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BACKGROUND: Hepatocellular carcinoma (HCC) has become the sixth most common cancer and the third leading cause of cancer death in the world. Although the research achievements of tumor immunotherapy have made great progress, especially the combination of immune targeted therapy has achieved good curative effect in HCC, but only a few patients are suitable for it and benefit from it. Therefore, there is an urgent need to find new effective drugs to treat HCC or to enhance the sensitivity of immunotherapy. METHODS: Meloxicam, a COX2 inhibitor with strong anti-HCC potential, was screened from 800 small molecules approved by FDA. The effect of meloxicam on the proliferation, invasion, and migration of HCC cell lines was evaluated by cell phenotype analysis. The Human Protein Atlas database and the TISCH database were used to analyze COX2 data in single cells, and the TISIDB database was used to analyze the correlation of COX2 with immune function. The real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to evaluate the level of PD-L1 and CD155 in HCC cell lines treated with meloxicam and further explore its possible mechanism. In vivo experiments were applied to verify the effect of meloxicam combined with anti-PD1 therapy on HCC tumor growth in mice. RESULTS: Meloxicam can significantly inhibit the proliferation, invasion, and migration of HCC cells. The TISIDB database indicated that the COX2 was strongly associated with immunoinhibitors and immunostimulators. Meloxicam upregulated the level of PD-L1 in HCC cell lines and animal models. In terms of mechanism, meloxicam inhibited microRNA-200, thereby upregulating PD-L1. In vitro experiments showed that both meloxicam and anti-PD1 had inhibitory effects on the growth of HCC tumors. Compared with meloxicam and anti-PD1 alone, the combination therapy showed stronger antitumor properties. Immunohistochemical analysis confirmed that meloxicam enhanced the antitumor immune activity in the tumor microenvironment. CONCLUSION: Our study showed meloxicam inhibited HCC progression and enhanced the sensitivity of immunotherapy via the microRNA-200/PD-L1 pathway.
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Objective To optimize the transfecfion parameters for transfecting small interfering RNA (siR-NA) to endothelium of mouse angioma (EOMA) cells mediated by lentiviral vector. Methods According to Poly-brene existing or not(8 μg/ml), series of multiplicity of infection (MOI) (1, 5, 10, 15, 20)and the time of infec-tion(4, 6, 12,24 h), EOMA cells were divided into 40 groups. 140 hours after transfection, cells were counted un-der fluorescent microscope to determine the percentage of the cells transfected under each condition. The cell viability was calculated by using Typan Blue. Results The percentage of positive cells was as high as 83% in the group with Polybrene (8 μg/ml), MOI(5) and the time of tranfectian (6 h), and the livability of EOMA in this group was 96%. After that, the transfection efficiency was not increased with the increasing of MOI, the time of transfection, but the mortality of EOMA was increased markedly. Conclusion The transfection efficiency and cell viability are dependent on the Polybrene(8 μg/ml),correct MOI (5)and the time of transfection (6 h).
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[Objective]To discuss the results of the GIEBEL system in high tibial osteotomy to treat varus knee.[Method]Nineteen patients with medium varus knee were selected to be treated with osteotomy.Preoperatively,the mean varus angle was 12.29?,without deformity in other department of the knee joint.The main symptom was the pain in medial department.Accurate high tibial osteotomy with GIEBEL system fixation was performed in 31 knees of these patients.Weight-bearing extremity X-ray testing,varus angle,mechanical axle and anatomical axle were marked preoperatively and postoperatively.Joint space discrepancy between lateral and medial joint,the range of motion,Lysholm assessment and objective satisfactory survey were also performed to determine the outcome of the treatment.[Result]The mean follow-up of nineteen patients was 22 months.During this period,one case of temporary common fibular nerve paralysis occurred and healed at several days.All of the osteomy interface achieved bony healing.The corrected abnormality was 12.32?.The mechanism axle of the extremity maintained as the level just after operation during the follow-up and no degeneration of the joint space aggravated.The excellent and good rate of the treatment was 89.5%,and 84.2% of the patients expressed satisfactory for the operation.No difference of the range of motion was found before and after operation,but the Lysholm score,joint space discrepancy between lateral and medial joint and varus angle were improved after the osteotomy.[Conclusion]The GIEBEL system can fixate the bony interface of the high tibial osteotomy effectively,and possess the advantages of minimal invasion,stronger intensity and higher healing rate.
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[Objective]To estimate the results of the total knee replacement for osteoarthritis knee joint.[Method]Eighty-one patients(95 knees)with osteoarthritis of knee joint were selected for total knee replacement.The average age of the patients was 65.5 years with a range of 50~82 years,which involved 10 males and 71 females.Left knee was in 35 cases and right knee was in 26 cases.Bilateral knee replacement one time was 17 cases.The posterior crnciate ligament retaining prosthesis was 18 knees,posterior stabilizing prosthesis was 62 knees and mobile bearing prosthesis was 15 knees.[Result]All the patients were available at the follow-up,with a mean of 42 months(14~108 months).According to HSS system,80 knees(84.21%)had an excellent results;10 knees(10.53%),a good result;3 knees(2.86%),a fair result;and 2 knees(1.9%),poor result.The satisfactory rate was 95.23%.[Conclusion]Total knee replacement can decrease knee pain and improve knee function.The prosthesis choice,surgical technique and postoperative rehabilitation are key factors to the operation results.
