Background: Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism. Methods: An in vivo nude mouse model was established, and the expression of CD206, CD80, and M2 phenotype-related proteins (Arg-1, Fizz1) was obtained by flow cytometry and western blotting. The expressions of the M2 phenotype-related cytokines were examined by ELISA. Results: Qingrexiaoji recipe inhibited gastric tumor growth and downregulated the expression of CD206, IFN-γ, IL-13, IL-4, and TNF-α in vivo. Qingrexiaoji recipe deceased M2 phenotypic polarization by upregulating microRNA (miR)-29a-3p level. Luciferase activity assays showed that HDAC4 is a potential target of miR-29a-3p. In cells co-transfected with HDAC4 siRNA and miR-29a-3p inhibitor and treated with IL-4 and Qingrexiaoji recipe, the miR-29a-3p inhibitorinduced increase of M2 phenotypic polarization was reversed. Conclusion: In summary, these results suggested that the Qingrexiaoji recipe regulated M2 macrophage polarization by regulating miR-29a-3p/HDAC4, providing a different and innovative treatment for gastric cancer.

[This retracts the article DOI: 10.1155/2021/6664591.].

Abstract Objective Lithium is a monovalent cation that was introduced in 1949 by John Cade for the treatment of bipolar disorder，especially for mania.As for mood stabilizer, it should be effective in treatment of depression.To explore lithium alleviate the apoptosis of nerve cells through JNK/ C-Jun signaling pathway and improve the depressive symptoms in depressed mice. Methods 30 male mice were randomly divided into blank control(control) , model group(stress) and drug intervention group(stress+lithium). A model of depression was established by Chronic unpredictable mild stress (CUMS). Mice in stress+lithium group were given lithium from 4th weekend. The behavior of mice were evaluated and Western blot was used to detect expression levels of related proteins. Results Compared with control, stress+lithium group showed a significant decrease depressive symptoms (P< 0.01).Western blotting results show that compared with stress group, protein levels of P-JNK /JNK ,P-C-Jun/C-Jun ,caspase-3 and Bax in PFC of control were significantly increased (P < 0.01), Bcl-2 level significantly decreased (P < 0.01);Compared with the stress group, the protein levels of nerve cells p-JNK/JNK, P-C-Jun/C-Jun, aspase-3 and Bax in prefrontal cortex of mice in stress +lithium group were significantly decreased (P< 0.01), Bcl-2 level increased significantly (P < 0.01). Conclusions Lithium improve depression symptoms by reducing apoptosis of prefrontal cortex nerve cells through JNK/ C-Jun signaling pathway in depressive mice.

There is considerable heterogeneity in the genomic drivers of lung adenocarcinoma, which has a dismal prognosis. Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model. According to the risk score, a Kaplan-Meier cumulative curve was plotted to evaluate the prognostic value. Furthermore, a nomogram was established to predict the three-year and five-year survival of patients with LUAD based on their prognostic characteristics. Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, P< 0.0001). The Kaplan-Meier cumulative curve showed that low-risk patients had significantly better overall (P<0.0001). The validation dataset GSE68465 further confirmed the nomogram's robust ability to assess the prognosis of LUAD patients. A prognosis model of autophagy-related genes based on a LUAD dataset was constructed and exhibited diagnostic value in the prognosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3 and ITGB1 in LUAD cell lines. Two key autophagy-related genes have been suggested as prognostic markers for lung adenocarcinoma.

Gastric cancer (GC) is a common cancerous tumor, and is the third leading cause of cancer mortality worldwide. Although comprehensive therapies of GC have been widely used in clinical set ups, advanced gastric cancer carries is characterized by poor prognosis, probably due to lack of effective prognostic biomarkers. Mammalian histone deacetylase family, histone deacetylases (HDACs), play significant roles in initiation and progression of tumors. Aberrant expression of HDACs is reported in many cancer types including gastric cancer, and may serve as candidate biomarkers or therapeutic targets for GC patients. Gene Expression Profiling Interactive Analysis was used to explore mRNA levels of HDACs in GC. Kaplan-Meier plotter was used to determine the prognostic value of HDACs mRNA expression in GC. Genomic profiles including mutations of HDACs were retrieved from cBioPortal webserver. A protein-protein interaction network was constructed using STRING database. GeneMANIA was used to retrieve additional genes or proteins related to HDACs. R software was used for functional enrichment analyses. Analysis of mRNA levels of HDAC1/2/4/8/9 showed that they were upregulated in GC tissues, whereas HDAC6/10 was downregulated in GC tissues. Aberrant expression of HDAC1/3/4/5/6/7/8/10/11 was all correlated with prognosis in GC. In addition, expression levels of HDACs were correlated with different Lauren classifications, and clinical stages, lymph node status, treatment, and human epidermal growth factor receptor 2 status in GC. The findings of this study showed that HDAC members are potential biomarkers for diagnosis or prognosis of gastric cancer. However, further studies should be conducted to validate these findings.

