Research Progress of Signaling Pathways Related to Treatment of Colorectal Cancer with Chinese Medicine： A Review / 中国实验方剂学杂志

The occurrence and development of colorectal cancer as a complex disease involves the abnormality of multiple signaling pathways. Chinese medicine regulates a variety of biological processes such as tumor cell differentiation， cell proliferation， apoptosis， cell metastasis， cell cycle， and tumor angiogenesis to prevent the occurrence of colorectal cancer （inflammation-cancer transformation）， tumor metastasis （common metastases of colorectal cancer include liver metastasis， lung metastasis， bone metastasis， and lymphatic metastasis）， and multidrug resistance induced by chemotherapy， treat primary tumors， and mitigate the toxic and side effects of chemotherapy. The pathways of Chinese medicine in the treatment of colorectal cancer have been intensively studied. The available studies have demonstrated that Patrinia villosa Juss and Pien Tze Huang can regulate the Notch pathway to inhibit the growth of colorectal cancer cells. Curcumin and Quyu Jiedu decoction regulate Hippo pathway to inhibit the survival， proliferation， invasion， and migration of colorectal cancer cells. Kujin tea and luteolin suppress the proliferation of colorectal cancer cells and protect intestinal barrier by regulating Kelch-like epichlorohydrin-associated protein-1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/antioxidant response element （ARE） pathway. Icariin and ginkgolide C can regulate hepatocyte growth factor （HGF）/cellular-mesenchymal to epithelial transition factor （c-Met） pathway to induce apoptosis of colorectal cancer cells and prevent liver metastasis of colorectal cancer. Verbascoside and apigenin regulate p53 protein to promote apoptosis of colorectal cancer cells， reverse thymidylate synthase （TS）， and alleviate the multidrug resistance of colorectal cancer. Resveratrol and lycopene regulate insulin-like growth factor （IGF）/insulin-like growth factor receptor 1 （IGF1R） pathway to inhibit cancer cell metastasis and prolong disease-free survival. Cordycepin and Galla Chinensis water extract activate AMP-activated protein kinase （AMPK） pathway to inhibit the migration and invasion of cancer cells as well as the lung metastasis of colorectal cancer. The above summary aims to provide reference for the in-depth research on the treatment of colorectal cancer with Chinese medicine and inspire new research ideas.

Application of the island flap at the dorsum of the middle phalange with the pedicel of the digital proper artery / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore a method for the treatment of the skin defects at the distal phalanges of 2-5th fingers.</p><p><b>METHODS</b>The island flap at the dorsum of the middle phalange was designed with the pedicle of dorsal branches from the digital proper artery. When the flap was used to repair defect at finger pulp, the dorsal branch of the digital proper nerve in the flap was kept to be anastomosed to the digital proper nerve at the recipient finger. From Feb. 2005 to May. 2010, 54 cases with skin defects at the distal phalanges of 61 fingers were treated with the flap, including 35 defects at finger pulp and 26 defects at finger tip.</p><p><b>RESULTS</b>The maximum size of defects and flaps was 2.2 cm x 2.5 cm and 2.4 cm x 2.7 cm, respectively. 61 flaps survived completely. Blister was happened in 3 flaps 2 days after operation, which healed spontaneously without necrosis. 54 cases were followed up for 5 to 22 months (average, 11 months). The flaps had good texture and color match with normal sensation (grade S4). The 2-point discrimination distance was 6-9 mm. The interphalangeal joint had normal movement.</p><p><b>CONCLUSIONS</b>The island flap at the dorsum of the middle phalange is an ideal method for the skin defect at the distal phalange of finger.</p>

External fixation and bone grafting for collapsed and comminuted distal radius fracture / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To study the therapeutic effect of collapsed and comminuted distal radius fracture.</p><p><b>METHODS</b>Twenty-six patients with collapsed and comminuted distal radius fracture were hospitalized from July 1998 to June 2003. All fractures were treated by the methods of open reduction, sustained bone grafting and passing joint external fixator to restore the anatomic shape of distal radius.</p><p><b>RESULTS</b>All 26 cases were followed up, and the results showed that the fractures have been united radiographically. The joint surfaces were intact and there was no length discrepancy occurred in patient's radius. The average volar tilt was 6 to 15 degrees and the average ulnar tilt was 18 to 25 degrees. According to the Dieust criterion, 19 cases were rated as excellent and 7 as good.</p><p><b>CONCLUSIONS</b>The method that applying passing joint external fixator and bone grafting for the treatment of collapsed and comminuted distal radius fracture could maintain the stability of fracture and restore the length of radius and the intact of joint surface.</p>

The investigation of hematopoietic capacity of HPP-CFC derived from murine embryonic stem cells in vitro and in vivo / 生物工程学报

