Tamoxifen exerts anti-peritoneal fibrosis effects by inhibiting H19-activated VEGFA transcription.

BACKGROUND: Peritoneal dialysis (PD) remains limited due to dialysis failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported to treat fibrosis, but the underlying mechanism remains unknown. In this study, we sought to explore whether tamoxifen played an anti-fibrotic role by affecting transcription factor ESR1. METHODS: ESR1 expression was detected in the human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40 mM methylglyoxal for 2 weeks to establish PD-induced peritoneal fibrosis. Tamoxifen was administrated by daily gavage, at the dose of 10 mg/kg. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay were performed to validate ESR1 bound H19 promoter. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of H19 on the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells (HPMCs). Intraperitoneal injection of nanomaterial-wrapped 2'-O-Me-modified small interfering RNA was applied to suppress H19 in the mouse peritoneum. RNA immunoprecipitation and RNA pull-down assays demonstrated binding between H19 and p300. Exfoliated peritoneal cells were obtained from peritoneal dialysis effluent to analyze the correlations between ESR1 (or H19) and peritoneal solute transfer rate (PSTR). RESULTS: ESR1 was increased significantly in the peritoneum after long-term exposure to PD dialysate. Tamoxifen treatment ameliorated high glucose-induced MMT of HPMCs, improved ultrafiltration rate, and decreased PSTR of mouse peritoneum. Tamoxifen reduced the H19 level by decreasing the ESR1 transcription of H19. Depletion of H19 reversed the pro-fibrotic effect of high glucose while ectopic expression of H19 exacerbated fibrotic pathological changes. Intraperitoneal injection of nanomaterial-wrapped 2'-O-Me-modified siRNAs targeting H19 mitigated PD-related fibrosis in mice. RNA immunoprecipitation (RIP) and RNA pull-down results delineated that H19 activated VEGFA expression by binding p300 to the VEGFA promoter and inducing histone acetylation of the VEGFA promoter. ESR1 and H19 were promising targets to predict peritoneal function. CONCLUSIONS: High glucose-induced MMT of peritoneal mesothelial cells in peritoneal dialysis via activating ESR1. In peritoneal mesothelial cells, ESR1 transcribed the H19 and H19 binds to transcription cofactor p300 to activate the VEGFA. Targeting ESR1/H19/VEGFA pathway provided new hope for patients undergoing peritoneal dialysis.

Vibrio harveyi co-infected with Cryptocaryon irritans to orange-spotted groupers Epinephelus coioides.

The orange-spotted grouper (Epinephelus coioides) is a high economic value aquacultural fish in China, however, it often suffers from the outbreak of parasitic ciliate Cryptocaryon irritans as well as bacterium Vibrio harveyi which bring great loss in grouper farming. In the present study, we established a high dose C. irritans local-infected model which caused the mortality of groupers which showed low vitality and histopathological analysis demonstrated inflammatory response and degeneration in infected skin, gill and liver. In addition, gene expression of inflammatory cytokines was detected to assist the estimate of inflammatory response. Furthermore, we also found that the activity of Na+/K+ ATPase in gill was decreased in groupers infected C. irritans and the concentration of Na+/Cl- in blood were varied. Base on the morbidity symptom occurring in noninfected organs, we hypothesized that the result of morbidity and mortality were due to secondary bacterial infection post parasitism of C. irritans. Moreover, four strains of bacteria were isolated from the infected site skin and liver of local-infected groupers which were identified as V. harveyi in accordance of phenotypic traits, biochemical characterization and molecular analysis of 16S rDNA genes, housekeeping genes (gyrB and cpn60) and species-specific gene Vhhp2. Regression tests of injecting the isolated strain V. harveyi has showed high pathogenicity to groupers. In conclusion, these findings provide the evidence of coinfections with C. irritans and V. harveyi in orange-spotted grouper.

Serum metabolic alterations in peritoneal dialysis patients with excessive daytime sleepiness.

