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Background Acmella radicans: (Jacquin) R.K. Jansen is a new invasive species record for Yunnan Province, China. Native to Central America, it has also been recently recorded invading other parts of Asia. To prevent this weed from becoming a serious issue, an assessment of its ecological impacts and potential distribution is needed. We predicted the potential distribution of A. radicans in China using the MaxEnt model and its ecological impacts on local plant communities and soil nutrients were explored. Results: Simulated training using model parameters produced an area under curve value of 0.974, providing a high degree of confidence in model predictions. Environmental variables with the greatest predictive power were precipitation of wettest month, isothermality, topsoil TEB (total exchangeable bases), and precipitation seasonality, with a cumulative contribution of more than 72.70% and a cumulative permutation importance of more than 69.20%. The predicted potential suitable area of A. radicans in China is concentrated in the southern region. Projected areas of A. radicans ranked as high and moderately suitable comprised 5425 and 26,338 km2, accounting for 0.06 and 0.27% of the Chinese mainland area, respectively. Over the 5 years of monitoring, the population density of A. radicans increased while at the same time the population density and importance values of most other plant species declined markedly. Community species richness, diversity, and evenness values significantly declined. Soil organic matter, total N, total P, available N, and available P concentrations decreased significantly with increasing plant cover of A. radicans, whereas pH, total K and available K increased. Conclusion: Our study was the first to show that A. radicans is predicted to expand its range in China and may profoundly affect plant communities, species diversity, and the soil environment. Early warning and monitoring of A. radicans must be pursued with greater vigilance in southern China to prevent its further spread. [ABSTRACT FROM AUTHOR]

Objective: We aimed to reveal a spatial proteomic and immune signature of kidney function regions in lupus nephritis (LN). Material and methods: The laser capture microdissection (LCM) was used to isolate the glomerulus, tubules, and interstitial of the kidney from paraffin samples. The data-independent acquisition (DIA) method was used to collect proteomics data. The bioinformatic analysis was performed. Results: A total of 49,658 peptides and 4056 proteins were quantitated. Our results first showed that a high proportion of activated NK cells, naive B cells, and neutrophils in the glomerulus, activated NK cells in interstitial, and resting NK cells were accumulated in tubules in LN. The immune-related function analysis of differential expression proteins in different regions indicated that the glomerulus and interstitial were major sites of immune disturbance and regulation connected with immune response activation. Furthermore, we identified 7, 8, and 9 hub genes in LN's glomerulus, renal interstitial, and tubules. These hub genes were significantly correlated with the infiltration of immune cell subsets. We screened out ALB, CTSB, LCN2, A2M, CDC42, VIM, LTF, and CD14, which show higher performance as candidate biomarkers after correlation analysis with clinical indexes. The function within three regions of the kidney was analyzed. The differential expression proteins (DEGs) between interstitial and glomerulus were significantly enriched in the immune-related biological processes, and myeloid leukocyte-mediated immunity and cellular response to hormone stimulus. The DEGs between tubules and glomerulus were significantly enriched in cell activation and leukocyte-mediated immunity. While the DEGs between tubules and interstitial were enriched in response to lipid, antigen processing, and presentation of peptide antigen response to oxygen-containing compound, the results indicated a different function within kidney regions. Conclusions: Collectively, we revealed spatial proteomics and immune signature of LN kidney regions by combined using LCM and DIA. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the possible role of plasma and peripheral blood mononuclear cells (PBMCs) circular RNA (circRNA) in systemic lupus erythematosus (SLE). Method: Total RNA was extracted from blood plasma samples obtained from 10 patients with SLE and 10 healthy controls and subjected to microarray analysis to define the profile of circRNA expression. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) amplification was conducted. The overlapped circRNA between PBMCs and plasma was performed, the interactions with microRNAs were predicted, the miRNA target mRNA was predicted, and the GEO database was used. The Gene ontology and pathway analysis was performed. Results: One hundred thirty-one upregulated and 314 significantly downregulated circRNAs were identified in the plasma of patients with SLE by the Fold change criteria (≥ 2.0) and P < 0.05. The qRT-PCR results showed that the expression of has-circRNA-102531, has-circRNA-103984, and has-circRNA-104262 was increased in plasma of SLE, and the expression of has-circRNA-102972, has-circRNA-102006, has-circRNA-104313 was decreased in plasma of SLE. Twenty-eight upregulated circRNAs and 119 downregulated circRNAs were overlapped from PBMCs and plasma, and ubiquitination was enriched. Furthermore, the circRNA-miRNA-mRNA network was constructed in SLE after analyzing dataset GSE61635 from GEO. The circRNA-miRNA-mRNA network comprises 54 circRNAs, 41 miRNAs, and 580 mRNAs. In addition, the TNF signaling pathway and the MAPK pathway were enriched from the mRNA of the miRNA target. Conclusion: We first revealed the differentially expressed circRNAs in plasma and PBMCs, and then the circRNA-miRNA-mRNA network was constructed. The network's circRNAs could be a potential diagnostic biomarker and potentially play an important role in the pathogenesis and development of SLE. Key Points • This study analyzed the circRNAs expression profiles combined with the plasma and PBMCs, which provided a comprehensive overview of circRNAs expression patterns in SLE. • The network of the circRNA-miRNA-mRNA in SLE was constructed, which contributes to a better understanding of the pathogenesis and development of SLE. [ABSTRACT FROM AUTHOR]

