AIM:To investigate the therapeutic effect of recombinant human interleukin-37(rhIL-37)inter-vention on extracellular matrix deposition in human bronchial epithelial cells exposed to fine particulate matter(PM2.5),and to explore the underlying mechanisms.METHODS:An airway injury cell model was established using normal human bronchial epithelial 16HBE cells treated with various concentrations(6.25,12.5,25 and 50 mg/L)of PM2.5.Western blot and immunofluorescence were employed to assess the expression level of Wnt family member 5a(Wnt5a).The con-centration of PM2.5 that maximized Wnt5a expression was identified as the optimal concentration for further analysis.The cells were divided into 3 groups,PM2.5+siRNA,PM2.5+Wnt5a siRNA and control+Wnt5a siRNA,to evaluate the expres-sion of fibronectin,the secretion of IL-6 and IL-1β,and the production of reactive oxygen species(ROS).A subsequent set of experiments was organized into PM2.5+rhIL-37,PM2.5 and control groups to determine whether rhIL-37 down-regu-lates the expression of Wnt5a and fibronectin,and reduces the secretion of IL-6 and IL-1β.RESULTS:(1)After 24 h of exposure to various concentrations of PM2.5,the expression of Wnt5a in 16HBE cells was significantly elevated,except at 50 mg/L,compared with control group(P＜0.05).The highest Wnt5a expression was observed at 12.5 mg/L PM2.5(P＜0.01).(2)Fibronectin expression peaked after 24 h of exposure to PM2.5 at 12.5 mg/L(P＜0.01).(3)Successful knock-down of Wnt5a resulted in decreased levels of fibronectin and nuclear factor E2-related factor(Nrf2).Additionally,the production of ROS and the secretion of IL-6 and IL-1β were significantly reduced compared with control group(P＜0.01).(4)The administration of rhIL-37 before PM2.5 exposure led to decreased levels of Wnt5a,fibronectin and Nrf2 compared with PM2.5 group(P＜0.05).Furthermore,rhIL-37 treatment reduced the ROS production and the secretion of IL-6 and IL-1β(P＜0.05).CONCLUSION:In vitro cell models demonstrate that PM2.5 can induce extracellular matrix deposition in bronchial epithelial cells,potentially through the modulation of inflammatory response and oxidative stress influenced by Wnt5a.Additionally,rhIL-37 appears to mitigate inflammatory response and oxidative stress by down-regulating Wnt5a.

AIM:To investigate the therapeutic effect of recombinant human interleukin-37(rhIL-37)inter-vention on extracellular matrix deposition in human bronchial epithelial cells exposed to fine particulate matter(PM2.5),and to explore the underlying mechanisms.METHODS:An airway injury cell model was established using normal human bronchial epithelial 16HBE cells treated with various concentrations(6.25,12.5,25 and 50 mg/L)of PM2.5.Western blot and immunofluorescence were employed to assess the expression level of Wnt family member 5a(Wnt5a).The con-centration of PM2.5 that maximized Wnt5a expression was identified as the optimal concentration for further analysis.The cells were divided into 3 groups,PM2.5+siRNA,PM2.5+Wnt5a siRNA and control+Wnt5a siRNA,to evaluate the expres-sion of fibronectin,the secretion of IL-6 and IL-1β,and the production of reactive oxygen species(ROS).A subsequent set of experiments was organized into PM2.5+rhIL-37,PM2.5 and control groups to determine whether rhIL-37 down-regu-lates the expression of Wnt5a and fibronectin,and reduces the secretion of IL-6 and IL-1β.RESULTS:(1)After 24 h of exposure to various concentrations of PM2.5,the expression of Wnt5a in 16HBE cells was significantly elevated,except at 50 mg/L,compared with control group(P＜0.05).The highest Wnt5a expression was observed at 12.5 mg/L PM2.5(P＜0.01).(2)Fibronectin expression peaked after 24 h of exposure to PM2.5 at 12.5 mg/L(P＜0.01).(3)Successful knock-down of Wnt5a resulted in decreased levels of fibronectin and nuclear factor E2-related factor(Nrf2).Additionally,the production of ROS and the secretion of IL-6 and IL-1β were significantly reduced compared with control group(P＜0.01).(4)The administration of rhIL-37 before PM2.5 exposure led to decreased levels of Wnt5a,fibronectin and Nrf2 compared with PM2.5 group(P＜0.05).Furthermore,rhIL-37 treatment reduced the ROS production and the secretion of IL-6 and IL-1β(P＜0.05).CONCLUSION:In vitro cell models demonstrate that PM2.5 can induce extracellular matrix deposition in bronchial epithelial cells,potentially through the modulation of inflammatory response and oxidative stress influenced by Wnt5a.Additionally,rhIL-37 appears to mitigate inflammatory response and oxidative stress by down-regulating Wnt5a.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

