Optical coherence tomography (OCT) - versus angiography-guided strategy for percutaneous coronary intervention: a meta-analysis of randomized trials.

BACKGROUND: Optical coherence tomography (OCT) guidance in percutaneous coronary intervention (PCI) has been shown to improve procedural outcomes. However, evidence supporting its superiority over angiography-guided PCI in terms of clinical outcomes is still emerging and limited. This study aimed to compare the efficacy and safety of OCT-guided PCI versus angiography-guided PCI in patients with coronary artery disease (CAD). METHODS: A systematic search of electronic databases was conducted to identify randomized control trials (RCTs) comparing the clinical outcomes of OCT-guided and angiography-guided PCI in patients with CAD. Clinical endpoints including all-cause mortality, myocardial infarction (MI), target lesion revascularization (TLR), stent thrombosis and major adverse cardiac events (MACE) were assessed. RESULTS: Eleven RCTs, comprising 2,699 patients in the OCT-guided group and 2,968 patients in the angiography-guided group met inclusion criteria. OCT-guided PCI was associated with significantly lower rates of cardiovascular death(RR 0.56; 95%CI: 0.32-0.98; p = 0.04; I2 = 0%), stent thrombosis(RR 0.56; 95%CI: 0.33-0.95; p = 0.03; I2 = 0%), and MACE (RR 0.79; 95%CI: 0.66-0.95; p = 0.01; I2 = 5%). The incidence of all-cause death (RR 0.71; 95%CI: 0.49-1.02; p = 0.06; I2 = 0%), myocardial infarction (RR 0.86; 95%CI: 0.67-1.10; p = 0.22; I2 = 0%) and TLR (RR 0.98; 95%CI: 0.73-1.33; p = 0.91; I2 = 0%) was non-significantly lower in the OCT-guided group. CONCLUSIONS: Among patients undergoing PCI, OCT-guided PCI was associated with lower incidences of cardiovascular death, stent thrombosis and MACE compared to angiography-guided PCI. TRIAL REGISTRATION: PROSPERO registration number: CRD42023484342.

The role of VdSti1 in Verticillium dahliae: insights into pathogenicity and stress responses.

Sti1/Hop, a stress-induced co-chaperone protein, serves as a crucial link between Hsp70 and Hsp90 during cellular stress responses. Despite its importance in stress defense mechanisms, the biological role of Sti1 in Verticillium dahliae, a destructive fungal pathogen, remains largely unexplored. This study focused on identifying and characterizing Sti1 homologues in V. dahliae by comparing them to those found in Saccharomyces cerevisiae. The results indicated that the VdSti1-deficient mutant displayed increased sensitivity to drugs targeting the ergosterol synthesis pathway, leading to a notable inhibition of ergosterol biosynthesis. Moreover, the mutant exhibited reduced production of microsclerotia and melanin, accompanied by decreased expression of microsclerotia and melanin-related genes VDH1, Vayg1, and VaflM. Additionally, the mutant's conidia showed more severe damage under heat shock conditions and displayed growth defects under various stressors such as temperature, SDS, and CR stress, as well as increased sensitivity to H2O2, while osmotic stress did not impact its growth. Importantly, the VdSti1-deficient mutant demonstrated significantly diminished pathogenicity compared to the wild-type strain. This study sheds light on the functional conservation and divergence of Sti1 homologues in fungal biology and underscores the critical role of VdSti1 in microsclerotia development, stress response, and pathogenicity of V. dahliae.

Preoperative Prediction of Perineural Invasion in Oesophageal Squamous Cell Carcinoma Based on CT Radiomics Nomogram: A Multicenter Study.

