[Effects of recombinant human interleukin-11 on LPS-induced intestinal epithelial cell injury in rats].

OBJECTIVE: To study the effects of recombinant human interleukin-11 (rhIL-11) on the proliferation and apoptosis of rat intestinal epithelial cell line (IEC-6). METHODS: IEC-6 cells were treated with LPS to establish necrotizing enterocolitis (NEC) model in vitro. rhIL-11 (100 ng/mL) was administered following LPS treatment and these cells were used as the IL-11 treatment group. The cells treated with normal saline only served as the control group. MTT assay was used to determine an optimal concentration (5-200 µg/mL) and time (1-24 h). MTT assay was used to measure the proliferation of IEC-6 cells at 3, 6, 9 and 12 hours after rhIL-11 treatment. Flow cytometry was used to evaluate the apoptosis of IEC-6 cells. RESULTS: IEC-6 cells treated with various concentrations of LPS at various time points showed a lower proliferation than the control group (P<0.05). After 9 hours of rhIL-11 treatment, the proliferation activity of IEC-6 cells in the IL-11 treatment group significantly increased compared with the NEC model group without rhIL-11 treatment (P<0.05), reaching to the level of the control group. The total apoptotic and necrotic rate of IEC-6 cells in the IL-11 treatment group decreased significantly compared with the NEC model group without rhIL-11 treatment (P<0.01), but were still higher than the control group (P<0.05). CONCLUSIONS: rhIL-11 can promote proliferation and reduce apoptotic and necrotic rates of IEC-6 cells treated with LPS.

[Perinatal high-risk factors for necrotizing enterocolitis in preterm infants: a case-control study].

OBJECTIVE: To study the timing of presentation and perinatal high-risk factors for necrotizing enterocolitis (NEC) in preterm infants with a gestational age of <33 weeks. METHODS: A case-control study was conducted in 49 preterm infants with NEC (gestational age <33 weeks) who were admitted to the Neonatal Intensive Care Unit of Beijing Bayi Children's Hospital between October 1, 2010 and December 30, 2012, as well as preterm infants without NEC during the same period. The timing of presentation of NEC was retrospectively analyzed, and the perinatal high-risk factors for NEC were determined by multivariate logistic regression analysis. RESULTS: The median age of onset was 17.5 days (range: 3-106 d) in preterm infants with NEC. Sex, being small for gestational age, delivery mode and antenatal corticosteroid therapy were not associated with the development of NEC; low gestational age, low birth weight and neonatal asphyxia increased the risk of NEC, and low gestational age was identified as an independent high-risk factor for the development of NEC. CONCLUSIONS: Low gestational age is an important risk factor for the development NEC in preterm infants under 33 weeks' gestation, and the median age of onset is 17.5 days.

A new isopimarane-type diterpene with anti-inflammatory activity from the Clinacanthus nutans.

A new isopimarane-type diterpene clinacanoid A (1) together with seven known terpenoids (2-8) were obtained from the Clinacanthus nutans. Their structures were elucidated based on extensive spectroscopic analysis (NMR, HR-ESI-MS), and the absolute configuration of 1 was established based on single crystal X-ray diffraction. The inhibitory activity of all the compounds on NO production in lipopolysaccharide-induced (LPS) mouse leukemic monocyte macrophage RAW264.7 cells was evaluated. Among them, compounds 1 and 3 showed potential anti-inflammatory activities, with IC50 values of 13.3 ± 0.3 and 12.4 ± 0.4 µM, respectively.

Expression of terpene synthase-related genes in parents and offspring of Flammulina filiformis based on differences in volatile aroma components.

Flammulina filiformis (F. filiformis) is one of the four major edible types of fungus in the world and has been cultivated in China since 800 CE (Anno Domini). Some of the most essential criteria for evaluating the quality of F. filiformis are the types and contents of volatile components present. A focused study on screened the terpene synthase genes involved in the aroma of offspring and compared key terpenoids between parents and offspring, which is helpful for the development and application of F. filiformis. Firstly, the volatile aroma components of parent and offspring F. filiformis were extracted using two pretreatment procedures, and then were semi-quantified by an internal standard. Forty-eight, fifty-eight, and forty-eight volatile compounds were identified in parents and offspring of three different strains, and 15, 22, and 12 aroma compounds (OAVs ≥ 1) were further screened out via calculating their odor activity values (OAVs). Terpenoids, in particular linalool and eucalyptol, which contribute more to the aroma, result in the unique green and grassy aroma of the offspring. At last, the F. filiformis genome was resequenced and the coordinates of genes related to terpenoid synthase were determined. The results showed that Scaffolds, including scaffold3.t874 and scaffold9.t157 were connected to terpenoid synthesis of offspring (No. 61523). The variant genes g269 and g61 were related to terpenoid synthase sequences. This study provides a theoretical foundation for the cultivation of more diverse and unique varieties of F. filiformis.

