Single-crystal growth, structure and thermal transport properties of the metallic antiferromagnet Zintl-phase ß-EuIn2As2.

Zintl-phase materials have attracted significant research interest owing to the interplay of magnetism and strong spin-orbit coupling, providing a prominent material platform for axion electrodynamics. Here, we report the single-crystal growth, structure, magnetic and electrical/thermal transport properties of the antiferromagnet layer Zintl-phase compound ß-EuIn2As2. Importantly, the new layered structure of ß-EuIn2As2, in rhombohedral (R3̄m) symmetry, contains triangular layers of Eu2+ ions. The in-plane resistivity ρ(H, T) measurements reveal metal behavior with an antiferromagnetic (AFM) transition (TN ∼ 23.5 K), which is consistent with the heat capacity Cp(H, T) and magnetic susceptibility χ(H, T) measurements. Negative MR was observed in the temperature range from 2 K to 20 K with a maximum MR ratio of 0.06. Unique 4f7J = S = 7/2 Eu2+ spins were supposed magnetically order along the c-axis. The Seebeck coefficient shows a maximum thermopower |Smax| of about 40 µV K-1. The kink around 23 K in the Seebeck coefficient originates from the effect of the antiferromagnetic phase on the electron band structure, while the pronounced thermal conductivity peak at around 10 K is attributed to the phonon-phonon Umklapp scattering. The results suggest that the Eu2+ spin arrangement plays an important role in the magnetic, electrical, and thermal transport properties in ß-EuIn2As2, which might be helpful for future potential technical applications.

[Diagnosis of allergen components in fungi and microbial communities: patient sensitization characteristics and main sensitizing proteins].

The human body, as a highly complex ecosystem, harbors diverse microbial communities, with major factors triggering allergic reactions encompassing the skin microbiome and fungi. The global diversity of fungi is estimated to range from approximately 600 000 to 1 million species, and theoretically, IgE-mediated sensitization may occur to any fungal species. As of now, the World Health Organization/IUIS official database records 113 fungal allergens originating from 30 different fungi species, covering 42 allergen families. Regarding the skin microbiome, 14 distinct Malassezia allergens have been identified, all derived from three different Malassezia fungi species--M. furfur, M. sympodialis, and M. globosa. The conditions of patients with these allergies are exceptionally complex. This article extensively discusses the latest research advancements and clinical applications related to skin microbiome and fungal allergies from the European Academy of Allergy and Clinical Immunology (EAACI) publication, "Molecular Allergology User's Guide 2.0". Additionally, it compiles information on the sources of fungal allergens, characteristics of allergen component protein families, clinical relevance, and management strategies, both domestically and internationally. The aim is to enhance the profound understanding of allergen components among relevant professionals. Through the application of advanced allergen component diagnostic techniques, the goal is to achieve precise diagnosis and treatment of fungal allergy patients and explore the mechanisms underlying fungal sensitization and pathogenesis, laying the foundation for studying the fungal allergen protein sensitization spectrum in the Chinese population.

[Analysis of the effect of early subcutaneous specific immunotherapy on the levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism].

Objective: To investigate the effects of subcutaneous immunotherapy (SCIT) on patients' immune markers and metabolic levels in the early stage of allergen treatment, and to gain insight into the role of SCIT in regulating immune responses and metabolic levels, so as to provide reference data for the further discovery of potential biomarkers. Methods: A longitudinal study was used to include 40 subjects who underwent SCIT with dust mite allergens in the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University between November 2017 and February 2022, including 20 subjects each of single mite subcutaneous immunotherapy (SM-SCIT) and double mite subcutaneous immunotherapy (DM-SCIT). In this study, levels of dust mite allergen-specific antibodies and polyunsaturated fatty acid metabolism were measured before and 12 months after treatment, while pulmonary function tests were performed. The therapeutic effects of the patients were followed up by visual analogue scale (VAS), asthma control test (ACT) and total medication scores (TMS). The results were statistically analyzed using t-test and Mann-Whitney U-test. Results: After 12 months of treatment with SCIT, both groups showed a significant decrease in total VAS score (SM-SCIT:Z=-2.298, P<0.05; DM-SCIT:Z=-3.411, P<0.001); total ACT score (SM-SCIT:Z=-2.054, P<0.05; DM-SCIT:Z=-2.014, P<0.05) and total medication scores (SM-SCIT:Z=-3.799, P<0.000 1; DM-SCIT:Z=-3.474, P<0.001) were significantly higher, in addition to significantly higher MMEF75/25 values in the DM-SCIT group (t=-2.253, P<0.05). There was no significant change in sIgE in the SM-SCIT group (P>0.05), and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 2, and p 21 fractions were significantly elevated (Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, and -3.285, respectively, all P<0.05); The sIgE of Der p 2, f 2, p 7 and p 23 fractions(Z=-2.651, -3.771, -2.949, -2.912, -2.725, -2.128, -3.285, all P<0.05) and the sIgG4 levels of the Der p, Der f, p 1, p 2, f 1, f 2, p 10, p 21 and p 23 fractions (Z=-3.808, -3.845, -3.061, -2.688, -2.464, -3.211, -2.371, -2.091, -2.427, all P<0.05) of the DM-SCIT group were significantly elevated. Metabolomics analysis showed that arachidonic acid, docosahexaenoic acid, docosapentaenoic acid, eicosapentaenoic acid, 5, 9, 12-octadecatrienoic acid, 5(S)-hydroxylated eicosatetraenoic acid, and dihomo-gamma-linolenic acid were significantly elevated at the beginning of the treatment period after SM-SCIT treatment (Z of -2.191, -2.497, -1.988, -2.090, -2.19, -2.803, -2.073, all P<0.05); 5(S)-hydroxylated eicosatetraenoic acid showed elevated and alpha-linolenic acid, eicosadienoic acid, and eicosapentaenoic acid were significantly decreased in the DM-SCIT group after treatment (Z=-1.988, -2.090, -2.497, -1.988, respectively, all P<0.05). Correlation analysis showed that arachidonic acid was significantly negatively correlated with changes in dust mite-specific IgG4 (r=-0.499, P<0.05), and that alpha-linolenic acid, 5, 9, 12-octadecatrienoic acid, and eicosapentaenoic acid were positively correlated with the ΔsIgG4 of the dust mite der p 2 (r=0.451, 0.420, 0.474, respectively; all P<0.05). Conclusion: Significant changes in allergen-specific antibody levels and polyunsaturated fatty acid metabolism levels occur during SCIT, and the two may interact and influence each other.

