Map of benzoapyrene metabolites-DNA adducts in human bronchial epithelial-like cells: Based on chromatin immunoprecipitation followed by sequencing technology / 环境与职业医学

Background The active metabolite of benzo[a]pyrene (BaP), 7,8-dihydroxy-9,10-epoxybenzo[a]pyrene (BPDE), can form adducts with DNA, but the spectrum of BPDE-DNA adducts is unclear. Objective To identify the distribution of BPDE adduct sites and associated genes at the whole-genome level by chromatin immunoprecipitation followed by sequencing (ChIP-Seq), and serve as a basis for further exploring the toxicological mechanisms of BaP. Methods Human bronchial epithelial-like cells (16HBE) were cultured to the fourth generation inthe logarithmic growth phase. Cells were harvested and added to chromatin immunoprecipitation lysis buffer. The lysate was divided into experimental and control groups. The experimental group received a final concentration of 20 μmol·L−1 BPDE solution, while the control group received an equivalent volume of dimethyl sulfoxide solution. The cells were then incubated at 37 °C for 24 h. Chromatin fragments of 100-500 bp were obtained through sonication. BPDE-specific antibody (anti-BPDE 8E11) was used to enrich DNA fragments with BPDE adducts. High-throughput sequencing was conducted to detect BPDE adduct sites. The top 1000 peak sequences were subjected to motif analysis using MEME and DREME software. BPDE adduct target genes at the whole-genome level were annotated, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of BPDE adduct target genes were conducted using bioinformatics techniques. Results The high-throughput sequencing detected a total of 842 BPDE binding sites, distributed across various chromosomes. BPDE covalently bound to both coding and non-coding regions of genes, with 73.9% binding sites located in intergenic regions, 19.6% in intronic regions, and smaller proportions in upstream 2 kilobase, exonic, downstream 2 kilobase, and 5' untranslated regions. Regarding the top 1000 peak sequences, four reliable motifs were identified, revealing that sites rich in adenine (A) and guanine (G) were prone to binding. Through the enrichment analysis of binding sites, a total of 199 BPDE-adduct target genes were identified, with the majority located on chromosomes 1, 5, 7, 12, 17, and X. The GO analysis indicated that these target genes were mainly enriched in nucleic acid and protein binding, participating in the regulation of catalytic activity, transport activity, translation elongation factor activity, and playing important roles in cell division, differentiation, motility, substance transport, and information transfer. The KEGG analysis revealed that these target genes were primarily enriched in pathways related to cardiovascular diseases, cancer, and immune-inflammatory responses. Conclusion Using ChIP-Seq, 199 BPDE adduct target genes at genome-wide level are identified, impacting biological functions such as cell division, differentiation, motility, substance transport, and information transfer. These genes are closely associated with cardiovascular diseases, tumors, and immune-inflammatory responses.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Two new phenylpropanoids from wine-processed Corni Fructus / 中国中药杂志

Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-β-glucopyranoside(3),(-)-isolariciresinol 3α-O-β-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-β-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) μmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 μmol·L~(-1) was 96.09%±1.77%.

Preliminary immunological evaluation of Mycobacterium tuberculosis multicomponent protein vaccine candidates EPDPA015f and EPDPA015m / 中华微生物学和免疫学杂志