Objective:To evaluate the role of aryl hydrocarbon receptor (AhR) in the down-regulation of Clara cell secretory protein (CCSP) expression during endotoxin-induced lung injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) using a random number table method: normal control group (group C), acute lung injury (ALI) group, ALI+ AhR antagonist group, and ALI+ vehicle group. Lipopolysaccharide(LPS) 1 mg/kg was intratracheally instilled to develop the model of lung injury, while the equal volume of normal saline was given instead in group C. At 2 h before LPS injection, AhR antagonist 6, 2′, 4′-trimethoxyflavone solution 5 mg/kg (diluted to 1 ml in dimethyl sulfoxide solution) was intraperitoneally injected in ALI+ AhR antagonist group, while dimethyl sulfoxide solution 1 ml was given in ALI+ vehicle group. The rats were sacrificed under anesthesia at 48 h after LPS administration. The left lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay, and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry. Results:Compared with group C, the expression of CCSP in the bronchial epithelium was significantly down-regulated, and the concentrations of CCSP in BALF were decreased in the other three groups ( P<0.05 or 0.01). Compared with ALI group and ALI+ vehicle group, the histopathological injury was significantly reduced, the expression of CCSP in the bronchial epithelium was up-regulated, and the concentrations of CCSP in BALF were increased in ALI+ AhR antagonist group ( P<0.01). Conclusions:AhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.

Objective To explore the association between malaria epidemic situation and some natural and social factors in high?incidence areas of Shandong Province,so as to provide evidences for malaria elimination in these areas. Methods Twenty towns of 10 counties(cities,districts,)in the high incidence areas of malaria in Shandong Province were selected as the study sites,and the residents in the study sites were investigated by questionnaires with one household as a unit,so as to understand the related natural and social factors. In addition,the malaria epidemic data in the study sites from 2006 to 2010 were collected, and the correlation between these factors and the epidemic situation of malaria was analyzed by Spearman rank correlation and multiple stepwise regression. Results The square root of malaria incidence rate(Y)was negatively related to the rate of house?holds using insecticide(X3),and the rate of households using screen doors and windows(X4)(both P<0.05),but was positive?ly related to the rate of housing surrounding water environment and exposure ratio(X6)(both P<0.05). The regression equa?tion established was Y=0.032X5+0.048X6-0.495,R2=0.973. Conclusions Malaria incidence is obviously associated with some natural and social factors. The measures such as clearing the breeding place of mosquito,protecting the exposure popula?tion at nightfall,as well as using door?window screen and repellents correctly,can effectively control malaria.

Objective To evaluate the effect of high-frequency chest well oscillation expectoration system on ventilator-associated pneumonia (VAP) and time for withdrawing mechanical ventilation (MV) system in ICU patients with invasive mechanical ventilation (IMV). Methods 100 ICU patients with IMV were divided into observationgroup (n = 50) and control group (n = 50). The high-frequency chest well oscillation expectoration was used in the former group and the mechanical vibration expectoration was used in the latter. The two groups were compared in terms of amount of sputum, vital signs (heart rate, breathing, systolic blood pressure and blood oxygen saturation), time for withdrawing MV system and VAP rate. Results On days 1, 2, 3, 4 and 5, the amount of sputum in the observationgroup was (33.5 ± 4.2)mL/d, (41.1 ± 3.0)mL/d, (38.2± 3 .5) mL/d, (34.8 ± 2.5) mL/d and (31.1 ± 2.1) mL/d, and those of the control group respectively was (27.4 ± 3.1) mL/d, (30.3 ± 3.6) mL/d, (28.1 ± 2.2) mL/d, (25.7±1.8)mL/d and (20.8 ± 1.7)mL/d. The differences between the two groups were statistically significant (P < 0.05). After sputum expectoration, the blood oxygen saturation of the observationgroup was significantly higher than the control group [(97.5 ± 0.9) vs. (95.2 ± 1.0)] (P <0.05), but there were no statistical differences in heart rate, breathing and systolic blood pressure (P > 0.05). The time for withdrawing MV system in the observationgroup and the control group respectively was (5.8 ± 2.2)d and (9.5 ± 1.8)d, (P < 0.05). The rates of VAP in the observationgroup and the control group respectively was 30.0% (15/50) and 52.0% (26/50), with significant difference between them (P < 0.05). Conclusion The high-frequency chest well oscillation expectoration for ICU patients with invasive mechanical ventilation can promote sputum expectoration , improve blood oxygen saturation , shorten the time for withdrawing the ventilator, and prevent the incidence of VAP.

Objective To understand the awareness status of malaria control knowledge of primary and secondary school stu-dents in malaria endemic areas of Shandong Province,so as to provide the baseline information for formulating the malaria control strategy. Methods A cross-sectional survey was conducted in 5 TypeⅡmalaria-endemic counties in Shandong Province. A struc-tured questionnaire survey was administrated to students in primary and secondary schools. Results A total of 1 884 students were completed with the questionnaires and all were effective. The total awareness rate of malaria control knowledge was 65.9%, and 54.7% of the students knew the transmission route of malaria and only 31.5% of the students were aware of the preventive methods of malaria. There were significant differences of the awareness scores of malaria control knowledge among different malar-ia endemic areas but there were no significant differences between the awareness rates of male and female students and between two different education levels. Conclusions The awareness of malaria control knowledge of primary and secondary school stu-dents in Shandong Province is poor;therefore,the health education of malaria control knowledge for primary and secondary school students should be strengthened.

