Various extracts from centipedes have therapeutic effects on liver cancer. This study aims to illustrate the impact and mechanism of centipede polypeptide (CP) on liver cancer. The suitable CP concentration and liver cancer cells were screened through CCK-8 analysis. The expression of proteins was analysed by Western blot. The level of cytokines and markers was measured by ELISA and biochemical kits. The apoptosis rate of cells was analysed by TUNEL staining and flow cytometry. Histopathological changes were observed by HE staining. The expression of Ki-67 and caspase-3 was assessed by IHC staining. The combination of CP and p53 was simulated by molecular docking. 200 μg/mL CP and HepG2 cells were applied in experiments. CP significantly upregulated p53, TNF-associated apoptosis-inducing ligand (TRAIL), TRADD and TRAF expression in HepG2 cells and tumour tissues ( p  < 0.05), suggesting p53-dependent activation of the TRAIL pathway. CP raised the levels of IL-6, IL-1β, TNF-α, MDA and ROS, and decreased those of IL-10, TGF-β1 and SOD in HepG2 cell supernatant and serum of nude mice ( p  < 0.05). CP promoted cell apoptosis and reduced the levels of ALT and AST to inhibit the progression of cancer. Molecular docking showed that CP could bind stably to p53 ( p  < 0.05). Silencing of p53 restrained the activation of the p53/TRAIL pathway and reduced the level of inflammatory reaction and ferroptosis, thus reversing the therapeutic effect of CP on liver cancer ( p  < 0.05). CP affected the inflammatory reaction and ferroptosis of liver cancer cells through the p53/TRAIL pathway.

Abstract Background: Blood vessels play a significant role in the pathogenesis of hepatocellular carcinoma (HCC). Emerging evidence suggests that dysregulation of the circadian clock gene, period 1 (PER1), is closely associated with HCC tumorigenesis. However, it remains unknown whether PER1 regulate the angiogenesis in HCC. Methods: The Cancer Genome Atlas data was utilized for bioinformatics analysis to evaluate the potential clinical significance of PER1. Western Blot (WB) was employed to detect expression of PER1 in tumors and adjacent tissues. Subcutaneous xenograft models were used to investigate the biological function of PER1. Hematoxylin and eosin staining, immunohistochemical analysis, WB, RT-qPCR, and co-immunoprecipitation techniques were employed to elucidate the underlying mechanism of PER1. Results: The expression of PER1 was significantly downregulated and exhibited a positive correlation with favorable clinicopathological characteristics in HCC patients. Overexpression of PER1 led to decreased cell proliferation and contributed to the maintenance of vascular normalization in nude mice. Conversely, silencing of PER1 resulted in the opposite effect. Mechanistically, PER1 orchestrated the balance between proangiogenic and antiangiogenic factors by binding to HIF-1α, thereby promoting malignant tumor progression. Conclusion: Our findings demonstrated that the PER1/HIF-1α signaling axis plays a critical role in promoting vascular normalization in HCC by effectively balancing proangiogenic and antiangiogenic factors.

ETHNOPHARMACOLOGICAL RELEVANCE:'Xiayuxue decoction' (XYXD) is a traditional Chinese medicine compound, composing of three natural medicines: Rheum officinale Baill., Prunus persica (L.) Batsch and Eupolyphaga sinensis Walker. It is derived from the famous traditional Chinese medical classics 'Jingui Yaolue' and has been used for thousands of years. In the Guidelines for the Diagnosis and Treatment of Primary liver Cancer issued by China's Health Commission, XYXD was applied in the treatment of primary liver cancer. AIM OF THE STUDY:To clarify the pharmacodynamic material basis and mechanism of XYXD in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS:Firstly, the active components of XYXD and its distribution in vivo were identified by Ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Then, the effective components and mechanism of XYXD against HCC were explored by network pharmacology combined with cell experiments in vitro. Furthermore, the anti-HCC effect of XYXD was determined by animal experiments in vivo. Metagenomic sequencing was used to detect its effect in gut microbiota, and targeted metabolism was used to detect the changes of bile acids in the liver. Finally, the related targets of NKT cell immune function activation were detected by RT-qPCR and Elisa. RESULTS:A total of 113 active ingredients in XYXD were identified, and the distribution of active ingredients in blood, liver, tumor, cecum, intestinal contents and feces was clarified. The circulation process and active ingredient group of XYXD were preliminarily clarified. In addition, we found five anti-HCC active ingredients in XYXD through network pharmacology combined with cell experiments in vitro, among which aloe emodin had the most significant effect, and predicted the potential mechanism of XYXD against HCC through NKT cell pathway. Moreover, the inhibitory effect of XYXD on liver tumor growth was clarified by animal experiments in vivo. The mechanism was mainly to promote the production of bile salt hydrolase (BSH) by increasing the abundance of Bacteroides and Lactobacillus, BSH converts conjugated bile acids into primary bile acids, and reduces the conversion of primary bile acids to secondary bile acids by reducing the abundance of Eubacterium, thereby increasing the content of primary bile acids. Primary bile acids trigger NKT cells in the liver to produce interferon-γ to exert anti-HCC immune effects. CONCLUSION:This study found that the traditional Chinese herbal formula XYXD can trigger the immune effect of NKT cells against HCC by regulating the interaction between gut microbiota and bile acids.

