Glycoprotein hormone α-subunit promotes cell proliferation and tumorigenesis in breast cancer

The glycoprotein hormone α-subunit (CGA) is implicated in the occurrence and progression of a number of solid tumors. However, its role in breast cancer remains unclear. The present study aimed to investigate the biological functions and mechanisms of action of CGA in breast cancer. CGA protein expression was evaluated in clinical breast cancer specimens using immunohistochemistry. The association between CGA expression and patient prognosis was determined using the Kaplan-Meier method and Mantel-Cox test. At the same time, CGA mRNA and protein expression was explored in a normal mammary epithelial cell line and breast cancer cell lines. Breast cancer cell lines overexpressing or deficient in CGA were established, and the effect of CGA on cell proliferation was evaluated in vitro, and in vivo using a mouse xenograft tumor model. Intracellular signaling pathway activities were evaluated using western blotting in CGA-overexpressing or -depleted cells. Increased CGA protein expression was significantly associated with a poor prognosis in patients with breast cancer. Furthermore, while CGA mRNA and protein expression level was negligible in normal mammary epithelial cells, it was elevated in breast cancer cell lines. In vitro and in vivo experiments showed that CGA overexpression enhanced breast cancer cell proliferation via activation of the epidermal growth factor receptor, extracellular signal-regulated kinase 1/2 and serine/threonine kinase Akt signaling cascades. The present results suggest that CGA is upregulated in breast cancer tissues and that it is associated with a poor prognosis. CGA may serve as a candidate for developing targeted therapies for breast cancer.     

癸酸能够活化CD8+ T细胞并提高其抗肿瘤免疫反应能力

目的：探究中链脂肪酸癸酸对CD8+ T细胞活化的影响,及其对CD8+ T细胞介导的抗肿瘤免疫反应的作用和机制。方法：建立C57BL/6小鼠黑色素瘤B16F10 皮下荷瘤模型,随机分为癸酸组（10 mg/kg 癸酸灌胃）和对照组（等量溶剂灌胃）,观察癸酸对小鼠肿瘤生长以及生存率的影响,采用流式细胞术检测肿瘤微环境中浸润CD8+ T细胞的活化水平。建立B16F10-OVA和OT-I T细胞共培养体系,采用流式细胞术检测癸酸对CD8+ T细胞的肿瘤细胞杀伤能力的影响。采用α-CD8抗体清除B16F10 荷瘤小鼠体内CD8+ T细胞,观察对小鼠肿瘤体积的影响。小鼠原代CD8+ T细胞经癸酸处理后,采用WB、ELISA及qPCR、流式细胞术检测T细胞受体（TCR）活化、效应细胞因子产生以及增殖和代谢水平。在B16F10荷瘤小鼠模型中,观察α-PD-1抗体联合癸酸给药对小鼠肿瘤生长以及生存率的影响。结果：在小鼠黑色素瘤荷瘤模型中,与对照组相比,癸酸组小鼠移植瘤体积显著降低且生存率显著提高（均P<0.05）,肿瘤浸润CD8+ T细胞IFN-γ和TNF-α的表达水平显著升高（P<0.01）。经癸酸处理的OT-I T细胞对B16F10-OVA细胞的杀伤水平显著升高（P<0.01）。在荷瘤小鼠模型中用α-CD8 抗体清除CD8+ T 细胞后,癸酸对移植瘤的抑制作用显著降低（P<0.000 1）。小鼠原代CD8+ T细胞经癸酸处理后,TCR活化水平显著升高、细胞因子IL-2和IFN-γ的产生增多、线粒体代谢水平显著上调（均P<0.05）。在黑色素瘤荷瘤小鼠模型中,癸酸与α-PD-1抗体联用,能够显著抑制小鼠移植瘤生长并提高其生存率（均P<0.05）。结论：癸酸能够促进CD8+ T细胞活化、增强其抗肿瘤免疫反应能力。     

Investigating the Mechanical Properties and Durability of Metakaolin-Incorporated Mortar by Different Curing Methods

