Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

OBJECTIVE To construct the simulated traditional Chinese medicine pharmacy based on virtual simulation technology， and assist in the development of the new mode of traditional Chinese medicine dispensing education training. METHODS The field research and questionnaire surveys were conducted to identify the needs of Chinese medicine students and practitioners for the content and presentation of knowledge on the construction of simulated traditional Chinese medicine pharmacy. Taking the laws and regulations on the construction of traditional Chinese medicine pharmacy and the related teaching materials and literature on traditional Chinese medicine preparation as the knowledge source， the virtual simulation technology was applied to build a simulated traditional Chinese medicine pharmacy so as to achieve the functions of browsing the traditional Chinese medicine pharmacy， learning the knowledge of traditional Chinese medicine preparation and practical skills training. A multi-site simulated traditional Chinese medicine pharmacy evaluation scale study was conducted based on platform operational testing. RESULTS A simulated traditional Chinese medicine pharmacy was constructed， consisting of four core modules： video teaching， animation video， simulated pharmacy， and simulated experience. The overall score of evaluation scale was 93.31， with all entries scoring above 80； the ones with evaluation scales above 90 accounted for 92.31% （60/65）. CONCLUSIONS Simulated traditional Chinese medicine pharmacy based on virtual simulation technology meets the learning needs of users and enhances the teaching effect of traditional Chinese medicine dispensing technology training.

Background Current evidence on whether occupational sulfur dioxide (SO₂) exposure affects the risk of hypertension is still limited, and the research results of the effect of environmental SO₂ exposure on risk of hypertension remain inconsistent. Objective To analyze the association between self-reported occupational exposure to SO₂ and the risk of hypertension, and the potential dose-response relationship between the years of exposure to SO₂ and the risk of hypertension. Methods Based on the Jinchang cohort, a nested case-control study design was adopted. A total of 841 newly diagnosed hypertension patients were followed up as the case group, and the control group was selected with 1∶1 individual matching based on non-occupational factors and occupational factors, respectively. The former matching conditions included age ±2 years old, same gender, working age ±2 years, and home address in the same sub-district. The latter was limited to working in the same workshop on the basis of the former conditions. Finally, the former included 717 controls and the latter included 488 controls. A unified questionnaire was used to collect general demographic characteristics, lifestyle habits, history of diabetes, family history of hypertension, and information on occupational exposure to SO₂ (self-reported history of occupational exposure to SO₂ and years of exposure to SO₂). Conditional logistic regression model was used to analyze the association between occupational exposure to SO₂ and hypertension, and the dose-response relationship between the years of SO₂ exposure and the risk of hypertension. Results In the nested case-control study matching with the non-occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO₂ was 2.39 (95%CI: 1.68-3.39); while when matching with the occupational factors, the OR of hypertension in workers with self-reported occupational exposure to SO₂ was 1.48 (95%CI: 1.04-2.12). The results of the dose-response relationship showed that as the SO₂ exposure years increased from 1-9 years, 10-19 years, 20-29 years, and 30 years and above, in the nested case-control study matching with non-occupational factors, the ORs of hypertension were 1.85 (95%CI: 0.68-5.08), 1.46 (95%CI: 0.58-3.67), 1.64 (95%CI: 1.00-2.67), and 4.95 (95%CI: 2.63-9.31), respectively; in the nested case-control study matching with occupational factors, the ORs of hypertension were 0.98 (95%CI: 0.40-2.41), 1.84 (95%CI: 0.72-4.70), 1.37 (95%CI: 0.82-2.29), and 2.44 (95%CI: 1.37-4.35), respectively. The two dose-response relationships were positive by χ² trend test (P_trend<0.05). Conclusion Self-reported occupational exposure to SO₂ is associated with the risk of hypertension in the study population, and the hypertension risk increases with the increase of SO₂ exposure years.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which causes great economic losses. At the moment, no effective neutralizing antibody is available for scientific research and treatment. Therefore, developing a method for screening the neutralizing monoclonal antibodies is of great significance for the prevention and treatment of PRRSV and the screening of antigen sites. Monoclonal antibodies have been widely used in the treatment and diagnosis of many human and animal diseases. Therefore, screening effective neutralizing antibodies for different pathogens is an urgent task. Among the methods for monoclonal antibody screening, B cell immortalization is an effective method to obtain neutralizing monoclonal antibody. Specifically, in this study, the bcl-6 and bcl-xl genes were connected by f2a and then the yielded product was ligated to a vector for retrovirus packaging. The swine lymphocytes immunized with PRRSV were infected the yielded mature viruses and cultured in the complete medium containing CD40L and IL21 cytokines. Then, CD21 was used as the marker to screen B cells with the magnetic bead method. Finally, monoclonal B cells were obtained and the secretion of antibodies was tested. The results showed that the plasmid, either being transfected alone or with the packaged plasmids, could be expressed, and that the packaged retrovirus could infect the cells. Moreover, the infected lymphocytes secreted antibodies, so did the screened B cells. Therefore, the method for screening monoclonal antibody against PRRSV was successfully established.
