Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium.

AIM: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms. MATERIALS AND METHODS: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation. RESULTS: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent. CONCLUSIONS: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.

Colorectal cancer microbiome programs DNA methylation of host cells by affecting methyl donor metabolism.

BACKGROUND: Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC. METHODS: Metagenomic sequencing of fecal samples was performed on matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome was profiled with 16S rRNA gene sequencing on tumor (n = 24) and tumor-adjacent normal (n = 24) tissues of CRC patients, while host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals. RESULTS: Our analysis revealed substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Of note, we observed a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues, a phenomenon notably absent in tumor tissues. Furthermore, we established consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa. CONCLUSIONS: This study emphasizes the pivotal role of the gut microbiota and pathogenic bacteria in dynamically shaping DNA methylation patterns, impacting physiological homeostasis, and contributing to CRC tumorigenesis. These findings provide valuable insights into the intricate host-environment interactions in CRC development and offer potential avenues for therapeutic interventions in this disease.

Effects of Functional Strength Training Combined with Aerobic Training on Body Composition, Physical Fitness, and Movement Quality in Obese Adolescents.

This study aimed to compare the effects of 12 weeks of functional strength training combined with aerobic training (TG) and traditional resistance training combined with aerobic training (CG) on the body composition, physical fitness, and movement quality of obese adolescents. Forty participants were randomly assigned to either the TG group (n = 20) or the CG group (n = 20). Each group underwent training five times per week, lasting 120 min each time, over a total period of 12 weeks. All participants followed a strict dietary program. Anthropometric parameters, body composition, physical fitness, and movement quality were evaluated at baseline and after intervention. A two-way repeated measures ANOVA observed a significant interaction between time and group for body mass (p = 0.043), body fat percentage (p = 0.045), body mass index (p = 0.025), neck circumference (p = 0.01), chest circumference (p = 0.027), left-hand grip strength (p = 0.043), right-hand grip strength (p = 0.048), standing broad jump (p = 0.044), and total Functional Movement Screen score (p = 0.003), and the improvement was greater for TG in comparison to CG. TG was found to be more effective than CG in enhancing body composition, physical fitness, and movement quality in obese adolescents.

Wireless Technologies in Flexible and Wearable Sensing: From Materials Design, System Integration to Applications.

Wireless and wearable sensors attract considerable interest in personalized healthcare by providing a unique approach for remote, noncontact, and continuous monitoring of various health-related signals without interference with daily life. Recent advances in wireless technologies and wearable sensors have promoted practical applications due to their significantly improved characteristics, such as reduction in size and thickness, enhancement in flexibility and stretchability, and improved conformability to the human body. Currently, most researches focus on active materials and structural designs for wearable sensors, with just a few exceptions reflecting on the technologies for wireless data transmission. This review provides a comprehensive overview of the state-of-the-art wireless technologies and related studies on empowering wearable sensors. The emerging functional nanomaterials utilized for designing unique wireless modules are highlighted, which include metals, carbons, and MXenes. Additionally, the review outlines the system-level integration of wireless modules with flexible sensors, spanning from novel design strategies for enhanced conformability to efficient transmitting data wirelessly. Furthermore, the review introduces representative applications for remote and noninvasive monitoring of physiological signals through on-skin and implantable wireless flexible sensing systems. Finally, the challenges, perspectives, and unprecedented opportunities for wireless and wearable sensors are discussed.

Macromolecular Engineered Multifunctional Room-Temperature Phosphorescent Polymers through Reversible Deactivation Radical Polymerization.

Despite the intensive research in room-temperature phosphorescent (RTP) polymers, the synthesis of RTP polymers with well-defined macromolecular structures and multiple functions remains a challenge. Herein, reversible deactivation radical polymerization was demonstrated to offer a gradient copolymer (GCP) architecture with controlled heterogeneities, which combines hard segment and flexible segment. The GCPs would self-assemble into a multiphase nanostructure, featuring tunable stretchability, excellent RTP performance, and intrinsic healability without compromising light emission under stretching. The mechanical performance is tunable on demand with elongation at break ranging from 5.0% to 221.7% and Young's modulus ranging from 0.5 to 225.0 MPa.

Prognosis of patients with familial hypertrophic cardiomyopathy: A single-center cohort study with ten-year follow-up by propensity score matching analysis.

