A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

[Research status and prospect of tissue engineering technology in treatment of atrophic rhinitis].

Objective: To review the research progress of the feasibility of a new treatment method for atrophic rhinitis (ATR) based on tissue engineering technology (seed cells, scaffold materials, and growth factors), and provide new ideas for the treatment of ATR. Methods: The literature related to ATR was extensively reviewed. Focusing on the three aspects of seed cells, scaffold materials, and growth factors, the recent research progress of ATR treatment was reviewed, and the future directions of tissue engineering technology to treat ATR were proposed. Results: The pathogenesis and etiology of ATR are still unclear, and the effectiveness of the current treatments are still unsatisfactory. The construction of a cell-scaffold complex with sustained and controlled release of exogenous cytokines is expected to reverse the pathological changes of ATR, promoting the regeneration of normal nasal mucosa and reconstructing the atrophic turbinate. In recent years, the research progress of exosomes, three-dimensional printing, and organoids will promote the development of tissue engineering technology for ATR. Conclusion: Tissue engineering technology can provide a new treatment method for ATR.

Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Bioactive ECM-Loaded SIS Generated by the Optimized Decellularization Process Exhibits Skin Wound Healing Ability in Type I Diabetic Rats.

Patients with diabetes have 15-25% chance for developing diabetic ulcers as a severe complication and formidable challenge for clinicians. Conventional treatment for diabetic ulcers is to surgically remove the necrotic skin, clean the wound, and cover it with skin flaps. However, skin flap often has a limited efficacy, and its acquisition requires a second surgery, which may bring additional risk for the patient. Skin tissue engineering has brought a new solution for diabetic ulcers. Herein, we have developed a bioactive patch through a compound culture and the optimized decellularization strategy. The patch was prepared from porcine small intestinal submucosa (SIS) and modified by an extracellular matrix (ECM) derived from urine-derived stem cells (USCs), which have low immunogenicity while retaining cytokines for angiogenesis and tissue regeneration. The protocol included the optimization of the decellularization time and the establishment of the methods. Furthermore, the in vitro mechanism of wound healing ability of the patch was investigated, and its feasibility for skin wound healing was assessed through an antishrinkage full-thickness skin defect model in type I diabetic rats. As shown, the patch displayed comparable effectiveness to the USCs-loaded SIS. Our findings suggested that this optimized decellularization protocol may provide a strategy for cell-loaded scaffolds that require the removal of cellular material while retaining sufficient bioactive components in the ECM for further applications.

Leptin Promotes Angiogenesis via Pericyte STAT3 Pathway upon Intracerebral Hemorrhage.

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.

Analysis of the Risk Factors for Elevated D-Dimer Level After Breast Cancer Surgery: A Multicenter Study Based on Nursing Follow-Up Data.

D-dimer level is often used to assess the severity of trauma as well as the risk of thrombosis. This study investigated the risk factors for high postoperative D-dimer level. This study included a total of 2706 patients undergoing breast cancer surgery to examine the associations between various clinicopathological factors and variation in D-dimer levels. After adjusting for other factors, T stage, neoadjuvant chemotherapy, blood loss, surgery type, diabetes, and elevated leukocyte and neutrophil counts were found to be significant risk factors for D-dimer variation. This study identified several factors associated with elevated D-dimer levels and consequent thrombosis after breast cancer surgery, which may aid in the development of more precise preventive measures and interventions as well as serve as a reference for future research.

Shape-Recoverable Hyaluronic Acid-Waterborne Polyurethane Hybrid Cryogel Accelerates Hemostasis and Wound Healing.

