Hepatic arterial infusion chemotherapy (HAIC) is one of the local treatment modalities employed for liver metastases. HAIC targets the delivery of chemotherapy drugs to the affected area by inserting a catheter into the tumor’s blood-supplying artery. This approach not only enhances drug concentration within the tumor site, but also significantly reduces systemic side effects. Currently, there are various chemotherapeutic regimens available for HAIC in liver metastases; however, determining the optimal therapeutic agent remains elusive. This article provides a comprehensive review of HAIC dosing regimens and multimodal therapy for liver metastases originating from colorectal, breast, and gastric cancers. Meanwhile, this paper briefly outlines ongoing research on HAIC treatment for liver metastases associated with esophageal cancer, gastroenteropancreatic neuroendocrine tumors, and uveal melanoma.
Apatinib has been shown to apply to a variety of solid tumors, including advanced hepatocellular carcinoma. Preclinical and preliminary clinical results confirmed the synergistic antitumor effects of apatinib in combination with anti-programmed death-1 (PD-1) inhibitors. In this study, we investigated camptothecin (CPT) enhances the anti-tumor effect of low-dose apatinib combined with PD-1 inhibitor on hepatocellular carcinoma. CPT combined with a PD-1 inhibitor enhances the anti-tumor effects of low-dose apatinib in hepatocellular carcinoma which was evaluated in making use of the H22 mouse model (n = 32), which was divided into four groups. Immunohistochemical staining and western blotting were used to detect nuclear factor erythroid 2-related factor 2 (Nrf2) as well as sequestosome 1 (p62), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), PD-1, and programmed cell death ligand 1 (PD-L1). The results showed that the average size of the tumor of the combination group (Group D) was significantly less than that of the apatinib + PD-1 inhibitor group (Group C). The expression levels of Nrf2, p62, VEGFA, VEGFR2, PD-1, and PD-L1 in the apatinib + PD-1 inhibitor group(Group C) were lower than those in the control group (Group A) (P < 0.05). The expression levels of these genes in the apatinib + PD-1 inhibitor group (Group C) were significantly lower in the combination group (Group D) (P < 0.05). There was no obvious difference in body weight and liver and kidney functions between the four groups of mice. In conclusion, CPT improves the anti-tumor effect of low-dose apatinib combined with PD-1 inhibitor on hepatocellular carcinoma
Ferroptosis is a type of controlled cell death caused by lipid peroxidation, which results in the rupture of the cell membrane. ferroptosis has been repeatedly demonstrated over the past ten years to be a significant factor in a number of diseases. The liver is a significant iron storage organ, thus ferroptosis will have great potential in the treatment of liver diseases. Ferroptosis is particularly prevalent in HCC. In the opening section of this article, we give a general summary of the pertinent molecular mechanisms, signaling pathways, and associated characteristics of ferroptosis. The primary regulating mechanisms during ferroptosis are then briefly discussed, and we conclude by summarizing the development of a number of novel therapeutic strategies used to treat HCC in recent years. Ferroptosis is a crucial strategy for the treatment of HCC and offers new perspectives on the treatment of liver cancer.
Abstract Background Apatinib is a selective vascular endothelial growth factor receptor 2-tyrosine kinase inhibitor (TKI) that has been shown to apply to a variety of solid tumors, including advanced hepatocellular carcinoma(HCC). Clinical outcome prove that the combination of apatinib and anti programmed death 1 (PD-1) inhibitors has a cooperate with anti-tumor effect. In this study, we investigated the synergistic enhancement of the antitumor effect of PD-1 inhibitor in HCC by camptothecin (CPT) and low-dose apatinib. Methods The effect of low-dose apatinib in combination with CPT on the antitumor effects of PD-1 inhibitor was evaluated in making use of the H22 mouse model (n = 32), which was divided into four treatment groups. Immunohistochemical staining and western blotting were used to detect nuclear factor erythroid 2-related factor 2 (Nrf2) as well as sequestosome 1 (p62), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), PD-1, and programmed cell death ligand 1 (PD-L1). Results The results showed that the average size of the tumor of the combination group was significantly less than that of the apatinib + PD-1 inhibitor group. The expression levels of Nrf2, p62, VEGFA,VEGFR2, PD-1, and PD-L1 in the apatinib + PD-1 inhibitor group were lower than those in the control group (P < 0.05). The expression levels of these genes were significantly lower in the combination group (P < 0.05). Conclusion There was no obvious difference in body weight and liver and kidney functions between the four groups of mice. In conclusion, CPT synergistically enhanced the antitumor effect of PD-1 inhibitor in HCC with low-dose apatinib.