Depression is an increasingly common but extremely serve mood disorder that remains poorly understood and inadequately treated. Fast-spiking parvalbumin-positive interneurons (PVIs), a subpopulation of GABAergic interneurons (GABA, g-aminobutyric acid), exhibit a widespread distribution throughout the hippocampus, and has been reported to play an important role in a variety of mental disorders. However, the relationship between depression and hippocampal PVIs remains unclear. Here in this present study, a series of experiments were conducted to clarify the potential relationship. Here, chronic unpredicted mild stress (CUMS) and Lipopolysaccharide (LPS) injection were introduced to induce depression-like behavior in mice, and led to a clear decline in PVIs numbers in the ventral hippocampal (vHPC), particularly in the ventral dentate gyrus (vDG) subfield. After a selectively removal of the PVIs in PV-ires-Cre::Ai14 mice, we confirmed that ablation of PVIs from the vDG induced depression-like behavior. Furthermore, we found that the removal of vDG-PVIs induced depression likely to be accounted for upregulation of neuroinflammation. These findings facilitate us better understand the role of hippocampal PVIs in depression.

Hypoxia-inducible factor 1 can sufficiently control the progress of neurological symptoms after ischemic stroke owing to their actions associated with its downstream genes. In this study, we evaluated the role of HIF-1α in attenuating brain damage after endothelin-1 injection. Focal cerebral ischemia in mice were induced by endothelin-1 microinjection. Hypoxia-inducible factor 1 activator, dimethyloxalylglycine (DMOG), and HIF-1α inhibitor, acriflavine (ACF), were used to evaluate the hypoxia-inducible factor 1 activity during cerebral ischemia. The expression levels of HIF-1α, glial fibrillary acidic protein (GFAP), interleukin-10 (IL-10), inducible nitric oxide synthase (iNOS), phosphorylated I-kappa-B-alpha/total I-kappa-B-alpha (p-IκBα/IκBα) and nuclear factor kappa B (NF-kB) were assessed. Besides, mRNA levels of IL-10, tumor necrosis factor- alpha (TNF-α), and NF-kB were also analyzed. Results showed a noticeable increase in hypoxia-inducible factor 1 and IL-10 levels in the DMOG group with a decline in iNOS, TNF-α, and NF-kB levels, implying the anti-inflammatory role of hypoxia-inducible factor 1 activator following stroke. These findings were further corroborated by GFAP immunostaining that showed astrocytic activation to be inhibited 12 days post-ischemia, as well as histological and TEM analyses that demonstrated hypoxia-inducible factor 1 induction to alleviate neuronal soma damage and cell death. Based on our study, HIF-1α could be a potential therapeutic target for ischemic stroke.

目的 建立大鼠异嗜高岭土模型,研究温胆汤治疗化疗所致迟发性呕吐(CINV)的疗效及对胃肠激素分泌的影响,对其作用机制进行初步探讨.方法 30只大鼠先行适应性高岭土饲养,然后随机分为6组:对照组,模型组,昂丹司琼组,温胆汤低、中、高剂量组,每组5只,除对照组外,其余各组均腹腔注射顺铂以制造化疗所致的大鼠嗜高岭土模型,观察并记录造模后48 h内大鼠正常饲料及高岭土的耗用量;测定外周血血管活性肠肽(VIP)、表皮生长因子(EGF)、胃泌素(Gas)及大鼠胃窦组织P物质(SP)的表达.结果 实验成功建立大鼠异嗜高岭土模型.在造模后48 h内,与模型组相比,温胆汤高、中剂量组大鼠的摄食量明显增加(P＜0.05);温胆汤高、中剂量组大鼠对高岭土的耗用量明显减少(P＜0.01);温胆汤高、中、低剂量组均能显著降低异嗜大鼠外周血中VIP(P＜0.01)和Gas(P ＜0.05)的含量,均可促进异嗜大鼠外周血中EGF的表达(P＜0.01);温胆汤高、中剂量组能显著减少异嗜大鼠胃窦组织SP免疫组化表达(P＜0.01).结论 温胆汤对化疗所致迟发性呕吐有一定疗效,其作用机制与调节胃肠激素分泌,保护胃肠黏膜,促进胃排空并抑制胃窦组织SP的表达等有关.

