C-C motif chemokine ligand 2 (CCL2) and its receptor CCR2 are closely related to tumorigenesis and tumor progression. The CCL2/CCR2 signaling axis promotes tumor progression through multiple mechanisms: CCL2 binds to CCR2 on the surface of tumor cells, and thus promotes tumor growth/survival and metastasis; more importantly, CCL2 recruits a variety of immunosuppressive cells to aggregate in the tumor microenvironment, and inhibits the function and activity of immune cells, promoting tumor progression. The article reviews the CCL2/CCR2 signaling axis and its role in tumors and tumor microenvironment, with particular focus on the advances in clinical research on drugs targeting CCL2/CCR2 signaling axis, in order to gain an in-depth and overall understanding of the mechanism of action of CCL2/CCR2 axis in tumor progression and develop more effective anti-tumor immunotherapeutic agents.

Objective:To investigate the repair effects and mechanism of mesenchymal stem cell osteogenesis-derived exosomes deliver miRNA-222-5p on tendon cell injury.Methods:Mesenchymal stem cell exosomes were collected, isolated and characterized. The mice achilles tendon was collected after cutting one week later. The tendon cells were isolated and cultured to obtain a tendon cell injury model (injury group). The subjects were divided into three groups. During the process of osteogenic differentiation, mesenchymal stem cells were co-cultured with tendon cells (co-culture group). Further, miRNA-222-5p mimics were transfected into mesenchymal stem cells, the co-cultured mesenchymal stem cells and tendon cells during the process of osteogenic differentiation (miRNA-222-5p group). Clone formation and Transwell were used to detect the ability of mesenchymal stem cells to secrete exosomes and exosomes transported miRNA-222-5p to repair damaged tendon cells. qPCR, Western-blot and fluorescence staining were used to detect the expression levels of cartilage-related proteins and bone-related proteins on mRNA and protein. Western-blot was used to detect the expression of signal pathway factors.Results:The shape of the exosomes was a typical cup - like structure. The exosome proteins marker was all expressed positively ( P<0.05). After counting the colony formation and Transwell test, the number of cell communities and cell invasion were significantly increased in the co-culture group compared with those in the injury group. The number of those in miRNA-222-5p group were significantly increased compared with those in co-culture group ( P<0.05). The qPCR, Western-blot and fluorescent staining test results showed that the mRNA and protein expression levels of SOX-9, COL2A1, ACAN, BMP2, Runx2, and OPN in the co-culture group were significantly increased compared with the injury group. The mRNA and protein expression levels of the above proteins in the miRNA-222-5p group were significantly increased compared with those in co-culture group ( P<0.05). We also detected the protein expression levels of signal pathway related factors. Western-blot results showed that the expression levels of NF-κB, Erk2, STAT3, STAT5 and Smad2 in the co-culture group were significantly increased compared with those in the injury group. The expression levels of the above factors in the miRNA-222-5p group were significant increased compared with the co-culture group ( P<0.05). Conclusion:The co-culture of mesenchymal stem cells and achilles tendon cells could promote the osteogenic differentiation of achilles tendon cells. Exosomes derived from mesenchymal stem cells could further promote the osteogenic differentiation of achilles tendon cells by transporting miRNA-222-5p. The mechanism may be related to the up-regulation of signal pathway factors in injured tendons, including NF-κB, Erk2, STAT3, STAT5 and Smad2.

Objective To study on the CDKN2/P16 gene in primary osteosarcoma.Method By using molecular biological methods that inclued genome DNA extraction from paraffined tissue and PCR SSCP analysis technique, we studied alternations of CDKN2/P16 gene in 25 primary osteosarcomas.Results (1)The deletions frequency in differentiation degree of osteosarcomas was① bone brood cell, 16.7% ;② cartilage brood cell,12.5% ;③ Fiber brood cell:20% ,(P >0.05).(2)The deletion frequency in male patients was 17.6% , female patients 12.5% ,(P >0.05).(3)In early metastatic osteosarcomas the deletion rate was 33.3% ,which was significantly higher than that of the control group with the rate of 10.5% (P< 0.05).(4)The deletion rate was 16% and the mutations were not found.Conclusion (1)The deletion rate was 16% and the mutations were not found.This suggests that the deletions of CDKN2/P16 gene were closely related to the genesis of primary osteosarcoma and that the main type of the alternation of CDKN2/P16 gene was deletion.(2)In early metastatic osteosaarcomas the deletion rate was 33.3% , which was significantly higher than that of the control group with the rate of 10.5% .This indicates to great extend that the deletions of CDKN2/P16 gene were closely related to the metastatic ability.(3)The deletions frequency had no significant relationship with differentiation degree of osteosarcomas, so was with the sex of the patient.