Sorafenib is a targeted drug for hepatocellular carcinoma (HCC), however, its efficacy is limited. Nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to sorafenib resistance. The present study investigated camptothecin (CPT) as a Nrf2 inhibitor to sensitize HCC to sorafenib. The effect of CPT on sorafenib sensitivity in HCC was assessed in vivo using H22 mice model (n=32) and VX2 rabbit models (n=32), which were sorted into four treatment groups. The expression levels of Nrf2, its downstream genes, including heme oxygenases-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1), and the epithelial-mesenchymal transition markers Snail and N-cadherin in tumors were determined using immunohistochemical staining and western blotting. Magnetic resonance imaging was used to monitor changes in tumor microcirculation and activity before and after treatment. Mouse body weights, liver and kidney function were monitored to evaluate the safety of combined therapy. The results revealed that the mean tumor size of the combined group was significantly smaller than that of sorafenib group for both models. The expression levels of Nrf2, heme oxygenase-1, NAD(P)H quinone oxidoreductase 1, Snail, and N-cadherin in the sorafenib group were significantly higher than control group (P<0.05). However, the expression levels of these genes were decreased in the combined group (P<0.05). Microcirculation perfusion and tumor activity in the combined group were also lower than sorafenib group. There were no significant differences in mouse body weight or liver and kidney function among the four groups. In summary, CPT is a Nrf2 inhibitor that could enhance the efficacy of sorafenib against HCC.
Drug-eluting bead transarterial chemoembolization (DEB-TACE) has been widely used in the treatment of liver cancer; however, the utilization rate of chemotherapeutic drugs after embolization is low. Chemotherapy resistance mediated by high nuclear factor E2-related factor 2 (NRF2) expression limits DEB-TACE efficacy. Camptothecin (CPT), an NRF2 inhibitor, exerts chemosensitizing effects. We designed a controlled experiment to determine the efficacy and feasibility of DEB-TACE combined with CPT for the treatment of rabbit VX2 hepatoma. DEB-TACE activated NRF2 expression in the tumor region. NRF2 activation could be inhibited by the combined use of CPT. After DEB-TACE alone, the tumor necrosis was incomplete, there were still highly active tumor residues, and the apparent diffusion coefficient (ADC) value, which was negatively correlated with tumor activity observed by magnetic resonance imaging, remained low. After DEB-TACE combined with CPT, the relative necrosis of the tumor was more complete, the ADC value was higher, and the ADC change was greater. The single application of CPT did not result in evident liver function and physical burden to the rabbits. The combined use of CPT and DEB-TACE did not significantly increase DEB-TACE imaging of liver function and body. In conclusion, CPT can also inhibit high NRF2 expression after DEB-TACE treatment. Combining CPT with DEB-TACE can improve the sensitivity of DEB-TACE in the treatment of VX2 tumors, improve the therapeutic effect, and has no evident toxic and side effects. This study explored the methods for enhancing the efficacy of DEB-TACE in liver cancer from a new perspective and performed model experiments, which provided a theoretical basis for future clinical treatment.