Objective:To preliminarily evaluate the immunogenicity and efficacy of two novel tuberculosis vaccine candidates (a fusion multicomponent protein EPDPA015f and a mixed multicomponent protein EPDPA015m) and to provide a new antigen combination for the development of tuberculosis vaccines.Methods:Recombinant plasmids for the expression of EPDPA015f and EPDPA015m proteins were constructed. Six-week-old BALB/c mice were immunized with EPDPA015f or EPDPA015m in combination with aluminium adjuvant (50 μg/mouse) for three times with an interval of 10 d. The mice were sacrificed 10 d after the last immunization to collect blood and spleen samples. Serum antibody titers and cytokine levels were measured by ELISA, Luminex technique and enzyme-linked immunospot assay (ELISPOT). Mycobacterial growth inhibition assay (MGIA) was used to detect the ability of mouse splenocytes to inhibit the growth of Mtb in vitro. One-way analysis of variance and t-test were used for statistical analysis. Results:Both EPDPA015f and EPDPA015m could induce the production of various cytokines and IgG antibodies at a high level. The levels of cytokines related to Th1 (IL-2, TNF-α, IFN-γ), Th2 (IL-4, IL-6, IL-10) and Th17 (IL-17) as well as other proinflammatory cytokines (GM-CSF, IL-12) were higher in the EPDPA015f group than in the adjuvant group ( P<0.05). The titer of IgG antibody induced by EPDPA015f was as high as 1∶4×10 6. The results of MGIA showed that the numbers of Mtb (lgCFU) in the PBS, adjuvant, EPDPA015f and EPDPA015m groups were 3.46±0.11, 3.51±0.06, 2.98±0.09 and 3.19±0.08, respectively. The number of colonies in the EPDPA015f group was the least as compared with that in the other three groups ( P<0.001, P<0.001, P<0.01). Conclusions:The vaccine candidate EPDPA015f could elicit more comprehensive and high-level cellular and humoral immune responses, and exhibited superior in vitro inhibitory activity against the growth of Mtb. EPDPA015f had the potential to be used as a preventive vaccine or a booster vaccine

Analysis of bacterial spectrum and variability of drug resistance of bile in patients with common bile duct stones and biliary tract infections / 中华消化杂志

Objective:To analyze the distribution of pathogenic bacteria in bile culture in patients with common bile duct stones and biliary tract infections, in order to guide clinical optimization of antibiotics application.Methods:From March 30, 2017 to December 31, 2021, at Affiliated Hospital of Qingdao University, 753 patients with common bile duct stones and biliary tract infections and received endoscopic retrograde cholangiopancreatography were selected. Bile samples were obtained for bacterial culture, strain type identification and drug sensitivity test in order to analyze bile pathogenic bacteria distribution, change trend and drug resistance. Chi-square test was used for statistical analysis.Results:From 2017 to 2021, the total positive rate of bile culture in 753 patients with choledocholithiasis complicated with biliary tract infection was 90.17% (679/753). From 2017 to 2021, the positive rates of bile culture were 82.05% (64/78), 88.81% (119/134), 88.03% (125/142), 93.87% (199/212), and 91.98% (172/187), respectively, and the difference was statistically significant ( χ2=10.78, P=0.029). The positive rate of bile culture in 2017 was lower than those in 2020 and 2021, and the differences were statistically significant ( χ2=9.43 and 5.57, P=0.002 and 0.018). There were no significant differences in the positive rates of bile culture among the other years (all P>0.05). A total of 1 033 pathogenic bacteria were detected in the 679 bile specimens with positive bile culture results. Among which the total proportion of Gram-negative bacilli was 57.02% (589/1 033), and from 2017 to 2021 the proportions were 66.38% (77/116), 66.47% (111/167), 59.43% (104/175), 54.75% (173/316), and 47.88% (124/259), respectively. The total proportion of Gram-positive cocci was 41.05% (424/1 033), and from 2017 to 2021 the proportions were 31.90% (37/116), 31.74% (53/167), 38.86% (68/175), 44.30% (140/316), and 48.65% (126/259), respectively. The total proportion of fungus was 1.94% (20/1 033), and from 2017 to 2021 the proportions were 1.72% (2/116), 1.80% (3/167), 1.71% (3/175), 0.95% (3/316), and 3.47% (9/259), respectively. From 2017 to 2021, the proportion of Gram-negative bacilli gradually decreased, while the proportion of Gram-positive cocci gradually increased, and the differences were statistically significant ( χ2=20.14 and 17.91, P<0.001 and =0.001). From 2017 to 2021, the change in the proportion of fungus was not statistically significant ( P>0.05). The main Gram-negative bacilli in the bile culture were Escherichia coli (31.36%, 324/1 033) and Klebsiella pneumoniae (12.68%, 131/1 033); the main Gram-positive cocci were Enterococcus faecalis (14.04%, 145/1 033) and Streptococcus salivarius (4.36%, 45/1 033). From 2017 to 2021, the proportions of Escherichia coli were 39.66% (46/116), 38.92% (65/167), 33.14% (58/175), 28.48% (90/316), and 25.10% (65/259), respectively, with gradual decrease and the difference was statistically significant ( χ2=14.34, P=0.006). From 2017 to 2021 the detection rates of extended-spectrum β-lactamase (ESBL) in Escherichia coli and Klebsiella pneumoniae were 30.43% (14/46), 26.15% (17/65), 29.31% (17/58), 38.89% (35/90), 40.00% (26/65), and 4/15, 20.00% (5/25), 20% (5/25), 24.32% (9/37), and 31.03% (9/29), and there were no significant differences in the detection rates of ESBL between different years (both P>0.05). Conclusions:From 2017 to 2021, the positive rate of bile culture in patients with choledocholithiasis complicated with biliary tract infection showed an overall increasing trend. Gram-negative bacilli were still dominated in bile pathogenic bacteria, while the proportion of Gram-positive cocci remarkably increased, and the bile bacterial spectrum significantly changed. Clinicians should adjust the antibiotic dosing regimens according to the variation of bacterial spectrum and drug resistance.

