Objective:To explore the application of online challenge training mode and analyze its application effect in standardized training of new nurses.Methods:Using the map training mode of the online training platform, a challenge game was designed and applied in the standardized training of new nurses. Using the convenience sampling method, 309 new nurses who joined Beijing Friendship Hospital, Capital Medical University from 2020 to 2021 were selected and grouped according to their starting date. The 103 nurses who joined in 2020 were set as the control group and traditional training was used. The 206 nurses who joined in 2021 were set as the research group and a challenge training mode was used. The scores and pass rates of theoretical assessment and OSCE assessment as well as the scores of core competency were compared between the two groups after training. A self-made questionnaire for satisfaction survey was used to investigate the satisfaction of nurses in the research group with the challenge training mode. The t-test and chi-square test were perform using SPSS 23.0. Results:Compared with the control group, the research group showed significantly higher score [(83.32±6.30) vs. (81.59±7.62)] and pass rate (94.66% vs. 83.50%) of theoretical assessment, significantly higher score [(92.19±5.08) vs. (90.66±5.47)] and pass rate (100.00% vs. 97.09%) of OSCE assessment, and a significantly higher total score of core competencies [(193.61±34.94) vs. (177.55±36.91)] ( P<0.05). Moreover, 98.06% (202) of nurses believed that the challenge training mode could stimulate learning interest and motivation, and preferred the online challenge mode training method. Additionally, 93.69% (193) of nurses believed that online learning was more efficient, and 96.60% (199) of nurses thought that online training saved time. Conclusions:The online challenge training mode can effectively stimulate the learning interest of new nurses, improve their core abilities, and increase their satisfaction with the training. This method is worth implementing and promoting in standardized nurse training.

Objective To explore esomeprazole(EMZ)on acetaminophen(APAP)pharmacokinetics and intestinal microbial balance.Methods A total of 14 rats were randomly allocated into two groups,with 7 rats in each group:acetaminophen group(APAP group),and acetaminophen+esomeprazole combination group(APAP+EMZ group),respectively.Rats in the combination group were fed in the metabolic cage.Equivalent 3.6 mg·kg-1·d-1 esomeprazole was administered intragastrically to the combination group for 14 days;Similarly,an equal volume of 0.9％sodium chloride soution(NaCl)was fed to the APAP group for 14 days.During this period,fecal samples were collected from the rats before and after 14 days of EMZ administration for microbial 16S rRNA sequencing.On the 15th day,both the APAP group and APAP+EMZ groups were administratered an equivalent of 44.82 mg·kg-1 APAP by the same method after the regular EMZ administration.The concentrations of APAP in rat plasma were determined by the UPLC-MS/MS method.Main pharmacokinetic parameters were processed and compared using the software DAS 3.0.1 and SPSS 24.0.Results The pharmacokinetic parameter Cmax of APAP was significantly different between APAP group and APAP+EMZ group(P＜0.05).Compared with APAP group,Cmax increased by 120.38％in the APAP+EMZ group.The pharmacokinetic parameters(AUC(0-∞)、CL、t 1/2、tmax)of APAP showed no statistical differences between APAP group and APAP+EMZ group(P＞0.05).The results of 16SrRNA of intestinal flora showed that the abundance of Lactobacillus,Bacteroides,Clostridium,and Escherichia decreased compared with that before drug administration,while the abundance of Bifidobacterium increased.However,the relative abundance of the above flora showed no prominent differences before and after the EMZ intervention(P＞0.05).Conclusions This study showed that when combining EMZ with APAP,the relative abundance of those related flora,which may influence the β-Glucuronidase,all changed to some extent,but made no difference in statistics.The effect of EMZ on the Cmax of APAP was statistically significant.However,the use of EMZ for two weeks did not alter the other pharmacokinetics of APAP by affecting the gut microbiota.