Background Immune aberrations in end-stage renal disease (ESRD) are characterized by systemic inflammation and immune deficiency. The mechanistic understanding of this phenomenon remains limited. Methods We generated 12 981 and 9578 single-cell transcriptomes of peripheral blood mononuclear cells (PBMCs) that were pooled from 10 healthy volunteers and 10 patients with ESRD by single-cell RNA sequencing. Unsupervised clustering and annotation analyses were performed to cluster and identify cell types. The analysis of hallmark pathway and regulon activity was performed in the main cell types. Results We identified 14 leukocytic clusters that corresponded to six known PBMC types. The comparison of cells from ESRD patients and healthy individuals revealed multiple changes in biological processes. We noticed an ESRD-related increase in inflammation response, complement cascade and cellular metabolism, as well as a strong decrease in activity related to cell cycle progression in relevant cell types in ESRD. Furthermore, a list of cell type-specific candidate transcription factors (TFs) driving the ESRD-associated transcriptome changes was identified. Conclusions We generated a distinctive, high-resolution map of ESRD-derived PBMCs. These results revealed cell type-specific ESRD-associated pathways and TFs. Notably, the pooled sample analysis limits the generalization of our results. The generation of larger single-cell datasets will complement the current map and drive advances in therapies that manipulate immune cell function in ESRD. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of systemic lupus erythematosus (SLE) is complicated. This study explores the expression of circular RNAs (circRNAs), which are closed non-coding RNAs in which the 5′ and 3′ ends are covalently linked and which work by sponging microRNAs. CircRNAs were extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients to identify novel circRNA species that might be used for SLE diagnosis. Methods: Microarray was applied to screening circRNAs changes in PBMCs obtained from SLE patients (n = 10) and healthy participants (n = 10), paired for age and sex. We then verified the selected circRNAs in PBMCs using quantitative reverse transcription-polymerase chain reaction amplification (qRT-PCR) in another cohort, including ten paired SLE patients and healthy participants. The correlation between the differential circRNAs and clinical pathology of SLE were analyzed. Results: 182 up-regulated and 563 significantly down-regulated circRNAs in PBMCs of patients with SLE were identified. Besides, the qRT-PCR results were consistent with the microarray results. The correlation analysis revealed that has_circRNA_100236, has_circRNA_102489, and has_circRNA_101413 were correlated with positive anti-dsDNA, thrombocytopenia, and positive IgG, respectively. Lastly, their miRNAs targets and the binding sites were predicted. Conclusion: We identified some dysregulated circRNAs in PBMCs from SLE patients, and these circRNAs may be developed as the novel biomarkers for the diagnosis of SLE. [ABSTRACT FROM AUTHOR]

Background: Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. Methods: In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. Results: Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. Conclusions: Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN. [ABSTRACT FROM AUTHOR]