Analysis of clinical characteristics and risk factors of gastrointestinal hemorrhage in gastric inflammatory fibroid polyp / 中国内镜杂志

Objective To investigate the risk factors and clinical characteristics of gastric inflammatory fibroid polyp(GIFP)for gastrointestinal hemorrhage.Methods 66 patients(68 lesions in total)with GIFP diagnosed by endoscopic or surgical resection from January 1,2013 to September 30,2022 were collected.According to the presence or absence of gastrointestinal hemorrhage,the patients were divided into bleeding group(n = 16)and non-bleeding group(n = 50).Collect clinical data on gender,age,clinical manifestations,lesion location and size,endoscopic characteristics,Helicobacter pylori infection,surgical methods and pathological results of each group of patients.Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of endoscopic characteristics of GIFP for gastrointestinal hemorrhage,and summarize the clinical characteristics of GIFP with gastrointestinal hemorrhage,then calculate the rate of correct diagnosis.Results The age of the bleeding group was significantly younger than that of the non-bleeding group,and the lesion size was significantly larger than that of the non-bleeding group,with statistically significant differences(P＜0.05).The incidences of endoscopic neoplasm-like elevation of lesions,surface with erosion or ulceration,accompanied by ballvalve syndrome and ultrasonic gastroscopy with blood flow signals in the bleeding group were significantly higher than those in the non-bleeding group,and the differences were statistically significant(P＜0.05),but there were no statistical differences in other indicators between the two groups(P＞0.05).In order to further investigate the relationship between endoscopic characteristics and gastrointestinal hemorrhage,multivariate Logistic regression analysis showed that neoplasm-like elevation,submucosal eminence,ulcer or erosion on the surface and ball valve syndrome were risk factors for gastrointestinal hemorrhage in GIFP(O(R)＞1,P＜0.05).The overall rate of GIFP correct diagnosis before surgery was 27.94%.The rate of diagnosis in patients echoendoscope before surgery was 38.78%,it was significantly higher than that without undergoing echoendoscope(χ2 = 20.82,P = 0.000).Conclusion The shape of the lesion,presence of ulcers or erosion on the surface,and presence of ball valve syndrome are risk factors for gastrointestinal hemorrhage.Preoperative endoscopic ultrasonography can improve the accuracy of preoperative diagnosis.When there is a risk of gastrointestinal hemorrhage in GIFP,early endoscopic diagnosis and therapeutic resection should be performed to avoid unnecessary surgical procedures,which can improve prognosis and improve patient quality of life.

