Objective To investigate the effects of thioridazine(TZ) on the proliferation, adhesion and migration of human esophageal cancer cells and the mechanism, with the aim of providing new evidence and potential drug candidates for targeted therapy of esophageal cancer.MethodsHuman esophageal carcinoma OE19 cell line was cultured in vitro and divided into control group(without intervention), positive drug group(6 μmol/L doxorubicin), TZ + inhibitor group(80 μg/mL TZ + 2 μmol/L XAV939), TZ + activator group(80 μg/mL TZ + 20 μmol/L SKL2001) and TZ groups with different concentrations(40, 80 and 160 μg/mL), which was treated for at 37 ℃ 24 h. The cell viability of human esophageal carcinoma OE19 cells was determined by CCK-8 assay. The cell proliferation was measured by 5-acetylidene-2 'deoxyuracil nucleoside(EdU)method. The adhesion ability was determined by cell adhesion test. The migration ability was measured in Transwell chamber. The telative expression leaves of Wnt/β-catenin pathway-associated proteins were measured by Western blot.ResultsCompared with the control group, the cell viability of the 80, 160 μg/mL TZ and the positive drug groups significantly decreased(t = 8. 401, 9. 637 and 9. 466, respectively, each P < 0. 05). In the subsequent experiments, compared with the control group, the cell proliferation rate, the number of adhering cells, the number of migrating cells, and the protein expression levels of Wnt and β-catenin in the 80 μg/mL TZ and the positive drug groups all decreased significantly(t = 2. 819-17. 612,each P < 0. 05). Additionally, the cell proliferation rate, the number of adhering cells, the number of migrating cells, and the relative protein expression levels of Wnt and β-catenin in the TZ + inhibitor group were fsignificantly reduced compared with the 80 μg/mL TZ group(t = 3. 098-15. 105, each P < 0. 05), whereas the above indicators significantly increased in the TZ +activator group(t = 2. 449-5. 502, each P < 0. 05).ConclusionTZ can inhibit the proliferation, adhesion and migration of OE19 cells, and the mechanism may be related to the inhibition of Wnt/β-catenin pathway transduction.

Adenovirus(Ad) vector vaccines use the modified Ad as a delivery tool to deliver the gene encoding the target antigen to the host cell, inducing humoral and cellular immune response, which have good characteristics such as stable expression of heterologous genes, strong immunogenicity and low pathogenicity, and can be produced on a large scale. The SARS-CoV-2 vaccine prepared by this platform not only curbs the spread of the epidemic in a short period of time, but also provides a technical platform and valuable experience for dealing with emerging infectious diseases in the future. It has shown significant potential in the prevention and control of infectious diseases and has become an important direction of current vaccine research. In this paper, the latest clinical application progress of Ad vector vaccines, the key challenges in the process of clinical transformation and the molecular mechanism of inducing host immune response are reviewed, in order to provide reference for related research.

