Correlation between left atrial appendage morphology based on fractal dimension quantification and its hemodynamic parameters in patients with atrial fibrillation.

AIMS: To investigate the relationship between left atrial appendage (LAA) morphology, quantified based on fractal dimension (FD), and LAA hemodynamic parameters in patients with atrial fibrillation (AF), in an effort to reveal the effect of LAA shape on blood flow. MATERIALS AND METHODS: 225 patients with AF who underwent cardiac computed tomography angiography (CTA) and transesophageal echocardiography (TEE) were enrolled. LAA morphology was quantified based on FD on cardiac CTA images, and LAA hemodynamic parameters, including injection fraction (EF), filling peak flow velocity (FV), maximum speed of emptying (PEV), and wall motion velocity (WMV), were assessed using TEE. RESULTS: We divided the patients with AF into two groups based on a mean LAA FD of 1.32: the low FD group (n=124) and the high FD group (n=101). Compared to the low FD group, there were more patients with LAA circulatory stasis/thrombus (P=0.008) in the high FD group, as well as lower LAA FV (P=0.004), LAA PEV (P=0.007), and LAA WMV (P=0.007). LAA FD was an independent and significant determinant of LAA EF (ß = -11.755, P=0.001), LAA FV (ß = -17.364, P=0.004), LAA PEV (ß = -18.743, P<0.001), and LAA WMV (ß = -7.740, P=0.001) in multiple linear regression analysis. CONCLUSIONS: LAA FD is an essential determinant of LAA hemodynamic parameters, suggesting that the relatively complex morphology of the LAA may influence its hemodynamics, which can correlate with embolic events.

Relationship between pericoronary fat-attenuation values quantified by coronary computed tomography angiography and coronary artery disease severity.

AIM: To explore the relationship between pericoronary fat-attenuation index (FAI) values and coronary artery disease (CAD) severity measured using coronary computed tomography angiography (CCTA). MATERIALS AND METHODS: This study retrospectively included 428 patients with CAD who were eligible and underwent CCTA at our hospital. CAD severity on CCTA images including obstructive stenosis and extensive lesions, and segment stenosis and involvement score (SSS, SIS), and CAD-RADS classification were assessed. FAI values for left anterior descending (LAD), left circumflex (LCX) branches, and right coronary artery (RCA) were quantified using fully automated software. The relationship between FAI values and CAD severity was assessed using univariate and multivariate regression models. RESULTS: Univariate analyses showed that sex and current smoking were associated with elevated FAILAD and FAILCX values (all P<0.05), whereas CAD severity was not relevant (all P>0.05). Not only clinical factors such as sex, current smoking, and hypertension were associated with elevated FAIRCA, but also indicators to assess CAD severity including obstructive stenosis, SIS, and SSS were related to it (all P<0.05). Multivariate analysis demonstrated that after correcting for the effects of other conventional cardiovascular risk factors and CCTA imaging features, current smoking was an independent risk factor for elevated FAI values (odds ratio [OR] = 0.569, 0.458, and 0.517; all P<0.05), whereas that SSS (OR=1.041, P=0.027) for elevated FAIRCA values. CONCLUSION: Following correction for conventional cardiovascular risk factors and imaging characteristics, current smoking was an independent clinical risk factor for elevated FAI values, and SSS was an independent risk factor for elevated FAIRCA values.

[Role of liver sinusoidal endothelial cell damage in the developmental process of hepatic sinusoidal obstruction syndrome: a focus on the research progress of immune inflammatory mechanisms].

Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

Bacterial biota associated with the invasive insect pest Tuta absoluta (Meyrick).