[Gastric cancer-derived mesenchymal stem cells regulate the M2 polarization of macrophages within gastric cancer microenvironment via JAK2/STAT3 signaling pathway].

Objective: To investigate the role and mechanism of tumor-derived mesenchymal stem cells in regulating the M2 polarization of macrophages within gastric cancer microenvironment. Methods: Gastric cancer tissues and the adjacent non-cancerous tissues were collected from patients underwent gastric cancer resection in the First People's Hospital of Lianyungang during 2018. In our study, THP-1-differentiated macrophages were co-cultured with gastric cancer-derived mesenchymal stem cells (GC-MSCs). Then, the M2 subtype-related gene, the markers expressed on cell surface and the cytokine profile were analyzed by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry and Luminex liquid chip, respectively. The key cytokines mediating the inducing effect of GC-MSCs on macrophage polarization into the M2 subtype were detected and screened by Luminex liquid chip, which were further confirmed by the neutralizing antibody test. The expressions of macrophage proteins involved in M2 polarization-related signaling pathways under the different co-culture conditions of GC-MSCs were detected by western blot. Results: In Mac+ GC-MSC-culture medium (CM) group, the expression levels of Ym-1 and Fizz-1 (1.53±0.32 and 13.22±1.05, respectively), which are markers for M2 subtype, were both significantly higher than those of Mac group (1.00±0.05 and 1.21±0.38, respectively, P<0.05). The level of iNOS in Mac+ GC-MSC-CM group (0.60±0.41) was significantly lower than that of Mac group (1.06±0.38, P=0.023). In Mac+ GC-MSC-Transwell (TW) group, the expression levels of Ym-1 and Fizz-1 (1.47±0.09 and 13.16±2.77, respectively) were both significantly higher than those of Mac group (1.00±0.05 and 1.21±0.38, respectively, P<0.05). The level of iNOS in Mac+ GC-MSC-CM group (0.56±0.03) was significantly lower than that of Mac group (1.06±0.38, P=0.026). The ratios of CD163(+) /CD204(+) cells in Mac+ GC-MSC-CM and Mac+ GC-MSC-TW groups (3.80% and 4.40%, respectively) were both remarkably higher than that of Mac group (0.60%, P<0.05). The expression levels of IL-10, IL-6, MCP-1 and VEGF in Mac+ GC-MSC-CM group were (592.60±87.52), (1 346.80±64.70), (11 256.00±29.03) and (1 463.90±66.67) pg/ml, respectively, which were significantly higher than those of Mac group [(41.03±2.59), (17.35±1.79), (5 213.30±523.71) and (267.12±12.06) pg/ml, respectively, P<0.05]. The levels of TNF-α, IP-10, RANTES and MIP-1α were (95.57±9.34), (410.48±40.68), (6 967.30±1.29) and (1 538.70±283.04) pg/ml, which were significantly lower than those of Mac group [(138.01±24.31, (1 298.60±310.50), (14 631.00±4.21) and (6 633.20±1.47) pg/ml, respectively, P<0.05]. The levels of IL-6 and IL-8 in GC-MSCs [(11 185.02±2.82) and (12 718.03±370.17) pg/ml, respectively] were both strikingly higher than those of MSCs from adjacent non-cancerous gastric cancer tissues [(270.71±59.38) and (106.04±32.84) pg/ml, repectively, P<0.05]. The ratios of CD86(+) cells in Mac+ IL-6-blocked-GC-MSC-CM and Mac+ IL-8-blocked-GC-MSC-CM groups (28.80% and 31.40%, respectively) were both higher than that of Mac+ GC-MSC-CM group (24.70%). Compared to Mac+ GC-MSC-CM group (13.70%), the ratios of CD204(+) cells in Mac+ IL-6-blocked-GC-MSC-CM and Mac+ IL-8-blocked-GC-MSC-CM groups (9.90% and 8.70%, separately) were reduced. The expression levels of p-JAK2 and p-STAT3, which are proteins of macrophage M2 polarization-related signaling pathway, in Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, respectively) were significantly higher than those of Mac group (0.50±0.01 and 0.82±0.01, respectively, P<0.05). The expression levels of p-JAK2 in Mac+ IL-6-blocked-GC-MSC-CM group (0.47±0.02) were significantly lower those that of Mac+ GC-MSC-CM group (0.86±0.01, P<0.05). The expression levels of p-JAK2 and p-STAT3 in Mac+ IL-8-blocked-GC-MSC-CM group (0.50±0.01 and 0.85±0.01, respectively) were both significantly lower than those of Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, P<0.05). The expression levels of p-JAK2 and p-STAT3 in Mac+ IL-6/IL-8-blocked-GC-MSC-CM group (0.37±0.01 and 0.65±0.01, respectively) were both significantly lower than those of Mac+ GC-MSC-CM group (0.86±0.01 and 1.08±0.01, P<0.05). Conclusion: GC-MSCs promote the activation of JAK2/STAT3 signaling pathway in macrophages via high secretions of IL-6 and IL-8, which subsequently induce the macrophage polarization into a pro-tumor M2 subtype within gastric cancer microenvironment.