Applications of functional genomics in research of benzo[a]pyrenetoxicity：a review / 预防医学

Abstract@#Benzo [a] pyrene ( B [a] P ) is a well-recognized environmental pollutant. Exposure to B[a]P elicits many adverse biological effects, including tumorigenesis, immunosuppression, teratogenicity, and hormonal effects. In addition to B [a] P exposure-induced genetic damages, a growing number of studies demonstrate that epigenetic changes play an important role in chemically induced carcinogenesis. In order to provide better understanding of epigenetic changes of B [a] P and their potential association with genotoxic endpoints, this review summarizes the advances in the applications of functional genomics in the research of B [a] P toxicity, including functional genomics techniques, regulation of human genome expression, DNA sequence variability, model organisms research, and bioinformatics studies, so as to provide insights into the management of B [a] P exposure-induced health injuries and use of genomics techniques to unravel the mechanisms underlying the toxicity of other environmental pollutants.

Clinical factors associated with composition of lung microbiota and important taxa predicting clinical prognosis in patients with severe community-acquired pneumonia / 医学前沿

Few studies have described the key features and prognostic roles of lung microbiota in patients with severe community-acquired pneumonia (SCAP). We prospectively enrolled consecutive SCAP patients admitted to ICU. Bronchoscopy was performed at bedside within 48 h of ICU admission, and 16S rRNA gene sequencing was applied to the collected bronchoalveolar lavage fluid. The primary outcome was clinical improvements defined as a decrease of 2 categories and above on a 7-category ordinal scale within 14 days following bronchoscopy. Sixty-seven patients were included. Multivariable permutational multivariate analysis of variance found that positive bacteria lab test results had the strongest independent association with lung microbiota (R2 = 0.033; P = 0.018), followed by acute kidney injury (AKI; R2 = 0.032; P = 0.011) and plasma MIP-1β level (R2 = 0.027; P = 0.044). Random forest identified that the families Prevotellaceae, Moraxellaceae, and Staphylococcaceae were the biomarkers related to the positive bacteria lab test results. Multivariable Cox regression showed that the increase in α-diversity and the abundance of the families Prevotellaceae and Actinomycetaceae were associated with clinical improvements. The positive bacteria lab test results, AKI, and plasma MIP-1β level were associated with patients' lung microbiota composition on ICU admission. The families Prevotellaceae and Actinomycetaceae on admission predicted clinical improvements.

Total Flavones of Spatholobi Caulis Regulate Hippocampal Neuroplasticity in Depressed Rats Through CREB/BDNF Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total flavones of Spatholobi Caulis （TFSC） against depression in rats. MethodThe fifty KM mice were randomly divided into the normal group and high-， medium-， and low-dose （1， 0.5， 0.25 g·kg-1） TFSC groups and gavaged with the corresponding drugs for 12 successive days. One hour after the last administration， the immobility time in forced swimming test and tail suspension test was recorded. The SD rats were randomly divided into the normal group， model group， fluoxetine （5 mg·kg-1） group， and high- and low-dose （1， 0.25 g·kg-1） TFSC groups. Following the exposure of rats to two different kinds of stimuli daily for inducing chronic unpredictable stress， they were administered with the corresponding drugs for 21 d. After the experiment， the levels of serum neurotransmitters and inflammatory factors in rats were detected by enzyme-linked immunosorbent assay （ELISA）. The changes in hippocampal neurons of rats were observed by hematoxylin-eosin （HE） and Nissl staining. The mRNA expression levels of nuclear factor-κB （NF-κB） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of cAMP-response element binding protein （CREB）， phosphorylated CREB （p-CREB）， and brain-derived neurotrophic factor （BDNF） in hippocampal tissues by Western blot. ResultCompared with the normal group， TFSC significantly shortened the immobility time of mice in tail suspension and swimming tests （P<0.05）. Compared with the normal group， the model group exhibited reduced sucrose intake and wilderness activity （P<0.01）， decreased 5-HT， DA， NE （P<0.05， P<0.01）， MAO， IL-6， TNF-α （P<0.05， P<0.01）， damaged neurons， increased mRNA levels of TNF-α and NF-κB （P<0.01）， and down-regulated BDNF and CREB protein expression （P<0.05）. Compared with the model group， TFSC significantly enhanced sucrose intake and wilderness activity of rats （P<0.05）， increased the serum 5-HT， DA and NE （P<0.05， P<0.01）， and decreased the serum MAO， IL-6， and TNF-α （P<0.05， P<0.01） as well as NF-κB and TNF-α mRNA expression （P<0.01）， up-regulated the protein expression levels of BDNF and CREB （P<0.01）， and improved the pathological symptoms of hippocampus. ConclusionTFSC improved the hippocampal neurons of rats via CREB/BDNF signaling pathway and reduced depressive pathological damage， thus relieving depression.

