[摘 要] 目的：探究甘氨胆酸（GCA）对肺腺癌A549细胞移植瘤小鼠放射治疗敏感性的影响及其机制。方法：建立A549人肺腺癌细胞裸鼠移植瘤模型，随机分为移植瘤对照组（对照组）、GCA组、放疗组（RT组）和GCA + 放疗组（GCA + RT组）。RT组和GCA + RT组接受单次10  Gy照射，GCA组及GCA + RT组连续7 d每日灌胃GCA 280  mg/kg。间隔2 d测量1次移植瘤体积，末次给药后处死小鼠并取移植瘤组织，检测移植瘤组织中超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GSH-Px）活性，qPCR法和WB法分别检测放疗关键基因（MCM6、ITGA6、CASP3等）mRNA和蛋白表达水平，H-E染色观察移植瘤组织的形态变化。通过GEO（GSE276500、GSE294906、GSE218171）及TCGA数据库数据验证放疗关键基因。结果：GCA单用对瘤体生长有一定抑制作用，但联合放疗的GCA + RT组相比单纯放疗组表现出放疗抵抗的效应（P < 0.05）。GCA处理显著提高移植瘤组织SOD活性（P < 0.01）、降低GSH-Px活性（P < 0.01），提示GCA可改变移植瘤抗氧化酶平衡，减弱放疗诱导的氧化应激。GCA干预上调移植瘤组织中MCM6与ITGA6 mRNA表达、下调CASP3 mRNA表达（均P < 0.05）。GCA + RT组移植瘤组织中的MCM6蛋白表达显著高于对照组（P < 0.05）。H-E染色显示，GCA组部分瘤组织坏死，而GCA + RT组坏死组织面积较RT组有所缩小。GEO和TCGA数据库验证支持MCM6、ITGA6高表达与放疗抵抗和预后不良相关。结论：GCA通过增强SOD活性、降低GSH-Px活性并上调ITGA6、MCM6的表达改变氧化应激与关键信号网络，从而削弱A549移植瘤对放疗的敏感性。

Objective To investigate the potential protective mechanism of tanshinone ⅡA against acetaminophen （APAP）-induced acute liver injury. Methods Thirty mice were randomly divided into the normal group, model group, low-dose tanshinone ⅡA group （5 mg/kg）, medium-dose tanshinone ⅡA group （10 mg/kg） and high-dose tanshinone ⅡA group （20 mg/kg）. All groups were intragastrically administered once daily for 7 consecutive days. On the 7th day, except for the normal group, mice in the remaining groups were intraperitoneally injected with 400 mg/kg APAP to establish the acute lung injury （ALI） model. The protective effect of tanshinone ⅡA was evaluated based on the liver weight ratio, the levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）, and HE staining. Targets of tanshinone ⅡA were predicted by the Traditional Chinese Medicine Systems Pharmacology （TCMSP）, and a shared target protein-protein interaction （PPI） network was constructed by Search Tool for the Retrieval of Interacting Genes/Proteins （STRING） 11.5 in combination with disease targets from GeneCards. The Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed by Database for Annotation, Visualization and Integrated Discovery （DAVID）, and the component-target-pathway network was constructed. The molecular docking between tanshinone ⅡA and the core targets was performed by AutoDock and visualised. Results Compared with the normal group, the liver weight ratio and serum aminotransferase level of mice with acute liver injury were significantly elevated （P<0.05）, and the pathological injury of liver tissue was obvious. After tanshinone ⅡA treatment, the above index were significantly reduced （P<0.05）, and the pathological injury was significantly improved. Further network pharmacological analysis was carried out and found that KEGG pathway enrichment analysis focused on IL-17 signaling pathway and tumor necrosis factor （TNF） signaling pathway, etc. In addition, the PPI core network showed that the key targets of tanshinone ⅡA to ameliorate acute liver injury mainly included TP53, AKT1, SRC, TNF and JUN. The molecular docking results showed that tanshinone ⅡA had high binding scores with the targets of MMP9, NFKB1, TNF, EP300 and SMAD3; and was able to bind to the targets of TP53, AKT1, SRC and JUN. Conclusion Tanshinone ⅡA may play a protective role against acute liver injury by regulating genes such as AKT1, JUN and TNF, and participating in signaling pathways such as TNF and IL-17.

