Uveal melanoma(UM)is the most common primary intraocular malignancy in adults, characterized by high invasiveness and unique metastatic biological features. Although local treatments(such as proton beam therapy and brachytherapy)can effectively control the primary lesion, approximately 50% of patients eventually develop distant metastasis, with the liver being the primary target organ(occurring in 90% of cases). This highlights a paradigm shift in treatment focus from mere local control to systemic prevention and management. For metastatic UM(mUM), current treatment strategies encompass biomarker-guided molecular targeted therapy, immunotherapy(including Tebentafusp, vaccines, and oncolytic virus therapy), and liver-directed therapy. Focusing on the synergy between local and systemic prevention and control, this article systematically elaborates on the precision local treatment for primary UM, the decision-making pathway for systemic treatment of metastatic UM based on molecular subtyping, the integration of local and systemic therapies for liver metastases, and the translational value of nanomedicine in addressing therapeutic bottlenecks. It provides insights for optimizing clinical management of mUM and developing novel therapeutic strategies.

[摘 要] 目的：探究外周血1型辅助性T细胞（Th1）/Th2/Th17细胞相关细胞因子IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α、IL-17A对Ⅲ~Ⅳ期肺鳞状细胞癌（LSCC）患者一线免疫治疗联合化疗疗效和预后的预测价值及其动态变化的意义。方法：回顾性分析2020年1月至2023年12月在内蒙古医科大学附属医院接受一线免疫治疗联合化疗的58例Ⅲ~Ⅳ期LSCC患者的临床资料，采集基线及治疗2、4、6周期后和疾病进展时的外周血，用流式细胞术检测Th1/Th2/Th17细胞分泌的细胞因子水平，用受试者工作特性曲线（ROC）确定各细胞因子基线的最佳截断值，据此将患者分为高、低表达组；根据RECIST 1.1标准，将患者分为客观缓解（ORR）[完全缓解（CR） + 部分缓解（PR）]组、非ORR[（疾病稳定（SD） + 疾病进展（PD）]组、疾病控制（DCR）（CR + PR + SD）组和非DCR（即PD）组；根据PD-L1表达评分将患者分为PD-L1 ≥ 1%组和PD-L1 < 1%或未知组。比较组间疗效的差异；分析临床病理特征与疗效的相关性；用广义估计方程（GEE）评估细胞因子动态变化与疗效的关系；用Kaplan-Meier法绘制生存曲线，Log-Rank检验比较组间差异，COX比例风险回归模型进行单因素及多因素预后分析。结果：IL-2和IFN-γ高表达组患者的客观缓解率（ORR）显著高于低表达组患者（P < 0.001）。IL-2、IFN-γ高表达组和IL-10、TNF-α低表达组患者的疾病控制率（DCR）均显著高于对应低/高表达组（P < 0.001）。PD-L1 ≥ 1%组DCR显著高于PD-L1 < 1%或未知组（P < 0.001）。动态分析显示，在4周期及6周期时，有效组患者血清中IL-6表达水平显著低于无效组（P < 0.05），控制组IL-6表达水平显著低于未控制组（P < 0.001）；治疗前及6周期时有效组IFN-γ表达水平显著高于无效组（P < 0.05），治疗前控制组IFN-γ表达水平显著高于未控制组（P < 0.05）。生存分析显示，IL-2低表达组、IL-10高表达组、TNF-α高表达组和IFN-γ低表达组患者的中位PFS显著缩短（均P < 0.05）。COX多因素分析证实，治疗前IL-2 < 2.45 pg/mL和IL-10 ≥ 3.52 pg/mL 是PFS的独立危险因素。结论：外周血Th1/Th2/Th17细胞相关细胞因子的基线水平及动态变化对Ⅲ~Ⅳ期LSCC患者一线免疫治疗联合化疗的疗效和预后具有预测价值。

