Effect of different levels of stroke volume variation on the endothelial glycocalyx of patients undergoing colorectal surgery: A randomized clinical trial.

NEW FINDINGS: What is the central question of this study? Massive infusion can destroy the endothelial glycocalyx. We compared the serum concentrations of endothelial glycocalyx components and atrial natriuretic peptide and the outcomes of patients with different levels of stroke volume variation (SVV). What is the main finding and its importance? With a decrease in SVV, the serum concentrations of endothelial glycocalyx components and atrial natriuretic peptide increased, whereas the oxygenation index decreased. When the intraoperative SVV was maintained at 7-10%, the patients had better postoperative recovery and shorter postoperative hospital stays. Therefore, it is advisable to maintain the SVV between 7 and 10%. ABSTRACT: Dynamic haemodynamic parameters, such as stroke volume variation (SVV), can be used for blood volume monitoring. However, studies have determined the SVV threshold but not the optimal level. The endothelial glycocalyx (EG) plays an important role in maintaining vascular permeability. Moreover, rapid and massive infusion can lead to the degradation, shedding and destruction of the EG. We aimed to explore the effects of different SVV values (11-14, 7-10 or 3-6%) on the EG in 54 patients who were scheduled for elective colorectal tumour surgery and to identify the optimal peri-operative fluid therapy strategy. The concentrations of EG degradation products (heparin sulphate, hyaluronic acid and syndecan-1) and atrial natriuretic peptide were higher when the SVV was maintained between 3 and 6% after fluid therapy compared with pre-infusion (P < 0.05). Comparison of postoperative complications and hospitalization time among the three SVV levels was not statistically significant (P > 0.05). The postoperative hospitalization time in patients with SVV of 7-10% was shorter than that in patients with SVV of 3-6%. Infusion of a large volume of fluid, with increasing EG degeneration and atrial natriuretic peptide concentrations, might be related to postoperative outcomes.

The Application of Transbronchial Lung Cryobiopsy and Uniportal and Tubeless Video-Assisted Thoracic Surgery in the Multidisciplinary Diagnosis of Interstitial Lung disease-A Real-World Prospective Study.

The application of transbronchial lung cryobiopsy (TBLC) and uniportal and tubeless video-assisted thoracic surgery (UT-VATS) in the multidisciplinary diagnosis of interstitial lung disease (ILD) has not been demonstrated in real-world clinical practice. This prospective study included 137 patients with no definitive diagnosis who were the subject of two multidisciplinary discussion (MDD) sessions. As indicated in the first MDD, 67 patients underwent UT-VATS and 70 underwent TBLC. The specificity of biopsy information and its contribution to final MDD diagnosis were evaluated in the second MDD. The post-operative complications and hospitalization costs associated with the two biopsy methods were compared. UT-VATS was favored for patients initially diagnosed with idiopathic pulmonary fibrosis (IPF), bronchiolitis-associated interstitial lung disease (RB-ILD)/desquamative interstitial pneumonia (DIP) and undefined idiopathic interstitial pneumonia (UIIP), while TBLC was preferred for pulmonary lymphangioleiomyomatosis (PLAM) and pulmonary alveolar proteinosis (PAP). The spirometry parameters were better in patients who underwent UT-VATS than those who underwent TBLC. UT-VATS provided more specific pathological results than TBLC (85.7 vs 73.7%, p = 0.06). In patients initially diagnosed with UIIP, pathological information from UT-VATS was more clinically useful than that obtained from TBLC, although both tests contributed similarly to cases initially diagnosed as interstitial pneumonia with auto-immune features (IPAF)/connective tissue disease-related ILD (CTD-ILD). The safety of UT-VATS was comparable with TBLC although TBLC was cheaper during hospitalization (US$4,855.7 vs US$3,590.9, p < 0.001). multidisciplinary discussion decisions about biopsies were driven by current knowledge of sampling and diagnosis capacity as well as potential risks of different biopsy methods. The current MDD considered UT-VATS more informative than TBLC in cases initially diagnosed as UIIP although they were equally valuable in patients initially diagnosed with IPAF/CTD-ILD.