Animals ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Humans ; Porcine Reproductive and Respiratory Syndrome/prevention & control* ; Porcine respiratory and reproductive syndrome virus/genetics* ; Swine

Objective:To explore the predictive value of MB isoenzyme of creatine kinase (CK-MB) and poisoning severity score (PSS) in the clinical prognosis of patients with wasp sting.Methods:A retrospective study was conducted. The clinical data of patients who were stung by wasps admitted to emergency department of the First Affiliated Hospital of Henan University of Science and Technology from July 2017 to November 2019 were collected. The 24-hour acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), CK-MB and PSS scores of the patients were collected after admission, and 28-day outcome was recorded. Spearman correlation analysis method was used to analyze the correlation between CK-MB and PSS score. Logistic regression model was used to construct joint predictors, and the receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of various indicators for 28-day prognosis of patients with wasp stings.Results:Finally 90 patients were included in the analysis. There were 67 patients survived at 28 days, and 23 dead with the 28-day mortality of 25.6%. APACHEⅡ score, CK-MB and PSS score in the death group were significantly higher than those in the survival group [APACHEⅡscore: 19.7±2.7 vs. 13.7±2.3, CK-MB (U/L): 183 (151, 243) vs. 36 (21, 75), PSS score: 17.7±2.6 vs. 9.3±4.5, all P < 0.01]. The correlation analysis showed that CK-MB and PSS score were positively correlated ( r = 0.843, P < 0.01). Logistic regression model fitted CK-MB and PSS score, and Hosmer-Lemeshow test showed that the model fitted well. ROC curve analysis showed that the area under ROC curve (AUC) of CK-MB for predicting 28-day outcome was 0.957, the sensitivity was 91.3%, and the specificity was 88.1%; the AUC of PSS score was 0.908, the sensitivity was 91.3%, and the specificity was 90.8%. The AUC of CK-MB combined with PSS score was 0.964, the sensitivity was 100%, and the specificity was 79.4%, indicating that CK-MB combined with PSS score had higher predictive value and higher sensitivity for 28-day prognosis of patients with wasp sting. Conclusions:High CK-MB level and high PSS score in early stage of wasp sting injury indicate poor prognosis. Both CK-MB and PSS score can be used as predictors for predicting the prognosis of patients with wasp stings. In addition, CK-MB combined with PSS score have greater predictive value .