Excessive daytime sleepiness (EDS) is associated with quality of life and all-cause mortality in the end-stage renal disease population. This study aims to identify biomarkers and reveal the underlying mechanisms of EDS in peritoneal dialysis (PD) patients. A total of 48 nondiabetic continuous ambulatory peritoneal dialysis patients were assigned to the EDS group and the non-EDS group according to the Epworth Sleepiness Scale (ESS). Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the differential metabolites. Twenty-seven (male/female, 15/12; age, 60.1 ± 16.2 years) PD patients with ESS ≥ 10 were assigned to the EDS group, while twenty-one (male/female, 13/8; age, 57.9 ± 10.1 years) PD patients with ESS < 10 were defined as the non-EDS group. With UHPLC-Q-TOF/MS, 39 metabolites with significant differences between the two groups were found, 9 of which had good correlations with disease severity and were further classified into amino acid, lipid and organic acid metabolism. A total of 103 overlapping target proteins of the differential metabolites and EDS were found. Then, the EDS-metabolite-target network and the protein-protein interaction network were constructed. The metabolomics approach integrated with network pharmacology provides new insights into the early diagnosis and mechanisms of EDS in PD patients.

Production of monoclonal antibody against grouper (Epinephelus coioides) CD4-1 and the distribution of CD4-1+ cells.

CD4-a transmembrane glycoprotein molecule expressed on the surface of helper T (Th) cells-plays a central role in adaptive immune protection. In the current study, we developed a monoclonal antibody (mAb) against the grouper CD4-1. Western blotting and immunohistochemistry results revealed that the CD4-1 mAb could recognize the recombinant and natural protein of grouper CD4-1 as well as the CD4-1+ cells in the various tissues from grouper. Tissue distribution analyses revealed that the grouper CD4-1+ cells were expressed in all tissues tested in the healthy grouper, with greater localization in the thymus, head kidney, and spleen tissues. In addition, we tested the changes in the proportion of CD4-1+ cells in the thymus, head kidney, and the gills of grouper post the infection by C. irritans. Our data suggest that the CD4-1 mAb produced against grouper in the current study can be used as a tool to characterize CD4-1+ cells and to investigate the functions of the grouper CD4-1+ cells in the host response against pathogens infection.

Mucosal immunoglobulin response in Epinephelus coioides after Cryptocaryon irritans infection.

The teleost mucosal immune system consists mainly of the skin, gills and gut, which play crucial roles in local immune responses against invading organisms. Immunoglobulins are essential molecules in adaptive immunity that perform crucial biological functions. In our study, a mucosal immunity model was constructed in Epinephelus coioides groupers after Cryptocaryon irritans infection, according to previous experience. Total IgM and IgT in the groupers increased in the serum and mucus in the immune group, whereas only pathogen-specific IgM were detected existence. More critically, pathogen-specific IgM was detected in the head kidney, gill and skin supernatants, thus suggesting that the systematic immune and mucosal immune system secreted immunoglobulins. Furthermore, an early response in the skin was observed, on the basis of the detection of pathogen-specific IgM in the skin supernatant. In conclusion, this research characterized the grouper IgM and IgT in mucosal immune responses to pathogens in the gills and skin, thus providing a theoretical basis for future studies on vaccines against C. irritans.

Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis.

As a convenient, effective and economical kidney replacement therapy for end-stage renal disease (ESRD), peritoneal dialysis is available in approximately 11% of ESRD patients worldwide. However, long-term peritoneal dialysis treatment causes peritoneal fibrosis. In recent years, the application potential of molecular hydrogen in the biomedicine has been well recognized. Molecular hydrogen selectively scavenges cytotoxic reactive oxygen species (ROS) and acts as an antioxidant. In this experiment, a high glucose-induced peritoneal fibrosis mouse model was successfully established by intraperitoneal injection of high glucose peritoneal dialysate, and peritoneal fibrosis mice were treated with hydrogen-rich peritoneal dialysate. In addition, in vitro studies of high glucose-induced peritoneal fibrosis were performed using MeT-5A cells. In vitro and in vivo experiments show that molecular hydrogen could inhibit peritoneal fibrosis progress induced by high glucose effectively. Furthermore, it has been found that molecular hydrogen alleviate fibrosis by eliminating intracellular ROS and inhibiting the activation of the PTEN/AKT/mTOR pathway. The present data proposes that molecular hydrogen exerts the capacity of anti-peritoneal fibrosis through the ROS/PTEN/AKT/mTOR pathway. Therefore, molecule hydrogen is a potential, safe, and effective treatment agent, with peritoneal protective property and great clinical significance.

