The Causal Relationship between PCSK9 Inhibitors and Osteoporosis Based on Drug-Targeted Mendelian Combined Mediation Analysis.

PCSK9 inhibitors have been shown to lower serum low density lipoprotein cholesterol (LDL-C) levels and are considered integral in the treatment of cardiovascular diseases. However, the potential association between PCSK9 inhibitors and osteoporosis is unclear now. In this study, drug-targeted mendelian randomization (MR) was utilized in conjunction with mediation analysis including bone mineral density (BMD), total 25-hydroxyvitamin D (T25(OH)D) levels and calcium supplementation to investigate the causal relationship between PCSK9 inhibitors and osteoporosis. The LDL-C level was chosen as the exposure variable in a sample size of 173,082 individuals. We conducted a MR analysis on the relationship between PCSK9 inhibitors and osteoporosis, elucidating the mediators involved. Utilizing the inverse variance weighted (IVW) method, we found the risk of osteoporosis was reduced by 0.6% in those who used PCSK9 inhibitors compared with non-users (OR: 0.994, 95%CI: 0.991-0.998, P < 0.001). In people aged 30-45 years, the risk of low BMD was 1.176 times higher among PCSK9 inhibitor users compared to non-users (OR: 1.176, 95%CI: 1.017-1.336, P = 0.045). Conversely, people aged 45-60 years who used PCSK9 inhibitors had a 14.9% lower risk of low BMD compared to non-users (OR: 0.851, 95%CI: 0.732-0.968, P = 0.007). Mediation analysis revealed that 43.33% of the impact of PCSK9 inhibitors on osteoporosis was mediated through BMD levels, with the remaining 56.67% being a direct effect. Effects of PCSK9 inhibitors on BMD levels varied in different ages. In addition, the risk of high serum T25(OH)D levels were 1.091 times among PCSK9 inhibitor users compared to non-users (OR: 1.091, 95%CI: 1.065-1.112, P < 0.001), providing valuable insights for clinicians.

Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer.

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sjögren's syndrome by integrated bioinformatics analysis.

Primary Sjögren's syndrome (pSS) is known as autoimmune disease characterized by damage to endocrine glands, such as the salivary and lacrimal glands. This study aimed to identify potential biomarkers for pSS using integrated bioinformatics analysis and explore the relationship between differentially expressed genes (DEGs) and immune infiltration. Three pSS datasets (GSE7451, GSE23117, and GSE40611) from the gene expression omnibus database were integrated. All the datasets were processed in R (version 4.0.3). A total of 16 immune cells and 13 immune functions were obtained. The top immune cell and immune function were "activated" dendritic cells and major histocompatibility complex class I. Correlation analysis showed the top correlation among 16 immune cells were B cells and tumor infiltrating lymphocytes, check-point and T cell co-stimulation, respectively. In comparisons of immune score, "activated" dendritic cells (.657 vs 594, P < .001), B cells (.492 vs 434, P = .004), macrophages (.631 vs 601, P = .010), inflammation-promoting (.545 vs 478, P < .001), Type I interferon Reponse (.728 vs 625, P < .001) and so on were higher in pSS than control group. In correlation analysis, the up-regulation of interferon induced protein with tetratricopeptide repeats 1 gene was strongly correlated with Type I interferon response with a correlation coefficient of .87. The receiver operating characteristic curve of 5 genes showed that the area under curve was.891. In the verification model, the area under curve was.881. In addition, disease ontology analysis supported the association between DEGs and pSS. In summary, pSS has a variety of DEGs in immune infiltration, which is worthy of the attention from clinicians.

Causality between depression and ankylosing spondylitis in a European population: Results from a Mendelian randomization analysis.

