Many clinicians are very busy for clinical works to have no time taking into account scientific research, so that they are daunting the application of scientific research funds. However, when clinicians in the actual work can keep their strong curiosity for the unknown, not cling to the so-called classical point of view, develop a good habit of critical thinking, have the courage to question the unresolved clinical problems, as well as read the latest literature of their specialty regularly, they may find the breakthrough point of scientific research to carry out scientific research within our ability. The results obtained in the process of scientific research aim to provide new methods and new technologies to solve clinical problems. Therefore, we could get a better way to serve the patients through the integration of clinical practice and scientific research to improve the development of clinical medicine. This article will focus on the aspects of selecting scientific research topic, and raising, establishment and solution of scientific problems etc, so as to helping clinicians to successfully get the support of the scientific funds.

Objective: To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy. Materials and Methods: Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis. Results: The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028). Conclusion For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.

Objective: To analyze the correlations between intraoperative ultrasound and MRI metrics of the spinal cord in degenerative cervical myelopathy and identify novel potential predictive ultrasonic indicators of neurological recovery for degenerative cervical myelopathy. Materials and Methods: Twenty-two patients who underwent French-door laminoplasty for multilevel degenerative cervical myelopathy were followed up for 12 months. The Japanese Orthopedic Association (JOA) scores were assessed preoperatively and 12 months postoperatively. Maximum spinal cord compression and compression rates were measured and calculated using both intraoperative ultrasound imaging and preoperative T2-weight (T2W) MRI. Signal change rates of the spinal cord on preoperative T2W MRI and gray value ratios of dorsal and ventral spinal cord hyperechogenicity on intraoperative ultrasound imaging were measured and calculated. Correlations between intraoperative ultrasound metrics, MRI metrics, and the recovery rate JOA scores were analyzed using Spearman correlation analysis. Results: The postoperative JOA scores improved significantly, with a mean recovery rate of 65.0 ± 20.3% (p < 0.001). No significant correlations were found between the operative ultrasound metrics and MRI metrics. The gray value ratios of the spinal cord hyperechogenicity was negatively correlated with the recovery rate of JOA scores (ρ = -0.638, p = 0.001), while the ventral and dorsal gray value ratios of spinal cord hyperechogenicity were negatively correlated with the recovery rate of JOA-motor scores (ρ = -0.582, p = 0.004) and JOA-sensory scores (ρ = -0.452, p = 0.035), respectively. The dorsal gray value ratio was significantly higher than the ventral gray value ratio (p < 0.001), while the recovery rate of JOA-motor scores was better than that of JOA-sensory scores at 12 months post-surgery (p = 0.028). Conclusion For degenerative cervical myelopathy, the correlations between intraoperative ultrasound and preoperative T2W MRI metrics were not significant. Gray value ratios of the spinal cord hyperechogenicity and dorsal and ventral spinal cord hyperechogenicity were significantly correlated with neurological recovery at 12 months postoperatively.

Objective In order to understand the chondrogenesis differentiation of mesenchymal stem cells in either hydrogel or pellet culture,we applied the two methods and reveal the possible mechanism and for further investigation.Methods In C3H10T1/2 chondrogenic differentiation,we apply extracellular matrix hydrogel mixed the cell suspensions of freshly prepared (including scaling chondroitin sulfate,sodium hyaluronate synthesis and cross-linking agent) co-culture system and high cell density pellet formed by centrifugation.Chondrogenic differentiation of C3H10T1/2 was induced by treatment with TGF-β3 (10 ng/ml),dexamethasone (100 nmol/L),ascorbic acid (50 ug/ml),1 ∶ 100 dilution ITS+Premix and high glucose-DMEM medium with 0.2 volume fraction fetal bovine serum.And high glucose-DMEM medium with 0.2 volume fraction fetal bovine serum is for control group.Histochemistry staining was utilized to identify extracellular proteoglycan and real-time PCR was performed to assess gene expression of SOX9,collagen Ⅱa1/Ⅹa1 and aggrecan for the 1st,2nd and 3rd week respectively.Results In the hydrogel model for 3 weeks chondrogenic differentiation,the expression of master transcription factor SOX9 was upregulated in both culture models.While the marker genes of collagen Ⅱa1 and collagen Ⅹa1 were all promoted in hydrogel culture,the aggrecan gene expression was peaked in pellet culture.In addition,immunocytochemistry analysis of the hydrogel and pellet for 3 week illustrated the expression of extracellular matrix and more obviously in the hydrogel model.Conclusion In compared with pellet culture,the MSCs in the hydrogel were more likely promoted chondrogenesis leading to the eventual expression of marker genes.And the hydrogel would be applied in regeneration of cartilage injury.