Transcriptomic analysis reveals innate immune mechanisms of an underlying parasite-resistant grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus).

Hybridization is an artificial breeding strategy for generating potentially desirable offspring. Recently, a novel Hulong grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus) yielded significant growth superiority over its parent. Improved innate immunity is considered as another desirable feature during hybridization. However, whether this Hulong grouper achieved disease resistance has not yet been revealed. In this study, we first examine the infection intensity of C. irritans in the Hulong grouper, and found that the Hulong grouper is less susceptible to C. irritans primary infection. A higher immobilization titer was found in the infected Hulong grouper at Day 2 when compared with the control grouper. Furthermore, severe hyperplasia was observed in the orange-spotted grouper, but not in the Hulong grouper's skin epidermis. To further understand the innate immune mechanism against C. irritans, we conducted a comparative transcriptome analysis of the Hulong grouper during the infection. There are 6464 differentially expressed genes (DEGs) identified in the skin between the control and infected Hulong grouper. This indicates that the innate immune components, such as the complement system, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Interleukin 17 (IL-17) signaling pathway, and Toll-like receptor (TLR) signaling pathway were up-regulated during the infection. These results show that the C. irritans infection can induce a remarkable inflammatory response in the Hulong grouper. Moreover, a total of 75 pairs of orthologs with the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions ＞1, considered rapidly evolving genes (REGs), was identified between the Hulong and orange-spotted grouper. More critically, most REGs were enriched in the immune system, suggesting that rapid evolution of the immune system might occur in the Hulong grouper. These results provide a more comprehensive understanding of the innate immunity mechanism of the hybrid Hulong grouper.

Delayed bowel perforation after instilling over warmed peritoneal dialysate.

BACKGROUND: Peritoneal dialysis (PD) is a safe and home-based treatment for end-stage renal disease (ESRD) patients. The direct thermal damage of abdominal organs is very rare. CASE PRESENTATION: We report a peritoneal dialysis patient presented abdominal pain and feculent effluent 3 weeks after he instilled hot dialysis solution. In spite of emergency exploratory laparotomy and active treatment, the patient died of septic shock. Biopsy revealed necrosis and perforation of the intestines. CONCLUSIONS: Delayed bowel perforation by hot fluid is very rare. Standardized performance is of the first importance for peritoneal dialysis patients.

Identification and characterization of c-raf from orange-spotted grouper (Epinephelus coioides).

C-Raf proto-oncogene serine/threonine kinase is a mitogen-activated protein kinase (MAP) kinase kinase, which can initiate a mitogen-activated protein kinase (MAPK) cascade by phosphorylating the dual-specific MAP kinase kinases (MEK1/2), and in turn activate the extracellular signal-regulated kinases (ERK1/2). To study the function of c-Raf in teleost fish, a c-Raf cDNA sequence from orange-spotted grouper (Epinephelus coioides) was cloned. Ecc-Raf shared 81%-99% amino acid identity with other vertebrate c-Raf molecules, and shared the highest amino acid identity (99%) with Lates calcarifer c-Raf. Genomic structure analysis revealed that grouper c-Raf shared a conserved exon structure with other vertebrates. Tissue distribution showed that Ecc-Raf was mainly transcribed in systemic immune organs. Ecc-Raf was distributed throughout the cytoplasm of transfected GS cells and the overexpression of Ecc-Raf only slightly enhanced the activation of Activator protein 1. The phosphorylation levels of Ecc-Raf can be induced by PMA and H2O2 treatment, in contrast to DMSO or untreated HKLs. Moreover, the phosphorylation level of the Raf-MEK-ERK axis was downregulated after 24 h of SGIV infection. On the other hand, the total level and phosphorylation level of c-Raf significantly increased post C. irritans infection and showed an enhanced level post immunization. The results of this study suggested that the Raf-MEK-ERK cascade was involved in the response to viral or parasitic infections.