[摘 要] 目的：探究肌动蛋白样蛋白6A（ACTL6A）通过调控铁死亡参与弥漫大B细胞淋巴瘤（DLBCL）细胞多柔比星（DOX）耐药的机制。方法：培养亲本DLBCL细胞SU-DHL-4与耐药细胞SU-DHL-4/DOX，qPCR和WB法检测ACTL6A表达变化；通过转染携带靶向ACTL6A干扰序列（sh-ACTL6A）及其阴性对照（sh-NC）的质粒，构建敲减ACTL6A的SU-DHL-4/DOX，qPCR和WB法检测转染后细胞中ACTL6A、铁死亡相关蛋白谷胱甘肽过氧化酶4（GPX4）、溶质载体家族7成员11（SLC7A11）、长链酰基辅酶A合成酶4（ACSL4）的表达水平，染色质免疫沉淀（ChIP）、双萤光素酶报告基因实验验证ACTL6A与GPX4间的靶向结合与调控作用。将SU-DHL-4/DOX细胞分为对照组、sh-NC组、sh-ACTL6A组、sh-NC + oe-GPX4组和sh-ACTL6A + oe-GPX4组，用转染试剂将相应质粒转染至细胞中，qPCR和WB法检测各组细胞中ACTL6A和GPX4表达水平，CCK-8法检测不同浓度DOX处理后各组细胞存活率，FerroOrange探针检测各组细胞中亚铁离子（Fe2+）水平，Liperfluo探针检测各组细胞中脂质过氧化物水平，DCFH-DA探针检测各组细胞中活性氧（ROS）水平，比色法检测各组细胞中谷胱甘肽（GSH）和丙二醛（MDA）含量。结果： 与SU-DHL-4细胞相比，SU-DHL-4/DOX细胞中ACTL6A mRNA和蛋白均呈高表达（均P < 0.05）；ACTL6A与GPX4间存在靶向结合关系；敲减ACTL6A后SU-DHL-4/DOX细胞中ACTL6A和GPX4 mRNA及其蛋白表达水平均明显下降（均P < 0.05），表明ACTL6A可调控GPX4的表达；敲减ACTL6A可抑制SU-DHL-4/DOX细胞的存活率，促进细胞内Fe2+、脂质过氧化物、ROS、MDA的生成，抑制GSH生成（均P < 0.05）；而在敲减ACTL6A的同时过表达GPX4可上调SU-DHL-4/DOX细胞中GPX4的mRNA及其蛋白表达水平（均P < 0.05），并提高细胞存活率，抑制细胞内Fe2+、脂质过氧化物、ROS、MDA的生成，并增加GSH生成（均P < 0.05）。结论：ACTL6A在DOX耐药DLBCL细胞中高表达，通过调控GPX4表达抑制铁死亡，促进DLBCL细胞耐药。

[摘 要] 目的：探究环状核酸适配体-药物偶联物（ApDC）联合抗CD19嵌合抗原受体T/NK（CAR19-T/NK）细胞对Nalm6白血病细胞杀伤效果的增强作用。方法： 用数据库分析寻找白血病细胞的标志物蛋白酪氨酸激酶7（PTK7），设计合成靶向PTK7的核酸适配体sgc8，进一步合成两种ApDC：核酸适配体偶联吉西他滨（sgc8-GEM）和环状核酸适配体偶联吉西他滨（C-sgc8-GEM），琼脂糖凝胶电泳分析其稳定性。用CD19-CAR过表达慢病毒转染人外周血T/NK细胞构建CAR19-T和CAR19-NK细胞，流式细胞术检测sgc8与Nalm6细胞的结合力，CCK-8法和流式细胞术检测sgc8-GEM、C-sgc8-GEM，以及其分别与CAR19-T和CAR19-NK细胞联合应用对Nalm6细胞的杀伤能力。结果： PTK7 mRNA在白血病细胞中呈高表达（P < 0. 01）；C-sgc8-GEM比sgc8-GEM稳定性更高，与GEM比较，sgc8-GEM更能有效杀伤Nalm6细胞（P < 0.001）；C-sgc8-GEM或sgc8-GEM分别与CAR19-T/NK细胞联合应用比单独用C-sgc8-GEM、sgc8-GEM、CAR19-T/NK细胞对Nalm6细胞的毒性均更强（P < 0.001）。结论：成功建立环状ApDC与CAR19-T/NK细胞联合应用法，通过双靶点有效提高了对Nalm6细胞的毒性，为急性淋巴细胞白血病提供了新的治疗思路。