This study reported the analysis of plasma phospholipid metabolism of the rats and the pathological biomarkers between the type 2 diabetes model control group (MC) and the normal control group (NC). SD rats were randomly divided into 2 groups: NC and MC. To investigate state of plasma metabolite profiling in normal body, type 2 diabetes mellitus (T2DM) model group using UPLC-Q-TOF/MS which was used as analysis tool in this research. The compounds were identified by UPLC-Q-TOF/MS based on MS/MS fragment ions information, element composition in MassLynx 4.1 and the Lipid Maps database. The sign of two groups of samples in specific markers for screening was through a software package in R software (BioMark software). The results show that the pathological markers were mainly phosphatidylcholine (PC) and triglycerides (TG); the 2-acyl PC in the MC group was less more obviously than that in the NC group; high carbon number and high degree of unsaturation of the TG was reduced under the condition of type 2 diabetes. In the state of type 2 diabetes, metabolic changes occurred in rat plasma phospholipids obviously, which had a close relationship with the occurrence and development of T2DM.

Objective To explore the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) approach in treating patients with cancer- related fatigue during periods of chemotherapy in non-small cell lung cancer (NSCLC) patients in China. Methods A total of 162 participants who treated with GP chemotherapy were randomly assigned to three groups: 66 cases in control group, 61 cases in TEAS group, 67 cases in Sham TEAS group. The following acupoints were used in this study: Qihai (CV 6), Keshu (UB 17), and Zusanli (ST 36). Participants in TEAS group and Sham TEAS group received eight 30-min sessions of TEAS over 28 days. The Revised Piper Fatigue Scale (RPFS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) were used to measure cancer related fatigue (CRF) on the day before chemotherapy days 8 and 28 separately. The differences among three groups were analyzed. Results Finally, 167 patients were included in this study, 56 cases in control group, 57 cases in TEAS group, 49 cases in Sham TEAS group. At the 28th day, the outcomes of the RPFS for TEAS group, Sham TEAS group and control groupscored 2.06 ± 0.90, 2.80 ± 1.34, 3.00 ± 1.29 respectively. There were significantly different among three groups (F=9.784,P<0.01). At the 28th day, the outcomes of the EORTC-QLQ-C30 for TEAS group, Sham TEAS group and control groupscored 64.56 ± 5.00, 54.90 ± 6.25, 54.48 ± 9.68 respectively. There were significantly different among three groups (F=34.119, P<0.01). Conclusions TEAS could help to relived cancer-related fatigue.

Objective To investigate the feasibility of reducing bolus?tracking monitor frequency in coronary CT angiography (CTA). Methods This prospective study including 120 patients with suspected coronary artery disease (CAD). According to the examination registration order, the patients were divided into groups A, B and C (n=40 for each group). All patients underwent coronary CTA with bolus?tracking technology, and were monitored at 10 s after the injection of contrast. The monitoring frequency of bolus?tracking for Group A was every 1.14 s, that for Group B was every 1.47 s , and for Group C was every 2.00 s, while the trigger threshold was set as 100 HU. To evaluate the image quality, the objective evaluation included signal noise ratio (SNR) and contrast noise ratio (CNR) of aorta (AO), CNR of left main coronary artery (LM) and right coronary artery (RCA), and the subjective score was recorded for each coronary artery segment. The monitoring times when CT density of the region of interest (ROI) reached the threshold, the CT value and the effective dose (ED) in the 3 groups were recorded. Objective image quality, monitoring parameters and radiation dose were compared using analysis of variance method, subjective image quality was compared withχ2 tests. Results There was no significant difference in AO (SNR and CNR), LM (CNR) and RCA (CNR) among the 3 groups, respectively (P>0.05). Subjective image quality scores of groups A, B, C were (1.879±0.042), (1.876±0.042), (1.881±0.042 ), with no significant difference (χ2=0.003,P>0.05). The monitoring times of to reach the threshold in groups A, B, C were (4.78±2.37), (3.76±1.39), (2.77±0.99), and ED were (0.058±0.031),(0.031±0.011), (0.021±0.007) mSv, with the significant difference (F=9.009, 31.998, respectively, P<0.01). Peak CT values during monitoring among three groups were (133 ± 24), (142 ± 39), (137±26) HU, respectively, with no significant difference (F=0.575,P=0.565). Conclusions It is feasible to reduce monitoring times when performing coronary CTA in dual?source CT scanner. The bolus?tracking monitor frequency in every 2 seconds can not only obtain satisfactory image quality, but also significantly reduce radiation dose.