RATIONALE AND OBJECTIVES: To investigate the value of computed tomography (CT) radiomics nomogram in the preoperative prediction of perineural invasion (PNI) in oesophageal squamous cell carcinoma (ESCC) through a multicenter study. MATERIALS AND METHODS: We retrospectively collected postoperative pathological data of 360 ESCC patients with definite PNI status (131 PNI-positive and 229 PNI-negative) from two centres. Radiomic features were extracted from the arterial-phase CT images, and the least absolute shrinkage and selection operator and logistic regression algorithm were used to screen valuable features for identifying the PNI status and calculating the radiomics score (Rad-score). A radiomics nomogram was established by integrating the Rad-score and clinical risk factors. A receiver operating characteristic curve was used to evaluate model performance, and decision curve analysis was used to evaluate the predictive performance of the radiomics nomogram in the training, internal validation, and external validation sets. RESULTS: Twenty radiomics features were extracted from a full-volume tumour region of interest to construct the model, and the radiomics nomogram combined with radiomics features and clinical risk factors was superior to the clinical and radiomics models in predicting the PNI status of ESCC patients. The area under the curve values of the radiomics nomogram in the training, internal validation, and external validation sets were 0.856 (0.794-0.918), 0.832 (0.742-0.922), and 0.803 (0.709-0.898), respectively. CONCLUSION: The radiomics nomogram based on CT has excellent predictive ability; it can non-invasively predict the preoperative PNI status of ESCC patients and provide a basis for preoperative decision-making.

Detecting Muscle Invasion of Bladder Cancer: An Application of Diffusion Kurtosis Imaging Ratio and Vesical Imaging-Reporting and Data System.

BACKGROUND: Independent factors are needed to supplement vesical imaging-reporting and data system (VI-RADS) to improve its ability to identify muscle invasive bladder cancer (MIBC). PURPOSE: To assess the correlation between MIBC and diffusion kurtosis imaging (DKI) ratio, VI-RADS, and other factors (such as tumor location). STUDY TYPE: Retrospective. POPULATION: Sixty-eight patients (50 males and 18 females; age: 70.1 ± 9.5 years) with bladder urothelial carcinoma. FIELD STRENGTH/SEQUENCE: 1.5 T, conventional diffusion-weighted imaging (DWI), and DKI (single shot echo-planar sequence). ASSESSMENT: Three radiologists independently measured the diffusion parameters of each bladder cancer (BCa) and obturator internus, including the mean apparent diffusion coefficient (ADCmean), mean kurtosis (MK), and mean diffusion (MD). And the ratio of diffusion parameters between BCa and obturator internus was calculated (diffusion parameter ratio = bladder cancer:obturator internus). Based on the VI-RADS, the target lesions were independently scored. Furthermore, the actual tumor-wall contact length (ACTCL) and absolute tumor-wall contact length (ABTCL) were measured. STATISTICAL TESTS: Multicollinearity among independent variables was evaluated using the variance inflation factor (VIF). Multivariable logistic regression analysis was used to determine the independent risk factors of MIBC. The receiver operating characteristic curve was used to evaluate the efficacy of each variable in detecting MIBC. The DeLong test was used to compare the area under the curve (AUC). A P < 0.05 was considered statistically significant. RESULTS: MKratio (median: 0.62) and VI-RADS were independent risk factors for MIBC. AUCs for MKratio, VI-RADS, and MKratio combined with VI-RADS in assessing MIBC were 0.895, 0.871, and 0.973, respectively. MKratio combined with VI-RADS was more effective in diagnosing MIBC than VI-RADS alone. DATA CONCLUSIONS: MKratio has potential to assist the assessment of MIBC. MKratio can be used as a supplement to VI-RADS for detecting MIBC. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.

Low Skeletal Muscle Mass and the Incidence of Delirium in Hospitalized Older Patients: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Both low skeletal muscle mass and delirium are prevalent in older hospitalized patients, while their associations are unclear. This systematic review and meta-analysis aim to investigate the associations between low skeletal muscle mass and the incidence of delirium in hospitalized patients. Methods: The PubMed, Web of Science, and Embase were searched for relevant studies published before May 2022, and we conducted this systematic review and meta-analysis according to the PRISMA and MOOSE guidelines. The summary odds ratios (OR) and 95% confidence intervals (CI) were estimated, and subgroup analyses were also conducted according to the age and major surgeries. Results: Finally, nine studies with 3 828 patients were included. The pooled result showed no significant association between low skeletal muscle mass and the incidence of delirium (OR 1.69, 95% CI 0.85 to 2.52). However, sensitivity analysis suggested that one study caused a significant alteration of the summary result, and the meta-analysis of the remaining 8 studies showed that low skeletal muscle mass was significantly associated with an 88% increased incidence of delirium (OR 1.88, 95% CI 1.43 to 2.33). Furthermore, subgroup analyses indicated that low skeletal muscle mass was associated with a higher incidence of delirium in patients ≥75 years old or undergoing major surgeries instead of those <75 years old or without surgeries, respectively. Conclusions: Hospitalized patients with low skeletal muscle mass might have higher incidence of delirium, particularly in those of older age and undergoing major surgeries. Therefore, great attention should be paid to these patients.