[摘 要] 目的：探讨嗜酸性粒细胞（Eos）和其他循环血细胞和炎症指标在预测小细胞肺癌（SCLC）免疫治疗疗效和免疫相关不良反应（irAE）中的价值。方法:回顾分析2013年8月至2023年7月期间海军军医大学第一附属医院呼吸科收治的410例SCLC患者临床信息；在化疗或免疫治疗前，以及治疗后的3个周期，分别检测患者全血细胞计数和细胞因子等指标；记录irAE的发生时间、类型、分级，以及随访情况。结果: 接受化疗联合免疫检查点抑制剂（ICI）治疗（简称联合治疗）的患者116例，其中一线联合治疗患者91例、后线联合治疗25例。联合组患者的总有效率（ORR）为44.8%，疾病控制率（DCR）为90.5%，单用化疗（单化）组患者的ORR为38.4%，DCR为85.0%。联合组中位PFS为8.9（7.2～10.5）个月，中位OS为17.7（13.9～21.5）个月。将联合组与单化组行倾向得分匹配（PSM）法配对，对比二组治疗后3周期的绝对嗜酸性粒细胞计数（AEC）水平、相对嗜酸性粒细胞计数（REC）水平；计算历次复查Eos水平与基线Eos水平的比值（AECT1/0、AECT2/0、AECT3/0、RECT1/0、RECT2/0、RECT3/0），联合组的AECT3/0和RECT3/0显著高于单化组。单因素分析表明，基线AEC和REC的升高与较好的治疗至失败时间（TTF）和OS显著相关（P < 0.05）；治疗后Eos水平与基线水平的比例（AECT3/0、RECT3/0）与较好的PFS和TTF显著相关（P < 0.05）；RECT3/0升高同样与OS改善显著相关（P < 0.05）。多因素分析提示，AECT3/0 > 0.41与较好的PFS和TTF显著相关（P < 0.05）；当RECT3/0 > 0.32时，与较好的PFS、TTF、OS均显著相关（P < 0.05）；RECT3/0 > 0.27仅与较好的TTF、OS显著相关（P < 0.05）。亚组分析发现，缓解组的RECT3/0显著高于非缓解组（P < 0.05）。一线应用ICI与二线/后线应用ICI患者的PFS、TTF、OS无统计学差异，但一线应用ICI时ORR（50% vs 25%，P < 0.05）和DCR（93.48% vs 79.17%，P < 0.05）显著优于二线/后线。116例联合治疗患者发生43例irAE（35.34%）, 最常见的为免疫相关性皮炎8.62%；Ⅲ级以上的irAE共17例（14.66%）；因irAE停药10例（8.62%），死亡2例;发生irAE的患者PFS较未发生irAE的患者显著延长（P < 0.05），而TTF和OS无统计学差异。发生irAE患者的RECT3较未发生irAE患者显著升高（P < 0.05），AECT3/0 > 0.29的患者irAE发生率显著增高（P < 0.05）。结论: Eos是SCLC接受ICI治疗的保护性因素，通过监测AECT3/0、RECT3/0，并结合患者的临床病理生理特征、细胞因子和炎症标志物水平进行综合评估，可有效预测SCLC患者的免疫治疗疗效和irAE的发生。

Abstract The prevalence of hyperuricemia (HUA) in children and adolescents is rising rapidly and presents a trend towards younger age groups, establishing it as the most prevalent metabolic abnormality and a major public health concern. To curb the damage of persistent HUA to children and adolescents development and health, the review systematically addresses the epidemiology, diagnosis, health impairments, and pathogenesis of pediatric HUA, summarizes risk factors and tiered interventions, and discusses future directions including diagnostic precision, the advancement of intervention windows, and the dual role of uric acid, with the goal of informing early prevention and control strategies for HUA in children and adolescents.

Objective: To explore the association between vegetable intake with glucose and lipid metabolism levels among school aged children, so as to provide scientific basis for dietary intervention on children s metabolic health. Methods: Based on a natural population cohort in Jiulongpo District and Fengdu County of Chongqing, 2 133 school aged children aged 6-9 years were enrolled in the baseline survey in 2014, and 2 029 children completed the follow up in 2019. Questionnaire surveys were used to collect vegetable intake, general demographic and lifestyle data. Height, weight and waist circumference were measured, and glucose and lipid metabolism indicators such as fasting blood glucose (FBG), triglyceride (TG) and total cholesterol (TC), low densith lipoprotein triglyceride (LDL-C), high densith lipoprotein triglyceride (HDL-C) were detected. Mann-Whitney U test and Kruskal-Wallis H test were used for intergroup comparisons in multivariate analysis, and mixed effects linear regression model was used to analyze the association between vegetable intake and glucose and lipid metabolism. Results: The levels of FBG, TG, TC, HDL-C and LDL-C at baseline and follow up were [4.09(3.90,4.48), 0.84(0.60,1.14), 3.49(3.09,3.91), 1.25(1.09,1.46), 1.69 ( 1.39 ,2.02)；4.31(4.00,4.64), 0.92(0.71,1.22), 3.49(3.12,3.87), 1.36(1.16,1.57), 1.77(1.51,2.06)] mmol/L, respectively. Among these indicators, FBG, TG, HDL-C and LDL-C all increased significantly ( Z =-12.08, -7.82, -9.82, -5.37, all P < 0.01 ). The detection rate of low HDL-C levels at follow up (13.11%) was significantly lower than that at baseline (18.10%) ( χ 2=19.57, P <0.05). At baseline, there were significant differences in FBG, TC, TG, HDL-C and LDL-C among children with different vegetable intake levels ( H =68.47, 30.16, 11.02, 13.27, 44.70); at followup, only HDL-C showed significant intergroup differences ( H =13.10)(all P <0.05). Mixed effects linear regression model showed that after adjusting for confounding factors, vegetable intake was significantly negatively correlated with blood glucose levels among school aged children ( β=-0.03, 95%CI = -0.05 to -0.01, P <0.01). Conclusion Higher vegetable intake can independently reduce the risk of abnormal blood glucose in school aged children, which is of great significance for maintaining glucose metabolic health.

