Objective:To evaluate the effect of dexmedetomidine on the expression of DNA methyltransferases in septic mice with acute lung injury.Methods:Forty-eight clean-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation + dexmedetomidine group(group Sham+ DEX), sepsis group (group Sepsis) and sepsis + dexmedetomidine group(group Sepsis+ DEX). Sepsis model was established by cecal ligation and puncture(CLP)in anesthetized mice. At 30 min before model preparation, dexmedetomidine 0.05 μg/g (in 0.5 ml of normal saline) was administered in Sham + DEX and Sepsis + DEX groups, and normal saline 0.5 ml was given instead in Sham and Sepsis groups. The mice were sacrificed at 24 h after CLP, and the lung tissue was taken to determine the wet to dry lung weight ratio, contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and high mobility group box-1 (HMGB-1), activities of superoxide dismutase (SOD) and myeloperoxidase (MPO), and content of malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), global DNA methylation (by colorimetric assay), and expression of DNA methyltransferases (DNMTl, DNMT3a, DNMT3b) (by Western blot) and to examine the histopathological changes of lung tissues (by HE staining) which were scored. Results:Compared with group Sham, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly increased, SOD activity was decreased, and the expression of DNMT1 and DNMT3a was up-regulated in group Sepsis and group Sepsis+ DEX ( P<0.05), and no significant change was found in the aforementioned indexes in group Sham+ DEX ( P>0.05). Compared with group Sepsis, the lung injury score, wet/dry lung weight ratio, contents of IL-6, TNF-α and HMGB1 and MDA, MPO activity and global DNA methylation were significantly decreased, SOD activity was increased, and the expression of DNMT1 and DNMT3a was down-regulated in group Sepsis+ DEX ( P<0.05). Conclusions:The mechanism by which dexmedetomidine reduces acute lung injury is related to inhibition of up-regulation of DNMT1 and DNMT3a expression in septic mice.

Objective:To evaluate the role of DNA methyltransferase in acute lung injury in septic mice.Methods:Forty-eight healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (group Sham), sham operation+ DNA methyltransferase inhibitor group (group Sham+ 5-Aza), sepsis group (group Sepsis) and sepsis+ DNA methyltransferase inhibitor group (group Sepsis+ 5-Aza). Sepsis model was developed by cecal ligation and puncture (CLP) in anesthetized mice.Mice were sacrificed at 24 h after CLP, and lung tissues were obtained, DNA was extracted to determine the global DNA methylation by colorimetry, and RNA was extracted to detect the expression of DNA methyltransferase (DNMTl, DNMT3a, DNMT3b) mRNA by real-time fluorescent quantitative polymerase chain reaction, the wet/dry lung weight ratio (W/D ratio) was measured, the histopathological changes of lung tissues were determined by HE staining, the contents of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), high-mobility group box 1 protein (HMGB1) and malondialdehyde (MDA) and activities of superoxide dismutase (SOD) and catalase were measured by enzyme-linked immunosorbent assay. Results:Compared with group Sham, the global DNA methylation was significantly increased, the expression of DNMT1 and DNMT3a mRNA was up-regulated, the lung injury score, W/D ratio, and contents of IL-6, TNF-α, HMGB1 and MDA were increased, and activities of SOD and CAT were decreased at 24 h after CLP in group Sepsis and group Sepsis+ 5-Aza ( P<0.05), and no significant change was found in the indexes mentioned above in group Sham+ 5-Aza ( P>0.05). Compared with group Sepsis, the global DNA methylation was significantly decreased, the expression of DNMT1 and DNMT3a mRNA was down-regulated, the lung injury score, W/D ratio, contents of IL-6, TNF-α, HMGB1 and MDA were decreased, and the activities of SOD and CAT were increased in group Sepsis+ 5-Aza ( P<0.05). Conclusions:DNA hypermethylation mediated by DNMT1 and DNMT3a is involved in the process of acute lung injury in septic mice.

