ObjectiveWith the epidermal growth factor receptor（EGFR）/Signal Transducers and Activators of Transcription（STAT3）/Hexokinase 2（HK2） signaling pathway in atherosclerosis （AS） and ovarian cancer （OC） as the entry point， this paper discusses the molecular mechanism of Gypenoside L （Gyp-L） treating AS and OC with different diseases， provides a new perspective and theoretical basis for TCM treating AS and OC with EGFR-STAT3-HK2 pathway， and enriches the scientific connotation of the theory of "cytoskeleton in the heart". MethodsCCK-8 was used to detect the proliferation of HUVEC and OVCAR-3 cells， in order to determine the intervention concentration for subsequent experiments. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. Western blot was used to detect the expression levels of relevant proteins. Furthermore， two cell models overexpressing EGFR were constructed and co treated with Gyp-L. HUVEC cells were divided into control， ox-LDL， OE-NC， OE-EGFR， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. OVCAR-3 cells were divided into control， OE-NC， OE-EGFR ， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Western blot was used to detect the expression levels of EGFR-STAT3-HK2 pathway related proteins. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. ResultsGyp-L can significantly reduce the NO content of HUVEC and the pyruvate and LDH content of two cell lines （P<0.05）； Inhibit the proliferation and migration ability of OVCAR-3 cells； Reduce the expression levels of EGFR/STAT3/HK2 pathway related proteins in HUVEC and OVCAR-3 cell lines （P<0.05）， and inhibit the glycolysis pathway. ConclusionGyp-L can inhibit glycolysis in HUVEC and OVCAR-3 cells through the EGFR/STAT3/HK2 pathway，thereby suppressing the occurrence and development of AS and OC.

ObjectiveTo construct a large language model （LLM）-based intelligent pre-consultation system for traditional Chinese medicine （TCM） to improve efficacy of clinical practice. MethodsA TCM large language model was fine-tuned using DeepSpeed ZeRO-3 distributed training strategy based on YAYI 2-30B. A weighted undirected graph network was designed and an agent-based syndrome differentiation model was established based on relationship data extracted from TCM literature and clinical records. An agent collaboration framework was developed to integrate the TCM LLM with the syndrome differentiation model. Model performance was comprehensively evaluated by Loss function， BLEU-4， and ROUGE-L metrics， through which training convergence， text generation quality， and language understanding capability were assessed. Professional knowledge test sets were developed to evaluate system proficiency in TCM physician licensure content， TCM pharmacist licensure content， TCM symptom terminology recognition， and meridian identification. Clinical tests were conducted to compare the system with attending physicians in terms of diagnostic accuracy， consultation rounds， and consultation duration. ResultsAfter 100 000 iterations， the training loss value was gradually stabilized at about 0.7±0.08， indicating that the TCM-LLM has been trained and has good generalization ability. The TCM-LLM scored 0.38 in BLEU-4 and 0.62 in ROUGE-L， suggesting that its natural language processing ability meets the standard. We obtained 2715 symptom terms， 505 relationships between diseases and syndromes， 1011 relationships between diseases and main symptoms， and 1 303 600 relationships among different symptoms， and constructed the Agent of syndrome differentiation model. The accuracy rates in the simulated tests for TCM practitioners， licensed pharmacists of Chinese materia medica， recognition of TCM symptom terminology， and meridian recognition were 94.09%， 78.00%， 87.50%， and 68.80%， respectively. In clinical tests， the syndrome differentiation accuracy of the system reached 88.33%， with fewer consultation rounds and shorter consultation time compared to the attending physicians （P＜0.01）， suggesting that the system has a certain pre- consultation ability. ConclusionThe LLM-based intelligent TCM pre-diagnosis system could simulate diagnostic thinking of TCM physicians to a certain extent. After understanding the patients' natural language， it collects all the patient's symptom through guided questioning， thereby enhancing the diagnostic and treatment efficiency of physicians as well as the consultation experience of the patients.