ObjectiveTo investigate the therapeutic effect of proanthocyanidins （PC） on rats with type 2 diabetes mellitus （T2DM） complicated with cognitive impairment （CI） and to explore its potential mechanism by inhibiting the NOD-like receptor family pyrin domain-containing protein 3 （NLRP3）/cysteine-aspartic acid protease-1 （Caspase-1） pathway. MethodsA T2DM rat model was established by high-fat diet combined with intraperitoneal streptozotocin （STZ） injection. Thirty-six diabetic rats complicated with CI were screened by Morris water maze test and randomly divided into model group， PC low-dose （50 mg/kg） group， PC medium-dose （100 mg/kg） group， and PC high-dose （200 mg/kg） group. Another 9 normal rats served as the normal control group. Each group was administered with the corresponding doses of PC or an equal volume of distilled water by gavage for 8 weeks. After the intervention， spatial learning and memory abilities were evaluated using the Morris water maze test. Fasting blood glucose， body weight， and organ coefficients were measured. Pathological changes in the hippocampus were observed by hematoxylin-eosin （HE） staining. Reactive oxygen species （ROS） levels， as well as levels of inflammatory cytokines tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue， were detected by enzyme-linked immunosorbent assay （ELISA）. The protein expression levels of NLRP3， Caspase-1， IL-1β， and IL-18 in the hippocampus were determined by Western blot. ResultsCompared with the normal control group， the model group exhibited significantly increased blood glucose and decreased body weight （P<0.05）. In the Morris water maze test， the model group showed prolonged escape latency， fewer platform crossings， and lower percentages of time and path length in the target quadrant （P<0.05）. Disordered arrangement and pyknotic nuclei were observed in hippocampal neurons. ROS and the levels of TNF-α and IL-1β were elevated， and the protein expression levels of NLRP3， Caspase-1， IL-1β and IL-18 were upregulated （P<0.05）. Compared with the model group， all PC-treated groups， especially the high-dose group， presented dose-dependent improvements in the above indicators， including reduced blood glucose （P<0.05）， improved spatial memory performance in the Morris water maze （P<0.01）， alleviated hippocampal pathological damage， decreased ROS and inflammatory cytokine levels （P<0.05）， and significantly downregulated expression of NLRP3/Caspase-1 pathway-related proteins （P<0.05）. ConclusionProanthocyanidins can ameliorate glycolipid metabolic disorder， visceral organ injury as well as cognitive dysfunction in T2DM rats. The underlying mechanism may be associated with reduced hippocampal ROS levels， inhibition of the NLRP3/Caspase-1 signaling pathway， and attenuated neuroinflammation in the hippocampus， with the optimal effect observed at a dose of 200 mg/kg.

Objective:To analyze the effects of biodegradable-polymer sirolimus-eluting stents (BP-SES) and durable polymer sirolimus-eluting stents (DP-SES) implantation on serum endothelin 1 levels and the incidence of coronary restenosis in patients with coronary heart disease (CHD).Methods:A total of 114 patients with CHD admitted to the First People's Hospital of Xianyang in Shaanxi Province from May 2022 to January 2024 were selected. According to the principle of comparable baseline characteristics between groups, patients were divided into two groups by random number table method, with 57 cases in each group. After pretreatment of diseased vessels, DP-SES group underwent implantation of DP-SES with appropriate length and diameter, while BP-SES group underwent implantation of BP-SES with appropriate length and diameter. After implantation, non-compliant balloons were used for in-stent post-dilation. Comparisons of vascular endothelial function, levels of inflammatory factors and hemodynamic indicators before operation and at 6 months between groups were made postoperatively, also, the incidence rates of major adverse cardiovascular events (MACE) and coronary restenosis within 6 months were also compared. Measurement data with normal distribution was expressed as “xˉ±s”, independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:At 6 months after surgery, the levels of endothelin 1 and VEGF were lower in BP-SES group compared to DP-SES group,[(72±5) ng/L vs. (77±7) ng/L, (147±25) ng/L vs. (157±27) ng/L, t=3.76, P<0.001, t=2.16, P=0.033]. The level of nitric oxide was higher in BP-SES group compared to DP-SES group [(79±7) μmol/L vs. (76±8) μmol/L, t=2.46, P<0.001]. At 6 months after surgery, the levels of TNF-α, IL-1 and CRP in DP-SES group were higher than those before surgery, and were all higher compared to BP-SES group[(81±5) ng/L vs. (75±5) ng/L, (159±18) ng/L vs. (151±16) ng/L, (31±4) mg/L vs. (29±3) mg/L, t=6.87, P<0.001, t=2.24, P=0.027, t=2.51, P=0.014]. At 6 months after surgery, the level of whole blood viscosity and plasma viscosity in both group were lower than those before surgery, and the level of Hct in BP-SES group was lower than those before surgery, the differences were statistically significant ( P<0.001), while the differences between groups were not statistically significant( P>0.05). The difference of incidence rates of MACE and coronary restenosis within 6 months between groups before surgery and 6 months after surgery were not statistically significant [7.0%(4/57) vs. 12.3%(7/57), χ2=0.91, P=0.341; 3.7%(2/57) vs. 8.3%(5/57), χ2=0.61, P=0.443]. Conclusion:Both BP-SES implantation and DP-SES implantation could effectively restore coronary blood supply, and are highly safe. However, the former can reduce damage to vascular wall and better improve endothelial function in patients.