[Research progression of gene fusion detection technology based on next generation sequencing in tumor companion diagnostics].

Gene fusion is one of the mechanisms that promote tumor development. It is also an important cause for the poor prognosis of patients. The detection of gene fusion is crucial for the recognition of tumor biomarker, cancer subtype classification, and clinical medication guidance. Appropriate methods can help the early diagnosis and avoid ineffective medication. Traditional tests include fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), reverse transcription of PCR (RT-PCR), and next generation sequencing (NGS). The next generation sequencing (NGS) mainly includes: whole genome sequencing (WGS), whole transcriptome sequencing (WTS) and target sequencing (hybridization capture method/amplicon method). In clinical concomitant diagnostic applications, some factors such as operability, time/money costs, and the level of expertise required for data analysis should be considered. This article concludes with a discussion of the technical principles of different detection methods and advantages/limitations. Meanwhile, it provides reference opinions for the detection methods of gene fusion.

[The establishment and application of testing methods of tetraspanin 7 autoantibody in type 1 diabetes].

Objective: To establish the luciferase immunoprecipitation system assay (LIPS) to test tetraspanin 7 autoantibody (TSPAN7A) and evaluate its value in Chinese type 1 diabetes (T1D) patients. Methods: Renilla luciferase-tagged TSPAN7 plasmids were transfected into 293T cells to obtain Renilla luciferase-tagged TSPAN7 fusion protein. The cell lysate was incubated with sera overnight, followed by addition of protein A-agarose and extensive wash. Finally, the substrate of Renilla luciferase was added and luminescence was detected. Sera from 100 T1D patients [64 males and 36 females,with a mean age of (28±16) years], 119 type 2 diabetes (T2D) patients [78 males and 41 females,with a mean age of (47±12) years] and 98 healthy volunteers [55 males and 43 females,with a mean age of (28±12) years] from the Department of Metabolism and Endocrinology of the Second Xiangya Hospital, Central South University from 2014 to 2017, were tested by LIPS to evaluate the frequency of TSPAN7A. Radioligand binding assay (RLA) was used to test glutamic acid decarboxylase autoantibodies (GADA), protein tyrosine phosphatase-2 autoantibodies (IA-2A) and zinc transporter 8 autoantibodies (ZnT8A). Results: The frequencies of GADA, IA-2A, ZnT8A and TSPAN7A in T1D patients were 72.0%, 40.0%, 29.0% and 25.0%, respectively. After Bonferroni correction, the positivity of TSPAN7A was lower than GADA (P<0.001), but similar with IA-2A (P=0.035) and ZnT8A (P=0.630). The positivity of TSPAN7A in T1D patients was significantly higher than that in T2D (0.84%, P<0.001) and in healthy controls (1.02%, P<0.001). In combination with TSPAN7A, the positivity of islet autoantibodies in T1D patients increased from 82% to 85%. There was no significant difference in clinical characteristics between TSPAN7A-positive T1D and the other three islet autoantibodies-positive patients. Conclusion: This study succeeded in establishing LIPS method to assay TSPAN7A. Moreover, TSPAN7A are valid islet autoantibodies for T1D patients in China.