Immunoglobulin A nephropathy (IgAN) is a type of glomerular disorder associated with immune dysregulation, and understanding B‑/T‑cell receptors (BCRs/TCRs) may be valuable for the development of specific immunotherapeutic interventions. In the present study, B and T cells were isolated from IgAN patients and healthy controls, and the composition of the BCR/TCR complementarity‑determining region (CDR)3 was analyzed by multiplex polymerase chain reaction, high‑throughput sequencing and bioinformatics. The present results revealed that the BCR/TCR CDR3 clones were expressed at very low frequencies, and the composition of clone types in patients with IgAN was skewed; the majority of clones were unique, and only 12 BCR and 228 TCR CDR3 clones were public ones, of which 16 were expressed at a significantly higher frequency in patients with IgAN (P<0.001). There were also certain conserved amino acid residues between unique clones or groups, and the residues GMDV, EQY and EQF were recurring only in the IgAN group. In addition, some VDJ gene recombinations indicated great variation between groups, including 4 high‑frequency VDJ gene recombinations in the IgAN patients (P<0.001). Immune repertoires provide novel information, and conserved BCR/TCR CDR3 clones and VDJ gene recombinations with great variation may be potential therapeutic targets for IgAN patients. [ABSTRACT FROM AUTHOR]

Objective: This study aims to provide a new perspective of determining the pathophysiology of chronic hepatitis B (CHB) development by analyzing the gene regulatory network in CHB patients using single-cell ATAC sequencing. Background: Hepatitis B virus (HBV)-related liver disease induces liver damage by hepatic immune and inflammatory responses. The exact mechanism is unknown. As such, there is an urgent need to address this problem and study the relationship between aberrant peripheral blood mononuclear cell (PBMC) immune response and progression of liver disease. Method: The sequencing of the chromatin accessibility of 8016 cells from the whole venous blood of normal control (NC) individuals and CHB patients was performed through assay for transposase-accessible chromatin in single-cell sequencing (ScATAC-seq). Unsupervised clustering and annotation analyses were performed by Signac (version 1.7.0) and Seurat clustering to identify different cell types. Then, TF motif enrichment analysis and differentially expressed peak analysis were performed to identify cell-type-specific candidate open chromatins related to CHB. Result: We identified 12 leukocytic clusters corresponding to five cell types. The specific cell types associated with CHB were found to be located in B-0 and T-3. We have drawn the regulatory network of the hepatitis B signal pathway composed of genes linked to the differentially expressed peaks of these two CHB disease-specific cell types. Further, we profoundly explored the potential mechanisms of B-0-associated TF motif IRF2 and T-3-associated TF motif FOXC2 in the occurrence of CHB. Conclusion: We have drawn a systematic and distinguishing gene regulatory network of CHB-related PBMCs. Key Points • Peripheral blood mononuclear cells were robustly clustered based on their types without using antibodies. • We draw a systematic and distinctive gene regulatory network of CHB-related PBMC through ScATAC-seq. [ABSTRACT FROM AUTHOR]

Background: COVID-19 has been shown to increase the risk of extracorporeal coagulation during hemodialysis in patients, but the underlying mechanism remains unclear. This study aimed to investigate the effect and mechanism of COVID-19 on the risk of extracorporeal coagulation in patients with chronic kidney disease undergoing hemodialysis. Methods: A retrospective analysis of the extracorporeal coagulation status of 339 hemodialysis patients at our center before and after COVID-19 infection was performed, including subgroup analyses. Post-infection blood composition was analyzed by protein spectrometry and ELISA. Results: Compared to the pre-COVID-19 infection period, COVID-19-induced extracorporeal coagulation predominantly occurred in patients with severe/critical symptoms. Further proteomic analysis demonstrated that in patients with severe/critical symptoms, the coagulation cascade reaction, platelet activation, inflammation, and oxidative stress-related pathways were significantly amplified compared to those in patients with no/mild symptoms. Notably, the vWF/FBLN5 pathway, which is associated with inflammation, vascular injury, and coagulation, was significantly upregulated. Conclusions: Patients with severe/critical COVID-19 symptoms are at a higher risk of extracorporeal coagulation during hemodialysis, which is associated with the upregulation of the vWF/FBLN5 signaling pathway. These findings highlight the importance of early anticoagulant therapy initiation in COVID-19 patients with severe/critical symptoms, particularly those undergoing hemodialysis. Additionally, vWF/FBLN5 upregulation may be a novel mechanism for virus-associated thrombosis/coagulation. [ABSTRACT FROM AUTHOR]

