A novel iheyamine A derivative L42 suppresses acute myeloid leukemia via dual regulation of the PI3K/AKT/FOXO3a axis and TNF signaling pathway.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies and the development of new drugs is crucial for the treatment of this lethal disease. Iheyamine A is a nonmonoterpenoid azepinoindole alkaloid from the ascidian Polycitorella sp., and its anticancer mechanism has not been investigated in leukemias. Herein, we showed the significant antileukemic activity of L42 in AML cell lines HEL, HL-60 and THP-1. The IC50 values were 0.466±0.099 µM, 0.356±0.023 µM, 0.475±0.084 µM in the HEL, HL-60 and THP-1 cell lines, respectively, which were lower than the IC50 (2.594±0.271 µM) in the normal liver cell line HL-7702. Furthermore, L42 significantly inhibited the growth of peripheral blood mononuclear cells (PBMCs) from an AML patient. In vivo, L42 effectively suppressed leukemia progression in a mouse model induced by Friend murine leukemia virus (F-MuLV). Mechanistically, we showed that L42 induced cell cycle arrest and apoptosis in leukemia cell lines. RNA sequencing analysis of L42-treated THP-1 cells revealed that the differentially expressed genes (DEGs) were enriched in the cell cycle and apoptosis and predominantly enriched in the PI3K/AKT pathway. Accordingly, L42 decreased the expression of the phospho-PI3K (p85), phospho-AKT and phospho-FOXO3a. Docking and CETSA analysis indicated that L42 bound to the PI3K isoform p110α (PIK3CA), which was implicated in the suppression of the PI3K/AKT pathway. L42 was also shown to initiate the TNF signaling-mediated apoptosis. Moreover, L42 exhibited stronger anti-leukemia activity and sensitivity in IDH2-mutant HEL cells than in IDH2-wild-type control. In conclusion, L42 effectively suppresses cell proliferation and triggers apoptosis in AML cell lines in part through inhibition of the PI3K/AKT signaling pathway to restore FOXO3a expression and activation of the TNF signaling pathway. Thus, the iheyamine A derivative L42 represents a novel candidate for AML therapy.

Urea regulates soil nematode population by enhancing the nematode-trapping ability of nematode-trapping fungi.

As the most abundant animal in the soil, nematodes are directly or indirectly involved in almost all soil ecological processes. Studying soil nematode population regulation is essential to understanding soil ecological processes. This study found urea combines nematode-trapping fungi to regulate the population of soil nematodes. In soil, compared with no urea, adding 0.2 mg/mL urea after applying Arthrobotrys oligospora and Dactylellina ellipsospora reduced the number of nematodes by 34.7% and 31.7%. Further, the mechanism of urea couple nematode-trapping fungi to regulate the nematode population was explored in the medium environment. The results showed that the addition of 0.2 mg/ml urea accelerated the trap formation of A. oligospora and D. ellipsosporas by 50% and 46.5%, and increased the yield of traps of A. oligospora and D. ellipsosporas by 39.5% and 40.6%, thus, the predatory efficiency of A. oligospora and D. ellipsospora on nematodes was increased by 34.2% and 32.7%. In conclusion, urea regulates the predation ability of A. oligospora and D. ellipsosporas to regulate the soil nematode population. This study deepens the understanding of the regulatory pathways of the soil nematodes but also provides a potential new strategy for harmful nematode bio-control.

Diagnosis and treatment principles of liver injury induced by antithyroid drugs / 临床肝胆病杂志

Pharmacotherapy is the primary treatment method for hyperthyroidism. Antithyroid drugs can induce liver injury， and the diagnosis of drug-induced liver injury is mostly exclusive based on medical history collection， clinical symptoms， serum biochemistry， radiological examination， and histology. According to the severity of liver injury， drug-induced liver injury can be classified into mild， moderate， severe， and fatal degrees. Drug withdrawal may not be necessary for patients with mild liver injury， but regular monitoring of liver function is required； in severe cases， patients may develop liver failure， which may lead to a mortality rate， and early identification， timely drug withdrawal， and reasonable pharmacotherapy can help to avoid fatal consequences. The treatment principles of liver injury induced by antithyroid drugs include promoting the recovery of liver injury， preventing the severe exacerbation and chronicity of liver injury， and reducing the risk of death. Standardized medication， timely monitoring， early identification， and early treatment are important measures for the prevention and treatment of liver injury induced by antithyroid drugs.

