OBJECTIVE To investigate the effect of Curcumol on lipid metabolism in non-small cell lung cancer(NSCLC)and its related molecular mechanism.METHODS A nude mouse xenograft tumor model was established,and Curcumol was administered for 14 d.The volume and weight of subcutaneous tumors were recorded.Hematoxylin-eosin(HE)and immunohistochemical staining were used to observe the pathological morphology of tumor tissues and organs,as well as the expression levels of Ki67 protein.Bio-chemical kits were used to detect the levels of lipids in tumor tissues.Western blot was used to detect the expression levels of SREBP-1,FASN,and EGFR proteins in tumor tissues.The qPCR and immunofluorescence were used to detect the expression of SREBP-1 in tumor tissues.Curcumol was used to treat human NSCLC cell line A549 and A549 cells overexpressing SREBP-1.The EdU assay was used to detect the proliferation ability of lung cancer cells;the MTT colorimetric method was used to detect cell viability;the Transwell assay was used to detect tumor cell migration and invasion;flow cytometry was used to detect cell apoptosis;biochemical kits were used to detect lipid levels in cells;and Western blot was used to detect the expression levels of SREBP-1,FASN,and EGFR proteins.RE-SULTS In the in vivo experiment,compared with the control group,Curcumol significantly inhibited the growth of subcutaneous xen-ografts,inhibited tumor cell proliferation(P<0.05,P<0.01),reduced the levels of triglycerides(TG),total cholesterol(T-CHO),and free fatty acids(FFA)in tumor tissues(P<0.05,P<0.01),downregulated the expression of SREBP-1,FASN,and p-EGFR pro-teins(P<0.01),and inhibited the expression of SREBP-1 mRNA in tumor tissues(P<0.05,P<0.01).In the in vitro experiment,compared with the control group,Curcumol significantly inhibited the proliferation,migration,and invasion of A549 cells,reduced cell viability(P<0.05,P<0.01),promoted tumor cell apoptosis(P<0.01),downregulated the levels of FFA,T-CHO,and TG in A549 cells(P<0.05,P<0.01),and inhibited the expression of SREBP-1,FASN,and p-EGFR proteins(P<0.05,P<0.01).Additionally,overexpression of SREBP-1 antagonized the inhibitory effects of Curcumol on lipid synthesis and EGFR activation,and weakened the inhibitory effects of Curcumolc on tumor cells.CONCLUSION Curcumol inhibits the expression levels of SREBP-1 and FASN,re-duces lipid synthesis,blocks EGFR signal transduction,and slows down the occurrence and development of NSCLC.

OBJECTIVE To investigate the effect of Curcumol on lipid metabolism in non-small cell lung cancer(NSCLC)and its related molecular mechanism.METHODS A nude mouse xenograft tumor model was established,and Curcumol was administered for 14 d.The volume and weight of subcutaneous tumors were recorded.Hematoxylin-eosin(HE)and immunohistochemical staining were used to observe the pathological morphology of tumor tissues and organs,as well as the expression levels of Ki67 protein.Bio-chemical kits were used to detect the levels of lipids in tumor tissues.Western blot was used to detect the expression levels of SREBP-1,FASN,and EGFR proteins in tumor tissues.The qPCR and immunofluorescence were used to detect the expression of SREBP-1 in tumor tissues.Curcumol was used to treat human NSCLC cell line A549 and A549 cells overexpressing SREBP-1.The EdU assay was used to detect the proliferation ability of lung cancer cells;the MTT colorimetric method was used to detect cell viability;the Transwell assay was used to detect tumor cell migration and invasion;flow cytometry was used to detect cell apoptosis;biochemical kits were used to detect lipid levels in cells;and Western blot was used to detect the expression levels of SREBP-1,FASN,and EGFR proteins.RE-SULTS In the in vivo experiment,compared with the control group,Curcumol significantly inhibited the growth of subcutaneous xen-ografts,inhibited tumor cell proliferation(P<0.05,P<0.01),reduced the levels of triglycerides(TG),total cholesterol(T-CHO),and free fatty acids(FFA)in tumor tissues(P<0.05,P<0.01),downregulated the expression of SREBP-1,FASN,and p-EGFR pro-teins(P<0.01),and inhibited the expression of SREBP-1 mRNA in tumor tissues(P<0.05,P<0.01).In the in vitro experiment,compared with the control group,Curcumol significantly inhibited the proliferation,migration,and invasion of A549 cells,reduced cell viability(P<0.05,P<0.01),promoted tumor cell apoptosis(P<0.01),downregulated the levels of FFA,T-CHO,and TG in A549 cells(P<0.05,P<0.01),and inhibited the expression of SREBP-1,FASN,and p-EGFR proteins(P<0.05,P<0.01).Additionally,overexpression of SREBP-1 antagonized the inhibitory effects of Curcumol on lipid synthesis and EGFR activation,and weakened the inhibitory effects of Curcumolc on tumor cells.CONCLUSION Curcumol inhibits the expression levels of SREBP-1 and FASN,re-duces lipid synthesis,blocks EGFR signal transduction,and slows down the occurrence and development of NSCLC.

