Diosmetin has therapeutic efficacy in colitis regulating gut microbiota, inflammation, and oxidative stress via the circ-Sirt1/Sirt1 axis.

Diosmetin (3',5,7 -trihydroxy-4'-methoxy flavone) is a natural flavonoid compound in the citrus species, it exhibits a variety of pharmacological activities, but little is known of its effects on colitis. In this study we evaluated the therapeutic effects of diosmetin on mouse models of chronic and acute colitis. Chronic colitis was induced in mice by drinking water containing 3% dextran sulfate sodium (DSS) from D0 to D8, followed by administration of diosmetin (25, 50 mg · kg-1 · d-1) for another 8 days. Acute colitis was induced by drinking water containing 5% DSS from D0 to D7, the mice concomitantly received diosmetin (25, 50 mg · kg-1 · d-1) from D1 to D7. During the experiments, body weight and disease activity index (DAI) were assessed daily. After the mice were sacrificed, colon tissue and feces samples were collected, and colon length was measured. We showed that in both models, diosmetin administration significantly decreased DAI score and ameliorated microscopic colon tissue damage; increased the expression of tight junction proteins (occludin, claudin-1, and zonula occludens-1), and reduced the secretion of proinflammatory cytokines IL-1ß, IL-6, TNF-α, and Cox-2 in colon tissue. We found that diosmetin administration remarkably inhibited colon oxidative damage by adjusting the levels of intracellular and mitochondrial reactive oxygen species, GSH-Px, SOD, MDA and GSH in colon tissue. The protection of diosmetin against intestinal epithelial barrier damage and oxidative stress were also observed in LPS-treated Caco-2 and IEC-6 cells in vitro. Furthermore, we demonstrated that diosmetin markedly increased the expression of Nrf2 and HO-1 and reduced the ratio of acetylated NF-κB and NF-κB by activating the circ-Sirt1/Sirt1 axis, which inhibited oxidative stress and inflammation in vivo and in vitro. Diosmetin reversed the effects of si-circSirt1 and si-Sirt1 in LPS-treated Caco-2 and IEC-6 cells. When the gut microbiota was analyzed in the mouse model of colitis, we found that diosmetin administration modulated the abundance of Bacteroidetes, Actinobacteria, Cyanobacteria and Firmicutes, which were crucial for inflammatory bowel disease. Our results have linked colitis to the circ-Sirt1/Sirt1 signaling pathway, which is activated by diosmetin. The results imply that diosmetin may be a novel candidate to alleviate DSS-induced colitis and can be a lead compound for future optimization and modification.

Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-κB/Snail signaling pathway.

BACKGROUND: Parthenolide (PTL) is a natural molecule isolated from Tanacetum parthenium that exhibits excellent anti-inflammatory and antitumor activities. Pulmonary fibrosis (PF), especially idiopathic pulmonary fibrosis (IPF), is a chronic lung disease that lacks a proven effective therapy. The present study evaluated the therapeutic effect of PTL on PF. METHODS: Serum-starved primary lung fibroblasts and HFL1 cells were treated with different doses of PTL, and cell viability and the migration rate were measured. Western blot analysis and a dual-luciferase assay were used to analyze the epithelial-mesenchymal transition (EMT)-related transcription factors influenced by PTL treatment in A549 cells and primary lung epithelial cells. Mice with bleomycin (BLM)-induced pulmonary fibrosis were treated with different doses of intragastric PTL, and pathological changes were evaluated using Hematoxylin-eosin (H&E) staining and immunohistochemical analysis. RESULTS: Our results demonstrated that PTL reduced the cell viability and migration rate of lung fibroblasts and inhibited the expression of EMT-related transcription factors in lung epithelial cells. In vivo studies demonstrated that PTL attenuated BLM-induced pulmonary fibrosis and improved the body weight and pathological changes of BLM-treated mice. We further demonstrated that PTL attenuated BLM-induced PF primarily via inhibition of the NF-κB/Snail signaling pathway. CONCLUSION: These findings suggest that PTL inhibits EMT and attenuates BLM-induced PF via the NF-κB/Snail signaling pathway. PTL is a worthwhile candidate compound for pulmonary fibrosis therapy.