Objective To systematically evaluate the diagnostic accuracy and clinical applicability of recognition of stroke in the emergency room (ROSIER) scale by systematic review and Meta-analysis. Methods The Chinese and English literatures concerning the diagnostic accuracy of ROSIER published from January 1st 2005 to December 31st 2018 by PubMed, Embase, Wanfang, VIP and CNKI databases were searched comprehensively and systematically. The sensitivity, specificity, and diagnostic odds ratio (DOR) of ROSIER in total population and subgroup analysis were pooled by using bivariate mixed effects model. Sensitivity analysis was used to evaluate the stability of the results. Deek funnel plot was utilized to evaluate publication bias. The clinical applicability of ROSIER was evaluated by Fagan Nomogram. Results A total of 28 studies incorporating 7 579 subjects were enrolled in this Meta-analysis. Meta-analysis in total population showed that the pooled sensitivity, specificity and DOR of ROSIER was 0.89 [95% confidence interval (95%CI) = 0.86-0.91, P = 0.00], 0.74 (95%CI = 0.67-0.80, P = 0.00) and 22.09 (95%CI =14.86-32.82, P = 0.00), respectively. Subgroup analysis of pooled sensitivity of ROSIER showed that Asian patients was significantly higher than European patients [0.89 (95%CI = 0.86-0.92) vs. 0.74 (95%CI = 0.66-0.82), P < 0.01], prospective study was significantly higher than retrospective study [0.89 (95%CI = 0.87-0.92) vs. 0.74 (95%CI = 0.61-0.88), P < 0.05], pre-hospital emergency was significantly higher than emergency department [0.87 (95%CI = 0.80-0.94) vs. 0.85 (95%CI = 0.81-0.90), P < 0.01], study with sample size ≤ 200 was significantly higher than study with sample size > 200 [0.88 (95%CI = 0.83-0.93) vs. 0.82 (95%CI = 0.76-0.88), P < 0.05], but there was no significant difference between different evaluators or different male to female ratio subgroups. Subgroup analysis of pooled specificity of ROSIER showed that European patients was significantly higher than Asian patients [0.81 (95%CI = 0.73-0.89) vs. 0.79 (95%CI = 0.73-0.85), P < 0.05], retrospective study was significantly higher than prospective study [0.88 (95%CI =0.78-0.97) vs. 0.79 (95%CI = 0.73-0.84), P < 0.05], pre-hospital emergency was significantly higher than emergency department [0.82 (95%CI = 0.73-0.91) vs. 0.79 (95%CI = 0.73-0.85), P < 0.01], emergency physicians was significantly higher than other medical workers [0.80 (95%CI = 0.74-0.86) vs. 0.79 (95%CI = 0.69-0.90), P < 0.05], study with sample size ≤ 200 was significantly higher than study with sample size > 200 [0.82 (95%CI = 0.76-0.89) vs. 0.78 (95%CI = 0.71-0.85), P < 0.05], but there was no significant difference between different male or female ratio subgroups. Sensitivity analysis showed that there was no significant change in pooled DOR before and after excluding each study, indicating that the results were stable. Funnel plot showed that there was a significant publication bias in the total population (P = 0.04), but there was no publication bias in the European population (P = 0.57) or the Asian population (P = 0.08). According to the results of the Fagan Nomogram, with the pretest probability of 50%, when ROSIER was positive, the probability of being diagnosed with stroke increased to 77%, and when ROSIER was negative, the probability of being diagnosed with non-stroke decreased to 13%. It was suggested that ROSIER had good applicability and high clinical diagnostic value. Conclusions ROSIER has high diagnostic sensitivity and specificity, and has high clinical diagnostic value. It is a valid stroke identification tool which can be widely used in Asian population, pre-hospital emergency and be utilized by trained medical worker.

To evaluate the prognostic value of early white blood cell count (WBC) in patient of acute paraquat poisoning. Methods The literatures about the studies on early WBC and prognosis after paraquat poisoning published in journals at home and abroad were searched. The Chinese literature database contained CNKI, VIP, Wanfang Database, and China Biomedicine Database (CBM), and the journals were limited to the core journals. The foreign language database included PubMed, Embase and Cochrane library clinical controlled trial database. The retrieval date was from the initial publication to April 22nd in 2019, without the limitation of languages. Two researchers independently extracted literature information, and the Newcastle-Ottawa Scale (NOS) was used to evaluate literature quality. The odds ratio (OR), sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic (SROC) were combined and analyzed through the Stata 15.0 software to evaluate the predictive value of early WBC after acute paraquat poisoning. Publication bias was analyzed by Deeks funnel graph. Results There were 7 retrospective studies and 1 prospective study in a total of 980 paraquat poisoning patients, 5 of them were English literatures, the others were Chinese literatures. There was no heterogeneity among the studies (I 2 = 43.5%, P > 0.05). The OR and its 95% confidence interval (95%CI) of the literature was combined through the fixed effect model. The Meta-analysis results were statistically significant (OR = 18.63, 95%CI = 13.63-25.48, P < 0.001), suggesting that the WBC was significantly correlated with the mortality of patients. The combined sensitivity, specificity, PLR, NLR and DOR were 0.75 (95%CI = 0.66-0.82), 0.85 (95%CI = 0.80-0.90), 5.14 (95%CI = 3.86-6.86), 0.29 (95%CI = 0.22-0.39), 17.53 (95%CI = 12.23-25.13) respectively, and the area under the SROC of the WBC was 0.88 (95%CI = 0.85-0.91). Deeks funnel plot was symmetrical (P = 0.21), and there was no obvious publication bias. Conclusion The early WBC has a certain predictive value for the prognosis of acute paraquat poisoning patients.