急性肠系膜缺血是由不同病因引起的肠系膜血运障碍导致肠管缺血及炎症损伤甚至肠坏死的一类少见的危及生命的急腹症 [1, 2]。病因可能为肠系膜上动脉栓塞、狭窄并血栓形成、肠系膜上静脉血栓形成或非阻塞性病变 [3]。尽管现代诊治手段丰富,急性肠系膜缺血的总体病死率仍为50%~70% [4]。预后较差的原因主要是患者早期临床表现常无特异性,造成诊断不及时,延误治疗时机。老年人肠系膜上动脉不同程度狭窄的比例可达17.5% [5],随着老龄化社会的到来,急性肠系膜缺血的发病率可能会不断增加 [6]。随着介入技术的进步及手术室条件的改善,近年来复合手术逐渐开展并兴起,介入技术与开放手术的复合应用可以互为补充,起到事半功倍的效果。我院将一站式复合手术应用于2例肠系膜上动脉狭窄继发血栓形成合并肠坏死的急性肠系膜缺血患者,临床效果满意,现报告如下。
Lenvatinib plus transarterial chemoembolization (TACE)have become the first choice for patients with hepatocellular carcinoma (HCC) that are unsuitable for TACE. Sorafenib plus TACE therapy for patients with portal vein tumor thrombus (PVTT) achieved positive results. However, Lenvatinib plus TACE appeared to achieve a more advantageous result for these patients based on the phase 3 REFLECT trial. Both TACE and lenvatinib therapy have immune-stimulating effects, so would lenvatinib plus TACE and immune checkpoint inhibitors be an advantageous therapy for unresectable HCC (uHCC)? Thirteen articles from PubMed were explored to determine the efficacy and safety of lenvatinib plus TACE with or without PD-1 inhibitors therapy. Most of the adverse events (AEs) were manageable. Lenvatinib plus TACE therapy was superior to lenvatinib monotherapy with intermediate stage HCC especially beyond up-to-seven criterion and was superior to TACE monotherapy in patients with uHCC or sorafenib plus TACE therapy in patients with PVTT. Objective response rates (ORRs) of 53.1%-75%, median progression free survival (PFS) of 6.15-11.6 months, and median overall survival (OS) of 14.5-18.97 months were achieved in the lenvatinib plus TACE group. Levatinib plus TACE and PD-1 inhibitors achieved ORRs of 46.7% -80.6%, median PFS of 7.3-13.3 months, and median OS of 16.9-24 months. Control studies also confirmed the triple therapy was superior to lenvatinib plus TACE in patients with uHCC. Overall, the triple therapy is a promising treatment for patients with uHCC, including main PVTT and extrahepatic metastasis. Lenvatinib plus TACE therapy was also preferable for intermediate stage HCC beyond up-to-seven criterion and for patients with PVTT.
车把综合征所致的股动脉损伤是下肢缺血的重要病因之一。由于股动脉受到撞击导致的钝挫伤常继发血栓形成而引起肢体缺血。临床上通常需要切开探查进行血管修复甚至血管重建。本文报道2例车把综合征导致股动脉损伤引起下肢动脉缺血的患者,血管具体损伤类型不同,均合并下肢动脉远端栓塞,急诊行股动脉血运重建同时在DSA引导下行下肢动脉精准取栓的杂交手术取得了较好的治疗效果,可供临床借鉴以提高保肢率。
Higher oxidant stress capacity could promote invasion and metastasis. A previous study showed hepatocellular carcinoma (HCC) expressed more Nrf2 than para-carcinoma tissue. The chemotherapeutics such as epirubicin (EPI) could increase Nrf2 expression, while Camptothecin (CPT) could inhibit tumor growth by down-regulating the key molecule of antioxidant stress signal—Nrf2. The role of Nrf2 in invasion and metastasis was still unclear. In this study, we use EPI and CPT to determine the invasion and metastasis in Huh7 cells, H22 and Huh7 mouse models. In Huh7 cells, Nrf2 expression and ROS level were found increased after incubation with EPI by western blot and flow cytometry assay. But with the combination of EPI and CPT, inhibition of Nrf2 could decrease proliferation, invasion, and metastasis, which were investigated by CCK8 assay, wound healing, and Transwell assays. In Huh7 and H22 mouse models, EPI promoted Nrf2 up-regulation and nucleus translocation. Tumor growth was obviously inhibited with a single application of EPI or CPT. The combination of EPI and CPT could inhibit Nrf2 expression but demonstrated more suppressing effect of tumor growth than EPI. Western blot and immunohistochemical staining study revealed that Nrf2 inhibition was beneficial in decreasing the expression of N-cadherin, MMP9, Snail as well as Twist, and increasing E-cadherin, which were associated with epithelial–mesenchymal transition (EMT). Nrf2 down-regulation promoted lung metastasis of H22 cells in vivo. In addition, H&E staining and immunofluorescence staining of VEGFR suggested angiogenesis of Huh7 and H22 tumors was reduced. In conclusion, down-regulation of Nrf2 demonstrated inhibition of invasion, metastasis, and angiogenesis of hepatoma, which may provide a potential therapy in HCC.