[Clinical and prognostic study of anti-N-methyl-D-aspartate receptor encephalitis children with paroxysmal sympathetic hyperactivity syndrome].

The data of clinical characteristics, medical cost and prognosis of 22 anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis children from the Department of Neurology, Capital Institute of Pediatrics between May 2018 and January 2021 were analyzed, and 6 of them occurred paroxysmal sympathetic hyperactivity syndrome (PSH). It was found that the anti-NMDAR encephalitis children with PSH had severer consciousness disorder [median Glasgow Coma Scale (GCS) score at admission: 7.5], longer duration of consciousness disorder (median time: 53 days), higher hospitalization cost (median cost: 230 000 RMB), severer neurological injury at onset [median modified Rankin Scale (mRS) score at admission: 4], and longer recovery time of neurological function (median time of mRS score recovered to 0-2: 7 months), compared with those without PSH (all P<0.05). Therefore, more attention should be paid to sympathetic excited symptoms of anti NMDAR encephalitis, and thus identify and intervene early on PSH to reduce the neurological damage and economic burden.

[Advances of allergen component detection in the prevention and control of allergic diseases].

The incidence of allergic diseases in China is increasing year by year, which has caused heavy public health burden to individuals and society. The detection of specific IgE (sIgE) is an important way to diagnose the etiology of allergic disease. Currently, the diagnosis of allergic rhinitis In vitro mainly focus on the specific IgE of crude extracts in clinical practice, while the detection of sIgE in allergen components is rarely carried out. Clinicians, especially non-allergists, do not have sufficient understanding about the importance of sIgE in allergen component detection. Knowing the related types and clinical significance of allergen components can improve the diagnostic level of allergic diseases. Allergen component detection can distinguish the major components of common allergens, identify cross-sensitization, predict the risk of anaphylaxis, guide allergen immunotherapy and develop precise dietary regimens, so as to provide accurate prevention and control recommendations for patients.

Characteristics and roles of severe acute respiratory syndrome coronavirus 2-specific antibodies in patients with different severities of coronavirus 19.

The diagnosis of coronavirus 19 (COVID-19) relies mainly upon viral nucleic acid detection, but false negatives can lead to missed diagnosis and misdiagnosis; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody detection is convenient, safe and highly sensitive. Immunoglobulin (Ig)M and IgG are commonly used to serologically diagnose COVID-19; however, the role of IgA is not well known. We aimed to quantify the levels of SARS-CoV-2-specific IgM, IgA and IgG antibodies, identify changes in them based on COVID-19 severity, and establish the significance of combined antibody detection. COVID-19 patients, divided into a severe and critical group and a moderate group, and non-COVID-19 patients with respiratory disease were included in this study. A chemiluminescence method was used to detect the levels of SARS-CoV-2-specific IgM, IgA and IgG in the blood samples from the three groups. Epidemiological characteristics, symptoms, blood test results and other data were recorded for all patients. Compared to the traditional IgM-IgG combined antibodies, IgA-IgG combined antibodies are more effective for diagnosing COVID-19. During the disease process, IgA appeared first and disappeared last. All three antibodies had significantly higher levels in COVID-19 patients than in non-COVID-19 patients. IgA and IgG were also higher for severe and critical disease than for moderate disease. All antibodies were at or near low levels at the time of tracheal extubation in critical patients. Detection of SARS-CoV-2-specific combined IgA-IgG antibodies is advantageous in diagnosing COVID-19. IgA detection is suitable during early and late stages of the disease. IgA and IgG levels correspond to disease severity.

[Effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats].

OBJECTIVE: To explore the effect of subchronic combined oral exposure of titanium dioxide nanoparticles and glucose on levels of serum folate and vitamin B12 in young SD rats. METHODS: At first, the physical and chemical properties of titanium dioxide nanoparticles, such as particle size, shape, crystal form and agglomeration degree in solution system, were characterized in detail. Eighty 4-week-old young SD rats were randomly divided into 8 groups (10 rats in each group, half male and half female). The rats were exposed to titanium dioxide nanoparticles through intragastric administration at 0, 2, 10 and 50 mg/kg body weight with or without 1.8 g/kg glucose daily for 90 days. At last, the concentrations of serum folate and vitamin B12 were detected. RESULTS: Titanium dioxide nanoparticles were anatase crystals, closely spherical shape, with an average particle size of (24±5) nm. In male young rats, compared with the control group, the serum folate concentration was significantly increased when exposed to titanium dioxide nanoparticles (10 mg/kg) and glucose. The difference was statistically significant (P<0.05). However, in female and male young rats, compared with glucose (1.8 g/kg) exposure group, titanium dioxide nanoparticles (50 mg/kg) and glucose significantly reduced the serum folate concentration. The difference was statistically significant (P<0.05). Through statistical analysis of factorial design and calculation of interaction, obvious antagonistic effect was observed between titanium dioxide nanoparticles and glucose on the serum folate concentration in the young female SD rats. The combined oral exposure of titanium dioxide nanoparticles and glucose had little effect on the concentration of serum vitamin B12 in the young SD rats, with no significant interaction between the two substances. It was only found that titanium dioxide nanoparticles (2 mg/kg) and glucose significantly increased the serum vitamin B12 concentration, compared with glucose (1.8 g/kg) exposure group. The difference was statistically significant (P<0.05). CONCLUSION: Subchronic combined oral exposure of titanium dioxide nanoparticles and glucose had an obvious antagonistic effect on serum folate concentrations in young SD rats.