Objective:To explore the adverse reactions to sintilimab in patients with non-small cell lung cancer (NSCLC) and Hodgkin lymphoma (HL).Methods:The clinical data of all NSCLC and HL patients who were treated with sintilimab during hospitalization in the Fifth Medical Center of the PLA General Hospital from January 2019 to August 2020 were collected by searching Hospital Information System. The clinical data including patients′ basic information (gender, age, diagnosis), medication (initial treatment or retreatment with sintilimab, single and cumulative dose, combined medication), and occurrence of adverse reactions (involved organs or systems, clinical manifestations, occurrence time, intervention and outcome) were recorded and analyzed retrospectively. The correlation between sintilimab and adverse reactions and the grade of adverse reactions were evaluated according to Hand Book of Adverse Drug Reaction Reporting and Monitoring in China and the International Adverse Reaction Evaluation System of Cancer Chemotherapy Drugs.Results:A total of 90 patients were enrolled in the analysis, including 75 NSCLC patients and 15 HL patients, aged from 16 to 81 years with the median age of 63 years; 81 patients were initially treated with sintilimab and 9 were retreated. Eighty-eight patients received sintilimab 200 mg per cycle and 2 patient received 100 mg per cycle. The cumulative dose was 200, >200-1 000, and >1 000 mg in 39, 35, and 16 cases, respectively; 32 patients were treated with sintilimab alone and 58 were treated with sintilimab combined with other regimens. Fifty-three (58.9%) patients had adverse reactions, among which, 41 (45.6%) and 12 cases (13.3%) had grade 1-2 and ≥ grade 3 adverse reactions, respectively. The occurrence time was 1-242 days after treatment. Among the 53 patients, 37 were male and 16 were female, aged 28-80 years; 48 were with NSCLC and 5 with HL. The incidence of adverse reactions in NSCLC patients was significantly higher than that in HL patients [64.0% (48/75) vs. 33.3% (5/15), χ2=4.856, P=0.028]. Forty-eight patients were initially treated and 5 were retreated. Fifty-two patients received sintilimab 200 mg per cycle and 1 patient received 100 mg per cycle. The cumulative dose was 200, >200-1 000, and >1000 mg in 16, 26, and 11 cases, respectively. The difference in the incidences of adverse reactions among patients with different cumulative doses was significant ( χ2=9.21, P=0.01). Fourteen patients were treated with sintilimab alone and 39 patients were treated with sintilimab combined with other therapeutic regimens; the incidence of adverse reactions in patients with sintilimab combined with other therapeutic regimens was higher than that in patients with sintilimab monotherapy, and the difference was statistically significant [66.1% (39/58) vs. 43.8% (14/32), χ2=4.701, P=0.03]. A total of 101 times of adverse reactions to sintilimab occurred in 53 patients (1, 2, 3, 4 and 5 kinds of adverse reactions occurred in 24, 16, 9, 2, and 2 patients, respectively), 52 times of them were recorded in the medical records, and 49 times were found by rechecking the results of laboratory and auxiliary tests; 1, 3, and 97 times of adverse reactions were evaluated as "certainly", "probably", and "possibly", respectively. Eighty-nine times (88.1%) of adverse reactions were grade 1-2 and 12 times (11.9%) were equal to or greater than grade 3. Multiple systems or organs were involved in the adverse reactions including blood, hepatobiliary, gastrointestinal, endocrine, respiratory, skin and appendix, heart, skeletal muscle and connective tissue, urinary, and nervous systems, and those with the top 5 incidence rates were blood, hepatobiliary, gastrointestinal, endocrine, and respiratory system adverse reactions[24.4% (22/90), 15.6% (14/90), 14.4% (13/90), 12.2% (11/90), and 11.1% (10/90)]. Twelve patients stopped sintilimab due to adverse reactions, 4 were only closely monitored without special treatment, and 49 received one day to seven months of symptomatic treatments. Among the 53 patients, 8 were cured, 29 were improved, 6 were not improved, 9 were unknown, and 1 died. Conclusions:Sintilimab could lead to adverse reactions in multiple systems or organs in patients with NSCLC and HL, such as blood, hepatobiliary, gastrointestinal, endocrine, respiratory, and skin and appendages. The incidence and grade of adverse reactions were lower than those documented in the drug label, and no new adverse reactions were detected.

