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 investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

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.

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 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 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 This study aimed to investigate the expression of CTLA-4 and PD-L1 in pulmonary lympho-epithelial carcinoma(PLEC)and to explore their relationships with patient prognosis and with tumor-infiltrating lym-phocytes(TILs).Methods Fifty cases of PLEC were retrospectively collected,together with 23 samples of adjacent normal lung tissue.Immunohistochemistry was performed to detect CTLA-4 and PD-L1 expression in both PLEC and adjacent normal lung tissues,as well as to quantify CD4+and CD8+T-lymphocytes infiltration within the tumor micro-environment.CTLA-4,PD-L1,and the distributions of CD4+T cells and CD8+T cells were then correlated with the clinicopathological features of PLEC.Results The positive rate of CTLA-4 in PLEC was significantly higher than that in adjacent normal lung tissue(P＜0.05).PD-L1 expression differed significantly across TNM stages of PLEC(P＜0.05)and was positively correlated with TNM stages(r=0.31,P=0.03).CD4+and CD8+T-lymphocytes were pre-dominantly localized in the tumor stroma,with CD4+T cells density exceeding that of CD8+(P＜0.05).Within canc-er nests,CD8+T cells density was significantly higher than CD4+(P＜0.05).Conclusion Both PD-L1 and CTLA-4 are frequently expressed in PLEC,suggesting they represent potential immunotherapeutic targets.In the PLEC micro-environment,lymphocytes primarily infiltrated the stromal compartment,and CD4+T cells are more abundant than CD8+T cells in that locale.

BACKGROUND:The micro/nanostructured gradient biomimetic surface of implant materials can simulate the structure of the extracellular environment in human bone tissue,thereby achieving perfect bone integration function.However,further research is needed on the mechanisms by which the surface microstructure of bone implant materials regulates cell function and promotes osteogenesis. OBJECTIVE:To analyze the effect of titanium sheet microstructure surface on osteogenic differentiation of MC3T3-E1 osteoblasts. METHODS:(1)At a constant voltage of 5 V or 20 V,nanotube arrays of different diameters were prepared on the surface of titanium sheets by acid etching and anodic oxidation techniques,and were recorded as group R5 and group R20,respectively.The surface morphology,roughness,and hydrophilicity of pure titanium sheet(without acid etching or anodizing treatment)were measured in group R5 and group R20.(2)MC3T3-E1 osteoblasts of logarithmic growth stage were inoculated on the surface of pure titanium sheets,R5 group and R20 group respectively.After 24 hours of osteogenic induction culture,the expression of mechanical sensitive channel protein 1 was analyzed by RT-PCR and immunofluorescence staining.Osteoblast inducible base with or without the mechanosensitive channel protein 1 activator Yada1 was added,and alkaline phosphatase staining was performed after 7 days of culture.Alizarin red staining was performed after 14 days of culture. RESULTS AND CONCLUSION:(1)The surface of pure titanium sheets was smooth under scanning electron microscope.Relatively uniform and orderly nanotube arrays with average diameters of about 30 nm and 100 nm were observed on the surface of titanium sheets of groups R5 and R20,respectively.The results of scanning electron microscope were further verified by atomic force microscopy.The surface roughness of titanium sheet of group R5 was higher than that of pure titanium(P<0.05),and the water contact angle was lower than that of pure titanium(P<0.05).The surface roughness of titanium sheet in group R20 was higher than that in group R5(P<0.05),and the water contact angle was lower than that in group R5(P<0.05).(2)RT-PCR and immunofluorescence staining showed that the expression of mechanosensitive channel protein 1 in group R5 was higher than that in pure titanium group(P<0.05),and the expression of mechanosensitive channel protein 1 in group R20 was higher than that in group R5(P<0.05).Under the osteogenic induction,compared with the condition without Yada1,there were no significant changes in the activity of alkaline phosphatase and the deposition of calcified nodules in pure titanium group after Yada1 addition,while the activity of alkaline phosphatase and the deposition of calcified nodules in groups R5 and R20 after Yada1 addition were significantly increased(P<0.05).With or without Yada1,the alkaline phosphatase activity and calcified nodule deposition in group R5 were higher than those in pure titanium group(P<0.05),and the alkaline phosphatase activity and calcified nodule deposition in group R20 were higher than those in group R5(P<0.05).(3)The results show that the surface microstructure of titanium sheet can promote the osteogenic differentiation of osteoblast MC3T3-E1 by activating mechanosensitive channel protein 1.

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.