Acmella radicans (Jacquin) R.K. Jansen is a new invasive species recorded in Yunnan Province, China, and little is known about its allelopathic potential and allelochemicals. In this study, the allelopathic effects of the essential oil (EO) of A. radicans on seed germination and seedling growth of four common plants, Brassica napus, Brassica rapa ssp. chinensis, Digitaria sanguinalis, and Lolium multiflorum, were explored. The results showed that the seed germination index, germination rate, root length, stem length, and biomass of B. napus and B. rapa ssp. chinensis were significantly inhibited at all EO concentrations of A. radicans, but there was a 'low-promotion and high-inhibition effect' on the root length of D. sanguinalis and L. multiflorum at low concentrations of 0.5 μL·mL−1 and 0.5–1.0 μL·mL−1, respectively. With increasing concentrations of EO, the inhibition rates of seed germination and seedling growth of four common plants gradually increased, and D. sanguinalis and L. multiflorum were the most inhibited, followed by B. rapa ssp. chinensis, and the least inhibited was B. napus. Thirty-two components were identified using GC–MS, representing 99.07% of the EO in A. radicans. The major components were 2-tridecanone (30.46%), caryophyllene oxide (19.18%), 4,8,11,11-tetramethylbicyclo[7.2.0]undec-3-en-5-ol (7.84%), β-caryophyllene (7.67%), and widdrol (4.7%). Among the compounds we identified, (E,E)-2,4-decadienal, 2-tridecanone, γ-cadinene, δ-cadinene, (E)-α-cadinol, spathulenol, caryophyllene oxide, and widdrol have been previously reported as having possible allelopathic effects. Our study was the first to show that A. radicans could potentially release allelochemicals to influence neighboring plants during its invasion and expansion. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by the production of multiple autoimmune antibodies and potentially involves any organ or tissue with a broad range of clinical manifestations. Conventional therapy still utilizes glucocorticoids and immunosuppressants. However, some patients show inadequate responses to glucocorticoids and immunosuppression, which may induce secondary immune dysfunction and severe infection as well as lead to an increased tumor risk. The lack of in vitro models has hampered progress in understanding and treating SLE. Patient-derived induced pluripotent stem cells (iPSCs) may provide a unique opportunity for modeling in vitro diseases as well as a platform for drug screening in individual patients. We isolated peripheral blood mononuclear cells from blood to explore the establishment of an in vitro model platform for SLE and directly purified CD34+ cells and seeded them for expansion. CD34+ cells were forced to express seven pluripotency factors, OCT4, SOX2, NANOG, LIN28, c-MYC, KLF4, and SV40LT, through transduction in lentiviral vectors. The morphological characteristics of induced pluripotent stem-like cells, such as prominent nucleoli and a high nucleus-to-cytoplasm ratio, were observed. The pluripotency of established SLE patient-derived iPSCs was confirmed by the expression of embryonic stem cell (ESC) markers and the ability of cells to differentiate into multiple cell lines. SLE patient-derived iPSCs exhibited human ESC properties, including morphology; growth characteristics; expression of pluripotency, genes, and surface markers; and teratoma formation. In conclusion, we generated SLE patient-derived iPSCs and validated their pluripotency. This study is a first but critical step that can provide a model platform for research aimed at understanding the SLE mechanism, which may lead to the discovery of new targets or compounds for the treatment of this disease. [ABSTRACT FROM AUTHOR]

Emerging evidence has shown the involvement of dysregulated transfer RNAs (tRNAs) and small RNAs derived from transfer RNAs (tsRNAs) in the pathophysiology of human diseases. The role of tRNAs and tsRNAs in systemic lupus erythematosus (SLE) remains unclear. Therefore, this study aims to investigate the possible regulatory roles of tRNAs and tsRNAs in the pathological mechanism of SLE. Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 20 SLE patients and 20 normal controls (NCs) to obtain tRNAs and tsRNAs, followed by tRNA and tsRNA expression profiling by the NextSeq system. Target genes were predicted by informatics analysis. Subsequently, to explore the function of messenger RNA (mRNA) in these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database, and Cytoscape software. A total of 101 tRNAs and 355 tsRNAs were found to be differentially expressed in SLE patients versus NCs by RNA microarray. GO analysis revealed that the altered target genes of the selected tRNAs and tsRNAs were most enriched similarly in immune response and the immune system process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tRNAs were most enriched in systemic lupus erythematosus, while the altered target genes of tsRNAs were most enriched in the T cell receptor signalling pathway, Th1 and Th2 cell differentiation and primary immunodeficiency. These pathways may be related to the initiation of SLE. Our results provide a novel perspective for studying the tRNA-related and tsRNA-related pathogenesis of SLE. • The expression levels of tRNA and tsRNA in PBMC of patients with SLE were different from those of normal people. • The biological functions involved in differentially expressed genes are all related to the immune system. • The potential role of tRNAs and tsRNAs in systemic lupus erythematosus was investigated. [ABSTRACT FROM AUTHOR]

