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。

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.

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 summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

Objective To investigate the influencing factors of pulmonary and extrapulmonary acute re-spiratory distress syndrome(ARDS)caused by sepsis.Methods A total of 126 patients with ARDS admitted to the Department of Critical Care Medicine,General Hospital of Ningxia Medical University,from January 2022 to June 2024 were selected.Patients were divided into pulmonary ARDS and extrapulmonary ARDS groups based on the etiology of ARDS.General data,inflammatory indicators,and prognostic outcomes were compared between the two groups.COX regression analysis was used to identify prognostic factors.Results A-mong the 126 patients,72 were diagnosed with pulmonary ARDS and 54 with extrapulmonary ARDS.The pulmonary ARDS group had significantly lower SOFA scores,fewer organ dysfunctions,a lower incidence of arrhythmia,shorter mechanical ventilation duration,higher Murray scores,and higher Charlson Comorbidity Index(CCI)compared to the extrapulmonary ARDS group(P<0.05).Inflammatory markers,including pro-calcitonin(PCT),C-reactive protein(CRP),interleukin(IL)-4,IL-6,IL-10,and tumor necrosis factor-α(TNF-α),were significantly lower in the pulmonary ARDS group,while interferon-γ(INF-γ)levels were higher(P<0.05).For pulmonary ARDS,CCI and TNF-α were identified as independent risk factors for prog-nosis(P<0.05),with the combination of CCI and TNF-α yielding the highest predictive accuracy(AUC=0.81,95%CI:0.71-0.91).For extrapulmonary ARDS,CCI and CRP were independent risk factors(P<0.05),and their combination achieved the highest predictive performance(AUC=0.91,95%CI:0.84-0.98).Conclusion Inflammatory profiles between pulmonary and extrapulmonary ARDS caused by sepsis are different.CCI and TNF-α are independent risk factors for mortality in pulmonary ARDS,while CCI and CRP are independent risk factors in extrapulmonary ARDS.

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 This study aims to explore the effects of Minimally Invasive Extracorporeal Circulation(MECC)on systemic inflammatory response and transfusion requirements following Coronary Artery Bypass Grafting(CABG).Methods A total of 126 patients who underwent CABG from January 2023 to January 2024 were selected and randomly divided into an observation group and a control group,with 63 patients in each group.The observation group received MECC,while the control group was treated with Conventional Extracorporeal Circulation(CECC).Inflammatory response indicators,immune system function,coagulation function,renal function,cardiac function,and clinical symptoms were monitored preoperatively and at 24,48,and 72 hours postoperatively for comparison and analysis.Results At 24 hours postoperatively,CRP,IL-6 and TNF-α levels in the observation group were(18.5±3.7)mg/L,(15.2±3.4)pg/mL and(25.3±5.6)pg/mL,respectively,which were significantly lower than those in the control group(P＜0.05).At 48 hours postoperatively,the CD4+/CD8+ratio in the observation group was 1.6±0.3,which was higher than that in the control group(P＜0.05).At 72 hours postoperatively,the PT and APTT in the observation group were(12.1±1.2)seconds and(30.4±3.2)seconds,respectively,which were significantly lower than those in the control group(P＜0.05).Additionally,72 hours after surgery,SCr and BUN in the observation group were(1.1±0.2)mg/dL and 14.6±3.1 mg/dL,respectively,which were significantly lower than those in the control group(P＜0.05).In terms of cardiac function indexes,at 24 hours postoperatively,CI,LVEF,cTnⅠ and BNP in the observation group were(2.6±0.5)L/min/m2,(55.6±4.0)％,(0.14±0.03)ng/mL,and(280±30)pg/mL,respectively,which were significantly better than those in the control group(P＜0.05).At all postoperative time points,the VAS score,complication rate,length of hospital stay and ICU stay were significantly better in the observation group than in the control group(P＜0.05),with the VAS score at 24 hours postoperatively being(4.8±1.2)compared to(5.5±1.3)in the control group(P＜0.05).Conclusions MECC demonstrates significant advantages in attenuating systemic inflammatory response after CABG,protecting multi-system function,reducing postoperative blood transfusion requirements,and improving postoperative recovery.Compared with traditional extracorporeal circulation,MECC effectively reduce postoperative inflammatory reactions and complications,enhancing the quality of life for patients post-surgery,and shows broad clinical application prospects.