The aim of this study was to explore the application of Mendelian randomization (MR) Egger and inverse variance weighted (IVW) in a causal effect on depression and ankylosing spondylitis (AS). Instrumental variables (IVs) were determined using genome-wide association studies. The 2-sample MR analysis was conducted by MR Egger to test the causal effect between depression and AS. The pleiotropy of potential instrumental variables was evaluated. The results of MR Egger and IVW were further compared. A total of 3 single nucleotide polymorphisms as the construct IVs were included. IVW results showed a significant causal effect between depression and AS (P < .001). Depression could promote the risk of AS (odds ratio = 1.060, 95% confidence interval: 1.026-1.094). However, the MR Egger showed no causal effect (P = .311). Heterogeneity statistics suggested that no heterogeneity was existed (P > .05). It was also suggested that there was no horizontal pleiotropy in IVs (MR Egger intercept: -0.0004, P = .471). Reverse MR analysis suggested that there was no causal effect between AS and depression (P > .05). Gene expression quantitative trait locus (QTLs) suggested that rs2517601 and RNF39 were positively correlated (beta = 1.066, P < .001). Depression may be one of the causes of AS by MR analysis in a European population. We can estimate the causal effect based on IVW when horizontal pleiotropy is very tiny.

Chlorpyrifos induces male infertility in pigs through ROS and PI3K-AKT pathway.

Chlorpyrifos (CPF) has been shown to have male reproductive toxicity in mice and rat. However, the association of CPF and male reproduction in pigs remains unknown. Therefore, this study attempts to investigate the damage of CPF on male reproduction in pigs and its potential molecular mechanisms. First, ST cells and porcine sperms were treated with CPF and then cell proliferation, apoptosis, motility of sperm, and oxidative stress levels were examined, respectively. Meanwhile, RNA sequencing was performed on ST cells before and after the treatment of CPF. The results of experiments in vitro showed that CPF had broad-spectrum toxic effects on ST cells and porcine sperms. The RNA-sequencing data and WB results indicated that CPF may regulate cell survival through the PI3K-AKT pathway. In conclusion, this study may lay the foundation for improving male fertility in pigs and provide theoretical information for human infertility.

Bioinspired Natural Magnolol-Based Adhesive with Strong Adhesion and Antibacterial Properties for Application in Wet and Dry Environments.

The development of environmentally friendly, green, and nontoxic adhesives with excellent dry and wet adhesion properties is of great attraction. In nature, barnacles and mussels exhibit strong adhesion by secreting a hydroxyl-rich dopa. Inspired by their adhesion mechanism, a simple biobased MAG-PETMP (MP) adhesive was prepared from magnolol (MAG) and pentaerythritol tetra (3-mercaptopropionate) (PETMP) by a thiol-ene click chemistry reaction. MP as an adhesive exhibits high bond strength with other substrates due to hydrogen bonds formed by the abundant hydroxyl groups at the interface and shows an inherent thermosetting network structure. Since MP has a thermosetting network, it exhibits excellent thermal stability, solvent resistance, and high mechanical strength, which make the adhesive stable in a humid environment. The cross-linking degree of MP can be easily controlled by adjusting the molar ratio of MAG and PETMP. Among the synthesized samples, the elongation at break of the MP 1 formulation is 174.27%, which makes it promising for use as a flexible adhesive. Moreover, the inherent antibacterial properties of MAG enable MP to exhibit antimicrobial properties and antibacterial adhesion to some extent. This work provides a simple biomimetic strategy that could enable the application of MAG for adhesives.

Development and assessment of a predictive model for early diagnosis of rheumatoid arthritis in southwest China: A new nomogram.

Rheumatoid arthritis (RA) is a disease complicated with inflammatory synovitis, which seriously affects the life quality of patients. Early diagnosis is important for prognosis of RA. Here, we aimed to develop and assess a model for early diagnosis of RA in southwest China. A nomogram including 44 patients with an early diagnosis of RA was developed. Variables were filtered by least absolute contraction selection operator and multiple logistic regression. The efficiency and clinical application range were evaluated. This nomogram showed that rheumatoid factor, erythrocyte sedimentation rate, RA33, facet joint and knee joint had high positive predictive value for RA. The area under curve was 0.920 [95% confidence interval (CI): 0.865-0.975]. In the validation model, area under curve was 0.942 (95% CI: 0.893-0.991). Calibration and decision curve suggested that this nomogram was helpful within the threshold probability range of 0.02 to 1.00. Using this nomogram will help clinicians in the early diagnosis of RA. Laboratory indicators such as rheumatoid factor, erythrocyte sedimentation rate, RA33, and clinical symptoms such as morning stiffness, facet joint and knee joint are very important, which deserves the attention of clinicians.

