Chemotherapy resistance represents a formidable obstacle in oncological therapeutics, substantially compromising the efficacy of adjuvant chemotherapy regimens and contributing to unfavorable clinical prognoses. Emerging evidence has elucidated the pivotal involvement of exosomes in the dissemination of chemoresistance phenotypes among tumor cells and within the tumor microenvironment. This review delineates two distinct intra-tumoral resistance mechanisms orchestrated by exosomes: (1) the exosome-mediated sequestration of chemotherapeutic agents coupled with enhanced drug efflux in neoplastic cells, and (2) the horizontal transfer of chemoresistance to drug-sensitive cells through the delivery of bioactive molecular cargo, thereby facilitating the propagation of resistance phenotypes across the tumor population. Furthermore, the review covers current in vivo experimental data focusing on targeted interventions against specific genetic elements and exosomal secretion pathways, demonstrating their potential in mitigating chemotherapy resistance. Additionally, the therapeutic potential of inhibiting exosome-mediated transporter transfer strategy is particularly examined as a promising strategy to overcome tumor resistance mechanisms.

减重与代谢外科在我国快速发展,虽然目前我国主流术式源于西方国家,但中国减重与代谢外科医生也在不停的探索更适合我国病人的新术式.探索新术式初衷虽好,但是新术式在开展前要对手术的规范性、安全性、有效性进行严格评估,不可直接大范围推广.减重与代谢外科的相关行业学术组织也应发挥正面引导作用,提升经济效益与社会效益,助力我国减重与代谢外科更快更好发展.

In more than half a century of the development of bariatric metabolic surgery, a variety of classic surgical methods have been formulated. However, the improvement and innovation of bariatric metabolic surgery has never stopped. The replacement of new and old surgical methods in clinical application and development reflects the vitality and progress in the field of bariatric metabolic surgery, and also promotes the development of bariatric metabolic surgery to the best balance between benefits and risks. In the early stages, studies in metabolic surgery are more inclined to confirm the efficacy, safety and mechanism of classical procedures. In recent years, metabolic surgeons around the world have become more inclined to focus on the exploration and innovation of new procedures. In addition, the improvement of biliopancreatic diversion with duodenal switch and the sleeve gastrectomy plus procedures have gradually become hot spots for surgical innovation. However, the new techniques are diverse, scattered and partially overlapping. The authors make a comment on this content, in order to provide assistance to clinical and scientific research.

Analysis of the layout and proportion of classic and innovative surgical procedures of bariatric and metabolic surgery throughout the world, the sleeve gastrectomy is beco-ming the most accepted and respected surgical procedure with its increasingly prominent advan-tages, and its operation number has even exceeded the "gold standard" surgery of the roux-en-Y gastric bypass. This trend is even more pronounced in China. With a small number of physicians lacking experience in gastrointestinal surgery and more and more young physicians joining in the field of bariatric and metabolic surgery, operation related complications and the consequences of insufficient perioperative management experience have occurred successively in clinical practice, such as gastrointestinal leakage, bleeding, lumen and anastomotic stenosis, internal hernia and obstruction, venous thromboembolism, etc. Bariatric and metabolic surgery is a branch of gastro-intestinal surgery, and physicians in the field should have the ability to prevent, predict and manage short- and long-term complications after surgery. The authors believe that through the comprehen-sive evaluation of laboratory indexes, patient signs and related examinations, physicians should have the basic qualities of decisively choosing the surgical timing, choosing the right decision-making, and taking effective measures.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.021.].

Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.

A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of 'old drugs newly used' to target TME communication and clarified a new line to prevent tumor malignant capacity.

背 景 肥胖代谢外科手术是目前治疗肥胖症及相关代谢病最有效的方式之一,手术量逐年稳步增长[1].中国肥胖代谢外科数据库2019年度报告统计估算2019年中国年手术量超过10000例[2],相关手术方式也越来越多.然而其中不少手术方式并不规范或尚缺乏中长期疗效数据及充分的循证医学证据,开展时需慎重考量[3,4].为此,中国医师协会外科医师分会肥胖和糖尿病外科医师委员会(Chinese Society for Metabolic & Bariatric Surgery,CSMBS)与中国肥胖代谢外科研究协作组(COMES Collaborative)组织我国肥胖代谢外科专家,先后经问卷调查、会议讨论后制定本立场声明,以规范我国肥胖代谢外科手术方式选择,旨在为开展肥胖代谢外科手术的医生在临床决策、术式选择上提供参考和依据,促进行业规范健康地发展.

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.

Bariatric and metabolic surgery has been in China for more than 30 years, which has developed rapidly. However, it can be predicted that there will be many opportunities and challenges in the future development of bariatric and metabolic surgery, including the replacement of classic surgical methods, the guarantee of surgical safety, the brave exploration of new surgical methods, the decisive abandonment of bad surgical methods, the implementation of surgical standardization, and the breakthrough of basic and clinical research all mean more efforts. With the continuous rise of the incidence rate of metabolic syndrome and the continuous improvement of people′s health needs, these opportunities and challenges are particularly significant. Bariatric and metabolic surgery will also play a crucial role in overcoming obesity and metabolic diseases.

