Total body water percentage and 3rd space water are novel risk factors for training-related lower extremity muscle injuries in young males.

PURPOSE: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis. METHODS: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q1, Q3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. RESULTS: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, odds ratio = 3.114) and 3rd space water > 0.95% (p = 0.045, odds ratio = 2.342) were independent risk factors for lower extremity muscle injuries. CONCLUSION: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

TGF-ß/Alk5 signaling prevents osteoarthritis initiation via regulating the senescence of articular cartilage stem cells.

Osteoarthritis (OA) is the most common joint disease. The surface of joint cartilage is a defensive and first affected structure of articular cartilage (AC) during the pathogenesis of OA. Alk5 signaling is critical for maintaining AC homeostasis, however, the role and underlying mechanism for the involvement of Alk5 signaling in the phenotypes of articular cartilage stem cells (ACSCs) at the surface of AC is still unclear. The role of Alk5 in OA development was explored using an ACSCs-specific Alk5-deficient (cKO) mouse model. Alterations in cartilage structure were evaluated histologically. Senescence was detected by SA-ß-gal, while reactive oxygen species (ROS), MitoTracker, and LysoTracker staining were used to detect changes related to senescence. In addition, mice were injected intra-articularly with ganciclovir to limit the detrimental roles of senescent cells (SnCs). Alk5 cKO mice showed a decreased number of the slow-cell cycle cells and less lubricant secretion at the surface accompanied with drastically accelerated cartilage degeneration under ageing and surgically induced OA conditions. Further studies showed that Alk5 deficient ACSCs exhibited senescence-like manifestations including decreased proliferation and differentiation, more SA-ß-gal-positive cells and ROS production, as well as significantly swollen mitochondria and lysosome breakdown. We further found that local limitation of the detrimental roles of SnCs can attenuate the development of posttraumatic OA. Taken together, our findings suggest that Alk5 signaling acts as an important regulator of the SnCs in the superficial layer during AC maintenance and OA initiation.

FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice.

OBJECTIVES: This study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis. METHODS: Mice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and µCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis. RESULTS: R3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice. CONCLUSIONS: Our study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.

HER2 immunohistochemical scores provide prognostic information for patients with HER2-type invasive breast cancer.

AIMS: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in-situ hybridisation (ISH) positivity are suitable for anti-HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different. METHODS AND RESULTS: We analysed the clinicopathological information of 886 consecutive cases of HER2-positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti-HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut-off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers. CONCLUSION: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2-positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis.

Outlier Detection Using Improved Support Vector Data Description in Wireless Sensor Networks.

Wireless sensor networks (WSNs) are susceptible to faults in sensor data. Outlier detection is crucial for ensuring the quality of data analysis in WSNs. This paper proposes a novel improved support vector data description method (ID-SVDD) to effectively detect outliers of sensor data. ID-SVDD utilizes the density distribution of data to compensate SVDD. The Parzen-window algorithm is applied to calculate the relative density for each data point in a data set. Meanwhile, we use Mahalanobis distance (MD) to improve the Gaussian function in Parzen-window density estimation. Through combining new relative density weight with SVDD, this approach can efficiently map the data points from sparse space to high-density space. In order to assess the outlier detection performance, the ID-SVDD algorithm was implemented on several datasets. The experimental results demonstrated that ID-SVDD achieved high performance, and could be applied in real water quality monitoring.

Postnatal deletion of Alk5 gene in meniscal cartilage accelerates age-dependent meniscal degeneration in mice.

Activation of transforming growth factor-ß (TGF-ß) signaling has been used to enhance healing of meniscal degeneration in several models. However, the exact role and molecular mechanism of TGF-ß signaling in meniscus maintenance and degeneration are still not understood due to the absence of in vivo evidence. In this study, we found that the expression of activin receptor-like kinases 5 (ALK5) in the meniscus was decreased with the progression of age and/or osteoarthritis induced meniscal degeneration. Col2α1 positive cells were found to be specifically distributed in the superficial and inner zones of the anterior horn, as well as the inner zone of the posterior horn in mice, indicating that Col2α1-CreERT2 mice can be a used for studying gene function in menisci. Furthermore, we deleted Alk5 in Col2α1 positive cells in meniscus by administering tamoxifen. Alterations in the menisci structure were evaluated histologically. The expression levels of genes and proteins associated with meniscus homeostasis and TGF-ß signaling were analyzed by quantitative real-time PCR analysis (qRT-PCR) and immunohistochemistry (IHC). Our results revealed severe and progressive meniscal degeneration phenotype in 3- and 6-month-old Alk5 cKO mice compared with Cre-negative control, including aberrantly increased hypertrophic meniscal cells, severe fibrillation, and structure disruption of meniscus. qRT-PCR and IHC results showed that disruption of anabolic and catabolic homeostasis of chondrocytes may contribute to the meniscal degeneration phenotype observed in Alk5 cKO mice. Thus, TGF-ß/ALK5 signaling plays a chondro-protective role in menisci homeostasis, in part, by inhibiting matrix degradation and maintaining extracellular matrix proteins levels in meniscal tissues.