随着在华医学留学生规模的扩大,如何提高教学及管理质量成为各高校共同面临的问题.本文在调查留学生教学实际和分析所在问题基础上,提出了融合式、趋同化管理模式,在实践中改革和完善医学留学生管理工作,通过对留学生在改革前后对教学满意度的变化,证明了该管理模式的可行性和有效性,有望为同类高校的管理改革提供借鉴和思路.
Hepatocellular carcinoma (HCC) has more recently become a leading cause of cancer-associated mortality worldwide. Particularly at an advanced stage, the prognosis is generally poor due to lack of effective treatments. Transarterial chemoembolization (TACE) is now a recognized therapy for advanced HCC, serving to deprive tumors of feeder arteries through induced ischemic necrosis. However, there is also a potential for undesired circulatory toxicity owing to drug ref lux from tumor artery to surrounding healthy tissues. Although effective chemotherapeutic drug concentrations are thus lowered, the side effects of systemic chemotherapy are aggravated. The mid-2000 emergence of drug-eluting beads (DEB) loaded with anti-neoplastic drugs has proven particularly advantageous, enabling localized treatment and directed delivery of chemotherapeutics. DEB-TACE (dTACE) augments local infusion of anti-neoplastic agents to prolong agent/tumor contact, expanding upon conventional TACE. At present, data on DEB use in China are limited, particularly in terms of proprietary microspheres (CalliSpheres; Hengrui Medicine Co.). To explore the efficacy and safety of CalliSpheres, A total of 90 patients receiving this means of dTACE for advanced HCC were assessed in the present study. Clinical efficacy was evaluated based on tumor response and overall survival rates using the National Cancer Institute Common Terminology Criteria for Adverse Events to assess tolerability. The satisfactory tumor response and acceptable tolerability demonstrated in the follow‐up confirm the promising utility of CalliSpheres in treating patients with advanced HCC.
Hepatocellular carcinoma (HCC) has more recently become a leading cause of cancer-associated mortality worldwide. Particularly at an advanced stage, the prognosis is generally poor due to lack of effective treatments. Transarterial chemoembolization (TACE) is now a recognized therapy for advanced HCC, serving to deprive tumors of feeder arteries through induced ischemic necrosis. However, there is also a potential for undesired circulatory toxicity owing to drug reflux from tumor artery to surrounding healthy tissues. Although effective chemotherapeutic drug concentrations are thus lowered, the side effects of systemic chemotherapy are aggravated. The mid-2000 emergence of drug-eluting beads (DEB) loaded with anti-neoplastic drugs has proven particularly advantageous, enabling localized treatment and directed delivery of chemotherapeutics. DEB-TACE (dTACE) augments local infusion of anti-neoplastic agents to prolong agent/tumor contact, expanding upon conventional TACE. At present, data on DEB use in China are limited, particularly in terms of proprietary microspheres (CalliSpheres; Hengrui Medicine Co.). To explore the efficacy and safety of CalliSpheres, A total of 90 patients receiving this means of dTACE for advanced HCC were assessed in the present study. Clinical efficacy was evaluated based on tumor response and overall survival rates using the National Cancer Institute Common Terminology Criteria for Adverse Events to assess tolerability. The satisfactory tumor response and acceptable tolerability demonstrated in the follow-up confirm the promising utility of CalliSpheres in treating patients with advanced HCC.