Ozone therapy for high-grade glioma: an overview.

High-grade gliomas (grades III and IV) are highly malignant and aggressive brain tumors that present significant treatment challenges. Despite advances in surgery, chemotherapy, and radiation therapy, the prognosis for patients with glioma remains poor, with a median overall survival (mOS) range of 9-12 months. Therefore, exploring new and effective therapeutic strategies to improve glioma prognosis is of utmost importance and ozone therapy is a viable option. Ozone therapy has been used in various cancers, such as colon, breast, and lung, yielding significant results in preclinical studies and clinical trials. Only a few studies have been conducted on gliomas. Furthermore, since the metabolism of brain cells involves aerobic glycolysis, ozone therapy may improve the oxygen condition and enhance glioma radiation treatment. However, understanding the correct ozone dosage and optimal time of administration remains challenging. Herein, we hypothesize that ozone therapy should be more effective in gliomas compared with other tumors. This study provides an overview of the use of ozone therapy in high-grade glioma, including mechanisms of action, preclinical data, and clinical evidence.

Bidirectional associations between cellular phone use behaviors and depressive symptoms in college students: a follow up study / 中国学校卫生

Objective@#The study aimed to describe the prevalence of mobile phone use and depressive symptoms and to examine the bidirectional associations between the two among college students, providinb evidence for mental health promotion among college students.@*Methods@#A longitudinal study with follow up at 6 month intervals was conducted in 1 135 students from 2 universities in Hefei, Anhui Province and Shangrao, Jiangxi Province who were selected between April and May 2019. The last follow up was conducted between April and May 2021 based on questionnaire survey, and 999 valid participants were obtained after matching. The self designed questionnaire was used to investigate the duration of cellular phone use and use of cellular phone functions among college students. The Self rating Questionnaire for Adolescent Problematic Mobile Phone Use (SQAPMPU) and the Patient Health Questionnaire-9 (PHQ-9) were used to assess cellular phone dependence and depressive symptoms among college students. Pearson correlation analysis was used to examine the correlation between cellular phone use behavior and depressive symptoms at baseline and 2 years later; linear regression model was used to analyze the linear association between cellular phone use behavior and depressive symptoms scores; autoregressive cross lagged model was used to analyze the bidirectional associations between cellular phone use behaviors and depressive symptoms among college students over time.@*Results@#The prevalence of mobile phone dependence and depressive symptoms among college students at baseline were 24.3% and 42.4%, respectively. The mean duration of mobile phone use among college students at baseline and the 2 year follow up were (2.84±0.90)h/d and (2.02±1.05)h/d, respectively; the mean scores of mobile phone dependence were (23.30±9.00) and (23.29±10.45), respectively; the mean scores of mobile phone function use were (30.12±6.66) and (29.12±7.27), respectively; and the mean scores of depressive symptoms were (4.51±4.76) and (2.61±4.40), respectively. Pearson correlation analysis showed there were significant positive correlations between duration of cellular phone use, cellular phone dependence, use of cellular phone functions at baseline or 2 years later and depressive symptoms 2 years later( r =0.08-0.50, P <0.05). Linear regression models showed a significant positive association between cellular phone dependence at baseline and depressive symptoms ( β=0.26, 95%CI =0.23-0.29) at baseline and 2 years later ( β=0.12, 95%CI =0.09-0.15). Autoregressive cross lagged models showed that cellular phone dependence at baseline positively predicted depressive symptoms 2 years later ( β =0.04) and depressive symptoms at baseline positively predicted cellular phone dependence 2 years later( β =0.23)( P <0.05).@*Conclusion@#There was a bidirectional association between cellular phone dependence and depressive symptoms among college students. Reducing cellular phone dependence is of positive significance for improving college students mental health.