In this paper, the traditional, silicate-based Portland cement (PC) was employed as the control to explore the impact of adding varying amounts of metakaolin (MK) on the mechanical properties of cement mortar. In fact, as a mineral admixture, metakaolin (MK) has the ability to significantly improve the early strength and sulfate resistance of cement mortar in traditional, silicate-based Portland cement (PC). In addition to this, the performance of Portland cement mortar is greatly affected by the curing mode. The previous research mainly stays in the intermittent curing and alkaline excitation mode, and there are few studies on the influence of relatively humidity on it. Moreover, the paper investigated the impact of four different curing methods about humidity on the mechanical properties and sulfate resistance. The results show that the best content of metakaolin in Portland cement is 10% (M10), and the best curing method is 95% humidity in the first three days followed by 60% humidity in the later period (3#). Based on previous literature that suggests that adding MK thickens water film layer on the surface of mortar, the mechanism of MK increasing the early strength of cement was analyzed. The compressive strength of the Portland cement containing 10% MK (M10) after 1 day curing is 3.18 times that of pristine PC mortar, and is comparable if PC is cured for three days under the same curing conditions. The traditional PC mortar is highly dependent on the wet curing time, and normally requires a curing time of at least seven days. However, the incorporation of MK can greatly reduce the sensitivity of Portland cement to water; MK cement mortar with only three days wet curing (3#M10) can reach 49.12 MPa after 28 days, which can greatly shorten the otherwise lengthy wet curing time. Lastly, the cement specimens with MK also demonstrated excellent resistance against sulfate corrosion. The work will provide a strong theoretical basis for the early demolding of cement products in construction projects. At the same time, this study can also provide a theoretical reference for the construction of climate drought and saline land areas, which has great reference value.     

中医护理在老年慢性心力衰竭中的应用效果

目的:观察中医护理在老年慢性心力衰竭(CHF)中的应用效果.方法 :选取80例老年CHF患者,按随机数字表法分为观察组与对照组各40例.2组均给予常规西药治疗,对照组给予常规护理,观察组在此基础上实施中医护理(包括情志护理、穴位贴敷及饮食护理),2组均干预1个月.比较2组治疗前后的心功能指标、汉密尔顿抑郁量表(HAMD...     

Molecular phenotypes reveal heterogeneous engraftments of patient-derived hepatocellular carcinoma xenografts

ObjectivePatient-derived xenograft (PDX) models provide a promising preclinical platform for hepatocellular carcinoma (HCC). However, the molecular features associated with successful engraftment of PDX models have not been revealed.MethodsHCC tumor samples from 76 patients were implanted in immunodeficient mice. The molecular expression was evaluated by immunohistochemistry. Patient and tumor characteristics as well as tumor molecular expressions were compared for PDX engraftment using the Chi-square test. The independent prediction parameters were identified by logistic regression analyses.ResultsThe engraftment rate for PDX models from patients with HCC was 39.47% (30/76). Tumors from younger patients and patients with elevated preoperative alpha-fetoprotein level had higher engraftment rates. Tumors with poor differentiation and vascular invasion were related to engraftment success. The positive expression of CK19, CD133, glypican-3 (GPC3), and Ki67 in tumor samples was associated with engraftment success. Logistic regression analyses indicated that GPC3 and Ki67 were two of the strongest predictors of PDX engraftment. Tumors with GPC3/Ki67 phenotypes showed heterogeneous engraftment rates, with 71.9% in GPC3⁺/Ki67⁺ tumors, 30.8% in GPC3⁻/Ki67⁺ tumors, 15.0% in GPC3⁺/Ki67⁻ tumors, and 0 in GPC3⁻/Ki67⁻ tumors. ConclusionsSuccessful engraftment of HCC PDXs was significantly related to molecular features. Tumors with the GPC3⁺/Ki67⁺ phenotype were the most likely to successfully establish HCC PDXs.     

宫颈上皮内瘤变与宫颈癌中乙酰肝素酶的表达

目的:探讨乙酰肝素酶在宫颈黏膜上皮内瘤变(CIN)与宫颈鳞癌中的表达.方法:应用免疫组化SP法检测乙酰肝素酶在56例CIN(CINⅠ12例,CINⅡ26例,CINⅢ18例),宫颈鳞癌54例(伴有淋巴结转移的20例)中的表达.结果:在CINⅠ,CINⅡ,CIN Ⅲ组织中乙酰肝素酶阳性表达率分别为33.33%,38.48%,44.44%,宫颈鳞癌中乙酰肝素酶阳性表达率为48.14%.CIN与宫颈鳞癌的表达对比统计学无意义(P＞0.05).20例宫颈鳞癌伴淋巴结转移者,其癌组织内乙酰肝素酶阳性表达(70.00%)明显高于无转移组(35.29%),差异有显著性(P＜0.01)结论:乙酰肝素酶表达与宫颈鳞癌发生、发展无关.与宫颈鳞癌淋巴结转移有关.     

