Objective To investigate the long non-coding RNA(lncRNA) MRAK08838 regulates macrophage function to influence the development of asthmatic airway inflammation. Methods MRAK088388 gene knockout (MRAK088388^-/-) mouse model was prepared and allergic asthma was induced by dust mite protein Dermatophagoides farinae 1 (Der f1). The mice were sacrificed after 28 days of modeling, and serum was collected to measure IgE and IgG. The FinePointe RC system was used to measure airway hyperresponsiveness and evaluate lung function in mice. Lung tissue was taken for HE staining, and periodic acid-Schiff (PAS) staining was used to evaluate inflammatory infiltration and mucus secretion in mouse lungs. Fluorescence quantitative PCR was used to detect the expression level of lncRNA MRAK08838 in bronchoalveolar lavage fluid (BALF) cells and lung tissue of asthmatic mice. ELISA was used to detect the levels of inflammatory cytokines IFN-γ, IL-4, IL-5, IL-13, IL-10 and IL-17A. Flow cytometry was used to evaluate the phenotype of macrophages in BALF and lung tissue, as well as the proportion of neutrophils, eosinophils, and alveolar macrophages. The changes of the above indicators were detected in mice by adoptive transfer of bone marrow-derived macrophages (BMDM). Results Under the challengle of Der f1, MRAK088388^-/- mice showed reduced allergic airway inflammation, including reduced eosinophils in BALF and reduced production of IgE and IgG1. In addition, Der f1-treated MRAK088388^-/- mice had fewer M2 macrophages than wild-type asthmatic mice. Wild-type mouse BMDM (M0) and Der f1-treated MRAK088388^-/- mice also showed mild inflammatory response. Conclusion Knockout of MRAK088388 alleviates airway inflammation in asthmatic mice by inhibiting M2 polarization of airway macrophages.
Animals ; Mice ; Mice, Knockout ; RNA, Long Noncoding/genetics* ; Asthma/genetics* ; Macrophages ; Immunoglobulin E

【Objective】 To investigate the association between the long-stranded non-coding ribonucleic acid (lncRNA) MRAK088388 and allergic asthma in children. 【Methods】 A total of 15 healthy children and 15 children with asthma were monitored for disease progression over a 2-year period. Blood samples were collected from patients during the chronic phase of the disease for lncRNA/mRNA expression microarray analysis. Competing endogenous RNA networks (MRAK088388/miR-30a/ATG5) were identified by bioinformatics analysis. In vitro cultured bronchial epithelial (16HBE) cells were used to quantify gene and associated protein expression levels by real-time fluorescent quantitative polymerase chain reaction (qPCR) and protein blotting, respectively. Cell Counting Kit-8 and transwell assays were used to assess the proliferation and migration of 16HBE cells and verify the effects of MRAK088388, miR-30a and ATG5 on asthma. 【Results】 Six lncRNA-miRNA-mRNAs were identified by correlation analysis. By qRT-PCR analysis, MRAK088388/miR-30a/ATG5 was selected to construct the ceRNA network in this study. mRAK088388 and ATG5 expressions were high in the peripheral blood of children with asthma, while the expression of miR-30a was low (P<0.05). The expression level of E-cadherin was significantly higher in 16HBE cells after si-MRAK088388+TGF-β1 group, while the expression levels of Vimentin and α-SMA were significantly lower (P<0.05), indicating that knockdown of MRAK088388 inhibited the epithelial mesenchymal transition in 16HBE cells. Compared with si-NC+ TGF-β1 group, the cell morphology of si-MRAK088388+TGF-β1 group was similar to that of the control group, indicating that MRAK088388 knockdown attenuated TGF-β1-induced cell morphological changes; in addition, MRAK088388 knockdown inhibited TGF-β1-induced proliferation and migration of 16HBE cells. MRAK088388 was confirmed by qPCR and protein blotting to promote the progression of childhood asthma by targeting the miR-30a/ATG5 axis. 【Conclusion】 Childhood asthma is associated with the MRAK088388/miR-30a/ATG5 axis, and MRAK088388 is involved in the process of childhood allergic asthma by negatively regulating miR-30a expression and regulating elevated ATG5 expression levels to affect bronchial epithelial cell mesenchymal transition, proliferation, and migration.