Objectives: Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy. However, few studies have investigated the prognosis of familial HCM (FHCM) through clinical data. The purpose of this study was to compare the clinical outcomes of FHCM and non-FHCM through propensity score matching analysis. Methods and results: The cohort study included 1243 patients with HCM between 1996 and 2013 in Fuwai Hospital, Chinese Academy of Medical Sciences, among whom 125 patients had FHCM. During a mean follow-up of 7.6 ± 3.8 years (interquartile range: (IQR) 5.0-10.0 years), 217 (16.57%) of the 1243 patients had died, including 3 patients who underwent cardiac transplantation. Using 30 demographic and clinical variables, a 4:1 propensity score matched cohort for FHCM was established. The stepwise variable selection procedure for the Cox proportional hazards model was performed to identify the factors associated with mortality and competing risk regression analysis was performed to analyze the competitive risk of cardiovascular and non-cardiovascular mortality. The results showed that FHCM patients had a higher risk of cardiovascular mortality/cardiac transplantation (log-rank χ2 = 6.8, P = 0.0084) and an increased tendency of sudden cardiac death (SCD) (log-rank χ2 = 3.2, P = 0.074) compared with non-FHCM patients, but there was no difference in all-cause mortality (log-rank χ2 = 2.7, P = 0.1) between the two groups. Moreover, the Cox model showed that FHCM was an independent prognostic predictor for cardiovascular mortality/cardiac transplantation in HCM patients. Conclusion: FHCM patients had a higher risk of cardiovascular mortality/cardiac transplantation and a higher tendency of SCD than non-FHCM patients, but there was no difference in all-cause mortality. Moreover, FHCM was an independent prognostic predictor for cardiovascular mortality/cardiac transplantation in HCM patients.

The checkpoint inhibitor PD-1H/VISTA controls osteoclast-mediated multiple myeloma bone disease.

Multiple myeloma bone disease is characterized by the development of osteolytic bone lesions. Recent work identified matrix metalloproteinase 13 as a myeloma-derived fusogen that induces osteoclast activation independent of its proteolytic activity. We now identify programmed death-1 homolog, PD-1H, as the bona fide MMP-13 receptor on osteoclasts. Silencing PD-1H or using Pd-1h-/- bone marrow cells abrogates the MMP-13-enhanced osteoclast fusion and bone-resorptive activity. Further, PD-1H interacts with the actin cytoskeleton and plays a necessary role in supporting c-Src activation and sealing zone formation. The critical role of PD-1H in myeloma lytic bone lesions was confirmed using a Pd-1h-/- myeloma bone disease mouse model wherein myeloma cells injected into Pd-1h-/-Rag2-/- results in attenuated bone destruction. Our findings identify a role of PD-1H in bone biology independent of its known immunoregulatory functions and suggest that targeting the MMP-13/PD-1H axis may represent a potential approach for the treatment of myeloma associated osteolysis.

Multi-phase FZA lensless imaging via diffusion model.

Lensless imaging shifts the burden of imaging from bulky and expensive hardware to computing, which enables new architectures for portable cameras. However, the twin image effect caused by the missing phase information in the light wave is a key factor limiting the quality of lensless imaging. Conventional single-phase encoding methods and independent reconstruction of separate channels pose challenges in removing twin images and preserving the color fidelity of the reconstructed image. In order to achieve high-quality lensless imaging, the multiphase lensless imaging via diffusion model (MLDM) is proposed. A multi-phase FZA encoder integrated on a single mask plate is used to expand the data channel of a single-shot image. The information association between the color image pixel channel and the encoded phase channel is established by extracting prior information of the data distribution based on multi-channel encoding. Finally, the reconstruction quality is improved through the use of the iterative reconstruction method. The results show that the proposed MLDM method effectively removes the influence of twin images and produces high-quality reconstructed images compared with traditional methods, and the results reconstructed using MLDM have higher structural similarity and peak signal-to-noise ratio.

Lactobacillus plantarum-derived indole-3-lactic acid ameliorates colorectal tumorigenesis via epigenetic regulation of CD8+ T cell immunity.