[Effects of titanium dioxide nanoparticles on fecal metabolome in rats after oral administration for 90 days].

OBJECTIVE: To explore the effects and related mechanisms of oral exposure titanium dioxide nanoparticles (TiO2 NPs) for 90 days on the intestinal and the gut microbiota of rats, through fecal metabolomics. METHODS: Twelve 4-week-old clean-grade Sprague Dawley (SD) rats were randomly de-vided into 2 groups by body weight, treated with TiO2 NPs at dose of 0 or 50 mg/kg body weight everyday respectively for 90 days. The solution of each infection was freshly prepared and shocked fully by ultrasonic. Characterization of the particle size, crystal form, purity, and specific surface area of TiO2 NPs was conducted. And the fresh feces of the rats were collected on the 90th day. After lyophilized and hydrophilic phase extraction, ultra performance liquid chromatography-Q-exactive orbitrap-high-resolution mass spectrometry system (UPLC-QEMS) was utilized for non-targeted determination of fecal meta-bolites. The metabolites were identified and labeled through Compound Discoverer 3.0 software, and used for subsequent metabolomics analysis. Bioinformatics analysis was carried out including unsupervised principal component analysis and supervised orthogonal projection to latent structure discriminant analysis for the differential metabolites between the two groups. The differential metabolites were followed-up for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: Compared with the control group, the body weight of the rats was significantly reduced (P<0.05) in the treatment group. A total of 22 metabolites in fecal metabolomics showed significant changes. Among them, xanthine, 1-methyladenine, 3-hydroxypyridine, methionine sulfoxide, pyridoxine, 1,5-isoquinolinediol, N-acetylornithine, N-acetyl-D-galactosamine, L-citrulline, L-methionine, leucine, DL-tryptophan, L-ornithine, 4-methyl-5-thiazoleethanol, and L-glutamic acid totaled 15 metabolites increased significantly. N-acetylhistamine, D-pipecolinic acid, imidazolelactic acid, L-valine, 2,3,4,6-tetramethylpyrazine, caprolactam, and histamine totaled 7 metabolites decreased significantly. N-acetylhistamine, L-valine and methionine sulfoxide were changed more than 16 times. Analysis of KEGG pathway revealed that the two metabolic pathways arginine biosynthesis and aminoacyl-tRNA biosynthesis were significantly changed (false discover rate < 0.05, pathway impact > 0.1). CONCLUSION: Oral exposure to TiO2 NPs for 90 days could disrupt the metabolism of the intestine and gut microbiota, causing significant changes in metabolites and metabolic pathways which were related to inflammatory response, oxidative stress, glucose homeostasis, blood system and amino acid homeostasis in rat feces. It is suggested that the toxic effect of TiO2 NPs on rats may be closely related to intestinal and gut microbiota metabolism.

[Effect of exosome-derived miR-223 from macrophages on the metastasis of gastric cancer cells].

Objective: To investigate the effect and mechanism of exosome-derived miR-223 from macrophage on gastric cancer (GC) cell metastasis. Methods: Exosomes isolated from macrophages culture medium were characterized and cocultured with GC cell, the miRNA level was detected by qRT-PCR. The migration and invasion of GC cell were detected by transwell. The internalization of exosomes, transfer of miR-223 was observed by immunofluorescence. Macrophage were transfected with a miR-223 inhibitor or negative control, transwell and scratch test were employed to explore the effect of macrophage derived exosome on the migration and invasion of GC cell. Western blot and RT-PCR assay were performed to uncover the underlying mechanisms of miR-223 and PTEN-PI3K/AKT pathway. Results: This study showed that macrophage and macrophage-derived exosomes promoted the migration and invasion of gastric cancer cell(253.2±6.3, 451.8±12.8, 453.4±14.4, all P<0.01, and 98.4±5.1, 276.5±10.3, 257.3±8.5, all P<0.01, respectively). miR-223 was enriched in macrophage-derived exosomes, which was transferred to the co-cultivated gastric cancer cells. miR-223 knockdown in macrophage reversed the migration and invasion of exosomes on gastric cancer cells(215.6±9.2, 402.5±11.6, 253.7±10.4, all P<0.01, and 91.5±8.2,263.4±9.3,105.8±9.3,all P<0.01, respectively).Functional studies revealed that exosomal miR-223 derived from macrophage promoted the metastasis of GC cells via the PTEN-PI3K/AKT pathway. In addition, itshowed thatthe actin cytoskeleton was altered, and multiple proteins associated with epithelial-mesenchymaltransition (EMT) were upregulated. Conclusion: Exosomal transfer of macrophage-derived miR-223 promote the metastasis of GC cells through targeting the PTEN-PI3K/AKT pathway.

