ABSTRACT
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.
ABSTRACT
Objective:To explore the effects of donor, basic recipient characteristics and intraoperative findings before orthotopic liver transplantation(OLT)on postoperative pulmonary complications and the influence of postoperative pulmonary complications on postoperative outcomes and long-term survival of patients.Methods:From January 2016 to December 2019, clinical data were retrospectively reviewed for 313 OLT recipients at First Affiliated Hospital, Nanjing Medical University.According to clinical manifestations, laboratory parameters and imaging findings within 7 days post-operation, they were divided into two groups of with and without postoperative pulmonary complications.Univariate and multivariate Logistic regression analyses were performed for general parameters of donors/recipients and perioperative variables of recipients in two groups.And Kaplan-Meier survival analysis was conducted for postoperative survival of two groups.Results:Multiariate Logistic regression analysis indicated that age, concurrent chronic diseases, low preoperative platelet count, intraoperative massive bleeding(>1 500 ml)and severe hypotension after perfusion were all independent risk factors for postoperative pulmonary complications.Compared with those without postoperative pulmonary complications, intensive care unit(ICU)stay, postoperative mechanical ventilation duration and hospital stay were significantly prolonged in patients with postoperative pulmonary complications.And rate of re-intubation, incidence of acute kidney injury and hospital mortality spiked markedly( P<0.05). Among OLT patients with benign liver diseases, overall survival rate of patients without postoperative pulmonary complications was significantly better than that of those with postoperative pulmonary complications( P<0.05). Conclusions:Age, concurrent chronic diseases, low preoperative platelet count, massive intraoperative bleeding(>1 500 ml)and severe hypotension after perfusion boost the risks of early postoperative pulmonary complications and adversely affect the outcomes of OLT recipients.
ABSTRACT
Objective:To evaluate the effect of donor age factor on intraoperative and early postoperative complications in the patients undergoing orthotopic liver transplantation (OLT).Methods:The clinical data of patients underwent OLT from January 2016 to December 2019 were retrospectively collected.The patients were divided into elderly donor group (age ≥65 yr) and non-elderly donor group (age<65 yr) according to the donor age.The preoperative and intraoperative clinical data of the two groups were matched by 1∶2 propensity score matching.The primary outcome measures were intraoperative postreperfusion syndrome and acute kidney injury and postoperative pulmonary complications within 7 days after surgery.The secondary outcome measures were time of intensive care unit stay, assisted mechanical ventilation time, postoperative length of hospital stay, rate of reintubation, and 6-month and 1-year survival and recurrence-free survival after surgery.Results:After propensity score matching was performed, 66 patients were enrolled, including 22 in elderly donor group and 44 in non-elderly donor group.There was no significant difference in the incidence of intraoperative postreperfusion syndrome, acute kidney injury and postoperative pulmonary complications within 7 days after operation, time of intensive care unit stay, assisted mechanical ventilation time, postoperative length of stay, 6-month and 1-year survival and recurrence-free survival rate between elderly donor group and non-elderly donor group ( P>0.05). Conclusion:Age factors do not exert effect on the incidence of intraoperative and early postoperative complications in the patients undergoing OLT.
ABSTRACT
Objective To explore the curative effectiveness of comprehensive voice training methods on teachers' voice disorders patients by using subjective and objective assessment. Methods Forty-seven teachers' voice disorders patients suffering from voice symptoms without organic disease and complete follow-up data as the research object were treated with a three-month comprehensive voice training program. Training content included relieving laryngeal muscle tension, improving the throat vocal cord movement and reconstruction methods of pronunciation. The use of voice acoustic analysis and voice handicap index(VHI) were compared before and after training. Results The jitter and shimmer were significantly decreased after comprehensive voice training from 1.06(0.79,1.38)％and 2.71(2.16,3.24)％to 0.78 (0.59, 0.99)％ and 1.64(1.03,2.45)％, the differences were significant (Z=3.249,-4.121, P<0.05). Maximum phonation time and dysphonia severity index were significantly increased obviously from (9.87 ± 2.61)s and-2.23±0.75 to (12.81±1.97)s and-0.43±1.65 respectively, the differences were significant (t=-6.057,-5.273, P<0.05). After the training, the VHI score of voice disorder index decreased from (37.41±4.96)points to (26.31± 4.29) points after the comprehensive voice training. In addition to emotional function, the difference was statistically significant(t=12.715, 5.881, 11.483, P<0.05). Conclusions Voice training can reduce the degree of voice disorders effectively, increase the power of the respiratory system, therefore improve the voice quality of teachers with voice disorders. The subjective and objective combination assessment can evaluate the quality of the patient′s voice more thoroughly and evaluate the clinical efficacy of voice training further.
ABSTRACT
OBJECTIVE@#Comparative analysis of the clinical curative effect of manipulative reduction and TRV- CRP treatment of BPPV, comfort degree during reset and quality of life improvement.@*METHOD@#One hundred and thirty-two patients with BPPV were randomly divided into two groups ,one group underwent the traditional manip- ulative reduction, the other group with TRV-CRP. DRI and VAS was evaluated in the pre and after treatment and evaluation of the efficacy was conducted. The results of two groups were compared.@*RESULT@#The effective rate of manipulative reduction after a week treatment was 89. 23% and TRV-CRP.was 98. 51%, which was higher in TRV-CRP group than that of the manipulation reduction group(P0. 05), the score of the two groups were decreased after a week of reduction, but the improvement of TRV-CRP group was higher than that of manipulation reduction group(P<0. 05).@*CONCLUSION@#The success rate of TRV-CRP was higher than that of manipulative reduction,but manipulative reduction comfort degree was higher than TRV-CRP, the two methods can both improve the quality of life of patients with BPPV. TRV-CRP has many advantages over manipulative reduction, but manipulative reduction is simple with low cost, and the effect is still a great advantage. In clinical work, we should reasonable combine the two methods,so as to improve the cure rate of RPPV.