Inhibition of miR-199a-5p rejuvenates aged mesenchymal stem cells derived from patients with idiopathic pulmonary fibrosis and improves their therapeutic efficacy in experimental pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related disease with no cure. Mesenchymal stem cell (MSC)-based therapy has emerged as a novel strategy for IPF treatment. Nevertheless, MSCs derived from patients with IPF (IPF-MSCs) become senescent, thereby reducing their beneficial effects in IPF. MicroRNAs (miRNAs) mediate the senescence of MSCs, but the underlying mechanisms are not fully understood. We investigated the mechanisms by which miR-199a-5p regulates IPF-MSC senescence and whether its inhibition could rejuvenate IPF-MSCs and enhance their therapeutic efficacy. METHODS: Control-MSCs and IPF-MSCs were isolated from the adipose tissue of age-matched healthy and IPF donors, respectively. Cell senescence was examined by senescence-associated ß-galactosidase (SA-ß-gal) staining. The level of miR-199a-5p was measured by RT-PCR. Autophagy was determined using a transmission electron microscope (TEM). The therapeutic efficacy of anti-miR-199a-5p-IPF-MSCs was assessed using a mouse model of bleomycin-induced lung fibrosis. RESULTS: Despite similar surface makers, IPF-MSCs exhibited increased cellular senescence and decreased proliferative capacity compared with control-MSCs. The expression of miR-199a-5p was significantly enhanced in the serum of IPF patients and IPF-MSCs compared with that of healthy donors and control-MSCs. The upregulation of miR-199a-5p induced senescence of control-MSCs, whereas the downregulation rescued IPF-MSC senescence. Mechanistically, miR-155-5p suppressed autophagy of MSCs via the AMPK signaling pathway by downregulating the expression of Sirtuin 1(Sirt1), resulting in cellular senescence. Accordingly, miR-155-5p inhibition promoted autophagy and ameliorated IPF-MSC senescence by activating the Sirt1/AMPK signaling pathway. Compared with IPF-MSCs, the transplantation of anti-miR-199a-5p-IPF-MSCs increased the ability to prevent progression of pulmonary fibrosis in bleomycin-treated mice. CONCLUSIONS: Our study shows that miR-199a-5p regulates MSC senescence in patients with IPF by regulating the Sirt1/AMPK signaling pathway and miR-199a-5p is a novel target to rejuvenate IPF-MSCs and enhance their beneficial effects.

Complex Involvement of the Extracellular Matrix, Immune Effect, and Lipid Metabolism in the Development of Idiopathic Pulmonary Fibrosis.

Background and objective: Idiopathic pulmonary fibrosis (IPF) is an aggressive fibrotic pulmonary disease with spatially and temporally heterogeneous alveolar lesions. There are no early diagnostic biomarkers, limiting our understanding of IPF pathogenesis. Methods: Lung tissue from surgical lung biopsy of patients with early-stage IPF (n = 7), transplant-stage IPF (n = 2), and healthy controls (n = 6) were subjected to mRNA sequencing and verified by real-time quantitative PCR (RT-qPCR), immunohistochemistry, Western blot, and single-cell RNA sequencing (scRNA-Seq). Results: Three hundred eighty differentially expressed transcripts (DETs) were identified in IPF that were principally involved in extracellular matrix (ECM) remodeling, lipid metabolism, and immune effect. Of these DETs, 21 (DMD, MMP7, POSTN, ECM2, MMP13, FASN, FADS1, SDR16C5, ACAT2, ACSL1, CYP1A1, UGT1A6, CXCL13, CXCL5, CXCL14, IL5RA, TNFRSF19, CSF3R, S100A9, S100A8, and S100A12) were selected and verified by RT-qPCR. Differences in DMD, FASN, and MMP7 were also confirmed at a protein level. Analysis of scRNA-Seq was used to trace their cellular origin to determine which lung cells regulated them. The principal cell sources of DMD were ciliated cells, alveolar type I/II epithelial cells (AT cells), club cells, and alveolar macrophages (AMs); MMP7 derives from AT cells, club cells, and AMs, while FASN originates from AT cells, ciliated cells, and AMs. Conclusion: Our data revealed a comprehensive transcriptional mRNA profile of IPF and demonstrated that ECM remodeling, lipid metabolism, and immune effect were collaboratively involved in the early development of IPF.

