[摘 要] 目的：探讨麻疹-流行性腮腺炎-风疹联合减毒活疫苗（MMR）通过诱导免疫原性细胞死亡（ICD）对三阴性乳腺癌（TNBC）的免疫调节机制。方法：体外实验采用CCK-8法检测MMR对TNBC细胞4T1和MDA-MB-231存活率的影响，免疫荧光法检测MDA-MB-231细胞中钙网蛋白（CALR）表达，磷钼酸比色法检测MDA-MB-231细胞内ATP的含量，ELISA检测细胞上清液中高迁移率族蛋白B1（HMGB1）的表达水平，通过GEPIA网站分析CALR和HMGB1对乳腺癌患者生存期的影响。体内实验中经皮下注射4T1-Luc细胞于雌性BALB/c小鼠乳腺脂肪垫构建TNBC小鼠模型。设Control组、盐酸阿霉素（Dox）组、MMR组，按照分组每两天静脉给药1次，连续给药3次。动物活体成像系统观察肿瘤体积变化；记录小鼠体质量及各器官指数初步评估疫苗安全性；H-E染色观察肿瘤病理变化；免疫组化和Western blotting检测肿瘤中CALR和HMGB1蛋白的表达。流式细胞术分析小鼠脾T淋巴细胞亚群及肿瘤树突状细胞和巨噬细胞比例；免疫组化检测肿瘤CD8+ T淋巴细胞浸润；ELISA检测血清中促炎细胞因子IL-6和TNF-α含量。结果：MMR对4T1细胞的活性抑制作用较弱；MMR对MDA-MB-231细胞抑制率达90.39%（P < 0.001）。与Control组相比，MMR组MDA-MB-231细胞中ICD相关蛋白（CALR、ATP、HMGB1）表达上调（P < 0.001）。GEPIA网站分析表明，CALR和HMGB1高表达的患者总生存期有所延长。MMR延缓了荷瘤小鼠肿瘤体积增长（P < 0.001），延长小鼠的生存期，且28 d内MMR组荷瘤小鼠体重与Control组无显著性差异（P > 0.05）；H-E染色显示，与Control组相比，MMR组小鼠肿瘤组织坏死区域扩大且有免疫细胞浸润；MMR上调肿瘤ICD相关蛋白CALR、HMGB1的表达水平；MMR组脾CD4+、CD8+ T淋巴细胞及肿瘤树突状细胞和M1型巨噬细胞的比例增加（P < 0.05），CD8+ T淋巴细胞在肿瘤组织中的浸润增加（P < 0.001），且促炎细胞因子IL-6和TNF-α水平升高（P < 0.01）。结论：MMR减毒活疫苗对TNBC的抗肿瘤作用可能与诱导肿瘤发生ICD进而激活抗肿瘤免疫相关。

OBJECTIVE

This paper reports a rare presentation of diffuse intraocular inflammation following reversed vaulted multipiece intraocular lens (IOL) implanted in the sulcus of a 7-year-old child.

This is a case report.

A 7-year-old child presented with persistent posterior pole inflammation and optic disc swelling after an improperly placed multipiece intraocular lens in the sulcus. Comprehensive eye and wholebody evaluations were performed with the aid of optical coherence tomography (OCT), magnetic resonance imaging (MRI) and systemic work-up to rule out other causes of uveitis to definitively diagnose the case. The reverse-vaulted lens was eventually explanted. After 1 week post-explantation, the visual acuity improved markedly to 20/100 with the appropriate spectacle prescription. The patient recovered from the ocular inflammation 8 months postoperatively.

This paper reports significant posterior pole inflammation as an uncommon yet potentially visually-disabling consequence of a reverse-vaulted sulcus placement of a multipiece intraocular lens in a child. Careful attention is warranted to ensure proper IOL orientation during implantation, especially in pediatric cataract surgery. Visual rehabilitation is important postoperatively

BACKGROUND

State universities in the Philippines should comply with the 2020 Occupational Safety and Health (OSH) standards for government workers and must be guided by the 2017 ASEAN University Network’s Healthy University Framework (HUF) for them to become healthy universities. Both policy documents identify OSH policy and programs as key components.