Enhanced activation of circulating plasmacytoid dendritic cells in patients with Chronic Obstructive Pulmonary Disease and experimental smoking-induced emphysema.

Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naïve CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.

Data Fusion Using Improved Support Degree Function in Aquaculture Wireless Sensor Networks.

For monitoring the aquaculture parameters in pond with wireless sensor networks (WSN), high accuracy of fault detection and high precision of error correction are essential. However, collecting accurate data from WSN to server or cloud is a bottleneck because of the data faults of WSN, especially in aquaculture applications, limits their further development. When the data fault occurs, data fusion mechanism can help to obtain corrected data to replace abnormal one. In this paper, we propose a data fusion method using a novel function that is Dynamic Time Warping time series strategy improved support degree (DTWS-ISD) for enhancing data quality, which employs a Dynamic Time Warping (DTW) time series segmentation strategy to the improved support degree (ISD) function. We use the DTW distance to replace Euclidean distance, which can explore the continuity and fuzziness of data streams, and the time series segmentation strategy is adopted to reduce the computation dimension of DTW algorithm. Unlike Gauss support function, ISD function obtains mutual support degree of sensors without the exponent calculation. Several experiments were finished to evaluate the accuracy and efficiency of DTWS-ISD with different performance metrics. The experimental results demonstrated that DTWS-ISD achieved better fusion precision than three existing functions in a real-world WSN water quality monitoring application.

Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke.

Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

Prognostic factors of primary resected retroperitoneal soft tissue sarcoma: Analysis from a single asian tertiary center and external validation of gronchi's nomogram.

BACKGROUND: Surgery is the potentially curative treatment for retroperitoneal sarcoma (RS), but complete resectability is frequently a challenge. This study aimed to characterize the clinical features, prognostic factors and treatment outcomes. METHODS: A cohort of 144 patients with RS was surveyed retrospectively from January 1st, 2000 to July 30th, 2011. The prognostic influence of clinicopathological characteristics as well as treatments on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS), were examined by univariate and multivariate analyses. A histology-specific nomogram developed by Gronchi et al was used for validation. RESULTS: Liposarcoma, leiomyosarcoma, and malignant peripheral sheath tumor (MPNST) were the most common histologies (70%). Multivariate analysis revealed FNCLCC tumor grade was the most significant prognostic factor for OS (P = 0.001) and DMFS (P < 0.001) and complete resection was the only significant prognostic factor for LRFS (P = 0.043). Incomplete resection of grade 3 tumor was significantly associated with a worse OS. Despite some differences in characteristics between our patients and Gronchi's cohort, external validation of Gronchi's nomogram demonstrated excellent concordance in predicting survival. CONCLUSIONS: Our study demonstrated tumor grade and surgical margins had significant prognostic influence and the Gronchi's nomogram has an excellent applicability in predicting survival of STS patients. J. Surg. Oncol. 2016;113:355-360. © 2016 Wiley Periodicals, Inc.

Spatial Temporal Dynamics and Molecular Evolution of Re-Emerging Rabies Virus in Taiwan.

Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10(-4)-4.75 × 10(-4) substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers.

Thyroid metastasis from breast cancer presenting with diffuse microcalcifications on sonography: a case report.

Microcalcifications are frequently associated with papillary thyroid cancers. Metastatic nodules from extrathyroid malignancies may mimic primary thyroid neoplasm on sonography, but do not present with microcalcifications. We report the case of a 45-year-old woman with a history of invasive ductal carcinomas of bilateral breasts, status post surgery and neoadjuvant chemotherapy. Four years after surgery, thyroid sonography revealed diffuse microcalcifications without nodular component. Core needle biopsy confirmed thyroid metastasis from primary breast cancer.

Research trends and perspective of low-intensity pulsed ultrasound in orthopedic rehabilitation treatment based on Web of Science: A bibliometric analysis.