A qualitative study on high risk behaviors of HIV/AIDS among young adult males in Shandong Province / 中国学校卫生

Objective@#To identify high risk behaviors and infection related factors among young adult males diagnosed with HIV/AIDS in Shandong Province, to provide evidence for targeted AIDS prevention and control strategies.@*Methods@#By using convient sampling method, an face to face in depth interview on HIV related behaviors was conducted among young adult males newly diagnosed with HIV/AIDS in Shandong Province in July 2021.@*Results@#A total of 31 young adult males diagnosed with HIV/AIDS were interviewed. All were male and infected through homosexuality behavior. Average age was (20.6±1.8) years. Totally 90.3% (28/31) were enrolled in tertiary education at the time of diagnosis. The findings revealed that 93.5% (29/31) of participants got infection due to unprotected homosexual behavior with the temporary partner whose HIV infection status was unknown, and 86.2% (25/29) got in touch with these temporary partner by social software. The awareness rate of knowledge about AIDS among all the participants was 100%, however, 83.9% (26/31) reported occasion condom usage while having homosexual behavior, and 16.1% (5/31) never did. Totally 74.2% (23/31) of the young adult males diagnosed with HIV/AIDS had a history of HIV testing before diagnosis.@*Conclusion@#The primary high risk behavior of HIV infection in young adult students are unawareness of HIV infection status for temporary sexual partner and the separation of knowing and doing. A targeted strategy should be developed to control the spread of HIV in young adult students.

Transapical transcatheter aortic valve replacement in bicuspid aortic valve patients: In-hospital outcomes / 中国胸心血管外科临床杂志

@#Objective    To compare the in-hospital outcomes of transapical transcatheter aortic valve replacement (TA-TAVR) for bicuspid aortic valve (BAV) patients and tricuspid aortic valve (TAV) patients. Methods    Patients (including BAV and TAV patients) who underwent TA-TAVR with the J-ValveTM in West China Hospital from July 2014 to July 2020 were included consecutively. The clinical outcomes of the patients were analyzed. Results    A total of 354 patients were included in the study, 75 in the BAV group and 279 in the TAV group. There were 229 males and 125 females with a mean age of 72.2±6.0 years. No death occurred during the procedure, and the overall technical success rate was 97.7%. The all-cause in-hospital mortality rate was 1.4%. Twenty (26.7%) patients with BAV and 46 (16.5%) patients with TAV had mild or higher perivalvular leaks immediately after the procedure. No patients with BAV required permanent pacemaker implantation postoperatively, while 13 (4.7%) TAV patients required permanent pacemaker implantation, with an overall pacemaker implantation rate of 3.7%. One (1.3%) BAV patient and 7 (2.5%) TAV patients developed acute kidney injury postoperatively. One (1.3%) BAV patient and 1 (0.4%) TAV patient developed peri-operative myocardial infarction. The average postoperative hospital stay was 7.6±3.6 d for BAV patients and 8.6±6.1 d for TAV patients. There was no statistical difference in primary or secondary in-hospital outcomes between BAV and TAV patients (P>0.05). Conclusion    Compared to TAV patients, BAV patients have similar in-hospital outcomes, with a low incidence of adverse clinical outcomes, which provides preliminary evidence for its implementation in Chinese patients with a high proportion of BAV.

Phenotype and genotyping of Yersinia pestis in China / 中华地方病学杂志

Objective:To study the phenotype and genotype distribution of Yersinia pestis ( Y. pestis) in different natural foci of plague in China, so as to provide scientific basis for plague prevention and control. Methods:A total of 2 184 strains of Y. pestis isolated from different time periods, regions, hosts and vectors in 11 plague natural foci of China since 1943 were selected for biochemical type identification, glycolysis test, virulence factor test [capsule antigen (F1), pesticin Ⅰ (Pst Ⅰ), virulence antigen factor (VWa), pigmentation factor (Pgm)], different region (DFR) typing and clustered regularly interspaced short palindromic repeats (CRISPR) typing. Results:There were 16 biochemical types of Y. pestis in the natural foci of plague in China, and each biochemical type showed obvious regional distribution in each foci. Most strains were positive for ass hide glue glycolysis (89.79%, 1 961/2 184), maltose (80.13%, 1 750/2 184), glycerol (94.23%, 2 058/2 184), and denitrification (82.78%, 1 808/2 184), and negative for rhamnose (88.78%, 1 939/2 184) and melibiose (85.62%, 1 870/2 184). Virulence factor test results showed that 99.95% (2 183/2 184) of Y. pestis were F1 positive; 99.73% (2 178/2 184) of Y. pestis can produce Pst Ⅰ; 73.31% (1 601/2 184) of Y. pestis were VWa positive and 26.69% (583/2 184) were VWa negative; Pgm positive strains accounted for 72.62% (1 586/2 184), Pgm negative strains accounted for 21.52% (470/2 184), and Pgm mixed type strains accounted for 5.86% (128/2 184). According to DFR typing results, there were 52 genotypes in 2 184 strains of Y. pestis, of which 19 were major genotypes and 33 were minor genotypes. CRISPR typing revealed 16 major genotypes, of which 7 were newly discovered. Conclusion:The phenotypes and genotypes of Y. pestis in various natural foci of plague in China are diverse and have geographical distribution characteristics.