原发性肝癌是一种发病率高、死亡率高的恶性肿瘤,中医药具有延缓病情进展、改善肿瘤预后等优势.中医认为,情志与肝脏的生理病理改变密切相关.肝癌属心身疾病,探讨异常情志可通过直接损伤肝脏、影响气血运行、破坏阴阳平衡3个途径,影响肝癌的发生发展,而肝癌的发生发展亦可加重情志失衡.据此,提出了"调节情志"的肝癌治疗方法 .并解析四逆散通过调肝理气助疏泄、和血柔肝荣肝阴、和谐阴阳扶正气3个方面,发挥调节情志疗肝癌的作用,为临床运用四逆散调节情志治疗肝癌提供理论基础.

目的 分析消化道恶性肿瘤的证素基本特征及核心证候分布规律.方法 遵循临床流行病学调查原则,选取大样本回顾性研究设计.收集2012年1月-2021年12月湖南中医药大学第一附属医院1 739例消化道恶性肿瘤患者的病历资料,自拟《消化道恶性肿瘤中医证候学临床调查表》进行调查,提取病性、病位等证素信息,建立Excel数据库,采用SPSS26.0统计软件进行因子分析和聚类分析,分析消化道恶性肿瘤的核心证候分布规律.结果 共纳入73项有效四诊信息条目,常见病位证素包括脾、胃、肝,常见病性证素包括气虚、气滞、气郁、血瘀、水湿.聚类分析结果显示,证候可依次归纳为脾气亏虚证(31.24%)、瘀血内阻证(28.37%)、胃气亏虚证(17.43%)、脾虚湿盛证(11.97%)、气机阻滞证(10.99%).结论 消化道恶性肿瘤病机繁复庞杂,总的病机为本虚标实,其核心证候可归纳为"中虚血积".

BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China. However, current studies focus on antimicrobial and anticoagulation agents rather than tumors. The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated. It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines. AIM To purify, characterize, and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism. METHODS An antihepatoma peptide (scolopentide) was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis, a Sephadex G-25 column, and two steps of high-performance liquid chromatography (HPLC). Additionally, the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity. The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry (QTOF MS), and the sequence was matched by using the Mascot search engine. Based on the sequence and molecular weight, scolopentide was synthesized using solid-phase peptide synthesis methods. The synthetic scolopentide was confirmed by MS and HPLC. The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro. The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo. In the tumor xenograft experiments, qualified model mice (male 5-week-old BALB/c nude mice) were randomly divided into 2 groups (n = 6): The scolopentide group (0.15 mL/d, via intraperitoneal injection of synthetic scolopentide, 500 mg/kg/d) and the vehicle group (0.15 mL/d, via intraperitoneal injection of normal saline). The mice were euthanized by cervical dislocation after 14 d of continuous treatment. Mechanistically, flow cytometry was conducted to evaluate the apoptosis rate of HepG2 cells after treatment with extracted scolopentide in vitro. A Hoechst staining assay was also used to observe apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro. CCK8 assays and morphological changes were used to compare the cytotoxicity of synthetic scolopentide to liver cancer cells and normal liver cells in vitro. Molecular docking was performed to clarify whether scolopentide tightly bound to death receptor 4 (DR4) and DR5. qRT-PCR was used to measure the mRNA expression of DR4, DR5, fas-associated death domain protein (FADD), Caspase-8, Caspase-3, cytochrome c (Cyto-C), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), x-chromosome linked inhibitor-of-apoptosis protein and Cellular fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein in hepatocarcinoma subcutaneous xenograft tumors from mice. Western blot assays were used to measure the protein expression of DR4, DR5, FADD, Caspase-8, Caspase-3, and Cyto-C in the tumor tissues. The reactive oxygen species (ROS) of tumor tissues were tested. RESULTS In the process of purification, characterization and synthesis of scolopentide, the optimal enzymatic hydrolysis conditions (extract ratio: 5.86%, IC50: 0.310 mg/mL) were as follows: Trypsin at 0.1 g (300 U/g, centipede-trypsin ratio of 20: 1), enzymolysis temperature of 46 degrees C, and enzymolysis time of 4 h, which was superior to freeze-thawing with liquid nitrogen (IC50: 3.07 mg/mL). A peptide with the strongest antihepatoma activity (scolopentide) was further purified through a Sephadex G-25 column (obtained A2) and two steps of HPLC (obtained B5 and C3). The molecular weight of the extracted scolopentide was 1018.997 Da, and the peptide sequence was RAQNHYCK, as characterized by QTOF MS and Mascot. Scolopentide was synthesized in vitro with a qualified molecular weight (1018.8 Da) and purity (98.014%), which was characterized by MS and HPLC. Extracted scolopentide still had an antineoplastic effect in vitro, which inhibited the proliferation of Eca-109 (IC50: 76.27 mu g/mL), HepG2 (IC50: 22.06 mu g/mL), and A549 (IC50: 35.13 mu g/mL) cells, especially HepG2 cells. Synthetic scolopentide inhibited the proliferation of HepG2 cells (treated 6, 12, and 24 h) in a concentration-dependent manner in vitro, and the inhibitory effects were the strongest at 12 h (IC50: 208.11 mu g/ mL). Synthetic scolopentide also inhibited the tumor volume (Vehicle vs Scolopentide, P = 0.0003) and weight (Vehicle vs Scolopentide, P = 0.0022) in the tumor xenograft experiment. Mechanistically, flow cytometry suggested that the apoptosis ratios of HepG2 cells after treatment with extracted scolopentide were 5.01% (0 mu g/mL), 12.13% (10 mu g/mL), 16.52% (20 mu g/mL), and 23.20% (40 mu g/mL). Hoechst staining revealed apoptosis in HepG2 cells after treatment with synthetic scolopentide in vitro. The CCK8 assay and morphological changes indicated that synthetic scolopentide was cytotoxic and was significantly stronger in HepG2 cells than in L02 cells. Molecular docking suggested that scolopentide tightly bound to DR4 and DR5, and the binding free energies were-10.4 kcal/mol and-7.1 kcal/mol, respectively. In subcutaneous xenograft tumors from mice, quantitative real-time polymerase chain reaction and western blotting suggested that scolopentide activated DR4 and DR5 and induced apoptosis in SMMC-7721 Liver cancer cells by promoting the expression of FADD, caspase-8 and caspase-3 through a mitochondria-independent pathway. CONCLUSION Scolopentide, an antihepatoma peptide purified from centipedes, may inspire new antihepatoma agents. Scolopentide activates DR4 and DR5 and induces apoptosis in liver cancer cells through a mitochondria-independent pathway.

癌痛严重影响癌症患者的心身状态.基于治疗癌痛的临床实践,提出"卒病痼疾,荣亏瘀伤"的癌痛辨治理念,将癌痛病因病机归结于"卒病痼疾"与"荣亏瘀伤",将中医"卒病痼疾"理念与西医"急慢性癌痛综合征"相融合,认为"荣亏瘀伤"的癌痛病机特点为中州胃气不足、下元精血虚衰,导致气血乏源,阳气亏损,气血津液运行无力形成瘀血等有形之邪,邪气阻络而痛.治疗上首要辨清癌痛病因,根据"卒病痼疾"的缓急原则进行治疗,察胃气以衡攻补,建中填精以养荣,温阳活血以通瘀,佐以补肾平肝防转移,标本兼顾,通补相合,共奏止痛之功.

