The role of SPP1 as a prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies and has a low 5-year survival rate. Mounting evidence suggests that oral potentially malignant disorders, such as oral leukoplakia (OLK), may progress to HNSCC. Given that OLK and HNSCC are often insidious and asymptomatic, the identification of markers of OLK malignant transformation and therapeutic targets in HNSCC is critical. Using various online tools and publicly available gene expression datasets, the secreted phosphoprotein 1 gene (SPP1) was identified as a significant differentially expressed gene among OLK, HNSCC, and non-cancerous tissues. SPP1 mRNA levels were elevated in HNSCC tissues and were associated with cancer stage, tumor grade, and human papillomavirus infection status. High SPP1 mRNA levels were correlated with poor overall survival of HNSCC patients. In contrast, SPP1 mutations were not significantly associated with overall survival, although their frequency in HNSCC was very low (0.6%). Furthermore, SPP1 expression levels in HNSCC were positively correlated with the infiltration of CD4⁺ cells, macrophages, neutrophils, and dendritic cells. The study results suggest that SPP1 may represent a diagnostic and prognostic biomarker, as well as a potential therapeutic target in HNSCC.     

Survival in node-positive early oral squamous cell carcinoma: sentinel node biopsy versus elective neck dissection

Patients undergoing sentinel node biopsy (SLNB) for early oral squamous cell carcinoma (OSCC) who harbour occult metastases (pN+ve) may be at greater risk of mortality due to prolonged overall treatment times than those identified as pN+ve on elective neck dissection (ELND). A retrospective comparative survival analysis was therefore undertaken to test this hypothesis. Patients were identified from the South Glasgow multidisciplinary team (MDT) database. Group 1 comprised 38 patients identified as pN+ve, or who were false negative, on sentinel lymph node biopsy (SLNB). Group 2 comprised 146 patients staged pN+ve on ELND. The groups were compared with the Kaplan Meier method and Cox proportional hazards model. In addition, a matched-pair analysis was performed. A unique and specifically designed algorithm was deployed to optimise the pairings. No difference in disease-specific or overall survival was found between the groups. Patients undergoing SLNB as the initial neck staging modality in early OSCC and are identified as pN+ve do not appear to be at a survival disadvantage compared with those staged with ELND.     

Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

Functions of the endothelium and its role in hematopoietic cell transplantation

The endothelium is a single-layered structure that responds to physical and chemical signals with various factors it synthesizes. In the early days of its discovery, as the inner wall of the vessels, the endothelium was thought to be a simple barrier that lays on the surface. Over time it is discovered that endothelium maintains body homeostasis with the molecules it synthesizes, despite its simple single-layer structure. It has been accepted as an important organ that contributes to the maintenance of vascular tone, cell adhesion, inflammation, vascular permeability and coagulation. Any imbalance in these physiological and pathological events causes endothelial dysfunction. This can cause many diseases such as atherosclerosis, hypertension, diabetes, or it can occur because of these. Endothelial related disorders may also complicate hematopoietic stem cell transplantation (HSCT), which is used to treat various hematologic and neoplastic diseases. These life-threatening complications include graft-versus-host disease, hepatic veno-occlussive disease, transplant-associated thrombotic microangiopathy and diffuse alveolar hemorrhage. They share a similar pathophysiology involving endothelial cells with different clinical presentations. Therefore, current researche on the issue is putting the endothelium under the spotlight for novel markers and treatment options that should be used to monitor or treat at least some of these complications following HSCT.     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.     