BACKGROUND: Ultrasound has a long history as a diagnostic and therapeutic tool. Low-intensity pulsed ultrasound (LIPUS), whose intensity is below 300 mW/cm2, has been widely used in orthopedic rehabilitation treatment. However, the detailed bioeffects and underlying mechanisms of LIPUS treatment need to be explored. OBJECTIVE: To make a comprehensive view of the field, bibliometric and visualization analysis was used to reveal the global research trends of LIPUS in orthopedics and rehabilitation treatment between 1994 and 2023. METHODS: All literature data on LIPUS were retrieved from the Web of Science Core Collection database. VOSviewer and CiteSpace were applied for the bibliometric and visualization analysis. RESULTS: A total of 760 publications were included. The distribution of publications generally showed an unstable rising trend. China had the highest number of publications (28.0%), and Chong Qing Medical University was the organization with the highest number of publications (5.8%). Ultrasound in Medicine and Biology had the highest number of publications (8.8%), while BMJ-British Medical Journal had the highest impact factor among the retrieved journals. Ling Qin from the Chinese University of Hong Kong was the most active researcher. Our overlay visualization map showed that the keywords such as pain, knee osteoarthritis, apoptosis, chondrocytes, cartilage, and autophagy, which link to osteoarthritis, have becoming the new research trends and hotspots. CONCLUSION: LIPUS is a popular and increasingly important area of orthopedic rehabilitation, and collaboration of authors from different countries should be further strengthened. Predictably, clinical application of LIPUS on chronic inflammation-related diseases and regenerative medicine, and in-depth biological mechanisms are the orientations of LIPUS in orthopedic rehabilitation treatment.

Lymphatic vessels: roles and potential therapeutic intervention in rheumatoid arthritis and osteoarthritis.

Lymphatic vessel networks are a main part of the vertebrate cardiovascular system, which participate in various physiological and pathological processes via regulation of fluid transport and immunosurveillance. Targeting lymphatic vessels has become a potent strategy for treating various human diseases. The presence of varying degrees of inflammation in joints of rheumatoid arthritis (RA) and osteoarthritis (OA), characterized by heightened infiltration of inflammatory cells, increased levels of inflammatory factors, and activation of inflammatory signaling pathways, significantly contributes to the disruption of cartilage and bone homeostasis in arthritic conditions. Increasing evidence has demonstrated the pivotal role of lymphatic vessels in maintaining joint homeostasis, with their pathological alterations closely associated with the initiation and progression of inflammatory joint diseases. In this review, we provide a comprehensive overview of the evolving knowledge regarding the structural and functional aspects of lymphatic vessels in the pathogenesis of RA and OA. In addition, we summarized the potential regulatory mechanisms underlying the modulation of lymphatic function in maintaining joint homeostasis during inflammatory conditions, and further discuss the distinctions between RA and OA. Moreover, we describe therapeutic strategies for inflammatory arthritis based on lymphatic vessels, including the promotion of lymphangiogenesis, restoration of proper lymphatic vessel function through anti-inflammatory approaches, enhancement of lymphatic contractility and drainage, and alleviation of congestion within the lymphatic system through the elimination of inflammatory cells. At last, we envisage potential research perspectives and strategies to target lymphatic vessels in treating these inflammatory joint diseases.

The circUbqln1, regulated by XBP1s, interplays with 14-3-3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism.

INTRODUCTION: Osteoarthritis (OA) is a degenerative bone disease associated with ageing, characterized by joint pain, stiffness, swelling and deformation. Currently, pharmaceutical options for the clinical treatment of OA are very limited. Circular RNAs(cirRNAs) have garnered significant attention in OA and related drug development due to their unique RNA sequence characteristics.Therefore,exploring the role of cirRNAs in the occurrence and development of OA is of paramount importance for the development of effective medications for OA. OBJECTIVES: To identify a novel circRNA, circUbqln1, for treating osteoarthritis and elucidate its pathophysiological role and mechanisms in the treatment of OA. METHODS: The circUbqln1 expression and distribution were determined by qRT-PCR and FISH. XBP1 gene knockout(XBP1 cKO) spontaneous OA and DMM model and WT mouse CIOA model were used to explore the role of XBP1 and circUbqln1 in OA.Overexpression or knockdown of circUbqln1 lentivirus was used to observe the impacts of circUbqln1 on primary chondrocytes,C28/I2 and mice in vitro and in vivo.Chromatin immunoprecipitation,luciferase reporter assay,RNA pulldown,mass spectrometry,RNA immunoprecipitation,fluorescence in situ hybridization,and flow cytometry to explore the molecular mechanisms of circUbqln1. RESULTS: It was found that cartilage-specific XBP1 cKO mice exhibited a faster OA progression compared to normal's.Importantly,transcript factor XBP1s has the capacity to impede the biogenesis of circUbqln1,derived from Ubqln1. The circUbqln1 promotes cartilage catabolism and inhibits anabolism, therefore accelerates the occurrence of OA.Mechanismly,circUbqln1 can translocate to the chondrocyte nucleus with the assistance of phosphorylated 14-3-3ζ, upregulate the transcriptional activity of the proline dehydrogenase(Prodh) promoter and PRODH enzyme activity. Consequently, this leads to the promotion of proline degradation and the inhibition of collagen synthesis,ultimately culminating in the impairment of cartilage and its structural integrity. CONCLUSION: CircUbqln1 plays a crucial role in the occurrence and development of OA, indicating that the inhibition of circUbqln1 holds promise as a significant approach for treating OA in the future.