Cyanidin-3-O-Glucoside Induces the Apoptosis of Human Gastric Cancer MKN-45 Cells through ROS-Mediated Signaling Pathways.

Cyanidin-3-O-glucoside (C3G), an active ingredient in anthocyanins, mainly exists in dark cereals. C3G was investigated for its effect on human gastric cancer (GC) cells, together with its molecular mechanism. The CCK-8 assay results showed that C3G had significant antiproliferative effects on GC cells, but it had little effect on normal cells. Western blot and flow cytometry results showed that C3G regulated the reduction of mitochondrial membrane potential and arrested the cell cycle in the G2/M phase through the AKT signaling pathway, causing the cells to undergo apoptosis. Additionally, in MKN-45 cells, C3G markedly raised intracellular reactive oxygen species (ROS) levels. The wound healing assay and Transwell assay results showed that MKN-45 cell migration was significantly inhibited. Western blot results showed that the expression of E-cadherin protein was upregulated and the expressions of ß-catenin, N-cadherin, and Vimentin were downregulated. Additionally, following N-acetylcysteine treatment, the expression levels of these proteins were reduced. In conclusion, C3G caused MKN-45 cells to undergo apoptosis; arrested the cell cycle in the G2/M phase; hindered cell migration; and activated the MAPK, STAT3, and NF-κB signaling pathways, by inducing an increase in ROS levels. Thus, C3G may be a promising new medication for the treatment of GC.

Bioinformatics analysis identified immune infiltration, risk and drug prediction models of copper-induced death genes involved in salivary glands damage of primary Sjögren's syndrome.

This study aimed to identify copper-induced death genes in primary Sjögren's syndrome (pSS) and explore immune infiltration, risk and drug prediction models for salivary glands (SGs) damage. The 3 datasets, including GSE40611, GSE23117, and GSE7451 from the Gene Expression Omnibus database were downloaded. The datasets were processed using the affy in R (version 4.0.3). In immune cells, copper-induced death genes were strongly expressed in "activated" dendritic cells (aDCs), macrophages and regulatory T cells (Treg). In immune functions, copper-induced death genes were strongly expressed in major histocompatibility complex (MHC) class I, human leukocyte antigen (HLA) and type I interferon (IFN) response. Correlation analysis showed that 5 genes including SLC31A1, PDHA1, DLD, ATP7B, and ATP7A were significantly correlated with immune infiltration. The nomogram suggested that the low expression of PDHA1 was significant for predicting the risk of pSS and the area under curve was 0.678. Drug model suggested that "Bathocuproine disulfonate CTD 00001350," "Vitinoin CTD 00007069," and "Resveratrol CTD 00002483" were the drugs most strongly associated with copper-induced death genes. In summary, copper-induced death genes are associated with SGs injury in pSS, which is worthy of clinicians' attention.

Predicting bacterial infection risk in patients with ANCA-associated vasculitis in southwest China: development of a new nomogram.

OBJECTIVES: The aim of this study was to develop and assess a risk nomogram of bacterial infection in patients with ANCA-associated vasculitis (AAV) in southwest China. METHOD: We established a prediction model based on a training dataset of 249 AAV patients. The least absolute shrinkage and selection operator (Lasso) was used to screen feature variables. Multivariate logistic regression analysis was used to build a prediction model for feature variables. Nomogram was used to predict the risk of bacterial infection in AAV patients. Receiver operating characteristic (ROC) curve was used to evaluate and verify the prediction accuracy of the model. Calibration and clinical useful range was assessed using calibration curve and decision curve analysis, respectively. RESULTS: Bactericidal permeability enhancement protein of ANCAs (BPI-ANCAs), procalcitonin (PCT), and white blood cell (WBC) were the characteristic variables in this study. Nomogram showed that positive BPI-ANCAs and PCT had higher positive predictive value for bacterial infection in AAV patients. The area under curve (AUC) of the model was 0.703 (95% confidence interval: 0.640-0.766). In the validation model, the AUC was 0.745 (95% confidence interval: 0.617-0.872). Decision curve analysis showed that the nonadherence nomogram was clinically useful within the threshold probability range of 0.31-0.85. CONCLUSIONS: Nomogram combined with BPI-ANCAs and PCT has the guiding significance for predicting bacterial infection risk in AAV. As an ANCA-specific autoantibody, BPI-ANCAs is helpful for clinicians to understand the role of specific autoantibodies in the pathogenesis of AAV. Key Points • BPI-ANCAs, PCT, and WBC could predict bacterial infection in AAV patients. • Nomogram showed that positive BPI-ANCAs had a high positive predictive value for bacterial infection in AAV patients.