Background: Arteriovenous fistula (AVF) is defined as an abnormal communication between the high flow arterial system and the low flow venous network, which directly connects the arterial feeding vessels and the near draining veins without normal intervening capillary bed. Arteriovenous fistula incurs in preauricular region is exceeding rare. Most of these fistulae occur as a result of an iatrogenic injury, the volume is small, feeding and draining vessels of feeding and draining are simple, and can be cured easily. However, the treatment of the large and complicated AVF after incidental trauma in preauricular region is a challenge even for senior neurosurgeon. In this study, the authors discuss the management of a traumatic AVF through combined therapeutic method of surgical ligation and transarterial embolization. It is fed by ipsilateral superficial temporal artery, internal maxillary artery, posterior auricular artery, and their accessory branches and is drained by ipsilateral common facial vein and external jugular vein. Also the etiology, clinical manifestations, pathology, diagnosis, and management are summarized. Conclusion: Large and complicated traumatic AVF in preauricular region is rare, often due from an injury in maxillofacial region, combined therapy needed.
Objective To study the influences of ectogenous nitric oxide (NO) on morphologic and apoptotic bodies of in vitro cultured normal and injured human umbilical vein endothelial cell (HUVEC),and to discuss the repair mechanism.Methods We built the injured HUVEC model,and assessed the intervention of ectogenous NO sodium nitroprusside on injured HUVEC.HUVEC was divided into three groups:normal group,injury group and intervention group.The morphological changes of the cells and apoptotic bodies after the Hoechst33258 blue fluorescence staining in the light microscope was observed.The expression of endothelial nitric oxide synthase (eNOS) and Caspase-7 was tested by Western blot,vascular endothelial growth factor (VEGF) by ELISA and proliferating cell nuclear antigen (PCNA)by immunohistochemistry.Results Normal HUVEC were injured by oxidative stress induced by H2O2,the cellular morphological change and apoptotic bodies was observed.The morphological change in intervention group was negligible,and apoptotic bodies decreased significantly.Expression of eNOS decreased in injury group,which recovered in intervened group.No expression of Caspase-7 in normal group was observed,as it could be detected in injury group,while it decreased significantly in intervention group.Level of VEGF as higher in intervention group than those in other two groups,with significant difference (P<0.05) between intervention and injury groups.Expression of PCNA in intervention group [(9.87±0.75)%]was almost equal to that in normal group [(10.25± 0.63)%],and was higher than that in injury group[(3.04±0.34)%].There was a significant difference (P<0.05) between intervention and injury groups.Conclusions Intervention of a certain dose of ectogenous NO can upregulate the expression of eNOS gene and eNOS self-synthesis,improve repairing of endothelial cells,resist apoptosis and protect function of proliferation,synthesis and excretion of endothelial cells.