ObjectiveWith the epidermal growth factor receptor（EGFR）/Signal Transducers and Activators of Transcription（STAT3）/Hexokinase 2（HK2） signaling pathway in atherosclerosis （AS） and ovarian cancer （OC） as the entry point， this paper discusses the molecular mechanism of Gypenoside L （Gyp-L） treating AS and OC with different diseases， provides a new perspective and theoretical basis for TCM treating AS and OC with EGFR-STAT3-HK2 pathway， and enriches the scientific connotation of the theory of "cytoskeleton in the heart". MethodsCCK-8 was used to detect the proliferation of HUVEC and OVCAR-3 cells， in order to determine the intervention concentration for subsequent experiments. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. Western blot was used to detect the expression levels of relevant proteins. Furthermore， two cell models overexpressing EGFR were constructed and co treated with Gyp-L. HUVEC cells were divided into control， ox-LDL， OE-NC， OE-EGFR， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. OVCAR-3 cells were divided into control， OE-NC， OE-EGFR ， OE-NC+Gyp-L， and OE-EGFR+Gyp-L group. The colorimetric method was used to detect the NO content in HUVEC and the contents of pyruvate and LDH in two cell lines. Western blot was used to detect the expression levels of EGFR-STAT3-HK2 pathway related proteins. Cell cloning experiments and scratch experiments reflect the proliferation and migration ability of OVCAR-3 cells. ResultsGyp-L can significantly reduce the NO content of HUVEC and the pyruvate and LDH content of two cell lines （P<0.05）； Inhibit the proliferation and migration ability of OVCAR-3 cells； Reduce the expression levels of EGFR/STAT3/HK2 pathway related proteins in HUVEC and OVCAR-3 cell lines （P<0.05）， and inhibit the glycolysis pathway. ConclusionGyp-L can inhibit glycolysis in HUVEC and OVCAR-3 cells through the EGFR/STAT3/HK2 pathway，thereby suppressing the occurrence and development of AS and OC.

Objective To provide technical support for the formulation of scientific and reasonable supervision measures for enterprises engaged in the exploitation and utilization of ores with associated radionuclides in Guangxi Province, China. Methods A radionuclide analysis was performed on solid materials generated during production processes such as zirconium-titanium ore dressing and processing in multiple enterprises in Guangxi Province. The radiation levels of effluents was measured. Measurement and analysis were performed on the environmental air radon concentration levels and environmental γ-radiation dose rates at the factory boundaries of these enterprises and the surrounding environmental protection targets. Results The air absorption dose rate of γ radiation, the concentrations of radon and its daughters, and the radiation levels of surface water and aerosols at the factory boundaries and in the surrounding environment were all at normal levels. The specific activities of nuclides ²³⁸U, ²³²Th, and ²²⁶Ra in the raw ore, zirconium products, rutile products, and monazite products within the factory area were relatively high. The γ radiation air absorption dose rates in the corresponding workshops were also relatively high, with the zirconium-rutile workshop being the area with the highest values. Materials such as zirconium products, rutile, and monazite all showed a certain amount of radon exhalation. Conclusion The radiation level of tailings met the criteria of monitoring exemption, and the enterprises did not generate radioactive solid waste. Attention should be paid to the personal dose of the staff in areas with high radiation dose rates.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.

Objective: To explore glymphatic impairment in pediatric refractory epilepsy (RE) using multi-parameter magnetic resonance imaging (MRI), assess its relationship with white-matter (WM) abnormalities and clinical indicators, and preliminarily evaluate the performance of multi-parameter MRI in discriminating RE from drug-sensitive epilepsy (DSE). Materials and Methods: We retrospectively included 70 patients with DSE (mean age, 9.7 ± 3.5 years; male:female, 37:33) and 26 patients with RE (9.0 ± 2.9 years; male:female, 12:14). The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index as well as fractional anisotropy (FA), mean diffusivity (MD), and nodal efficiency values were measured and compared between patients with RE and DSE. With sex and age as covariables, differences in the FA and MD values were analyzed using tract-based spatial statistics, and nodal efficiency was analyzed using a linear model. Pearson’s partial correlation was analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the discrimination performance of the MRI-based machine-learning models through five-fold cross-validation. Results: In the RE group, FA decreased and MD increased in comparison with the corresponding values in the DSE group, and these differences mainly involved the callosum, right and left corona radiata, inferior and superior longitudinal fasciculus, and posterior thalamic radiation (threshold-free cluster enhancement, P < 0.05). The RE group also showed reduced nodal efficiency, which mainly involved the limbic system, default mode network, and visual network (false discovery rate, P < 0.05), and significantly lower DTI-ALPS index (F = 2.0, P = 0.049). The DTI-ALPS index was positively correlated with FA (0.25 ≤ r ≤ 0.32) and nodal efficiency (0.22 ≤ r ≤ 0.37), and was negatively correlated with the MD (-0.24 ≤ r≤ -0.34) and seizure frequency (r = -0.47). A machine-learning model combining DTI-ALPS, FA, MD, and nodal efficiency achieved a cross-validated ROC curve area of 0.83 (sensitivity, 78.2%; specificity, 84.8%). Conclusion Pediatric patients with RE showed impaired glymphatic function in comparison with patients with DSE, which was correlated with WM abnormalities and seizure frequency. Multi-parameter MRI may be feasible for distinguishing RE from DSE.

To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi‐target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.