Ultra-low dose rituximab as add-on therapy in anti-MDA5-positive patients with polymyositis /dermatomyositis associated ILD.

OBJECTIVES: To evaluate the efficacy and safety of ultra-low dose (100 mg) rituximab (RTX) administration in anti-melanoma differentiation-associated gene 5 (MDA5) positive patients with polymyositis/dermatomyositis (PM/DM) associated interstitial lung disease. METHODS: This retrospective study included anti-MDA5 antibody positive ILD subjects in the First Affiliated Hospital of Guangzhou Medical University from November 2017 to March 2019. Independent predictors for 180-day mortality were measured by Cox regression analysis. Patients were divided into 3 groups: Group 1 (non-cyclophosphamide (CTX)/RTX) (n = 10), Group 2 (CTX only) (n = 19) and Group 3 (RTX with/without CTX) (n = 11). The 180-day mortality was compared among 3 groups with Kaplan-Meier analysis. Post-RTX serological parameters as well as adverse events were evaluated. RESULTS: Forty patients were included with the mean age of 51.3 years. Elevated IL-10 level and CD4+/8+ ratio were considered as risk factors of 180-day mortality. Kaplan-Meier analysis showed a trend toward decrease, albeit non-significant, in 180-day mortality in Group 3 (P = 0.26). The administration of 100 mg RTX brought down B cell within 7 days that lasted for 180 days. There were 7 and 6 infection events observed within 2 months of CTX/RTX treatment in Group 2 and 3, with 5 and 2 fatal cases respectively. Cytomegalovirus infection accounted for half infection events in Group 3. CONCLUSION: We found a pronounced and prolonged B cell depletion following 100 mg RTX infusion and RTX add-on may be effective in anti-MDA5 positive ILD patients. However, infection, especially opportunistic infection, should be concerned during the treatment.

The interstitial lung disease spectrum under a uniform diagnostic algorithm: a retrospective study of 1,945 individuals.

BACKGROUND: Reported data on the disease spectrum of interstitial lung diseases (ILDs) of China are sparse and varied. We aimed to investigate the spectrum of ILDs and the distribution of diagnostic methods under a uniform diagnosis. METHODS: This retrospective study enrolled ILDs cases from Guangzhou Institute of Respiratory Health (GIRH). All cases were classified into specific subgroups of ILDs according to updated guidelines. RESULTS: A total of 1,945 subjects were enrolled from January 2012 to December 2017. The mean age was 57.9 years, and 1,080 (55.5%) patients were male. The most common subtype of ILDs was idiopathic pulmonary fibrosis (IPF, 20.3%), followed by interstitial pneumonia with autoimmune features (IPAF, 17.9%), connective tissue disease associated ILD (CTD-ILD, 18.3%) and unclassifiable idiopathic interstitial pneumonia (UIIP, 14.7%). A total of 818 (42.1%) patients underwent lung biopsy in order to obtain a histological diagnose. TBLB was performed in 565 (29.0%) patients, eleven of whom underwent SLB because TBLB failed to obtain lung samples. SLB was performed in 213 (11.0%) patients and TBCB was performed in 51 (2.6%) patients. Among them, histological results were considered clinically helpful in 722 (88.3%) cases, and provided definitive histopathological diagnoses in 368 cases. Surgical lung biopsy (SLB) was performed in 213 (10.9%) subjects, while 115 (54.0%) cases were performed among the idiopathic interstitial pneumonia (IIP). Among SLB cases in IIP, the highest rate of SLB was desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease (DIP/RB-ILD, 10/10), lymphoid interstitial pneumonia (LIP, 9/9), followed by cryptogenic organizing (COP, 18/26), nonspecific interstitial pneumonia (NSIP, 22/53), IPF (43/395), UIIP (13/285). CONCLUSIONS: IPF was the most common ILDs in our ILD center, followed by IPAF, CTD-ILD and UIIP. Histological information may help to establish diagnostic algorithm in ILD.