Previous studies have shown that Lactobacillus species play a role in ameliorating colorectal cancer (CRC) in a mouse model. However, the underlying mechanisms remain largely unknown. Here, we found that administration of a probiotic strain, Lactobacillus plantarum L168 and its metabolite, indole-3-lactic acid, ameliorated intestinal inflammation, tumor growth, and gut dysbiosis. Mechanistically, we indicated that indole-3-lactic acid accelerated IL12a production in dendritic cells by enhancing H3K27ac binding at the enhancer regions of IL12a that contributed to priming CD8+ T cell immunity against tumor growth. Furthermore, indole-3-lactic acid was found to transcriptionally inhibit Saa3 expression related to cholesterol metabolism of CD8+ T cells through changing chromatin accessibility and subsequent enhancing function of tumor-infiltrating CD8+ T cells. Together, our findings provide new insights into the epigenetic regulation of probiotics-mediated anti-tumor immunity and suggest the potential of L. plantarum L168 and indole-3-lactic acid to develop therapeutic strategies for patients with CRC.

Multiple spectral comparison of dissolved organic matter in the drainage basin of a reservoir in Northeast China: Implication for the interaction among organic matter, iron, and phosphorus.

Dissolved organic matter (DOM) plays a major role in ecological systems, affecting the fate and transportation of iron (Fe) and phosphorus (P). To better understand the geochemical cycling of these components, soil and sediment samples were collected around a reservoir downstream of a typical temperate forest in Northeast China. The DOM fractions from these soils, river, and reservoir sediments were extracted and then characterized by spectroscopic techniques. Comparative characterization data showed that the DOM pool of the Xishan Reservoir was partly autochthonous and derived from runoff and deposition of material in terrestrial ecosystems upstream. The upper reaches of the reservoir had significantly lower total Fe (TFe) content in the DOM extracts than those found in the reservoir (p < 0.05). Within the DOM, TFe was correlated with the amino acid tryptophan (p < 0.01). There was also a strong positive correlation between total P (TP) concentrations in DOM and tyrosine (p < 0.01). Organic P (Po) comprised most of the DOM TP, and was related to dissolved organic carbon (DOC) content and the amino acid tyrosine (p < 0.01). The interaction among DOM, Fe, and P appears to be due to complexation with tryptophan (Fe) and tyrosine (P). This suggests that the formation of Fe-DOM-P would be produced more readily than DOM-Fe-P complexes under optimal conditions. The interaction among DOM, Fe, and P can promote the coordinated migration, transformation, and ultimate fate of components that are complex with DOM from riverine and reservoir ecosystems, ultimately leading to accumulation within a reservoir and transport to downstream regions when reservoir dams are released. Reservoir dams can effectively intercept DOM and minerals prevent its flow downstream; however, it is important to understand the co-cycling of DOM, Fe and P within reservoirs, downstream rivers, and ultimately oceans. The involvement of amino acid components of DOM, tyrosine and tryptophan, in DOM complexation is an issue that requires further study.

Phase separation in innate immune response and inflammation-related diseases.

Inflammation induced by nonspecific pathogenic or endogenous danger signals is an essential mechanism of innate immune response. The innate immune responses are rapidly triggered by conserved germline-encoded receptors that recognize broad patterns indicative of danger, with subsequent signal amplification by modular effectors, which have been the subject of intense investigation for many years. Until recently, however, the critical role of intrinsic disorder-driven phase separation in facilitating innate immune responses went largely unappreciated. In this review, we discuss emerging evidences that many innate immune receptors, effectors, and/or interactors function as "all-or-nothing" switch-like hubs to stimulate acute and chronic inflammation. By concentrating or relegating modular signaling components to phase-separated compartments, cells construct flexible and spatiotemporal distributions of key signaling events to ensure rapid and effective immune responses to a myriad of potentially harmful stimuli.

Integrated multiple microarray studies by robust rank aggregation to identify immune-associated biomarkers in Crohn's disease based on three machine learning methods.