Clustered regularly interspaced short palindromic repeats genotyping of Yersinia pestis in Yushu Tibetan Autonomous Prefecture, Qinghai Province / 中华地方病学杂志

Objective:To learn about the clustered regularly interspaced short palindromic repeats (CRISPR) genotyping of Yersinia pestis in Yushu Tibetan Autonomous Prefecture (Yushu for short), Qinghai Province, and to explore its genetic characteristics. Methods:In this study, 44 representative strains isolated from local natural plague focus in Yushu from 1963 to 2007 were selected as experimental objects to extract DNA. Primers targeting the three CRISPR loci (YPa, YPb, and YPc) were designed for PCR amplification. The amplified products were sequenced and analyzed to identify the CRISPR spacer, and to determine the CRISPR genotypes and clusters.Results:Twenty-three spacers including 14 of YPa, 6 of YPb and 3 of YPc were observed among 44 strains, of which 2 spacers (a106 and a107) were firstly identified. According to the spacer arrays, the strains were divided into 15 CRISPR genotypes and classified into 6 CRISPR clusters which were Cb4, Cc3', Ca7, Ca7', CaΔ5' and Ca35', respectively. Among them, Ca7 was the most epidemic dominant cluster (34 strains) in Yushu.Conclusion:The CRISPR loci of Yersinia pestis in Yushu have multiple genotypes, high genetic polymorphism, and complex population structure.

Clinical characteristics of hypersensitivity pneumonitis: non-fibrotic and fibrotic subtypes / 中华医学杂志(英文版)

BACKGROUND@#The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis.@*METHODS@#In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis.@*RESULTS@#A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP.@*CONCLUSIONS@#Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.

Chest wall muscle mass depletion is related to certain pulmonary functions and diseases in patients with bronchiectasis.

BACKGROUND AND OBJECTIVE: Many bronchiectasis patients suffer dyspnea, decreased exercise tolerance, and low body mass index. Chest wall muscles play a special role in respiratory movement and make up parts of skeletal muscles. This study aimed to examine the chest wall muscle thickness and their relationship with disease severity in bronchiectasis. METHODS: We retrospectively included 166 patients with bronchiectasis and 62 patients with pneumonia as comparators. The thickness of chest wall muscle as determined in chest CT, pulmonary function, and Bronchiectasis Severity Index (BSI) score were recorded. We compared the thickness of the chest wall muscle in two groups and assessed the relationships among chest wall muscle thickness, pulmonary function, and BSI score. RESULTS: Chest wall muscle thickness of the anterior midclavicular line and posterior exterior scapula were thinner in bronchiectasis patients than comparators both above the aortic arch level and at the aortic arch window level. Muscle thickness of the posterior interior scapula above the aortic arch level was significantly thinner in bronchiectasis patients. Chest wall muscle thickness at the anterior midclavicular line both the above aortic arch level and at the level of the aortic arch window were related to diffuse capacity in bronchiectasis patients. Anterior chest wall muscle thickness above the aortic arch was found to be a risk factor of disease severity. CONCLUSION: Anterior chest wall muscles in the upper and middle chest were thinner in bronchiectasis patients than in comparators, and had relationship with spirometry and diffuse compacity factors. We provide another method to conveniently assess bronchiectasis severity.