Kidney Bean Fermented Broth Alleviates Hyperlipidemic by Regulating Serum Metabolites and Gut Microbiota Composition.

Hyperlipidemia with fat accumulation and weight gain causes metabolic diseases and endangers human body health easily which is accompanied by metabolic abnormalities and intestinal flora disorders. In this study, the kidney bean fermented broth (KBF) was used in rats that were fed a high-fat diet to induce hyperlipidemia in order to subsequently analyse the serum metabolomics and gut microbiota modulatoration. The results show that the contents of the total polyphenols and total flavonoids in the KBF were up three and one times, while energy and carbohydrates decreased. In the HFD-induced hyperlipidemic model, body weight, organ weight, and the level of blood lipids (ALT, AST, TG, TC) were lower in rats treated with KBF than in the controls. Metabonomics indicate that there were significant differences in serum metabolomics between the KBF and the HFD. KBF could significantly improve the glycerophospholipids, taurine, and hypotaurine metabolism and amino acid metabolism of hyperlipidemic rats and then improve the symptoms of hypersterol and fat accumulation in rats. The relative abundance of beneficial bacteria increased while pathogenic bacteria decreased after the intervention of KBF. KBF ameliorates dyslipidemia of HFD-induced hyperlipidemic via modulating the blood metabolism and the intestinal microbiota. Collectively, these findings suggest that KBF could be developed as a functional food for anti-hyperlipidemia.

Clinical significance of HEp-2 cell cytoplasmic patterns in anti-neutrophil cytoplasmic antibody associated vasculitis.

ABSTRACT: The study was to investigate the clinical characteristics and significance of antinuclear antibody (ANA) cytoplasmic patterns in ANCA-associated vasculitis (AAV) from Southwest China.A retrospective study including 232 AAV patients from Peoples Hospital of Deyang City was performed. These included 115 patients with ANA cytoplasmic pattern as observation group and 117 patients without ANA cytoplasmic pattern as control group.Chest involvement (60.00 vs 46.15, P = .035), cardiovascular involvement (5.21 vs 29.91, P < .001), and renal involvement (37.39 vs 77.78, P = .001) were different between groups.Total protein (69.55 vs 64.01, P < .001), triglyceride (1.41 vs 1.18, P = .023), mean cell volume (89.76 vs 87.59, P = .040), and estimated glomerular filtration rate (76.67 vs 50.87, P = .035) were higher in ANA cytoplasmic patterns group. Creatinine (73.00 vs 117.50, P = .011), white blood cell (6.93 vs 8.86, P = .001), platelet (196.0 vs 239.0, P = .017), anti-myeloperoxidase (2.44 vs 3.42, P = .042), and anti-proteinase 3 (1.00 vs 4.93, P = .007) were lower in this group. In multivariate analysis, creatinine (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.06-1.38), triglyceride (OR = 1.97, 95% CI: 1.10-3.48), and anti-myeloperoxidase (OR = 1.64, 95% CI: 1.37-1.95) were independent risk factors of AAV renal involvement. Total protein (OR = .95, 95% CI: 0.91-0.99) was an independent protective factor of AAV renal involvement. Chi-square test showed that speckled pattern was different among anti-neutrophil cytoplasmic antibody patterns (χ2 = 18.526, P < .001).In summary, HEp-2 cell cytoplasmic patterns have certain clinical significance in AAV, which is a new exploration of the clinical value of ANA.