PURPOSE: Isocryptotanshinone (ICTS) is a natural bioactive product that is isolated from the roots of the widely used medical herb Salvia miltiorrhiza. However, few reports exist on the mechanisms underlying the therapeutic effects of ICTS. Here, we report that ICTS has anticancer activity and describe the mechanism underlying this effect. METHODS: The antiproliferative effect of ICTS was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and clonogenic assays. The effect of ICTS on the cell cycle was measured using flow cytometry. Apoptosis was determined by Hoechst 33342 staining, DNA fragmentation assays, and Western blotting for apoptotic proteins. Finally, the effect of ICTS on mitogen-activated protein kinases (MAPKs) was determined by Western blotting. RESULTS: ICTS significantly inhibited proliferation of MCF-7 and MDA-MB-231 human breast cancer cells, HepG2 human liver cancer cells, and A549 human lung cancer cells in vitro. Among the tested cell lines, MCF-7 cells showed the highest sensitivity to ICTS. ICTS significantly inhibited colony formation by MCF-7 cells. Furthermore, exposure of MCF-7 cells to ICTS induced cell cycle arrest at the G1 phase and decreased mitochondrial membrane potential. Hoechst 33342 staining and Western blot analysis for apoptotic proteins suggested that ICTS induced apoptosis in MCF-7 cells. In addition, ICTS activated MAPK signaling in MCF-7 cells by inducing time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK. CONCLUSION: Our results suggest that ICTS inhibited MCF-7 cell proliferation by inducing apoptosis and activating MAPK signaling pathways.
Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Cell Cycle ; Cell Cycle Checkpoints ; Cell Line ; DNA Fragmentation ; Flow Cytometry ; G1 Phase ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Lung Neoplasms ; MCF-7 Cells* ; Membrane Potential, Mitochondrial ; Mitogen-Activated Protein Kinases ; p38 Mitogen-Activated Protein Kinases ; Phosphorylation ; Salvia miltiorrhiza

Neocryptotanshinone (NCTS) is a natural product isolated from traditional Chinese herb Salvia miltiorrhiza Bunge. In this study, we investigated its anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated mouse macrophage (RAW264.7) cells. MTT results showed that NCTS partly reversed LPS-induced cytotoxicity. Real-time PCR results showed that NCTS suppressed LPS-induced mRNA expression of inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Moreover, NCTS could decrease LPS-induced nitric oxide (NO) production. Western blotting results showed that NCTS could down-regulate LPS-induced expression of inducible nitric oxide synthase (iNOS), p-IκBα, p-IKKβ and p-NF-κB p65 without affecting cyclooxygenase-2 (COX-2). In addition, NCTS inhibited LPS-induced p-NF-κB p65 nuclear translocation. In conclusion, these data demonstrated that NCTS showed anti-inflammatory effect by suppression of NF-κB and iNOS signaling pathways.

Objective To investigate the clinicopathologic features and prognostic significance of BRCA1 and Ki-67 expression in breast cancer.Methods The expression levels of BRCA1 and Ki-67 were assayed by immunohistochemistry in 194 cases of breast cancer tissues.The correlations of BRCA1 and Ki-67 expression with patients' clinicopathologic features were also analysed.Results Low expression of BRCA1 was detected in the lymph node metastasis group,ER/PR negative group,and HER-2 positive group in 194 patients with breast cancer (P ＜ 0.05),as well as in the triple negative breast cancer (TNBC) group compared to non-TNBC group (P ＜0.05).High expression of Ki-67 was detected in patients with higher histological grade,negative ER/PR,and positive HER-2 (P ＜ 0.05).Furthermore,negative correlation was found between the expression of BRCA1 and Ki-67 (P ＜ 0.05).The combination of low expression of BRCAl and high expression of Ki-67 was mostly found in the patients with postmenopausal,lower histological grade,lymph node metastasis,negative ER/PR and positive HER-2 (P ＜ 0.05).However,there was no significant difference between TNBC and non-TNBC.Conclusion Joint detection of BRCA1 and Ki-67 might play an important role in predicting clinical outcomes of breast cancer,especially BRCA1 may be one of prognostic factors in TNBC.