目的 应用RNA干扰(RNAi)技术干扰BECN1基因的表达,探讨蛇六谷石油醚提取物对BECN1基因敲减的人胃癌SGC-7901细胞增殖的影响.方法 用前期实验构建成功的GV112(LV-BECN1-RNAi)重组慢病毒表达载体转染人胃癌SGC-7901细胞.MTT法检测蛇六谷石油醚提取物抑制胃癌细胞增殖的有效浓度,确定实验药物浓度.每24h(共120h)用CCK法检测人胃癌SGC-7901细胞KD+蛇六谷(BECN1基因敲减组)、NC+蛇六谷(阴性对照组)、CON+蛇六谷(空白组)的细胞活性.结果 蛇六谷石油醚提取物能有效抑制人胃癌SGC-7901细胞增殖,且呈明显的浓度依赖性(P＜0.01);当人胃癌SGC-7901细胞BECN1基因敲减时则会降低其抑制作用(P＜0.05).结论 BECN1基因敲减能减弱蛇六谷石油醚提取物抑制人胃癌SGC-7901细胞增殖的能力,这可能是通过调节BECN1基因的表达诱导细胞自噬,从而抑制人胃癌SGC-7901细胞增殖.

表皮生长因子受体抑制剂(Epidermal growth factor receptor inhibitors,EGFRIs)作为一种研究较成熟的靶向药物,已被广泛应用于肺癌、结直肠癌等恶性肿瘤的治疗,但其相关的不良反应不容忽视,其中皮疹最为常见,中医药在EGFRIs相关皮疹的治疗方面有独特的优势.笔者将从中医辨证分型、中医药内服及外敷等方面,综述中医药治疗EGFRIs相关皮疹的研究进展.

Osteoarthritis (OA) is the most common arthropathy, characterized by progressive degeneration of the articular cartilage. Currently, there are no disease-modifying approaches for OA treatment. Adeno-associated virus (AAV)-mediated gene therapy has recently become a potential treatment for OA due to its exceptional characteristics; however, the tropism and transduction efficiency of different AAV serotypes to articular joints and the safety profile of AAV applications are still unknown. The present study aims to screen an ideal AAV serotype to efficiently transfer genes to arthritic cartilage. AAV vectors of different serotypes expressing eGFP protein were injected into the knee joint cavities of mice, with all joint tissues collected 30 days after AAV injection. The transduction efficiency of AAVs was quantified by assessing the fluorescent intensities of eGFP in the cartilage of knee joints. Structural and morphological changes were analyzed by toluidine blue staining. Changes to ECM metabolism and pyroptosis of chondrocytes were determined by immunohistochemical staining. Fluorescence analysis of eGFP showed that eGFP was expressed in the cartilage of knee joints injected with each AAV vector. Quantification of eGFP intensity indicated that AAV2, 7 and 8 had the highest transduction efficiencies. Both toluidine blue staining and Mankin score showed that AAV6 aggravated cartilage degeneration. The analysis of key molecules in ECM metabolism suggested that AAV5 and 7 significantly reduced collagen type II, while AAV9 increased ADAMTS-4 but decreased MMP-19. In addition, transduction with AAV2, 5, 7 and 8 had no obvious effect on pyroptosis of chondrocytes. Comprehensive score analysis also showed that AAV2 had the highest score in intra-articular gene transfer. Collectively, our findings point to AAV2 as the best AAV serotype candidate for gene transfer on arthritic cartilage, resulting in minimal impact to ECM metabolism and pyroptosis of chondrocytes.

目的 探讨Beclin1基因对β-榄香烯抗人胃癌SGC-7901细胞增殖及自噬诱导的影响.方法 用前期实验构建成功的GV112-Beclin1-shRNA1(short hairpin RNA,短发夹RNA)慢病毒载体感染人胃癌SGC-7901细胞.采用四甲基偶氮唑盐微量酶反应比色法(MTT)检测β-榄香烯对SGC-7901细胞增殖的抑制作用,以及沉默Beclin1基因后对β-榄香烯抗增殖能力的影响.免疫蛋白印迹(Western blot)检测自噬相关蛋白LC3-II、P62的表达,评价β-榄香烯作用SGC-7901后的自噬水平和Beclin1基因沉默对β-榄香烯诱导自噬的影响.结果 MTT法显示,β-榄香烯能够抑制胃癌SGC-7901细胞增殖,抑制作用随浓度的增加而递增(浓度为20、50、100μg/mL比0μg/mL时,抑制率为21.5%、31.7%、37.4%比0,P＜0.05);沉默Beclin1基因后β-榄香烯抑制胃癌SGC-7901细胞抑制率增加(42.3%比36.1%,P＜0.05).Western blot法显示,β-榄香烯能诱导SGC-7901细胞发生保护性自噬,自噬相关蛋白LC3-Ⅱ表达上调,P62蛋白表达下降,沉默Beclin1基因可抑制β-榄香烯对SGC-7901细胞保护性自噬的增强,LC3-Ⅱ蛋白表达水平下降,P62蛋白表达增加.结论 β-榄香烯可诱导胃癌SGC-7901细胞发生保护性自噬,下调Beclin1基因有助于降低保护性自噬的发生,从而增强β-榄香烯的抗癌效果.

