Fusion variations of neurotrophic receptor tyrosine kinase (NTRK) are oncogenic drivers in various solid tumors such as breast cancer, salivary gland carcinoma, infant fibrosarcoma, etc. Gene rearrangements involving NTRK1/2/3 lead to constitutive activation of the tropomyosin receptor kinase (TRK) domain, and the expressed fusion proteins drive tumor growth and survival. NTRK fusions are estimated to occur at a frequency of approximately 0.1% to 1% in non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) mutations are prevalent in NSCLC, but the frequency of EGFR G719A mutation is relatively low (about 2%), and EGFR mutations are typically mutually exclusive with NTRK fusion variants. The study presented the first documented case of lung adenocarcinoma harboring both EGFR G719A mutation and LMNA-NTRK1 fusion. A review of the literature was conducted to elucidate the role of NTRK fusion mutations in NSCLC and their relationship with EGFR mutations, aiming to enhance the understanding of NTRK fusion mutations in NSCLC.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung ; ErbB Receptors/genetics* ; Lamin Type A/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Receptor, trkA/metabolism*

BACKGROUND:Acute exercise tends to cause skeletal muscle tissue damage and lipid metabolism disorders in vivo,but the mechanism by which acute exercise combined with electroacupuncture modulates metabolic and autophagic pathways in vivo is unclear. OBJECTIVE:To observe the changes in metabolic enzymes and autophagy levels in skeletal muscle of rats subjected to acute exercise by electroacupuncture at the acupoints of"Zusanli"and"Huantiao." METHODS:Fifty male Sprague-Dawley rats were randomly divided into three groups:quiet control group(n=10),model group(n=20),and reverse electroacupuncture group(n=20).The latter two groups were set up with two time points,i.e.immediate and 3 hours after exercise groups(n=10 per time point).The model group and the reverse electroacupuncture group underwent acute exercise training after adaptive treadmill training.The rats in the reverse electroacupuncture group underwent electroacupuncture treatment(parameters:electroacupuncture on both sides of the rats at the acupoints of"Zusanli"and"Huantiao,"continuous wave,frequency of 2 Hz,intensity of 2 mA,leaving the needle in the body for 30 minutes,once a day for 7 consecutive days)before treadmill training.Bilateral gastrocnemius muscle tissues were taken under anesthesia immediately after exercise and 3 hours after exercise,and hematoxylin-eosin staining was used to observe the histopathological changes of rat skeletal muscle.ELISA kit was used to detect the activities of hepatic lipase,fatty acid synthase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 in rat skeletal muscle tissues.Immunohistochemistry and western blot were used to detect the changes in the expression of autophagy genes. RESULTS AND CONCLUSION:After hematoxylin-eosin staining,the arrangement of gastrocnemius muscle fibers in the model group was disturbed,swollen and ruptured immediately after exercise and 3 hours after exercise.In the reverse electroacupuncture group,gastrocnemius muscle fibers were tightly arranged and the number of swollen and ruptured cells was greatly reduced immediately after exercise and 3 hours after exercise,and there was no significant difference when compared with the quiet control group.Compared with the quiet control group,the activities of hepatic lipase and fatty acid synthase were lower while the activities of lipoprotein lipase,hormone-sensitive lipase,and carnitine palmitoyltransferase 1 were higher in the model group and the reverse electroacupuncture group 3 hours after exercise(P＜0.05 or P＜0.01).Compared with the model group,the activities of lipoprotein lipase and carnitine palmitoyltransferase 1 were higher in the reverse electroacupuncture group immediately after exercise(P＜0.05),while the activity of lipoprotein lipase was higher and the activity of hormone-sensitive lipase was lower in the reverse electroacupuncture group 3 hours after exercise(P＜0.01).Immunohistochemical results showed that compared with the quiet control group,the expression of P62,autophagy-related gene 5 and autophagy-related gene 7 was higher in the model group immediately and 3 hours after exercise,as well as in the reverse electroacupuncture group immediately after exercise(P＜0.05 or P＜0.01);compared with the model group,the expression of P62 and autophagy-related gene 7 was lower in the reverse electroacupuncture group immediately and 3 hours after exercise(P＜0.05).Western blot results showed that the protein expression of P62 and autophagy-related gene 7 in the reverse electroacupuncture group was lower than that in the model group immediately after exercise(P＜0.05);the protein expression of Parkin in the model group was higher than that in the quiet control group immediately and 3 hours after exercise(P＜0.05);and the protein expression of Parkin in the reverse electroacupuncture group was lower than that in the model group immediately and 3 hours after exercise(P＜0.05).To conclude,acute exercise induces disorders,swelling and rupture of gastrocnemius muscle fibers in rats and electroacupuncture on both sides of the acupoints of"Zusanli"and"Huantiao"can improve the level of lipid metabolism and regulate autophagy cells in rat skeletal muscle,preventing the disorders of lipid metabolism and damage of gastrocnemius muscle tissues caused by acute exercise.The mechanism may be closely related to the regulation of autophagy-related factor P62,autophagy-related gene 5,autophagy-related gene 7,and Parkin protein expression to promote the occurrence of autophagy or regulate the autophagy pathway in rat skeletal muscle cells.