Klinefelter syndrome (KS) is one of the most common congenital disorders of male infertility. Given its high heterogeneity in clinical and genetic presentation, the relationship between transcriptome, clinical phenotype, and associated co-morbidities seen in KS has not been fully clarified. Here, we report a 47,XXY Chinese male with infertility and analyzed the differences in gene expression patterns of peripheral blood mononuclear cells (PBMCs) with regard to a Chinese male and a female control with normal karyotype by single-cell sequencing. A total of 24,439 cells were analyzed and divided into 5 immune cell types (including B cells, T cells, macrophage cells, dendritic cells, and natural killer cells) according to marker genes. Using unsupervised dimensionality reduction and clustering algorithms, we identified molecularly distinct subpopulations of cells between the KS patient and both controls. Gene ontology enrichment analyses yielded terms associated with well-known comorbidities seen in KS as well as an affected immune system and type I diabetes mellitus. Based on our data, we identified several candidate genes which may be implicated in regulating the phenotype of KS. Overall, this analysis provides a comprehensive map of the cell types of PBMCs in a KS patient at the single-cell level, which will contribute to the prevention of comorbidity and improvement of the life quality of KS patients. [ABSTRACT FROM AUTHOR]

Background: Aerobic glycolysis has been recognized as one of the growth-promoting metabolic alterations of cancer cells. Emerging evidence indicates that nuclear factor κB (NF-κB) plays significant roles in metabolic adaptation in normal cells and cancer cells. However, whether and how NF-κB regulates metabolic reprogramming in hepatocellular carcinoma (HCC), specifically hepatitis B virus X protein (HBx)-initiated HCC, has not been determined. Methods: A dataset of the HCC cohort from the TCGA database was used to analyse the expression of NF-κB family members. Expression of NF-κBp65 and phosphorylation of NF-κBp65 (p-p65) were detected in liver tissues from HBV-related HCC patients and normal controls. A newly established HBx+/+/NF-κBp65f/f and HBx+/+/NF-κBp65Δhepa spontaneous HCC mouse model was used to investigate the effects of NF-κBp65 on HBx-initiated hepatocarcinogenesis. Whether and how NF-κBp65 is involved in aerobic glycolysis induced by HBx in hepatocellular carcinogenesis were analysed in vitro and in vivo. Results: NF-κBp65 was upregulated in HBV-related HCC, and HBx induced NF-κBp65 upregulation and phosphorylation in vivo and in vitro. Hepatocyte-specific NF-κBp65 deficiency remarkably decreased HBx-initiated spontaneous HCC incidence in HBx-TG mice. Mechanistically, HBx induced aerobic glycolysis by activating NF-κBp65/hexokinase 2 (HK2) signalling in spontaneous hepatocarcinogenesis, and overproduced lactate significantly promoted HCC cell pernicious proliferation via the PI3K (phosphatidylinositide 3-kinase)/Akt pathway in hepatocarcinogenesis. Conclusion: The data elucidate that NF-κBp65 plays a pivotal role in HBx-initiated spontaneous HCC, which depends on hyperactive NF-κBp65/HK2-mediated aerobic glycolysis to activate PI3K/Akt signalling. Thus, phosphorylation of NF-κBp65 will be a potential therapeutic target for HBV-related HCC. [ABSTRACT FROM AUTHOR]