Role of GLP-1R signaling pathway in sevoflurane postconditioning-induced attenuation of myocardial ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective:To evaluate the role of glucagon-like peptide-1 receptor (GLP-1R) signaling pathway in sevoflurane postconditioning-induced attenuation of myocardial ischemia-reperfusion (I/R) injury in rats.Methods:Eighty SPF healthy adult male Sprague-Dawley rats, aged 8-10 weeks, weighing 300-340 g, were divided into 4 groups ( n=20 each) by a random number table method: sham operation group (group S), myocardial I/R group (group I/R), myocardial I/R plus sevoflurane postconditioning group (group ISP), and myocardial I/R plus sevoflurane postconditioning plus GLP-1R antagonist group (group ISPE). The myocardial I/R injury model was developed by ligating the left anterior descending branch of the coronary artery for 40 min followed by 2-h reperfusion in anesthetized rats.In group ISP, the rats inhaled 2.4% sevoflurane for 15 min starting from the beginning of reperfusion.In group ISPE, GLP-1R antagonist Exendin9-39 50 μg/kg (in 1 ml 0.9% normal saline) was intraperitoneally injected once a day from 28 days before development of the model, the last intraperitoneal injection was completed at 40 min before inhalation of sevoflurane, and the other treatments were the same as those previously described in group ISP.Blood samples from the abdominal aorta were collected immediately after reperfusion to determine the serum levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH). Then the rats were sacrificed, and the hearts were obtained for microscopic examination of the histopathological changes of myocardial tissues (by HE staining) and the ultrastructure of cardiomyocytes (with a transmission electron microscope) for determination of the myocardial infarct size (TTC staining), expression of GLP-1R in myocardium (by immunohistochemical staining), expression of GLP-1R, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), cAMP response element-binding protein (CREB), phospho-CREB (p-CREB), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated x protein (Bax) in myocardium (by Western blot). The ratios of p-CREB/CREB and Bcl-2/Bax were calculated. Results:Compared with group S, the serum levels of CK-MB and LDH and percentage of myocardial infarct size were significantly increased, the expression of GLP-1R was up-regulated, the expression of cAMP and PKA was down-regulated, and the p-CREB/CREB ratio and Bcl-2/Bax ratio were decreased in group I/R ( P<0.05). Compared with group I/R, the serum levels of CK-MB and LDH and percentage of myocardial infarct size were significantly decreased, the expression of GLP-1R, cAMP and PKA was up-regulated, and p-CREB/CREB ratio and Bcl-2/Bax ratio were increased in group ISP ( P<0.05). Compared with group ISP, the serum levels of CK-MB and LDH and percentage of myocardial infarct size were significantly increased, the expression of GLP-1R, cAMP and PKA was down-regulated, and the p-CREB/CREB ratio and Bcl-2/Bax ratio were decreased in group ISPE ( P<0.05). Conclusions:Sevoflurane postconditioning can attenuate myocardial I/R injury by activation of GLP-1R signal pathway and inhibition of cardiomyocyte apoptosis in rats.

CRISPR genotyping of Yersinia pestis in the plague natural foci of Qinghai-Tibet Plateau / 中华地方病学杂志

Objective:To investigate the genotypes of clustered regularly interspaced short palindromic repeats (CRISPR) of Yersinia pestis ( Y. pestis) and it's regional distribution in the plague natural foci of Qinghai-Tibet Plateau. Methods:In this study, 1 004 strains of Y. pestis isolated from different hosts and vectors in different regions from 1954 to 2011 were selected as experimental objects, which preserved in Qinghai Institute for Endemic Disease Prevention and Control, and DNA of Y. pestis was extracted by traditional phenol-chloroform method. Three CRISPR loci (YPa, YPb and YPc) were amplified by PCR and sequenced, respectively, and the CRISPR sequences were compared with the CRISPRDictionary database recently reported in the literature to identify CRISPR spacer. For the spacer discovered for the first time at each CRISPR locus, Blast sequence alignment was performed in the National Center for Biotechnology Information (NCBI) database to speculate the source of gene sequence. Genotyping of Y. pestis from Qinghai-Tibet Plateau was performed based on the polymorphism of CRISPR spacer array. Results:A total of 53 spacers were found in 1 004 strains of Y. pestis, of which 6 spacers were newly discovered, namely a105, a106, a107, b51, b52 and c14. The 1 004 strains of Y. pestis were divided into 10 groups with 44 different CRISPR genotypes, and 15 new genotypes were found. The dominant genotypes of Y. pestis were G26-a1', G7, G22, G24-a1', G22-a1', G9 and G26-a1'a60 in Himalayan Marmot plague natural foci, and G37-a6' in Qinghai Microtinae plague natural foci. Conclusion:The CRISPR genotypes of Y. pestis in the plague natural foci of Qinghai-Tibet Plateau are high diverse and have significant regional distribution characteristics.