Gut bacterium promotes host fitness in special ecological niche by affecting sugar metabolism in Drosophila suzukii.

As an important fruit pest of global significance, Drosophila suzukii occupies a special ecological niche, with the characteristics of high sugar and low protein contents. This niche differs from those occupied by other fruit-damaging Drosophila species. Gut bacteria substantially impact the physiology and ecology of insects. However, the contribution of gut microbes to the fitness of D. suzukii in their special ecological niche remains unclear. In this study, the effect of Klebsiella oxytoca on the development of D. suzukii was examined at physiological and molecular levels. The results showed that, after the removal of gut microbiota, the survival rate and longevity of axenic D. suzukii decreased significantly. Reintroduction of K. oxytoca to the midgut of D. suzukii advanced the development level of D. suzukii. The differentially expressed genes and metabolites between axenic and K. oxytoca-reintroduced D. suzukii were enriched in the pathways of carbohydrate metabolism. This advancement was achieved through an increased glycolysis rate and the regulation of the transcript level of key genes in the glycolysis/gluconeogenesis pathway. Klebsiella oxytoca is likely to play an important role in increasing host fitness in their high-sugar ecological niche by stimulating the glycolysis/gluconeogenesis pathway. As a protein source, bacteria can also provide direct nutrition for D. suzukii, which depends on the quantity or biomass of K. oxytoca. This result may provide a new target for controlling D. suzukii by inhibiting sugar metabolism through eliminating the effect of K. oxytoca and thus disrupting the balance of gut microbial communities.

Metatranscriptome of human lung microbial communities in a cohort of mechanically ventilated COVID-19 Omicron patients.

The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.

Scavenger receptor B1 mediates phagocytosis and the antimicrobial peptide pathway in the endoparasitic wasp Micropilits mediator.

Scavenger receptors (SRs) are a family of pattern recognition receptors (PRRs) in the immune system. They are required for phagocytosis and act as co-receptors of Toll-like receptors to regulate immune signaling pathways in the fight against pathogens. Little is known about the function of SRs in insects. Here, we reported on a member of the SR family from the parasitic wasp Micropilits mediator (designated MmSR-B1) that is responsive to bacterial infection. The recombinant extracellular CD36 domain of MmSR-B1 produced in Escherichia coli cells is capable of binding to peptidoglycans and bacterial cells, causing agglutination of bacteria. Furthermore, we demonstrated that double-stranded RNA-mediated knockdown of MmSR-B1 impedes hemocyte phagocytosis and downregulates the expression of antimicrobial peptide (AMP) genes defensins and hymenoptaecins. Knockdown of MmSR-B1 led to increased death of the wasps when challenged by bacteria. Our study suggests that MmSR-B1 mediates phagocytosis and the production of AMPs in M. mediator wasps.

Clinical Analysis of Severe Radiation Pneumonia.

OBJECTIVE: The present study aims to discuss the clinical characteristics, factors, and treatment methods affecting the prognosis in patients with severe radiation pneumonia (RP). METHODS: The radiotherapy status, clinical features, imaging characteristics, laboratory examination results, treatment methods, and prognoses of 34 patients with severe RP treated in our department between January 2011 and July 2017 were retrospectively analyzed. The severe RP grading was based on the Common Terminology Criteria for Adverse Events version 4.0; patients who scored Grade ≥3 were considered to have a severe case of RP. RESULTS: The results of the present study showed that 22 patients had lung cancer, 6 had esophageal cancer, 5 had breast cancer, and 1 had colon cancer with lung metastasis. The total radiation dose was 37.5-66 Gy, and the overall average dose was 53 Gy; the average dose in the patients who died was 52.9 Gy. A total of 28 patients presented with a cough and sputum as the initial symptom, and 24 presented with wheezing as an accompanying symptom; of the 24 patients, 8 experienced fever, 2 experienced wheezing as the only symptom, 1 had chest pain, and 1 had chest tightness. In 26 patients, the changes were in the radiation field, and in 8 cases, the changes appeared both inside and outside the radiation field. After the use of glucocorticoid methylprednisolone, respiratory support, and anti-infection treatment, 18 patients were cured, 8 showed a condition improvement, and 8 died. CONCLUSION: The prognosis of severe RP was not significantly correlated with the administered radiation dose; however, lung cancer, a high Acute Physiology and Chronic Health Evaluation score, and delayed diagnosis were risk factors for patient death. However, a combination of antibiotic therapy, ventilator-assisted respiration, and steroid therapy could improve patient prognosis.