BACKGROUND: Although previous studies have shown that meteorological factors such as temperature are related to the incidence of bacillary dysentery (BD), researches about the non-linear and interaction effect among meteorological variables remain limited. The objective of this study was to analyze the effects of temperature and other meteorological variables on BD in Beijing-Tianjin-Hebei region, which is a high-risk area for BD distribution. METHODS: Our study was based on the daily-scale data of BD cases and meteorological variables from 2014 to 2019, using generalized additive model (GAM) to explore the relationship between meteorological variables and BD cases and distributed lag non-linear model (DLNM) to analyze the lag and cumulative effects. The interaction effects and stratified analysis were developed by the GAM. RESULTS: A total of 147,001 cases were reported from 2014 to 2019. The relationship between temperature and BD was approximately liner above 0 °C, but the turning point of total temperature effect was 10 °C. Results of DLNM indicated that the effect of high temperature was significant on lag 5d and lag 6d, and the lag effect showed that each 5 °C rise caused a 3% [Relative risk (RR) = 1.03, 95% Confidence interval (CI): 1.02-1.05] increase in BD cases. The cumulative BD cases delayed by 7 days increased by 31% for each 5 °C rise in temperature above 10 °C (RR = 1.31, 95% CI: 1.30-1.33). The interaction effects and stratified analysis manifested that the incidence of BD was highest in hot and humid climates. CONCLUSIONS This study suggests that temperature can significantly affect the incidence of BD, and its effect can be enhanced by humidity and precipitation, which means that the hot and humid environment positively increases the incidence of BD.
Beijing/epidemiology* ; China/epidemiology* ; Dysentery, Bacillary/epidemiology* ; Humans ; Humidity ; Temperature

Objective : To study the effect of ubiquinol⁃cytochrome C reductase subunit 2 (QCR2) on cell cycle arrest of cervical cancer SiHa cell line , and to explore related mechanisms. Methods : The log⁃phase SiHa cells were taken , and QCR2 siRNA and control siRNA were transfected into SiHa cells by liposome transfection , which were set as QCR2 siRNA group and control siRNA group , and untreated cells were set as a blank group. qRT⁃PCR and Western blot were used to determine the relative expression of QCR2 , p53 mRNA and protein. Propidium iodide(PI) staining was used to determine cell cycle. The cells in the QCR2 siRNA group were taken , and were intervened with a final concentration of 50 nmol/L ubiquitin⁃proteasome inhibitor PS341 as the QCR2 siRNA + PS341 group. In addition , the cells in the QCR2 siRNA group were intervened with the same amount of normal saline (NS) and set as the QCR2 siRNA + NS group. Western blot was used to determine the relative expression of p53 protein. The immunoprecipitation test was used to determine the level of p53 ubiquitination. Results : Observed under a fluorescence microscope , the transfection efficiency of QCR2 siRNA group and control siRNA group were both > 80% . Compared with the blank group and control siRNA group , the relative expression of QCR2 mRNA and protein in the QCR2 siRNA group decreased (P < 0. 05) , the proportion of G0/G1 increased (P < 0. 05) , and the proportion of S , G2/M decreased (P < 0. 05) . There was no significant difference in the relative expression of p53 mRNA between the groups. Compared with the blank group and control siRNA group , the relative expression of p53 protein in the QCR2 siRNA group increased (P < 0. 05) . Compared with the blank group and QCR2 siRNA + PS341 group , the relative expression of p53 protein in the QCR2 siRNA group and QCR2 siRNA + NS group increased (P < 0. 05) . Compared with the blank group and control siRNA group , the degree of p53 ubiquitination in the QCR2 siRNA group was reduced ( P < 0. 05 ) . Conclusion Silencing QCR2 can block SiHa cells in G0/G1 phase. Its mechanism may be related to the inhibition of p53 ubiquitination and the increase of its protein expression.