Objective To investigate the protective effect of complement 5a receptor 1 (C5aR1) antagonist on ascending urinary tract infection in mice.Methods (1) Female C57BL/6 mice were randomly divided into experimental and control groups:38 mice in each group,and inoculated with E.coli by urethral catheterization to set up the ascending urinary tract infection model.C5aR1 antagonist (W54011 or PMX53) and corresponding control (PBS or control peptide) were initially given either at 2 h before or 3 h after infection by intraperitoneal injection.Mice were sacrificed to assess the infection in bladder and kidney at 24 or 48 h after infection.The bacterial load of bladder and kidney tissue was measured by agar plate assay.The mRNA expression of renal inflammatory factors was detected by real-time RCR.The renal tissue injury and inflammatory cell infiltration were assessed by HE staining and pathological scores.(2) Primary cultured renal tubular epithelial cells were randomly divided into antagonist and control groups to detect and compare the bacterial adhesion to renal tubular epithelial cells in vitro.Results Compared with control groups,the initial delivery of C5aR1 antagonist (W54011 or PMX53) before E.coli inoculation reduced the bacterial load in bladder and kidney tissue 48 h after infection (all P ＜ 0.01).In experimental group given W54011 before infection,the renal pathological scores were reduced (both P ＜ 0.05),as well as renal inflammatory factor expressions:CXCL-1 mRNA,IL-6 mRNA and TNF-o mRNA (all P ＜ 0.05).Compared with corresponding control groups,the initial delivery of PMX53 after E.coli inoculation could also reduce the bacterial load in bladder and kidney tissue 48 h after infection (both P ＜ 0.01).Furthermore,C5aR1 antagonists W54011 and PMX53 could decrease bacteria adhesion to renal tubular epithelial cells in vitro,compared with control groups (both P ＜ 0.05).Conclusions C5aR1 antagonists can significantly attenuate renal tissue injury,ameliorate renal inflammation and the adhesion of bacteria to renal epithelial cells.C5aR1 may be an effective target for the prevention and treatment of urinary tract infection.

Objective To evaluate the effect of levosimendan on prognosis and circulation disorders of sepsis patients. Methods With the guidance of these following Chinese or English key words, such as sepsis, severe sepsis, septic shock, simendan, levosimendan, etc., some of Chinese and foreign published literatures on randomized controlled trials (RCTs) concerning the effects of levosimendan on the prognosis and circulatory function of septic patients were searched through China National Knowledge Infrastructure (CNKI) internet, VIP and Wanfang Databases, China Biomedicine Database (CMB), Pubmed in American National library, Holland Medical Abstract Database (Embase), Cochrane Library, etc databases, from the creation of above various databases to May 2017. The quality of the collected RCTs was evaluated by modified Jadad score; Revman 5.3 software was used to carry out Meta analysis; the publication bias was assessed by the funnel plots. Results A total of 18 RCTs, 9 in Chinese and 9 in English, but only half of the literatures were of high quality, and the other 9 of low quality, containing 688 cases in control group and 704 cases in experimental group were ultimately enrolled in this analysis. The Meta analyses showed that there was no statistical significant difference in the mortality between the experimental group and the control group [relative risk (RR) = 0.92, 95% confidence interval (95%CI) = 0.80 - 1.06, P = 0.27]; compared with control group, the time of stay in ICU was shortened [mean difference (MD) = -2.02, 95%CI = -2.90 to -1.13, P < 0.000 01], cardic output index was increased (MD = 0.63, 95%CI = 0.39 - 0.87, P < 0.000 01), and blood lactate level was decreased (MD = -1.37, 95%CI = -1.51 to-1.23, P < 0.000 01) in the experimental group, being significantly improved after levosimendan therapy. The funnel map evaluation showed that there might be a certain bias in the publication of the literature. Conclusion Levosimendan can improve circulatory disorders and reduce the time of stay in ICU for septic patients, but can not reduce their mortality.