Objective:To evaluate the diagnostic value of MRI findings in differentiating between tophus and giant cell tumors of the tendon sheath (GCTTS) in the knee.Methods:The study was a case-control study. The clinical and MRI data of patients diagnosed with knee tophus or GCTTS was retrospectively analyzed at the Affiliated Hospital of Qingdao University from September 2018 to September 2024. The study included 23 cases of tophus and 22 cases of GCTTS. MRI sequences, including T 1WI, fat-suppressed T 2WI, and proton density weighted imaging, were evaluated. Parameters including lesion signal intensity and homogeneity, margin, maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, synovial hyperplasia, joint effusion, and periarticular soft tissue swelling were recorded. Independent sample t-tests, χ2 tests, or Fisher exact tests were used to compare MRI findings between the two groups. Multivariate logistic regression was performed to identify independent predictive factors. Results:Significant differences in terms of maximum diameter, location (inside or outside the synovial cavity), ligament/tendon involvement, ligament/tendon parenchymal changes, adjacent bone erosion, bone marrow edema, and periarticular soft tissue swelling between the two groups were found (all P<0.05). No significant differences for other parameters were observed (all P>0.05). Lesion location and ligament/tendon parenchymal involvement demonstrated the highest sensitivity and specificity for distinguishing the two diseases. The sensitivity and specificity values for lesion location were 0.78 and 0.95. The sensitivity and specificity values for ligament/tendon involvement were 0.78 and 1.00. Multivariate logistic regression identified lesion location (inside or outside the synovial cavity) as an independent predictor for differentiating tophus from GCTTS ( OR=31.48, 95% CI 1.58-625.69, P=0.024). Conclusion:The location of the lesion (inside or outside the synovial cavity) and involvement of ligament/tendon parenchyma are critical factors in differentiating knee tophus from GCTTS. Additionally, lesion location serves as an independent predictor for distinguishing between the two conditions.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To analyze the effects of biodegradable-polymer sirolimus-eluting stents (BP-SES) and durable polymer sirolimus-eluting stents (DP-SES) implantation on serum endothelin 1 levels and the incidence of coronary restenosis in patients with coronary heart disease (CHD).Methods:A total of 114 patients with CHD admitted to the First People's Hospital of Xianyang in Shaanxi Province from May 2022 to January 2024 were selected. According to the principle of comparable baseline characteristics between groups, patients were divided into two groups by random number table method, with 57 cases in each group. After pretreatment of diseased vessels, DP-SES group underwent implantation of DP-SES with appropriate length and diameter, while BP-SES group underwent implantation of BP-SES with appropriate length and diameter. After implantation, non-compliant balloons were used for in-stent post-dilation. Comparisons of vascular endothelial function, levels of inflammatory factors and hemodynamic indicators before operation and at 6 months between groups were made postoperatively, also, the incidence rates of major adverse cardiovascular events (MACE) and coronary restenosis within 6 months were also compared. Measurement data with normal distribution was expressed as “xˉ±s”, independent sample t-test was used on comparison between groups, paired t-test was used for intra-group comparisons before and after treatment. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Results:At 6 months after surgery, the levels of endothelin 1 and VEGF were lower in BP-SES group compared to DP-SES group,[(72±5) ng/L vs. (77±7) ng/L, (147±25) ng/L vs. (157±27) ng/L, t=3.76, P<0.001, t=2.16, P=0.033]. The level of nitric oxide was higher in BP-SES group compared to DP-SES group [(79±7) μmol/L vs. (76±8) μmol/L, t=2.46, P<0.001]. At 6 months after surgery, the levels of TNF-α, IL-1 and CRP in DP-SES group were higher than those before surgery, and were all higher compared to BP-SES group[(81±5) ng/L vs. (75±5) ng/L, (159±18) ng/L vs. (151±16) ng/L, (31±4) mg/L vs. (29±3) mg/L, t=6.87, P<0.001, t=2.24, P=0.027, t=2.51, P=0.014]. At 6 months after surgery, the level of whole blood viscosity and plasma viscosity in both group were lower than those before surgery, and the level of Hct in BP-SES group was lower than those before surgery, the differences were statistically significant ( P<0.001), while the differences between groups were not statistically significant( P>0.05). The difference of incidence rates of MACE and coronary restenosis within 6 months between groups before surgery and 6 months after surgery were not statistically significant [7.0%(4/57) vs. 12.3%(7/57), χ2=0.91, P=0.341; 3.7%(2/57) vs. 8.3%(5/57), χ2=0.61, P=0.443]. Conclusion:Both BP-SES implantation and DP-SES implantation could effectively restore coronary blood supply, and are highly safe. However, the former can reduce damage to vascular wall and better improve endothelial function in patients.