The hematopoietic system of the mouse arises from extraembryonic mesoderm that migrate through primitive streak to the presumptive yolk sac at day 7.0 of gestation. However, the mechanisms regulating mesoderm commitment to hematopoietic lineages remain poorly understood. Previous studies demonstrated that the development kinetics and growth factor responsiveness of hematopoietic precursors derived from embryonic stem cells (ES cells) is similar to that found in the yolk sac, indicating that the onset of hematopoiesis within the embryoid bodies (EBs) parallels that found in the embryo. Furthermore, in vitro differentiation of ES cells to hematopoietic cells is valuable for establishment of therapeutic clone against a variety of hematological disorders. Despite the identification of multipotential hematopoietic progenitors in EBs, a subset of more primitive progenitors, identical to the high proliferative potential colony-forming cells (HPP-CFC) derived from human and murine hematopoietic tissues, have not been clearly identified regarding particular their replating potential in vitro. HPP-CFC is among the most primitive hematopoietic multipotent precursors cultured in vitro. In this study, our aim was to investigate the in vitro and in vivo hematopoietic capacity of HPP-CFC within the day 12 EBs, rather than the expansion of more committed progenitors. In this study the HPP-CFC could be detected within EBs differentiated for 5 to 14 days of murine ES cells, but the development dynamics of the HPP-CFC differed greatly among distinct serum lots. Qualitatively HPP-CFC is capable of forming secondary colonies. As to our expectation the ES cells-derived HPP-CFC demonstrated similar regeneration capacity to those from yolk sac, giving rise to secondary granulocyte, erythrocyte, macrophage and mast cells, however largely differed from the counterparts of adult bone marrow. In addition, by RT-PCR ES cells-derived HPP-CFC were found to express transcription factors associated closely with stem cell proliferation including SCL, GATA-2 and AML1 as well as various receptors of hematopoietic growth factors such as c-kit, GM-CSF receptor and interleukin 3 receptor et al. Finally, in order to understand the in vivo hematopoietic capacity of the ES cells-derived HPP-CFC, spleen colony-forming unit (CFU-S) assay was performed. Nevertheless, typical CFU-S was not observed after transplantation of the day 12 EB cells or HPP-CFC colonies into lethally irradiated adult murine. In conclusion the HPP-CFC differentiated from murine ES cells displayed robust hematopoietic activity in vitro, however their in vivo reconstitution ability was not detected. The difference between in vitro and in vivo hematopoietic activities of ES cells-derived primitive hematopoietic precursors deserves further investigation.

Establishment of a Human Umbilical Vein Endothelial Cell Line Supporting Hematopoiesis In Vitro / 中国实验血液学杂志

Endothelial cells are the critical cell component of hematopoietic microenvironment. For the purpose of facilitating the study on modulating effect of endothelial cells in hematopoiesis, a human umbilical vein cell line, IEC, was established. Primary human umbilical vein endothelial cells were transfected with the plasmid pSV(3neo) carried SV40 large T antigen by lipofection. The IEC cells expressed factor VIII and the UEA I-binding ratio was about 97%. The chromosome variation was existed in the cell line, with the karyotype 45, XX, -18, 18q(+). The cell line retained the proliferative capacity at least 25 passages. IEC cells stimulated the growth of granulocyte-macrophage progenitor cells in coculture of cord blood CD34(+) cells with IEC cells. It is concluded that IEC cell line possessed the biological features of endothelial cell and supported hematopoiesis in vitro.

Maintaining Growth of Long-Term Culture Initiating Cells from Human Cord Blood on Feeder Layers of Bone Marrow Stromal Cells Transfected with FL and/or TPO Genes / 中国实验血液学杂志

Long-tem culture initiating cells(LTC-IC), and in vitro assay of hematopoietic stem/progenitor cells, still represent a heterogeneous population in terms of proliferative capacity and sensitivity to different growth factors. Human umbilical cord (CB) is rich of hematopoietic progenitor cells measured by clonogenic assays and stem cells capable of reconstituting the marrow after transplantation. The influence of culture conditions on the in vitro behavior of LTC-IC from CB was evaluated. First, by using IRES sequence, FL and TPO cDNA were recombined with retroviral vector pLXSN by gene recombination technology. The recombinant plasmid pLFSN, pLTSN, pLFTSN were transfected into human stromal cell line HFCL. Then, LTC-IC were evaluated in long term cultures, comparing five types of stromal feeder layers: human bone marrow stromal cell, human stromal cell line HFCL, and stromal cell lines HDF tranfected with FL gene, HLT transfected with TPO gene or HFT co-transfected with FL and TPO genes. The results were demonstrated that after 8 weeks of coculture, three types of stromal cell lines that supported the maintenance of CFU-C for up to 3 weeks in vitro were identified. However, cocultivation of human bone marrow stromal cell and CB CD34(+) cells on HFT, CFU-C production continued up to 6 weeks or longer on these stroma. The absolute LTC-IC frequency in CD34(+) cells on human bone marrow stromal cell (2.65 +/- 0.76/1 000 cells) was no significant difference with on HFT (3.65 +/- 0.58/1 000 cells). Thus, HFT acts by direct contact to maintain the phenotype and function of the most primitive and quiescent human progenitors. Furthermore, HFT cell line was selected as the optimal one for supporting long-term culture feeder. It was concluded that LTC-IC progenitors from cord blood maintain growing upon the FL/TPO gene-modified stromal feeder layers in vitro.

Human umbilical vein endothelial cells support hematopoiesis and expansion of hematopoietic stem/progenitor cells in vitro / 军事医学科学院院刊

Objective: To investigate the role of human umbilical vein endothelial cells (HUVEC) in supporting hematopoiesis and the expansion of hematopoietic stem/progenitor cells in vitro. Methods: According to the fact that HUVEC supernatant has colony stimulating activity shown by methylcellulose colony-forming assay and HUVEC can maintain the survival of mononuclear cells for at least four weeks in vitro, CD34+ cells from umbilical cord blood were seeded with (HUVEC group) or without (control group) HUVEC monolayer. Every week cells were collected and counted, the frequency of CFU-GM was measured by using methylcellulose colony-forming assay, and the percentage of CD34+ and CD41a+ cells was measured by flow cytometry. Results: In control group，all the CD34+ cells died in two weeks. However, in HUVEC group,most nucleated cells and CD34+ cells were expanded by 68.1±14.8 fold and 6.6±1.4 fold，respectively at the third week while CFU-GM expansion reached its peak (5.7±2.1 fold) at the week 2. Moreover, the percentage of CD41a+ cells was enhanced significantly, reaching a maximum (15.6%) at the week 3. Conclusions:HUVEC can support hematopoiesis in vitro and expand the hematopoietic progenitor cells and CD41a+ cells in direct contact coculture.