Crohn's disease (CD) is a complex autoimmune disorder presumed to be driven by complex interactions of genetic, immune, microbial and even environmental factors. Intrinsic molecular mechanisms in CD, however, remain poorly understood. The identification of novel biomarkers in CD cases based on larger samples through machine learning approaches may inform the diagnosis and treatment of diseases. A comprehensive analysis was conducted on all CD datasets of Gene Expression Omnibus (GEO); our team then used the robust rank aggregation (RRA) method to identify differentially expressed genes (DEGs) between controls and CD patients. PPI (protein‒protein interaction) network and functional enrichment analyses were performed to investigate the potential functions of the DEGs, with molecular complex detection (MCODE) identifying some important functional modules from the PPI network. Three machine learning algorithms, support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and least absolute shrinkage and selection operator (LASSO), were applied to determine characteristic genes, which were verified by ROC curve analysis and immunohistochemistry (IHC) using clinical samples. Univariable and multivariable logistic regression were used to establish a machine learning score for diagnosis. Single-sample GSEA (ssGSEA) was performed to examine the correlation between immune infiltration and biomarkers. In total, 5 datasets met the inclusion criteria: GSE75214, GSE95095, GSE126124, GSE179285, and GSE186582. Based on RRA integrated analysis, 203 significant DEGs were identified (120 upregulated genes and 83 downregulated genes), and MCODE revealed some important functional modules in the PPI network. Machine learning identified LCN2, REG1A, AQP9, CCL2, GIP, PROK2, DEFA5, CXCL9, and NAMPT; AQP9, PROK2, LCN2, and NAMPT were further verified by ROC curves and IHC in the external cohort. The final machine learning score was defined as [Expression level of AQP9 × (2.644)] + [Expression level of LCN2 × (0.958)] + [Expression level of NAMPT × (1.115)]. ssGSEA showed markedly elevated levels of dendritic cells and innate immune cells, such as macrophages and NK cells, in CD, consistent with the gene enrichment results that the DEGs are mainly involved in the IL-17 signaling pathway and humoral immune response. The selected biomarkers analyzed by the RRA method and machine learning are highly reliable. These findings improve our understanding of the molecular mechanisms of CD pathogenesis.

Soluble interleukin 2 receptor is risk for sarcopenia in Men with high fracture risk.

Background & aims: Sarcopenia is an age-related disease that increases the risk of falls and fractures in older adults. However, there is no blood biochemical marker to help to predict or diagnose sarcopenia in clinical practice. Soluble interleukin 2 receptor (sIL-2R) was reported to be associated with muscle satellite cell dysfunction which played an important role in the pathogenesis of sarcopenia. Thereby, we aimed to explore the association between serum sIL-2R and sarcopenia in older adults at high risk of fractures. Methods: A total of 429 hospitalized older adults (age ≥55 years) were enrolled in this cross-sectional study (mean age â€‹= â€‹66.62 â€‹± â€‹6.59 years; 62.7% female). Logistic regression analysis was performed to assess the association of sIL-2R with sarcopenia, muscle mass, muscle strength, and physical performance, respectively. The optimal models for the diagnosis of sarcopenia and low hand grip strength (HGS) were established by multivariable binary logistic regression analysis with backward selection, and further were evaluated for the diagnostic values by receiver operating characteristic (ROC) curve. Results: Higher sIL-2R levels were found in sarcopenia than no-sarcopenia group in male (median 421 U/mL (interquartile range [IQR] 217 U/mL) vs median 362 U/mL (IQR 157 U/mL); n â€‹= â€‹77 vs 83; p â€‹< â€‹0.01). Compared to the lowest sIL-2R tertile, the highest tertile of sIL-2R was independently associated with the risk of low HGS (odds ratio [OR] 4.608, 95% confidence interval [CI] 1.673-12.695) and the risk of sarcopenia (OR 3.306, 95% CI 1.496-7.302) in men. ROC curves revealed that the Area Under the Curve (AUC) of the optimal models for diagnosing sarcopenia and low HGS was 0.752 and 0.846. Conclusion: Our results suggest that serum sIL-2R is the independent risk factor for sarcopenia and low muscle strength only in men. sIL-2R may be developed to be a biochemical marker for sarcopenia and low muscle strength diagnoses in older men at high risk of fractures, but more prospective studies are needed to prove it. The translational potential of this article: Our results showed that the highest tertile of sIL-2R was independent of low risk of HGS and sarcopenia in men, compared to the lowest tertile. As the population ages, sIL-2R may become a potential diagnostic tool for predicting low HGS and sarcopenia among men at high risk of fractures.

IFN-γR/STAT1 signaling in recipient hematopoietic antigen-presenting cells suppresses graft-versus-host disease.