OBJECTIVE To provide reference for improving the professional identity of clinical pharmacists and the quality of pharmaceutical care ，and promoting the effects of clinical pharmaceutical intervention. METHODS A questionnaire survey was conducted among clinical pharmacists in secondary and tertiary hospitals in 31 provinces（autonomous regions and municipalities ） in 2019 by stratified semi-random sampling. Through descriptive analysis of survey data ，their job satisfaction status was evaluated ； χ 2 test and Logistic regression analysis were used to analyze the influential factors of job satisfaction ；the robustness test of study results by propensity score matching method and replacement regression model ，and grouping Logistic regression of samples from hospital on different levels. Targeted improvement measures were put forward according to the results of survey . RESULTS There was statistical significance in the difference of job satisfaction among pharmacists of different professional titles （P＜0.05）. Results of Logistic regression showed that whether to participate in standardized training ，whether to obtain communication and support from patients ，whether the pharmaceutical management rules and regulations were sound ，whether to set up economic compensation means such as pharmaceutical service fee ，whether to work overload ，and whether to smoothly perform pharmaceutical care duties were significant influential factors for job satisfaction of clinical pharmacists （P＜0.05）. These results showed good robustness as tested by propensity score matching method and replacement regression model. Heterogeneity analysis results showed that the job satisfaction of clinical pharmacists in tertiary hospitals was more significantly affected by economic compensation ，while clinical pharmacists in secondary hospitals were more concerned about training opportunities and workload conditions （P＜0.05）. CONCLUSIONS The job satisfaction level of Chinese clinical pharmacists remains to be improved. Accordingly ，it is compulsory to continue the promotion of standardized training courses ，consummate the pharmaceutical management system ，and fair remuneration structure in order to improve the job satisfaction of clinical pharmacists and build a high-level clinical pharmacist team.

Objective:To compare the immune responses to simply mixed and fused recombinant DNA vaccines of herpes simplex virus type 2 glycoprotein D (HSV-2 gD) and molecular adjuvant CCL19 in mice and to evaluate the protective effects.Methods:Gene recombination technology was used to construct recombinant DNA vaccines expressing HSV-2 gD and CCL19 alone or fused together. After verification by sequencing, Western blot and ELISA, BALB/c mice were immunized twice by intramuscular injection. Serum samples and vaginal lavage fluids were collected regularly after immunization. Splenocytes, mesenteric lymph node cells and rectal tissues were collected after immunization. Differences in humoral and cellular immune responses to the two forms of vaccines and their protective effects in mice were analyzed using end-point ELISA, in vitro neutralization assay, immunohistochemical staining, chemotaxis assay, vaginal virus challenge, fluorescence quantitative PCR, weighing and disease severity assessment. Results:The fused recombinant pgD-IZ-CCL19 plasmid could express gD protein and CCL19 protein in vitro, but the level of expressed CCL19 protein by pCCL19-IZ-gD plasmid was less than that by pgD-IZ-CCL19. The mice immunized with pgD-IZ-CCL19 showed higher levels of IgG in sera and IgA in vaginal lavage fluids ( P<0.01) and stronger neutralization ability than the mice vaccinated with pgD+ pCCL19. Compared with other groups, more lymphocytes were recruited in the rectal mucosa, the spleen and mesenteric lymph nodes of mice immunized with pgD-IZ-CCL19. Weight loss or disease symptoms were not observed in the pgD-IZ-CCL19 group after virus challenge. In addition, the positive rate of HSV-2 in vaginal mucosa and the mortality rate in the pgD-IZ-CCL19 group were the lowest. However, pCCL19-IZ-gD turned out ineffective in preventing HSV-2 infection. Conclusions:The fused recombinant DNA vaccine pgD-IZ-CCL19 could induce stronger immune responses in mice and provide better protective effects, which was superior to the simply mixed DNA vaccine.

Objective: To analyze associated factors of HIV infection among college students who are young men and have sex with men (YMSM) in Tianjin, providing reference for HIV prevention and control among YMSM college students. Methods: During Aug. 1st, 2018 to Dec. 31st, 2018, SHENLAN recruited college students who were YMSM aged 18-24 years from gay baths, gay bars, QQ, WeChat and gay dating app BLUED. HIV infection status and associated factors (general demographic characteristics, unsafe sexual behaviors, addictive substance using, basic knowledge of HIV) was collected and analyzed. Results: A total of 470 college students, including 21 HIV infected (4.47%), were enrolled in this study. Univariate Logistic regression analyses indicated that age, age at first sex behavior, HIV related knowledge, tobacco use, recreational drug usage, syphilis infection was associated with HIV infection among YMSM students (P<0.05). Multivariate analysis found age of first sex (OR=21.20，95%CI=3.09-145.43), recreational drug use (OR=5.07，95%CI=1.77-14.48), lack of HIV related knowledge (OR=3.38，95%CI=1.33-8.63)were associated with HIV infection (P<0.05). Conclusion College students who are YMSM in Tianjin have a high rate of HIV infection, who deserves further attention. Targeted campus HIV/AIDS prevention program should be developed combined with specific characteristics of this population.