A detailed understanding of the gene-regulatory network in ankylosing spondylitis (AS) is vital for elucidating the mechanisms of AS pathogenesis. Assaying transposase-accessible chromatin in single cell sequencing (scATAC-seq) is a suitable method for revealing such networks. Thus, scATAC-seq was applied to define the landscape of active regulatory DNA in AS. As a result, there was a significant change in the percent of CD8+ T cells in PBMCs, and 37 differentially accessible transcription factor (TF) motifs were identified. T cells, monocytes-1 and dendritic cells were found to be crucial for the IL-17 signaling pathway and TNF signaling pathway, since they had 73 potential target genes regulated by 8 TF motifs with decreased accessibility in AS. Moreover, natural killer cells were involved in AS by increasing the accessibility to TF motifs TEAD1 and JUN to induce cytokine-cytokine receptor interactions. In addition, CD4+ T cells and CD8+ T cells may be vital for altering host immune functions through increasing the accessibility of TF motifs NR1H4 and OLIG (OLIGI and OLIG2), respectively. These results explain clear gene regulatory variation in PBMCs from AS patients, providing a foundational framework for the study of personal regulomes and delivering insights into epigenetic therapy. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE), an autoimmune disease that causes multiorgan injury, has an unclear etiology and complex pathogenesis. Numerous studies have found abnormal alterations in mRNAs, proteins and/or metabolites in SLE patients. These findings have extended our understanding of the pathogenesis of SLE. Novel omics techniques, such as transcriptome, proteome and metabolome profiling, can identify and quantify large numbers of biomarkers of human diseases. However, in most cases, biological reactions are the consequences of interactions among genes, proteomes, and metabolites. Single biomolecules or signaling pathways cannot fully explain biological traits or functions. Therefore, integrative multi-omics analysis can help us systematically comprehend the intrinsic molecular mechanisms underlying biological function and pathogenesis. Integrating transcriptome, proteome, and metabolome KEGG enrichment analysis data will expand our knowledge of the pathogenesis of SLE. This review discusses the application, research progress and outlook on integrative multi-omics analysis in SLE research. [ABSTRACT FROM AUTHOR]

Background: Endoscopic variceal sequential ligation (EVSL) is currently endorsed in our hospital, as the preferred endoscopic treatment for prevention of variceal rebleeding and achieving adequate hemostasis. There is currently a lack of consensus surrounding EVSL-induced changes in esophageal motor function and abnormal reflux.Aims: To explore alterations in esophageal motor function and risk of abnormal gastroesophageal reflux in liver cirrhosis patients with esophageal varices, after EVSL.Methods: Twenty-one liver cirrhosis patients with esophageal varices were studied using manometry and 24-h pH monitoring 1 day prior to and 1 month following EVSL. The EVSL consisted of performing esophageal variceal ligation using a multi-band ligator, which was repeated every 4 weeks until the varices were eradicated.Results: The amplitude and duration of peristaltic contraction waves and the percentage of abnormal esophageal contraction waveforms were unaltered in both the proximal (P > 0.05) and the distal (P > 0.05) esophagus after EVSL. However, the lower esophageal sphincter pressure was decreased following EVSL (16.1 ± 7.9 mmHg vs 21.1 ± 6.3 mmHg (P < 0.05)). Various quantitative parameters including percentage of total monitoring time with pH < 4.0, total number of reflux episodes, number of reflux episodes > 5 min, and DeMeester scores were not increased in post-EVSL patients. Abnormal reflux monitored by 24-h pH monitoring occurred in ten (47.6%) pre-EVSL patients and 11 (52.4%) post-EVSL patients.Conclusions: Although EVSL affects esophageal motility by relatively decreasing LES pressure, it does not induce substantial motor abnormalities nor increase risk of abnormal gastroesophageal reflux disease in cirrhosis patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a malignant disease caused by a variety of factors. However, the genomic and molecular aberrations in HCC are largely unknown. Herein, pituitary tumor transforming gene 1 (PTTG1) was discovered as a potential inflammation‐related oncogene in HCC, and its functions and molecular mechanisms were investigated. mRNA expression microarray, real‐time polymerase chain reaction (PCR), immunohistochemistry, and western blotting analyses revealed that PTTG1 is upregulated in HCC. Further in vitro and in vivo studies indicated that the proinflammatory cytokine tumor necrosis factor‐α (TNF‐α) induces PTTG1 expression, and PTTG1 was found to upregulate c‐myc, a well‐known oncogene. Downregulation of PTTG1 reduced c‐myc and proliferating cell nuclear antigen (PCNA) expression and inhibited cell proliferation. Interestingly, inhibition of c‐myc by 10058‐F4 did not affect PTTG1, which suggests that PTTG1 regulates c‐myc expression. Furthermore, PTTG1 expression levels are inversely correlated with HCC patient survival, indicating an independent prognostic biomarker for patients with HCC. Our data demonstrate that PTTG1 is involved in TNF‐α‐related HCC via c‐myc induction and that PTTG1 may be a potential therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