Wound dressings that promote quick hemostasis and are highly efficient in healing wounds are urgently needed to meet the increase in clinical demands worldwide. Herein, a dihydrazide-modified waterborne biodegradable polyurethane emulsion (PU-ADH) and oxidized hyaluronic acid (OHA) were autonomously cross-linked to form a hybrid hyaluronic acid-polyurethane (HA-PU) cryogel by hydrazone bonding at -20 °C. Through its specific macroporous structure (which is approximately 220 µm) constructed by aggregated PU-ADH particles and long-chain OHA, a dried cryogel can have a dramatically compressed volume (1/7 of its original volume) with stable fixation, and it can swell rapidly by absorbing water or blood to approximately 22 and 16 times its dried weight, respectively, in a few minutes. This instantaneous shape-recovering ability favors fast hemostasis in minimally invasive surgery. Moreover, this cryogel is superior to gauze, has excellent biocompatibility, and quickly coagulates blood (in approximately 2 min) by activating the endogenous coagulation system. Comparably, an injectable HA-PU hydrogel with the same components as the HA-PU cryogel was prepared at room temperature, and it exhibited good self-healing properties. An in vivo evaluation of a rat liver hemostasis model and rat skin defect model revealed that the cryogel in fast hemostasis has great potential and superior wound-healing abilities, decreases immune inflammation, and promotes the regeneration of angiogenesis and hair follicles. Consequently, this work proposes a versatile method for constructing biodegradable hybrid cryogels via autonomous cross-linking between synthesized polymer emulsions and natural polymers. The hybrid cryogels demonstrated great potential for applications as high-performance wound dressings.

Tumor-derived IL-6 and trans-signaling among tumor, fat, and muscle mediate pancreatic cancer cachexia.

Most patients with pancreatic adenocarcinoma (PDAC) suffer cachexia; some do not. To model heterogeneity, we used patient-derived orthotopic xenografts. These phenocopied donor weight loss. Furthermore, muscle wasting correlated with mortality and murine IL-6, and human IL-6 associated with the greatest murine cachexia. In cell culture and mice, PDAC cells elicited adipocyte IL-6 expression and IL-6 plus IL-6 receptor (IL6R) in myocytes and blood. PDAC induced adipocyte lipolysis and muscle steatosis, dysmetabolism, and wasting. Depletion of IL-6 from malignant cells halved adipose wasting and abolished myosteatosis, dysmetabolism, and atrophy. In culture, adipocyte lipolysis required soluble (s)IL6R, while IL-6, sIL6R, or palmitate induced myotube atrophy. PDAC cells activated adipocytes to induce myotube wasting and activated myotubes to induce adipocyte lipolysis. Thus, PDAC cachexia results from tissue crosstalk via a feed-forward, IL-6 trans-signaling loop. Malignant cells signal via IL-6 to muscle and fat, muscle to fat via sIL6R, and fat to muscle via lipids and IL-6, all targetable mechanisms for treatment of cachexia.

Procyanidins-crosslinked small intestine submucosa: A bladder patch promotes smooth muscle regeneration and bladder function restoration in a rabbit model.

Currently the standard surgical treatment for bladder defects is augmentation cystoplasty with autologous tissues, which has many side effects. Biomaterials such as small intestine submucosa (SIS) can provide an alternative scaffold for the repair as bladder patches. Previous studies have shown that SIS could enhance the capacity and compliance of the bladder, but its application is hindered by issues like limited smooth muscle regeneration and stone formation since the fast degradation and poor mechanical properties of the SIS. Procyanidins (PC), a natural bio-crosslinking agent, has shown anti-calcification, anti-inflammatory and anti-oxidation properties. More importantly, PC and SIS can crosslink through hydrogen bonds, which may endow the material with enhanced mechanical property and stabilized functionalities. In this study, various concentrations of PC-crosslinked SIS (PC-SIS) were prepared to repair the full-thickness bladder defects, with an aim to reduce complications and enhance bladder functions. In vitro assays showed that the crosslinking has conferred the biomaterial with superior mechanical property and anti-calcification property, ability to promote smooth muscle cell adhesion and upregulate functional genes expression. Using a rabbit model with bladder defects, we demonstrated that the PC-SIS scaffold can rapidly promote in situ tissue regrowth and regeneration, in particular smooth muscle remodeling and improvement of urinary functions. The PC-SIS scaffold has therefore provided a promising material for the reconstruction of a functional bladder.

Hypoxic preconditioning of human urine-derived stem cell-laden small intestinal submucosa enhances wound healing potential.