[Study on prescription combination and design method based on dichotomy and greedy algorithm].

The prescription combinations of traditional Chinese medicine (TCM) focuses on the taste and channel tropism, the Qi movement, as well as the compatibility according to multiple combination principles and medicinal property and flavor combination of several traditional Chinese medicines. With the in-depth study on the prescription compatibility, researchers have realized that the medicinal property theory is the core of TCM combinations. However, there is no definite method for combinations based on medicinal properties. In this paper, the authors put forward an method for designing prescription combinations based on bipartite graph and the greedy algorithm. With the medicinal property combinations of Siweilurong Pills for example, the authors proved this method could provide ideas for quickly choosing herbal medicines for prescription combinations, and discussed the prospect of this method in substituting previous and endangered herbal medicines and banned medicinal materials.

[Formula method of medicated diet based on medicinal property combination patterns].

To propose a formula method of medicated diet based on medicinal property combination patterns in this paper under the context of lack of innovation in medicated diets. By analyzing the property combination patterns of traditional Chinese medicine and commonly used foods recorded in the pharmacopoeia, medicated diet formulae were optimized by using the greedy algorithm, with the property combination patterns of classical formulae based on the syndrome differentiation and treatment. In this paper, the Baihu Rensheng decoction, which is a classical formula for treating lung and stomach heat-derived diabetes, was taken for example in the formula design. As a result, totally 18 medicated diet formulae were developed and proved to be rational in the analysis on traditional Chinese medicines and nutriology. This method expands the way of thinking for personalized diet therapies and provides theoretical basis the industrial development and clinical application of medicated diets.

Exploring the Pathogenesis of Autoimmune Liver Diseases from the Heterogeneity of Target Cells.

The incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.

Screening for anti-influenza virus compounds from traditional Mongolian medicine by GFP-based reporter virus.

Introduction: Screening for effective antiviral compounds from traditional Mongolian medicine not only aids in the research of antiviral mechanisms of traditional medicines, but is also of significant importance for the development of new antiviral drugs targeting influenza A virus. Our study aimed to establish high-throughput, rapid screening methods for antiviral compounds against influenza A virus from abundant resources of Mongolian medicine. Methods: The use of GFP-based reporter viruses plays a pivotal role in antiviral drugs screening by enabling rapid and precise identification of compounds that inhibit viral replication. Herein, a GFP-based reporter influenza A virus was used to identify potent anti-influenza compounds within traditional Mongolian medicine. Results: Our study led to the discovery of three active compounds: Cardamonin, Curcumin, and Kaempferide, all of which exhibited significant antiviral properties in vitro. Subsequent analysis confirmed that their effectiveness was largely due to the stimulation of the antiviral signaling pathways of host cells, rather than direct interference with the viral components, such as the viral polymerase. Discussion: This study showcased the use of GFP-based reporter viruses in high-throughput screening to unearth antiviral agents from traditional Mongolian medicine, which contains rich antiviral compounds and deserves further exploration. Despite certain limitations, fluorescent reporter viruses present substantial potential for antiviral drug screening research due to their high throughput and efficiency.

Dinucleotide composition representation -based deep learning to predict scoliosis-associated Fibrillin-1 genotypes.