Objective To evaluate the risk of cardiac adverse events in patients with malignant tumors after chemotherapy by using a combination of acoustic cardiography and blood indices.Methods A total of 171 patients with malignant tumor who received chemotherapy were included.They were divided into cardiac adverse event group and non-cardiac adverse event group in accordance with whether cardiac adverse events occurred after chemotherapy.The general data,blood indices before chemotherapy,and acoustic cardiography-related indices in the early stage(1-3 cycles)of chemotherapy of the two groups were analyzed.The possible influencing factors were determined by binary logistic regression analysis,and the nomogram was drawn.The receiver operating characteristic(ROC)curve was used to evaluate the prediction ability of the nomogram.Results Cardiac adverse events occurred in 44 of 171 patients with malignant tumors after chemotherapy,and the incidence of cardiac adverse events was 25.73%.Binary logistic regression results showed that age,red blood cell distribution width(RDW)before chemotherapy,activated partial throm-boplastin time(APTT),and electromechanical activation time(EMAT)at the early stage of chemother-apy were independent predictors of cardiac adverse events in chemotherapy patients.The area under the ROC curve of the nomogram was 0.768(95%CI:0.693-0.843,P<0.001).Conclusion A nomogram based on age,pre-chemotherapy RDW,APTT,and EMAT at the early stage of chemotherapy is useful for early assessment of the risk of cardiac adverse events in chemotherapy patients.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has spread worldwide since it was first identified in Wuhan, China, at the end of 2019. With the global transmission of the virus, a large number of SARS-CoV-2 variants have also appeared, especially, emerging strains that have recently been discovered in the United Kingdom (variant 20I/501Y.V1, lineage B.1.1.7), South Africa (variant 20H/501Y.V2, lineage B.1.351), and Brazil (variant 20 J/501Y.V3, and lineage P.1). The common feature of these variants is that they share the N501Y mutation involving the SARS-CoV-2 spike (S) protein, which is precisely the target of most COVID-19 vaccines. Furthermore, mutations such as N501Y, E484K, and K417N in the S protein may affect viral fitness and transmissibility. However, current research on the impact of these variants on COVID-19 vaccines is still lacking. Herein, we briefly explain why most COVID-19 vaccines target the S protein, update the progress of research regarding S protein-related COVID-19 vaccines, review the latest studies concerning the effects of S protein variants on COVID-19 vaccines, and finally, propose certain strategies to deal with SARS-CoV-2 variants.

OBJECTIVE：To develop a metho d for determining the plasma concentration of sulfasalazine （SSZ）metabolite sulfapyridine（SP）in rats ，and to investigate the effects of esomeprazole （ESOM）on the pharmacokinetic behavior of SSZ in rats. METHODS：Male SD rats were randomly divided into SSZ group and SSZ+ESOM group ，with 6 rats in each group. SSZ+ESOM group were given Esomeprazole enteric-coated tablets [ 90 mg/（kg·d）] intragastrically for 14 days. On the 15th day ，the rats in 2 groups were given Sulfasalazine enteric coated tablets （90 mg/kg）intragastrically，and blood sample was collected from the inner canthus at 0.5，1，1.5，2，3，4，6，8，10，12，24，36，48，72 h after administration. After protein precipitation with methanol ， using diazepam as internal standard ，Agilent XDR-C 18 column was adopted with methanol- 0.1％ formic acid solution （gradient elution）as mobile phase. The concentration of SSZ metabolite SP in plasma was determined by LC-MS/MS. The pharmacokinetic parameters were calculated by using DAS 3.0.1 software and compared between 2 groups. RESULTS ：The linear range of SP were 2-1 000 ng/mL. The methodology met the requirements of Chinese Pharmacopeia . There was no statistical significance in pharmacokinetic parameters of SP between 2 groups，such as AUC 0－t，tmax，t1/2z，cmax，MRT0－t（P＞0.05）. CONCLUSIONS ：The established method is simple ，rapid and sensitive ；it can be used for the concentration determination of SSZ metabolite SP in plasma. ESOM has no significant effect on the pharmacokinetic behavior of SSZ in rats.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has spread worldwide since it was first identified in Wuhan, China, at the end of 2019. With the global transmission of the virus, a large number of SARS-CoV-2 variants have also appeared, especially, emerging strains that have recently been discovered in the United Kingdom (variant 20I/501Y.V1, lineage B.1.1.7), South Africa (variant 20H/501Y.V2, lineage B.1.351), and Brazil (variant 20 J/501Y.V3, and lineage P.1). The common feature of these variants is that they share the N501Y mutation involving the SARS-CoV-2 spike (S) protein, which is precisely the target of most COVID-19 vaccines. Furthermore, mutations such as N501Y, E484K, and K417N in the S protein may affect viral fitness and transmissibility. However, current research on the impact of these variants on COVID-19 vaccines is still lacking. Herein, we briefly explain why most COVID-19 vaccines target the S protein, update the progress of research regarding S protein-related COVID-19 vaccines, review the latest studies concerning the effects of S protein variants on COVID-19 vaccines, and finally, propose certain strategies to deal with SARS-CoV-2 variants.