Objective: To construct a risk prediction model for pediatric metabolic dysfunction associated steatotic liver disease (MASLD), so as to provide practical tool for the early identification of high risk children. Methods: A healthy cohort of children in Southwest China was established from January 2021 to April 2025. A nested case-control study design was used to include 507 cases MASLD group and 507 cases in non MASLD group. Data on physical measurements, blood biochemical parameters, and liver ultrasound indicators were collected. Conditional Logistic regression was used to analyze the relationship between individual variables and MASLD, Lasso regression was applied for multivariable screening, and a high risk prediction model was constructed and presented in the form of a nomogram. Internal validation was performed using 10 repeated ten fold cross validations to assess model discrimination, accuracy, sensitivity, and specificity. Results: Logistic regression analysis showed that MASLD was associated with central obesity ( OR=22.11, 95%CI =15.62-31.29), apolipoprotein B ( OR=30.24, 95%CI =12.42-73.63), increased hepatorenal echo ( OR=326.00, 95%CI =183.87-578.01), hepatomegaly ( OR=24.98, 95%CI =16.66-37.46) (all P <0.05). The Lasso regression jointly selected 6 key variables, including hepatorenal echo, central obesity, hepatomegaly, right liver lobe inclination, body mass index, and alanine amino transferase. The results of cross validation showed that the average area under the curve (AUC) was 0.999 5, the average accuracy was 98.74%, and the sensitivity and specificity were 98.21% and 99.22% respectively, indicating a good predictive effect of the model. Conclusion The risk prediction model for high risk MASLD among children based on ultrasound and clinical indicators has good prediction effect, which is helpful for the early identification and risk stratification of pediatric MASLD.

BACKGROUND AND OBJECTIVES

The global pandemic caused by Coronavirus Disease 2019 (COVID-19) has affected millions, with growing evidence of the potential role of ocular tissues in viral transmission. At the time of writing, local data regarding the phenomenon was limited. This study investigated external ocular manifestations in patients with COVID-19 at a referral center in the Philippines, examined correlations between demographics, systemic manifestations, and laboratory results with ocular manifestations, and determined their timing relative to systemic symptoms.

METHODS

This single-center, descriptive cross-sectional study was carried out from December 8 to 18, 2020 at the adult COVID-19 wards of the Philippine General Hospital involving 72 participants. Data collection involved relevant clinical history taking and performing gross eye examination. The prevalence of ocular manifestations was described with 95% confidence intervals. Correlations between ocular manifestations and quantitative variables were analyzed with point-biserial correlation, and associations with qualitative variables were tested using chi-square or Fisher’s exact tests.

RESULTS

Among participants, 31.9% presented with ocular manifestations with foreign body sensation as the most prevalent ocular symptom (11.1%) and conjunctival hyperemia as the most prevalent ocular finding (19.4%). The median age of patients with ocular manifestations was 41 years old with a higher prevalence in the male population (73.9%, CI=95%, p=0.001). No significant correlation was observed between presence of external ocular manifestations and the different systemic and ocular co-morbidities as well as with COVID-19 clinical classification. Among those who experienced symptoms, majority (29.2%) of the patients experienced systemic symptoms prior to the onset of ocular symptoms. Ocular complaints may present as the sole manifestation (13.9%). Several laboratory parameters were measured and only temperature and AST levels showed a low positive correlation with the presence of ocular manifestations. 