时辰给药是一种新的给药方法,在肿瘤治疗中的应用仅局限于化疗药物,鲜有肿瘤中医治疗的时辰给药研究.根据天地人的阳气生长规律以及肿瘤的增殖转移规律,探讨时辰给药在肿瘤中医治疗中的意义,提出平旦、日中、日西3个时间段内肿瘤治疗的理法方药.平旦之治,当益肾填精以扶阳气,轻可扶助人体阳气以抗癌,重可回阳救逆,挽救生命,根据阴阳亏损的程度给予方药.日中之治,当补益脾胃以蓄气血,既可借天地阳气鼓邪外出,又可防止日西阳衰,正不胜邪,根据补脾胃、畅六腑之法给予方药.日西之治,当温阳解毒以攻邪实.一则抑制肿瘤夜间转移,二则顾护阳气防止正伤,根据内、外治法给予方药.

BACKGROUND Hepatocellular carcinoma (HCC) is characterized by dysregulation of the immune microenvironment and the development of chemoresistance. Specifically, expression of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis, an immune checkpoint, may lead to tumour immune escape, resulting in disease progression. The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha (HIF-1α), and simultaneous inhibition of HIF-1α and PD-L1 has the potential to enhance the host’s antitumour immunity. Moreover, inhibition of the PD-1/PD-L1 axis may mitigate tumour chemoresistance. Shuyu pills (SYPs) contain immunity-enhancing and antitumour components, making them a potential HCC treatment. AIM To investigate the efficacy of SYPs for HCC treatment via simultaneous HIF-1α and PD-L1 inhibition and the mechanism involved. METHODS A subcutaneous xenograft tumour model was first established in BALB/c nude mice by the subcutaneous injection of 1 × 107 SMMC-7721 cells. Male mice (male, 5 weeks old; n = 24) were then randomly divided into the following four groups (n = 6): Control (0.9% normal saline), SYP (200 mg/kg), SYP + cisplatin (DDP) (200 mg/kg + 5 mg/kg DDP weekly via intraperitoneal injection), and DDP (5 mg/kg cisplatin weekly via intraperitoneal injection). The dose of saline or SYPs for the indicated mouse groups was 0.2 mL/d via intragastric administration. The tumour volumes and body weights of the mice were measured every 2 d. The mice were euthanized by cervical dislocation after 14 d of continuous treatment, and the xenograft tissues were excised and weighed. Western blot assays were used to measure the protein expression of HIF-1α, PD1, PD-L1, CD4+ T cells, and CD8+ T cells in HCC tumours from mice. Quantitative reverse transcription polymerase chain reaction was used for real-time quantitative detection of PD-1, PD-L1, and HIF-1α mRNA expression. An immunofluorescence assay was conducted to examine the expression of CD4+ T cells and CD8+ T cells. RESULTS Compared to mice in the control group, those in the SYP and SYP + DDP groups exhibited reduced tumour volumes and tumour weights. Moreover, the protein and mRNA expression levels of the oncogene HIF1α and that of the negative immunomodulatory factors PD-1 and PD-L1 were decreased in both the SYP and SYP + DDP groups, with the decrease effects being more prominent in the SYP + DDP group than in the SYP group (HIF-1α protein: Control vs SYP, P = 0.0129; control vs SYP + DDP, P = 0.0004; control vs DDP, P = 0.0152, SYP + DDP vs DDP, P = 0.0448; HIF-1α mRNA: control vs SYP, P = 0.0009; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SYP vs SYP + DDP, P = 0.0192. PD-1 protein: Control vs SYP, P = 0.0099; control vs SYP + DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0009; SYP + DDP vs DDP, P < 0.0001; PD-1 mRNA: control vs SYP, P = 0.0002; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SPY vs SYP + DDP, P = 0.0003; SYP + DDP vs DDP, P = 0.0002. PD-L1 protein: control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0040; SYP + DDP vs DDP, P = 0.0010; PD-L1 mRNA: Control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P = 0.0014). Additionally, the quantitative and protein expression levels of CD4+ T cells and CD8+ T cells were simultaneously upregulated in the SYP + DDP group, whereas only the expression of CD4+ T cells was upregulated in the SYP group. (CD4+ T cell quantitative: Control vs SYP + DDP, P < 0.0001, SYP vs SYP + DDP, P = 0.0005; SYP + DDP vs DDP, P = 0.0002. CD4+ T cell protein: Control vs SYP, P = 0.0033; Control vs SYP + DDP, P < 0.0001; Control vs DDP, P = 0.0021, SYP vs SYP + DDP, P = 0.0004; SYP + DDP vs DDP, P = 0.0006. Quantitative CD8+ T cells: Control vs SYP + DDP, P = 0.0013; SYP vs SYP + DDP, P = 0.0347; SYP + DDP vs DDP, P = 0.0043. CD8+ T cell protein: Control vs SYP + DDP, P < 0.0001; SYP vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P < 0.0001). Finally, expression of HIF-1α was positively correlated with that of PD-1/PD-L1 and negatively correlated with the expression of CD4+ T cells and CD8+ T cells. CONCLUSION SYPs inhibit immune escape and enhance chemosensitization in HCC via simultaneous inhibition of HIF-1α and PD-L1, thus inhibiting the growth of subcutaneous xenograft HCC tumours.