Objective: To explore the clinical application value of enhanced recovery after surgery (ERAS) in the laparoscopic surgery for cholecystolithiasis comorbid with choledocholithiasis. Methods: The prospective study was conducted. The clinicopathological data of 52 patients with cholecystolithiasis comorbid with choledocholithiasis who were admitted to the Third Affiliated Hospital of Zunyi Medical University from September 2016 to September 2018 were collected. Patients were divided into 2 groups by random number table: patients in observation group received laparoscopic cholecystectomy + choledocholithotomy + choledochoscopic exploration + T-tube drainage (or primary suture of common bile duct) and perioperative management guided by the concept of enhanced recovery after surgery (ERAS), and patients in control group received traditional perioperative management. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) postoperative complications; (4) postoperative pain scores; (5) changes in hepatic function and blood routine during perioperative period. Follow-up using outpatient examination and telephone interview was performed to detect complications during the postoperative 6 months up to March 2019. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the paired t test or repeated ANOVA. Count data were described as absolute numbers and percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Results: Fifty-two patients were screened for eligibility, including 20 males and 32 females, aged 25-68 years, with an average age of 53 years. There were 30 patients in the observation group and 22 in the control group. (1) Surgical situations: the operation time and volume of intraoperative blood loss were (133±19)minutes and (47±21)mL in the observation group, and (136±22)minutes and (49±23)mL in the control group, respectively, showing no significant difference between the two groups (t=-0.386, -0.211, P>0.05). (2) Postoperative situations: time to out-of-bed activity, time to initial food intake, time to first anal flatus, duration of postoperative hospital stay, and hospital expenses were (18±4)hours, (19±5)hours, (28±2)hours, (4.0±1.0)days, and (1.82±0.22)×10⁴ yuan in the observation group, and (29±7)hours, (46±9)hours, (37±4)hours, (6.6±1.6)days, and (2.25±0.29)×10⁴ yuan in the control group, respectively, showing significant differences between the two groups (t=-7.054, -14.169, -9.426, -6.582, -5.809, P<0.05). (3) Postoperative complications: 1 of 30 patients in the observation group had postoperative biliary leakage, with a postoperative complication rate of 3.3%, and was cured after symptomatic support treatment. Six of 22 patients in the control group had postoperative complication, with a postoperative complication rate of 27.3%, including 2 of biliary leakage, 1 of hemorrhage, 1 of abdominal infection, 1 of pulmonary infection, 1 of urinary infection, and they were cured after symptomatic support treatment. There was a significant difference between the two groups (χ²=4.358, P<0.05). (4) Postoperative pain scores: from postoperative 6 hours to 48 hours, the postoperative pain score changed from 2.4±0.7 to 1.9±0.9 in the observation group, and from 4.1±0.7 to 2.9±0.9 in the control group, respectively, showing a significant difference in the changing trend between the two groups (F=78.053, P<0.05). (5) Changes in hepatic function and blood routine during perioperative period: from preoperation to postoperative 3 days, levels of alamine aminotransferase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBil), and count of white blood cells in the observation group changed from (77±20)U/L to (53±12)U/L, from (85±22)U/L to (61±17)U/L, from (166±39)U/L to (55±24)U/L, from (40±13)μmol/L to (29±12)μmol/L, from (7.0±2.0)×10⁹/L to (6.8±1.9)×10⁹/L, and changed from (79±23)U/L to (62±14)U/L, from (88±24)U/L to (64±17)U/L, from (179±34)U/L to (74±29)U/L, from (45±13)μmol/L to (35±12)μmol/L, from (7.9±2.4)×10⁹/L to (7.5±1.9)×10⁹/L in the control group, respectively. The levels of ALT, AST, GGT, TBiL, and count of WBC showed increasing at postoperative 1 day, and decreasing at postoperative 3 days. There was no significant difference in the changing trend between the two groups (F=0.058, 0.471, 3.021, 1.593, 2.172, P>0.05). Conclusion ERAS is safe and effective in the laparoscopic surgery for choledocholithiasis comorbid with cholecystolithiasis.