A retrospective analysis of the funding of respiratory projects supported by the National Natural Science Foundation of China from 2009 to 2019 / 中华医学科研管理杂志

Objective:To understand the status quo of basic research projects on respiratory diseases in China.Methods:Descriptive statistical methods were used to review the project number, funding input, funding categories and distribution of National Natural Science Foundation of China (NSFC) respiratory disease funding projects from 2009 to 2019.Results:according to the research, the number of NSFC respiratory projects and funding increased significantly, which promoted the development of respiratory science. However, due to the heavy burden of respiratory diseases, it is still necessary to increase the investment in respiratory diseases.Conclusions:taking into account of the importance of respiratory science, this paper suggests that NSFC should increase investment and support for respiratory diseases projects, strengthen the development of existing respiratory advantages, encourage cross-cutting and frontier research on respiration, cultivate a group of internationally influential scientists and research teams, and promote academic innovation in respiratory science.

Analysis of antibiotic usage for viral community-acquired pneumonia in adults / 医学前沿

The rationale for the antibiotic treatment of viral community-acquired pneumonia (CAP) in adults was analyzed to develop a clinical reference standard for this condition. Clinical data from 166 patients diagnosed with viral pneumonia across 14 hospitals in Beijing from November 2010 to December 2017 were collected. The indications for medications were evaluated, and the rationale for the use of antibiotics was analyzed. A total of 163 (98.3%) patients with viral pneumonia were treated with antibiotics. A combination of C-reactive protein (CRP) and procalcitonin (PCT) was used as markers to analyze the possible indications for antibiotic use. With threshold levels set at 0.25 µg/L for PCT and 20 mg/L for CRP, the rate of unreasonable use of antibiotics was 55.2%. By contrast, at a CRP level threshold of 60 mg/L, the rate of antibiotic misuse was 77.3%. A total of 39 of the 163 (23.9%) patients did not meet the guidelines for drug selection for viral CAP in adults. The unreasonable use of antibacterial drugs for the treatment of viral CAP in adults is a serious concern. Clinicians must reduce the unnecessary use of antibiotics.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study / 中华医学杂志(英文版)

BACKGROUND@#Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.@*METHODS@#We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.@*RESULTS@#Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.@*CONCLUSION@#A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study / 中华医学杂志(英文版)

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Analysis of curative effects of Tolterodine combined with Desmopressin acetate in the treatment of overactive bladder in children with diurnal urinary incontinence / 中华实用儿科临床杂志