Tuta absoluta (the tomato pinworm) is an invasive insect pest with a highly damaging effect on tomatoes causing between 80 and 100% yield losses if left uncontrolled. Resistance to chemical pesticides have been reported in some T. absoluta populations. Insect microbiome plays an important role in the behavior, physiology, and survivability of their host. In a bid to explore and develop an alternative control method, the associated microbiome of this insect was studied. In this study, we unraveled the bacterial biota of T. absoluta larvae and adults by sequencing and analyzing the 16S rRNA V3-V4 gene regions using Illumina NovaSeq PE250. Out of 2,092,015 amplicon sequence variants (ASVs) recovered from 30 samples (15 larvae and 15 adults), 1,268,810 and 823,205 ASVs were obtained from the larvae and adults, respectively. A total of 433 bacterial genera were shared between the adults and larval samples while 264 and 139 genera were unique to the larvae and adults, respectively. Amplicon metagenomic analyses of the sequences showed the dominance of the phylum Proteobacteria in the adult samples while Firmicutes and Proteobacteria dominated in the larval samples. Linear discriminant analysis effect size (LEfSe) comparison revealed the genera Pseudomonas, Delftia and Ralstonia to be differentially enriched in the adult samples while Enterococcus, Enterobacter, Lactococcus, Klebsiella and Wiessella were differentially abundant in the larvae. The diversity indices showed that the bacterial communities were not different between the insect samples collected from different geographical regions. However, the bacterial communities significantly differed based on the sample type between larvae and adults. A co-occurrence network of significantly correlated taxa revealed a strong interaction between the microbial communities. The functional analysis of the microbiome using FAPROTAX showed that denitrification, arsenite oxidation, methylotrophy and methanotrophy as the active functional groups of the adult and larvae microbiomes. Our results have revealed the core taxonomic, functional, and interacting microbiota of T. absoluta and these indicate that the larvae and adults harbor a similar but transitory set of bacteria. The results provide a novel insight and a basis for exploring microbiome-based biocontrol strategy for this invasive insect pest as well as the ecological significance of some of the identified microbiota is discussed.

Reversible Switching Based on Truly Intramolecular Long-Range Proton Transfer─Turning the Theoretical Concept into Experimental Reality.

Herein, we demonstrate a working prototype of a conjugated proton crane, a reversible tautomeric switching molecule in which truly intramolecular long-range proton transfer occurs in solution at room temperature. The system consists of a benzothiazole rotor attached to a 7-hydroxy quinoline stator. According to the experimental and theoretical results, the OH proton is delivered under irradiation to the quinolyl nitrogen atom through a series of consecutive proton transfer and twisting steps. The use of a rigid rotor prevents undesired side processes that decrease the switching performance in previously described proton cranes and provides an unprecedented switching efficiency and fatigue resistance. The newly designed system confirms the theoretical concept for the application of proton transfer-initiated intramolecular twisting as the switching mechanism, developed more than 10 years ago, and provides unique insights for the further development of tautomeric molecular switches and motors, molecular logic gates, and new molecular-level energy storage systems.

A novel chemokine biomarker to distinguish active tuberculosis from latent tuberculosis: a cohort study.

BACKGROUND: Interferon-γ release assays (IGRAs), which are widely used to diagnose tuberculosis (TB), cannot effectively discriminate latent TB infection (LTBI) from active TB (ATB). This study aimed to identify potential antigen-specific biomarkers for differentiating LTBI cases from ATB cases. METHODS: Ongoing recruitment was conducted of individuals meeting study inclusion criteria at Beijing Chest Hospital from May 2020 to April 2022; 208 participants were enrolled and assigned to three groups: HC (60 healthy controls), LTBI (52 subjects with LTBI) and ATB (96 ATB patients). After participants were assigned to the discovery cohort (20 or 21 subjects/group), all others were assigned to the verification cohort. Discovery cohort blood levels of 40 chemokines were measured using Luminex assays to identify chemokines that could be used to discriminate LTBI cases from ATB cases; candidate biomarkers were verified using enzyme-linked immunosorbent assay-based testing of validation cohort samples. RESULTS: Luminex results revealed highest ATB group levels of numerous cytokines, growth factors and chemokines. Receiving operating characteristic curve-based analysis of 40 biomarkers revealed CCL8 (AUC = 0.890) and CXCL9 (AUC = 0.883) effectively discriminated between LTBI and TB cases; greatest diagnostic efficiency was obtained using both markers together (AUC = 0.929). Interpretation of CCL8 and CXCL9 levels for validation cohort IGRA-positive subjects (based on a 0.658-ng/ml cutoff) revealed ATB group CCL8-based sensitivity and specificity rates approaching 90.79% and 100.00%, respectively. CONCLUSION: TB-specific chemokines hold promise as ATB diagnostic biomarkers. Additional laboratory confirmation is needed to establish whether CCL8-based assays can differentiate between ATB and LTBI cases, especially for bacteriologically unconfirmed TB cases.