Reactive oxygen species and antimicrobial peptides are sequentially produced in silkworm midgut in response to bacterial infection.

The silkworm, Bombyx mori, is utilized as a research model in many aspects of biological studies, including genetics, development and immunology. Previous biochemical and genomic studies have elucidated the silkworm immunity in response to infections elicited by bacteria, fungi, microsporidia, and viruses. The intestine serves as the front line in the battle between insects and ingested harmful microorganisms. In this study, we performed RNA sequencing (RNA-seq) of the larval silkworm midgut after oral infection with the Gram-positive bacterium Bacillus bombysepticus and the Gram-negative bacterium Yersinia pseudotuberculosis. This enables us to get a comprehensive understanding of the midgut responses to bacterial infection. We found that B. bombysepticus induced much stronger immune responses than Y. pseudotuberculosis did. Bacterial infection resulted in more energy consumption including carbohydrates and fatty acids. The midgut immune system was characterized by the generation of reactive oxygen species and antimicrobial peptides. The former played a critical role in eliminating invading bacteria during early stage, while the latter executed during late stage. Our results provide an integrated insight into the midgut systematic responses to bacterial infection.

[An experimental study of bronchoscopic lung volume reduction medicine].

OBJECTIVE: To evaluate the effect and safety of experimental bronchoscopic lung volume reduction (BLVR) using an one-way valve designed independently. METHODS: The animal study was carried out from June to December 2008. Totally 36 valves were implanted in the target bronchi of 12 healthy male goats. CT scan, artery blood gas exchange and lung pathology were performed after 2, 4, 8 and 12 weeks. RESULTS: All the valves were implanted successfully, but 3 valves were expectorated at the end. The procedure was well tolerated. CT scan showed that for more than 45% (15/33) of the valves, the target lung tissue had collapsed. Lung pathology showed that the alveolar space was deflated and collapsed. Lymphocytes and monocytes infiltrated the interstitial tissue with some degree of fibrosis. CONCLUSIONS: This animal study showed that the independently manufactured one way valve was effective and safe. The one way valve may be useful in the treatment of severe emphysema in the future.

Analysis and recognition of characteristics of digitized tongue pictures and tongue coating texture based on fractal theory in traditional Chinese medicine.

Simple fractal dimensions have been proposed for use in the analysis of the characteristics of digitized tongue pictures and tongue coating texture, which could further the establishment of objectified classification criteria under the conditions of expanding sample size. However, detailed descriptions on simple fractal dimensions have been limited. Therefore, BP (back propagation) neural network model classifiers could be designed by further calculation of the multiple fractal spectrum characteristics of digitized tongue pictures in order to classify and recognize the thin/thick or greasy characteristics of tongue coating. The fractal dimensions of sample data of 587 digitized tongue pictures were collected in a standard environment. A statistical analysis was conducted on the calculation results of the sample data, and the sensitivity of the fractal dimensions to the thin/thick and greasy characteristics of digitized tongue pictures was observed. As the overlap region resulted from a range of values of a single parameter, another 8 characteristic parameters of the multiple fractal spectra of the digitized tongue pictures were further proposed as the elements in the input layer of the three-layers BP neural network. Automatic recognition classifiers were designed and trained for the characteristics of digitized tongue pictures and tongue coating textures. The simple fractal dimension was sensitive to the thin/thick and greasy characteristics of digitized tongue pictures and could better judge the characteristics of the thickness of the tongue coating. A classifier with characteristic parameters of multiple fractal spectra as the input vectors identified by the BP neural network models could effectively increase the accuracy rate judged by the characteristics of the tongue coating texture.

The effect of text message reminders on medication adherence among patients with coronary heart disease: A systematic review and meta-analysis.

BACKGROUND: To determine the effectiveness of text message reminders (TMR) on medication adherence (MA) and to investigate the effects of TMR on clinical outcomes. METHODS: The PubMed, Cochrane library, EMbase, and China Biology Medicine databases were searched for randomized-controlled trials with TMR as the intervention for patients with coronary heart disease. Two reviewers independently extracted data and assessed the risk of bias. Meta-analysis was conducted using Stata 15.0 software. RESULTS: In total, 1678 patients in 6 trials were included. Compared with the control group, the MA was 2.85 times greater among the intervention group (RR [relative risk] 2.85; 95% confidence interval [CI] 1.07-7.58). TMR reduced systolic blood pressure (BP) (weighted mean difference) = -6.51; 95% CI -9.79 to -3.23), cholesterol (standard mean difference = -0.26; 95% CI -0.4 to -0.12) and increased the number of patients with BP <140/90 mm Hg (RR 1.39; 95% CI 1.26-1.54). CONCLUSION: TMR significantly promoted MA and reduced systolic BP, cholesterol level, and body mass index, but had no effect on mortality, diastolic BP, or lipoproteins. However, substantial heterogeneity existed in our analyses.