This study aimed to explore the challenges and opportunities in the implementation of health and safety policies and programs in a state university in the Philippines.

A case study design was used with a state university as its study site. Investigators conducted 14 key informant interviews and nine focus group discussions which were participated by system officials, campus officials, academic teaching staff, academic non-teaching Staff, support staff, and students. Thematic analysis was used to identify and understand emerging patterns and themes.

The results generated seven themes consisting of Policy and Committee, Dedicated Personnel and Unit,Budget and Technology, Collaboration, Programs and Services, Working and Learning Environment, and Role Models. The identified challenges in the implementation of health and safety programs in the university were: (1) limited budget to implement initiatives, (2) lack of collaboration among its offices, and (3) absence of a dedicated unit and staff. There were also opportunities to improve implementation: (1) strong implementation of certain policies and programs, (2) presence of a good working and learning environment, and (3) existence of role models.

The identified challenges and opportunities correspond to the elements of the system and infrastructure considered as principal determinants of a healthy university. There is a need to recognize the interrelatedness of such elements to ensure effective implementation of health and safety programs in the university. It also underscores the relevance of the HUF in promoting OSH within a university context.

Introduction: Periprosthetic joint infection (PJI) represents a serious burden in orthopaedic oncology. Through the years,several local expedients have been proposed to minimise the risk of periprosthetic infection. In this study, we report our outcomes using topical vancomycin powder (VP) with the aim to prevent PJIs.Materials and methods: Fifty oncological cases treated with massive bone resection and the implant of a megaprosthesis were included in our study. Among them, 22 [(GGroup A) received one gram of vancomycin powder on the surface of the implant and another gram on the surface of the muscular fascia]. The remaining 28 did not receive such a treatment (Group B). The rest of surgical procedures and the follow-up were the same for the two groups. Patients underwent periodical outpatient visits, radiographs and blood exams’ evaluations. Diagnosis of PJIs and adverse reactions to topical vancomycin were recorded.Results: None of the cases treated with topical vancomycin developed infections, whereas 6 of the 28 cases (21.4%) who did not receive the powder suffered from PJIs. These outcomes suggest that cases treated with VP had a significantly lower risk of post-operative PJI (p=0.028).None of our cases developed acute kidney failures or any other complication directly or indirectly attributable to the local administration of VP. Conclusions: The topical use of vancomycin powder on megaprosthetic surfaces and the overlying fascias, alongside with a correct endovenous antibiotic prophylaxis, can represent a promising approach in order to minimise the risk of periprosthetic infections in orthopaedic oncology surgery.