总结尹周安从气血津液精"盈虚通滞"理论辨治垂体泌乳素腺瘤的经验,尹周安认为本病与肾精不足、肝失疏泄所致气血津液精"盈虚通滞"改变相关,"盈"与"通"难成此病,多由"阻滞""虚损"发病.阻滞病变责之气、血、津液不通,虚损病变咎于精、血、气不足,两者均可导致气郁、血瘀、津停的产生.阻滞病变,以通为补,首畅肝气;虚损病变,以补为通,首补精血.提出了调畅少阳三焦、解除筋膜挛急、疏通气血津液精阻滞的治疗方法,同时重调神、畅情志以缓解患者紧张恐慌的情绪,达到身心同治的目的.

目的 观察薯蓣丸对肿瘤微环境中HIF-1α与p53的表达以及线粒体损伤的影响,及其对肝细胞癌的治疗作用.方法 制备人肝癌裸鼠皮下移植瘤模型,雄性BALB/c裸鼠(n=24,5周龄),随机分为4组,每组6只:模型组(0.9％生理盐水0.2 mL/d)、薯蓣丸组(薯蓣丸0.4 g/d),薯蓣丸+顺铂组(薯蓣丸0.4 g/d+每周腹腔注射顺铂5 mg/kg)、顺铂组(每周腹腔注射顺铂5 mg/kg).每只裸鼠灌胃剂量为0.2 mL/d,每2天测量1次肿瘤体积与小鼠体质量,连续干预14 d后脱颈处死,剥离皮下移植瘤;电镜下观察肿瘤组织线粒体结构和数量;Western blot与RT-qPCR法分别检测人肝癌裸鼠皮下移植瘤中HIF-1α、p53的蛋白及mRNA表达.结果 与模型组相比,薯蓣丸组可抑制人肝癌裸鼠皮下移植瘤的生长,抑制HIF-1α的mRNA与蛋白表达(P<0.05),上调抑癌基因p53的m-RNA与蛋白表达(P<0.05),同时改善线粒体结构损伤;与薯蓣丸组或顺铂组相比,薯蓣丸联合顺铂组对HIF-1α、p53基因表达及改善线粒体结构作用更显著(P<0.05).结论 薯蓣丸可通过促使HIF-1α的失活与p53的活化,改善线粒体结构损伤,从而抑制人肝癌裸鼠皮下移植瘤的生长,与顺铂联用后具有协同增效作用.

恶性肿瘤的发病率连年升高,现已证明许多恶性肿瘤属于心身疾病范畴.心理因素在肿瘤的形成与发展阶段产生了不可忽视的作用,在肿瘤形成后亦导致了一系列心身症状,影响肿瘤的临床治疗效果.然而,临床医师对肿瘤患者的心身症状存在识别率较低,治疗方法不足的问题 [1],常将心理因素与躯体症状割裂开看待,使得临床疗效欠佳.心身症状是指与心理社会因素密切相关的症状,患者常因躯体症状就诊于非精神科室,但症状的严重程度与疾病并不相符.临床常见的肿瘤相关心身症状包括焦虑、抑郁、癌痛、失眠、疲乏、自主神经功能紊乱如恶心呕吐等 [2].焦虑、抑郁是最常见的肿瘤心身症状,虽然属于心理症状,但常作为其他躯体症状的伴见因素,治疗肿瘤心身症状多可以从识别、治疗焦虑、抑郁着手.本文将分享笔者对肿瘤心身症状中焦虑、抑郁的临床诊疗 体悟.