Comparative efficacy of various antimicrobial lock solutions for preventing catheter-related bloodstream infections: A network meta-analysis of 9099 patients from 52 randomized controlled trials.

OBJECTIVES: It remains uncertain which catheter lock solution (CLS) to prevent catheter-related bloodstream infections (CRBSI) works best and is safest for patients. This study was performed to compare the efficacy of different CLSs for the prevention of CRBSI and ranked these CLSs for practical consideration. METHODS: The PubMed, Web of Science, Embase, and MEDLINE databases, earlier relevant meta-analyses, and the reference lists of included studies were searched. The primary outcome was CRBSI; secondary outcomes were catheter-related thrombosis and exit-site infections. A network meta-analysis was performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 52 randomized controlled trials involving 9099 patients and evaluating 13 CLSs (single and combinations) were included. With regard to the quality of the evidence, the risk of bias was typically low or unclear (45 out of 52 trials, 86.5%). In the network meta-analysis, saline (OR 8.44, 95% CI 2.19-32.46), gentamicin+citrate (OR 2.92, 95% CI 1.32-6.42), ethanol (OR 5.33, 95% CI 1.22-23.32), and cloxacillin+heparin (OR 2.07, 95% CI 1.19-5.49) were associated with a greater effect on CRBSI than heparin. CONCLUSIONS: This network meta-analysis showed that minocycline-ethylenediaminetetraacetic acid (EDTA) seemed to be the most effective for the prevention of CRBSI and exit-site infection, and cefotaxime+heparin seemed to be the most effective for catheter-related thrombosis.

Insights into the venom protein components of Microplitis mediator, an endoparasitoid wasp.

Endoparasitoid wasps deliver a variety of maternal factors, such as venom proteins, viruses, and virus-like particles, from their venom and calyx fluid into hosts and thereby regulate the hosts' immune response, metabolism and development. The endoparasitoid, Microplitis mediator, is used as an important biological agent for controlling the devastating pest Helicoverpa armigera. In this study, using an integrated transcriptomic and proteomic analysis approach, we identified 75 putative venom proteins in M. mediator. The identified venom components were consistent with other known parasitoid wasps' venom proteins, including metalloproteases, serine protease inhibitors, and glycoside hydrolase family 18 enzymes. The metalloprotease and serpin family showed extensive gene duplications in venom apparatus. Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomics revealed 521 proteins that were differentially expressed at 6 h and 24 h post-parasitism, including 10 wasp venom proteins that were released into the host hemolymph. Further analysis indicated that 511 differentially expressed proteins (DEP) from the host are primarily involved in the immune response, material metabolism, and extracellular matrix receptor interaction. Taken together, our results on parasitoid wasp venoms have the potential to enhance the application of endoparasitoid wasps for controlling insect pest.

A Metalloprotease Homolog Venom Protein From a Parasitoid Wasp Suppresses the Toll Pathway in Host Hemocytes.

Parasitoid wasps depend on a variety of maternal virulence factors to ensure successful parasitism. Encapsulation response carried out by host hemocytes is one of the major host immune responses toward limiting endoparasitoid wasp offspring production. We found that VRF1, a metalloprotease homolog venom protein identified from the endoparasitoid wasp, Microplitis mediator, could modulate egg encapsulation in its host, the cotton bollworm, Helicoverpa armigera. Here, we show that the VRF1 proenzyme is cleaved after parasitism, and that the C-terminal fragment containing the catalytic domain enters host hemocytes 6 h post-parasitism. Furthermore, using yeast two-hybrid and pull-down assays, VRF1 is shown to interact with the H. armigera NF-κB factor, Dorsal. We also show that overexpressed of VRF1 in an H. armigera cell line cleaved Dorsal in vivo. Taken together, our results have revealed a novel mechanism by which a component of endoparasitoid wasp venom interferes with the Toll signaling pathway in the host hemocytes.

Comparative analysis of peptidoglycan recognition proteins in endoparasitoid wasp Microplitis mediator.