[摘 要] 目的：探究hsa_circ_0078607在结直肠癌组织和患者血清中的表达水平及其与结直肠癌患者临床病理特征的关系，评价其能否作为结直肠癌潜在的分子诊断标志物及治疗靶标。方法：收集2018年6月至2022年1月于柳州市人民医院胃肠外科接受结直肠癌切除手术患者的58对癌及癌旁组织标本，收集2020年1月至2022年12月于柳州市人民医院初次确诊的结直肠癌患者、结直肠息肉患者及健康人体检血清共152例；从结直肠癌差异表达circRNA谱中挑选特异性高表达的hsa_circ_0078607作为候选标志物，采用qPCR法检测其在结直肠癌细胞、组织、患者血清及结直肠息肉患者血清中的相对表达量，分析其与临床病理特征的关系。采用ROC曲线评估hsa_circ_0078607对结直肠癌及结直肠息肉的诊断价值。通过Circular RNA Interactome数据库预测与hsa_circ_0078607结合的miRNA，并用Cytoscape 3.9.1软件构建circRNA-miRNA-mRNA调控网络，同时通过GO/KEGG富集分析进一步了解其功能。结果：与癌旁组织或健康人血清相比，hsa_circ_0078607在结直肠癌细胞、组织和血清及息肉患者血清中呈高表达（P<0.001），其中有52例（89.7%）患者癌组织中表达上调，6例（10.3%）表达下调。结直肠癌组织中hsa_circ_0078607的相对表达量与肿瘤位置（P=0.029）、分化程度（P=0.046）和远处转移（P=0.043）有关联。ROC结果显示，在结直肠癌组织和血清中其诊断结直肠癌的AUC分别为0.845 7[95%CI（0.772 8，0.918 6），P<0.000 1]和0.868 3[95%CI（0.790 7，0.945 9），P<0.000 1]；在息肉患者血清中，hsa_circ_0078607诊断结直肠息肉的AUC为0.710 1 [95%CI（0.610 0，0.810 1）]。GO/KEGG富集分析结果表明，hsa_circ_0078607下游的miRNA可能参与RNA聚合酶Ⅱ启动子转录调控、蛋白K48-连锁泛素化、Wnt、Hippo及MAPK信号通路调控等多个生物过程。结论：Hsa_circ_0078607在结直肠癌细胞、组织和血清中呈高表达，其在结直肠癌组织中的表达水平与肿瘤位置、分化程度和远处转移有关联，提示其可作为结直肠癌潜在的分子诊断标志物；其还可能介导结直肠癌的发生发展过程，对发现结直肠癌潜在的治疗靶点有重要意义。

[Abstract] Objective: To analyze the expression of miR-185 and cell division cyclin 42 (CDC42) in osteosarcoma tissues and cells, and to preliminarily explore whether miR-185 affects the proliferation and migration of osteosarcoma MG63 cells by regulating CDC42. Methods: The cancer tissues and para-cancerous tissues of 28 patients with osteosarcoma that pathologically confirmed in the Fourth People&#39;s Hospital of Hengshui City from January 2020 to January 2021 were collected for this study. Immunohistochemistry was used to detect the expression of CDC42 in osteosarcoma tissues, and qPCR was used to detect the expression of miR-185 in osteosarcoma tissues. Dual-luciferase reporter gene experiment was applied to verify the targeting relationship between CDC42 and miR-185. According to different transfectants, MG63 cells were divided into miR-185 mimic group, miR-NC group, miR-185 inhibitor group, NC-inhibitor group, CDC42 group (transfected with CDC42 over-expression vector), and negative control (NC) group. The effects of miR-185 and CDC42 expression on the migration, proliferation and cell cycle of MG63 cells were detected by scratch healing assay, CCK-8 method and FCM, respectively. A nude mouse xenograft model was constructed by inoculating osteosarcoma MG63 cells. Immunohistochemistry, qPCR and WB methods were used to detect the effects of over-expression or knock-down of miR-185 on the expression of Ki67 and CDC42 in transplanted tumor tissues. Results: Compared with para-cancerous tissues, the expression of miR-185 in osteosarcoma tissues was significantly decreased, while the expression of CDC42 was significantly increased (all P<0.01). CDC42 was verified to be a target gene of miR-185. Compared with the control group, the migration and proliferation of MG63 cells in the miR-185 mimic group were inhibited (all P<0.01), while the migration and proliferation of MG63 cells in the CDC42 group were increased and the cell cycle was arrested in the S phase (all P<0.01). Compared with the miR-185 group, the migration and proliferation abilities of MG63 cells in the miR-185+CDC42 group were promoted, and the proportion of cells in S phase was increased (all P<0.01). Compared with the control group, the expression of Ki67 and CDC42 in the transplanted tumor tissues of miR-185 mimic group was significantly decreased (all P<0.01), while the opposite results were observed in miR-185 inhibitor group (all P<0.01). Conclusion: miR-185 is lowly expressed while CDC42 is highly expressed in osteosarcoma tissues. miR-185 can inhibit the proliferation and migration of osteosarcoma MG63 cells by negatively regulating the expression of CDC42.