[Effects of air pollution exposure on olfaction of rats in Beijing].

Objective: To evaluate the effects of exposure of fine particle matter (PM2.5) and ozone (O3) in Beijing as the main pollutants on olfaction of SD rats. Methods: In October 16, 2018, twenty 8-week-old SD rats were randomly divided into two groups, 10 rats in the exposure group and 10 rats in the control group. They were fed in air pollutant exposure system and clean experimental environment respectively, and the concentrations of PM2.5 and O3 in each system were measured. The degree of olfaction damage of SD rats at different feeding time was assessed by using the buried food test (BFT). The difference of BFT time between the two groups was analyzed by performing the repeated measures analysis of variance. Results: The results showed that the concentrations of PM2.5 and O3 in the exposure group were (22.65±11.47) µg/m3 and (12.36±5.87) µg/m3, respectively, while those in the control group were both 0 µg/m3. The repeated measures analysis of variance showed that the time of BFT in the exposure group was longer than that in the control group (F=6.49, P=0.031). With the increase of feeding time, the time of BFT was prolonged (F=61.69, P<0.001). Conclusion: Exposure to PM2.5 and O3 in the atmosphere might lead to olfaction damage in rats.

[Predictive value of N-terminal B-type natriuretic peptide on outcome of elderly hospitalized non-heart failure patients].

Objective: To investigate the predictive value of N-terminal type B natriuretic peptide（NT-proBNP) on the prognosis of elderly hospitalized patients without heart failure（non-heart failure). Method: Elderly patients aged 65 years or older, who were admitted to Beijing Hospital from September 2018 to February 2019, were enrolled in this study. Patients with clinical diagnosis of heart failure or left ventricular ejection fraction（LVEF)<50% were excluded. The patients were divided into 2 groups based on the serum NT-proBNP level: low NT-proBNP group （<125 ng/L) and high NT-proBNP group（≥125 ng/L). Patients were followed up at 3, 6, and 12 months after enrollment, and the major adverse events were recorded. The composite endpoint events included all-cause mortality, readmission or Emergency Department visits. Cardiovascular events include death, readmission or emergency room treatment due to cardiogenic shock, myocardial infarction, angina pectoris, arrhythmia, heart failure or stroke/transient ischemic attack. Results: A total of 600 elderly patients with non-heart failure were included in the analysis. The average age was （74.9±6.5) years, including 304（50.7%) males. The median follow-up time was 344（265, 359) days. One hundred and seventy-eight（29.7%) composite endpoint events were recorded during the follow-up, 19（3.2%) patients died, and 12（2.0%) patients were lost to follow-up. There were 286(47.7%) cases in low NT-proBNP group and 314 cases（52.3%) in high NT-proBNP group. Patients were older, prevalence of atrial fibrillation and myocardial infarction was higher; MMSE scores and ADL scores, albumin and creatinine clearance rate were lower in high NT-proBNP group than in low NT-proBNP group（all P<0.05). At 1-year follow-up, the incidence of composite endpoint events was significantly higher in high NT-proBNP group than in low NT-proBNP group（33.4%（105/314) vs. 24.8%（71/286), P = 0.02). Cardiovascular events were more common in high NT-proBNP group than in low NT-proBNP group（17.5%（55/314) vs. 8.4%（24/286), P = 0.001). Kaplan-Meier survival analysis showed both composite endpoint events（Log-rank P=0.016) and cardiovascular events（Log-rank P=0.001) were higher in high NT-proBNP group than in low NT-proBNP group. All-cause mortality was also significantly higher in highNT-proBNP group than in lowNT-proBNP group（4.8%（15/314) vs. 1.4%（4/286), P = 0.020), and Kaplan-Meier survival analysis demonstrated borderline statistical significance（Log-rank P = 0.052). Cox proportional hazard regression analysis showed that after adjusting for age, sex, creatinine clearance rate, myocardial infarction, and atrial fibrillation, NT-proBNP remained as an independent risk factor for composite endpoint events（HR=1.376，95%CI 1.049-1.806, P=0.021), and cardiovascular events（HR=1.777, 95%CI 1.185-2.664, P=0.005), but not for all-cause mortality（P=0.206). Conclusions: NT-proBNP level at admission has important predictive value on rehospitalization and cardiovascular events for hospitalized elderly non-heart failure patients. NT-proBNP examination is helpful for risk stratification in this patient cohort.

[Systematic evaluation of neuromuscular blocking agents on prognosis of patients with moderate to severe acute respiratory distress syndrome].