Objective To understand the infection status of intestinal parasites and related knowledge and behavior factors of the residents in north-west Shandong Province,so as to provide the evidence for taking targeted preventive measures. Meth-ods Eighteen villages were randomly selected as survey spots by the stratified multi-stage sample method. The Kato-Katz tech-nique was used to detect intestinal parasite eggs among the residents and the cellophane tape anus test was used to detect Entero-bius vermicularis eggs among 3-12 years old children. Questionnaires were applied to investigate related knowledge and behavior factors about the intestinal parasite infections in the residents. Results Totally 6 366 residents were detected for intestinal para-sites and the infection rate was 0.28%(18 cases). Totally 895 children were detected for E. vermicularis and the infection rate was 5.70%(51 cases). Totally 2 915 residents were investigated by questionnaires and the awareness rate of knowledge about preventing parasitic diseases was 26.72%. The formation rates of washing hands before meal and after WC,washing fruit and vegetable before eating,never drinking unboiled water were 55.42%,42.87%,43.54%and 83.04%respectively. The aware-ness rate of knowledge about preventing parasitic diseases of 3-12 years old children was 12.24%;and the formation rates of washing hands before meal and after WC were 47.04%and 30.44%respectively. Conclusions The total infection rate of intesti-nal parasites is low but the E. vermicularis infection rate is high among children in north-west Shandong Province. The awareness rate of knowledge about preventing parasitic diseases and the formation rates of healthy behaviors are all low. Therefore ,the tar-geted health education should be taken to increase the awareness rate and guide the residents to develop their healthy behaviors.

Objective To understand the capacity of Plasmodium detection and helminth detection and the mastery degree of basic knowledge of parasitic diseases. Methods Three professionals from each city were selected as contestants. The content of the competition contained three parts. The first part included making blood slides and Giemsa staining of Plasmodium,and identifi-cation of species and number with microscopy,the second part included making stool slides with Kato-Katz technique and identifi-cation of common helminth eggs with microscopy,and the third part was basic knowledge of parasitic diseases. Results Totally 51 contestants took part in the competition. The average score of the test of making blood slides was 14.8±3.3,and the passing rate was 82.4%. The average score of the identification of species and number of Plasmodium with microscopy was 19.2 ± 9.3,and the passing rate was 29.4%. The average score of the test of making stool slides was 9.3±0.7,and the passing rate was 100%. The aver-age score of the identification of common helminth eggs with microscopy was 28.0±2.6,and the passing rate was 100%. The aver-age score of basic knowledge of parasitic diseases was 76.3±11.9,and the passing rate was 88.2%. The average score of the test of making blood slides in the female was higher than that in the male(15.7vs.13.5,P<0.05),and the average score of the test of making blood slides in the intermediate title contestants was higher than that in the junior title contestants(16.1vs.14.1,P <0.05). The average score of the basic knowledge of parasitic diseases in the contestants from cities was higher than that in the con-testants from towns(83.2vs.72.6,P<0.05),and the average score of basic knowledge of parasitic diseases in the contestants from high economic level cities was higher than that in the contestants from low economic level cities(82.4vs.71.5,P<0.01). Conclu-sions For professionals in Shandong Province,the capacity of helminth detection was strong and the basic knowledge of parasitic diseases was mastered well,while the capacity of Plasmodium detection was weak.

Objective To understand the malaria situation of Shandong Province in 2013,so as to provide the evidence for formulating targeted prevention and control strategy and measures. Methods The data of malaria cases of Shandong Province in 2013 were collected from the Information Management System for Infectious Diseases Report and Information Management Sys-tem for Parasitic Diseases Control and Prevention. The data of epidemiological characteristics of malaria situation and the diagno-sis and treatment of malaria cases were analyzed by Microsoft Excell2007. Results There were 131 malaria cases reported in 2013,all of them were imported cases,and 127 cases(96.95%)were imported from African countries. A total of 116 cases (88.55%)were falciparum malaria cases. Totally 97.71%of the cases were male and the average age of malaria cases was 39 years. A total of 61.83%of the cases were peasants and 65.65%of the cases only received junior high school education. The dis-tribution of malaria cases was concentrated in Tai’an City(32 cases),Yantai City(19 cases)and Weihai City(17 cases),total-ly acounting for 53.13%. There was no significant seasonal variation in the reporting time of the cases. The median time from on-set to seeing doctor was four days and the median time from seeing doctor to being diagnosed was one day. Totally 35.88%of the cases were misdiagnosed when the first visit to a doctor. All of the cases were laboratory confirmed and 100%of them received the standard treatment after diagnosis. Conclusions All of the malaria cases were imported cases in Shandong Province in 2013. To control the imported malaria in Shandong Province,it is necessary to further strengthen the multi-sectoral cooperation, health education,malaria screening and professional training.