The accurate segmentation of the right ventricle is crucial for cardiac disease research,but its low contrast with surrounding tissues and complex structure make segmentation challenging.To address these issues,a dual-encoder segmentation model combining nested multi-scale feature fusion and feature repurposing modules is proposed.Specifically,the nested multi-scale feature fusion module captures boundary detail features through multi-scale dilated convolutions and reduces the semantic gap between the encoder and decoder using short skip connections,while the feature repurposing module enhances feature extraction ability by leveraging fine-grained features from shallow layers.Ablation experiments show that the inclusion of these two modules improves the Dice similarity coefficient of U-Net by 3.14%.On the ACDC dataset,the proposed model achieves a Dice similarity coefficient of 90.31%and a mean Hausdorff distance of 5.21 mm,outperforming other comparative models.Additionally,its generalization ability is validated on the M&Ms dataset.Experimental results demonstrate the excellent performance and robustness of the proposed model in right ventricle segmentation.

Objective:To investigate the clinical value of Delphian lymph node (DLN) metastasis (DLNM) in predicting regional lymph node involvement in patients with intrathyroidal papillary thyroid carcinoma (PTC).Methods:Clinical and pathological data from 345 consecutive patients with pathologically confirmed DLN status, who underwent initial surgical treatment at the Department of Surgical Oncology, First Affiliated Hospital of Zhejiang University School of Medicine between Jan 2020 and Dec 2022, were retrospectively analyzed.Results:DLNM was identified in 61 patients (17.7%). Univariate analysis revealed significant associations between DLNM and male sex, elevated preoperative thyroglobulin levels, larger tumor size, maximum tumor diameter >10 mm, bilateral lesions, multifocality, lymphovascular invasion, and lymph nodes metastases in pretracheal, paratracheal, and lateral cervical(all P ≤0.001). Elevated thyroglobulin antibody levels ( χ2=6.201, P=0.013) and Hashimoto's thyroiditis ( χ2=11.340, P<0.001) were protective factors for DLNM. Multivariate analysis identified male sex, lymphovascular invasion, pretracheal, and paratracheal lymph node metastases ( χ2=6.689, P=0.010; χ2=8.163, P=0.004; χ2=7.605, P=0.006; χ2=8.324, P=0.004) as independent risk indicators for DLNM. Patients with DLNM exhibited significantly higher risks of lymph nodes metastases in pretracheal ( χ2=27.307, P<0.001), paratracheal ( χ2=38.697, P<0.001), and lateral cervical ( χ2=36.459, P<0.001). Conclusion:DLNM demonstrates predictive value for both central compartment and lateral cervical lymph node metastases, warranting particular attention to meticulous dissection of the prelaryngeal region during surgery.

Objective:To explore the intervention effect of ultra-pure double-lumen dialyzer paired with online hemodiafiltration (PHF) on the microinflammatory state in maintenance hemodialysis patients.Methods:A total of 112 maintenance hemodialysis patients admitted to the Huadu District People′s Hospital of Guangzhou from January 2020 to December 2023 were prospectively enrolled. Using a parallel control and before-after control method, the patients were divided into an observation group and a control group according to the odd and even numbers of their enrollment sequence, with 56 cases in each group. The observation group received PHF during hemodiafiltration, while the control group received hemodiafiltration with a high-flux dialyzer. Venous blood samples were collected from both groups before treatment and 6 months after treatment to detect the levels of serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon (IFN)-γ. The dialysis efficacy of the two groups was compared by evaluating the changes in microinflammatory index levels.Results:Before treatment, there were no significant differences in serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and hs-CRP between the two groups (all P>0.05). After treatment, various inflammatory indicators in the observation group were significantly lower than those before treatment (all P<0.05), while there were no significant differences in inflammatory indicators in the control group before and after treatment (all P>0.05). Moreover, there were significant differences in inflammatory indicators between the observation group and the control group after treatment ( P<0.05). Conclusions:Ultra-pure double-lumen dialyzer paired with online hemodiafiltration can significantly improve the inflammatory state in hemodialysis patients.