Objective:To evaluate the efficacy and safety of palonosetron in preventing chemotherapy-induced vomiting. Meth-ods:A multi-center, randomized, double-blind, and self-cross-over positively controlled clinical trial design was used. All patients were randomized into two groups, as follows:Regiment A (61 cases) and Regiment B (64 cases). Regimen A with palonosetron hydrochlo-ride injection (test agent) was used in the treatment cycle A, whereas granisetron hydrochloride injection (control drug) was used in the cycle B. Treatments were randomly administered on the patients of the two groups. Regimen B was on the contrary, the control drug was used in the cycle A, and the test agent was used in the treatment cycle B. All patients treated with the test agent were classified as the test group, whereas those treated with the control drug were classified as the control group. Complete control rate and adverse reac-tion of acute and delayed vomiting in the two groups during the two cycles of chemotherapy regimen were compared. Results: In Group One, the complete control rate of delayed vomiting was significantly higher in the palonosetron administration cycles than in the granisetron cycles (76.92%vs. 55.38%, P=0.0110). In the same group, the frequency of vomiting was significantly less in palonosetron cycles than in the granisetron cycles during day 1 to day 5 (1.32±3.42 vs. 1.94±3.03, P=0.0096). The incidences of adverse effects were low in both groups. No grades 3 and 4 adverse effects were observed. Conclusion: Palonosetron showed efficacy in preventing the acute and delayed chemotherapy-induced vomiting. The drug is superior to granisetron, specifically in delaying vomiting in Group One. Palonosetron hydrochloride showed slight adverse effects. Hence, this drug can be used in clinic.

Objective To investigate the effect of neutrophil elastase (NE) inhibitor on the blood-brain barrier(BBB) permeabili-ty and hydrocephalus in rats with traumatic brain injury (TBI) .Methods 99 SD rats were randomly divided into the control group , the TBI group and the intervention group(dividing into 5 sub-groups:6 ,24 ,48 ,72 ,168 h) .The hydraulic impact model of rats was duplicated .Sivelestat sodium was given in the intervention group .The NE concentration in the brain tissue ,BBB permeability and brain water content were detected in each group and performed the comparative analysis .Results The NE concentration in the brain tissue ,BBB permeability and brain water content at each timepoint in the TBI group and the intervention groups were higher than those in the control group .The NE concentration at 24 ,48 ,72 ,168 h in the intervention group was lower than that in the TBI group .The BBB permeability and the brain water content at 48 ,72 ,168 h in the intervention group were lower than those in the TBI group(P<0 .05) .Conclusion Sivelestat sodium can inhibit the NE release in TBI rat brain tissue ,reduce the BBB permeability and the occurrence of hydrocephalus ,which indicating that sivelestat sodium has the protective effect on TBI secondary lesion in rat .

Lung cancer is the leading cause of cancer-related mortality worldwide. Despiting the great progress on target agents, majority of people who do not harbor a mutation could not get beneift from them. Immunotherapy, through stimulating the body's immune system to improve the antitumor immunity effect, has been a new therapeutic method for non-small cell lung cancer (NSCLC). Study had been reported that immune checkpoint molecules, including programmed death-1 (PD-1)/PD-ligand (L) 1 axis, are closedly related with cancer generation and development, and play a key role on clinical signiifcance of NSCLC. Activation of PD-1/PD-L1 pathway contributes to tumor immune escape, and block PD-1/PD-L1 pathway can enhance endogenous antimuor immunity. Currently increasing clinical trials suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies turned out to be beneifcial and safe in NSCLC. Here, we provide a review on the progress of PD-1/PD-L1 pathway and immune checkpoint inhibitors in NSCLC.