Objective:To explore the predictive value of systemic immune inflammation index (SII) for the risk of hospital death in critically ill patients.Methods:The basic information and clinical data of critically ill patients were extracted from the Medical Information Mart for Intensive Care database-Ⅳ (MIMIC-IV) database, including demographic data, vital signs, blood routine, Logistic organ dysfunction score (Lods), Oxford acute severity of illness score (Oasis), simplified acute physiology score (Saps-Ⅱ), acute physiology score Ⅲ (APS-Ⅲ), sequential organ failure score (SOFA) and outcome. The main outcome was hospital death, and the secondary outcomes were length of hospital stay, continuous renal replacement therapy (CRRT), invasive ventilation and 1-year mortality. Patients were divided into two groups according to in-hospital death, and the differences between the groups were compared. According to the SII tripartite for inter-group comparison, the patients were further divided into three groups for comparison, and Logistic regression model was used to analyze the odd ratio ( OR) of the three groups. Results:A total of 32 450 critically ill patients were included in the study, of which 3765 died in hospital, with a mortality rate of 11.6%. ① Compared with the survival group, the SII in the death group were significantly higher ( P < 0.05). ② The mortality for the SII tripartite grouping (<817; 817~2 151; >2 151) were 8.4%, 10.2% and 16.3%, respectively, and the differences between groups were statistically significant. ③ Further, Logistic regression model analysis showed that the risk of death increased gradually with the increase of groups (the first group was the reference group, OR of the second group was 1.38, 95% CI 1.24-1.54, and OR of the third group was 2.03, 95% CI 1.83-2.24 ( P < 0.05). Conclusions:SII has a certain value in predicting hospital death in critically ill patients. It is easy to obtain and can be used for risk stratification of critically ill patients.

BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) have been induced to differentiate into cardiomyocyte-like cells in vitro.OBJECTIVE:To explore the association between GATA-4, Nkx-2.5 and α-myosin heavy chain (α-MHC) expression and cell morphological changes and structure formation in the process of BMSCs differentiation into cardiomyocyte-like cells.METHODS:By using myocardial lysate, BMSCs were induced to differentiate into cardiomyocytes.Immunocytochemistry staining was used to detect cardiac troponin T (cTnT) and connexin43, for the identification of cardiomyocytes. In the process of directional differentiation, RT-PCR was used to detect the expression of GATA-4,Nkx2.5 and α-MHC.RESULTS AND CONCLUSION:During the directional differentiation of BMSCs, the cells were changed from long fusiform to short rod, forming protrusions that were interconnected to form mesh-like, bamboo-like or myotube-like structure. When the cells were interconnected like a bamboo, cTNT and connexin43 positive cells were visible, and then the number of positive cells increased with the presence of myotube-like structure. RT-PCR results showed that during the induced directional differentiation of BMSCs, GATA-4, Nkx2.5 and α-MHC mRNA levels increased continuously. When interconnected cells formed a mesh-like structure, GATA-4 expression reached the peak and then kept a high level. When adjacent cells were fused into a myotube-like structure, α-MHC reached the peak. Additionally, the expression of Nkx2.5presented a time-dependent increase trend. Overall, during the induced differentiation of BMSCs into cardiomyocyte-like cells, the expression of cardiomyocyte specific genes, characterized by temporality and spatiality, is related to the changes of cell morphology and special structure formation.