Fate mapping RNA-sequencing reveal Malat1 regulates Sca1+ progenitor cells to vascular smooth muscle cells transition in vascular remodeling.

Regeneration of smooth muscle cells (SMCs) is vital in vascular remodeling. Sca1+ stem/progenitor cells (SPCs) can generate de novo smooth muscle cells after severe vascular injury during vessel repair and regeneration. However, the underlying mechanisms have not been conclusively determined. Here, we reported that lncRNA Metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was down-regulated in various vascular diseases including arteriovenous fistula, artery injury and atherosclerosis. Using genetic lineage tracing mice and veingraft mice surgery model, we found that suppression of lncRNA Malat1 promoted Sca1+ cells to differentiate into SMCs in vivo, resulting in excess SMC accumulation in neointima and vessel stenosis. Genetic ablation of Sca1+ cells attenuated venous arterialization and impaired vascular structure normalization, and thus, resulting in less Malat1 down-regulation. Single cell sequencing further revealed a fibroblast-like phenotype of Sca1+ SPCs-derived SMCs. Protein array sequencing and in vitro assays revealed that SMC regeneration from Sca1+ SPCs was regulated by Malat1 through miR125a-5p/Stat3 signaling pathway. These findings delineate the critical role of Sca1+ SPCs in vascular remodeling and reveal that lncRNA Malat1 is a key regulator and might serve as a novel biomarker or potential therapeutic target for vascular diseases.

MicroRNA-146a Promotes Embryonic Stem Cell Differentiation towards Vascular Smooth Muscle Cells through Regulation of Kruppel-like Factor 4.

OBJECTIVE: Vascular smooth muscle cell (VSMC) differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension, atherosclerosis, and restenosis. MicroRNA-146a (miR-146a) has been proven to be involved in cell proliferation, migration, and tumor metabolism. However, little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells (ESCs). This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs. METHODS: Mouse ESCs were differentiated into VSMCs, and the cell extracts were analyzed by Western blotting and RT-qPCR. In addition, luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed. Finally, C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs, and immunohistochemistry, Western blotting, and RT-qPCR assays were carried out on tissue samples from these mice. RESULTS: miR-146a was significantly upregulated during VSMC differentiation, accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin (SMαA), smooth muscle 22 (SM22), smooth muscle myosin heavy chain (SMMHC), and h1-calponin. Furthermore, overexpression of miR-146a enhanced the differentiation process in vitro and in vivo. Concurrently, the expression of Kruppel-like factor 4 (KLF4), predicted as one of the top targets of miR-146a, was sharply decreased in miR-146a-overexpressing ESCs. Importantly, inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs. In addition, miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors, including serum response factor (SRF) and myocyte enhancer factor 2c (MEF-2c). CONCLUSION: Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.

Achieving Good Bonding Strength of the Cu Layer on PET Films by Pretreatment of a Mixed Plasma of Carbon and Copper.

Cu layers were fabricated on PET films with and without pretreatment by a mixed plasma composed of carbon and copper using a magnetron sputtering technique for potential application as the flexible copper-clad laminate (FCCL) in 5G technology. In order to evaluate the effect of carbon plasma on the composited layer, the graphite target current was adjusted from 0.5 to 2.0 A. The microstructures and properties of Cu layers on PET films with different treatments were measured by an X-ray powder diffractometer, X-ray photoelectron spectroscope, Raman spectroscope, scanning electron microscope, transmission electron microscope, scratching test, indentation test, and four-probe detector. The results showed that the organic polymer carbon structure on the surface of PET films was changed to inorganic amorphous carbon due to the effect of the carbon plasma. At the same time, the active free radicals formed in the transition process react with metal copper ions to form organometallic compounds. Under the treatment of a mixed plasma of carbon and copper, the C/Cu mixed layer was formed on the PET film at the top of the substrate. Due to the presence of C/Cu mixed interlayers, the bonding strengths between the final Cu layers and the PET film substrates were improved, and the strongest bonding strength appeared when the graphite target current was 1.0 A. In addition, the presence of the C/Cu mixed interlayer enhanced the toughness of the Cu layer on PET film. It was proposed that the good bonding strength in combination and the enhanced toughness for the Cu layer on a PET film was due to the formation of a C/Cu mixed interlayer induced by the pretreatment of a mixed plasma of carbon and copper.