Given the opposing effects of Akt and AMP-activated protein kinase (AMPK) on metabolic homeostasis, this study examined the effects of deletion of Akt2 and AMPKα2 on fat diet-induced hepatic steatosis. Akt2–Ampkα2 double knockout (DKO) mice were placed on high fat diet for 5 months. Glucose metabolism, energy homeostasis, cardiac function, lipid accumulation, and hepatic steatosis were examined. DKO mice were lean without anthropometric defects. High fat intake led to adiposity and decreased respiratory exchange ratio (RER) in wild-type (WT) mice, which were ablated in DKO but not Akt2−/− and Ampkα2−/− mice. High fat intake increased blood and hepatic triglycerides and cholesterol, promoted hepatic steatosis and injury in WT mice. These effects were eliminated in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet promoted fat accumulation, and enlarged adipocyte size, the effect was negated in DKO mice. Fat intake elevated fatty acid synthase (FAS), carbohydrate-responsive element-binding protein (CHREBP), sterol regulatory element-binding protein 1 (SREBP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor-α (PPARα), PPARγ, stearoyl-CoA desaturase 1 (SCD-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and diglyceride O-acyltransferase 1 (DGAT1), the effect was absent in DKO but not Akt2−/− and Ampkα2−/− mice. Fat diet dampened mitophagy, promoted inflammation and phosphorylation of forkhead box protein O1 (FoxO1) and AMPKα1 (Ser485), the effects were eradicated by DKO. Deletion of Parkin effectively nullified DKO-induced metabolic benefits against high fat intake. Liver samples from obese humans displayed lowered microtubule-associated proteins 1A/1B light chain 3B (LC3B), Pink1, Parkin, as well as enhanced phosphorylation of Akt, AMPK (Ser485), and FoxO1, which were consolidated by RNA sequencing (RNAseq) and mass spectrometry analyses from rodent and human livers. These data suggest that concurrent deletion of Akt2 and AMPKα2 offers resilience to fat diet-induced obesity and hepatic steatosis, possibly through preservation of Parkin-mediated mitophagy and lipid metabolism.

PURPOSE: With continuous positive airway pressure (CPAP) being the treatment of choice for Obstructive Sleep Apnea (OSA), adherence rates to CPAP are still low without a clear consensus of causes. The Self-Determination Theory (SDT) is a general theory of human motivation that emphasizes the extent to which behaviors are relatively autonomous based on the psychological needs that are critical to supporting the process of internalization and the development of optimal motivation. This study sought to determine whether the implementation of an SDT-based intervention is effective in improving: (1) perceived competence, (2) treatment self-regulation, (3) CPAP treatment adherence, and (4) Apnea–hypopnea index (AHI) of OSA patients. METHODS. Using a true experimental pretest-posttest design, 30 purposively selected participants were randomly allocated to experimental and control groups. The SDT-based intervention included group sessions, individual sessions, and follow up phone calls in three weeks. Written permission to conduct the study was obtained from the Institutional Review Board of the University of the East - Ramon Magsaysay Memorial Medical Center, Inc. (UERMMMCI) and the Lung Center of the Philippines. Participation was voluntary and all participants had the right to refuse or discontinue their participation at any time during the study. Data were analyzed using two way repeated-measures ANOVA, student&#39;s T-test, and chi-square. RESULTS AND CONCLUSION: The participants in the experimental group have increased adherence rates from Time 1 (60%) to Time 2 (92.9%) and Time 3 (85.7%). Although, when compared to the control group, no significant difference was noted across the different periods of measurement (p=0.70810, p=0870, p=0.2403). There were higher proportions of patients who eventually became adherent in the experimental group compared to the control group immediately after and 5 weeks after the intervention (p=0.0001). The experimental group had significantly better improvement in AHI compared to the control group immediately after (p=0.0152) and 5 weeks after the intervention (p=0.0022). Considering the importance of CPAP adherence in effectively treating OSA, measures to improve adherence such as SDT-based intervention could be usefully incorporated into OSA patients&#39; treatment plans.
Continuous Positive Airway Pressure ; Personal Autonomy ; Sleep Apnea, Obstructive