AIM:To establish an optimal protocol for isolating and extracting mouse hepatocellular carcinoma H22 cell-detrived microparticles(H22-MPs),evaluate their stimulating effect on dendritic cells(DC),and investigate the cytotoxic capacity of CD8+T cells induced by H22-MPs on hepatocellular carcinoma cells.METHODS:The H22-MPs were extracted by high-speed differential centrifugation,and the morphology of H22-MPs was observed by transmis-sion electron microscopy.The particle size distribution of H22-MPs was detected by dynamic light scattering,and the ex-pression of vesicle surface markers was detected by Western blot.The protein components and pathways involved by MPs were analyzed by labeling free quantitative proteomics combining with bioinformatics GO and KEGG enrichment methods.The effect of MPs antigen on the expression of CD11c,a mature marker of DC,was detected by laser confocal microscopy.Next,CD8+T cells were sorted by magnetic beads,and the secretion of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and interleukin-2(IL-2)in the supernatant of CD8+T cells stimulated by DC loaded with H22-MPs was detected by ELISA.Lactate dehydrogenase(LDH)test was conducted to evaluate the specific killing effect of CD8+T cells induced by DC loaded with H22-MPs on hepatocellular carcinoma cells.RESULTS:The results showed that the morphology,size and vesicle markers of H22-MPs met the requirements.Most of the H22-MPs protein antigens were derived from its parent cell H22 and coordinated various signal transduction pathways in the cells.Subsequently,it was detected that H22-MPs increased the expression of CD11c on the surface of DC,and H22-MPs were mainly localized in the lysosomes of DC.In addition,DC loaded with H22-MPs stimulated CD8+T to release high levels of TNF-α,IFN-γ and IL-2,and it also pro-moted CD8+T to overexpress CD69,thus inducing CD8+T to killhepatocellular carcinoma cells specifically.CONCLU-SION:H22-MPs promote the maturation of DC,and the mature DC may induce CD8+T cells to play an anti-hepatocellu-lar carcinoma immune response by promoting the activation of CD8+T cells.

AIM:To establish an optimal protocol for isolating and extracting mouse hepatocellular carcinoma H22 cell-detrived microparticles(H22-MPs),evaluate their stimulating effect on dendritic cells(DC),and investigate the cytotoxic capacity of CD8+T cells induced by H22-MPs on hepatocellular carcinoma cells.METHODS:The H22-MPs were extracted by high-speed differential centrifugation,and the morphology of H22-MPs was observed by transmis-sion electron microscopy.The particle size distribution of H22-MPs was detected by dynamic light scattering,and the ex-pression of vesicle surface markers was detected by Western blot.The protein components and pathways involved by MPs were analyzed by labeling free quantitative proteomics combining with bioinformatics GO and KEGG enrichment methods.The effect of MPs antigen on the expression of CD11c,a mature marker of DC,was detected by laser confocal microscopy.Next,CD8+T cells were sorted by magnetic beads,and the secretion of tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ)and interleukin-2(IL-2)in the supernatant of CD8+T cells stimulated by DC loaded with H22-MPs was detected by ELISA.Lactate dehydrogenase(LDH)test was conducted to evaluate the specific killing effect of CD8+T cells induced by DC loaded with H22-MPs on hepatocellular carcinoma cells.RESULTS:The results showed that the morphology,size and vesicle markers of H22-MPs met the requirements.Most of the H22-MPs protein antigens were derived from its parent cell H22 and coordinated various signal transduction pathways in the cells.Subsequently,it was detected that H22-MPs increased the expression of CD11c on the surface of DC,and H22-MPs were mainly localized in the lysosomes of DC.In addition,DC loaded with H22-MPs stimulated CD8+T to release high levels of TNF-α,IFN-γ and IL-2,and it also pro-moted CD8+T to overexpress CD69,thus inducing CD8+T to killhepatocellular carcinoma cells specifically.CONCLU-SION:H22-MPs promote the maturation of DC,and the mature DC may induce CD8+T cells to play an anti-hepatocellu-lar carcinoma immune response by promoting the activation of CD8+T cells.

