Wilson disease （WD） is one of the few treatable neurogenetic disorders. Currently， Western medicine remains the main treatment method for WD， while since the 1990s， multiple studies conducted by Professor Yang Renmin and his team have shown that traditional Chinese medicine （TCM） also has a favorable therapeutic effect. Based on the principle of low-copper diet for WD， this article systematically elaborates on the advantages， limitations， and key considerations of current Western medicine therapies （pharmacotherapy， liver transplantation， and splenectomy） and reviews the research findings of TCM in China， especially the wide application of Gandou Decoction in clinical practice. Studies have shown that Gandou Decoction can effectively improve neurological symptoms， protect hepatic and renal function， and avoid the adverse drug reactions associated with metal chelating agents， and therefore， it can be used an effective long-term adjuvant therapy for WD. It should be noted that symptoms and signs should be considered in integrated traditional Chinese and Western medicine therapy for WD， and high-copper TCM drugs should be avoided to prevent deterioration.

Objective:To discuss the effect of long non-coding RNA(lncRNA)DUXAP8 in exosomes(Exo)derived from the lung cancer A549 cells on the growth and immune escape of the lung cancer cells,and to clarify the mechanism.Methods:The human lung cancer cell line A549 was cultured,and its exosomes were extracted and identified.The A549 cells were treated with PKH67-labeled Exo to observe the uptake of Exo by A549 cells.Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression level of lncRNA DUXAP8 in A549 cells before and after Exo treatment.The A549 cells were divided into control group(no treatment),Exo group(A549 cells treated with Exo),Exo+sh-NC group(A549 cells treated with Exo and then transfected with sh-NC),and Exo+sh-DUXAP8 group(A549 cells treated with Exo and then transfected with sh-DUXAP8).RT-qPCR method was used to detect the expression level of lncRNA DUXAP8 in A549 cells in various groups;colony formation assay was used to detect the colony formation abilities of the A549 cells in various groups;5-ethynyl-2'-deoxyuridine(EdU)staining method was used to detect the proliferation abilities of the A549 cells in various groups.After co-culturing A549 cells in various groups with human peripheral blood lymphocytes,flow cytometry was used to detect the percentages of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in various groups;3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)method was used to detect the killing rates of human peripheral blood lymphocytes on the A549 cells in various groups.Results:The diameter of Exo vesicles was 50-150 nm,and the exosome-specific marker proteins cluster of differentiation 63(CD63),cluster of differentiation 9(CD9),tumor susceptibility gene 101(TSG101),and heat shock protein 70(HSP70)were positively expressed,indicating successful exosome extraction.A549 cells efficiently took up PKH67-labeled Exo.The RT-PCR results showed that compared with A549 cells cultured alone,the expression level of lncRNA DUXAP8 in the A549 cells was increased after treatment with Exo derived from A549 cells(P<0.05).compared with control group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the expression level of lncRNA DUXAP8 in the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there were no significant difference in the expression level of IncRNA DUXAP8 in the cells in Exo+sh-NC group(P>0.05).The colony formation assay results showed that compared with control group,the number of colony formation of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the number of colony formation of the A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the number of colony formation of the A549 cells in Exo+sh-NC group(P>0.05).The EdU staining results showed that compared with control group,the EdU-positive rate of the A549 cells in Exo group was increased(P<0.05);compared with Exo group,the EdU-positive rate in A549 cells in Exo+sh-DUXAP8 group was decreased(P<0.05),while there was no significant difference in the EDU-positive rate in the cells in Exo+sh-NC group(P>0.05).The flow cytometry results showed that compared with control group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo group was decreased(P<0.05);compared with Exo group,the percentage of activated CD8+T lymphocytes in the human peripheral blood lymphocytes in Exo+sh-DUXAP8 group was increased(P<0.05),while there was no significant difference in the percentage of activated CD8+T lymphaytes in Exo+sh-NC group(P>0.05).The MTT assay results showed that compared with control group,the killing rate of human peripheral blood lymphocytes on the A549 cells in Exo group was decreased(P<0.05);compared with Exo group,the killing rate of human peripheral blood lymphocytes on A549 cells in Exo+sh-DUXAP8 group was increased(P<0.05),while no significant difference was observed in Exo+sh-NC group(P>0.05).Conclusion:The lncRNA DUXAP8 in exosomes derived from the lung cancer A549 cells promotes the proliferation of lung cancer cells and tumor immune escape.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective:To analyze the application effect of the case-based learning (CBL), lecture-based learning (LBL) and seminar three-track stereoscopic model in the teaching of health management for chronic diseases.Methods:In this non-randomized controlled trial, a total of 70 five-year clinical medicine major undergraduate students were continuously selected as the research subjects in the Air Force Medical University during 2023-2024 year. The students enrolled the chronic disease health management course. Thirty-five cases in 2023 were assigned to the control group, while 35 cases in 2024 were assigned to the experimental group. The control group were taught by the traditional teaching method, while experimental group were taught with a combined model of CBL, LBL, and Seminar. The number of class hours for both groups were 30, with a class frequency of 2 class hours per week. The intervention period began with the first class and ended after the last class, totaling 15 weeks. The general information, medical professional courses and basic knowledge of chronic disease health management scores in the two groups were collected before intervention. The learning effect and satisfaction rate were evaluated through teaching satisfaction score, assessment assignments, practical ability score and excellent rate, autonomous learning ability score at 15 weeks after the intervention.Results:Among the 70 participants, 37 were male and 33 were female, with a mean age of (21.00±0.27) years. Before the intervention, there was no statistically significant differences in the general information, medical professional courses and basic knowledge of chronic disease health management scores between the two groups (all P>0.05). Fifteen weeks after the intervention, the experimental group had significantly higher scores in teaching content score, teaching method score, assessment assignment, final grade, practical ability scores, excellent rate of practical ability, self-management ability score, information literacy score, and learning cooperation ability score when compared to those in the control group [(93.3±6.9) vs (80.1±7.8) points, (97.1±6.3) vs (81.0±9.6) points, (91.1±7.8) vs (80.1±8.9) points, (92.9±9.4) vs (81.8±9.8) points, (91.3±7.6) vs (80.3±8.7) points, 54.3% vs 22.9%, (27.3±4.8) vs (22.8±6.8) points, (26.9±3.9) vs (20.8±4.1) points, (35.9±8.1) vs (28.9±7.1) points] (all P<0.05). Conclusion:Implementing of CBL, LBL, and Seminar teaching model in the chronic disease health management curriculum significantly enhances teaching effectiveness and improves students' overall competencies.

