[摘 要] 目的：探讨环状RNA CEMIP（circCEMIP）对膀胱癌UMUC-3细胞增殖、迁移和侵袭的影响及其分子机制。方法：通过TCGA数据库分析circCEMIP在膀胱癌组织中的表达水平，分析其表达与膀胱癌患者临床分期及生存期的关系。采用qPCR法检测circCEMIP在膀胱癌细胞5637、UMUC-3、MGH-U3、J82和T24中的表达。利用RNA干扰技术，分别将si-circCEMIP及其阴性对照（si-NC）、anti-miR-335及其阴性对照（anti-miR-NC）转染UMUC-3细胞，记为si-circCEMIP组、si-NC组、si-circCEMIP + anti-miR-335组和si-circCEMIP + anti-miR-NC组。采用克隆形成实验、划痕愈合实验和Transwell实验分别检测circCEMIP和miR-335表达对UMUC-3细胞增殖、迁移和侵袭能力的影响，双萤光素酶报告基因实验验证circCEMIP与miR-335的靶向关系，WB法检测细胞中VEGF-C信号通路相关蛋白的表达。构建UMUC-3细胞裸鼠皮下移植瘤模型，观察敲低circCEMIP对移植瘤生长的影响。结果：膀胱癌组织中circCEMIP呈高表达（P < 0.01），其表达水平与膀胱癌的临床分期正相关（P < 0.01），circCEMIP高表达患者生存率较低（P < 0.01）。circCEMIP在膀胱癌5637、UMUC-3、MGH-U3、J82和T24细胞中呈高表达（均P < 0.01）。敲低circCEMIP显著降低UMUC-3细胞的增殖、迁移和侵袭能力（均P < 0.01）。circCEMIP可靶向结合miR-335（P < 0.01），敲低circCEMIP能显著上调miR-335表达（P < 0.01）。抑制miR-335表达能逆转敲低circCEMIP对UMUC-3细胞增殖、迁移和侵袭的抑制作用（均P < 0.01）。敲低circCEMIP能明显下调VEGF-C信号通路相关蛋白VEGF-C、MMP-2、MMP-9和β-catenin表达（均P < 0.01），抑制miR-335表达能部分逆转敲低circCEMIP对该通路相关蛋白表达的抑制作用（均P < 0.01）。体内实验证实，敲低circCEMIP能够抑制裸鼠膀胱癌移植瘤的生长（P < 0.01）。结论：敲低circCEMIP通过上调miR-335表达抑制膀胱癌UMUC-3细胞的增殖、迁移和侵袭。

Objective To analyze the clinical characteristics and risk factors of noninfectious fever after endovascular repair of aortic dilatation diseases, and to explore management strategies. Methods A retrospective analysis was conducted on the clinical data of patients who underwent endovascular aortic repair for aortic dilatation diseases from January 2021 to October 2023. Based on inclusion and exclusion criteria, the enrolled patients were divided into a febrile group and an afebrile group according to the presence of postoperative fever. Clinical data, including demographics and surgical details, were compared between the two groups. Multivariate logistic regression analysis was performed on indicators with P≤0.05 in the univariate analysis, and receiver operating characteristic (ROC) curves were generated to analyze the predictive value of risk factors for postoperative noninfectious fever. Results A total of 305 patients were included in the final analysis. Postoperative noninfectious fever occurred in 75.08% (229/305) of the patients, with 98.25% of cases occurring within the first two postoperative days. The febrile group (n=229) had a median age of 65.0 (IQR: 53.0, 73.0) years with 83.4% males, while the afebrile group (n=76) had a median age of 71.0 (IQR: 65.0, 76.7) years with 84.2% males. Univariate analysis showed that the age, prevalence of coronary heart disease, preoperative statin use, and prevalence of aortic aneurysm were significantly lower in the febrile group compared to the afebrile group. Logistic regression analysis indicated that age, surgical site, disease type, preoperative elevated body temperature, and stent type were significantly associated with noninfectious fever, while preoperative statin use was negatively correlated. ROC curve analysis demonstrated that age, surgical site, preoperative elevated body temperature, and stent type had significant predictive value for postoperative noninfectious fever (P<0.01). Conclusion Noninfectious fever is highly prevalent following aortic repair. The relationship between fever and infection should be comprehensively evaluated based on risk factors and changes in the patient's condition to promote the rational use of antibiotics.