半夏泻心汤对DSS诱导的溃疡性结肠炎小鼠肠道微生态及Th17/Treg细胞平衡的影响＊

目的 观察半夏泻心汤对饮用葡聚糖硫酸钠（DSS）诱导建立的溃疡性结肠炎（UC）模型小鼠Th17/Treg细胞平衡及肠道微生态的影响，从免疫失衡及菌群紊乱角度分析半夏泻心汤治疗UC的作用机制。方法 将40只C57BL/6J雄性小鼠随机分为空白组、模型组、阳性药（美沙拉嗪）组及半夏泻心汤组，除空白组外的各小鼠采用2.5% DSS水溶液自由饮用7天诱导建立UC小鼠模型。自实验第8日起，分别采用灭菌水、美沙拉嗪水溶液、半夏泻心汤水溶液给上述各组别小鼠灌胃。采用HE染色观察结肠组织病理学变化，ELISA方法检测组织炎症因子含量，流式细胞术检测Th17及Treg细胞的相对数量，16S rRNA测序技术进一步检测模型小鼠粪便中菌群的变化。结果 与空白组比较，模型组小鼠结肠损伤严重，血清炎症因子含量显著升高（P<0.01）；与模型组比较，中药干预组小鼠结肠损伤减轻，血清TNF-α、IFN-γ含量显著下降（P<0.05）。较空白组小鼠相比，模型组小鼠Th17细胞百分比显著升高（P<0.01），而Treg细胞百分比显著降低（P<0.01）。经半夏泻心汤干预后，其小鼠Th17细胞数量均显著降低（P<0.05），Treg细胞数量则显著升高（P<0.05）。同时，半夏泻心汤可升高门水平上Firmicutes、属水平上Lachnospiraceae_NK4A136_group、unclassified_f_Lachnospiraceae、Prevotellaceae_UCG-001、Alistipes；降低门水平上Actinobacteriota，科水平上Bifidobacteriaceae、Atopobiaceae、Clostridiaceae，属水平上Clostridium_sensu_stricto_1、Coriobacteriaceae_UCG-002、Bifidobacterium的相对丰度。结论 半夏泻心汤可使Treg细胞相对数量升高、Th17细胞相对数量降低，以维持Th17/Treg细胞动态平衡；同时可降低有害菌Clostridium_sensu_stricto_1、Coriobacteriaceae_UCG-002的相对丰度，升高产短链脂肪酸类菌Lachnospiraceae_NK4A136_group、Prevotellaceae_UCG-001、unclassified_f_Lachnospiraceae等菌属的相对丰度，调控肠道微生物结构及动态平衡，从而发挥治疗UC的作用。     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

术前SCC与CYFRA21-1在肺鳞癌患者表达上调及临床意义

目的 分析术前SCC、CYFRA21-1与肺鳞癌临床病理特征、预后之间的关系。方法 收集2017年3月~2018年4月在云南省肿瘤医院确诊的肺鳞癌患者100例为观察组，确诊为肺良性肿瘤患者90名为肺良性肿瘤组、以及正常人群90名为健康人群组。通过电化学发光法对SCC、CYFRA21-1两种指标进行检测。检测SCC、CYFRA21-1含量，分析在肺鳞癌中表达的临床意义。结果 SCC、CYFRA21-1在肺鳞癌中比在肺良性肿瘤、健康人群中含量要高，差异有统计学意义（P＜0.001），并且敏感性均高于其他两组；男性患者的SCC、CYFRA21-1含量高于女性患者，差异具有统计学意义（P＜0.05）；SCC、CYFRA21-1含量在年龄≥60岁的含量高于＜60岁患者，差异无统计学意义（P＞0.05）；有吸烟史患者的SCC含量高于无吸烟史患者，差异无统计学意义（P＞0.05）。CYFRA21-1在吸烟史患者中高表达，差异有统计学意义（P＜0.05）；SCC、CYFRA21-1在有淋巴结转移、远处转移、肿瘤直径≥5 cm、病理分期为晚期时高表达，差异具有统计学意义（P＜0.05）；SCC、CYFRA21-1阳性患者OS、PFS比阴性患者短；SCC、CYFRA21-1两者之间呈正相关,相关系数（r）为0.630。结论 SCC、CYFRA21-1在肺鳞癌中表达上调；SCC、CYFRA21-1与性别之间存在某种内在联系；SCC、CYFRA21-1与肺鳞癌的TNM分期呈正相关；SCC、CYFRA21-1阳性患者OS、PFS比阴性患者短；SCC、CYFRA21-1两者之间呈正相关,相关系数（r）为0.630。     

Management of blood pressure disorders in individuals with spinal cord injury

Blood pressure regulation is impacted by a spinal cord injury (SCI) due to impaired descending sympathetic vascular control. Common blood pressure problems in the SCI population include persistently low blood pressure with bouts of orthostatic hypotension and autonomic dysreflexia, which are more prevalent in individuals with lesions above the sixth thoracic vertebral level; however, they may occur regardless of the neurological level of injury. Although blood pressure disorders adversely impact daily function and quality of life, most individuals with SCI do not acknowledge this association. Few pharmacological options have been rigorously tested for safety and efficacy to manage blood pressure disorders in the SCI population. Furthermore, clinical management of any one blood pressure disorder may adversely impact others, as such treatment is complicated and not often prioritized.