癌因性疲乏属于中医“虚劳病”范畴,本文根据虚劳病的诊治,探讨六经辨证在癌因性疲乏中的辨证思路.笔者团队认为癌因性疲乏病机上总属“虚”和“郁”,因气血阴阳的不荣与不通发病.在治疗上,因“虚”致病,认为以太阴脾虚为本,治当扶太阴复形质;因“郁”致病,治当疏气机散积郁,根据正邪盛衰情况区分阴阳,正气尚充属阳证者从少阳病论治,阳虚正损属阴证者按厥阴病论治,以此为主线再辨兼夹证.同时注重调畅肿瘤患者的心理情致,以达到心身同治的目的.为构建癌因性疲乏运用六经辨证的经方诊治提供思路与借鉴.

BACKGROUND:Liver cancer is the sixth most frequently occurring cancer in the world and the fourth most common cause of cancer mortality. The pathogenesis of liver cancer is closely associated with inflammation and immune response in the tumor microenvironment. New therapeutic agents for liver cancer, which can control inflammation and restore cellular immunity, are required. Curcumin (Cur) is a natural anti-inflammatory drug, and total ginsenosides (TG) are a commonly used immunoregulatory drug. Of note, both Cur and TG have been shown to exert anti-liver cancer effects.AIM:To determine the synergistic immunomodulatory and anti-inflammatory effects of Cur combined with TG in a mouse model of subcutaneous liver cancer.METHODS:A subcutaneous liver cancer model was established in BALB/c mice by a subcutaneous injection of hepatoma cell line. Animals were treated with Cur (200 mg/kg per day), TG (104 mg/kg per day or 520 mg/kg per day), the combination of Cur (200 mg/kg per day) and TG (104 mg/kg per day or 520 mg/kg per day), or 5-fluorouracil combined with cisplatin as a positive control for 21 d. Tumor volume was measured and the protein expression of programmed cell death 1 and programmed cell death 1 ligand 1 (PD-L1), inflammatory indicators Toll like receptor 4 (TLR4) and nuclear factor-κB (NF-κB), and vascular growth-related factors nitric oxide synthases (iNOS) and matrix metalloproteinase 9 were analyzed by Western blot analysis. CD4+CD25+Foxp3+ regulatory T cells (Tregs) were counted by flow cytometry.RESULTS:The combination therapy of Cur and TG significantly inhibited the growth of liver cancer, as compared to vehicle-treated animals, and TG showed dose dependence. Cur combined with TG-520 markedly decreased the protein expression of PD-L1 (P < 0.0001), while CD4+CD25+Foxp3+ Tregs regulated by the PD-L1 signaling pathway exhibited a positive correlation with PD-L1. Cur combined with TG-520 also inhibited the cascade action mediated by NF-κB (P < 0.0001), thus inhibiting the TLR4/NF-κB signalling pathway (P = 0.0088, P < 0.0001), which is associated with inflammation and acts on PD-L1. It also inhibited the NF-κB-MMP9 signalling pathway (P < 0.0001), which is associated with tumor angiogenesis.CONCLUSION:Cur combined with TG regulates immune escape through the PD-L1 pathway and inhibits liver cancer growth through NF-κB-mediated inflammation and angiogenesis.

