MicroRNAs (miRNAs) are a small noncoding family of 22 ut RNAs that play an important role in the negative regulation of gene expression at the post-transcriptional level by base pairing to the 3'untranslated region of target messenger RNAs.miRNAs are involved in a variety of basic processes,such as cell proliferation and apoptosis,metabolism and signaling pathways.A lot of studies have indeed described the aberrant expression of miRNAs in human tumors and have investigated their potential role as oncogenes or tumor suppressor genes,depending on the targets they regulate.Furthermore,more and more studies have demonstrated that an important role of miRNAs in anticancer drug resistance and miRNA expression profiling can correlate with the development of anticancer drug resistance.A systematic and intensive study on the mechanisms of miRNA in anticancer drug resistance will provide us a strong rationale for the development of miRNA-based therapeutic strategies aiming to overcome cancer cell resistance.This paper has reviewed the recent development of miRNAs involved in anticancer drug resistance.

Objective To investigate the effects of microRNA-294 (miR-294) on tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6) and high mobility group box 1 (HMGB 1) secretion in sepsis by targeting triggering receptor expressed on myeloid cell-1 (TREM-1).Methods miRNA-294 was predicted to regulate TREM-1 specially through bioinformatics analysis.Mice macrophage cell lines RAW264.7 were cultured in vitro,the cells were divided into non-inflammatory stage and inflammatory stage,and the cells in the two stages were subdivided into five groups as follows:normal control (NC),NC mimic transfection (NCm),NC inhibitor transfection (NCi),miR-294 mimic transfection (miR-294m) and miR-294 inhibitor transfection (miR-294i) groups.The ability of miR-294 was confirmed with dual-luciferase activity assay.At non-inflammatory stage,the cells were transfected with mimic or inhibitor of miR-294 or NC using TurboFectTM siRNA Transfection Reagent for 48 hours,mRNA expression of TREM-1 was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR).At inflammatory stage,6 hours after stimulation by lipopolysaccharide (LPS,1 mg/L),the concentrations of TNF-α,IL-6 and HMGB1 were determined by enzyme linked immunosorbent assay (ELISA),the protein expression of TREM-1 was determined by Western Blot.Results ① Dual-luciferase activity assay demonstrated that TREM-1 was the target of miR-294.② In non-inflammatory stage,the expression of TREM-1 mRNA (2-ΔΔ~) in miR-294m group was significantly lower than that of the NC and NCm groups (0.673 ± 0.049 vs.1.000 ± 0.003,0.915 ± 0.039,t1=2.184,t2=5.421,both P＜0.001),the expression of TREM-1 protein (gray scale) was (50.00 ± 1.19)％ of NCm group (t=41.586,P＜0.001).③ In inflammatory stage,the concentrations of TNF-α (ng/L) in miR-294m group was significantly lower than that of the NC group (1 547.18 ±47.18 vs.2 702.11 ± 327.20,t=4.212,P=0.010),the concentrations of IL-6 (ng/L) was significantly lower than that of the NC and NCm groups (505.28 ± 33.33 vs.837.66 ± 69.43,918.72 ± 119.39,t1 =4.382,P1=0.015; t2=5.451,P2=0.021),the level of TREM-1 protein (gray scale) was (51.33 ±0.88)％ of NCm group (t=63.368,P＜0.001).Conclusion miR-294 reduce TNF-α and IL-6 secretion in LPS-induced RAW264.7 through inhibiting the expression of TREM-1 specifically.

Objective To analyze the differences in microRNA (miRNA) expression between A549 and A549/DDP cells and explore the association between miRNA expression and drug resistance in non-small cell lung cancer (NSCLC).Methods The drug resistance of A549/DDP cells was evaluated using CCK-8 assay and flow cytometry.Microarray technique and RT-PCR were used to analyze the differential expression of the miRNA between A549 and A549/DDP cells.Enforced or inhibited target miRNA expression in cisplatin resistant cell was used to investigate whether miRNA involve in modulating the sensitivity of NSCLC cells to chemotherapeutic agent,exploiting the emerging knowledge of miRNA for the development of new human therapeutic applications for overcoming anticancer drug resistance and trying to discover biomarkers that were better able to predict the cancer chemotherapy sensitivity.Results The drug resistance index of A549/DDP cells relative to the parental A549 cells was 18.Microarray analysis of A549 and A549/DDP cells identified 51 differentially expressed genes (≥4-fold),including 24 up-regulated and 27 down-regulated genes in A549/DDP cells.RT-PCR identified 9 miRNA that were differentially expressed between A549 and A549/DDP cells.Of these differentially expressed miRNA,miR-376c,miR-31,miR-29a,miR-221 showed significantly increased expression,and miR-196a,miR-20a,miR-20b,miR-17,miR-451 showed significantlylowered expression in A549/DDP cells as indicated by the results of microarray analysis and RT-PCR.DDP sensitivity was increased 11.7 ％ in A549/DDP cells transfected with miR-17,but the chemosensitivity was decreased when miR-451 was over-expressed or miR-29a was inhibited by selective inhibitor,the reduction was 15.5 ％,12.9 ％,respectively,whereas chemosensitivity did not change when miR-376c,miR-31,miR-221 were inhibited or miR-196a,miR-20b,miR-20a were over-expressed.Conclusion A549/DDP cells show a different miRNA expression profile from its parental A549 cells,suggesting the involvement of miRNA in tumor cell drug resistance.miR-17 has the potential to be an efficient agent for preventing and reversing DDP-resistance in NSCLC.These results provide a strong rationale for the development of miRNA-based therapeutic strategies aiming to overcome cancer cell resistance.