Background Ozone (O₃) is a major air pollutant. The existing monitoring system has uneven distribution of sites, insufficient coverage in underdeveloped areas, and low temporal resolution, making it difficult to obtain hourly data. This limits the dynamic identification of pollution and the formulation of prevention and control strategies. Objective To construct an hourly O₃ concentration estimation model based on ensemble machine learning, aiming to improve the accuracy of pollution exposure assessment and explore O₃ health impacts. Methods This study integrated land use regression modeling with modern machine learning techniques, employing random forest and XGBoost algorithms to construct base models, and stacking integration using non-negative least squares. The ensemble model was trained and validated across China using high-resolution, multi-source geographic data (e.g., meteorologicaldata, population density, land cover types, and aerosol optical thickness). It was tested in Taiyuan City, combined with a distributed lag non-linear model to analyze the association between O₃ and emergency admissions. Results The constructed ensemble model performed well in predicting O₃ concentration, with a higher coefficient of determination (R²) and a lower root-mean-square deviation (RMSE) compared to the single models. The R² improved from 0.90 to 0.92, and the RMSE decreased from 11.41 to 10.62, enhancing both prediction accuracy and generalization ability. In the application to Taiyuan City, the model successfully imputed the hourly-level data for the entire year. The distributed lag non-linear model analysis revealed that the relative risk (RR) values for the 6th to 8th days following O₃ exposure were 1.14 (95%CI: 1.01, 1.29), 1.16 (95%CI: 1.02, 1.31), and 1.14 (95%CI: 1.01, 1.29), respectively, which were significantly higher than 1, indicating a significant lagged association (lagged 6-8 d) between O₃ and the number of emergency room visits. Conclusion A high-precision, hourly-level O₃ concentration estimation model is successfully constructed by combining the land use regression model with an ensemble machine learning approach to provide a scientific basis for environmental policy formulation and public health intervention. The application of the model verifies its generalization ability and practical application value, which can provide a new technical framework for subsequent environmental health research.

Objective To investigate the activity concentrations of natural radionuclides in drinking water (tap water and well water) in urban and rural areas of Hohhot, assess the safety of drinking water, and to provide data support for local drinking water radioactivity monitoring and management. Methods Representative samples of well water and tap water were collected from nine banners/counties/districts in Hohhot. Activity concentrations were measured using a low-background gross α/β counter, an α spectrometer, inductively coupled plasma mass spectrometry, and a radium/radon analyzer. Results A total of nine tap water samples and nine well water samples were analyzed. For the tap water samples, gross α activity concentrations ranged from 0.093 to 0.193 Bq/L, gross β from 0.091 to 0.225 Bq/L, uranium mass concentrations from 2.32 to 10.36 μg/L, thorium mass concentrations from 0.09 to 0.20 μg/L,²¹⁰Po activity concentrations from below the minimum detectable limit to 0.41 mBq/L, and ²²⁶Ra activity concentrations from 8.70 to 13.35 mBq/L. For the well water samples, gross α activity concentrations ranged from 0.111 to 0.203 Bq/L, gross β from 0.111 to 0.270 Bq/L, uranium mass concentrations from 2.31 to 13.28 μg/L, thorium mass concentrations from 0.17 to 0.26 μg/L,²¹⁰Po activity concentrations from 1.03 to 2.12 mBq/L, and ²²⁶Ra activity concentrations from 15.38 to 23.63 mBq/L. Conclusion The activity concentrations of natural radionuclides in both well water and tap water in the Hohhot region were at environmental background levels and met national drinking water hygiene standards.

The red doctor spirit is the advanced culture of the Communist Party of China formed under a specific historical and cultural background. It can be summarized as “political firmness， excellent technology， working hard， and healing the wounded and rescuing the dying.” This content has many hidden similarities and integrations with the goal of cultivating humanistic literacy for medical students in military medical universities. This paper aimed to identify the important connection points between the red doctor spirit and the contents and goals of medical humanities teaching， as well as integrate the red doctor spirit into medical humanities teaching by various dimensions， including systematic reconstruction of textbook content， immersive innovation in teaching form， three-dimensional support in resource construction， and innovative implementation of narrative medicine teaching. It also further explored the extension of the red doctor spirit in military medical humanistic literacy， namely， revolutionary humanism and revolutionary heroism， thereby enhancing the effectiveness of medical humanistic teaching.

With the development of artificial intelligence and big data,indirect methods for establishing ref-erence intervals(RIs)are commonly used for special populations and special forms of RIs,including continu-ous RIs,personalized RIs,and universal RIs.This paper introduces the differences and application progress of indirect RIs algorithms based on TMC,refineR,Hoffmann,Bhattacharya,Kosmic,and provides references for indirect RIs and related clinical decisions.