Efficacy of levofloxacin and moxifloxacin in the treatment of experimentally infected guinea pigs with Yersinia pestis / 中华地方病学杂志

Objective:To observe the efficacy of levofloxacin and moxifloxacin in the treatment of experimental plague in guinea pigs.Methods:A total of 70 SPF guinea pigs, female, weighing 250 to 300 g, were selected and randomly divided into 7 groups according to body weight by random number table. There were 10 guinea pigs in each group: levofloxacin 24, 48, 72 h groups, moxifloxacin 24, 48, 72 h groups (drug treatment was carried out after being infected with Yersinia pestis for 24, 48 and 72 h, respectively) and control group (without treatment). Experimentally infected plague model was established through guinea pigs subcutaneous injection of 141 strains of Yersinia pestis [1 × 10 7 colony forming unit (CFU)]; referring to the adult dose in the "National Pharmacopoeia of the People's Republic of China", the daily dose of guinea pigs was converted by Shi Xinyou's animal conversion coefficient method for treatment, the doses of levofloxacin and moxifloxacin in each guinea pig were 12.0 and 9.6 mg/d, respectively for 9 days. The guinea pigs were killed 9 days after drug withdrawal for bacteriological examination and pathological observation, and the cure rate was calculated. Results:The cure rates of levofloxacin 24, 48 and 72 h groups were 100.0% (10/10), 70.0% (7/10) and 6/6, respectively. The cure rates of moxifloxacin 24, 48 and 72 h groups were 100.0% (10/10), 100.0% (10/10) and 5/7, respectively, and the cure rate of animals in the control group was 0 (0/10). Compared with the control group, there were significant differences in the efficacy of moxifloxacin 24, 48 and 72 h groups and levofloxacin 24, 48 and 72 h groups ( P < 0.05). There was no significant difference between the two drugs at the same starting time ( P > 0.05). Conclusion:The effects of levofloxacin and moxifloxacin on animal plague infection are ideal and the two drugs can be used as a substitute for streptomycin in plague treatment under special circumstances.

Etiology of Yersinia pestis in a plague natural foci of Qinghai-Tibet Plateau / 中华地方病学杂志

Objective:To analyze the pathogenic characteristics of Yersinia pestis in a plague natural foci in Qinghai-Tibet Plateau. Methods:In this study, 1 378 strains of Yersinia pestis isolated from different regions, hosts and vectors in Qinghai-Tibet Plateau from 1954 to 2016 were taken as the research objects. Phenotypic characteristics, plasmid spectrum and genotype of the strains were studied by using conventional techniques and molecular biological techniques. The etiology and geographical distribution of the plague were studied. Results:There were 6 biochemical types of Yersinia pestis in Qinghai-Tibet Plateau, namely Qinghai-Tibet Plateau, Qilian Mountain, Gangdis Mountain, Kunlun Mountain A, Kunlun Mountain B and Chuanqing Plateau. This study found that the Qinghai-Tibet Plateau type strain was not only distributed in north Tibet Plateau, but also distributed in south Tibet, and the distribution of Gangdis Mountain type strain extended to south Tibet. Four virulence factors (capsule antigen, yersinin, virulence antigen and pigmentation factor) were found in 79.97% (1 102/1 378) Yersinia pestis. The results also showed that there were 12 kinds of plasmids carried by Yersinia pestis strains in Qinghai-Tibet Plateau, which constituted 17 kinds of plasmid spectrum. There were 3 kinds of the largest plasmids with taxonomic properties, forming their respective relatively independent distribution areas. The study of different regions (DFR) type showed that 5, 8, 14, 19, 32 and 44 of 1 378 strains were the main genotypes, and the main genome types had obvious geographical distribution. Conclusions:All the tested strains have the characteristics of plague pathogen in Qinghai-Tibet Plateau. The polymorphism of the main hosts, vectors and the ecological landscape of plague geography in the plague foci in Qinghai-Tibet Plateau may lead to the diversity of biochemical characters, plasmid spectrum and geno types of Yersinia pestis.