Objective: To observe the clinical effects of stage-Ⅱ Meek skin grafting on adipose tissue after tangential excision in patients with extensive deep burns, and to explore the functional mechanism. Methods: The medical records of 26 extensively burned patients who met the inclusion criteria and were admitted to the Department of Burns and Plastic Surgery of the Fourth Medical Center of PLA General Hospital from May 2015 to December 2017 were retrospectively analyzed. According to the treatment methods, 14 patients were enrolled in stage-Ⅰ skin grafting group (10 males and 4 females, aged 27 to 75 years), and 12 patients were enrolled in stage-Ⅱ skin grafting group (10 males and 2 females, aged 31 to 76 years). Patients in the 2 groups all underwent debridement of tangential excision, and their healthy adipose tissue was preserved. Meek skin grafting was performed just after tangential excision in patients in stage-Ⅰ skin grafting group. In patients in stage-Ⅱ skin grafting group, porcine acellular dermal matrix (ADM) was applied to cover the wound after tangential excision, and 3 days later, it was removed and Meek skin grafting was performed. The times of complement skin grafting and the wound basic healing time of patients in the 2 groups were observed and recorded. In the stage-Ⅱ skin grafting group, the adipose tissue of patients were taken from the wound center immediately after tangential excision and immediately after the removal of porcine ADM, for the observation of structure of the fault surface of adipose tissue through hematoxylin and eosin staining and microvessel density (MVD) through immunohistochemical staining. Data were processed with independent sample t test and Fisher′s exact probability test. Results: (1) The times of complement skin grafting of patients in stage-Ⅱ skin grafting group was (1.83±0.17) times, which was obviously less than (3.36±0.63) times in stage-Ⅰ skin grafting group (t=2.19, P<0.05). The wound basic healing time of patients in stage-Ⅱ skin grafting group was (35.1±2.3) d, which was obviously shorter than (48.8±4.9) d in stage-Ⅰ skin grafting group (t=2.27, P<0.05). (2) Immediately after tangential excision, the intercellular substance was few between the adipose cells in adipose tissue of patients in stage-Ⅱ skin grafting group. Immediately after the removal of porcine ADM, there was regenerated granulation tissue in the intercellular space of adipose cells of adipose tissue of patients in stage-Ⅱ skin grafting group. Immediately after tangential excision, the MVD of adipose tissue of patients in stage-Ⅱ skin grafting group was 20.2±1.3 under per 400-time field, which was obviously less than 32.2±1.9 under per 400-time field immediately after the removal of porcine ADM (t=-5.38, P<0.01). Conclusions Meek skin grafting on the adipose tissue in stage-Ⅱ surgery after tangential excision could reduce the times of complement skin grafting and shorten wound healing time of patients with extensive deep burns. The mechanism may be related to the improvement of the recipient condition of adipose tissue.