Objective:To evaluate the efficacy and safety of Tolterodine combined with Desmopressin acetate in the treatment of overactive bladder in children with diurnal urinary incontinence.Methods:Clinical data of 55 overactive bladder children with diurnal urinary incontinence in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2016 to December 2018 were collected.The urodynamic examination on all patients excluded factors such as neurogenic bladder and spinal cord trauma from the causes of urinary incontinence.Twenty-eight patients underwent Tolterodine plus Desmopressin acetate, and the remaining 27 patients were treated with Tolterodine alone.The course of medication was determined according to whether the clinical symptoms disappeared or not.According to the ratings of overactive bladder, the treatment effects of all children were evaluated and divided into complete improvement, obvious improvement, and little or no improvement.The effectivity was defined as complete and obvious improvement, while the ineffectiveness was defined as little or no improvement.Meanwhile, adverse effects like dry mouth, blushing and constipation were observed.Results:In the Tolterodine+ Desmopressin acetate group, 15 cases were improved completely (53.6%, 15/28 cases), 11 cases were obviously improved (39.3%, 11/28 cases), 2 cases were slightly or not improved (7.1%, 2/28 cases). The effective rate was 92.9% (26/28 cases). In the Tolterodine group, 9 cases were improved completely (33.3%, 9/27 cases), 11 cases were obviously improved (40.7%, 11/27 cases), and 7 cases (25.9%, 7/27 cases) were not or slightly improved.The effective rate was 74.1% (20/27 cases). The difference of the effective rate between the 2 groups was statistically significant ( χ2=9.61, P<0.05). Six cases (21.4%, 6/28 cases) in the Tolterodine+ Desmopressin acetate group presented adverse reactions, and that number was 5 (18.5%, 5/27 cases) in the Tolterodine group.There was no significant difference in the proportion of adverse reaction events between the 2 groups. Conclusions:Tolterodine combined with Desmopressin acetate can significantly improve symptoms and reduce urinary incontinence events in children with overactive bladder and diurnal urinary incontinence.The combined use of Tolterodine and Desmopressin acetate is safe and well tolerated, with better efficacy than Tolterodine alone.Therefore, it is recommended as a new treatment for overactive bladder in children with diurnal urinary incontinence.

Correlation of parameters of lordosis type cervical spine saggitai plane in asymptomatic adults / 中国组织工程研究

BACKGROUND: Normal sagittal balance of cervical spine is the key to cervical spine orthopedic surgery. As the complexity of the anatomical structure and physiological function of the cervical spine, accurate measurement of sagittal balance parameters and correlation between parameters become an important reference for preoperative planning and postoperative evaluation of curative effect. Current research focuses on patients with clinical symptoms of cervical syondylosis. OBJECTIVE: To investigate the correlation of parameters of lordosis type cervical spine saggitai plane in asymptomatic adults. METHODS: Cervical anteroposterior and lateral DR images of 120 adult patients with asymptomatic lordosis type cervical spine were retrospectively analyzed. The subjects were divided into three groups according to age: Group A (21-40 years), group B (41-60 years), and group C (61-80 years). The sagittal parameters of the cervical spine were measured, including C2-C7 sagittal vertical axis (C2-C7SVA), central of gravity to C7 sagittal vertical axis (CG-C7 SVA), T1 slope, C0-C2 Cobb angle and C2-C7 Cobb angle. The correlation between different imaging parameters and age was analyzed. This study was approved by the Ethics Committee, First Hospital of Shijiazhuang and Second Hospital of Hebei Medical University. All subjects signed the informed consent. RESULTS AND CONCLUSION: (1) C2-C7 SVA (F=11.188, P < 0.001), CG-C7 SVA (F=6.132, P=0.003) and T, slope (F=11.682, P < 0.001) were significantly different among different groups. There was no significant difference in C0-C2 Cobb angle (F=1.178, P=0.311) and C2-C7 Cobb angle (F=0. 860, P=0. 426). (2) T1 slope was (51,63±5.85)°, (54.66±5.58)° and (57.48±4.74)° in groups A, B and C, respectively. Linear correlation analysis showed that T1 slope was positively correlated with age (r=0. 533, P < 0. 001). T1 slope was positively correlated with C2-C7 Cobb angle (r=0. 561, P< 0.001). These results indicated that T1 slope increased with age in asymptomatic cervical lordosis adults. Moreover, T1 slope was positively correlated with age.

Mechanisms for establishment of the placental defensive barrier / 生理学报

Placenta serves as a temporary fetal organ, which mediates maternal-fetal crosstalk and intrauterine fetal growth. Placental defensive barrier is a fundamental physiological function, which balances maternal immune tolerance to the fetus and resistance to pathogens. This review summarizes the latest research progress on the mechanisms of placental barrier formation from the view of placental development. Recent discoveries have shed light on the cellular and molecular properties of placental defensive mechanisms in syncytiotrophoblast, including autophagy, exosome mediated anti-pathogenic pathways, cell-cell junctions and cytoskeleton networks. We also present an overview of placental barrier dysfunction and its implications in intrauterine TORCH infections.