SIRT1 gene polymorphisms are associated with nondiabetic type 1 cardiorenal syndrome.

Type 1 cardiorenal syndrome (CRS1) is characterized by acute cardiac disease (e.g., acute heart failure [AHF]), leading to acute kidney injury. Sirtuin 1 (SIRT1), an NAD+ -dependent deacylase, has been found to be associated with CRS1. To confirm whether a correlation exists between SIRT1 variants and the risk of CRS1, the association between the prevalence of CRS1 and single-nucleotide polymorphisms (SNPs) within the SIRT1 gene was investigated in AHF patients. A total of 316 Chinese AHF participants (158 patients with CRS1 and 158 age- and sex-matched controls) were recruited for the present observational study to investigate the association between nine common SIRT1 SNPs (i.e., rs7895833 G > A, rs10509291 T > A, rs3740051 A > G, rs932658 A > C, rs33957861 C > T, rs7069102 C > G, rs2273773 T > C, rs3818292 A > G, and rs1467568 A > G) and the susceptibility to CRS1. Significant differences in genotype distribution between the control and CRS1 groups were found for rs7895833 and rs1467568. After applying a Bonferroni adjustment, the A allele of rs7895833 was still found to be protective (p = 0.001; odds ratio [OR] = 0.77) against CRS1 in this study population. The AA genotype of rs7895833 and the GA genotype of rs1467568 were associated with a significantly reduced risk of CRS1 (OR = 0.23 and 0.49, respectively). rs7895833 and rs1467568 were further analyzed as a haplotype, and the GA haplotype (rs7895833-rs1467568) exhibited a significant association with CRS1 (p = 0.008), while the AA haplotype showed a significant protective effect (p = 0.022). Our study showed that SIRT1 rs7895833 and rs1467568 polymorphisms had a significant effect on the risk of developing CRS1 in a population in China.

Characterization and functional analysis of grouper (Epinephelus coioides) MEK1 and MEK2.

MEK dual-specificity protein kinases are a group of mitogen-activated protein kinase kinases, which act as an integration point by transferring extracellular signals to the nucleus. To investigate the function of MEK in teleost fish, we cloned MEK1 and MEK2 cDNA sequences from the orange-spotted grouper (Epinephelus coioides). EcMEK1 and EcMEK2 shared 80% amino acid identity with each other. EcMEK1 had 89-99% amino acid identity with teleosts or mammals, whereas EcMEK2 shared 85-97% amino acid identity. The exon structures of the grouper MEK1/2 genes were conserved with zebrafish and human MEK1/2. Tissue distribution analysis showed that EcMEK1 and EcMEK2 had a similar expression pattern in grouper tissues and was mainly transcribe in systemic immune organs. Both EcMEK1 and EcMEK2 were distributed throughout the cytoplasm of transfected GS or HEK293T cells. Overexpression of EcMEK1 or EcMEK2 activated Activator protein 1 dependent luciferase. The phosphorylation levels of EcMEK1/2 and EcERK1/2 were significantly increased in head kidney leukocytes by stimulation with PMA treatment. The grouper MEK1/2-ERK1/2 axis was activated in Cryptocaryon irritans infection and showed an enhanced phosphorylation after immunization.

Metabolic profiles revealed synergistically antidepressant effects of lilies and Rhizoma Anemarrhenae in a rat model of depression.