Effect of PD-L1 Expression for the PD-1/L1 Inhibitors on Non-small Cell Lung Cancer: A Meta-analysis Based on Randomised Controlled Trials.

AIMS: As PD-L1 expression has been proposed as one of the cancer biomarkers for non-small cell lung cancer (NSCLC), the predictive value of tumour proportional score (TPS) in the effect of immunotherapy [programmed death protein-1/ligand 1 (PD-1/L1) inhibitors] for NSCLC is worth exploring further. Here, we aimed to summarise the outcomes of current NSCLC randomised controlled trials (RCTs) and explore the predictive value of TPS in clinical immunotherapy, including immune checkpoint inhibitors (ICIs) with or without chemotherapy. MATERIALS AND METHODS: RCTs published by PubMed, Medline, Embase and Scopus before February 2023 comparing immunotherapy (PD-1/L1 with or without other therapy) versus a control group in advanced or metastatic NSCLC were included to assess the prognosis according to the patients' TPS with 1% and 50% as the thresholds. The primary endpoints were overall survival and progression-free survival. RESULTS: In total, 28 RCTs containing 17 266 participants with advanced or metastatic NSCLC were included in this meta-analysis. Statistical results showed that compared with TPS <1%, ≥1% or within 1-49%, patients with TPS ≥50% benefited more significantly from the immunotherapy. A subgroup analysis showed that when TPS was <1%, ≥1% or within 1-49%, ICIs + chemotherapy had better efficacy than ICIs alone; PD-1 (such as pembrolizumab) inhibitors had better efficacy than PD-L1 inhibitors (such as atezolizumab). CONCLUSION: The efficacy of immunotherapy (PD-1/L1 inhibitors) for advanced or metastatic NSCLC is influenced by TPS.

Identification of vulnerable carotid plaque with CT-based radiomics nomogram.

AIM: To develop and validate a radiomics nomogram for identifying high-risk carotid plaques on computed tomography (CT) angiography (CTA). MATERIALS AND METHODS: A total of 280 patients with symptomatic (n=131) and asymptomatic (n=139) carotid plaques were divided into a training set (n=135), validation set (n=58), and external test set (n=87). Radiomic features were extracted from CTA images. A radiomics model was constructed based on selected features and a radiomics score (rad-score) was calculated. A clinical factor model was constructed by demographics and CT findings. A radiomics nomogram combining independent clinical factors and the rad-score was constructed. The diagnostic performance of three models was evaluated and validated by region of characteristic curves. RESULTS: Calcification and maximum plaque thickness were the independent clinical factors. Twenty-four features were used to build the radiomics signature. In the validation set, the nomogram (area under the curve [AUC], 0.977; 95% CI, 0.899-0.999) performed better (p=0.017 and p=0.031) than the clinical factor model (AUC, 0.862; 95% CI, 0.746-0.938) and radiomics signature (AUC, 0.944; 95% CI, 0.850-0.987). In external test set, the nomogram (AUC, 0.952; 95% CI, 0.884-0.987) and radiomics signature (AUC, 0.932; 95% CI, 0.857-0.975) showed better discrimination capability (p=0.002 and p=0.037) than clinical factor model (AUC, 0.818; 95% CI, 0.721-0.892). CONCLUSION: The CT-based nomogram showed satisfactory performance in identification of high-risk plaques in carotid arteries, and it may serve as a potential non-invasive tool to identify carotid plaque vulnerability and risk stratification.

Comprehensive review of glucagon-like peptide 1 receptor agonist treatment on the risk of cardiovascular outcomes and retinopathy as diabetic complications.