BACKGROUND:Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear.METHODS:The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments.RESULTS:We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression.CONCLUSIONS:Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.

Purpose Sorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC. Methods Bioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions. Results CISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened. Conclusion Inhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.

Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.

The tumor microenvironment represents a dynamically composed matrix into which cancer cells and many other cell types are embedded to form organ-like structures. The tumor immune microenvironment (TIME), composed of immune cells, is an inseparable part of the tumor microenvironment. Extracellular vesicles (EVs) participate in the occurrence and development of tumors by delivering various biologically active molecules between cells; their role in cancer immune escape in particular has been widely proven. EVs can carry a wide array of cargo, such as non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, which are selectively loaded by EVs, secreted, and transported to participate in the proliferation of immune cells. Hence, strategies to specifically target EV-ncRNAs could be attractive therapeutic options. In this review, we summarize the current research on the role of EV-ncRNAs in cancer immune escape, and discuss the latest research on the function and regulation mechanism of EV-ncRNAs in cancer immune escape, highlighting and elucidating the potential clinical applications of EV-ncRNAs, including in diagnosis and immunotherapy.

Intracellular organelle cross-talk is a new and important research area. Under stress conditions, the coordinated action of the autophagy and endosomal systems in tumor cells is essential for maintaining cellular homeostasis and survival. The activation of the IκB kinase (IKK) complex is also involved in the regulation of stress and homeostasis in tumor cells. Here, we try to explore the effects of constitutively active IKKβ subunits (CA-IKKβ) on autophagy and endosomal system interactions. We confirm that CA-IKKβ induces accumulation of autophagosomes and their fusion with MVBs to form amphisomes in cancer cells, and also drives the release of EVs containing autophagy components through an amphisome-dependent mechanism. We further demonstrate that CA-IKKβ inhibits the expression of RAB7, thereby weakening the lysosomal-dependent degradation pathway. CA-IKKβ also induces phosphorylation of SNAP23 at Ser95 instead of Ser110, which further promotes amphisome-plasma membrane fusion and sEV secretion. These results indicate that CA-IKKβ drives the formation and transport of amphisomes, thereby regulating tumor cell homeostasis, which may illuminate a special survival mechanism in tumor cells under stress.

胆囊切除是胆源性胰腺炎非常重要的治疗手段之一.对于胆系结石引起的胆源性胰腺炎,且病人身体条件允许时,均应行胆囊切除术.轻症胆源性胰腺炎应早期行腹腔镜胆囊切除术,可减少胰腺炎的复发.反复发作的特发性胰腺炎中,相当一部分病人为隐匿性胆源性胰腺炎,病因不明时,可否行胆囊切除术,目前尚无定论,建议加强随访,争取明确有无胆囊结石,如仍不能明确病因,须与病人充分沟通后,再行胆囊切除术.

Bariatric and metabolic surgery originated in the 1950s. After continuous verifications and improvements by bariatric and metabolic surgeons all over the world, bariatric surgery has been recognized as the 'gold standard’ for the treatment of metabolic diseases such as obesity. In the development of more than half a century, bariatric and metabolic surgery have formed a variety of classic surgical methods. At the same time, the new methods of bariatric surgery are emerging. Among them, the additional surgery based on sleeve gastrectomy has become a research hotspot. In the process of clinical applications of various new bariatric surgery methods, bariatric and metabolic surgeons should be objective, accurate, realistic, and move forward on the basis of criticizing and absorbing. The authors investigate the influence of new surgical methods on the development of bariatric and metabolic surgery.

In the development of more than half a century, many classical operation methods have been formed in the bariatric and metabolic surgery. Among them, LSG and LRYGB have withstood the tests of time with good efficacy and low postoperative complications, and are still the first choice in the field of bariatric and metabolic surgery. At the same time, new methods of bariatric surgery continue to appear. Bariatric and metabolic surgeons should steadily carry out multicenter and large-scale clinical researches of new surgical methods on the premise of fully mastering the operation principle, safety and clinical efficacy, and ultimately benefit patients.

Molecular oxygen (O 2 ) is a universal electron acceptor that is eventually synthesized into ATP in the mitochondrial respiratory chain of all metazoans. Therefore, hypoxia biology has become an organizational principle of cell evolution, metabolism and pathology. Hypoxia-inducible factor (HIF) mediates tumour cells to produce a series of glucose metabolism adaptations including the regulation of glucose catabolism, glycogen metabolism and the biological oxidation of glucose to hypoxia. Since HIF can regulate the energy metabolism of cancer cells and promote the survival of cancer cells, targeting HIF or HIF mediated metabolic enzymes may become one of the potential treatment methods for cancer. In this review, we summarize the established and recently discovered autonomous molecular mechanisms that can induce cell reprogramming of hypoxic glucose metabolism in tumors and explore opportunities for targeted therapy.