BACKGROUND:This network meta-analysis (NMA) aims to compare the relative efficacy of oral Chinese patent medicine combined with transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC). METHODS:Databases, including China National Knowledge Infrastructure, Wanfang, Weipu, PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL), were accessed from inception to the present to collect randomized controlled trials of different oral Chinese patent medicines (OCPMs). Objective response rate, 1-year survival rate, lymphocytes, nausea and vomiting were used as efficacy or tolerability outcomes. A Bayesian NMA was performed. RESULTS:Seventy-five randomized controlled trials involving 6912 participants and 9 OCPMs were included. The results of the NMA showed that the comparisons were all indirect. The NMA demonstrated that, regarding the objective response rate, TACE combined with all OCPMs showed the advantages over TACE monotherapy, of which Cidan capsule (odds ratio [OR] 3.5, 95% credible interval 2.3-4.9) was the most effective treatment. Among 9 OCPMs, Cidan capsule was the most effective for survival improvement (OR 5.1, 95% CrI 2.7-8.7)." Jinlong for immune function (OR 0.35, 95% CrI 0.14-0.57), and Shenyi for adverse event reduction (OR 0.39, 95% CrI: 0.18-0.87). CONCLUSION:OCPMs have significant efficacy in treating HCC combined with TACE. Cidan, Jinlong, and Shenyi capsules might be the optimum drugs for HCC adjuvant therapy.

Background: Hepatocellular carcinoma (HCC) is a common clinical malignant tumor of the digestive system. Hu-Qi-Zheng-Xiao (HQZX) decoction has been clinically found to prolong the survival of patients with hepatocellular carcinoma and improve the quality of patients’ survival, but its antitumor biological mechanism is still unclear. Methods: A nude mouse hollow fiber hepatocellular carcinoma model was constructed to analyze the in vivo efficacy of HQZX decoction against 7 different hepatocellular carcinoma cells. The subcutaneous graft tumor model was again validated. In vitro, the effect of HQZX decoction on the growth and metastasis of the cell line with the highest growth inhibition was evaluated. The cell line with the best efficacy response screened was again used to construct a hollow fiber hepatocellular carcinoma model and hollow fiber conduit cells were extracted to detect the expression of HIF-1α, VEGF, EMT-related molecules, LCSCs-related molecules, and to observe the density of the subcutaneous vascular network of hollow fiber conduits. The liver metastasis model of splenic injection was constructed to observe the effect of HQZX decoction on tumor metastasis. Results: The hollow fiber hepatocellular carcinoma model was evaluated for the efficacy of HQZX decoction, and it was found to have the highest growth inhibition of LM3-luc cells. In vitro, the CCK8 assay revealed that HQZX decoction could inhibit tumor migration and invasion and promote apoptosis. In addition, the mechanism study of extracting cells from hollow fiber tubes found that HQZX decoction could inhibit metastasis-associated HIF-1α, VEGF, EMT-related molecules, and LCSCs-related molecules expression. capillary network around subcutaneous fiber tubes was reduced in the HQZX decoction gavage group of mice. It inhibited tumor metastasis in nude mice. Conclusions: HQZX decoction inhibited the growth of a variety of hepatocellular carcinoma cells. HQZX decoction suppressed the expression of metastasis-associated VEGF, EMT-related molecules, and LCSCs-related molecules and inhibited tumor angiogenesis and growth and metastasis, which may be related to the inhibition of the HIF-1α signaling pathway. It reveals that HQZX decoction may be a promising herbal compound for anti-HCC therapy, and also reveals the accurate feasibility of the hollow fiber hepatocellular carcinoma model for in vivo pharmacodynamic evaluation and mechanism study.

The objective of this study is to analyze and summarize the characteristics of the clinical data of patients with systemic lupus erythematosus (SLE) complicated with liver failure, and to improve the cognition of the disease. The clinical data of patients with SLE complicated with liver failure hospitalized in Beijing Youan Hospital from January 2015 to December 2021 were collected retrospectively, including general information and laboratory examination data, and the clinical characteristics of the patients were summarized and analyzed. Twenty-one SLE patients with liver failure were analyzed. The diagnosis of liver involvement was earlier in 3 cases than that of SLE, and later in 2 cases. Eight patients were diagnosed with SLE and autoimmune hepatitis at the same time. The medical history is between 1 month and 30 years. This was the first case report of SLE complicated with liver failure. We found that: (1) among the 21 patients, organ cysts (liver and kidney cysts) were more common and the proportion of cholecystolithiasis and cholecystitis was higher than that in previous studies, but the proportion of renal function damage and joint involvement was lower. (2) The inflammatory reaction was more obvious in SLE patients with acute liver failure. The degree of liver function injury in SLE patients with autoimmune hepatitis was less than that in patients with other liver diseases. (3) The use of glucocorticoid in SLE patients with liver failure was worthy of further discussion.