Objective To evaluate the predicting value of circulating miRNAs for sepsis secondary to pneumonia in elderly patients.Methods From April 2016 to January 2017,44 cases with sepsis secondary to pneumonia,52 elderly patients with pneumonia and 21 healthy older adults as control were involved in this study.The expression levels of MiRNA-150 5p,miRNA-25-3p,miRNA-122 5p and miRNA-223-3p in plasma were evaluated by fluorescence quantitative PCR.The demographic characteristics,sequential organ failure assessment (SOFA)scores,prognosis and days stayed in ICU were recorded.The area under the receiver operating charaeteristic(ROC)curve was used to calculated the specificity and sensitivity of miRNA in identifying sepsis-associated pneumonia.Results There were significantly differences among levels of circulating miRNA-223-3p in pneumonia,sepsis and healthy control groups(F =36.441,P =0.000),△CT values were 2.39 ± 1.36,1.44± 1.43,and 4.58 ± 0.91,respectively.The relative expression levels of miRNA-223-3p in the three groups were significantly different (P =0.000),which were 0.189 (0.107,0.367),0.361 (0.221,0.735),and 0.044 (0.022,0.061),respectively.The AUC of miRNA-223-3p for predicting sepsis from pneumonia was 0.964(95 ％CI =0.925 1.000).At a cutoff value of 2.759,miRNA-223-3p yielded a sensitivity of 82.9％ and a specificity of 100.0％.Conclusions MiRNA-223-3p expression is up-regulated in patients with sepsis secondary to pneumonia compared to that of patients with pneumonia,and it could be used to predict sepsis associated pneumonia.

Objective: To explore the peri-operative application of GLP-1 analogue and insulin on myocardial perfusion and clinical prognosis in patients of acute ST segment elevation myocardial infarction (STEMI) with stress-induced hyperglycemia. Methods: Our research was a prospective single center randomized control study. A total of 114 consecutive STEMI patients received percutaneous coronary intervention (PCI) within 12h of onset were enrolled, the patients had no diabetes while blood glucose ≥11.1mmol/L at immediate admission. Based on random number table, the patients were divided into 2 groups: Observation group, the patients received GLP-1 analogue, n=59 and Control group, the patients received insulin, n=55. The post-operative myocardial perfusion, indicators of myocardial damage and cardiac function, myocardial infarct area (MIA) and myocardial salvage index (MSI) were compared between 2 groups. The patients were followed-up for 6 months to record the incidence of major adverse cardiovascular events (MACE). Results: At peri-operative period, compared with Control group, Observation group had decreased peak values of creatine kinase isoenzyme (CK-MB) and troponin T (cTnT), P<0.05. At 6 months post-operation, compared with Control group, Observation group showed increased myocardial perfusion and left ventricular ejection fraction (LVEF), P<0.05, reduced MIA (15±12) g vs (20±14) g, P<0.05 and 12% elevated MSI as (0.64±0.13) vs (0.56±0.12), P<0.001. The MACE incidence was similar between 2 groups, P=0.217. Conclusion: In STEMI patients with stress-induced hyperglycemia, peri-operative application of GLP-1 analogue may safely regulate blood glucose, improve cardiac perfusion and function, reduce MIA; while it had no influence on myocardial perfusion at peri-operative period and no impact on MACE occurrence at 6 months post-operation.

OBJECTIVE:To investigate the effects of triptolide(TP)on the proliferation of fibroblast-like synoviocytes(FLS) from patients with rheumatoid arthritis(RA)in vitro. METHODS:5 RA patients received knee arthroplasty or synovectomy to ob-tain synovial tissue. FLS was isolated,cultured and identified,and then incubated in the presence of TP [0 (blank control),50, 100 and 200 nmol/ml] for 24,48 and 72 h. The effects of TP on FLS was evaluated by MTT,and then proliferation inhibitory rate was calculated;flow cytometry was used to detect the apoptosis and cell cycle of FLS. RESULTS:The inhibitory rates of TP(50, 100 and 200 nmol/ml)on the proliferation of FLS were 17.46%-52.56%,which was positively correlated with drug concentration. Compared with blank control group,100 and 200 nmol/ml TP could increase the percentage of cells in G0/G1 phase and decrease the percentage of cells in S phase,with statistical significance(P<0.05);200 nmol/ml TP could induce cell apoptosis. CONCLU-SIONS:TP could inhibit the proliferation and also could induce the apoptosis of FLS in RA patients in vitro,which may be one of its mechanism for treating RA.