A trial of pirfenidone in hospitalized adult patients with severe coronavirus disease 2019

<正>To the Editor: Coronavirus disease 2019 (COVID-19), which broke out in 2019, has become a global pandemic. Similar to severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, SARS-CoV-2 could     

Effect of Fly Ash and Metakaolin on Properties and Microstructure of Magnesium Oxysulfate Cement

To improve the mechanical performance and lower the production cost of magnesium oxysulfate cement (MOSC), this article investigates the effects of single and compounded addition of metakaolin (MK) and/or fly ash (FA) on the setting time, mechanical strength, water resistance, hydration product, composition, and microstructure of the resulting cement. MOSC samples with different proportions, ranging from 0 to 30 wt.%, of FA and/or MK substituting magnesium oxide (MgO) were prepared. The microstructure was explored by scanning electron microscopy, X-ray diffraction, and mercury intrusion porosimetry. The findings suggest that adding FA can delay the setting of MOSC; however, the effect of adding MK to MOSC was reversed. Furthermore, the phase composition of the MOSC hydration products was unaltered upon adding FA and/or MK, but thicker and longer 517 phase crystals were observed. FA and MK can effectively fill the large pores of MOSC through filling and nucleation effects, reduce the pore size, and form a denser microstructure, thereby improving its mechanical properties. The optimal MOSC sample was found by substituting 10 wt.% of both FA and MK, resulting in a cement that exhibited a short setting time and an incredibly high mechanical strength and density. These findings will further the development of stronger, more cost-efficient, and more water-resistant MOSC products.     

2型糖尿病患者糖化血红蛋白、超氧化物歧化酶水平与角膜神经损伤的相关性

目的 探讨糖化血红蛋白、超氧化物歧化酶在2型糖尿病(T2DM)患者中的表达以及其与角膜神经损伤的相关性。方法 选取焦作市第二人民医院2019年12月至2021年12月收治的80例T2DM患者为研究组,选取同期95例健康体检人群作为对照组。检测受试者糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)和超氧化物歧化酶(SOD)水平,并检测角膜神经纤维密度(CNFD)、角膜神经分支密度(CNBD)和角膜神经纤维长度(CNFL),根据角膜神经损伤参数将患者分为损伤组与未损伤组。比较血液指标与角膜神经参数并通过Pearson相关性分析两者相关性。结果 研究组HbA1c、FPG和2 h PG水平高于对照组,SOD水平低于对照组(P<0.05)。研究组CNFD、CNBD和CNFL水平低于对照组(P<0.05)。研究组角膜神经损伤患者32例,未损伤患者48例。损伤组患者HbA1c、FPG和2 h PG均高于未损伤组,SOD水平低于未损伤组(P<0.05)。损伤组患者CNFD、CNBD和CNFL均低于未损伤组(P<0.05)。相关性分析结果显示,CNF...     

Circulating miR-130b mediates metabolic crosstalk between fat and muscle in overweight/obesity

Aims/hypothesis

Adipose tissue is a dynamic endocrine organ that regulates whole-body energy homeostasis through the secretion of signalling molecules. Recent reports suggest that secreted microRNAs (miRNAs) may function as biologically active molecules for intercellular communication. This study aims to identify obesity-related circulating miRNA that could be secreted from adipocytes and to explore its possible role in the pathogenesis of metabolic diseases.

Methods

Real-time RT-PCR was used to evaluate the circulating level of miR-130b in mouse models of obesity as well as in humans. Luciferase assay and immunoblotting were used to verify the miRNA target. The effect of miR-130b on mouse peroxisome proliferator-activated receptor γ coactivator-1α was also investigated by electrogene transfer.

Results

The circulating level of miR-130b was elevated in mouse models of obesity as well as in obese Chinese individuals. More interestingly, the circulating level of miR-130b was positively correlated with BMI. Moreover, circulating miR-130b was a better predictor of the metabolic syndrome than was triacylglycerol level. Mechanistically, adipocytes secreted miR-130b during adipogenesis. TGF-β, which is proportionately increased with obesity, stimulated miR-130b secretion from adipocytes. Furthermore, miR-130b was able to target muscle cells and reduce the expression of its direct target gene, PGC-1α (also known as PPARGC1A), which plays a key role in lipid oxidation in muscle.

Conclusions/interpretation

Circulating miR-130b reflects the degree of obesity and could serve as a potential biomarker for hypertriacylglycerolaemia and metabolic syndrome. Circulating miR-130b could function as a metabolic mediator for adipose–muscle crosstalk and might be involved in the pathogenesis of obesity-associated metabolic diseases.