Introduction: Scoliosis is a pathological spine structure deformation, predominantly classified as "idiopathic" due to its unknown etiology. However, it has been suggested that scoliosis may be linked to polygenic backgrounds. It is crucial to identify potential Adolescent Idiopathic Scoliosis (AIS)-related genetic backgrounds before scoliosis onset. Methods: The present study was designed to intelligently parse, decompose and predict AIS-related variants in ClinVar database. Possible AIS-related variant records downloaded from ClinVar were parsed for various labels, decomposed for Dinucleotide Compositional Representation (DCR) and other traits, screened for high-risk genes with statistical analysis, and then learned intelligently with deep learning to predict high-risk AIS genotypes. Results: Results demonstrated that the present framework is composed of all technical sections of data parsing, scoliosis genotyping, genome encoding, machine learning (ML)/deep learning (DL) and scoliosis genotype predicting. 58,000 scoliosis-related records were automatically parsed and statistically analyzed for high-risk genes and genotypes, such as FBN1, LAMA2 and SPG11. All variant genes were decomposed for DCR and other traits. Unsupervised ML indicated marked inter-group separation and intra-group clustering of the DCR of FBN1, LAMA2 or SPG11 for the five types of variants (Pathogenic, Pathogeniclikely, Benign, Benignlikely and Uncertain). A FBN1 DCR-based Convolutional Neural Network (CNN) was trained for Pathogenic and Benign/ Benignlikely variants performed accurately on validation data and predicted 179 high-risk scoliosis variants. The trained predictor was interpretable for the similar distribution of variant types and variant locations within 2D structure units in the predicted 3D structure of FBN1. Discussion: In summary, scoliosis risk is predictable by deep learning based on genomic decomposed features of DCR. DCR-based classifier has predicted more scoliosis risk FBN1 variants in ClinVar database. DCR-based models would be promising for genotype-to-phenotype prediction for more disease types.

[Suppression of mitochondrial oxidative phosphorylation on in vitro maturation, fertilization and developmental competence of oocytes].

OBJECTIVE: To investigate the roles of mitochondrial oxidative phosphorylation (OXPHOS) capacity in oocyte maturation, fertilization and embryo development. METHODS: Carbonyl cyanide p- (tri-fluromethoxy) phenyl-hydrazone (FCCP), a metabolic inhibitor of mitochondria, was introduced into culture medium. The integrity of spindle and chromosome alignment, reactive oxygen species (ROS) levels, and rates of maturation, germinal vesicle breakdown, fertilization and blastulation were assessed in vitro. RESULTS: Significant decreases were detected in the percentages of oocytes with nuclear maturation, normal spindle formation and chromosome alignment, ROS levels and capable for blastocyst formation between oocytes treated with FCCP and non-treated (control group), 55.8%, 37.9%, 0.67 and 57.9% (FCCP 10 nmol/L group), 47.3%,34.7%, 0.59 and 41.8% (FCCP 100 nmol/L group) versus 62.9%, 61.9%,0.94 and 68.3% (control group) respectively, P<0.05. However, No significant differences were found in the rates of GVBD and fertilization in oocytes from the FCCP treated and the control. CONCLUSION: Inhibition of mitochondrial metabolic capacity resulted in decreased the percentages of oocytes with nuclear maturation, normal spindle formation and chromosome alignment, ROS levels and capable for blastocyst formation. But the treatment of FCCP did not affect the rate of fertilization.

[Effects of controlled ovarian hyperstimulation on mitochondria copy number and functions in murine oocytes].

OBJECTIVE: To investigate the effect of whether controlled ovarian hyperstimulation (COH) on mitochondrial DNA (mtDNA) copy number, mitochondrial function, distribution, the level of reactive oxygen species (ROS) in oocytes and the mechanism of oocyte loss in COH. METHODS: Matured murine oocytes were classified into COH group and natural cycles (NC) group. The copies of mtDNA, the magnitude of mitochondrial membrane potential (Δφm) and oocyte adenosine triphosphate (ATP) content, pattern of mitochondrial distribution, and ROS levels were evaluated by realtime PCR, immunofluorescence and fluorescence-luciferase mensuration. RESULTS: The copies of mtDNA, the levels of Δφm, and ATP content in oocytes between COH and NC groups showed statistical difference [(1.15 ± 0.01)×10(5), 0.34 ± 0.03 and (241 ± 20) fmol/oocyte (COH)] versus [(2.15 ± 0.19)×10(5), 0.82 ± 0.07 and (325 ± 11) fmol/oocyte (NC)], respectively(P < 0.05). However, there were no significant differences in the rate of evenly distributed mitochondria and the level of ROS in oocytes from COH and NC [(76.5% (78/102) in COH versus 82.1% (69/84)]; 1.07 ± 0.07 in COH versus 0.93 ± 0.08 in NC (P > 0.05). CONCLUSION: It was indicated that non-physiological COH treatments inhibit mtDNA replication, alter mitochondrial function, which might partly be involved in the low development potential of COH oocyte.