Objective To investigate the status of cardiopulmonary resuscitation (CPR) in patients with sudden cardiac arrest (CA) in the emergency department. Methods A multicenter prospective observational study was conducted. The patients with CA admitted to 13 hospitals from 6 provinces in four different regions, including North China, Southern China, East China, Southwest China, from July 1st, 2015 to July 31st, 2017 were enrolled. A modified Utstein template was applied to collect clinical data, including general data, CA related data and prognosis, and primary outcome indicator was the return of spontaneous circulation (ROSC) rate, and the secondary outcome indicator was 28-day survival rate. The influence factors of ROSC were screened by Logistic regression analysis. Results The data of 613 patients with CA in 13 hospitals were enrolled. The ROSC rate in Beijing and Guangdong Province was higher, but there was no significant difference in 28-day survival rate among hospitals from different provinces. ① In 613 patients with CA, there were 413 patients suffering from in-hospital cardiac arrest (IHCA, 67.4%), and 200 suffering from out-hospital cardiac arrest (OHCA, 32.6%). 208 patients had ROSC at least once (33.9%), only 20 patients survived within 28 days (3.3%). ROSC rate in IHCA patients was significantly higher than that in OHCA patients [37.3% (154/413) vs. 27.0% (54/200), P < 0.01]. There was no statistic difference in 28-day survival rate between patients with IHCA and OHCA. The patients received manual chest compression, electric defibrillation, or epinephrine ≤ 4 mg had higher ROSC rate, but 28-day survival rate showed no significant difference. Multivariate Logistic regression analysis showed that IHCA [odds ratio (OR) = 1.893, 95% confidence interval (95%CI) = 1.253-2.858, P = 0.002], manual chest compression (OR = 0.506, 95%CI = 0.348-0.736, P = 0.000), electric defibrillation (OR = 0.458, 95%CI = 0.300-0.699, P = 0.000), and total adrenalin ≤ 4 mg (OR = 0.317, 95%CI = 0.216-0.464, P = 0.000) were the protective factors of ROSC in CA patients. ② In 200 OHCA patients, there were 49 patients had ROSC (24.5%), only 5 patients survived (2.5%). The patients aging < 65 years, with witnesses of CPR, received manual chest compression, electric defibrillation, or epinephrine ≤ 4 mg had higher ROSC rate, and the ROSC rate was higher in ambulances than that at home and in public sites, but 28-day survival rate showed no significant difference. Multivariable Logistic regression analysis showed that age < 65 years old (OR = 2.749, 95%CI = 1.192-6.336, P = 0.018), manual chest compressions (OR = 0.196, 95%CI =0.072-0.535, P = 0.001), electric defibrillation (OR = 0.263, 95%CI = 0.108-0.641, P = 0.003), total adrenaline dose ≤4 mg (OR = 0.122, 95%CI = 0.049-0.303, P = 0.000) and the ambulance CA (OR = 2.441, 95%CI = 1.334-4.468, P = 0.004) were protective factors of ROSC in OHCA patients. Conclusions The survival of sudden CA in emergency department was still poor. Early electric defibrillation, manual chest compression, CA occurred in hospital or in ambulance, and witness CPR can improve the ROSC rate of CA patients. Excessive use of adrenaline is not beneficial to patients with CA. Clinical Trial Registration Clinical Trials, NCT01987245.