Cardiovascular and microvascular disorders are serious complications of diabetes. Intensive glucose control is believed to hinder the pathological progression of these complications. In this review, we focus on the risk of diabetic retinopathy (DR) under intensive treatment with recently introduced glucose-lowering drugs, including glucagon-like peptide 1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1RAs are more suitable for patients with diabetes at risk for, or established, cardiovascular complications, while SGLT2 inhibitors are more appropriate for complications of heart failure and chronic renal diseases. Accumulating evidence indicates that GLP-1RAs may provide a greater reduction in the risk of DR in patients with diabetes compared to DPP-4 inhibitors, sulfonylureas, or insulin. GLP-1RAs may be ideal antihyperglycemic drugs with direct benefits for the retina, since GLP-1R can be expressed in photoreceptors. Topical administration of GLP-1RAs induces direct retinal neuroprotection against DR by multiple mechanisms, such as preventing both neurodysfunction and retinal neurodegeneration; relieving the disruption of the blood-retinal barrier and associated vascular leakage, and inhibiting oxidative stress, inflammatory action, and neuronal apoptosis. Hence, it seems reasonable to utilize this strategy to treat patients with diabetes and early-stage DR, rather than exclusively using neuroprotective agents.

[Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world].

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

[Multidisciplinary regenerative treatment and mechanisms for rescuing a severe calciphylaxis patient with human amnion-derived mesenchymal stem cells].

Calciphylaxis is a rare disease with severe pain and high-mortality due to cutaneous ischemic necrosis and infection that currently lacks proved effective therapies. The occurrence of calciphylaxis in end stage kidney disease (ESKD) patients is known as calcific uremic arteriolopathy (CUA), which is characterized histologically by dermal microvessel calcification, intimal fibroplasia and microthrombosis. Here we innovatively treated a severe CUA patient with human amnion-derived mesenchymal stem cells (hAMSCs). A 34-year-old uremic woman was presented with progressive, painful malodorous ulcers in buttocks and mummified lower limbs. Skin pathological features supported the diagnosis of calciphylaxis. The patient was refractory to conventional multidisciplinary symptomatic therapies. With the approval of our hospital ethics committee, she was treated with hAMSCs including intravenous and local intramuscular injection, and external application of hAMSC culture supernatant to the wound area. During 15-month follow-up, the patient had regeneration of skin and soft tissues, with improved blood biochemical, inflammatory, mineral and bone metabolic indices and immunoregulation effects. After 15-month hAMSC treatment, the score of pain visual analog scale (VAS) decreased from 10 to 0, Bates-Jensen wound assessment tool (BWAT) score decreased from 65 to 13, and wound-quality of life (Wound-QoL) questionnaire score decreased from 68 to 0. We propose that hAMSC treatment is promising for CUA patients. The therapy is potentially involved in the multiple beneficial effects of inhibiting vascular calcification, stimulating angiogenesis and myogenesis, modulating adverse inflammatory and immunologic responses, promoting re-epithelialization and restoring skin integrity.

Value of pseudopod sign on high-frequency ultrasound in predicting the pathological invasion of extramammary Paget's disease lesions.

BACKGROUND: Vertical invasion of extramammary Paget's disease (EMPD) is associated with poor prognosis. The usual vertical invasion route is directly downward or along the skin appendages. High-frequency ultrasound (HFUS) can be used to measure the EMPD lesion thickness, and visualize the pseudopod extensions due to skin appendage involvement. It is a non-invasive method for evaluating the extent of vertical invasion in EMPD. OBJECTIVE: To investigate the value of HFUS in predicting the extent of vertical invasion in EMPD. METHODS: In this retrospective study, 85 patients with EMPD were divided into two groups based on the pathology: invasive EMPD (iEMPD) group (n = 13) and in situ EMPD group (n = 72). The clinical and HFUS features of both the groups were analysed. The different types of pseudopodia morphology on HFUS were as follows: no pseudopodia, irregular bottom, small sphere, short strip, long strip, vase shape and nodular convex. These were further stratified into low-risk and high-risk levels. RESULTS: The clinical features were comparable between the two groups (P > 0.05). There were significant differences between the two groups in the HFUS features (lesion thickness, lesion shape, bottom shape, layer involvement, pseudopodia morphology and colour Doppler blood flow signal; all P < 0.05). The distribution of the pseudopodia morphology types in the in situ EMPD and iEMPD groups was as follows: no pseudopodia, 30/72 and 0/13; irregular bottom, 5/72 and 0/13; small sphere, 5/72 and 0/13; short strip, 21/72 and 0/13; long strip, 8/72 and 3/13; vase shape, 3/72 and 3/13; and nodular convex, 0/72 and 7/13 (P < 0.05 for all). The sensitivity and specificity of high-risk pseudopodia in identifying iEMPD were 100% and 84.7%, respectively. CONCLUSIONS: High-frequency ultrasound provides morphological information regarding EMPD lesions. Risk stratification for pseudopodia can help to distinguish between iEMPD and in situ EMPD lesions.