The burden of hepatitis C virus in the world, China, India, and the United States from 1990 to 2019.

Background and aim: Hepatitis C virus infection can lead to an enormous health burden worldwide. Investigating the changes in HCV-related burden between different countries could provide inferences for disease management. Hence, we aim to explore the temporal tendency of the disease burden associated with HCV infection in China, India, the United States, and the world. Methods: Detailed data on the total burden of disease related to HCV infection were collected from the Global Burden of Disease (GBD) 2019 database. Joinpoint regression models were used to simulate the optimal joinpoints of annual percent changes (APCs). Further analysis of the age composition of each index over time and the relationship between ASRs and the socio-demographic Index (SDI) were explored. Finally, three factors (population growth, population aging, and age-specific changes) were deconstructed for the changes in the number of incidences, deaths, and DALYs. Results: It was estimated that 6.2 million new HCV infections, 0.54 million HCV-related deaths, and 15.3 million DALYs worldwide in 2019, with an increase of 25.4, 59.1, and 43.6%, respectively, from 1990, are mainly due to population growth and aging. China experienced a sharp drop in age-standardized rates in 2019, the United States showed an upward trend, and India exhibited a fluctuating tendency in the burden of disease. The incidence was increasing in all locations recently. Conclusion: HCV remains a global health concern despite tremendous progress being made. The disease burden in China improved significantly, while the burden in the United States was deteriorating, with new infections increasing recently, suggesting more targeted interventions to be established to realize the 2030 elimination goals.

Collagen co-localized with macrovesicular steatosis better differentiates fibrosis progression in non-alcoholic fatty liver disease mouse models.

Background: Non-alcoholic fatty liver disease (NAFLD) is a global commonly occurring liver disease. However, its exact pathogenesis is not fully understood. The purpose of this study was to quantitatively evaluate the progression of steatosis and fibrosis by examining their distribution, morphology, and co-localization in NAFLD animal models. Methods: Six mouse NAFLD groups were established: (1) western diet (WD) group; (2) WD with fructose in drinking water (WDF) group; (3) WDF + carbon tetrachloride (CCl4) group, WDF plus intraperitoneal injection of CCl4; (4) high-fat diet (HFD) group, (5) HFD with fructose (HFDF) group; and (6) HFDF + CCl4 group, HFDF plus intraperitoneal injection of CCl4. Liver tissue specimens from NAFLD model mice were collected at different time points. All the tissues were serially sectioned for histological staining and second-harmonic generation (SHG)/two-photon excitation fluorescence imaging (TPEF) imaging. The progression of steatosis and fibrosis was analyzed using SHG/TPEF quantitative parameters with respect to the non-alcoholic steatohepatitis Clinical Research Network scoring system. Results: qSteatosis showed a good correlation with steatosis grade (R: 0.823-0.953, p < 0.05) and demonstrated high performance (area under the curve [AUC]: 0.617-1) in six mouse models. Based on their high correlation with histological scoring, qFibrosis containing four shared parameters (#LongStrPS, #ThinStrPS, #ThinStrPSAgg, and #LongStrPSDis) were selected to create a linear model that could accurately identify differences among fibrosis stages (AUC: 0.725-1). qFibrosis co-localized with macrosteatosis generally correlated better with histological scoring and had a higher AUC in six animal models (AUC: 0.846-1). Conclusion: Quantitative assessment using SHG/TPEF technology can be used to monitor different types of steatosis and fibrosis progression in NAFLD models. The collagen co-localized with macrosteatosis could better differentiate fibrosis progression and might aid in developing a more reliable and translatable fibrosis evaluation tool for animal models of NAFLD.

Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid-enhanced magnetic resonance imaging for evaluating fibrosis regression in chronic hepatitis C patients after direct-acting antiviral.

BACKGROUND: Direct acting antiviral (DAA) therapy has enabled hepatitis C virus infection to become curable, while histological changes remain uncontained. Few valid non-invasive methods can be confirmed for use in surveillance. Gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) is a liver-specific magnetic resonance imaging (MRI) contrast, related to liver function in the hepatobiliary phase (HBP). Whether Gd-EOB-DTPA-enhanced MRI can be used in the diagnosis and follow up of hepatic fibrosis in patients with chronic hepatitis C (CHC) has not been investigated. AIM: To investigate the diagnostic and follow-up values of Gd-EOB-DTPA-enhanced MRI for hepatic histology in patients with CHC. METHODS: Patients with CHC were invited to undergo Gd-EOB-DTPA-enhanced MRI and liver biopsy before treatment, and those with paired qualified MRI and liver biopsy specimens were included. Transient elastography (TE) and blood tests were also arranged. Patients treated with DAAs who achieved 24-wk sustained virological response (SVR) underwent Gd-EOB-DTPA-enhanced MRI and liver biopsy again. The signal intensity (SI) of the liver and muscle were measured in the unenhanced phase (UEP) (SIUEP-liver, SIUEP-muscle) and HBP (SIHBP-liver, SIHBP-muscle) via MRI. The contrast enhancement index (CEI) was calculated as [(SIHBP-liver/SIHBP-muscle)]/[(SIUEP-liver/SIUEP-muscle)]. Liver stiffness measurement (LSM) was confirmed with TE. Serologic markers, aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4), were also calculated according to blood tests. The grade of inflammation and stage of fibrosis were evaluated with the modified histology activity index (mHAI) and Ishak fibrosis score, respectively. Fibrosis regression was defined as a ≥ 1-point decrease in the Ishak fibrosis score. The correlation between the CEI and liver pathology was evaluated. The diagnostic and follow-up values of the CEI, LSM, and serologic markers were compared. RESULTS: Thirty-nine patients with CHC were enrolled [average age, 42.3 ± 14.4 years; 20/39 (51.3%) male]. Twenty-one enrolled patients had eligible paired Gd-EOB-DTPA-enhanced MRI and liver tissues after achieving SVR. The mHAI median significantly decreased after SVR [baseline 6.0 (4.5-13.5) vs SVR 2.0 (1.5-5.5), Z = 3.322, P = 0.017], but the median stage of fibrosis did not notably change (P > 0.05). Sixty pairs of qualified MRI and liver tissue samples were available for use to analyze the relationship between the CEI and hepatic pathology. The CEI was negatively correlated with the mHAI (r = -0.56, P < 0.001) and Ishak score (r = -0.69, P < 0.001). Further stratified analysis showed that the value of the CEI decreased with the progression of the stage of fibrosis rather than with the grade of necroinflammation. For patients with Ishak score ≥ 5, the areas under receiver operating characteristics curve of the CEI, LSM, APRI, and FIB-4 were approximately at baseline, 0.87-0.93, and after achieving SVR, 0.83-0.91. The CEI cut-off value was stable (baseline 1.58 and SVR 1.59), but those of the APRI (from 1.05 to 0.24), FIB-4 (from 1.78 to 1.28), and LSM (from 10.8 kpa to 7.1 kpa) decreased dramatically. The APRI and FIB-4 cannot be used as diagnostic means for SVR in patients with Ishak score ≥ 3 (P > 0.05). Seven patients achieved fibrosis regression after achieving SVR. In these patients, the CEI median increased (from 1.71 to 1.83, Z = -1.981, P = 0.048) and those of the APRI (from 1.71 to 1.83, Z = -2.878, P = 0.004) and LSM (from 6.6 to 4.8, Z = -2.366, P = 0.018) decreased. However, in patients without fibrosis regression, the medians of the APRI, FIB-4, and LSM also changed significantly (P < 0.05). CONCLUSION: Gd-EOB-DTPA-enhanced MRI has good diagnostic value for staging fibrosis in patients with CHC. It can be used for fibrotic-change monitoring post SVR in patients with CHC treated with DAAs.