目的:探讨黄芪多糖(APS)对脂多糖(LPS)诱导的THP-1源巨噬细胞产生细胞因子TNF-α、IL-12和IL-10的影响及其抗肿瘤的机制.方法:实验设置THP-1组(空白对照组)、THP-1+LPS组(模型组)、THP-1+LPS+APS低浓度组、THP-1+LPS+APS高浓度组,通过佛波酯(PMA)诱导THP-1细胞分化成巨噬细胞,并通过LPS刺激建立炎症模型,将APS作用于THP-1源巨噬细胞进行24h、48h体外实验,分别采用逆转录-聚合酶链反应(RT-PCR)及酶联免疫法(ELISA)检测THP-1源巨噬细胞的IL-10、IL-12和TNF-αmRNA转录水平及蛋白的表达水平.结果:模型组细胞IL-10、IL-12和TNF-αmRNA及蛋白表达水平均明显增加,与空白对照组细胞比较,均有显著意义(P<0.05).不同浓度APS组能够上调由LPS刺激引起的IL-12、TNF-αmRNA及其蛋白表达水平的增加,下调IL-10的表达.结论:黄芪多糖(APS)可能通过影响THP-1源巨噬细胞的IL-12、IL-10、TNF-αmRNA及蛋白的表达水平,从而起到调节细胞免疫功能,抑制肿瘤生长的作用,并呈一定的浓度与时间依赖性,其具体作用机制仍值得进一步探讨及研究.

蛇六谷,又名魔芋,性味辛寒,有小毒,具有化痰散结、行瘀消肿止痛等功效,作为抗癌中药在浙沪地区广泛使用.现代研究发现蛇六谷中魔芋葡甘露聚糖(KGM)含量最多,约占50％～60％,是蛇六谷抗肿瘤作用的主要成分[1].本实验在建立Lewis肺癌小鼠动物模型的基础上,采用酶联免疫吸附试验(ELISA)法检测KGM对荷瘤小鼠脾细胞核转录因子-κB(NF-κB)、核因子-κB抑制因子(IκB)表达的影响,为KGM的抗肿瘤作用提供一定的分子学依据.

*通信作者 前列腺癌是目前世界排名第二位的男性恶性肿瘤[1].全球每年约有160万男性被诊断,36.6万男性死于前列腺癌[2].2017年仅北美地区新发病例有约161~360例,占男性新发癌症病例的19% ;造成死亡26730例,占男性癌症死亡人数的8%[3].在中国,随着近年来人口老龄化、生活方式和饮食结构的改变,前列腺癌的发病率正呈逐年上升趋势[4].早期前列腺癌无明显的临床症状,因此大多数患者在确诊时已处于中晚期.内分泌治疗作为中晚期前列腺癌的重要治疗手段,能明显延长患者的生存期,但也存在一系列不良反应,且绝大多数患者在经历18~36个月内分泌治疗后会产生药物抵抗,进入去势抵抗性前列腺癌(CRPC)阶段[5].目前CRPC的治疗方法较局限,且治疗费用昂贵,中位生存时间短,总体预后差.因此,如何延缓前列腺癌向CRPC发展,如何针对CRPC采取有效的治疗措施是目前亟待解决的问题.中医药在整体观和辨证论治的思想指导下,善于通过阴阳平调,扶正祛邪,从而达到延缓或抑制肿瘤进展的目的.本文就近年来中医药在延缓和治疗前列腺癌去势抵抗、提高患者生活

To some extent, melancholia in different Traditional Chinese Medicine (TCM) Syndromes represents different "subtypes" of depression. Whether bipolar depression or general depression, whether accompanied with or without psychotic symptoms, or with or without cognitive impairment, there are clinical and possible biological differences in these depressions, which indicates that different "subtypes" of depression represented by different TCM syndromes not only are different clinical syndromes, but also imply that there may be some biomarkers. The melancholia with liver depression and stagnation is different from melancholia with deficiency of both heart and spleen in clinical symptoms, which may indicate that there are differences in some potential biological biomarkers. For example, central nervous transmitters, trace elements, electrophysiology, neuroendocrinology, brain imaging, and even genomics may differ among different TCM syndrome types of depression, which not only serves for the modernization of TCM, but also finds biological differences for different TCM syndrome types of depression.

