The treatment strategy for colon cancer with liver metastasis has always been a great challenge for clinical surgeons.Single treatment method such as surgical resection or systemic chemotherapy can no longer meet the treatment needs of such patients.With the extensive development of the multi-disciplinary team(MDT)for colorectal cancer based on surgery,more and more patients with advanced colorectal cancer have obtained better treatment effects and survival benefits.A case of descending colon cancer with huge hepatic metastasis diagnosed and treated by a multi-disciplinary team was reported,aiming to provide reference for clinical practice.

Stage T4 colon cancer is divided into two categories:tumor penetrating the visceral peritoneum(T4a)and tumor directly invading or attaching to adjacent organs or structures(T4b).Treatment of T4 colon cancer requires technically demanding surgical procedures,including total resection of adjacent infiltrating organs or structures,and is characterized by a high incidence of postoperative complications and a high rate of positive surgical margin microscopy.It has been found that taking laparoscopic surgery for T4 colon cancer may decrease long-term survival and increase the rate of peritoneal metastasis,but taking laparoscopic surgery for colon cancer also has the potential advantages in increasing perioperative benefits and improving the prognosis.With the upgrade of laparoscopic equipment and the improvement of surgeons'surgical skills,more and more surgeons have adopted laparoscopic surgery to treat T4 colon cancer.Currently,the oncologic safety of laparoscopic surgery for T4 colon cancer has not been effectively evaluated.Therefore,this article reviews the advantages,risks,and the choice of treatment strategies for laparoscopic surgery for T4 colon cancer,taking into account the current status and progress of domestic and international studies.

Objective : Angiotensin Ⅱ Type 2 receptor (AT2R) is a major receptor of angiotensin Ⅱ , which has a protective effect on damage to various tissues and organs．In this study，an overexpression plasmid of AT2R was con- structed to explore the effect of overexpression of AT2R on lipopolysaccharide ( LPS ) -induced inflammatory re- sponse in mouse hepatocytes (AML12 cells) ． Methods : Mice tissues and organs were used as samples to amplify the gene of interest (AT2R) fragments containing EcoR Ⅰ and Hind Ⅲ restriction sites，and then the final product was obtained by digestion and ligation．The final positive clones were sequenced and identified．The pCMV-Flag-N- AT2R plasmid was transfected into HEK 293T cells，and the expression of Flag protein was detected by the Western blot method after 24 h．AT2R expression on AML12 cells was observed by Western blot and laser confocal microsco- py．AML12 cells were treated differently and divided into control group，LPS treatment group，pCMV-Flag-N-AT2R group and pCMV-Flag-N-AT2R + LPS group，and cell viability was detected by CCK8．Western blot detected PCNA proteins and observed cell proliferation ; Cytoinflammatory factor levels were detected by qPCR ; Western blot detec- ted the expression level of nuclear transcription factor NF-кB (p65) in cells. Results : The identification and se- quencing results of EcoR I and Hind III double restriction showed that pCMV-Flag-N-AT2R plasmid was successful- ly constructed，and the detection results of the Western blot method showed successful expression of AT2R protein. Laser confocal observed that there were AT2R receptors on AML12 cells，and AT2R recombinant plasmids could be expressed on AML12; Compared with the control group，the viability and proliferation ability of LPS-treated AML12 cells were weakened，while the levels of IL-6 and TNF-α increased，and the expression level of nuclear transcription factor NF-кB (p65) increased．Compared with the LPS group，the viability and proliferation of cells in AML12 cells treated with pCMV-Flag-N-AT2R and LPS were enhanced，while the levels of IL-6 and TNF-α decreased．The ex- pression of the nuclear transcription factor NF-кB ( p65 ) decreased． Conclusion AT2R overexpression plasmids were successfully constructed and successfully expressed on AML12 cells，and AT2R could inhibit the inflammatory response of LPS-induced AML12 cells.

Organic acids are organic compounds that can be synthesized using biological systems. They often contain one or more low molecular weight acidic groups, such as carboxyl group and sulphonic group. Organic acids are widely used in food, agriculture, medicine, bio-based materials industry and other fields. Yeast has unique advantages of biosafety, strong stress resistance, wide substrate spectrum, convenient genetic transformation, and mature large-scale culture technology. Therefore, it is appealing to produce organic acids by yeast. However, challenges such as low concentration, many by-products and low fermentation efficiency still exist. With the development of yeast metabolic engineering and synthetic biology technology, rapid progress has been made in this field recently. Here we summarize the progress of biosynthesis of 11 organic acids by yeast. These organic acids include bulk carboxylic acids and high-value organic acids that can be produced naturally or heterologously. Finally, future prospects in this field were proposed.
Saccharomyces cerevisiae/metabolism* ; Organic Chemicals ; Carboxylic Acids/metabolism* ; Metabolic Engineering ; Fermentation ; Acids

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.