Adipose-Derived Mesenchymal Stem Cells Isolated from Patients with Abdominal Aortic Aneurysm Exhibit Senescence Phenomena.

Mesenchymal stem cells (MSCs) have shown beneficial effects in the treatment of abdominal aortic aneurysm (AAA). Nonetheless, the biological properties of adipose-derived MSCs (ASCs) from patients with AAA (AAA-ASCs) remain unclear. This study is aimed at investigating the properties of cell phenotype and function of AAA-ASCs compared with ASCs from age-matched healthy donors (H-ASCs). H-ASCs and AAA-ASCs were studied for cell phenotype, differentiation capacity, senescence, and mitochondrial and autophagic functions. Cellular senescence was examined by senescence-associated ß-galactosidase (SA-ß-gal) staining. Mitochondrial morphology was determined by MitoTracker staining. Despite the similar surface markers of AAA-ASCs and H-ASCs, AAA-ASCs exhibited altered multidifferentiation potential. Compared with H-ASCs, AAA-ASCs displayed enhanced senescence manifested by increased SA-ß-gal activity and decreased proliferation and migration ability. Furthermore, AAA-ASCs showed increased mitochondrial fusion, reactive oxygen species (ROS) production, and decreased mitochondrial membrane potential. In addition, AAA-ASCs exhibited decreased autophagy level, upregulation of IL-6 and TNF-α secretion, and downregulation of IL-10 secretion compared with H-ASCs. Nonetheless, treatment of AAA-ASCs with rapamycin (an autophagy activator) dramatically reduced secretion of IL-6 and TNF-α and enhanced secretion of IL-10. In conclusion, our study showed that AAA-ASCs exhibit senescence phenomena and decreased cell function. Understanding the specific alterations in AAA-ASCs will help explore novel strategies to restore cell function for AAA treatment.

The influence of Sr and H3PO4 concentration on the hydration of SrCaHA bone cement.

Sr-contained calcium hydroxyapatite (SrCaHA) cement is a potential biomaterial for in vivo bone repair and surgery fixation due to its excellent biodegradability, bioactivity, biocompatibility, easily shaping and self-hardening. We had ever reported the in vitro physiochemical properties, biocompatibility and in vivo degradability of the SrCaHA cement obtained by mixing a cement powder of Ca(4)(PO(4))(2)O/CaHPO(4)/SrHPO(4) and a cement liquid of diluted H(3)PO(4) aqueous solution. In the present study, we intensively studied the influences of both Sr content and H(3)PO(4) concentration in diluted phosphoric acid aqueous solution on the setting time, hydration heat-liberation behaviours, and real-time microstructure and phase evolutions of the SrCaHA cement. The results show that both PO(4)(3-) and H(+) ions in PA solution attended the hydration reaction as reactants, and thus the increase of the PA concentration not only promoted the dissolution of Ca(4)(PO(4))(2)O but also pushed the hydration progress of SrCaHA bone cement. Sr content exhibits a remarkable retardation role on the apatite transformation of the SrCaHA cement pastes which probably attributed to its higher degree of supersaturation for yielding apatite crystals and lower transformation rate when exposed to the Sr(2+)-containing hydration system. This present results contribute to a better understanding on the hydration mechanism of the new SrCaHA cement and help to the more precisely controlling of its hydration process.