Beneficial Effect of Kidney Bean Resistant Starch on Hyperlipidemia-Induced Acute Pancreatitis and Related Intestinal Barrier Damage in Rats.

Accumulating attention has been focused on resistant starch (RS) due to its blood-lipid-lowering activities. However, reports on the potential bioactivities of RS for preventing hyperlipidemia acute pancreatitis (HLAP) are limited. Therefore, in this study, an acute pancreatitis model was set up by feeding a hyperlipidemia diet to rats, and subsequently evaluating the anti-HLAP effect of RS in kidney beans. The results show that the IL-6, IL-1ß, and TNF-α of serum in each RS group were decreased by 18.67-50.00%, 7.92-22.89%, and 8.06-34.04%, respectively, compared with the model group (MOD). In addition, the mRNA expression of tight junction protein ZO-1, occludin, and antibacterial peptides CRAMP and DEFB1 of rats in each RS group increased by 26.43-60.07%, 229.98-279.90%, 75.80-111.20%, and 77.86-109.07%, respectively. The height of the villi in the small intestine and the thickness of the muscle layer of rats were also increased, while the depth of the crypt decreased. The present study indicates that RS relieves intestinal inflammation, inhibits oxidative stress, and prevents related intestinal barrier damage. These results support the supplementation of RS as an effective nutritional intervention for HLAP and associated intestinal injury.

Analysis of WDFY4 rs7097397 and PHLDB1 rs7389 polymorphisms in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To explore the relationship among patient-specific SNPs from one SLE family, lupus susceptibility, and laboratory indicators in a western Chinese population. METHODS: We previously performed whole exome sequencing in one SLE family and screened 5 SLE candidate SNPs. In this study, we verified them in 634 SLE patients and 400 healthy controls and analyzed the relationship between SNPs and laboratory indicators. RESULTS: Among the 5 candidate SNPs, PHLDB1 rs7389T/G (dominant model, OR = 0.627, 95%CI = 0.480-0.820, P = 0.001) and WDFY4 rs7097397G/A (dominant model, OR = 0.653, 95%CI = 0.438-0.973, P = 0.035) were associated with SLE susceptibility. In addition, the G allele of rs7389 was related to an increased level of TNF-α (q = 0.013). The A allele of rs7097397 was related to reduced levels of IL-1ß (q = 0.033) and IL-6 (q = 0.039) and high positive rate of antinuclear antibodies (q = 0.021). CONCLUSIONS: Our study indicated that both the rs7389T/G and rs7097397G/A polymorphisms were related to SLE susceptibility in western China. rs7389T/G was related to increased TNF-α content, while rs7097397G/A was associated with reduced IL-1ß and IL-6 content and increased antinuclear antibody positive rate. Key Points • The G allele of rs7389 was related to reduced susceptibility to SLE. • The A allele of rs7097397 was associated with reduced susceptibility to SLE. • The G allele of rs7389 was related to increased levels of TNF-α. • The A allele of rs7097397 was related to decreased concentrations of IL-1ß and IL-6, as well as an increased positive rate of antinuclear antibody.

Early treatment of rituximab combined with eltrombopag for secondary thrombocytopenic purpura in rheumatoid arthritis: A case report.

RATIONALE: Secondary immune thrombocytopenic purpura (ITP) is also known as acquired thrombocytopenic purpura, autoimmune disease is usually one of the important causes. There are few reports about treatment of refractory thrombocytopenic purpura in rheumatoid arthritis (RA). We report a case of refractory ITP in which changes in platelet-related markers with therapeutic agents are worthy of the attention of clinicians. PATIENT CONCERNS: A 69-year-old woman admitted for ecchymosis on the neck and arms for 15 days presented to our hospital. She was diagnosed with RA 5 years ago. DIAGNOSIS: The diagnosis met the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria. The disease activity score 28 (DAS-28) was 4.6, indicating that the disease activity was moderate. INTERVENTIONS: Treatment with first-line therapies and second-line treatment--eltrombopag (EPAG) were ineffective. Therefore, we performed rituximab combined with a low dose of EPAG. OUTCOMES: The patient received 2 cycles of rituximab combined with EPAG, and reported no new petechiae on her buccal mucosa and limbs during follow-up. LESSONS: This case suggests that early treatment of rituximab combined with EPAG is beneficial to patients with refractory ITP in RA. In terms of disease dynamic monitoring, immature platelet fraction (IPF) may be an auxiliary indicator for predicting efficacy, but its significance needs further study.