BACKGROUND: Urine-derived stem cells (USCs) are a valuable stem cell source for tissue engineering because they can be harvested non-invasively. Small intestine submucosa (SIS) has been used as scaffolds for soft tissue repair in the clinic. However, the feasibility and efficacy of a combination of USCs and SIS for skin wound healing has not been reported. In this study, we created a tissue-engineered skin graft, termed the SIS+USC composite, and hypothesized that hypoxic preconditioning would improve its wound healing potential. METHODS: USCs were seeded on SIS membranes to fabricate the SIS+USC composites, which were then cultured in normoxia (21% O2) or preconditioned in hypoxia (1% O2) for 24 h, respectively. The viability and morphology of USCs, the expression of genes related to wound angiogenesis and reepithelialization, and the secretion of growth factors were determined in vitro. The wound healing ability of the SIS+USC composites was evaluated in a mouse full-thickness skin wound model. RESULTS: USCs showed good cell viability and morphology in both normoxia and hypoxic preconditioning groups. In vitro, hypoxic preconditioning enhanced not only the expression of genes related to wound angiogenesis (VEGF and Ang-2) and reepithelialization (bFGF and EGF) but also the secretion of growth factors (VEGF, EGF, and bFGF). In vivo, hypoxic preconditioning significantly improved the wound healing potential of the SIS+USC composites. It enhanced wound angiogenesis at the early stage of wound healing, promoted reepithelialization, and improved the deposition and remodeling of collagen fibers at the late stage of wound healing. CONCLUSIONS: Taken together, this study shows that hypoxic preconditioning provides an easy and efficient strategy to enhance the wound healing potential of the SIS+USC composite.

[Wound-induced hair follicle neogenesis: a new perspective on hair follicles regeneration in adult mammals].

OBJECTIVE: To explore the research progress of the cell sources and related signaling pathways of the wound-induced hair follicle neogenesis (WIHN) in recent years. METHODS: The literature related to WIHN in recent years was reviewed, and the cell sources and molecular mechanism were summarized and discussed. RESULTS: Current research shows that WIHN is a rare regeneration phenomenon in the skin of adult mammals, with multiple cell origins, both hair follicle stem cells and epithelial stem cells around the wound. Its molecular mechanism is complicated, which is regulated by many signaling pathways. Besides, the process is closely related to the immune response, the immunocytes and their related cytokines provide suitable conditions for this process. CONCLUSION: There are still many unsolved problems on the cellular origins and molecular mechanisms of the WIHN. Further study on the mechanisms will enhance the understanding of adult mammals' hair follicle regeneration and may provide new strategy for functional healing of the human skin.

Withaferin A alleviates traumatic brain injury induced secondary brain injury via suppressing apoptosis in endothelia cells and modulating activation in the microglia.

Traumatic brain injury (TBI) is a major public health concern with high rates of morbidity and mortality worldwide. Currently used medications, though effective, are also associated with several adverse effects. Development of effective neuroprotective agents with fewer side-effects would be of clinical value. Previous studies have shown that withaferin compounds have a potential neuroprotective effect in nervous system disorders. However, the effect of withaferin compounds, especially withaferin A (WFA), on traumatic brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether WFA could exert a neuroprotective effect after TBI and were used to explore the associated mechanisms. The results showed that WFA significantly improved neurobehavioral function in a dose-dependent fashion and alleviated histological alteration of injury to tissues in TBI mice. In vitro models of TBI revealed that dose-dependent WFA treatment increased the viability of SH-SY5Y cells. In addition, WFA treatment could attenuate blood-brain barrier disruption and brain edema via suppressing apoptosis in endothelial cells. Furthermore, both our in vivo and in vitro results reveal that WFA treatment could significantly reduce levels of several neuroinflammation cytokines (IL-1ß, IL-6, and TNF-α), which correlate with an overall reduction in microglial activation. These data suggest that the neuroprotection by WFA is, at least in part, related to regulation of microglial activation and inhibition of vascular endothelial cell apoptosis. Taken together, these findings support further investigation of WFA as a promising therapeutic agent for promoting functional recovery after traumatic brain injury.

Glutathione alleviates acute intracerebral hemorrhage injury via reversing mitochondrial dysfunction.