• A risk prediction for IDH in HD-patients can be an important tool for clinical work. • LightGBM model plays as an interpretable and best-performing model for the task. • IDH-A and IDH-B model can usefully complement each other for risk prediction. Intradialytic hypotension (IDH) is closely associated with adverse clinical outcomes in HD-patients. An IDH predictor model is important for IDH risk screening and clinical decision-making. In this study, we used Machine learning (ML) to develop IDH model for risk prediction in HD patients. 62,227 dialysis sessions were randomly partitioned into training data (70%), test data (20%), and validation data (10%). IDH-A model based on twenty-seven variables was constructed for risk prediction for the next HD treatment. IDH-B model based on ten variables from 64,870 dialysis sessions was developed for risk assessment before each HD treatment. Light Gradient Boosting Machine (LightGBM), Linear Discriminant Analysis, support vector machines, XGBoost, TabNet, and multilayer perceptron were used to develop the predictor model. In IDH-A model, we identified the LightGBM method as the best-performing and interpretable model with C- statistics of 0.82 in Fall30Nadir90 definitions, which was higher than those obtained using the other models (P <0.01). In other IDH standards of Nadir90, Nadir100, Fall20, Fall30, and Fall20Nadir90, the LightGBM method had a performance with C- statistics ranged 0.77 to 0.89. As a complementary application, the LightGBM model in IDH-B model achieved C- statistics of 0.68 in Fall30Nadir90 definitions and 0.69 to 0.78 in the other five IDH standards, which were also higher than the other methods, respectively. Use ML, we identified the LightGBM method as the good-performing and interpretable model. We identified the top variables as the high-risk factors for IDH incident in HD-patient. IDH-A and IDH-B model can usefully complement each other for risk prediction and further facilitate timely intervention through applied into different clinical setting. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Aim: β‐Arrestins (β‐arrs) are regulators and mediators of G protein‐coupled receptor signaling that are functionally involved in inflammation. Nuclear factor‐κB p65 (NF‐κBp65) activation has been observed early in the onset of pancreatitis. However, the effect of β‐arrs in acute pancreatitis (AP) is unclear. The aim of this study is to investigate whether β‐arrs are involved in AP through activation of NF‐κBp65. Methods: Acute pancreatitis was induced by either caerulein injection or choline‐deficient supplemented with ethionine diet (CDE). β‐arr1 wild‐type and β‐arr1 knockout mice were used in the experiment. The survival rate was calculated in the CDE model mice. Histological and western blot analyses were performed in the caerulein model. Inflammatory mediators were detected by real‐time polymerase chain reaction in the caerulein‐induced AP mice. Furthermore, AR42J and PANC‐1 cell lines were used to further study the effects of β‐arr1 in caerulein‐induced pancreatic cells. Results: β‐Arr1 but not β‐arr2 is significantly downregulated in caerulein‐induced AP in mice. Targeted deletion of β‐arr1 notably upregulated expression of the pancreatic inflammatory mediators including tumor necrosis factor α and interleukin 1β as well as interleukin 6 and aggravated AP in caerulein‐induced mice. β‐Arr1 deficiency increased mortality in mice with CDE‐induced AP. Further, β‐arr1 deficiency enhanced caerulein‐induced phosphorylation of NF‐κBp65 both in vivo and in vitro. Conclusion: β‐Arr1 alleviates AP via repression of NF‐κBp65 activation, and it is a potentially therapeutic target for AP. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting thousands of people. There are still no effective biomarkers for SLE diagnosis and disease activity assessment. We performed proteomics and metabolomics analyses of serum from 121 SLE patients and 106 healthy individuals, and identified 90 proteins and 76 metabolites significantly changed. Several apolipoproteins and the metabolite arachidonic acid were significantly associated with disease activity. Apolipoprotein A-IV (APOA4), LysoPC(16:0), punicic acid and stearidonic acid were correlated with renal function. Random forest model using the significantly changed molecules identified 3 proteins including ATRN, THBS1 and SERPINC1, and 5 metabolites including cholesterol, palmitoleoylethanolamide, octadecanamide, palmitamide and linoleoylethanolamide, as potential biomarkers for SLE diagnosis. Those biomarkers were further validated in an independent cohort with high accuracy (AUC = 0.862 and 0.898 for protein and metabolite biomarkers respectively). This unbiased screening has led to the discovery of novel molecules for SLE disease activity assessment and SLE classification. [ABSTRACT FROM AUTHOR]