Objective: To evaluate the prognostic impact of neuromuscular blocking agents (NMBA) on patients with acute respiratory distress syndrome (ARDS). Method: Online search of MEDLINE, Embase, Web of Science, CNKI, CBM and other Chinese databases for randomized controlled trials (RCTs) of NMBA in patients with ARDS from January 1994 to June 2019 was done, and literature was selected according to inclusion and exclusion criteria. The patients were divided into NMBA group and non-NMBA group according to whether NMBA was adopted or not. The prognostic indicators (ICU mortality, 28 d mortality, 90 d mortality) and NMBA-related complications (ICU acquired muscle weakness, barometric injury, pneumothorax) of the patients in the two groups were mainly analyzed. Meta-analysis of the data was performed using RevMan 5.0 software. Results: A total of 6 RCTs were included, and 1 502 patients were enrolled, including 761 in the NMBA group and 741 in the no-NMBA group. The 90-day mortality in the NMBA group and no-NMBA group were 38.8% and 42.6%, OR=0.87 (95%CI: 0.70-1.07, P=0.190); the 28-day mortality rates were 32.5% and 36.5%, OR=0.71 (95%CI: 0.45-1.11, P=0.130); ICU mortality rates were 31.8% and 43.8%, OR=0.60 (95%CI: 0.41-0.88, P=0.009). Conclusion: NMBA can reduce the ICU mortality of moderate to severe ARDS patients, but not reduce 28-day and 90-day mortality.

[Correlation analysis of gut microbiota and biochemical indexes in patients with non-alcoholic fatty liver disease].

Objective: To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD. Methods: Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance. Results: Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant (P< 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant (P< 0.05). NAFLD group (P= 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower (P< 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant (P= 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower (P< 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant (P< 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels (r< 0,P< 0.05), and positively correlated with high-density lipoprotein levels (r> 0,P< 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha (r= -0.211,P= 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels (r> 0,P< 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level (r= 0.245,P= 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels (r > 0,P< 0.05). Megamonas was negatively correlated with high-density lipoprotein levels (r= -0.231,P= 0.027). Conclusion: A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.

Vitamin D receptor interacts with NLRP3 to restrict the allergic response.

Vitamin D receptor (VDR) mediates various biochemical activities between the cytoplasm and the nucleus in the cell. The nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) protein is involved in the T helper type 2 (Th2) response. This study tests a hypothesis that VDR interacts with NLRP3 to restrict the Th2-biased response. In this study, VDR-/- mice and WT (WT) mice were used. Th2 cell differentiation between VDR-/- mice and WT mice was observed. We observed that CD4+ T cell activation was higher in VDR-/- mice. The VDR-/-CD4+ T cells were prone to Th2 polarization. VDR-/- mice produced more immunoglobulin (Ig)E. VDR bound NLRP3 to prevent Th2 differentiation by restricting IL4 gene transcription. Th2 biased inflammation spontaneously developed in the intestine of VDR-/- mice. In conclusion, VDR binds NLRP3 to restrict IL4 gene transcription and prevent biased Th2 polarization.

Dietary pea fibre alters the microbial community and fermentation with increase in fibre degradation-associated bacterial groups in the colon of pigs.

This study was attempted to investigate the influence of dietary pea fibre (PF) on the community and quantity of colonic bacteria of piglets and finisher pigs using pyrosequencing data and real-time PCR. The concentration of acetate in colonic digesta from PF-fed piglets was significantly higher than that from control (p < .05). Feeding PF diet to finisher pigs increased the ratio of acetate to total volatile fatty acids (VFAs) but decreased the ratio of butyrate, as compared with the control pigs (p < .05 in both cases). The lower ratio of butyrate in samples from finisher pigs receiving PF suggested that this dietary fibre did not favour butyrate production in the hindgut. Supplementation of PF to piglets reduced abundance of Bacteroidetes, as compared with control animals. However, PF had opposite effects in finisher pigs, higher abundance of Bacteroidetes but lower of Firmicutes. Lactobacillus and Prevotella were found as the predominant genera in PF piglets. Prevotella accounted for nearly half of the total bacteria in the colon of finisher pigs in the PF group, but only one-third in the control animals. Quantitative PCR showed that Firmicutes/Bacteroidetes were significantly increased in the colon of PF piglets (p < .05) as compared with control animals, but decreased in PF finisher pigs. Bacteroidetes-Prevotella-Porphyromonas and Desulfovibrio desulfuricans which are involved in degradation of dietary fibres were more abundant in the PF finisher pigs than in the controls (p < .05), suggesting mutualism between host and its gut microbes.

Involvement of PKA signalling in anti-inflammatory effects of chitosan oligosaccharides in IPEC-J2 porcine epithelial cells.