Objective To study the effect and mechanism of dexmedetomidine combined with sufentanil on postoperative analgesia in elderly patients with abdominal surgery. Methods Ninety-six elderly patients having undergone abdominal surgery in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to June 2017 were enrolled, and they were divided into a control group and an observation group by random number table method, 48 cases in each group. General anesthesia was performed in the operation, and after surgery venous analgesic pump was used for analgesia in both groups. Analgesic method: the control group was given sufentanil 2 μg/kg and tropisetron 5 mg; the observation group was given dexmedetomidine 2 μg/kg, sufentanil 2 μg/kg and tropisetron 5 mg. The changes of pain and sedation score, conventional indexes [systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory rate (RR), pulse blood oxygen saturation (SpO2)], oxidative damage indexes [lipid peroxide (LPO), glutathione peroxidase (GSH-Px), Cu-Zn superoxide dismutase (Cu-Zn SOD)], stress response indexes [cortisol (Cor), epinephrine, norepinephrine (NE)], platelet activation indexes granule membrane protein-140 (GMP-140), thromboxane A2(TXA2) and the incidence of adverse reactions were observed in both groups. Results ① After surgery the visual simulation score (VAS) and Ramsay score in both groups were higher than those before surgery, and showed a tendency firstly increased and then decreased, and reached to peak value 2 hours after operation [VAS score:the control group was 3.24±0.98 vs. 1.95±0.93, observation group was 3.19±1.03 vs. 1.98±0.95; Ramsay score:the control group was 3.26±0.51 vs. 1.90±0.45, observation group was 3.77±0.53 vs. 1.92±0.42], began to decline 6 hours after operation, reached to valley value 48 hours after operation, and there was no significant difference in VAS scores between the two groups (2.02±0.64 vs. 1.98±0.95), Ramsay score was significantly higher in observation group than that in control group (2.59±0.41 vs. 2.10±0.21). ② Since 2 hours after the operation, the SBP, DBP, HR and RR in the observation group began to be lower than those in control group, 12 hours after surgery their values reached their valleys [SBP (mmHg, 1 mm Hg = 0.133 kPa): 113.2±13.5 vs. 122.1±10.3, DBP (mmHg): 67.5±9.9 vs. 76.4±8.6, HR (bpm): 64.5±6.9 vs. 71.4±7.5, RR (bpm): 14.8±1.1 vs. 15.8±0.8, all P < 0.05]; while SpO2did not change a great deal. ③ LPO, Cor, epinephrine, NE, GMP-140, TXA2of two groups after operation were higher than those before operation, GSH-Px and Cu-Zn SOD were lower than those before operation. However, LPO, Cor, epinephrine, NE, GMP-140, TXA2in observation group were significantly lower than those in control group [LPO (μmol/L): 6.4±0.8 vs. 9.8±1.1, Cor (ng/L): 148.2±19.1 vs. 239.3±27.8, epinephrine (μg/L): 124.2±13.9 vs. 207.1±23.5, NE (μg/L): 109.2±14.8 vs. 183.3±21.6, GMP-140 (μg/L): 27.13±3.82 vs. 39.06±4.83, TXA2(ng/L): 422.30±53.74 vs. 610.43±73.21, all P < 0.05], GSH-Px and Cu-Zn SOD in observation group were significantly higher than those in the control group [GSH-Px (U/L): 426.7±58.7 vs. 307.9±51.2, Cu-ZnSOD (μg/L): 311.3±42.5 vs. 231.6±34.1, all P < 0.05].④ The incidence of adverse reaction nausea in the observation group was significantly lower than that in the control group [4.17% (2/48) vs. 37.5% (18/48)]. Conclusion Dexmedetomidine combined with sufentanil used in elderly patients after abdominal surgery has significant analgesic effect, can effectively inhibit platelet activation, and decrease the contents of GMP-140 and TXA2.

Objective To investigate the effects of ginsenoside Rb1 pretreatment on the expression of brain derived neurotrophic factor (BDNF) in hippocampus of rat models under acute immobilization stress.Methods Eighteen Sprague-Dawley (SD) rats were randomly divided into three groups (each n =6):normal control group,acute immobilization stress model group,and ginsenoside Rbl group.The rats in acute immobilization stress model group and ginsenoside Rb1 group were exposed to acute immobilization for 2 hours.Thirty minutes before the modeling,ginsnoside Rb1 (40 mg/kg) was injected intraperitoneally into rats in the ginsenoside Rbl group,and the control group was not treated.The enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of plasma cortisol (CORT) and adrenocorticotropic hormone (ACTH).The real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of BDNF mRNA in rat hippocampus and its expression of BDNF protein was measured by Western Blot.Results In acute immobilization stress model group,compared with those before modeling,the plasma CORT and ACTH concentrations were significantly higher after modeling [CORT (μg/L):3.79 ± 0.50 vs.2.06 ± 0.35,ACTH (μg/L):1.69 ± 0.12 vs.0.94 ± 0.12,both P ＜0.05];compared with the normal control group,the mRNA and protein expressions of BDNF in hippocampus in the acute immobilization stress model group were decreased significantly [BDNF mRNA (A value):42.87 ± 5.56 vs.109.39 ± 9.11,BDNF protein (grey value):0.94 ± 0.02 vs.1.02 ± 0.03,both P ＜ 0.01];compared with acute immobilization stress model group,the mRNA (113.73 ± 6.24 vs.42.87 ± 5.56) and protein expressions (1.04 ± 0.02 vs.0.94 ± 0.02) of BDNF in hippocampus of pre-treatment groups were significantly higher (all P ＜ 0.05).Conclusions The results suggest that pretreatment with ginsenoside Rb1 alleviate hippocampus lesion induced by acute immobilization stress through regulating the BDNF mRNA and protein expressions in hippocampus.