Developing a New qFIBS Model Assessing Histological Features in Pediatric Patients With Non-alcoholic Steatohepatitis.

Background: The evolution of pediatric non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) is associated with unique histological features. Pathological evaluation of liver specimen is often hindered by observer variability and diagnostic consensus is not always attainable. We investigated whether the qFIBS technique derived from adult NASH could be applied to pediatric NASH. Materials and Methods: 102 pediatric patients (<18 years old) with liver biopsy-proven NASH were included. The liver biopsies were serially sectioned for hematoxylin-eosin and Masson trichrome staining for histological scoring, and for second harmonic generation (SHG) imaging. qFIBS-automated measure of fibrosis, inflammation, hepatocyte ballooning, and steatosis was estabilshed by using the NASH CRN scoring system as the reference standard. Results: qFIBS showed the best correlation with steatosis (r = 0.84, P < 0.001); with ability to distinguish different grades of steatosis (AUROCs 0.90 and 0.98, sensitivity 0.71 and 0.93, and specificity 0.90 and 0.90). qFIBS correlation with fibrosis (r = 0.72, P < 0.001) was good with high AUROC values [qFibrosis (AUC) > 0.85 (0.85-0.95)] and ability to distinguish different stages of fibrosis. qFIBS showed weak correlation with ballooning (r = 0.38, P = 0.028) and inflammation (r = 0.46, P = 0.005); however, it could distinguish different grades of ballooning (AUROCs 0.73, sensitivity 0.36, and specificity 0.92) and inflammation (AUROCs 0.77, sensitivity 0.83, and specificity 0.53). Conclusion: It was demonstrated that when qFIBS derived from adult NASH was performed on pediatric NASH, it could best distinguish the various histological grades of steatosis and fibrosis.

Exploration of the Function of Ginsenoside RD Attenuates Lipopolysaccharide-Induced Lung Injury: A Study of Network Pharmacology and Experimental Validation.

OBJECTIVE: Ginsenoside Rd (GSRd) displays a variety of pharmacological effects. However, the underlying role in acute lung injury (ALI) is not clear. In this study, the protective effect of GSRd on lipopolysaccharide (LPS)-induced ALI is investigated to explore the potential mechanisms. METHODS: GSRd-target-ALI-related gene set was constructed. And bioinformatics tools were used to discover the potential mechanism. We observed the survival of subjects for 72 h. In addition, male BALB/c mice were intraperitoneal injected with GSRd (25 and 50 mg/kg) after received one intratracheal instillation of LPS. Inflammatory changes, oxidative stress, and phosphorylation were assessed to study the biological effects. RESULTS: A total of 245 interaction genes were collected. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were enriched in immune-inflammatory system. Among them, PI3K-Akt signaling pathway was the highest-ranked pathway of inflammatory response. In vivo study, it was found that GSRd improved survival in endotoxemic mice and inhibited the major characteristic of ALI. And the p-PI3K and p-Akt expression was significantly decreased by GSRd treatment. CONCLUSION: GSRd could protect mice against LPS-induced ALI effectively by inhibiting the PI3K-Akt signaling pathway.

Three-dimensional digital measurement of the facet joint in normal individual and lumbar intervertebral disc herniation patients aged 13 - 18 years.