Glutathione (GSH) has been studied for its neuroprotection value in several diseases, but the effect of GSH on intracerebral hemorrhage (ICH) is unclear. In this study, we examined the protective effects of GSH in an experimentally induced ICH model and investigated the relative mechanisms. Adult male C57BL/6j mice were randomized into Sham, ICH and GSH treatment groups. GSH was injected with the dose of 50, 100 or 200 mg/kg once per day for 3 days, starting immediately after operation. The results revealed a GSH-mediated improvement of neurological deficits score (NDS), motor and sensory functions impairment in a dose-dependent manner three days post ICH (p < 0.01, GSH 200 vs ICH. Sham, n = 12; ICH, n = 9; GSH 50, n = 10; GSH 100, n = 10; GSH 200, n = 11) in addition to significantly reduced mortality rate (p = 0.2632, GSH 200 vs ICH. n = 12 per group) and damage volume (p < 0.05, GSH 200 vs ICH. n = 12 per group). GSH treatment also attenuated injury measured by decreased brain edema (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), blood-brain barrier disruption (p < 0.05, GSH 200 vs ICH. Sham, n = 10; ICH, n = 10; GSH 200, n = 12), and histopathological damage (p < 0.05, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) 72 h after ICH. In addition, GSH treatment also decreased cell apoptosis (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8) and resulted in up-regulated protein expression of complex I (p < 0.01, GSH 200 vs ICH. Sham, n = 6; ICH, n = 6; GSH 200, n = 8), which was consistent with an overall up-regulation of complex I function in mitochondria using Oxygraph-2 K high resolution respirometry (p < 0.05, GSH 200 vs ICH. Sham, n = 4; ICH, n = 5; GSH 200, n = 6). In conclusion, GSH effectively improved the prognosis of ICH mice by attenuating neurological impairment, decreasing neural damage, and inhibiting apoptosis. The neuroprotection by GSH resulted from the up-regulation of mitochondrial oxidative respiration function. The results of our study suggest that GSH can be a potential therapeutic agent for ICH.

The systemic activin response to pancreatic cancer: implications for effective cancer cachexia therapy.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal malignancy partly due to frequent, severe cachexia. Serum activin correlates with cachexia and mortality, while exogenous activin causes cachexia in mice. METHODS: Isoform-specific activin expression and activities were queried in human and murine tumours and PDAC models. Activin inhibition was by administration of soluble activin type IIB receptor (ACVR2B/Fc) and by use of skeletal muscle specific dominant negative ACVR2B expressing transgenic mice. Feed-forward activin expression and muscle wasting activity were tested in vivo and in vitro on myotubes. RESULTS: Murine PDAC tumour-derived cell lines expressed activin-ßA but not activin-ßB. Cachexia severity increased with activin expression. Orthotopic PDAC tumours expressed activins, induced activin expression by distant organs, and produced elevated serum activins. Soluble factors from PDAC elicited activin because conditioned medium from PDAC cells induced activin expression, activation of p38 MAP kinase, and atrophy of myotubes. The activin trap ACVR2B/Fc reduced tumour growth, prevented weight loss and muscle wasting, and prolonged survival in mice with orthotopic tumours made from activin-low cell lines. ACVR2B/Fc also reduced cachexia in mice with activin-high tumours. Activin inhibition did not affect activin expression in organs. Hypermuscular mice expressing dominant negative ACVR2B in muscle were protected for weight loss but not mortality when implanted with orthotopic tumours. Human tumours displayed staining for activin, and expression of the gene encoding activin-ßA (INHBA) correlated with mortality in patients with PDAC, while INHBB and other related factors did not. CONCLUSIONS: Pancreatic adenocarcinoma tumours are a source of activin and elicit a systemic activin response in hosts. Human tumours express activins and related factors, while mortality correlates with tumour activin A expression. PDAC tumours also choreograph a systemic activin response that induces organ-specific and gene-specific expression of activin isoforms and muscle wasting. Systemic blockade of activin signalling could preserve muscle and prolong survival, while skeletal muscle-specific activin blockade was only protective for weight loss. Our findings suggest the potential and need for gene-specific and organ-specific interventions. Finally, development of more effective cancer cachexia therapy might require identifying agents that effectively and/or selectively inhibit autocrine vs. paracrine activin signalling.

Establishment and Verification of a Bagged-Trees-Based Model for Prediction of Sentinel Lymph Node Metastasis for Early Breast Cancer Patients.