Apoptosis-stimulating protein p53 2 (ASPP2) is a member of the p53-binding protein family, which is closely related to tumor development. However, the precise mechanism of ASPP2 in liver inflammation and tumorigenesis remains largely unclear. We aimed to characterize the mechanistic significance and clinical implication of ASPP2 in hepatitis and hepatocellular carcinoma (HCC). In this study, ASPP2 knockout (APKO) mice were generated to confirm the role of ASPP2 in the development of hepatitis and HCC. Liver tissues from mice were analyzed by immunohistochemistry, Western blotting, proteomic analysis, ChIP-Seq, and qRT-PCR to evaluate the role of ASPP2 in DEN-induced hepatitis and HCC. We found that APKO promoted the formation of hepatitis/hepatocarcinoma and the increased expression of proinflammatory factors. The proteomics and Western blotting results showed that APKO activated the NF-κB signaling pathway. Further, ChIP-Seq results revealed that NF-κB target genes were dramatically increased in APKO mice. In contrast, blockade of the NF-κB pathway by QNZ reduced the expression of proinflammatory factors and the susceptibility of APKO mice to DEN-induced hepatocarcinogenesis. These results suggested that the absence of ASPP2 activates the NF-κB pathway to promote the occurrence of DEN-induced hepatocarcinogenesis, indicating that ASPP2 may be a potential target for the treatment of hepatocarcinoma.

中空纤维肿瘤模型(hollow fiber tumor model)或中空纤维测定法(Hollow Fiber Assay,HFA)是由美国国家癌症研究所(Nationa Cancer Institute,NCI)设计的一种新型抗癌药物初步筛选模型,可以简单快速、准确可行地进行初步体内疗效的评估.近年来已被广泛应用于抗肿瘤药物的研发过程中,并且有了新的改良优化和应用.本文系统综述了中空纤维肿瘤模型在抗肿瘤药物筛选方面的优势特点以及近10年最新应用进展,研究认为,HFA在抗肿瘤药物研究中占据了越来越重要的地位,HFA的改良模型在个体化癌症治疗和机制研究上有着广阔的应用前景.

Due to the refractory and partial sensitive treatments to malignant cancers, immunotherapy has increasingly become a hotspot in effective anti-tumor research. However, at present, existing animal models could not accurately describe the interaction between human tissue and tumor cells for preclinical trials. Furthermore, it is a tough obstacle to reconstitute the immune system and microenvironment in a mouse model identical to humans due to species differences. In the establishment of the humanized mouse model, the co-transplantation of human immunocytes with/without tissues and tumor cells is the key breakthrough to solve this problem. The compelling progress has been investigated in the preclinical drug test for diverse tumor types. This review mainly summarized the development of immunodeficient mice, and the construction and practicability of the humanized mouse model. Furthermore, the investigators also highlight the pros and cons, and recent progress in immunotherapy research for advanced utility of human cancer diseases.

目的 应用高频小动物超声观察人BT-B膀胱癌和人Huh7肝癌两种皮下移植瘤的血管生成情况,探讨超声造影评价肿瘤血管生成情况的价值.方法 采用皮下注射建立人BT-B膀胱癌和人Huh7肝癌两种皮下移植瘤模型,采用高频小动物超声成像系统的多种超声模式观察两种肿瘤内部结构和血管特性;采用探头式活体激光共聚焦观察肿瘤的小血管数量和大小;采用免疫组化法观察肿瘤的血管标志物CD31表达,计算微血管密度.结果 两组裸鼠均成功荷瘤.B超模式显示Huh7与BT-B皮下瘤均为不均质低回声结节;彩色多普勒模式及频谱多普勒模式显示BT-B皮下瘤血流信号和血流速度多于Huh7皮下瘤;超声造影显示Huh7肝癌组血管分布紊乱,BT-B膀胱癌组血管分布呈"分支状",与探头式活体激光共聚焦结果及病理结果一致.超声造影参数峰值强度(PI)与MVD呈正相关(r=0.844,P<0.05).结论 超声造影可以更好地显示肿瘤血管的分布情况,且PI与病理MVD呈正相关,可提示肿瘤血管的增殖情况,可以作为无创评价肿瘤血管生成的可靠方法.