BACKGROUND: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults. OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation. METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al. RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05). CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.

Zc3h12d, a Novel of Hypomethylated and Immune-Related for Prognostic Marker of Lung Adenocarcinoma.

BACKGROUND: Zc3h12d is a negative regulator which plays a crucial role in immune modulation. However, the role of zc3h12d in lung adenocarcinoma (LUAD) remains unclear. We aim to explore the prognostic of zc3h12d and investigate the relationship between zc3h12d expression and immune infiltration in LUAD. METHODS: TIMER site was used to analyze the expression of zc3h12d in LUAD. The zc3h12d protein levels in patient tissue samples were detected by immunohistochemistry staining assays. Meanwhile, based on UALCAN database and samples' data from our cohort, we explored the relationship of clinicopathological features and zc3h12d expression to determine the clinical effect of zc3h12d in LUAD. Several databases including GEPIA, Kaplan-Meier plotter and our samples' data were used to explore the prognostic value of zc3h12d in LUAD. Cox regression analysis was established to further evaluate the prognostic value of zc3h12d in LUAD. In addition, zc3h12d promoter methylation was analyzed by UALCAN database. Genetic alteration analysis was observed in the cBioPortal web. GO and KEGG analyses were conducted to elucidate the underlying mechanisms. Finally, the correlation between zc3h12d and tumor-infiltrating immune cells in LUAD was investigated by TIMER database. The B cells level was investigated by flow cytometry analysis of peripheral blood from our LUAD cohort. RESULTS: Zc3h12d expression was significantly higher in LUAD, compared with adjacent normal tissues. The clinical data from the UALCAN database demonstrated that zc3h12d expression was closely related with cancer stage and nodal metastasis. However, patient sample detection revealed that zc3h12d expression was closely related to pathological N (p = 0.0431) and grade (p = 0.004). Moreover, low zc3h12d expression was associated with poorer overall survival in LUAD. We analyzed the methylation level of zc3h12d in LUAD and found that the methylation levels of zc3h12d promoter in LUAD were significantly reduced. In addition, zc3h12d genetic alterations, including deep deletion, could be found in LUAD. GO and KEGG pathway analysis results indicated that zc3h12d has a certain value in immune infiltration. We investigated the expression of zc3h12d in tumor-immune interactions. It was found that zc3h12d might be associated with the immune infiltration and markers of infiltrating immune cells of LUAD. The results of patient sample detection confirmed that B cells level was significantly lower in the patients with low zc3h12d expression than those in the patients with high zc3h12d expression. CONCLUSION: zc3h12d might be considered as a potential biomarker for determining prognosis and immune-related therapeutic target in LUAD.

Comparison of patients hospitalized with COVID-19, H7N9 and H1N1.

BACKGROUND: There is an urgent need to better understand the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for that the coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. This paper was to differentiate COVID-19 from other respiratory infectious diseases such as avian-origin influenza A (H7N9) and influenza A (H1N1) virus infections. METHODS: We included patients who had been hospitalized with laboratory-confirmed infection by SARS-CoV-2 (n = 83), H7N9 (n = 36), H1N1 (n = 44) viruses. Clinical presentation, chest CT features, and progression of patients were compared. We used the Logistic regression model to explore the possible risk factors. RESULTS: Both COVID-19 and H7N9 patients had a longer duration of hospitalization than H1N1 patients (P < 0.01), a higher complication rate, and more severe cases than H1N1 patients. H7N9 patients had higher hospitalization-fatality ratio than COVID-19 patients (P = 0.01). H7N9 patients had similar patterns of lymphopenia, neutrophilia, elevated alanine aminotransferase, C-reactive protein, lactate dehydrogenase, and those seen in H1N1 patients, which were all significantly different from patients with COVID-19 (P < 0.01). Either H7N9 or H1N1 patients had more obvious symptoms, like fever, fatigue, yellow sputum, and myalgia than COVID-19 patients (P < 0.01). The mean duration of viral shedding was 9.5 days for SARS-CoV-2 vs 9.9 days for H7N9 (P = 0.78). For severe cases, the meantime from illness onset to severity was 8.0 days for COVID-19 vs 5.2 days for H7N9 (P < 0.01), the comorbidity of chronic heart disease was more common in the COVID-19 patients than H7N9 (P = 0.02). Multivariate analysis showed that chronic heart disease was a possible risk factor (OR > 1) for COVID-19, compared with H1N1 and H7N9. CONCLUSIONS: The proportion of severe cases were higher for H7N9 and SARS-CoV-2 infections, compared with H1N1. The meantime from illness onset to severity was shorter for H7N9. Chronic heart disease was a possible risk factor for COVID-19.The comparison may provide the rationale for strategies of isolation and treatment of infected patients in the future.