Objective To study the effect and histocompatibility of urethral extracellular matrix in repair of traumatic urethra defects in rabbits. Methods Model of traumatic urethral defects was made by resecting 1.0-1.5 cm segment of the urethra in 20 rabbits. Then, the defects were repaired by a tube of extracellular matrix of the same length. The dynamic changes of CD4+, CD8+ T cell and CD4+/CD8+ in peripheral blood were detected by flow cytometry at 1,2, 3 and 4 weeks after operation. In the meantime, the immunity response of rabbits was evaluated by lymphocyte transformation test. The repaired segments stained with hematoxylin-eosin (HE) and Van Giesen were studied by histologic and pathologic observations at 10 days, 3, 6 and 24 weeks postoperatively. The urodynamics, urethroscopy and urethrography were performed at 24 weeks postoperatively. Results There was no significant difference in aspects of stimulative index of lymphocyte transformation, T lymphocyte subsets CD4+, CD8+ T cell and CD4+/CD8+ between experimental group and negative control group. Urothelium covered the whole surface of the matrix tube three weeks after operation. The smooth muscle cells increased nearly to normal urethral wall at 24 weeks. Urethrosoopy and urethrography showed glossy matrix tube. There was no statistical difference upon urodynamies between experimental group and control group. Conclusion The urethral extracellular matrix has good histocompatibility and may be a safe and effective material for repairing urethra defects.

BACKGROUND: Vessel extracellular matrix (VECM) is a natural scaffold material obtained from vascular tissues, which can stimulate angiogenesis and accelerate vascularization of tissue-engineered graft, however, the mechanism is poorly understood.OBJECTIVE: To explore the vascularization effects of release of vascular endothelial growth factor (VEGF) from VECM in ureteral reconstitution.DESIGN, TIME AND SETTING: An in vitro cytology observation. The experiment was performed at the Biomedical Engineering Laboratory of First Clinical Medical Science College, Wuhan University, between April and August in 2009.MATERIALS: Abdominal aorta was obtained from 5 rabbits to prepare VECM.METHODS: The VEGF released from VECM in vitro was evaluated by ELISA, the effects of cell proliferation by the released VEGF was detected by MTT colorimetric assay. The defected ureters of rabbits were repaired by homologous VECM in vivo.Then the recovery of the defected ureters and the situation of vasculogenesis were detected at different time point.MAIN OUTCOME MEASURES: The detection of VEGF contents in VECM; and the effects of VECM on vascular endothelial cell proliferation and ureteral reconstitution.RESULTS: In vitro experiment presented that the peak amplitude concentration of VEGF released from VECM in PBS solution was (124.10±1.42) ng/L, which showed proliferative effect on vascular endothelial cells. In vivo, there were some blood vessels on the VECM at 2 weeks after implantation. Epithelial coverage was evident in the lumen of the marginal part of the VECM grafts and the smooth muscle extended from the transition zone. After 8 weeks, the quantity of the blood vessel was increased and the caliber of the blood vessels became wide. There was thickness epithelial lamina in the graft, and the muscle fibers had an organized spatial alignment, forming variably sized bundles. After 16 weeks, there were no significant differences between the regenerative tissue and the normal tissue in morphology.CONCLUSION: The homologous VECM can release VEGF when implanted as tissue engineer biomaterial and might be an ideal replacement biomaterial for ureteral reconstitution.

OBJECTIVETo analyze the long-term effect of primary combined tissue transplantation on hand reconstruction.

METHODSThe data of 8 kinds of combined tissue transplantations employed to reconstruct the severely injured hands of 26 patients over the past 2 to 11 years were studied retrospectively. Among them, combined tissue transplantation taking the anterior-lateral femoral flap as the main tissue unit was applied in 21 cases and taking the second toe as the main tissue unit was applied in 5 cases. Blood vessel anastomosis was performed in parallel in 16 cases, series in 6 cases and both in 4 cases.

RESULTSAmong the 60 free tissue units employed on 26 patients, 58 survived completely and the other 2 survived after dressing change because of postoperative partial necrosis. The patients were followed up for 2-11 years postoperatively, with an average of 3.5 years. According to the standard for function of reconstructed hands by Chinese Medical Association, excellent results were obtained in 10 cases, good in 12 cases, fair in 3 cases and bad in 1 case.

CONCLUSIONSPrimary combined tissue transplantation, which may preserve the tissue vitality of injured hands to the maximum and thus facilitate function restoration of the hands, is a promising method in reconstructing severely-injured hands.

Adolescent ; Adult ; Child ; Female ; Hand Injuries ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; Surgical Flaps ; Treatment Outcome