Peptidoglycan recognition proteins (PGRPs) are a family of innate immune receptors that specifically recognize peptidoglycans (PGNs) on the surface of a number of pathogens. Here, we have identified and characterized six PGRPs from endoparasitoid wasp, Microplitis mediator (MmePGRPs). To understand the roles of PGRPs in parasitoid wasps, we analyzed their evolutionary relationship and orthology, expression profiles during different developmental stages, and transcriptional expression following infection with Gram-positive and -negative bacteria and a fungus. MmePGRP-S1 was significantly induced in response to pathogenic infection. This prompted us to evaluate the effects of RNA interference mediated gene specific knockdown of MmePGRP-S1. The knockdown of MmePGRP-S1 (iMmePGRP-S1) dramatically affected wasps' survival following challenge by Micrococcus luteus, indicating the involvement of this particular PGRP in immune responses against Gram-positive bacteria. This action is likely to be mediated by the Toll pathway, but the mechanism remains to be determined. MmePGRP-S1 does not play a significant role in anti-fungal immunity as indicated by the survival rate of iMmePGRP-S1 wasps. This study provides a comprehensive characterization of PGRPs in the economically important hymenopteran species M. mediator.

Effect of recombinant human interleukin-11 on expressions of interleukin-11 receptor alpha-chain and glycoprotein 130 in intestinal epithelium cell line-6 after neutron irradiation.

AIM: To explore the effect of recombinant human interleukin-11 (rhIL-11) on the expressions of interleukin-11 receptor alpha-chain (IL-11Ralpha) and an additional signal transducer glycoprotein 130 (gp130) in intestinal epithelium cell line-6 (IEC-6) after neutron irradiation. METHODS: Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation. The apoptosis and necrosis rates and expressions of IL-11Ralpha and gp130 were observed by flow cytometry, immunohistochemistry, Western blot and image analysis. RESULTS: The apoptosis rate of IEC-6 cells was increased by irradiation at 6 h (P < 0.01), IL-11 stimulation resulted in a decreased apoptosis rate in irradiated IEC-6 cells (P < 0.05). In normal control IEC-6 cells, intense immunoreactivity of IL-11Ralpha was located within the cell membrane and cytoplasm. The level of IL-11Ralpha expression significantly decreased at 6 h after irradiation (P < 0.01) and restored at 24 h after irradiation. In IEC-6 cells treated with both radiation and rhIL-11, the level of IL-11Ralpha expression was higher than that of irradiated cells (P < 0.05). When it came to gp130 protein, it was located in the cytoplasm of IEC-6 cells. After irradiation, we found a progressive decrease in the expression of gp130 protein (P < 0.05) in 48 h post-radiation, while in rhIL-11-stimulated cells, it came back to normal level at 24 h after irradiation and decreased at 48 h, but was still higher than that of only irradiated cells (P < 0.05). CONCLUSION: rhIL-11 can protect IEC-6 cells from neutron irradiation. The protective effect of rhIL-11 might be connected with its ability to up-regulate the expressions of specific ligand-binding subunit IL-11Ralpha and signal-transducing subunit gp130.

Serum miR-125a-5p, miR-145 and miR-146a as diagnostic biomarkers in non-small cell lung cancer.

BACKGROUND: Lung cancer is becoming the leading cause of cancer-related deaths with high mortality worldwide and in China as well. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer accounting for approximately 85% of all cases. Over 70% of cases are at loco-regionally advanced stages or have distant metastasis at the time of presentation with subsequently poor prognosis. MiRNAs are stable molecules in blood and used as biomarkers for the early diagnosis of various malignancy. The purpose of this study was to evaluate whether circulating miR-125a-5p, miR-145 and miR-146a could be used as biomarkers for the diagnosis of NSCLC through measuring their expression and assess their relationship with clinical pathological factors. METHODS: Expression levels of serum miR-125a-5p, miR-145 and miR-146a were detected in 70 pairs of NSCLC patients and healthy controls using quantitative real-time PCR analysis. RESULTS: Serum miR-125a-5p, miR-145 and miR-146a were overexpressed in NSCLC patients compared with healthy controls. Their values of the area under the receiver -operating characteristic curve (AUC-ROC) were 0.71, 0.84 and 0.78. Optimal sensitivity and specificity were 73.53% and 55.71%, 92.75% and 61.43%, 84.06% and 58.57%, respectively in differentiating NSCLC patients from healthy controls. CONCLUSIONS: These preliminary data suggest that serum miR-125a-5p, miR-145 and miR-146a may be useful noninvasive biomarkers for the clinical diagnosis of NSCLC.