The accurate segmentation of the right ventricle is crucial for cardiac disease research,but its low contrast with surrounding tissues and complex structure make segmentation challenging.To address these issues,a dual-encoder segmentation model combining nested multi-scale feature fusion and feature repurposing modules is proposed.Specifically,the nested multi-scale feature fusion module captures boundary detail features through multi-scale dilated convolutions and reduces the semantic gap between the encoder and decoder using short skip connections,while the feature repurposing module enhances feature extraction ability by leveraging fine-grained features from shallow layers.Ablation experiments show that the inclusion of these two modules improves the Dice similarity coefficient of U-Net by 3.14%.On the ACDC dataset,the proposed model achieves a Dice similarity coefficient of 90.31%and a mean Hausdorff distance of 5.21 mm,outperforming other comparative models.Additionally,its generalization ability is validated on the M&Ms dataset.Experimental results demonstrate the excellent performance and robustness of the proposed model in right ventricle segmentation.

Objective:To investigate the clinical value of Delphian lymph node (DLN) metastasis (DLNM) in predicting regional lymph node involvement in patients with intrathyroidal papillary thyroid carcinoma (PTC).Methods:Clinical and pathological data from 345 consecutive patients with pathologically confirmed DLN status, who underwent initial surgical treatment at the Department of Surgical Oncology, First Affiliated Hospital of Zhejiang University School of Medicine between Jan 2020 and Dec 2022, were retrospectively analyzed.Results:DLNM was identified in 61 patients (17.7%). Univariate analysis revealed significant associations between DLNM and male sex, elevated preoperative thyroglobulin levels, larger tumor size, maximum tumor diameter >10 mm, bilateral lesions, multifocality, lymphovascular invasion, and lymph nodes metastases in pretracheal, paratracheal, and lateral cervical(all P ≤0.001). Elevated thyroglobulin antibody levels ( χ2=6.201, P=0.013) and Hashimoto's thyroiditis ( χ2=11.340, P<0.001) were protective factors for DLNM. Multivariate analysis identified male sex, lymphovascular invasion, pretracheal, and paratracheal lymph node metastases ( χ2=6.689, P=0.010; χ2=8.163, P=0.004; χ2=7.605, P=0.006; χ2=8.324, P=0.004) as independent risk indicators for DLNM. Patients with DLNM exhibited significantly higher risks of lymph nodes metastases in pretracheal ( χ2=27.307, P<0.001), paratracheal ( χ2=38.697, P<0.001), and lateral cervical ( χ2=36.459, P<0.001). Conclusion:DLNM demonstrates predictive value for both central compartment and lateral cervical lymph node metastases, warranting particular attention to meticulous dissection of the prelaryngeal region during surgery.

Objective:To explore the intervention effect of ultra-pure double-lumen dialyzer paired with online hemodiafiltration (PHF) on the microinflammatory state in maintenance hemodialysis patients.Methods:A total of 112 maintenance hemodialysis patients admitted to the Huadu District People′s Hospital of Guangzhou from January 2020 to December 2023 were prospectively enrolled. Using a parallel control and before-after control method, the patients were divided into an observation group and a control group according to the odd and even numbers of their enrollment sequence, with 56 cases in each group. The observation group received PHF during hemodiafiltration, while the control group received hemodiafiltration with a high-flux dialyzer. Venous blood samples were collected from both groups before treatment and 6 months after treatment to detect the levels of serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon (IFN)-γ. The dialysis efficacy of the two groups was compared by evaluating the changes in microinflammatory index levels.Results:Before treatment, there were no significant differences in serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and hs-CRP between the two groups (all P>0.05). After treatment, various inflammatory indicators in the observation group were significantly lower than those before treatment (all P<0.05), while there were no significant differences in inflammatory indicators in the control group before and after treatment (all P>0.05). Moreover, there were significant differences in inflammatory indicators between the observation group and the control group after treatment ( P<0.05). Conclusions:Ultra-pure double-lumen dialyzer paired with online hemodiafiltration can significantly improve the inflammatory state in hemodialysis patients.