[Role of pyroptosis pathway related molecules in acute lung injury induced by gas explosion in rats].

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.

[Exploring and bioinformatics analysis of differentially expressed genes in bronchial asthma].

Objective: To screen core differentially expressed genes of bronchial asthma and conduct bioinformatics analysis. Methods: Macrophage microarray data GSE22528 from asthma patients were downloaded from gene expression database (GEO). The dataset included transcriptome information from 10 human alveolar lavage fluid samples, and five of them were from allergic asthmatic subjects and five from control subjects. Differential expression genes (DEGs) were screened by R 4.0.4 software. Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to select DEGs using DAVID 6.8 database. Protein interaction network (PPI) was constructed from DEGs encoded proteins using STRING online database. Cytoscape software was used to construct core modules and determine core DEGs. Results: Alveolar lavage fluid samples were all collected from Caucasian Canadians, with age range as (20, 37) and (18, 36) years, respectively, including 3 males for each group. In asthmatic patients, 449 genes were up-regulated and 47 down-regulated. GO analysis showed that the up-regulated genes in asthmatic patients were mainly involved in biological processes such as response to folded proteins, and the molecular function was focused on binding of folded proteins and growth factors. Down-regulated genes were mainly involved in biological processes such as histone deacetylation and ubiquitin-mediated protein degradation, and their molecular functions focused on histone deacetylation activity. KEGG pathway enrichment analysis showed that pathways were mainly enriched by up-regulation genes, involving Hippo signaling pathway, hypertrophic cardiomyopathy, estrogen signaling pathway, arrhythmogenic right ventricular cardiomyopathy, basal cell carcinoma, neuro-activated receptor ligand interaction, dilated cardiomyopathy and adhesion and connection signaling pathways. Two core modules were obtained by PPI analysis, and 14 core DEGs were screened out. They were pro-melanin concentrating hormone (PMCH), prepronociceptin (PNOC), Sphingosinol-1-phosphate receptor 2 (S1PR2), Sphingosinol-1-phosphate receptor 5 (S1PR5), CC-type chemokine ligand 21 (CCL21), Kelch-like protein 25 (KLHL25), ubiquitin binding enzyme E2V2 (UBE2V2), F-box protein 17 (FBXO17), taste receptor type 2 member 3 (TAS2R3), somatostatin receptor 2 (SSTR2), metabolic glutamate receptor 2 (GRM2), Lister E3 ubiquitin protein ligase 1 (LTN1), LIM domain specific protein 7 (LMO7) and ring finger protein 19A gene(RNF19A), in which LTN1 and UBE2V2 were down-regulated and the rest were up-regulated. Conclusion: DEGs was found in macrophages of asthmatic and control individuals. PMCH, PNOC, S1PR2, S1PR5 and CCL21 might be the core genes in the pathological process of asthma.

[Study on serum metabolomics of combined injury induced by gas explosion in rats].