Muscle-derived extracellular vesicles improve disuse-induced osteoporosis by rebalancing bone formation and bone resorption.

Osteoporosis is a highly prevalent skeletal bone disorder worldwide with characteristics of reduced bone mass and increased risk of osteoporotic fractures. It has been predicted to become a global challenge with the aging of the world population. However, the current therapy based on antiresorptive drugs and anabolic drugs has unwanted side effects. Although cell-based treatments have shown therapeutic effects for osteoporosis, there are still some limitations inhibiting the process of clinical application. In the present study, we developed EVs derived from skeletal muscle tissues (Mu-EVs) as a cell-free therapy to treat disuse-induced osteoporosis. Our results showed that Mu-EVs could be prepared easily and abundantly from skeletal muscle tissues, and that these Mu-EVs had typical features of extracellular vesicles. In vitro studies demonstrated that Mu-EVs from normal skeletal muscles could be phagocytized by bone marrow stromal/stem cells (BMSCs) and osteoclasts (OCs), and promoted osteogenic differentiation of BMSCs while inhibited OCs formation. Correspondingly, Mu-EVs from atrophic skeletal muscles attenuated the osteogenesis of BMSCs and strengthened the osteoclastogenesis of monocytes. In vivo experiments revealed that Mu-EVs could efficiently reverse disuse-induced osteoporosis by enhancing bone formation and suppressing bone resorption. Collectively, our results suggest that Mu-EVs may be a potential cell-free therapy for osteoporosis treatment. STATEMENT OF SIGNIFICANCE: Osteoporosis is a highly prevalent skeletal bone disorder worldwide and has become a global health concern with the aging of the world population. The current treatment for osteoporosis has unwanted side effects. Extracellular veiscles (EVs) from various cell sources are a promising candidate for osteoporosis treatment. In the present study, our team established protocols to isolate EVs from culture supernatant of skeletal muscles (Mu-EVs). Uptake of Mu-EVs by BMSCs and osteoclasts influences the balance of bone remodeling via promoting the osteogenic differentiation of BMSCs and inhibiting the osteoclasts formation of monocytes. In addition, exogenous Mu-EVs from normal skeletal muscles are proved to reverse the disuse-induced osteoporosis. We provide experimental evidence that Mu-EVs therapy is a potential cell-free platform for osteoporosis treatment towards clinical application.

Local Elimination of Senescent Cells Promotes Bone Defect Repair during Aging.

Due to the declined function of bone marrow mesenchymal stem cells (BMSCs), the repair of bone defects in the elderly is retarded. Elimination of senescent cells emerges as a promising strategy for treating age-related diseases. However, whether the local elimination of senescent BMSCs can promote bone regeneration in the elderly remains elusive. To tackle the above issue, we first screened out the specific senolytics for BMSCs and confirmed their effect of eliminating senescent BMSCs in vitro. Treatment with quercetin, which is determined the best senolytics for senescent BMSCs, efficiently removed senescent cells in the population. Moreover, the self-renewal capacity was restored as well as osteogenic ability of BMSCs after treatment. We then designed a microenvironment-responsive hydrogel based on the MMPs secreted by senescent cells. This quercetin-encapsulated hydrogel exhibited a stable microstructure and responsively released quercetin in the presence of senescence in vitro. In vivo, the quercetin-loaded hydrogel effectively cleared the local senescent cells and reduced the secretion of MMPs in the bone. Due to the removal of local senescent cells, the hydrogel significantly accelerated the repair of bone defects in the femur and skull of old rats. Taken together, our study revealed the role of removing senescent cells in bone regeneration and provided a novel therapeutic approach for bone defects in aged individuals.

Fault detection for linear discrete time-varying systems with multiplicative noise based on parity space method.

This paper addresses the robust fault diagnosis problem for a class of linear discrete time-varying systems with multiplicative noise based on parity space method. A novel fault detection performance index, in terms of stochastic robustness/sensitivity ratio, is proposed to establish the residual generator. A computationally attractive recursive algorithm, is put forward to obtain the complex matrix involved in the aforementioned fault detection performance index. Drawing support of random matrix analysis and calculation, the corresponding solution is derived in an analytical form via solving a multi-objective optimization problem. By means of Randomized Algorithms, two fault detection threshold setting algorithms are provided subsequently to achieve residual performance assessment by taking into account the fault detection rate and false alarm rate in the probabilistic framework. Two illustrative examples are finally provided to illustrate the effectiveness of the proposed scheme.