[Screening, identification and characterization of a broadspectrum antagonistic strain in banyan rhizosphere soil]. / æ¦•æ ‘æ ¹é™ åœŸå£¤å¹¿è°±æ‹®æŠ—èŒæ ªçš„ç­›é€‰ã€é‰´å®šåŠç‰¹æ€§.

Rhizosphere soil samples were collected from an ancient banyan tree grown in the Wanli period of Ming Dynasty in Ji'an City, Jiangxi Province. Twenty-three kinds of indicator bacteria were used to screen soil actinomycetes by cylinder-plate method and mycelium growth rate method. A broad-spectrum antagonistic strain AHF-20 with stable passage was obtained. According to the morphological observation, physiological and biochemical tests, and molecular biological identification, the antagonistic strain was identified as Streptomyces. We examined the antibacterial active substance of the strain. The results showed that the fermentation products of Streptomyces AHF-20 had antagonistic effects on all the 23 test indicator bacteria. The antibacterial ability was stable, tolerant to temperature, light, ultraviolet, acid and alkali. Antibacterial activity still existed after heating at 121 ℃ for 20 min. The fermentation product was extracted with n-butanol according to the polarity of the active substance. The obtained crude n-butanol extract was diluted to 1 µg·mL-1, which still had inhibitory effect for Escherichia coli. The results indicated that it has well utilization potential for biocontrol and developing new microbial drug.

Effects of l-arginine on endometrial estrogen receptor α/ß and progesterone receptor expression in nutrient-restricted sheep.

This study aimed to determine the effects of l-arginine (L-Arg) supplementation on steroid hormone receptors in non-pregnant ovine endometrium. All experimental ewes were randomly assigned to either a control group (n = 6), a nutrient-restricted group (n = 6), or an L-Arg supplemented nutrient-restricted group (n = 6). The effects of L-Arg on estrogen receptor α/ß (ERα/ß) and progesterone receptor (PGR) expression in the ovine endometrium were assessed. Our results showed that levels of ERß and PGR expression were significantly increased by nutrient restriction, but L-Arg counteracted the effect of nutrient restriction on ERß and PGR expression (p < 0.05). Also, expression of endometrial ERα was substantially increased (p < 0.05) by L-Arg supplementation. Furthermore, ERα/ß and PGR were mainly detected in the endometrial luminal epithelium and glandular epithelium. Therefore, we isolated and identified endometrial epithelial cells (EECs) from sheep. Different concentrations of L-Arg were added to investigate the effects on ERα/ß and PGR in EECs. The expression levels of endothelial nitric oxide synthase, ERß, and PGR were significantly increased in response to low-concentration (200 µmol) L-Arg supplementation, which subsequently decreased with a high concentration (800 µmol) (p < 0.05). Otherwise, ERα expression was remarkably increased at both L-Arg concentrations in EECs (p < 0.05). Overall, the results indicated that L-Arg performed crucial roles in the regulation of ovine steroid hormone receptor expression in the endometrium. The results of this study provide a theoretical basis and technical means for the normal function of endometrium in response to low nutrient levels.