Journal of Medical VirologyVolume 92, Issue 10 p. 1728-1730 LETTER TO THE EDITOR Diagnosis and treatment of an acute severe pneumonia patient with COVID-19: Case report Zhe Deng, Zhe Deng College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSearch for more papers by this authorYuxing Hu, Yuxing Hu College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSearch for more papers by this authorPing Yang, Ping Yang Department of Respiration, Brain Hospital of Hunan Province, Changsha, ChinaSearch for more papers by this authorPiao Zheng, Piao Zheng College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSearch for more papers by this authorWenfeng Peng, Wenfeng Peng Department of Respiration, Brain Hospital of Hunan Province, Changsha, ChinaSearch for more papers by this authorBiqiong Ren, Biqiong Ren Laboratory Department, Brain Hospital of Hunan Province, Changsha, ChinaSearch for more papers by this authorXiangbo Zeng, Corresponding Author Xiangbo Zeng [email protected] orcid.org/0000-0002-9740-9229 Department of Respiration, Brain Hospital of Hunan Province, Changsha, China Correspondence Xiangbo Zeng, MD, Department of Respiration, Brain Hospital of Hunan Province, 427 Middle Furong Road, Changsha, 410007 Hunan, China. Email: [email protected] Xuefei Tian, PhD, Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Changsha, 410208 Hunan, China. Email: [email protected]Search for more papers by this authorXuefei Tian, Corresponding Author Xuefei Tian [email protected] College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, China Correspondence Xiangbo Zeng, MD, Department of Respiration, Brain Hospital of Hunan Province, 427 Middle Furong Road, Changsha, 410007 Hunan, China. Email: [email protected] Xuefei Tian, PhD, Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Changsha, 410208 Hunan, China. Email: [email protected]Search for more papers by this author Zhe Deng, Zhe Deng College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSearch for more papers by this authorYuxing Hu, Yuxing Hu College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSearch for more papers by this authorPing Yang, Ping Yang Department of Respiration, Brain Hospital of Hunan Province, Changsha, ChinaSearch for more papers by this authorPiao Zheng, Piao Zheng College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSearch for more papers by this authorWenfeng Peng, Wenfeng Peng Department of Respiration, Brain Hospital of Hunan Province, Changsha, ChinaSearch for more papers by this authorBiqiong Ren, Biqiong Ren Laboratory Department, Brain Hospital of Hunan Province, Changsha, ChinaSearch for more papers by this authorXiangbo Zeng, Corresponding Author Xiangbo Zeng [email protected] orcid.org/0000-0002-9740-9229 Department of Respiration, Brain Hospital of Hunan Province, Changsha, China Correspondence Xiangbo Zeng, MD, Department of Respiration, Brain Hospital of Hunan Province, 427 Middle Furong Road, Changsha, 410007 Hunan, China. Email: [email protected] Xuefei Tian, PhD, Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Changsha, 410208 Hunan, China. Email: [email protected]Search for more papers by this authorXuefei Tian, Corresponding Author Xuefei Tian [email protected] College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, China Correspondence Xiangbo Zeng, MD, Department of Respiration, Brain Hospital of Hunan Province, 427 Middle Furong Road, Changsha, 410007 Hunan, China. Email: [email protected] Xuefei Tian, PhD, Hunan Key Laboratory of TCM Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Changsha, 410208 Hunan, China. Email: [email protected]Search for more papers by this author First published: 30 March 2020 https://doi.org/10.1002/jmv.25802Citations: 9 Zhe Deng and Yuxing Hu are co-first authors. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES 1World Health Organization. Coronavirus disease 2019 (COVID-2019) Situation Report – 57. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/ Google Scholar 2Notice on the issuance of COVID-19 diagnosis and treatment programme (Pilot version 7). National Health Commission of the People's Republic of China. 2020. http://www.nhc.gov.cn/xcs/zhengcwj/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml Google Scholar 3Guan W, Ni Z, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. MedRxiv. 2020. https://doi.org/10.1101/2020.02.06.20020974 PubMedGoogle Scholar 4Bai Y, Yao L, Wei T, et al. Presumed asymptomatic carrier transmission of COVID-19. JAMA. 2020. https://doi.org/10.1001/jama.2020.2565 10.1001/jama.2020.2565 PubMedWeb of Science®Google Scholar 5World Health Organization. (2020). Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected human cases: interim guidance, 2 March 2020. World Health Organization. Google Scholar 6Kai-Wang TK, Tak-Yin TO, Chik-Yan YC, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis. 2020:ciaa149. PubMedWeb of Science®Google Scholar Citing Literature Volume92, Issue10Special Issue on New coronavirus (2019‐nCoV or SARS‐CoV‐2) and the outbreak of the respiratory illness (COVID‐19): Part‐VIOctober 2020Pages 1728-1730 ReferencesRelatedInformation

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