Objective To investigate the relationship between peripheral blood receptor-interacting protein kinase 1(RIPK1),bone morphogenetic protein-7(BMP-7),glucose-regulated protein 78(GRP78),NOD-like receptor pyrin domain-containing protein 3(NLRP3)inflammasome and prognosis in children with severe Mycoplasma pneumoniae pneumonia(SMPP).Methods A total of 228 children with SMPP admitted to Guangyuan Maternal and Child Health Hospital from June 2020 to June 2024 were selected as SMPP group.Based on prognosis,they were divided into a poor prognosis group(48 cases)and a good prognosis group(180 cases).Additionally,228 healthy children who underwent physical examinations during the same period were selected as control group.Peripheral blood levels of RIPK1,BMP-7,GRP78,and NLRP3 inflammasome-relat-ed factors[NLRP3,cysteinyl aspartate specific proteinase 1(Caspase-1),and apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)]mRNA were detected and compared between two groups.Pearson method was used to analyze the correlation between peripheral blood RIPK1,BMP-7,GRP78,and the expression of NLRP3 inflammasome-related factors in children with SMPP.Multivariate Logistic re-gression analysis was performed to determine the influencing factors of poor prognosis in children with SMPP.Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of pe-ripheral blood RIPK1,BMP-7,and GRP78 for poor prognosis in children with SMPP.Results The levels of RIPK1,GRP78,NLRP3 mRNA,Caspase-1 mRNA,and ASC mRNA in the SMPP group were higher than those in the control group(P＜0.05),while the level of BMP-7 was lower than that in the control group(P＜0.05).In children with SMPP,peripheral blood RIPK1 and GRP78 were positively correlated with NLRP3 mRNA,caspase-1 mRNA,and ASC mRNA(P＜0.05),whereas BMP-7 was negatively correlated with NLRP3 mRNA,caspase-1 mRNA,and ASC mRNA(P＜0.05).The body temperature upon admission,C-reactive protein,procalcitonin,NLRP3 mRNA,Caspase-1 mRNA,ASC mRNA,peripheral blood RIPK1,and GRP78 levels in the poor prognosis group were all higher than those in the good prognosis group(P＜0.05),while BMP-7 level was lower than that in the good prognosis group(P＜0.05).High peripheral blood levels of RIPK1 and GRP78,along with low BMP-7 level,were identified as independent risk factors for poor prognosis in children with SMPP(P＜0.05).The area under the curve(AUC)of the single detection of RIPK1,BMP-7,and GRP78 for predicting the poor prognosis was 0.786,0.781,and 0.767,respectively,while the combined detection yielded an AUC of 0.904.Conclusion High peripheral blood levels of RIPK1 and GRP78 and low level of BMP-7 are closely associated with NLRP3 inflammasome activation and poor prognosis in children with SMPP.The combined detection of RIPK1,BMP-7,and GRP78 in peripheral blood has high predictive val-ue for the prognosis in children with SMPP.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective To observe the effect of modified Banxia Xiexin Decoction on inflammatory factors in patients with polycystic ovary syndrome(PCOS)of stomach heat and spleen deficiency type through the regulatory mechanism of intestinal flora.Methods A total of 86 patients with PCOS of stomach heat and spleen deficiency type were randomly divided into control group(45 cases)and observation group(41 cases).The control group was treated with conventional western medicine,and the observation group was treated with modified Banxia Xiexin Decoction on the basis of treatment for the control group.One menstrual cycle constituted a course of treatment,and the treatment lasted for three continuous menstrual cycles.The two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome score,endometrial thickness,serum inflammatory factors of tumor necrosis factor α(TNF-α),C-reactive protein(CRP)and interleukin-6(IL-6),sex hormone levels of luteinizing hormone(LH),estradiol(E2),follicle stimulating hormone(FSH)and LH/FSH,as well as the intestinal flora before and after treatment.The clinical efficacy and pregnancy rate of the two groups were compared after treatment.Results(1)After 3 menstrual cycles of treatment,the total effective rate of the observation group was 87.80%(36/41),and that of the control group was 68.89%(31/45).The intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the scores of TCM syndromes in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was more significant than that in the control group(P<0.01).(3)After treatment,the endometrial thickness in the two groups was increased when compared with that before treatment(P<0.05),and the increase in the observation group was superior to that in the control group(P<0.01).(4)The pregnancy rate of the observation group was 92.68%(38/41),which was significantly higher than 73.33%(33/45)of the control group,and the difference was statistically significant(P<0.05).(5)After treatment,the levels of serum E2,LH and LH/FSH in the two groups were decreased when compared with those before treatment(P<0.05),but there was no significant change in the level of serum FSH before and after treatment(P>0.05).The comparison between the two groups showed that the decrease of serum E2,LH and LH/FSH levels in the observation group was significantly superior to that in the control group(P<0.01).(6)After tieatment,the levels of serum CRP,IL-6,TNF-α in patients of the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.01).(7)After treatment,the levels of Bifidobacteria and Lactobacilli in the intestinal flora of the two groups were higher than those before treatment(P<0.05),and the levels of Enterococcus faecalis and Bacteroides were lower than those before treatment(P<0.05),while the levels of Enterobacter did not change significantly before and after treatment(P>0.05).The comparison between the two groups showed that the increase of the levels of Bifidobacteria and Lactobacilli and the decrease of the levels of Enterococcus faecalis and Bacteroides in the observation group were significantly superior to those in the control group(P<0.05 or P<0.01).Conclusion Modified Banxia Xiexin Decoction has a significant clinical effect in the treatment of PCOS of stomach heat and spleen deficiency type.The decoction is effective on improving the clinical symptoms and inflammatory factor levels of patients by regulating intestinal flora.