Objectives To explore the effect of transient continuous subcutaneous insulin infusion (CSII) on β cell function, insulin resistance and vascular endothelial injury in newly diagnosed type 2 diabetic patients and its potential mechanism. Methods Ten patients with newly diagnosed type 2 diabetes mellitus (T2DM) accepted CSII for two weeks. Intravenous glucose tolerance test (IVGTT) and hyperinsulinemia euglycemia clamp test were performed before and after CSII. Serum soluble E-selectin (sE-selectin) was used to evaluate the injury of vascular endothelial cell, while serum high sensitivity C reactive protein (hsCRP) and soluble CD_(14) (sCD_(14)) were both used to assess inflammatory condition. Results (1) Compared with those before treatment, the blood glucose levels of IVGTT, the area under the curve of the blood glucose, glycosylated hemoglobin, TC and LDL-C in the patients were decreased after CSII (P < 0. 05 or 0. 01). (2) Compared with those before treatment, the insulin levels of IVGTT (except the fasting insulin), the area under the curve of insulin and acute insulin response were all increased after CSII(P < 0.05 or 0.01). (3) Compared with that before treatment, the glucose infusion ratio in the clamp test [(3.46±1.66)mg·kg~(-1)·min~(-1) increased to (7.14±2.37)mg·kg~(-1)·min~(-1)]and HOMA-β elevated, while HOMA-IR declined (P <0. 05 or 0. 01 in all). (4) Compared with those before treatment, the levels of serum sE-selectin, sCD_(14) and hsCRP were decreased (P < 0. 01, except for hsCRP) . Conclusion Transient intensive insulin therapy in patients with newly diagnosed T2DM is useful to restore 13 cell function, attenuate insulin resistance, repair vascular endothelial injury and improve the disorder of blood sugar and lipid. The mechanism may be related with the inhibition of inflammation in patients.

BACKGROUND: Pneumonectomy and sleeve resection are routine operations for the treatment of central non-small cell lung cancer (NSCLC), but some patients suffered of central NSCLC, whose pulmonary function is too poor to tolerate pneumonectomy, or the tumor involves the bronchus and pulmonary artery extensively,it is hard to perform bronchovascular sleeve lobectomy. The aim of this study is to assess the feasibility of lung autotransplantation in the treatment of central NSCLC. METHODS: The clinical data of 3 cases with central NSCLC treated by lung autotransplantation was reviewed from December 2016 to December 2018. One patient underwent double sleeve resection of left upper lobe with end-to-end anastomosis of the bronchus. Because the resection of the pulmonary artery was too long to perfrom a tension-free anastomosis, the inferior pulmonary vein was cut off, then the left lower lobe was moved up for an anastomosis of the inferior pulmonary vein and the stump of the superior pulmonary vein. In the other 2 cases, left pneumonectomy was performed directly, and the upper left lobe was excised in vitro. The lower left lobe was reset to the chest after trimming and flushing and then the bronchus, pulmonary artery and pulmonary vein were anastomosed in turn. RESULTS: The average operation time was 333 min, the average time of vascular occlusion was 86 min, the average blood loss was 450 mL, and the average hospital stay was 18.7 d; Perioperative complications included a case of bronchial obstruction, which improved after sputum aspiration through bronchofibroscope. The average follow-up period was 20 mon; One case died of cancer, one case had recurrence of anastomotic stoma and brain metastasis, one case had 4R lymph node metastasis (stable condition after chemotherapy), and one case survived without recurrence. CONCLUSIONS For patients with central NSCLC with extensive tumor invasion, thus inability to tolerate sleeve resection or pneumonectomy, autologous lung transplantation can preserve lung function to the greatest extent with a complete tumor resection and improve postoperative quality of life.

Objective    To explore the practical feasibility of the weaving technique for pectus carinatum. Methods    From January 2011 to December 2018, a total of 51 patients with pectus carinatum, including 47 males and 4 females at age of 9-29 (13.7±2.9) years, were applied with minimally invasive waving technique for the correction. The steel plate was inserted through the subcutaneous layer, intercostal space and over the sternal surface under direct thoracoscopic vision. The number of implanted steel plates was determined by the degree of chest wall deformity. The steel plate was removed 2 years after surgery. Results    All the operations were successfully completed, the average operation time was 63.9±15.8 min, the amount of bleeding was 19.8±8.8 mL, and the duration of postoperative hospitalization was 4.6±1.6 d. The adverse events included intercostal artery injury (n=2), pneumothorax (n=4), pleural effusion (n=3) and skin rupture (n=1). And there were 29 patients of moderate pain (numerical rating scale 4-6 points) on the first day after surgery, but no patient was asked to remove the steel palate due to intolerable discomfort. All patients were followed up after plate placement. Of the 51 patients, the plates were removed in 37 patients until 2 years after placement, and the duration of postoperative hospitalization was 1.4±0.5 d. After 33 (1-48) months of routine follow-up after the removal of the plate, 22 patients achieved excellent outcomes and 9 patients with good outcomes. Besides, there were 5 patients with fair outcome and 1 patient with poor outcome. No adverse effect was found in growth and development after the steel plate placement. Conclusion    Minimally invasive weaving technique is a safe, feasible, effective and individualized operation for pectus carinatum with substantial thoracic reconstruction.