The absence of IFN-γ receptor (IFN-γR) or STAT1 signaling in donor cells has been shown to result in reduced induction of acute graft-versus-host disease (GVHD). In this study, we unexpectedly observed increased activation and expansion of donor lymphocytes in both lymphohematopoietic organs and GVHD target tissues of IFN-γR/STAT1-deficient recipient mice, leading to rapid mortality following the induction of GVHD. LPS-matured, BM-derived Ifngr1-/- Stat1-/- DCs (BMDCs) were more potent allogeneic stimulators and expressed increased levels of MHC II and costimulatory molecules. Similar effects were observed in human antigen-presenting cells (APCs) with knockdown of Stat1 by CRISPR/Cas9 and treatment with a JAK1/2 inhibitor. Furthermore, we demonstrated that the absence of IFN-γR/STAT1 signaling in hematopoietic APCs impaired the presentation of exogenous antigens, while promoting the presentation of endogenous antigens. Thus, the indirect presentation of host antigens to donor lymphocytes was defective in IFN-γR/STAT1-deficient, donor-derived APCs in fully donor chimeric mice. The differential effects of IFN-γR/STAT1 signaling on endogenous and exogenous antigen presentation could provide further insight into the roles of the IFN-γ/STAT1 signaling pathway in the pathogenesis of GVHD, organ rejection, and autoimmune diseases.

Programmable multistage small-molecule nano-photosensitizer for multimodal imaging-guided photothermal therapy.

Photothermal therapy has become a promising approach as precision medicine to allow spatial control of therapeutic effect only in the site of interest. However, the full potential of PTT has not been realized due to the lack of simple photosensitizers (PSs) that can overcome multistage biological barriers and improve theranostic efficiency. Here, we develop a small molecule-based PS to enhance tumor-specific PTT by programming multistage transport and activation properties in molecular architecture. This PS can self-assemble into stable nanoparticles that accumulate passively in tumor, and then actively internalize through ligand-mediated endocytosis. Subsequently, the programmable degradable linkers are selectively cleaved, enabling size shrinkage for better tumor penetration, binding albumin to enhance the near-infrared fluorescence for low-background imaging, and activating photothermal conversion for tumor suppression. The self-delivery process can be programmed, representing the first multistage small-molecule nano-photosensitizer that overcomes multiple biological barriers and improves the PTT index of tumor. STATEMENT OF SIGNIFICANCE: Photothermal therapy has become a promising approach as precision medicine, but has not been realized due to the lack of simple photosensitizers that can overcome multistage biological barriers and improve theranostic efficiency. In this contribution, we solve this dilemma by developing a small molecule-based photosensitizer by programming multistage transport and activation properties in molecular architecture, which could self-assemble into stable nanoparticles that accumulate passively in tumor, and actively internalized through ligand-mediated endocytosis. Subsequently, the programmable activation by ROS triggered size reduction for tumor penetration and minimized the phototoxicity to normal tissue. The activatable fluorescence and photothermal properties made the photosensitizer intrinsically suitable for multimodal imaging-guided PTT, providing a promising supramolecular nanomedicine towards tumor precise diagnosis and therapy.

Prognosis for patients with apical hypertrophic cardiomyopathy: A multicenter cohort study based on propensity score matching.

BACKGROUND: Apical hypertrophic cardiomyopathy (AHCM) is a subtype of HCM, and few studies on the prognosis in AHCM are available. AIMS: This study aimed to explore the clinical prognosis for AHCM and non-AHCM patients through clinical data based on propensity score matching (PSM) in a large cohort of Chinese HCM patients. METHODS: The cohort study included 2268 HCM patients, 226 AHCM and 2042 non-AHCM patients from 13 tertiary hospitals, who were treated between 1996 and 2021. Fifteen demographic and clinical variables of 226 AHCM patients and 2042 non-AHCM patients were matched using 1:2 PSM. A Cox proportional hazard regression model was constructed to assess the effect of AHCM on mortality. RESULTS: During a median follow-up of 5.1 (2.4-8.4) years, 353 (15.6%) of the 2268 HCM patients died, of whom 205 died due to cardiovascular mortality/cardiac transplantation and 94 experienced sudden cardiac death (SCD). In the matched cohort, the ACHM patients had lower rates of all-cause mortality (P = 0.003), cardiovascular mortality/cardiac transplantation (P = 0.03), and SCD (P = 0.02) than the non-AHCM patients. Furthermore, the Cox proportional hazard regression model showed that AHCM was an independent prognostic predictor of all-cause HCM mortality (P = 0.004) and a univariable prognostic predictor of cardiovascular mortality/cardiac transplantation (P = 0.03) and for SCD (P = 0.03). However, AHCM was not significant in multivariable Cox regression models in relation to cardiovascular mortality/cardiac transplantation and SCD. CONCLUSION: AHCM had a favorable prognosis both before and after matching, with lower all-cause mortality, cardiovascular mortality/cardiac transplantation, and SCD than non-AHCM.

Activation of primary hepatic stellate cells and liver fibrosis induced by targeting TGF-ß1/Smad signaling in schistosomiasis in mice.