Objective To investigate the mechanisms of 6-hydroxygenistein(6-OHG)in the treatment of high-altitude hypoxia-induced lung injury.Methods The intersection targets of 6-OHG and high-altitude hypoxia-induced lung injury were identified using databases,including Swiss Target Prediction,SuperPred,GeneCards,and OMIM.The STRING database and Cytoscape software were used to construct a protein interaction network for the intersection targets of drugs and diseases,and targets with degree values greater than the median were identified as key targets.GO and KEGG enrichment analyses of key targets were performed using the DAVID database to identify relevant signaling pathways.The Maestro 13.7 software was used for molecular docking validation.A large hypobaric hypoxic chamber was used to establish a high-altitude lung injury model in mice.A total of 42 male BALB/c mice were randomly assigned to 3 groups(n=14 in each group),including a normal control group,which was exposed to the environmental conditions at the altitude of 1400 m and received a single intraperitoneal injection of normal saline,a model group,which received a single intraperitoneal injection of normal saline,and a 6-OHG group,which received a single intraperitoneal injection of 6-OHG at 100 mg/kg.Then,1 h after drug administration,mice in the model and 6-OHG groups were placed in a large hypobaric hypoxic simulation chamber for animal experiments.Then,they ascended to an altitude of 8 000 m at a speed of 10 m/s,remained in that environment for 24 h,and then descended to an altitude of 3500 m.Mice in the three groups were sacrificed,and their lung tissues were extracted to measure the water content in the lungs.Pathological changes were observed using HE staining,and the levels of malondialdehyde(MDA),H2O2,total superoxide dismutase(T-SOD),and glutathione(GSH)were measured.Western blot was performed to determine the expression levles of p-PI3K/PI3K,p-AKT/AKT,hypoxia-inducible factor 1α(HIF-1α),and vascular endothelial growth factor(VEGF)proteins.Results Key targets such as serine/threonine protein kinase 1(AKT1),HIF-1α,epidermal growth factor receptor(EGFR),matrix metalloproteinase 9(MMP9),and peroxisome proliferator-activated receptor A(PPARA)were identified.GO and KEGG enrichment analyses showed that the targets of 6-OHG in the treatment of high altitude hypoxia-induced lung injury were mainly involved in PI3K/AKT,HIF-1α/VEGF,tumor necrosis factor(TNF),and other signaling pathways.The results of animal experiments demonstrated that compared with the model group,the 6-OHG group showed significant improvement in the pathological damage of lung tissues induced by high altitude hypoxia,presenting statistically significant differences in the levels of MDA,H2O2,GSH,and T-SOD(P＜0.01).The results of Western blot assay revealed statistically significant differences in the p-PI3K/PI3K,p-AKT/AKT,HIF-1α,and VEGF levels in the lung tissues of the 6-OHG group compared with those of the model group(P＜0.01).The molecular docking results showed that 6-OHG could form stable binding with PI3K,AKT,HIF-1α,and VEGF.Conclusion 6-OHG may alleviate lung injury induced by high altitude hypoxia in mice by activating the PI3K/AKT signaling pathway and inhibiting the HIF/VEGF signaling pathway.