CONCLUSION

Ocular manifestations occur in roughly one third of patients with COVID-19 based on this study population. With some individuals presenting with ocular signs or symptoms as the initial and sole manifestation, healthcare practitioners must exercise caution and remain vigilant in managing patients who present as such. At the time of writing, this is the first local study investigating the different external ocular manifestations in patients with COVID-19. There is a need to pursue more robust studies and conduct more local investigations which will guide both ophthalmologists and other practitioners in strengthening existing guidelines regarding precautionary practices, clinical diagnosis, and management of COVID-19 patients.

Human ; Sars-cov-2 ; Covid-19 ; Philippines ; Adult ; Association ; Classification ; Collection ; Confidence Intervals ; Coronavirus ; Cross-sectional Studies ; Data Collection ; Demography ; Diagnosis ; Disease ; Exercise ; Eye ; Foreign Bodies ; History ; Hospitals ; Hospitals, General ; Hyperemia ; Laboratories ; Male ; Morbidity ; Ophthalmologists ; Pandemics ; Patients ; Population ; Prevalence ; Referral And Consultation ; Role ; Sensation ; Temperature ; Time ; Tissues ; Volition ; World Health Organization ; Writing

Congenital divided nevus of the eyelids is a rare form of melanocytic nevus which involves contiguous portions of the upper and lower eyelid margins unilaterally, hence the term ‘kissing nevus’. While usually present at birth, these nevi may also appear later in life. When the mass enlarges, it may cause cosmetic issues to the patient, as well as functional problems such as mechanical ptosis, ectropion, and epiphora.

We report three cases of congenital divided nevus of the eyelids, all presenting with unilateral upper and lower hyperpigmented lid masses since birth. The first case had an upper lid mass measuring 11 mm x 19 mm, and a lower lid mass measuring 55 mm x 47 mm, with both masses extending into the palpebral conjunctiva, and causing severe ptosis and corneal neovascularization due to chronic irritation. The second case presented with hyperpigmented masses at the lateral third of the right upper eyelid measuring 8 mm x 17 mm and of the lower eyelid measuring 9 mm x 15 mm on the lower lid with lashes growing through the masses. There was extension of the mass into the palpebral conjunctiva. The third case presented with a 23 x 18 mm hyperpigmented, well-circumscribed, verrucated mass at the medial half of the upper eyelid crossing the eyelid margin, and a 15 x 13 mm lesion at the medial third of the lower lid with the same characteristics, with small crusty lesions and clotted blood. All three patients underwent excision biopsy with lid reconstruction using full thickness skin grafts from the supraclavicular area. Six months postoperatively, the first case underwent a repeat full thickness skin graft due to graft contraction, and also received two sessions of fractional carbon dioxide (CO2 ) laser, two sessions of intralesional triamcinolone injections, and silicone gel application with further improvement of graft healing and scarring. The second case also underwent two sessions of intralesional steroid injection for scar management. During follow-up, which spanned 13 months for the first case, 10 months for the second case, and two months for the third case, improved functional and cosmetic outcomes were observed.

This case series highlights the outcomes of the most common surgical technique done for congenital divided nevi of the eyelids. Congenital divided nevi are usually diagnosed clinically and malignant degeneration is rare, hence lid reconstruction may be done without frozen section. The cases in the series were treated due to cosmetic and functional purposes, hence the importance of continuous post-operative follow-up to monitor for graft dehiscence, scar development, recurrence of the mass, malignant degeneration, and development of lid malposition. Additional procedures for scar management, such as CO2 laser and intralesional steroid injections, may be necessary to further enhance outcomes in complex cases. All three cases in this series exhibited improved functional and cosmetic outcomes post-operatively, with significant reduction in ptosis and scarring. Longterm follow-up revealed satisfactory recovery with minimal complications, with no recurrence nor malignant degeneration.

Human ; Male ; Female ; Adult: 25-44 Yrs Old ; Young Adult: 19-24 Yrs Old ; Nevus ; Nevus, Pigmented