Objective: To evaluate the safety and clinical short-term efficacy of interventional embolization with CalliSpheres-loaded microspheres in treating advanced hepatocellular carcinoma. Methods: A total of 25 patients with advanced hepatocellular carcinoma underwent transcatheter arterial chemoembolization (TACE) plus using CalliSpheres-loaded microspheres treatment. The clinical and imaging data, complications of interventional treatment and prognosis were summarized and analyzed by modified response evaluation criteria in solid tumors (mRECIST); follow-up was performed on all patients. Results: The follow-up lasted 6 months. According to mRECIST, the 3-month objective response rate (CR+PR) was 80% and disease control rate (CR+PR+SD) was 88%; the 6-month objective response rate (CR+PR) was 72% and disease control rate (CR+PR+SD) was 80%. At day 3 after the procedure, the levels of ALT, AST and TBIL were increased, with a statistical significance compared with those before the operation. However, there was no significant difference in the level of albumin. At 3 months postoperatively, the indications of liver function returned to the normal level. And there was no significant difference between pre- and post-operation. No severe complications, such as bile leak with infection, liver abscess, abdominal hemorrhage, bleeding due to tumor rupture and gastrointestinal bleeding occurred in these patients. Conclusion: TACE performed with CalliSpheres-loaded microspheres is a novel and safe option for patients with advanced hepatocellular carcinoma. Its clinical short-term efficacy was satisfied, yet its long-term efficacy needs further studies. Key words: Transcatheter arterial chemoembolization; Hepatocellular carcinoma; Drug-loaded microspheres; CalliSpheres
目的 临床工作中需要一种非侵入性、非创伤性和辐射性的诊断意见对冠状动脉硬化心脏病、冠脉狭窄进行诊断.本研究探讨冠状动脉狭窄与血压、血脂和血糖的关系,并结合年龄和性别建立冠脉狭窄logistics预测模型,以探索无创性诊断冠脉狭窄的可行性.方法 本文收集了接受冠状动脉血管造影患者894例,冠脉DSA检查结果分为狭窄组和无狭窄组.两组均测定安静时血压、空腹血糖、甘油三酯、血清总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇等生化指标.利用t检验分析两组之间各指标的差异是否具有统计学意义,并将其拟合logistic模型建立预测模型.结果 两组年龄、性别、空腹血糖、血清总胆固醇和高密度脂蛋白胆固醇差异具有统计学意义(P<0.05),狭窄组中高血压患者及男性患者比例高于无狭窄组,无狭窄组中女性患者比例高于男性患者.两组间甘油三酯和低密度脂蛋白胆固醇差异无统计学意义(P>0.05).将年龄、性别、血压、空腹血糖、血清总胆固醇和高密度脂蛋白胆固醇拟合logistics模型后,AUC为0.751.高密度脂蛋白对冠心病为保护性指标;老年男性、高血压、总胆固醇作为冠心病的危险因素,是老年人防治冠心痛的重点内容;降低胆固醇和血糖、对防治老年人,特别是男性人群的冠心病有积极的意义.结论 本文建立的logistics模型在预测冠脉狭窄情况上有一定作用,可以在一定程度上实现冠脉狭窄的无创性诊断.
女,28岁,无明显诱因发现左股部肿物2个月余,无疼痛不适。于5年余前曾于外院行左侧股部包块切除术,诊断为脂肪瘤,术后恢复良好。查体:双下肢等长等粗,左大腿内侧可见一长约5 cm手术瘢痕,愈合良好;左侧腹股沟下方区域大腿内侧可见一肿物,大小约7 cm×4 cm,质软,无压痛,活动度好,边界欠清楚,周围皮肤无红肿,未见色素沉着及溃疡形成。入院初步诊断:左股部肿物,血管瘤?入院后行ESR、CRP、肿瘤标志物检查未发现异常。
Objective To evaluate the clinical efficacy of transcatheter arterial infusion umbilical cord blood stem cells combined with TIPS for decompensated cirrhosis.Methods The changes of 50 patients with decompensated cirrhosis about ALT,AST,TBIL and prealbumin before and 2,4 weeks after treatment were retrospectively analyzed.The changes of esophageal and gastric varices,and liver volume before and 16 weeks after treatment were compared.Results Compared with pre-operation,the changes of ALT,AST,TBIL were not obvious 4 weeks after treatment.However the prealbumin [(51 ±28)μg/L vs (145 ±72)μg/L]and PTa [(37.0 ±10.5)% vs (61.0 ±28.4)%] were significantly higher(P <0.01).The esophageal and gastric varices improved and liver volume increased obviously 16 weeks after treatment [(971.3 ±307.7)cm3 vs (1220.4 ±198.5)cm3,P<0.05].Conclusions The combination therapy can significantly increase liver volume,improve liver synthetic function,reduce portal pressure.
目的观察针刀松解颈周腧穴治疗椎动脉型颈椎病的临床效果.方法选择2009年12月-2012年10月住院的椎动脉型颈椎病患者229例,按照随机编码分组法,分为治疗组113例和对照组116例,治疗组针刀松解颈周腧穴,对照组针刀松解寰枢区、枕下三角区和星状节部.两组均7d治疗1次,3次为1个疗程,1个疗程后统计近期疗效,3个月后统计远期疗效.计量资料采用t检验,计数资料采用x2检验,P<0.05为差异有统计学意义.结果治疗后治疗组颈性眩晕症状与功能评估量表积分[(22.07±3.83)分]与对照组[(20.53±3.85)分]比较差异有统计学意义(P<0.05),治疗后治疗组颈椎曲度值[(10.23±1.66).]与对照组[(8.97±1.18).]比较差异有统计学意义(P<0.05).两组近期疗效、远期疗效比较差异均无统计学意义(均P>0.05).结论针刀治疗颈椎病疗效确切,且针刀松解颈周腧穴降低了操作的风险和难度,容易掌握,更安全.