目的:探讨beclin-1基因沉默对蛇六谷提取物损伤人胃癌SGC-7901细胞的影响.方法:采用携带beclin-1-shRNA的慢病毒载体感染胃癌SGC-7901细胞,敲减beclin-1基因表达;蛇六谷提取物处理beclin-1基因敲减和未敲减的SGC-7901细胞,CCK-8法检测细胞活力,流式细胞术分析细胞凋亡率,Western blot检测beclin-1和LC3的蛋白表达水平.结果:Beclin-1-shRNA转染SGC-7901细胞抑制beclin-1的mRNA和蛋白表达,促进LC3蛋白表达,降低细胞活力,增加细胞凋亡率(P<0.05);蛇六谷提取物上调SGC-7901细胞的beclin-1和LC3蛋白表达,但下调beclin-1基因敲减的SGC-7901细胞的LC3蛋白表达,并显著降低细胞活力和增加细胞凋亡率(P<0.05).结论:Beclin-1基因沉默阻断蛇六谷提取物对beclin-1相关信号通路的激活,增强蛇六谷提取物对胃癌SGC-7901细胞活力的损伤作用.

目的:观察中药蛇六谷主要化学成分—魔芋葡甘露聚糖(Konjac glucomannan,KGM)对荷Lewis肺癌小鼠脾细胞转化生长因子-β(Transforming grwoth factor-β,TGF-β)mRNA、白细胞介素-10(Interleukin-10,IL叶10)mRNA表达的影响.方法:建立Lewis肺癌小鼠动物模型,随机分成5组:KGM高、中、低剂量组、生理盐水对照组及环磷酰胺(CTX)组,每组10只.建模第2天起,KGM高、中、低剂量组按300、200、100 mg/(kg·d)连续灌胃KGM 13 d,生理盐水组以等剂量灌胃13d,环磷酰胺组按30 mg/kg每周2次腹腔注射给药,共4次.第14天处死小鼠,取出脾脏,以实时定量PCR法,检测小鼠脾细胞TGF-β mRNA、IL-10 mRNA的表达.结果:与对照组比较,KGM3组荷瘤小鼠脾脏细胞中TGF-β mRNA、IL-10 mRNA表达量明显降低,差异均有统计学意义(P＜0.01),且高剂量KGM组与CTX组比较,无统计学差异(P＞0.05).结论:中药蛇六谷主要化学成分—魔芋葡甘露聚糖可以下调荷Lewis肺癌小鼠脾细胞TGF-βmRNA、IL-10mRNA的表达而产生抗肿瘤作用.

Background Early growth response proteins (EGRs), as a transcriptional regulatory family, are involved in the process of cell growth, differentiation, apoptosis, and even carcinogenesis. However, the role of EGRs in tumors, their expression levels, and their prognostic value remain unclear. Methods Using the Oncomine database, Kaplan–Meier Plotter, bcGenExMiner v4.2, cBioPortal, and other tools, the association between the survival data of breast carcinoma (BC) patients and transcriptional levels of four EGRs was investigated. Results According to the Oncomine database, in comparison to normal tissues, the expression level of EGR2/3 mRNA in BC tissues was decreased, but there was no difference in the expression level of EGR4 mRNA. On the basis of the Scarff-Bloom-Richardson (SBR) grading system, the downregulated expression level of EGR1/2/3 and upregulated expression level of EGR4 were correlated with an increased histological differentiation level, with significant differences (p < 0.05). Kaplan–Meier curves suggest that a reduction in EGR2/3 mRNA expression is related to recurrence-free survival (RFS) in BC patients. In addition, the mRNA expression level of EGR1/2/3 was related to metastatic relapse-free survival (MRFS) in BC patients with metastatic recurrence (p < 0.05). Conclusion EGR1/2/3 can be utilized as an important factor for evaluating prognosis and may be relevant to diagnosis. EGR4 may play a role in the occurrence and development of BC. The specific function and mechanism of EGRs in BC deserve further study.

陈培丰教授系浙江中医药大学附属第一医院主任中医师,从事中西结合肿瘤学临床、教学、科研工作三十余年,运用中医药治疗肺癌取得较好疗效.现介绍陈师治疗肺癌脑转移验案一则如下.