[摘 要] 目的：探讨Shc SH2结构域结合蛋白1（SHCBP1）基因在结直肠癌（CRC）中的表达及其调控CRC细胞（Caco-2）增殖、迁移和侵袭的机制。方法：将Caco-2细胞分为4个实验组：Con组（空白对照）、sh-NC组（转染阴性对照sh-NC）、sh-SHCBP1组（转染sh-SHCBP1）、sh-SHCBP1 + 740Y-P组（转染sh-SHCBP1后用30 μmol/L PI3K激活剂740Y-P处理1 h）。采用CCK-8法、细胞划痕和Transwell实验检测细胞增殖、迁移和侵袭能力，基于Matrigel进行三维培养实验检测SHCBP1对Caco-2细胞血管生成拟态（VM）形成能力的影响，qRT-PCR检测SHCBP1的mRNA表达情况，WB法检测SHCBP1、VM相关蛋白以及PI3K/AKT/mTOR信号通路相关蛋白的表达。结果：SHCBP1在CRC组织和细胞中呈高表达（P < 0.05）。与Con组和sh-NC组相比，sh-SHCBP1组的SHCBP1的mRNA和蛋白表达水平、细胞增殖活性、划痕修复率、穿膜细胞数和形成的小管数均显著降低（均P < 0.05）；低氧诱导因子1α（HIF-1α）、Ephrin A型受体2（EPHA2）、VEGFA、p-PI3K、p-AKT和p-mTOR蛋白表达水平均显著降低（均P < 0.05）。对比sh-SHCBP1组，sh-SHCBP1 + 740Y-P组的细胞增殖活性、划痕修复率、穿膜细胞数和形成的拟态血管数均显著增加（均P < 0.05）；HIF-1α、EPHA2、VEGFA、p-PI3K、p-AKT和p-mTOR蛋白表达水平均显著增加（均P < 0.05）。结论：SHCBP1在Caco-2细胞中表达显著上调，促进Caco-2细胞的增殖、迁移和侵袭，其机制可能与激活PI3K/AKT/mTOR信号通路促进VM过程有关。

Objective: In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis. Methods: Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples. Results: Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis. Conclusion This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.

Objective: In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis. Methods: Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples. Results: Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis. Conclusion This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.

Objective: In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis. Methods: Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples. Results: Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis. Conclusion This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.

BACKGROUND

A substantial number of COVID-19 recoverees are working-aged individuals, which makes return-towork (RTW) an essential part of rehabilitation. Many COVID-19 recoverees must deal with physical and mental symptoms of post-COVID conditions such as fatigue, dyspnea, difficulty concentrating, memory lapses, and anxiety. These symptoms coupled with often insufficient support from employers and the government can make the RTW process complicated. Although research related to RTW after COVID-19 has begun to emerge over the years, few primary studies have come out from developing countries.

This exploratory study aims to describe perceived work ability and health-related quality of life, lived experiences of the RTW process, and role of rehabilitation in a limited sample of Filipino COVID-19 recoverees. 

Using purposive sampling and a convergent parallel mixed-method design, the study draws on an online survey and group interviews to understand expectations, experiences, and self-rated work ability of working-age adults with post-COVID condition. We report the findings of the questionnaire data using descriptive statistics. From the questionnaire respondents, eight participants were interviewed to explore the RTW experiences from multiple perspectives. The group interview was conducted online, and narrative analysis was used to explore the data. This analytic process involved an iterative and inductive process between data gathering and data analysis.

Findings from our narrative analysis are reported under four themes: 1) The period of liminality; 2) A ‘positive’ problem; 3) Health as a psychosocial and justice issue; and 4) The reimagination of paid work. The narratives gathered document an overview of how selected Filipinos overcame the COVID-19 infection and their recovery and RTW process.

Results call for a re-examination of the concept of health and paid work for individuals undergoing rehabilitation and recovery.