Establishment and performance evaluation of a quantitative detection method for immunoglobulin G4 based on fluorescence immunochromatography / 中华胰腺病杂志

Objective:To establish a rapid and quantitative method for the determination of immunoglobulin G4 (IgG4) by fluorescence immunochromatography and to analyze its clinical application value.Methods:Fluorescence immunoassay for quantitative detection of IgG4 was obtained by means of preparation of kits in a competitive reaction mode and combining immunoassay with fluorescence quantitative assay. The linearity, precision, accuracy, anti-interference ability and stability of the method were evaluated, and compared with immune-scattering turbidimetry, receiver operating characteristic curve (ROC) was plotted, area under the curve (AUC) was calculated, and the critical value for the diagnosis of pancreatitis related diseases was determined, and sensitivity and specificity were calculated.Results:The linear range of fluorescence immunoassay for IgG4 was 0.2-10.0 g/L. The accuracy coefficient of variation was less than 15%, and the accuracy deviation was within ±15%. Bilirubin (2.5 g/L), triglyceride (10 g/L) and hemoglobin (10 g/L) had no significant effect on the quantitative determination. Within 14 months, 1.20 g/L and 2.65 g/L reference samples were detected with concentration deviations within ±15%. The kit validity period was >12 months. Serum samples of 200 healthy people were detected by fluorescence immunochromatography, and the normal reference value of IgG4 was <2.03 g/L. fluorescence immunochromatography and Immunoturbidimetry were used to detect IgG4 concentrations in 383 clinical serum samples. The results showed that the two methods were consistent ( P>0.05). Using 2.01g/L IgG4 as the critical value, the sensitivity and specificity of fluorescence immunochromatography were 96.3% and 95.5% by ROC curve analysis, respectively. Conclusions:Fluorescence immunochromatography was a simple, rapid and accurate method for the quantitative detection of IgG4, and had high sensitivity and specificity for the diagnosis of pancreatitis related diseases. It was suitable for quantitative detection of bulk samples in outpatient and emergency departments.

Correlation between disaster preparedness and psychological capital of clinical nurses / 中国实用护理杂志

Objective:To understand the status of psychological capital and disaster preparedness of clinical nurses and analyze the relationship between them.Methods:From August to October 2020, 508 clinical nurses were selected from 8 Class Ⅲ hospitals in Zhejiang province by convenience sampling method. General information questionnaire, nurses' psychological capital questionnaire and disaster preparedness questionnaire were used. A total of 508 questionnaires were sent out and 503 valid questionnaires were collected with an effective rate of 99.01%.Results:The total score of disaster preparedness score of 503 clinical nurses was (179.53±41.11) points, mean items score was (3.99±0.91) points, psychological capital was (91.86±14.68) points, mean items score was (4.49±0.73) points. Correlation analysis showed that nurses' psychological capital was positively correlated with disaster preparedness ( r value was 0.610, P<0.05). Regression analysis showed that psychological capital, department, working years, whether participated in disaster training and disaster event rescue had significant impact on disaster preparedness of clinical nurses ( t values were 2.002-16.770, P<0.01 or 0.05). Conclusions:The knowledge, skills and post disaster management of clinical nurses are still deficient. Psychological capital affects the level of disaster preparedness of nurses to a certain extent. Nursing managers should formulate targeted intervention measures to enhance the level of psychological capital of nurses, so as to better improve the disaster preparedness of clinical nurses.

cGAS/STING signaling pathways induces the secretion of type Ⅰ interferon in porcine alveolar macrophages infected with porcine circovirus type 2 / 生物工程学报

In order to study the signal pathway secreting type Ⅰ interferon in porcine alveolar macrophages (PAMs) infected with porcine circovirus type 2 (PCV2), the protein and the mRNA expression levels of cGAS/STING pathways were analyzed by ELISA, Western blotting and quantitative reverse transcriptase PCR in PAMs infected with PCV2. In addition, the roles of cGAS, STING, TBK1 and NF-κB/P65 in the generation of type I interferon (IFN-I) from PAMs were analyzed by using the cGAS and STING specific siRNA, inhibitors BX795 and BAY 11-7082. The results showed that the expression levels of IFN-I increased significantly at 48 h after infection with PCV2 (P<0.05), the mRNA expression levels of cGAS increased significantly at 48 h and 72 h after infection (P<0.01), the mRNA expression levels of STING increased significantly at 72 h after infection (P<0.01), and the mRNA expression levels of TBK1 and IRF3 increased at 48 h after infection (P<0.01). The protein expression levels of STING, TBK1 and IRF3 in PAMs infected with PCV2 were increased, the content of NF-κB/p65 was decreased, and the nuclear entry of NF-κB/p65 and IRF3 was promoted. After knocking down cGAS or STING expression by siRNA, the expression level of IFN-I was significantly decreased after PCV2 infection for 48 h (P<0.01). BX795 and BAY 11-7082 inhibitors were used to inhibit the expression of IRF3 and NF-κB, the concentration of IFN-I in BX795-treated group was significantly reduced than that of the PCV2 group (P<0.01), while no significant difference was observed between the BAY 11-7028 group and the PCV2 group. The results showed that PAMs infected with PCV2 induced IFN-I secretion through the cGAS/STING/TBK1/IRF3 signaling pathway.