Objective:To explore the adverse reactions to sintilimab in patients with non-small cell lung cancer (NSCLC) and Hodgkin lymphoma (HL).Methods:The clinical data of all NSCLC and HL patients who were treated with sintilimab during hospitalization in the Fifth Medical Center of the PLA General Hospital from January 2019 to August 2020 were collected by searching Hospital Information System. The clinical data including patients′ basic information (gender, age, diagnosis), medication (initial treatment or retreatment with sintilimab, single and cumulative dose, combined medication), and occurrence of adverse reactions (involved organs or systems, clinical manifestations, occurrence time, intervention and outcome) were recorded and analyzed retrospectively. The correlation between sintilimab and adverse reactions and the grade of adverse reactions were evaluated according to Hand Book of Adverse Drug Reaction Reporting and Monitoring in China and the International Adverse Reaction Evaluation System of Cancer Chemotherapy Drugs.Results:A total of 90 patients were enrolled in the analysis, including 75 NSCLC patients and 15 HL patients, aged from 16 to 81 years with the median age of 63 years; 81 patients were initially treated with sintilimab and 9 were retreated. Eighty-eight patients received sintilimab 200 mg per cycle and 2 patient received 100 mg per cycle. The cumulative dose was 200, >200-1 000, and >1 000 mg in 39, 35, and 16 cases, respectively; 32 patients were treated with sintilimab alone and 58 were treated with sintilimab combined with other regimens. Fifty-three (58.9%) patients had adverse reactions, among which, 41 (45.6%) and 12 cases (13.3%) had grade 1-2 and ≥ grade 3 adverse reactions, respectively. The occurrence time was 1-242 days after treatment. Among the 53 patients, 37 were male and 16 were female, aged 28-80 years; 48 were with NSCLC and 5 with HL. The incidence of adverse reactions in NSCLC patients was significantly higher than that in HL patients [64.0% (48/75) vs. 33.3% (5/15), χ2=4.856, P=0.028]. Forty-eight patients were initially treated and 5 were retreated. Fifty-two patients received sintilimab 200 mg per cycle and 1 patient received 100 mg per cycle. The cumulative dose was 200, >200-1 000, and >1000 mg in 16, 26, and 11 cases, respectively. The difference in the incidences of adverse reactions among patients with different cumulative doses was significant ( χ2=9.21, P=0.01). Fourteen patients were treated with sintilimab alone and 39 patients were treated with sintilimab combined with other therapeutic regimens; the incidence of adverse reactions in patients with sintilimab combined with other therapeutic regimens was higher than that in patients with sintilimab monotherapy, and the difference was statistically significant [66.1% (39/58) vs. 43.8% (14/32), χ2=4.701, P=0.03]. A total of 101 times of adverse reactions to sintilimab occurred in 53 patients (1, 2, 3, 4 and 5 kinds of adverse reactions occurred in 24, 16, 9, 2, and 2 patients, respectively), 52 times of them were recorded in the medical records, and 49 times were found by rechecking the results of laboratory and auxiliary tests; 1, 3, and 97 times of adverse reactions were evaluated as "certainly", "probably", and "possibly", respectively. Eighty-nine times (88.1%) of adverse reactions were grade 1-2 and 12 times (11.9%) were equal to or greater than grade 3. Multiple systems or organs were involved in the adverse reactions including blood, hepatobiliary, gastrointestinal, endocrine, respiratory, skin and appendix, heart, skeletal muscle and connective tissue, urinary, and nervous systems, and those with the top 5 incidence rates were blood, hepatobiliary, gastrointestinal, endocrine, and respiratory system adverse reactions[24.4% (22/90), 15.6% (14/90), 14.4% (13/90), 12.2% (11/90), and 11.1% (10/90)]. Twelve patients stopped sintilimab due to adverse reactions, 4 were only closely monitored without special treatment, and 49 received one day to seven months of symptomatic treatments. Among the 53 patients, 8 were cured, 29 were improved, 6 were not improved, 9 were unknown, and 1 died. Conclusions:Sintilimab could lead to adverse reactions in multiple systems or organs in patients with NSCLC and HL, such as blood, hepatobiliary, gastrointestinal, endocrine, respiratory, and skin and appendages. The incidence and grade of adverse reactions were lower than those documented in the drug label, and no new adverse reactions were detected.

Degenerative changes in autonomic nervous system happen in elderly. The cardiac function reduces, the ability of regulating the target organ decreases, and the stability of hemodynamics is not easy to maintain in old people. How to maintain the hemodynamic stability of elderly patients during anesthesia has become the focus of clinical research. Dexmedetomidine, as a new type of 2- alpha adrenergic agonist, has the function of anti-anxiety, sedation, analgesia and anti-sympathy, and which is wildly used in clinic. This article describes the research progress of dexmedetomidine used in elderly patients during anesthesia.

OBJECTIVE:To evaluate the economics of azithromycin vs. amocillin clavulante in the treatment of lower respirato-ry tract infections. METHODS:System evaluation was adopted to retrieve the randomized controlled trials(RCT)about azithromy-cin(test group)vs. amoxicillin clavulanate(control group)in the treatment of lower respiratory tract infections. Information was col-lected and Meta-analyses were performed. On this basis and short-term decision tree model,cost factors were added to conduct the pharmacoeconomics by the principle of PICO of Treeage Pro 2011 edition software. RESULTS:Totally 18 RCT were enrolled,in-volving 3 365 patients. Results of Meta-analysis showed that there were no significant differences in the effective rate [RR=0.93, 95%CI(0.55,1.55),P=0.77] and incidence of adverse reactions [RR=0.79,95%CI(0.62,1.0),P=0.05] between 2 groups. The av-erage treatment cost in test group and control group was respectively 790.4 yuan and 884.4 yuan,and cost-effectiveness ratio was respectively 216.0 and 245.7,and the incremental cost-effectiveness ratio(ICER)was -1 392.59. CONCLUSIONS:Azithromycin has similar efficacy and safety to amoxicillin clavulanate in the treatment of lower respiratory tract infection,however,azithromy-cin has better cost-effectiveness.