Depression is a major cause of illness and disability. We applied untargeted metabolomics using mass spectrometry to identify metabolic signatures associated with depression in serum and explored the antidepressant effects of lilies and Rhizoma Anemarrhenae on an experimental model of chronic unpredictable mild stress (CUMS). Meanwhile metabolomics based on UHPLC-Q-TOF-MS was used to study the change in metabolites in CUMS rat serum and to evaluate the effects of Rhizoma Anemarrhenae and lilies (alone and in combination). Partial least squares-discriminant analysis identified 30 metabolites as decisive marker compounds that discriminated the CUMS rats and the control rats. The majority of these metabolites were involved in amino acid metabolism, the tricarboxylic acid cycle, and phosphoglyceride metabolism. The reliability of the metabolites was evaluated by the administration of lilies, Rhizoma Anemarrhenae, fluoxetine and the combination of lilies and Rhizoma Anemarrhenae to the CUMS rats. Behavior studies demonstrated that treatment with the combination of lilies and Rhizoma Anemarrhenae resulted in optimal antidepressant effects. The combination treatment was almost as effective as fluoxetine. Our results suggest that lilies and Rhizoma Anemarrhenae demonstrate synergistically antidepressant effects in CUMS via the regulation of multiple metabolic pathways. These findings provide insight into the pathophysiological mechanisms underlying CUMS and suggest innovative and effective treatments for this disorder.

miR-98 protects endothelial cells against hypoxia/reoxygenation induced-apoptosis by targeting caspase-3.

Endothelial dysfunction is one of the main pathophysiological processes involved in renal ischemia reperfusion injury. Our previous microarray study demonstrated that miR-98 was upregulated in the kidney with ischemia reperfusion injury (IRI). The present study was performed to investigate whether miR-98 was involved in the regulation of endothelial apoptosis under hypoxia and re-oxygenation (H/R) conditions. The dynamic changes of miR-98 in mouse IRI kidney and H/R HUVECs was measured. HUVECs were treated with HIF-1α siRNA to investigate the role of HIF-1α on miR-98 expression. The potential target genes of miR-98 were predicted by bioinformatics analyses. HUVECs were transfected with miR-98 mimics or inhibitor to confirm the role of miR-98 on the expression of target genes and hypoxia-induced apoptosis. The target gene was finally confirmed by dual-luciferase reporter assay. Both of IRI and H/R induced significantly up-regulation of miR-98 in the ischemic kidney and hypoxic HUVECs. HIF-1α siRNA remarkably down-regulated the expression of miR-98 in both normal and hypoxic HUVECs. The putative target genes of miR-98 included IL-6, IL-10 and caspase-3. MiR-98 mimics significantly inhibit caspase-3 expression in HUVECs, while anti-miR-98 significantly up-regulated it. But no change of IL-6 and IL-10 levels was observed after miRNA transfection. miR-98 protected HUVECs against apoptosis induced by hypoxia, while anti-miR-98 had the reverse effect. Furthermore, the dual-luciferase reporter assay confirmed that miR-98 decreased the luciferase activity by targeting the 3' untranslated region of caspase-3. In conclusion, Renal IRI induces up-regulation of miR-98 dependent on HIF-1α, which protects endothelial cells against apoptosis by targeting caspase-3.

Predictors of poor sleep quality and excessive daytime sleepiness in peritoneal dialysis patients.