Metabolic syndrome and the risk of colorectal cancer: a systematic review and meta-analysis.

PURPOSE: Observational studies have reported an association between metabolic syndrome (MetS) and colorectal cancer risk with inconsistent risk estimates. We conducted this meta-analysis to evaluate the risk of colorectal cancer in individuals with MetS. METHODS: PubMed, Embase, and Web of Science were searched for related studies from database inception to 21 January 2021. Risk estimates for colorectal cancer were extracted from individual articles and pooled using a fixed-effect or random-effect model according to the heterogeneity. RESULTS: MetS was significantly associated with a higher risk of colorectal cancer in both sexes (relative risk [RR] 1.36, 95% confidence interval [CI] 1.26-1.47, P < 0.001), men (RR 1.33, 95% CI 1.21-1.47, P < 0.001), and women (RR 1.34, 95% CI 1.19-1.52, P < 0.001). The risk of colorectal cancer seemed to increase as the number of MetS components rose. Moreover, the high body mass index (BMI)/waist circumference (WC) and hyperglycemia were all significantly associated with a higher risk of colorectal cancer (RR 1.28 [1.20-1.37] and 1.31 [1.14-1.50] in both sexes, RR 1.31 [1.19-1.45] and 1.23 [1.03-1.46] in men, and RR 1.22 [1.02-1.46] and 1.63 [1.16-2.28] in women, respectively). CONCLUSIONS: MetS was significantly associated with a higher risk of colorectal cancer. The high BMI/WC or hyperglycemia might largely account for this association. Further analysis suggested that, as the number of MetS components increased, the risk of colorectal cancer rose.

Adipose Tissue-derived Microvascular Fragments as Vascularization Units for Dental Pulp Regeneration.

INTRODUCTION: The transplantation of dental pulp stem cells (DPSCs) has emerged as a novel strategy for the regeneration of lost dental pulp after pulpitis and trauma. Dental pulp regeneration of the young permanent tooth with a wide tooth apical foramen has achieved significant progress in the clinical trials. However, because of the narrow apical foramen, dental pulp regeneration in adult teeth using stem cells remains difficult in the clinic. Finding out how to promote vascular reconstitution is essential for the survival of stem cells and the regeneration of dental pulp after transplantation into the adult tooth. METHODS: Adipose tissue-derived microvascular fragments (ad-MVFs) were isolated from human adipose tissues. The apoptosis and senescence of DPSCs cultured in conditioned media were evaluated to explore the effects of ad-MVFs on DPSCs. DPSCs combined with ad-MVFs were inserted into the human tooth root segments and implanted subcutaneously into immunodeficient mice. Regenerated pulplike tissues were analyzed by hematoxylin and eosin and immunohistochemistry. The vessels in regenerated tissues were analyzed by Micro-CT and immunofluorescence. RESULTS: The isolated ad-MVFs contained endothelial cells and pericytes. ad-MVFs effectively prevented the apoptosis and senescence of the transplanted DPSCs both in vivo and in vitro. Combined with DPSCs, ad-MVFs obviously facilitated the formation of vascular networks in the transplants. DPSCs combined with ad-MVFs formed dental pulp-like tissues with abundant cells and matrix after 4 weeks of implantation. The supplementation of ad-MVFs led to more odontoblastlike cells and increased the formation of mineralized substance around the root canal. CONCLUSIONS: Cotransplantation with ad-MVFs promotes the angiogenesis and revascularization of transplanted DPSC aggregates, leading to robust regeneration of dental pulp.

Comparison of the incidence of cholelithiasis after sleeve gastrectomy and Roux-en-Y gastric bypass: a meta-analysis.