Drug resistance of Yersinia pestis in natural foci of plague in Inner Mongolia Autonomous Region / 中华地方病学杂志

Objective:To investigate the drug resistance of Yersinia pestis to 11 kinds of antibiotics in the natural foci of plague in Inner Mongolia Autonomous Region, and to provide a theoretical basis for scientifically and effectively selecting antibiotics for treatment of the plague. Methods:A total of 137 strains of Yersinia pestis isolated from the natural foci of plague in Inner Mongolia Autonomous Region at different times, regions, hosts and vectors were collected. According to Clinical and Laboratory Standard Institute (CLSI), the agar plate dilution method was used to determine the minimum inhibitory concentration (MIC) of the 11 kinds of antibiotics against 137 strains of Yersinia pestis, including ofloxacin, ciprofloxacin, kanamycin, streptomycin, ceftriaxone, ampicillin, chloramphenicol, spectinomycin, cefuroxime, tetracycline and sulfamethoxazole-trimethoprim. The MIC 50 and MIC 90 (the minimum concentration of drug which could inhibit 50% and 90% of bacterial growth) were calculated, and their sensitivity was determined according to CLSI standards. Results:Among 137 strains of Yersinia pestis tested, no strains of Yersinia pestis had single or multiple resistance to ofloxacin, ciprofloxacin, kanamycin, streptomycin, ceftriaxone, ampicillin, chloramphenicol, spectinomycin, cefuroxime, tetracycline and sulfamethoxazole-trimethoprim. According to CLSI standards, 137 strains of Yersinia pestis were all sensitive to the 11 kinds of antibiotics; among them, ofloxacin, ciprofloxacin, ceftriaxone and sulfamethoxazole-trimethoprim had higher antibacterial activity, with MIC 90 < 0.250 μg/ ml; the antibacterial activity of spectinomycin was the lowest, with MIC 90 of 16.000 μg/ml. Conclusions:The Yersinia pestis isolated from the natural foci of plague in Inner Mongolia Autonomous Region is not found to have single or multiple resistance to the 11 kinds of antibiotics. Continuous drug resistance monitoring of Yersinia pestis should be carried out to provide a basis for clinical medication.

Studies on drug and disinfectant resistance related genes of Yersinia pestis in China / 中华地方病学杂志

Objective:To understand whether there are drug resistant and disinfectant resistant Yersinia pestis strains in China, and to provide accurate information for clinical treatment of plague. Methods:A total of 2 753 Yersinia pestis strains isolated from 10 natural plague foci in China from 1943 to 2016 were collected. According to National Center for Biotechnology Information (NCBI) released sequences of aminoglycoside streptomycin resistant genes strA, strB, β-lactam antibiotics resistant genes TEM, SHV and CTX-M, sulfamilamide resistant genes sul1, sul2 and sul3, and disinfectant resistant gene qacE△1-sul1, a pair of primers of each gene was designed for above-mentioned genes. Genomic DNA of 2 753 strains of Yersinia pestis was extracted, and the 9 target genes of all DNA samples were amplified by PCR. Results:Negative and positive controls of PCR detection were established. No corresponding target bands of aminoglycoside streptomycin resistant genes strA, strB, β-lactam antibiotics resistant genes TEM, SHV and CTX-M, sulfamilamide resistant genes sul1, sul2 and sul3, and disinfectant resistant gene qacE△1-sul1 were found in the DNA samples of 2 753 strains of Yersinia pestis.Conclusion:The above-mentioned genes of drug resistance and disinfectant resistance have not been detected in Yersinia pestis of China, but the monitoring of drug resistance of Yersinia pestis still needs to be carried out continuously.