To explore the possible impact factors on daytime sleepiness among peritoneal patients from a single center in China. A cross-sectional study was conducted in 98 prevalent peritoneal dialysis (PD) patients using both the Pittsburgh Sleep Quality Index (PSQI) questionnaire of sleep quality and the Epworth Sleepiness Scale (ESS) questionnaire of excessive daytime sleepiness (EDS). Biochemical differences between daytime sleepiness and non-daytime sleepiness population were evaluated, following univariate and multivariable analysis to find the risk factors on sleep disturbance. The prevalence of "poor sleep quality" (PSQI > 5) was 74.49%, while daytime sleepiness (ESS ≥ 9) occurred in 22.45%. Mean PSQI was 9.06 ± 4.60 and EES was 6.31 ± 4.98. Compared to non-EDS cases, patients with ESS ≥ 9 had worse residual renal function (RRF), higher serum creatinine, higher serum magnesium and elevated serum ferritin. In univariate analysis, ESS correlated with serum albumin (r = 0.346, p = 0.015), phosphate (r = 0.313, p = 0.029), magnesium (r = 0.376, p = 0.008) and urinary Kt/V (r = -0.341, p = 0.029). Finally, multivariable linear regression indicated that urinary Kt/V, PSQI and magnesium were independent predictors of ESS score. EDS does exist in PD patients and is associated both with poor nighttime sleep quality and lower RRF. Hypermagnesemia may be a treatable risk factor to improve daytime tiredness.

Screening plasma miRNAs as biomarkers for renal ischemia-reperfusion injury in rats.

BACKGROUND: Acute kidney injury is a common clinical comorbidity and early diagnosis is crucial for improving prognosis, but there is still no ideal biomarker for early diagnosis. MATERIAL AND METHODS: miRNA microarray was used for detecting miRNA in kidney subjected to renal ischemia-reperfusion injury 12 h after reperfusion. Real-time PCR was performed to validate the results of microarray. miRNAs in the ischemia group were twice as high as in the sham group. Kidney-enriched miR-10a, miR-192, and miR-194 were detected in rat plasma to screen potential biomarkers for renal ischemia-reperfusion injury. Aberrant expressed miRNA in plasma at 12 h were further detected at 1 h, 2 h, 6 h, 12 h, and 24 h to observe the changing trend of these miRNAs and were compared to blood urea nitrogen and serum creatinine. RESULTS: Thirty-six miRNAs were aberrantly expressed in kidney of rats with renal ischemia-reperfusion injury, among which 15 miRNAs had a 2-fold greater change. Results of real-time PCR were generally in accordance with microarray results. Levels of the 15 miRNAs differentially expressed in injured kidney were not significantly different from those in sham kidney. However, miR-10a, miR-192, and miR-194 were significantly increased in plasma of rats with renal ischemia-reperfusion injury, among which miR-10a was elevated within 1 h after reperfusion, whereas miR-192 and miR-194 were elevated at 6 h after injury. Blood urea nitrogen was increased at 12 h and serum creatinine was increased at 6 h after injury. CONCLUSIONS: Plasma miR-10a, miR-192, and miR-194 were potential biomarkers for renal ischemia reperfusion injury in rats, and miR-10a might be the most promising plasma biomarker for renal injury because of its elevation within 1 h after renal injury, as well as renal specificity.

Advances in stem cell therapy for peritoneal fibrosis: from mechanisms to therapeutics.

Peritoneal fibrosis (PF) is a pathophysiological condition caused by a variety of pathogenic factors. The most important features of PF are mesothelial-mesenchymal transition and accumulation of activated (myo-)fibroblasts, which hinder effective treatment; thus, it is critical to identify other practical approaches. Recently, stem cell (SC) therapy has been indicated to be a potential strategy for this disease. Increasing evidence suggests that many kinds of SCs alleviate PF mainly by differentiating into mesothelial cells; secreting cytokines and extracellular vesicles; or modulating immune cells, particularly macrophages. However, there are relatively few articles summarizing research in this direction. In this review, we summarize the risk factors for PF and discuss the therapeutic roles of SCs from different sources. In addition, we outline effective approaches and potential mechanisms of SC therapy for PF. We hope that our review of articles in this area will provide further inspiration for research on the use of SCs in PF treatment.

Derivation and elimination of uremic toxins from kidney-gut axis.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relative toxin removal methods, and elucidate promising approaches to effectively remove toxins.

Identification of monocyte-associated pathways participated in the pathogenesis of pulmonary arterial hypertension based on omics-data.

