Objective To investigate the effect of parecoxib on postoperative hyperalgesia induced by remifentanil-based anesthesia.Methods One hundred ASA Ⅰ or Ⅱ patients,aged 21-64 yr,weighing 50-80 kg,undergoing elective laparoscopic operation,were randomly divided into 5 groups ( n =20 each):parecoxib group (group P),small dose remifentanil group (group S),large dose remifentanil group (group L),small dose remifentanil + parecoxib group (group SP) and large dose remifentanil + parecoxib group (group LP).Parecoxib 40 mg was injected intravenously at 30 min before anesthesia in groups P,SP and LP.Anesthesia was induced with midazolam0.05 mg/kg,etomidate 0.2 mg/kg,cisatracurium 0.15 mg/kg and remifentanil 1 μg/kg (fentanyl 4 μg/kg in group P).The patients was tracheal intubated and mechanically ventilated.PETCO2 was maintained at 35-45 mm Hg.Anesthesia was maintained with infusion of remifentanil at 0.05 μg·kg-1 ·min-1 (in groups S and SP) or at 0.3 μg· kg- 1· min- 1 (in groups L and LP) combined with inhalation of sevoflurane and infusion of cisatracurium at 0.12 mg·kg-1·h-1.At 30 min after operation,numeric rating scale (NRS) was used to assess the degree of pain at rest and during activity.Tramadol 1.5 mg/kg was injected intravenously after operation if needed.NRS scores were maintained ≤5.The use of tramadol and adverse effects during 24 h after operation were recorded.Results Compared with group P,NRS scores at rest and during activity were significantly increased at 30 min after operation in groups S and L,the incidence of shivering and the number of patients who needed tramadol were significantly increased in group L,and no change was found in NPS scores at rest and during activity at 30 min after operation,the incidence of adverse effects and the number of patients who needed tramadol in groups SP and LP.Compared with group S,NRS scores at rest and during activity at 30 min after operation,the incidence of shivering and the number of patients who needed tramadol were significantly increased in group L,NRS scores at rest and during activity at 30 min after operation were significantly decreased and no change was found in the incidence of adverse effects and the number of patients who needed tramadol in group SP.Compared with group L,NRS scores at rest and during activity at 30 min after operation,the incidence of shivering and the number of patients who needed tramadol were significantly decreased in group LP.Conclusion Intravenous injection of parecoxib 40 mg at 30 min before anesthesia can attenuate postoperative hyperalgesia induced by remifentanil-based anesthesia.

Objective:Clinical research is widely carried out in medical institutions, and there are differences in the use of research and conventional medical funds. This paper aimed to analyze the compliance issues of insurance fund in clinical research and explore the management strategies in the institutions conducting clinical trials or research.Methods:By consulting the literature, questionnaire, and work practice, this paper analyzed the current situation and existing problems of the compliance of the medical insurance fund in domestic clinical trials, proposed targeted management measures for the use of funds, and standardizes the corresponding workflow.Results:This paper summarized three payment methods of research-related funds and analyzed the main problems at present, including the definition of trial requirements, the payment of combined drugs specified in the protocol, the particularity of medical device trials, the payment of adverse events in clinical trial, the insurance of post-marketing research and clinical trial. According to the regulatory requirements and work practices, the corresponding management countermeasures were sorted out, including that the project funds and insurance audit should be carried out inside the medical institution. Clinical research, medical insurance management departments, ethics committees, and other departments should collaborate on establishing and improving a compliance management system. The research team should strengthen the management of adverse events, strengthen the publicity and education of the participants, and make good use of the sharing platform.Conclusions:The research institution should establish standardized and feasible processes, the research team should strengthen the management, and the use of the sharing platform is conducive to ensuring the compliance of the medical insurance fund and protecting the interests of the participants.

Objective:To explore the correlation between cannabinoid 2 receptor (CB2R) and pyroptosis-related indicators in mice with septic lung injury.Methods:Mice were randomly (ramdon number) divided into four groups ( n=6 per group): sham operation group (sham), mild sepsis group (ALIMi), moderate sepsis group (ALIMo) and severe sepsis group (ALIS). The model of septic lung injury was established by cecal ligation and puncture. The wet-dry weight ratio of lung tissues and lung injury scores were measured 12 hours after operation. The expression of CB2R protein was measured by western blot, and the expression of mRNA of CB2R, NLRP3, caspase-1/11, GSDMD were detected by RT-PCR. Meanwhile ELISA was used to measure the level of inflammatory factor IL-6 and TNF-α. SPSS 22.0 software was used for data analysis. Multiple comparison was analyzed by one-way analysis of variance (one-way ANOVA) and comparison between two groups was performed by LSD test or Games-Howell test. Then, the correlation between the expression of CB2R mRNA and the level of inflammatory cytokines as well as the expression of the pyroptosis-related indicators mRNA was analyzed by pearson correlation analysis, respectively. Results:The statistical value F was obtained by one-way ANOVA and comparison between two groups was performed. Compared to sham group, all above indicators increased with the aggravation of inflammation in the sepsis groups ( P<0.05). Compared to ALIMi group, the concentrations of IL-6 [(277.31±41.07) vs.(140.09±27.56), P<0.05] and TNF-α [(501.09±73.91) vs. (261.36±40.73), P<0.05] in lung tissue homogenate increased in ALIMo group. And the level of CB2mRNA [(2.99±0.28) vs. (2.02±0.19), P<0.05], the expression of CB2 protein [(0.44±0.08) vs.(0.23±0.05), P<0.05] and the level of NLRP3 [(2.53±0.26) vs.(1.61±0.15), P<0.05], caspase-1 [(6.02±0.35) vs.(3.60±0.38), P<0.05], caspase-11 [(11.43±0.83) vs.(6.30±0.65), P<0.05] and GSDMD [(10.46±0.62) vs. (5.67±0.54), P<0.05] mRNA also increased. Compared to ALIMo group, the concentrations of IL-6 [(475.90±67.65) vs. (277.31±41.07), P<0.05] and TNF-α [(713.93±58.85) vs. (501.09±73.91), P<0.05] in lung tissue homogenate increased in ALIS group. And the level of CB2mRNA [(4.00±0.19) vs.(2.99±0.28), P<0.05], the expression of CB2 protein [(0.61±0.05) vs.(0.44±0.08), P<0.05] and the level of NLRP3 [(4.75±0.40) vs.(2.53±0.26), P<0.05], caspase-1 [(8.76±0.72) vs.(6.02±0.35), P<0.05], caspase-11 [(16.31±1.13) vs.(11.43±0.83), P<0.05] and GSDMD [(16.46±1.22) vs. (10.46±0.62), P<0.05] mRNA also increased. Furthermore, correlation analysis showed that there was a highly positive correlation between the expression of CB2R mRNA and the expression of mRNA of NLRP3, caspase-1/11, and GSDMD respectively ( r>0.9, P<0.01). Conclusion:The correlation between the aggravation of inflammation, the indicators of pyroptosis and CB2R mRNA was highly positive in different degrees of septic lung injury. Consequently, CB2R may play a role in the regulatory process of inflammation.