Objective: To analyze the changes of serum metabolomics in rats with combined injuries caused by gas explosion and explore its possible mechanism. Methods: In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the gas explosion experiment. All 32 SD rats were randomly divided into four groups, control group (not involved in the explosion) , close range (40 m) group, medium range (160 m) group and long range (240 m) group, 8 in each group. The respiratory function at 2 hours and the neural behavior at 48 hours were detected after the explosion. The rats were anesthetized and sacrificed after 48 hours, and the serum, lung, liver and other tissues of the rats were isolated and histopathological changes of lung and liver tissues were observed by HE staining. Serum samples were detected by liquid chromatography-high resolution mass spectrometry (UPLC-Orbitrap Elite/MS) , and metabolic spectrum differences between groups were evaluated by principal component analysis. Differential metabolites were screened and identified, and metabolic pathways were analyzed. Results: Compared with control group, respiratory function indexes (respiratory frequency, minute ventilation, peak inspiratory flow rate, peak expiratory flow rate and 1/2 tidal volume expiratory flow) of rats in different explosion groups were significantly decreased (P<0.05) , but respiration pause, inspiratory time and 2/3 tidal volume required time were significantly increased (P<0.05) in 2 hours after the explosion. However, the residence times of the neurobehavioral indicators of the 40 m group and 160 m group were significantly increased (P<0.05) , and the movement distances were significantly decreased (P<0.05) in 48 hours after the explosion. HE staining results showed that the lung and liver tissues of the rats in the gas explosion group structurally damaged, and the cells were disordered, with inflammatory cell infiltration, bleeding and edema. Metabonomics analysis showed that there were significant differences in metabolic profiles between groups. A total of 18 differential metabolites were identified in serum samples, including aconitum acid, citric acid, niacinamide and pyruvate, which involved in 12 major metabolic pathways, including the glutamic acid and glutamine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glyoxylic acid and dicarboxylic acid metabolism, phenylalanine metabolism, nicotinic acid and nicotinamide metabolism, citric acid cycle (TCA cycle) . Conclusion: Gas explosion can cause multi-organ system damage in rats, the mechanism of which may be related to the biosynthesis of alanine, tyrosine and tryptophan, metabolism of niacin and niacinamide, metabolism of acetaldehyde and dicarboxylic acid, and TCA cycle, etc.

[Research progress on non-alcoholic fatty liver disease animal models].

In recent years, with the changes in living standards and dietary structure, the incidence of non-alcoholic fatty liver disease has been increasing year by year in China, and the incidence rate in the general population is as high as 29.81%. An increasingly epidemiological evidence suggests that non-alcoholic fatty liver disease has become one of the causes of increasing liver cirrhosis and liver cancer. However, its etiology and pathogenesis are complex and have not yet been fully elucidated. Therefore, establishing an appropriate non-alcoholic fatty liver disease animal models for pre-clinical research is essential to elucidate its pathogenesis. This article summarizes the latest research progress of non-alcoholic fatty liver disease animal models, which are common at home and abroad in recent years.

[Changes and significance of autophagy in rat lung injury induced by gas explosion].

Objective: To explore the changes and significance of autophagy in acute lung injury (ALI) induced by gas explosion in rats. Methods: In February 2018, the gas explosion in underground coal mine was simulated by large tunnel explosion experiment system, SD rats were randomly divided into control group and 6 distance groups (40 m, 80 m, 120 m, 160 m, 200 m, 240 m) with 18 rats in each group. The respiratory function of rats 24 h before and after explosion was detected. Post-explosion rats were anesthetized and sacrificed, histopathological changes of lung were observed by HE staining. Immunohistochemistry was performed to detect the in situ expression of autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3B) . The expression levels of autophagy related gene 12 (Atg12) , LC3B, P62, lysosomal associated membrane protein 2 (Lamp2) , B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl2 interaction protein (Beclin-1) were detected by Western blot. Results: After gas explosion, the rats in 80 m distance point group had the hightest mortality (n=13, 72.22%) and the most severe lung injury degree, and the histopathological scores was (4.00±0.00) point. After gas explosion, the minute ventilation volume (MVb) , maximum inspiratory flow rate (PIFb) and maximum expiratory flow rate (PEFb) of rats were lower than before the gas explosion (P<0.05) . The respiratory frequency of rats in 80 m, 200 m, and 240 m distance point groups were significantly higher than that in the control group (P<0.05) . The expression levels of LC3B in 40 m, 80 m, 120 m, 160 m, and 200 m distance point groups were higher than that in the control group (P<0.05) . The relative expression levels of Atg12 and LC3BⅡ/Ⅰ in lung tissues of rats in different distance point groups were higher than those in the control group (P<0.05) . The relative expression levels of Beclin1 in 40 m, 80 m, 120 m, and 160 m distance point groups were significantly higher than that in the control group (P<0.05) . The relative expression levels of P62 in 80 m, 160 m and 200 m distance point groups were lower than that in the control group (P<0.05) . The relative expression levels of Lamp2 and Bcl-2 in lung tissues of rats in all distance groups except 240 m distance group were lower than those in the control group (P<0.05) . Conclusion: Gas explosion could induce increased autophagy in lung tissues of ALI rats. Autophagy-related signaling pathway could be involved in the pathophysiological process of ALI in rats caused by gas explosion, then the autophagy and the severity of the lesion showed a significant positive correlation.