Establishment and evaluation of a nomogram model of systemic inflammatory response syndrome after percutaneous nephrolithotomy / 医学研究生学报

Objective The main cause of systemic inflammatory response syndrome(SIRS) after percutaneous nephrolithotomy(PCNL) was still unclear. The purpose of this study was to investigate the risk factors associated with SIRS after PCNL and establish the nomogram model. Methods A retrospective analysis of 213 cases of PCNL patients due to upper urinary calculi admitted to urology department in affiliated hospital of guilin medical college from December 2017 to December 2018 was performed. According to the occurrence of SIRS, patients were divided into SIRS group (SIRS patients) and control group (patients without SIRS). Logistic regression was used to analyze the risk factors of SIRS after PCNL, and a nomogram model was established based on logistic regression model. Results There were 54 cases in the SIRS group and 159 in the control group. Gender(OR=2.547, 95%cl:1.229-5.275), diabetes (OR=5.027, 95%cl: 1.442-17.525), calculi surface area (OR=2.657, 95%cl: 1.206-5.853), NLR immediately after surgery (OR=3.793, 95%cl: 1.749-8.02), operation time (OR=2.985, 95%cl: 1.305-6.826), and blood transfusion (OR=12.50, 95%cl: 12.50). 1.954-80.056) were the risk factors of SIRS after PCNL (P<0.05). Based on the results of the logistic multi-factor regression model mentioned above, visualized display of the model was achieved by using column and diagram. As the NLR ratio, operation time and stone surface area increased immediately after the operation, the score gradually increased, and the risk of SIRS gradually increased. The nomogram model established according to logistic regression model has good differentiation and model consistency (c-index =0.791). Conclusion According to the risk factors, such as gender, diabetes history, stone surface area, immediate postoperative NLR, the constructed nomogram model has good predictive efficacy, which is of guiding significance for clinical practice.

Evaluation of endoscopic submucosal dissection and surgery in the diagnosis and treatment of early gastric cancer / 中华消化内镜杂志

Objective@#To compare the efficacy and safety of endoscopic submucosal dissection(ESD) and surgery in the treatment of early gastric cancer.@*Methods@#Clinical data of patients with early gastric cancer who received ESD or surgery in Beijing Friendship Hospital from June 2012 to May 2018 were collected. Complete resection rate, complication incidence, hospital stay and expenses between the two groups were compared.@*Results@#There was no significant difference between two groups in complete resection rate[95.7%(245/256) VS 99.0%(97/98), P=0.191], or the complication incidence [5.9%(15/256) VS 8.2%(8/98), P=0.471]. Hospital stay was shorter in the ESD group than that in the surgery group(11.5±3.7 d VS 19.4±13.0 d, P=0.000). Expenses were less in the ESD group than those in the surgery group (27 383.1±10 143.0 yuan VS 78 004.3±79 027.8 yuan, P=0.000).@*Conclusion@#The efficacy and safety of ESD are comparable with surgery in the treatment of early gastric cancer, but ESD is superior to surgery in hospital stay and expenses.

Predictors for operation time of endoscopic submucosal dissection for superficial gastric lesions / 中华消化内镜杂志