Objective:To investigate the expression of miR-92a in colorectal cancer (CRC) and its effect on the regulation mechanisms of tumor angiogenesis. Methods:The miRNA-92a expression in 25 CRC tissues and HT29, SW620, SW480, and HCT116 CRC cells was detected using quantitative real-time polymerase chain reaction. The CD31 positive expression of blood microvessels in CRC tissues was measured by immunohistochemistry. Pearson correlation analysis was used to analyze the relationship between miR-92a and tu-mor angiogenesis. The miR-92a mimic or inhibitor was transfected into HCT116 and SW620 cells in vitro to upregulate or downregu-late the miR-92a expression. The effect of miR-92a overexpression or suppression on the formation of human umbilical vein endotheli-al cell (HUVEC) tubules was detected by tube formation assay. Changes in phosphatase and tensin homolog (PTEN) protein expression were measured by Western blot. Results:The expression level of miR-92a in CRC tissues was significantly higher than that in matched adjacent tissues (P<0.01). The expression levels of miR-92a in HT29, SW480, SW620, and HCT116 colon cancer cell lines were signifi-cantly higher than that of the normal colorectal epithelium control (P<0.05). The number of CD31 positive expression of microvessel density (MVD) in CRC tissues was significantly higher than that in adjacent tissues (P<0.01), and the miR-92a expression level was posi-tively correlated with the MVD in CRC tissues (r=0.580, P=0.01). The cell culture supernatant of HCT116 with miR-92a overexpression could significantly promote the formation of HUVEC tubules (P<0.05). The upregulation of miR-92a expression could significantly inhib-it the expression of PTEN protein in CRC cells (P<0.01). Conclusion:The miR-92a was highly expressed in CRC cells and tissues, which was closely related to the formation of tumor angiogenesis in CRC. The miR-92a could promote tumor angiogenesis in CRC by inhibit-ing PTEN expression.

An alternative method based on an off-line solid phase extraction ( SPE ) combined with programmable temperature vaporizer-based ( PTV) large volume injection-gas chromatography-flame ionization detection ( LVI-GC-FID ) was developed. The goal of this study was to determine mineral oil saturated hydrocarbons ( MOSH ) in camellia seed oils. The purification condition of SPE columns with silver impregnated the activated silica gel and activated aluminum oxide was optimized. The optimal SPE cartridge was loaded with 10 g of Ag-activated silica gel per 10 g of activated aluminum oxide. The PTV initial temperature was set at 75℃ for 1 min (split 200:1), and heated from 75℃ to 370℃ at 250℃/min. Then the diverter valve was closed for 1 min and opened again with the split flow ratio changing to 50:1 . The injection volume was 40μL. The calibration curve of paraffin oil was liner in the range of 5-500 mg/kg with correlation coefficient of 0. 998. The detection limit (LOD) and the quantification limit (LOQ) of paraffin oils in hexane were 0. 26 mg/kg and 0. 80 mg/kg, respectively. The recoveries from spiked oil samples were between 93 . 3% and 112 . 7%, with relative standard deviation ( RSD ) of 1 . 8%-5 . 2%, the RSD of intra-day and inter-day were less than 2 . 6% . This procedure was applied to analyze the MOSH in 11 commercial camellia seed oils and the contamination was found to range from 6. 8 mg/kg to 76. 7 mg/kg. The method is simple in operation with high sensitivity, good reproducibility and low cost, and suitable for determination of MOSH in vegetable oils.

This study aims to develop a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ivabradine and N-demethylivabradine in human plasma, and investigate effects of stable isotope labeled (SIL) internal standard (IS) on ivabradine. The analytes and IS were extracted from plasma by protein precipitation with acetonitrile, and chromatographied on a Capcell PAK C18 (100 mm x 4.6 mm, 5 μm) column using a mobile phase of methanol and 5 mmol x L(-1) ammonium acetate. Multiple reaction monitoring with electrospray ionization (ESI) was used in the positive mode for mass spectrometric detection. The effect of ivabradine isotope peak [M+H+3] + on IS and the effect of SIL IS purity on ivabradine were evaluated. An appropriate concentration of SIL IS was chosen to permit method selectivity and linearity of the assay over the required range. The standard curves were demonstrated to be linear in the range of 0.100 to 60.0 ng x mL(-1) for ivabradine, and 0.050 0 to 20.0 ng x mL(-1) for N-demethylivabradine. The intra and inter day precision and accuracy were within the acceptable limits for all concentrations. Besides, the interaction between IS and ivabradine did not impact the determination of analytes. This method was successfully applied to a pharmacokinetic study of hydrogen sulfate ivabradine sustained release tablets on Chinese healthy volunteers.

Objective To investigate the stress reaction of the medical staff who suffered workplace violence,and provide reference for nursing interventions.Methods 13 medical staff who suffered work-place violence were interviewed through semi-constitutional formula,the data were analyzed by phenomenological method of qualitative research.Results The psychological stress of medical staff mainly included 3 themes:complex emotions,eager to help; psychological adjustment required internal and external integration; different stress reaction affected the psychological state.Conclusions The medical staff suffer seriously from the workplace violence both on the physical and mental health,individuals should learn how to deal with it correctly,and the relevant departments should pay full attention to the humane care to victims of violence,guide them to view the stress correctly,and to take effective measures to prevent and control workplace violence.