An Hsp70 promoter-based mouse for heat shock-induced gene modulation.

Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli. In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-dependent mutant FGFR2-P253R or BMP4 respectively, thereby facilitating the premature closure of cranial sutures or the repair of calvarial defects. This novel mouse line holds significant potential for investigating the underlying mechanisms of physical therapy, tissue repair and regeneration, lineage tracing, and targeted modulation of gene expression of cells in local tissue stimulated by physical factor at the interested time points. KEY MESSAGES: In the study, an Hsp70-CreERT2 transgenic mouse was generated for heat shock-induced gene modulation. Heat shock, ultrasound, and laser stimulation effectively activated Cre expression in Hsp70-CreERT2; reporter mice, which leads to deletion of floxed DNA sequence in the tail, ear, and cultured calvaria tissues of mice. Local laser stimuli on cultured calvarias effectively induce Fgfr2-P253R expression in Hsp70-mTmG-Fgfr2-P253R mice and result in accelerated premature closure of cranial suture. Heat shock activated AAV9-FLEX-BMP4 expression and subsequently promoted the repair of calvarial defect of Hsp70-CreERT2; Rosa26-mTmG mice.

A Novel Cargo Delivery System-AnCar-ExoLaIMTS Ameliorates Arthritis via Specifically Targeting Pro-Inflammatory Macrophages.

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-ExoLaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-ExoLaIMTS show obvious differences. The AnCar-ExoLaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-ExoLaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-ExoLaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases.

Significance of incorporation of model for end-stage liver disease score with TNM staging in patients with hepatocellular carcinoma undergoing hepatic resection.

BACKGROUND/AIMS: Currently, the tumor-node-metastasis (TNM) system is used in hepatectomy patients for tumor staging of HCC patients. However this can only evaluate the histopathological factor. MELD score is an objective measure for liver function widely used as a severity index for priority on the waiting list for liver transplantation. Here we suggest a modified TNM staging system based on the MELD score and test its relation with post-operative outcome of HCC. METHODOLOGY: We retrospectively collected 922 HCC patients undergoing hepatic resection, with TNM stage I (n=239), stage II (n=375) and stage III (n=308); giving points 0 to 2 for each stage (from I to III). Pre-operative MELD score was calculated and assigned 0 points for MELD <6; 1 for 6-8; 2 for >8. The two scores were added together to form a modified MELD-base TNM stage score and tested the correlation of this new scoring system with outcome after liver resection. RESULTS: The modified MELD-base TNM stage score resulted in score 0 (n=114), score 1 (n=247), score 2 (n=335), score 3 (n=164), and score 4 (n=62). The disease-free survival in each group showed significant difference (p<0.05), the lower the score, the better the outcome. CONCLUSIONS: The MELD-based TNM staging system reliably separates patients with HCC into homogeneous groups with respect to post-resectional prognosis. Further prospective validation studies are required to confirm the feasibility of this strategy.

Ultraviolet light C in promoting rapid healing of delayed wound union: A case report.

INTRODUCTION AND IMPORTANCE: The purpose of this case is to present a useful phototherapy for rapid healing of recalcitrant postoperative wound disunion due to implantation of allogeneic bone and metal. CASE PRESENTATION: In this case, a middle-aged man was diagnosed as complex fracture of the left tibial plateau which caused movement loss, swelling and pain of the left knee. The patient's wound disunion was still present after been surgery for 26 days, with yellowish liquid persistently oozing out of the wound after several wound dressing. We treated the postoperative wound with ultraviolet light C (UVC) to promote wound healing. CLINICAL DISCUSSION: Incision disunion is a common complication of surgery, which increases patients' hospital days. Prevention and treatment of wound disunion is one of the key considerations for perioperative management. CONCLUSION: During 3-day consecutive UVC treatment, the yellowish wound exudate gradually reduced and disappeared. Subsequently, the non-healing postoperative wound scared over and healed rapidly. As a convenient, non-invasive, non-polluting and effectively physical therapy, UVC can promote rapid healing of recalcitrant wound disunion caused by implants in complex tibial plateau fracture.

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis.

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.