Objective:To explore the value of quantitative parameters of diffusion weighted imaging (DWI) combined with dynamic enhanced magnetic resonance imaging (DCE-MRI) in predicting the efficacy of neoadjuvant chemotherapy for locally advanced breast cancer (LABC) .Methods:A total of 97 patients with LABC admitted to the hospital from Mar. 2020 to Mar. 2023 were studied and received neoadjuvant chemotherapy to evaluate the therapeutic effect, and DWI and DCE-MRI scans were performed before and after treatment. The difference of DWI and DCE-MRI quantitative parameters before treatment in patients with different therapeutic effects was compared, and the correlation between the difference of DWI and DCE-MRI quantitative parameters and therapeutic effect was analyzed. The predictive value of quantitative parameters of DWI and DCE-MRI before treatment was analyzed. The quantitative parameters of DWI and DCE-MRI in patients with different pathological reactions were compared before treatment, and the quantitative parameters of DWI and DCE-MRI were compared before and after treatment.Results:The apparent diffusion coefficient (ADC) of patients with effective chemotherapy before treatment was higher, but transport constant (Ktrans) , extracellular space volume percentage (Ve) and rate constant (Kep) were lower ( t=5.0, 3.27, 3.55, 3.89, P < 0.05) ; Spearman correlation analysis showed that ADC was positively correlated with chemotherapy efficacy before treatment (r=0.66; P < 0.05) , while Kep, Ve, Ktrans were negatively correlated with it (r=-0.58, -0.47, -0.60; P < 0.05) ; ROC curves showed that the area under the curve (AUC) values of ADC, Kep, Ve and Ktrans in predicting chemotherapy efficacy before treatment were 0.771, 0.797, 0.664 and 0.715, respectively, while the combined AUC value of each indicator was 0.832; Compared with patients with non-significant pathological response, ADC before treatment was higher in patients with significant pathological response, Kep, Ve and Ktrans were lower ( t=4.46, 3.32, 3.60, 3.95, P < 0.05) ; Compared with before treatment, ADC value increased after treatment, while Kep, Ve and Ktrans decreased ( t=8.77, 6.22, 9.34, 10.26, P < 0.05) . Conclusion:Quantitative parameters of DWI and DCE-MRI can reflect the changes in the condition of patients with locally advanced neoadjuvant chemotherapy, and the combination of the two can help to improve the predictive value of chemotherapy efficacy in patients.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Objective:To investigate the effect of Gexia Zhuyu decoction on Toll-like receptor 4 (TLR4)/Nuclear factor-kappaB (NF-κB) signaling pathway on ulcerative colitis and intestinal mucosal barrier.Methods:A total of 86 cases of ulcerative colitis admitted to Xi′an Traditional Chinese Medicine (TCM) Hospital from March 2019 to July 2023 were prospectively included and divided into observation group and control group according to random number table method, with 43 cases in each group. The control group was treated with mesalazine enteric-coated tablets; The observation group was treated with mesalazine enteric-coated tablets combined with Gexia Zhuyu decoction for removing stasis. The clinical efficacy of the two groups was compared in terms of TCM syndrome score, intestinal mucosal barrier function index [diamine oxidase (DAO), D-lactic acid (D-LA)], TLR4/NF-κB signaling pathway expression and inflammatory factor index [interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α)] before and after treatment. The occurrence of adverse reactions was also compared.Results:The total effective rate of observation group was higher than that of control group (χ 2=4.074, P=0.044). Before treatment, there was no significant difference in TCM syndrome scores between the two groups (all P>0.05). After treatment, the TCM syndrome scores of both groups were lower than those before treatment (all P<0.05), and the TCM syndrome scores of the observation group were lower than those of the control group (all P<0.05). Before treatment, there were no significant differences in D-LA and DAO levels between the two groups (all P>0.05). After treatment, the levels of D-LA and DAO in both groups were lower than before treatment (all P<0.05), and the levels of D-LA and DAO in the observation group were lower than those in the control group (all P<0.05). After treatment, the mRNA expressions of TLR4 and NF-κB in both groups were decreased compared with those before treatment, and the mRNA expressions of TLR4 and NF-κB in the observation group were lower than those in the control group (all P<0.05). After treatment, the levels of IL-6, IL-8 and TNF-α in both groups were decreased compared with those before treatment (all P<0.05), and the levels of IL-6, IL-8 and TNF-α in the observation group were lower than those in the control group (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (χ 2=2.346, P=0.126). Conclusions:The application of Gexia Zhuyu decoction in the treatment of ulcerative colitis can not only effectively improve the clinical symptoms, signs and intestinal mucosal barrier function, but also improve the inflammatory response by mediating TLR4/NF-κB signaling pathway.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations. Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits. Results: Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01). Conclusion Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.