Objective The mouse autologous tumor model H22 is more valuable for tumor immunological-related research.This paper aims to establish mouse hepatic tumor cell line(H22-luc2-tdT)that stably express the tan-dem-dimer tomato(tdTomato)and luciferase genes.Establish an in vivo imaging model of cell line derived trans-planted tumors.Methods Using transplanted H22 tumor tissue,primary culture and continuous passage in vitro were performed to establish a continuous cell line.Cell proliferation,chromosome analysis,organoid culture,tumorigenicity,HE and ICH of aFP,CK7,CK15 were performed to charaterize the cell line.Then the luc2-tdT plasmid was transfected into H22 cells of P22,flow cytometry and in vitro/in vivo imaging were employed to screen and verify fluorescence expression.Mycoplasma detection and species verification of the established cell lines were performed.Results The H22 cells had been continuously passaged over 50 times.The cells of passsge 22(P22)were transplanted subcutaneously and intraperitoneally into C57 and Kunming mice,with a 100%tumor formation.The HE morphology of subcutaneous transplanted tumor were consistent with the original tumor.CK+/AFP+proved that it was of liver cancer origin.The H22 cells were hypo-triploid with a modal number of 40-44 chromosomes and telocentromeres,verifing its mouse origin.The latent phase for in vitro growth of H22 lasted from d0 to d3,while the exponential phaes d3 to d5,and reach plateou at d6.Successful transfection of H22 cells with the luc2-tdT were observed with in vitro/in vivo 100%fluorescence positivity,thus named H22-luc2-tdT.The transplanted tumor tissue of H22 cells could be primarily cultured to form organoids.The detection of Mycoplasma was negative,and its mouse origin confirmed by PCR.Conclusions H22 and H22-luc2-tdT cell lines are established and characterized,which can be used for the establishment and application of in vitro and in vivo liver cancer research and metastatic cell tracking.These cell lines are deposited at and can obtain from the National Biomedical Cell Resource Center(http://www.cellresource.cn).

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

OBJECTIVES: We propose a low-dose CT image restoration method based on central guidance and alternating optimization (FedGP). METHODS: The FedGP framework revolutionizes the traditional federated learning model by adopting a structure without a fixed central server, where each institution alternatively serves as the central server. This method uses an institution-modulated CT image restoration network as the core of client-side local training. Through a federated learning approach of central guidance and alternating optimization, the central server leverages local labeled data to guide client-side network training to enhance the generalization capability of the CT imaging model across multiple institutions. RESULTS: In the low-dose and sparse-view CT image restoration tasks, the FedGP method showed significant advantages in both visual and quantitative evaluation and achieved the highest PSNR (40.25 and 38.84), the highest SSIM (0.95 and 0.92), and the lowest RMSE (2.39 and 2.56). Ablation study of FedGP demonstrated that compared with FedGP(w/o GP) without central guidance, the FedGP method better adapted to data heterogeneity across institutions, thus ensuring robustness and generalization capability of the model in different imaging conditions. CONCLUSIONS FedGP provides a more flexible FL framework to solve the problem of CT imaging heterogeneity and well adapts to multi-institutional data characteristics to improve generalization ability of the model under diverse imaging geometric configurations.
Tomography, X-Ray Computed/methods* ; Humans ; Radiation Dosage ; Image Processing, Computer-Assisted/methods* ; Algorithms