tumors.With the in-depth exploration of tumor immunology and the development of genetic engineering technology,various new strategies have been attempted to enhance the efficacy and generalizability of CAR-T cell therapy.This paper presents a commentary on CAR-T cell therapy,with a focus on key clinical issues and corresponding countermeasures,providing valuable insights for future basic research and clinical transformation of CAR-T cell therapy.

Objective:To explore the clinicopathologic features differences between tall cell variant of papillary thyroid cancer (TCV-PTC) and PTC with tall cell features (PTC-TCF) and the factors influencing efficacy of 131I therapy in patients with TCV-PTC and PTC-TCF. Methods:A retrospective analysis was conducted on 84 patients (28 males, 56 females, age 43.5(35.0, 55.0) years) with pathologically confirmed TCV-PTC or PTC-TCF and who were treated with 131I therapy from January 2018 to June 2023 in the Department of Nuclear Medicine, the Affiliated Hospital of Qingdao University. The patients were divided into structural incomplete response (SIR) group and non-SIR group according to 131I treatment response. Data differences were analyzed by Wilcoxon rank sum test, Fisher exact test, or Mann-Whitney U test. Variables with P<0.1 were enrolled in logistic multivariate regression analysis. The ROC curve was used to obtain the cut-off value of stimulated thyroglobulin (sTg). Results:A total of 37 patients with non-SIR and 6 patients with SIR were found in TCV-PTC group ( n=43), and 33 non-SIR and 8 SIR cases were found in PTC-TCF group ( n=41). Univariate analysis revealed that sTg differed significantly between non-SIR patients and SIR patients in TCV-PTC group ( Z=-2.81, P=0.003), while no significant differences observed for sex, age, multifocality, capsular invasion, T stage, N stage, B-Raf proto-oncogene, serine/threonine-protein kinase (BRAF) V600E mutation, initial recurrence risk, number of metastatic lymph nodes, maximum tumor diameter ( Z values: from -0.74 to -0.11, all P>0.05). In TCV-PTC group, sTg also differed significantly between non-SIR patients and SIR patients ( Z=-4.40, P<0.001), while the other clinical factors above and the proportion of tall cells showed no significant difference ( Z values: from -1.90 to -0.22, all P>0.05). The logistic regression analysis confirmed sTg as an independent risk factor of SIR in both TCV-PTC group (odds ratio ( OR) = 25.156, 95% CI: 2.245-281.812, P=0.009) and PTC-TCF group ( OR=19.214, 95% CI: 2.537-145.502, P=0.004). The ROC curve indicated that the cut-off value of sTg for predicting SIR was 20.75μg/L in TCV-PTC group and 18.55μg/L in PTC-TCF group. Conclusions:sTg is the independent risk factor for predicting the poor prognosis of patients with TCV-PTC (sTg≥20.75μg/L) and PTC-TCF (sTg≥18.55μg/L). However, other clinical characteristics show no statistical difference between TCV-PTC group and PTC-TCF group, suggesting that the invasiveness of PTC-TCF may not be lower than that of TCV-PTC, which close attention should be paid to in clinical practice.

Objective:To explore the clinical efficacy of anterolateral thigh perforator flap (ALTPF) in treatment of extensive wound of Degree IV burns in limbs.Methods:A retrospective analysis was conducted on 9 patients who had extensive wound of Degree IV burns in limbs caused by stove burns admitted to Department of Burns and Plastic Surgery, the 988th Hospital of the Joint Logistics Support Force of the Chinese PLA between January 2017 and January 2024. Among the patients, there were 8 males and 1 female, aged between 36 and 63 years. Three patients had the wound from anterior leg to dorsal foot, 3 from leg down to ankle, 1 from forearm to hand and 2 from arm to forearm. Area of burns ranged from 20 cm × 15 cm to 30 cm × 25 cm, and all patients were treated by free ALTPF. According to whether the main artery at the recipient site was feasible for direct anastomosis with the vessels carried in flap, 4 patients were treated by bilateral parallel ALTPFs, and 5 were treated by unilateral ultra-long internally supercharged ALTPF. A total of 13 ALTPFs were harvested, with individual flap size at 20 cm × 8 cm to 46 cm × 12 cm. Donor sites were directly sutured. Time for flap harvesting, flap survival and wound healing time were records. Scheduled postoperative follow-up was conducted at outpatient clinic and via telephone interviews to evaluate functional recovery. Follow-up assessments included evaluation of flap condition, two-point discrimination (TPD), recovery of joint function at recipient sites, flap appearance and donor site recovery.Results:The time for flap harvest was 1.0 to 4.5 hours. All 13 ALTPFs successfully survived. The time from surgery to healing of recipient sites was 18 to 72 days, and all donor sites healed. Over the postoperative follow-up that lasted for 6 to 34 months, the recipient sites had found with good cosmetic outcomes, without osteomyelitis or deep tissue infection. Four ALTPFs in 2 patients were found swelling, which were revised at 6 months after surgery. Four ALTPFs in other 2 patients had pigment deposition at edges. One ALTPF was scalded, which healed after dressing changes but left with patchy scars. The remaining ALTPFs were soft, elastic, free from pain and well-perfused, with regained protective sensation at S 3. However, all of the ALTPFs failed to detect TPD. Six patients with lower limb injuries were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) ankle hindfoot scoring system: 2 patients were rated as excellent and 4 were rated as good. Three patients with upper limb injuries were evaluated using Evaluation Trial Standards of Upper Limb Partial Functional of Hand Surgery of Chinese Medical Association: 1 patient was rated as excellent and 2 were rated as good. Only linear scars left at the 13 donor sites, with normal blood supply to the distal limbs, and without restrictions in range of motion of knee joints nor muscle strength of quadriceps. Conclusion:The ALTPF offers advantages such as anatomical consistency, reliable blood supply and flexible combination in treatment of extensive wound of Degree Ⅳ burns in limbs. It is an ideal surgical procedure for treatment of large soft tissue defects of extremities.