BACKGROUND: Bariatric surgery could increase the risk of cholelithiasis, although it is unclear whether the incidence rates of cholelithiasis are similar after different bariatric procedures. OBJECTIVES: To compare the incidence rates of cholelithiasis after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in people with obesity. SETTING: Meta-analysis of cohort studies. METHODS: We searched the PubMed and Web of Science databases for relevant studies before December 2020, and estimated the summary odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model or fixed-effects model, according to the heterogeneity. RESULTS: In total, 8 cohort studies were included in this meta-analysis, and 94,855 and 106,844 participants received SG and RYGB, respectively. Compared with those receiving RYGB, the summary results showed that participants receiving SG had a 35% lower rate of cholelithiasis (OR, .65; 95% CI, .49-.86). Also, the participants receiving SG had a significantly lower incidence of cholecystectomy than those receiving RYGB (OR, .54; 95% CI, .30-.99). In a subgroup analysis, SG was associated with a significantly lower incidence of subsequent cholelithiasis than RYGB in both Western and non-Western countries. SG led to a significantly lower incidence of cholelithiasis than RYGB only when the follow-up was <2 years instead of over 2 years. CONCLUSION: Participants receiving SG had a significantly lower incidence of cholelithiasis than those receiving RYGB, particularly within the first 2 years after the bariatric surgery.

TNF-α-Induce Protein 8-Like 1 Inhibits Hepatic Steatosis, Inflammation, and Fibrosis by Suppressing Polyubiquitination of Apoptosis Signal-Regulating Kinase 1.

BACKGROUND AND AIMS: Characterized by hepatocyte steatosis, inflammation, and fibrosis, NASH is a complicated process that contributes to end-stage liver disease and, eventually, HCC. TNF-α-induced protein 8-like 1 (TIPE1), a new member of the TNF-α-induced protein 8 family, has been explored in immunology and oncology research; but little is known about its role in metabolic diseases. APPROACH AND RESULTS: Here, we show that hepatocyte-specific deletion of TIPE1 exacerbated diet-induced hepatic steatosis, inflammation, and fibrosis as well as systemic metabolic disorders during NASH pathogenesis. Conversely, hepatocyte-specific overexpression of TIPE1 dramatically prevented the progression of these abnormalities. Mechanically, TIPE1 directly interacted with apoptosis signal-regulating kinase 1 (ASK1) to suppress its TNF receptor-associated factor 6 (TRAF6)-catalyzed polyubiquitination activation upon metabolic challenge, thereby inhibiting the downstream c-Jun N-terminal kinase and p38 signaling pathway. Importantly, dramatically reduced TIPE1 expression was observed in the livers of patients with NAFLD, suggesting that TIPE1 might be a promising therapeutic target for NAFLD and related metabolic diseases. CONCLUSIONS: TIPE1 protects against hepatic steatosis, inflammation, and fibrosis through directly binding ASK1 and restraining its TRAF6-catalyzed polyubiquitination during the development of NASH. Therefore, targeting TIPE1 could be a promising therapeutic approach for NAFLD treatment.

Inflammatory bowel diseases and the risk of adverse health outcomes: Umbrella review of meta-analyses of observational studies.

BACKGROUND AND AIM: Accumulating evidence indicates a plausible association between inflammatory bowel diseases and the risk of adverse health outcomes. However, the conclusions are inconsistent. We aimed to perform an umbrella review of meta-analyses to appraise and grade the evidence of the association between inflammatory bowel diseases and the risk of adverse health outcomes. METHODS: Meta-analyses of observational studies that examined the associations between inflammatory bowel disease and the risk of adverse health outcomes in PubMed, EMBASE, and Web of Science were screened. RESULTS: This umbrella review identified 25 meta-analyses, which yielded 123 effect estimates for 60 unique putative health outcomes. Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes, including multiple cancers, cardiovascular disease, adverse pregnancy outcomes, adverse oral outcomes, and other adverse events. Moreover, inflammatory bowel diseases caused greater harm to health based on the presented evidence. However, none of the evidence was classified as "high" quality, only 15% was classified as "moderate," and 65% of outcomes were rated as "very low." CONCLUSION: Patients with inflammatory bowel diseases had a higher risk of adverse health outcomes and further studies should be conducted to draw firmer conclusions.

Inflammatory bowel disease and risk of gastric, small bowel and colorectal cancer: a meta-analysis of 26 observational studies.

PURPOSE: The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. METHODS: We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle-Ottawa-Scale. RESULTS: Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn's disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. CONCLUSIONS: IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.

MiR-30c-5p regulates adventitial progenitor cells differentiation to vascular smooth muscle cells through targeting OPG.