Objective: In the present study, we compare the influence of oxidized lipoprotein(a) [Lp(a)] and unoxidized Lp(a) on plasminogen activation in the process of fibrinolysis and elucidate the potential atherogenic mechanisms of oxidized Lp(a), focusing on its role in thrombosis. Methods: Chromogenic substrate assays were conducted to study the kinetics of plasminogen activation. Fibrin clots were generated by incubating fibrinogen with thrombin, and plasminogen activation was triggered with tissue plasminogen activator (tPA). Experiments were performed in low and high concentrations of Lp(a) or oxidized Lp(a) to evaluate their respective effects on plasmin generation. Oxidized Lp(a) was prepared by chemical oxidation of isolated Lp(a) samples. Results: Low concentrations of Lp(a) enhanced plasminogen activation and fibrinolysis, reflecting its physiological role. However, at higher concentrations, oxidized Lp(a) exhibited a significant inhibitory effect on plasminogen activation. Compared to unoxidized Lp(a), oxidized Lp(a) led to earlier plateauing of plasmin generation and reduced overall plasmin levels. The inhibitory effects of oxidized Lp(a) are likely due to its structural similarity to plasminogen and higher oxidized phospholipid content, which competes with plasminogen for fibrin binding—the enhanced competition with fibrin fragments and tPA by oxidized Lp(a) further impaired fibrinolysis. Conclusion This study demonstrates that while low levels of Lp(a) may support fibrinolysis, oxidized Lp(a) impairs this process by inhibiting plasminogen activation through structural and functional competition. These findings highlight the atherogenic potential of oxidized Lp(a) and its contribution to thrombotic cardiovascular risk.

BACKGROUND

A substantial number of COVID-19 recoverees are working-aged individuals, which makes return-towork (RTW) an essential part of rehabilitation. Many COVID-19 recoverees must deal with physical and mental symptoms of post-COVID conditions such as fatigue, dyspnea, difficulty concentrating, memory lapses, and anxiety. These symptoms coupled with often insufficient support from employers and the government can make the RTW process complicated. Although research related to RTW after COVID-19 has begun to emerge over the years, few primary studies have come out from developing countries.

This exploratory study aims to describe perceived work ability and health-related quality of life, lived experiences of the RTW process, and role of rehabilitation in a limited sample of Filipino COVID-19 recoverees. 

Using purposive sampling and a convergent parallel mixed-method design, the study draws on an online survey and group interviews to understand expectations, experiences, and self-rated work ability of working-age adults with post-COVID condition. We report the findings of the questionnaire data using descriptive statistics. From the questionnaire respondents, eight participants were interviewed to explore the RTW experiences from multiple perspectives. The group interview was conducted online, and narrative analysis was used to explore the data. This analytic process involved an iterative and inductive process between data gathering and data analysis.

Findings from our narrative analysis are reported under four themes: 1) The period of liminality; 2) A ‘positive’ problem; 3) Health as a psychosocial and justice issue; and 4) The reimagination of paid work. The narratives gathered document an overview of how selected Filipinos overcame the COVID-19 infection and their recovery and RTW process.

Results call for a re-examination of the concept of health and paid work for individuals undergoing rehabilitation and recovery.

Objective: To investigate whether syndecan-2(SDC2) can affect the proliferation, invasion and migration of cervical cancer cells by regulating ferroptosis and its possible mechanism. Methods : Normal cervical epithelial cells H8 and cervical squamous carcinoma cells C33A were cultured and divided into H8 group and C33A group. C33A cells were cultured and divided into control group, low SDC2 expression group, SDC2+ferroptosis inhibitor(ferrostation-1) group and SDC2 + ferroptosis inducer(erastin) group. Western blot was used to detect the protein levels of SDC2, solute carrier family 7 member 11(SLC7A11) and glutathione peroxidase 4(GPX4). RT-qPCR was used to detect the SDC2 mRNA level in C33A cells. ELISA kits were used to detect the levels of reactive oxygen species(ROS), glutathione(GSH) and ferrous ion(Fe2+) in C33A cells. The cloning ability of C33A cells was detected by plate cloning. The migration ability of C33A cells was detected by scratch test. Transwell assay was used to detect the invasion ability of C33A cells. Results : Compared with H8 group, the protein and mRNA expressions of SDC2, SLC7A11 and GPX4 in C33A group increased(P<0.05). Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells in the low SDC2 group decreased(P<0.05), the protein and mRNA expressions of SLC7A11 and GPX4 in C33A cells decreased(P<0.05), and the GSH level decreased. ROS and Fe2+levels increased(P<0.05). Compared with the low SDC2 group, the protein and mRNA expressions of SLC7A11 and GPX4 increased(P<0.05), the GSH level increased, and the ROS and Fe2+levels decreased(P<0.05) in the low SDC2+ferrostation-1 group. Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells with low SDC2+erastin expression decreased(P<0.05). Conclusion The expression of SDC2 increases in C33A cervical cancer cells. Low expression of SDC2 can activate SLC7A11/GPX4 pathway mediated ferroptosis, thereby reducing the proliferation, invasion and migration of C33A cells.