Objective:To establish a three-dimensional U-shaped residual coordinated attention network (URCA-Net) based on enhanced CT images for small bowel polyp detection and analyze its application effectiveness in intelligent detection of small bowel polyps.Methods:Abdominal CT data of patients with small bowel polyps were collected from the Air Force Medical Center between June 2019 and July 2023. All patients underwent bowel preparation followed by thin-slice spiral CT scanning to obtain enhanced CT arterial phase images. The data were randomly divided into training, validation and test sets in an 8∶1∶1 ratio. The URCA-Net deep learning model was used for small bowel polyp segmentation. The training set was used for model parameter training, the validation set for hyperparameter adjustment and monitoring of model generalization performance and the test set for final unbiased evaluation of the model. An early intelligent detection model for small bowel polyps was constructed, and its performance was evaluated. Evaluation metrics included pixel-level metrics for the segmentation task [Dice Similarity Coefficient (DSC)], as well as sensitivity and precision for polyp detection. A two-stage segmentation strategy was adopted: the first stage segmented the small bowel region to remove external interference, and the second stage performed polyp segmentation within the small bowel region.Results:A total of 78 subjects were included in the study, with an average age of (54±7) years. A total of 23 400 scan images were extracted, including 136 hyperplastic polyps, 298 hamartomatous polyps, 14 adenomatous polyps, and 4 cancerous polyps. On the test set, the average DSC for the first stage (small bowel segmentation) and the second stage (polyp segmentation) was 0.790 and 0.314, respectively. In the second stage task (polyp segmentation based on small bowel region), the polyp segmentation DSC increased to 0.701, with a precision of 0.836 (95% CI: 0.700-0.972) and a sensitivity of 0.759 (95% CI: 0.631-0.888) for polyp detection. Conclusion:The URCA-Net deep learning technique demonstrates good auxiliary diagnostic effectiveness in small bowel polyp detection and can provide a reference for screening and detection of small bowel polyps. The model is capable of generating high-quality segmentation results, which could facilitate evaluating polyp lesion morphology and provide support for downstream tasks such as preoperative navigation and risk prediction.

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.

Objective:To establish a three-dimensional U-shaped residual coordinated attention network (URCA-Net) based on enhanced CT images for small bowel polyp detection and analyze its application effectiveness in intelligent detection of small bowel polyps.Methods:Abdominal CT data of patients with small bowel polyps were collected from the Air Force Medical Center between June 2019 and July 2023. All patients underwent bowel preparation followed by thin-slice spiral CT scanning to obtain enhanced CT arterial phase images. The data were randomly divided into training, validation and test sets in an 8∶1∶1 ratio. The URCA-Net deep learning model was used for small bowel polyp segmentation. The training set was used for model parameter training, the validation set for hyperparameter adjustment and monitoring of model generalization performance and the test set for final unbiased evaluation of the model. An early intelligent detection model for small bowel polyps was constructed, and its performance was evaluated. Evaluation metrics included pixel-level metrics for the segmentation task [Dice Similarity Coefficient (DSC)], as well as sensitivity and precision for polyp detection. A two-stage segmentation strategy was adopted: the first stage segmented the small bowel region to remove external interference, and the second stage performed polyp segmentation within the small bowel region.Results:A total of 78 subjects were included in the study, with an average age of (54±7) years. A total of 23 400 scan images were extracted, including 136 hyperplastic polyps, 298 hamartomatous polyps, 14 adenomatous polyps, and 4 cancerous polyps. On the test set, the average DSC for the first stage (small bowel segmentation) and the second stage (polyp segmentation) was 0.790 and 0.314, respectively. In the second stage task (polyp segmentation based on small bowel region), the polyp segmentation DSC increased to 0.701, with a precision of 0.836 (95% CI: 0.700-0.972) and a sensitivity of 0.759 (95% CI: 0.631-0.888) for polyp detection. Conclusion:The URCA-Net deep learning technique demonstrates good auxiliary diagnostic effectiveness in small bowel polyp detection and can provide a reference for screening and detection of small bowel polyps. The model is capable of generating high-quality segmentation results, which could facilitate evaluating polyp lesion morphology and provide support for downstream tasks such as preoperative navigation and risk prediction.