Objective@#To investigate the risk factors of operation time of endoscopic submucosal dissection (ESD) for superficial gastric lesions.@*Methods@#Clinicopathologic data of 193 patients (195 lesions) diagnosed with early gastric cancer preoperatively who received ESD in Beijing Friendship Hospital from January 2015 to December 2017 were retrospectively collected, including basic information (age, gender, body mass index, comorbidities), lesion characteristics (size, location, morphology), the operators′ experience of ESD, operation time, and postoperative pathology, etc. Univariate analysis was performed to find the risk factors of ESD operation time, and logistic regression analysis was performed on the factors with statistical differences in univariate analysis to find the independent risk factors of ESD operation time over 120 min.@*Results@#The mean age of the patients was 63.34±9.11 years. The median time of ESD operation was 120.00 (95.00, 165.00) min and the median size of the lesions was 1.50 (1.00, 2.38) cm. Early gastric cancer was diagnosed by postoperative pathology in 164 lesions (84.10%), among which 162 lesions (98.78%) achieved en bloc resection, and 148 lesions (90.24%) achieved curative resection. The gender (P=0.018), location(P<0.001) and size (r=0.209, P=0.007) were risk factors of the operation time by univariate analysis, while age, body mass index, American Society of Anesthesiologists (ASA) grade, roughness of lesion surface, presence or absence of white moss and ulcer, depth of lesion invasion, operative period, gross shape of lesion, degree of differentiation, and experience of operator were not associated with operation time (all P>0.05). Multivariate analysis showed that the lesion located in cardia/fundus of stomach (OR=5.656, 95%CI: 2.291-13.964, P<0.001), body of stomach (OR=2.667, 95%CI: 1.048-6.785, P=0.040) and >2 cm in size (OR=2.761, 95%CI: 1.229-6.205, P=0.014) were independent risk factors for the operation time longer than 120 min.@*Conclusion@#Lesions located in the cardia/fundus, body of stomach and >2 cm in size are independent risk factors for long operation time of ESD.

The effects of salidroside on the apoptosis pathway of myocardial cells in acute exhausted rats / 中国应用生理学杂志

OBJECTIVE@#To investigate whether salidroside (Sal) plays a part in protecting myocardial cell through reducing the myocardial ischemia and the apoptosis pathway of both death receptors and mitochondria in acute exhausted rats.@*METHODS@#Male SD rats were randomly divided into 4 groups (n=6): control group(Con), acute exhaustive swimming group (EE), low-dose and high-dose Sal pre-treatment exhaustive swimming group (SLE, SHE). Rats were treated with Sal solution (15 or 30 mg/(kg·d)) or 0.9%NaCl (3 ml/(kg·d)) by intraperitoneal injection for 15 d, respectively. The Con group did not carry out swimming training. The next day after the end of intraperitoneal administration, the rats in EE, SLE and SHE group were forced to swim until they were exhausted followed the standard of Thomas. After the end of exhaustive exercise, the rats were anesthetized and the blood samples and hearts were collected immediately. The myocardial ischemia and hypoxia area and myocardial apoptosis index (AI) were also observed. Serum ischemia modified albumin (IMA), cardiac troponin I (cTnI), brain natriuretic peptide(BNP) and myocardial cell Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) were determined. The expressions of myocardial TNF receptor superfamily member 6 (Fas), cytochrome C (Cyto-c), aspartate proteolytic enzyme-3(Caspase-3), aspartate proteolytic enzyme-8(Caspase-8), and aspartate proteolytic enzyme-9(Caspase-9) were detected.@*RESULTS@#Compared with the Con group, the myocardial ischemia and hypoxia area in EE group was increased significantly. The serum levels of IMA, cTnI and BNP, AI and Bax levels and cardiac Fas, Cyto-C, Caspase-3, Caspase-8 and Caspase-9 protein expressions of EE group were also increased significantly (P＜0.01), while the protein expression of Bcl-2 in cardiac tissues was decreased significantly (P＜0.01). Compared with the EE group, the myocardial ischemia and hypoxia area, serum levels of IMA, cTnI and BNP, AI and Bax levels, and the protein expressions of cardiac Fas, Cyto-C, Caspase-3, Caspase-8 and Caspase-9 in Sal group were all decreased significantly(P＜0.01). while the protein expression of cardiac Bcl-2 in Sal group were increased significantly (P＜0.01).@*CONCLUSION@#Sal plays a role in protecting myocardial cell through reducing the myocardial ischemia and inhibiting myocardial cell apoptosis in exhaustive exercise rats. The mechanism of reducing myocardial cell apoptosis may be related to inhibiting the expressions of Fas, Cyto-C, Caspase-3, Caspase-8, Caspase-9 and increasing the expression of Bcl-2.