The value of anti-rods and rings antibodies in patients with nonhepatitis virus infection: A single-center retrospective study from Southwest China.

ABSTRACT: The aim of this study was to retrospectively investigate the clinical significance of anti-rods and rings (anti-RR) antibodies in nonhepatitis virus infection patients from Southwest China.Anti-RR antibodies were determined by indirect immunofluorescence assay in a group of 19,935 individuals with antinuclear antibodies test from January 2017 to December 2019. The laboratory and clinical data were collected. Finally, 66 samples with anti-RR antibodies (0.33%) were detected.In Wilcoxon rank sum test, gamma glutamyl transferase (Z = -3.364, P = .001), alpha-l-fucosidase (AFU) (Z = -2.312, P = .021), uric acid (Z = -1.634, P = .047) and red blood cell distribution width (Z = -2.285, P = .022) were higher in metabolic disease group than nonmetabolic disease group. In independent-samples t test, endogenous creatinine clearance was higher in metabolic disease group than nonmetabolic disease group (t = 2.061, P = .045). During the follow-up period of 37 patients with anti-RR antibodies for 1 to 60 months, the titers of anti-RR were significantly increased in the metabolic disease group (Z = -2.346, P = .019). In binary logistic regression analysis, triglycerides (odds ratio 3.679, 95% confidence interval 1.467-24.779, P = .048) was associated with elevated titers of anti-RR antibodies.In summary, anti-RR in non-hepatitis patients may be a manifestation of metabolic disorders, and has a certain correlation with routine laboratory indicators, which is worthy of the attention from clinicians.

Effects of different types of humic acid isolated from coal on soil NH3 volatilization and CO2 emissions.

Humic acid can improve soil nutrients and promote plant growth. Weathered coal and lignite can be used as agricultural resources due to high humic acid content, but their impact on soil NH3 volatilization and CO2 emissions are yet to be determined. In this study, a field experiment was carried out to compare the effects of four types of humic acid isolated from coal (pulverized weathered coal (HC), pulverized lignite (HL), alkalized weathered coal (AC) and alkalized lignite (AL)) on NH3 volatilization, CO2 emissions, pH, the C/N ratio and enzyme activities in soil cultivated with maize. The effect of biotechnology humic acids (BHA) was also examined for comparison. HL, AC, AL and BHA all increased cumulative NH3 losses by 147.7, 278.5, 113.9, and 355.3%, respectively, compared with the control (chemical fertilizer only), and notably, BHA caused an increase of 90.71% compared with the humic acids isolated from coal. A significant increase in cumulative CO2 losses was observed only under AL treatment, by 14.44-24.90% compared with all other treatments. Soil urease activity was positively correlated with cumulative NH3 losses (P < 0.001), while the soil C/N ratio (P < 0.001) and soil sucrase activity (P < 0.05) were positively correlated with cumulative CO2 losses. Since humic acid from pulverized weathered coal caused no increase in NH3 volatilization or CO2 emissions, it is therefore thought to be the most suitable humic acid for field application.

Clinical significance and influencing factors of fibrinogen in ANCA-associated vasculitis: A single-center retrospective study from Southwest China.