Pulmonary arterial hypertension (PAH) is one kind of chronic and uncurable diseases that can cause heart failure. Immune microenvironment plays a significant role in PAH. The aim of this study was to assess the role of immune cell infiltration in the pathogenesis of PAH. Differentially expressed genes based on microarray data were enriched in several immune-related pathways. To evaluate the immune cell infiltration, based on the microarray data sets in the GEO database, we used both ssGSEA and the CIBERSORT algorithm. Additionally, single-cell RNA sequencing (scRNA-seq) data was used to further explicit the specific role and intercellular communications. Then receiver operating characteristic curves and least absolute shrinkage and selection operator were used to discover and test the potential diagnostic biomarkers for PAH. Both the immune cell infiltration analyses based on the microarray data sets and the cell proportion in scRNA-seq data exhibited a significant downregulation in the infiltration of monocytes in PAH. Then, the intercellular communications showed that the interaction weighs of most immune cells, including monocytes changed between the control and PAH groups, and the ITGAL-ITGB2 and ICAM signaling pathways played critical roles in this process. In addition, ITGAM and ICAM2 displayed good diagnosis values in PAH. This study implicated that the change of monocyte was one of the key immunologic features of PAH. Monocyte-associated ICAM-1 and ITGAL-ITGB2 signaling pathways might be involved in the pathogenesis of PAH.

Risk factors of osteoporosis in elderly inpatients: A cross-sectional single-centre study.

Objective: This study aimed to identify factors significantly associated with the occurrence of osteoporosis in elderly and very elderly patients. Methods: Elderly hospitalized patients who were older than 60 years old, from the Rehabilitation Hospital from December 2019 to December 2020 were selected. Barthel index (BI), nutritional assessment, the causes of bone mineral density (BMD) reductions in elderly and elderly patients were analysed. Results: A total of 94 patients (83.56 ± 8.37 years old) were enrolled. With increasing age, the BMD of the lumbar spine, femoral neck, and femoral shaft of elderly patients significantly decreased, and the incidence of osteoporosis (OP) significantly increased. The BMD of the lumbar spine was negatively correlated with female and positively correlated with serum 25-hydroxyvitamin D levels, the difference between actual body weight and ideal body weight, and blood uric acid levels; The BMD of the femoral neck was negatively correlated with age and female, and positively correlated with height and geriatric nutrition risk index score. The BMD of the femoral shaft was negatively correlated with female and positively correlated with BI. Conclusion: With increasing age, the BMD of the lumbar spine and the femoral shaft significantly decreased, and the incidence of OP significantly increased in elderly and very elderly patients. Aric acid may protect bone health in elderly patients. Early attention to the nutritional status, exercise capacity, 25-hydroxyvitamin D level, and blood uric acid level in the elderly population can help identify high-risk elderly patients with OP.

The Spatial Distribution of Renal Fibrosis Investigated by Micro-probe Terahertz Spectroscopy System.

Renal fibrosis, which is characterized as progressive extracellular matrix accumulation, is a common feature of different stages of chronic kidney disease, and the degree of fibrosis is strongly associated with renal function. In clinical practice, precise understanding of the space distribution of fibrosis is extremely important for the diagnosis and prognosis of renal disease. Rapid advances in terahertz (THz) technology have been made, and this technology has a broad application in bio-detection, as it can interact and measure the collective vibrations and rotations of molecular groups. It is well known that hydroxyproline (HYP) is the key component of collagen, which is synthesized by fibroblasts to maintain the extracellular matrix, and HYP content detection in tissue homogenate can be achieved by classical biochemistry method. In this study, a THz microprobe system was employed to conduct THz microspatial scanning with a resolution of 20 µm. Both the content and distribution of HYP were directly characterized by the THz absorption spectrum. The absorption intensity in the THz spectrum was used to determine HYP density in renal tissues; therefore, the fibrosis change in the kidneys can be determined using THz scanning at micrometer resolution, which provides more possibilities for precise diagnosis of renal fibrosis.