Role of chemokines in the hepatocellular carcinoma microenvironment and their translational value in immunotherapy

The difficulty of early diagnosis,high tumor heterogeneity,and high recurrence and metastasis rates lead to an unsatisfactory treatment status for hepatocellular carcinoma(HCC).HCC is a typical inflammation-driven tumor.Chronic inflammation allows nascent tumors to escape immunosurveillance.Chemokines are small,soluble,secreted proteins that can regulate the activation and trafficking of immune cells during inflammation.Several studies have shown that various chemokines with overarching functions disrupt the immune microenvironment during the initiation and progression of HCC.The dysregulated chemokine network in HCC contributes to multiple malignant processes,including angiogenesis,tumor proliferation,migration,invasion,tumor low response,and resistance to immune therapy.Here,we summarize the current studies focusing on the role of chemokines and their receptors in the HCC immune microenvironment,highlighting potential translational therapeutic uses for modulating the chemokine system in HCC.

Fufang E’jiao Jiang’s effect on immunity,hematopoiesis,and angiogenesis via a systematic“compound-effect-target”analysis

Fufang E’jiao Jiang(FEJ)as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish qi and nourish blood,and it has a positive impact on women’s health.To find out the material basis and mechanism of FEJ,a systematic“compoundeffect-target”analysis including chemical composition resolution,zebrafish,network pharmacology,molecular docking,transcriptome,and bibliometric analysis was adopted.124 chemical components including ginsenosides,and phenylethanoid glycosides in FEJ were discovered,and effects of FEJ on promoting the generation of immune cells,erythropoiesis and angiogenesis in zebrafish were exhibited.Based on network pharmacology,molecular docking and in vivo activity assay,6 compounds including jionoside A1,isoacteoside,echinacoside,acteoside,lobetyolin,and rehmannioside D were identified as active components of FEJ.Transcriptome data showed that several pathways such as complement and coagulation cascades,ECM-receptor interaction,and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ.19 common targets were obtained through combined analysis of network pharmacology and transcriptomics,and 5 targets of them were verified by PCR.The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism,pathway in cancer,etc.,which was consistent with the results of network pharmacology and transcriptome.The studies suggested that FEJ could replenish qi and nourish blood through multi-compound and multi-targets.

EGFR和ALK基因异时性突变非小细胞肺癌1例报告并文献复习

多原发肺癌(multiple primary lung cancer,MPLC)指患者有两个或两个以上原发病灶的肺癌,根据发生时间的不同分为同时性多原发肺癌(synchronous MPLC,sMPLC)和异时性多原发肺癌(metachronous MPLC,mMPLC)。近年来,MPLC的检出率逐渐升高,但由于肿瘤的异质性,在鉴别MPLC和肺内转移(intrapulmonary metastasis,IM)上存在许多争议,特别是病理组织学类型相同时。考虑到目前二者在临床治疗策略及预后上的显著差异,对于MPLC和IM的精确诊断是个体化精准治疗的关键。分子遗传学及测序技术为检测肿瘤的克隆性起源提供了有效的策略,其中非小细胞肺癌表皮生长因子受体(epidermal growth factor receptor,EGFR)突变与间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合突变共存的病例陆续有报道,但ALK基因突变后再发EGFR突变的案例未见提及。本文通过分子遗传学技术准确诊断并回顾性分析了1例ALK突变型男性肺腺癌患者术后4年再发EGFR突变合并多发转移的临床资料,并复习相关文献,以期加深对mMPLC的认识,为该类病例的诊疗提供临床借鉴。

Understanding the dynamical-microphysical-electrical processes associated with severe thunderstorms over the Beijing metropolitan region

The Dynamical-microphysical-electrical Processes in Severe Thunderstorms and Lightning Hazards(STORM973)project conducted coordinated comprehensive field observations of thunderstorms in the Beijing metropolitan region(BMR)during the warm season from 2014 to 2018.The aim of the project was to understand how dynamical,microphysical and electrical processes interact in severe thunderstorms in the BMR,and how to assimilate lightning data in numerical weather prediction models to improve severe thunderstorm forecasts.The platforms used in the field campaign included the Beijing Lightning Network(BLNET,consisting of 16 stations),2 X-band dual linear polarimetric Doppler radars,and 4 laser raindrop spectrometers.The collaboration also made use of the China Meteorological Administration’s mesoscale meteorological observation network in the Beijing-Tianjin-Hebei region.Although diverse thunderstorm types were documented,it was found that squall lines and multicell storms were the two major categories of severe thunderstorms with frequent lightning activity and extreme rainfall or unexpected local short-duration heavy rainfall resulting in inundations in the central urban area,influenced by the terrain and environmental conditions.The flash density maximums were found in eastern Changping District,central and eastern Shunyi District,and the central urban area of Beijing,suggesting that the urban heat island effect has a crucial role in the intensification of thunderstorms over Beijing.In addition,the flash rate associated with super thunderstorms can reach hundreds of flashes per minute in the central city regions.The super(5%of the total),strong(35%),and weak(60%)thunderstorms contributed about 37%,56%,and 7%to the total flashes in the BMR,respectively.Owing to the close connection between lightning activity and the thermodynamic and microphysical characteristics of the thunderstorms,the lightning flash rate can be used as an indicator of severe weather events,such as hail and short-duration heavy rainfall.Lightning data can also be assimilated into numerical weather prediction models to help improve the forecasting of severe convection and precipitation at the cloud-resolved scale,through adjusting or correcting the thermodynamic and microphysical parameters of the model.

Specific generation of nitric oxide in mitochondria of cancer cell for selective oncotherapy

Nitric oxide(NO)gas therapy,especially,L-arginine(L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy.However,current strategies are unable to differentiate well between normal cells and cancer cells,which may lead to unpredictable toxicity.Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase(NOS),herein,a nanozyme-based NO generator,cerium oxide(CeO_(2))-AT,is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment.In this system,after being endocytosed into cancer cells,the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells,which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis.In addition,the generator with catalase(CAT)-like activity can catalyze H_(2)O_(2)to produce O_(2),which can promote the generation of NO and improve the performance of NO gas therapy.What is more,our system has no obvious impact on the viability of normal cells owing to the less production of NO.Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.