BACKGROUND: As the most important component of the vascular wall, vascular smooth muscle cells (VSMCs) participate in the pathological process by phenotype transformation or differentiation from stem/progenitor cells. The main purpose of this study was to reveal the role and related molecular mechanism of microRNA-30c-5p (miR-30c-5p) in VSMC differentiation from adventitial progenitor cells expressing stem cell antigen-1(Sca-1). METHODS: In this study, we detected the expression of miR-30c-5p in human normal peripheral arteries and atherosclerotic arteries. In vitro, a stable differentiation model from adventitial Sca-1+ progenitor cells to VSMCs was established using transforming growth factor-ß1 (TGF-ß1) induction and the expression of miR-30c-5p during the process was observed. Then, we explored the effect of miR-30c-5p overexpression and inhibition on the differentiation from adventitial Sca-1+ progenitor cells to VSMCs. The target genes of miR-30c-5p were identified by protein chip and biological analyses and the expression of these genes in the differentiation process were detected. Further, the relationship between the target gene and miR-30c-5p and its effect on differentiation were evaluated. Finally, the co-transfection of miR-30c-5p inhibitor and small interfering RNA (siRNA) of the target gene was implemented to verify the functional target gene of miR-30c-5p during the differentiation from adventitial Sca-1+ progenitor cells to VSMCs, and the dual-luciferase reporter gene assay was performed to detect whether the mRNA 3'untranslated region (UTR) of the target gene is the direct binding site of miR-30c-5p. RESULTS: The expression of miR-30c-5p in the human atherosclerotic arteries was significantly lower than that in the normal arteries. During the differentiation from adventitial Sca-1+ progenitor cells to VSMCs, the expression of VSMC special markers including smooth muscle α-actin (SMαA), smooth muscle-22α (SM22α), smooth muscle myosin heavy chain (SMMHC), and h1-caponin increased accompanied with cell morphology changing from elliptic to fusiform. Meanwhile, the expression of miR-30c-5p decreased significantly. In functional experiments, overexpression of miR-30c-5p inhibited SMαA, SM22α, SMMHC, and h1-caponin at the mRNA and protein levels. In contrast, inhibition of miR-30c-5p promoted the expression of SMαA, SM22α, SMMHC, and h1-caponin. The target gene, osteoprotegerin (OPG), was predicted through protein chip and bioinformatics analyses. Overexpression of miR-30c-5p inhibited OPG expression while inhibition of miR-30c-5p had an opposite effect. Co-transfection experiments showed that low expression of OPG could weaken the promotion effect of miR-30c-5p inhibitor on the differentiation from adventitial Sca-1+ progenitor cells to VSMCs and the dual-luciferase reporter gene assay demonstrated that miR-30c-5p could target the mRNA 3'UTR of OPG directly. CONCLUSIONS: This study demonstrates that miR-30c-5p expression was significantly decreased in atherosclerotic arteries and miR-30c-5p inhibited VSMC differentiation from adventitial Sca-1+ progenitor cells through targeting OPG, which may provide a new target for the treatment of VSMCs-associated diseases.

Circulating microRNAs in serum as novel biomarkers for osteoporosis: a case-control study.

AIMS: Osteoporosis is underdiagnosed because of the lack of a convenient diagnostic method. Circulating microRNAs (miRNAs) emerge as novel biomarkers for disease diagnosis. Here, we conducted a case-control study that included a total of 448 serum samples collected from 182 healthy participants, 132 osteopenia participants, and 134 osteoporosis patients. METHODS: Circulating miRNAs dysregulated during osteoporosis were screened and analyzed in three randomly determined sub-cohorts: the discovery cohort identified 22 candidate miRNAs; the training cohort tested the candidate miRNAs and constructed Index 1, comprising five miRNAs by logistic regression, and Index 2, comprising four miRNAs, was developed by linear combination. RESULTS: Both indices were tested in the validation cohort and showed statistically significant results in distinguishing osteoporosis patients from healthy and osteopenic patients. Moreover, Index 1 also showed improved performance over traditional bone turnover biomarkers type I pro-collagen (tPINP) and type I collagen (ß-CTx). CONCLUSION: In conclusion, circulating miRNAs are potential biomarkers for osteoporosis. The diagnostic panel of circulating miRNAs could be a complementary method for dual-energy X-ray absorptiometry (DXA) in mass screening and routine examination to enhance the osteoporosis detection rate.