Weaning is characterized by intestinal inflammation, which is a big challenge in pig industry. Control of intestinal inflammation is important for improvement of growth performance and health. Therefore, the study was focused on the anti-inflammatory activity of low-molecular-weight chitosan oligosaccharide (LCOS) in a porcine small intestinal epithelial cell line (IPEC-J2). The results showed that TNF-α, as inflammation inducer, significantly upregulated the mRNA expression of IL-8 and MCP-1. Afterwards, LCOS significantly attenuated mRNA expression of IL-8 and MCP-1 induced by TNF-α in the cells. Mannose (MAN), as ligand of mannose receptor, had no effect on the anti-inflammatory activity of LCOS, which suggested that mannose receptor may not involve in the anti-inflammatory activity of LCOS in IPEC-J2 cells. Interestingly, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide 2HCl hydrate (H89), as PKA (protein kinase A)-specific inhibitor, reversed the mRNA expression of IL-8 when co-cultured with LCOS. Furthermore, LCOS concentration dependent downregulated the mRNA expression of claudin-1 compared with TNF-α treatment. However, the trans-epithelial electric resistance (TEER) was not affected by LCOS when co-cultured with TNF-α in 3 hr. In conclusion, LCOS have a potent anti-inflammatory activity, and as a feed additives, may be useful for the inhibition of inflammatory process in weaning period of pigs with intestinal inflammation occurring.

[Therapeutic efficacy of ultraviolet combined with riboflavin for the rabbit bacterial keratitis].

Objective: To study the effects of ultraviolet light combined with riboflavin treatment (corneal collagen-crosslinking, CXL) on infectious control and stromal reconstruction of bacterial keratitis. Methods: Experimental Study. A Staphylococcus aureus rabbit keratitis model was established by injecting Staphylococcus aureus broth into the shallow stromal layer of the right eye cornea of New Zealand white rabbits. Forty-four rabbits that successfully established the model were randomly divided into four groups: corneal collagen cross-linking (CXL) group, antibiotic group, CXL+ antibiotic group and untreated group, with 11 rabbits in each group. Before the treatment and at 3, 7, 14 and 28 days after treatment, slit lamp corneal examination, AS-OCT and in vivo confocal microscopy (IVCM) were performed. Clinical efficacy of different treatments were evaluated at different time points. Parameters including conjunctival hyperemia, corneal ulcer, infiltration, edema, and neovascular. Histopathological examinations of corneal lesions were performed in order to detect the infiltration, inflammatory cells and repair in corneal tissue. Normal data were compared with paired t-test and non-normal data were compared with paired rank sum test before and after treatment. Kruskal-Wallis rank sum test was used to compare 4 groups of data and the generalized estimation equation is used to compare the repeated measurement data at each time point and the comparison between the groups of the treatment groups. Results: After treatment, different time points and specimens for pathological observation, we obtained the following results:Conjunctival hyperemia: in CXL and CXL+ antibiotic groups after treatment for 3 days from treatment before 3 (2, -4) and 3 (2, -3),The reduction was 2 (1, -3) and 2 (1, -2), the difference was statistically significant (Z=-3.91, -5.50; P<0.008); 14 days, the antibiotic group changed from 3 (3, -4) to 2 (1, -2) after treatment, the difference was statistically significant (Z=-5.11, P<0.008); the untreated group had no statistical significance before and after treatment. After 14 days of treatment, the area of corneal ulcer (0.08±0.11) cm(2), (0.07±0.05) cm(2) in CXL group and CXL+ antibiotic group was significantly lower than that before treatment (0.40±0.18) cm(2), (0.49±0.24) cm(2). The difference was statistically significant. Significance (Z=-3.29, -3.64; P<0.008); after 14 days of treatment, after 14 days of treatment, neovascularization in the CXL and CXL+ antibiotic groups began to resolve, 1 (1, -2) and 1 (0, -2) at 7 days of treatment. decreased to 1 (1, -1) and 0 (0, -1), the difference was statistically significant (Z=4.57, 3.80; P<0.012 5); The degree of corneal edema was significantly reduced in the CXL group and the CXL+ antibiotic group at 14 days after treatment, which was reduced from (650±154) µm and (785±255) µm before the treatment to (432±95) µm and (455±109) µm, the difference was statistically significant (t=4.50, 4.92; P=0.00); The density of corneal stromal cells was also reduced from (446±257)/mm(2), (321±145)/mm(2) to (107±66)/mm(2), (114±94)/mm(2), the difference was statistically significant (t=4.15, 4.76; P<0.05). Histopathological observation under light microscope showed that most of the corneal ulcers healed in the CXL group and the CXL+ antibiotic group at 7 days of treatment. The epithelial cells were clearly visible and misaligned, and a small amount of neutrophils in the stromal layer. The upper epithelial layer was treated for 14 days. The cells are arranged neatly, the structure is clear, and the inflammatory cells are significantly reduced. Conclusion: Ultraviolet light combined with riboflavin corneal collagen cross-linking has a certain therapeutic effect on rabbit bacterial keratitis infection control and ulcer repair, and can be used as an auxiliary treatment for antibiotics. (Chin J Ophthalmol, 2018, 54:902-910).