Hypercoagulable is an important pathological state in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Fibrinogen (FIB) is the main protein in coagulation process. In this study, we aimed to investigate the clinical significance and influencing factors of FIB in AAV from Southwest China.A retrospective study was performed on AAV patients from Peoples Hospital of Deyang City from January 2007 to December 2018. Demographic and clinical characteristics were collected.A total of 463 AAV patients were included. In Wilcoxon rank sum test, FIB was significantly higher in AAV active group than inactive group (P = .005). FIB was also higher in bacterial infection group than in non-infection group both in active group (P = .008) and inactive group (P = .017). In receiver operating characteristic (ROC) curve analysis, the critical value of FIB for diagnosis of bacterial infection between AAV active and inactive groups was 3.385 g/L (P = .030), with sensitivity of 70.2% and specificity of 52.9%. In the multivariate analysis of variance (MANOVA), estimated glomerular filtration rate (eGFR) was shown to be an independent factor for FIB (P = .001). Least-significant difference showed the concentration of FIB (P < .05) increased with renal impairment, especially in endstage kidney disease (ESKD).FIB identified a certain reference value in distinguishing AAV activity from bacterial infection. ESKD had a statistical effect on it. Influencing factors of FIB should be evaluated based on the renal function impairment of patients.

Identification of differentially expressed lncRNAs and mRNAs in luminal-B breast cancer by RNA-sequencing.

BACKGROUND: Luminal B cancers show much worse outcomes compared to luminal A. This present study aims to screen key lncRNAs and mRNAs correlated with luminal-B breast cancer. METHODS: Luminal-B breast cancer tissue samples and adjacent tissue samples were obtained from 4 patients with luminal-B breast cancer. To obtain differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between luminal-B breast cancer tumor tissues and adjacent tissues, RNA-sequencing and bioinformatics analysis were performed. Functional annotation of DEmRNAs and protein-protein interaction networks (PPI) construction were performed. DEmRNAs transcribed within a 100 kb window up- or down-stream of DElncRNAs were searched, which were defined as cis nearby-targeted DEmRNAs of DElncRNAs. DElncRNA-DEmRNA co-expression networks were performed. The mRNA and lncRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database to validate the expression patterns of selected DEmRNAs and DElncRNAs. RESULTS: A total of 1178 DEmRNAs and 273 DElncRNAs between luminal-B breast cancer tumor tissues and adjacent tissues were obtained. Hematopoietic cell lineage, Cytokine-cytokine receptor interaction, Cell adhesion molecules (CAMs) and Primary immunodeficiency were significantly enriched KEGG pathways in luminal-B breast cancer. FN1, EGFR, JAK3, TUBB3 and PTPRC were five hub proteins of the PPI networks. A total of 99 DElncRNAs-nearby-targeted DEmRNA pairs and 1878 DElncRNA-DEmRNA co-expression pairs were obtained. Gene expression results validated in TCGA database were consistent with our RNA-sequencing results, generally. CONCLUSION: This study determined key genes and lncRNAs involved in luminal-B breast cancer, which expected to present a new avenue for the diagnosis and treatment of luminal-B breast cancer.

Rehmannia glutinosa Libosch Extracts Prevent Bone Loss and Architectural Deterioration and Enhance Osteoblastic Bone Formation by Regulating the IGF-1/PI3K/mTOR Pathway in Streptozotocin-Induced Diabetic Rats.

Rehmanniae Radix Praeparata (RR, named as Shudihuang in traditional Chinese medicine), the steamed roots of Rehmannia glutinosa Libosch (Scrophulariaceae), has been demonstrated to have anti-diabetic and anti-osteoporotic activities. This study aimed to explore the protective effect and underlying mechanism of RR on diabetes-induced bone loss. It was found that RR regulated the alkaline phosphatase activity and osteocalcin level, enhanced bone mineral density, and improved the bone microarchitecture in diabetic rats. The catalpol (CAT), acteoside (ACT), and echinacoside (ECH) from RR increased the proliferation and differentiation of osteoblastic MC3T3-E1 cells injured by high glucose and promoted the production of IGF-1 and expression of related proteins in BMP and IGF-1/PI3K/mammalian target of rapamycin complex 1 (mTOR) signaling pathways. The verifying tests of inhibitors of BMP pathway (noggin) and IGF-1/PI3K/mTOR pathway (picropodophyllin) and molecular docking of IGF-1R further indicated that CAT, ACT, and ECH extracted from RR enhanced bone formation by regulating IGF-1/PI3K/mTOR signaling pathways. These findings suggest that RR may prove to be a promising candidate drug for the prevention and treatment of diabetes-induced osteoporosis.