BACKGROUND: In mice, liver fibrosis is the most serious pathologic change during Schistosoma japonicum (S. japonicum) infection. Schistosomiasis is mainly characterized by schistosome egg-induced granulomatous fibrosis. Hepatic stellate cells (HSCs) are mainly responsible for the net accumulation of collagens and fibrosis formation in the liver. Activated HSCs regulated by transforming growth factor-ß1 (TGF-ß1)/Smad signaling have emerged as the critical regulatory pathway in hepatitis virus or carbon tetrachloride-induced liver fibrosis. However, the detailed mechanism of HSC activation in schistosome-induced liver fibrosis is poorly understood. METHODS: Schistosoma japonicum-induced murine models and a control group were generated by abdominal infection with 15 (± 1) cercariae. The purity of cultured primary HSCs was evaluated by immunocytochemistry. The histopathological changes in the livers of infected mice were estimated by hematoxylin-eosin and Masson staining. Dynamic expression of pro-fibrotic molecules and microRNAs was detected by real-time quantitative PCR (RT-qPCR). Mainly members involved in the TGF-ß1/Smad signaling pathway were examined via RT-qPCR and Western blot. RESULTS: The egg-induced granulomatous inflammation formed at 4 weeks post-infection (wpi) and developed progressively. Alpha-smooth muscle actin (α-SMA), collagen I, collagen III, TGF-ß1, Smad2, Smad3, and Smad4 showed a significant increase in mitochondrial RNA (mRNA) and protein expression compared with the control group at 7 and 9 weeks post-infection (wpi), while an opposite effect on Smad7 was observed. In addition, the mRNA expression of microRNA-21 (miRNA-21) was significantly increased at 7 wpi, and the mRNA expression of miRNA-454 was decreased starting from 4 wpi. CONCLUSION: Our present findings revealed that HSCs regulated by the TGF-ß1/Smad signaling pathway play an important role in liver fibrosis in S. japonicum-infected mice, which may provide proof of concept for liver fibrosis in schistosomiasis.

A New Index Based on Serum Creatinine and Cystatin C Can Predict the Risks of Sarcopenia, Falls and Fractures in Old Patients with Low Bone Mineral Density.

As new screening tools for sarcopenia, the serum sarcopenia index (SI) and creatinine/cystatin C ratio (CCR) had not been confirmd in a population with a high fragility fracture risk. This study aimed to evaluate whether SI and CCR indicators are useful for diagnosing sarcopenia and to determine their prediction values for future falls and fractures. A total of 404 hospitalized older adults were enrolled in this longitudinal follow-up study (mean age = 66.43 ± 6.80 years). The receiver operating curve (ROC) was used to assess the diagnostic accuracy of SI and CCR. Backward-selection binary logistic regression was applied to develop the optimal models for the diagnosis of new falls and fractures. SI had a significantly higher area under the curve (AUC) than CCR for predicting sarcopenia. The optimal models had acceptable discriminative powers for predicting new falls and fractures. Lower SI and CCR are the independent risks for sarcopenia, new falls, and fractures in the low-BMD population. SI and CCR, as easily accessible biochemical markers, may be useful in the detection of sarcopenia and in predicting the occurrence of new falls and fractures in patients with low BMD who have not previously experienced falls or fractures. However, further external validations are required.

Superselective arterial microcoil embolization for delayed bleeding after peroral endoscopic myotomy.

Peroral endoscopic myotomy (POEM) has been shown to be an effective treatment for achalasia and with few adverse events. Only a few cases of delayed bleeding have been described. This current case report describes a patient with delayed bleeding in the submucosal tunnel on the eighth day after POEM. The patient was a 21-year-old woman with a 4-month history of dysphagia, vomiting and excessive weight loss. Achalasia was diagnosed according to her symptoms, barium oesophagogram, oesophageal manometry and endoscopy examination. POEM was performed by an experienced operator. On the eighth day after POEM, the patient suddenly developed continuous haematemesis presented with vomiting of fresh blood and melena. An emergency exploratory esophagogastroduodenoscopy was performed. A large number of blood clots were found at the wound and a long haematoma was found along the lining of the submucosal tunnel. Re-entry into the submucosal tunnel and exposure of the haemorrhagic site was attempted but failed because of severe submucosal tissue adhesion. An emergency angiography was undertaken and haemostasis was achieved with superselective arterial microcoil embolization.