Purpose: Lymph node metastasis is a multifactorial event. Several scholars have developed nomograph models to predict the sentinel lymph nodes (SLN) metastasis before operation. According to the clinical and pathological characteristics of breast cancer patients, we use the new method to establish a more comprehensive model and add some new factors which have never been analyzed in the world and explored the prospect of its clinical application. Materials and methods: The clinicopathological data of 633 patients with breast cancer who underwent SLN examination from January 2011 to December 2014 were retrospectively analyzed. Because of the imbalance in data, we used smote algorithm to oversample the data to increase the balanced amount of data. Our study for the first time included the shape of the tumor and breast gland content. The location of the tumor was analyzed by the vector combining quadrant method, at the same time we use the method of simply using quadrant or vector for comparing. We also compared the predictive ability of building models through logistic regression and Bagged-Tree algorithm. The Bagged-Tree algorithm was used to categorize samples. The SMOTE-Bagged Tree algorithm and 5-fold cross-validation was used to established the prediction model. The clinical application value of the model in early breast cancer patients was evaluated by confusion matrix and the area under receiver operating characteristic (ROC) curve (AUC). Results: Our predictive model included 12 variables as follows: age, body mass index (BMI), quadrant, clock direction, the distance of tumor from the nipple, morphology of tumor molybdenum target, glandular content, tumor size, ER, PR, HER2, and Ki-67.Finally, our model obtained the AUC value of 0.801 and the accuracy of 70.3%.We used logistic regression to established the model, in the modeling and validation groups, the area under the curve (AUC) were 0.660 and 0.580.We used the vector combining quadrant method to analyze the original location of the tumor, which is more precise than simply using vector or quadrant (AUC 0.801 vs. 0.791 vs. 0.701, Accuracy 70.3 vs. 70.3 vs. 63.6%). Conclusions: Our model is more reliable and stable to assist doctors predict the SLN metastasis in breast cancer patients before operation.

Collagen Hydrogel Functionalized with Collagen-Targeting IFNA2b Shows Apoptotic Activity in Nude Mice with Xenografted Tumors.

Interferon alpha 2b (IFNA2b) has been used in immunotherapy for cancers with certain success. To reduce fast diffusion of IFNA2b and consequent dose-dependent side effects, we constructed a collagen hydrogel loaded with IFNA2b fused to collagen-binding domain by using methods of tissue engineering. The fusion protein showed apoptotic activity similar to that of native IFNA2b against MCF-7 cells in vitro, but with relatively higher affinity for collagen type I. Accordingly, the former diffused out of the collagen matrix slower than the latter. Importantly, collagen hydrogels loaded with the fusion protein possessed apoptotic activity in vitro and released the engineered cytokine in a controlled manner. In addition, such hydrogels reduced tumor size and extended the survival of the mouse model with xenografted tumors, which suggested a moderate antitumor activity in vivo.

Evaluation of Decellularized Bovine Tendon Sheets for Achilles Tendon Defect Reconstruction in a Rabbit Model.

BACKGROUND: Achilles tendon (AT) defects frequently occur in trauma and chronic injuries. Currently, no method can satisfactorily reconstruct the AT with completely restored function. PURPOSE: To evaluate the postoperative outcomes of AT defect reconstruction with decellularized bovine tendon sheets (DBTSs) in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: DBTSs were prepared from bovine tendons after compression, decellularization, antigen extraction, freeze drying, and sterilization. Platelet-rich plasma (PRP) was obtained by differential centrifugation. Sixty-three rabbits were used in this study, and the AT defect model was created bilaterally. All rabbits were divided into 3 groups (n = 21). In the DBTS group and the DBTS + PRP group, 2-cm-long AT was excised and reconstructed by DBTSs or PRP-treated DBTSs. In the control group, the rabbits underwent AT transection, and stumps were sutured. After surgery, all rabbits were assessed by ultrasonography and magnetic resonance imaging and then sacrificed for histological examination and biomechanical testing at 4, 8, or 12 weeks. RESULTS: Gross observations demonstrated the absence of immunologic incompatibility and rejection. Histological examination showed that DBTSs promoted host cell infiltration and new fibrous tissue integration as compared with the control group. In each group, there was an AT-like structure formation and aligned collagen fiber deposition at 12 weeks. Mechanical properties of the reconstructed AT were not significantly different among the 3 groups at 4, 8, and 12 weeks after surgery ( P > .05). Ultrasonography and magnetic resonance imaging results illustrated that the reconstructed AT from each group maintained remodeling, and there was no significant difference in the echogenicity scoring ( P > .05) and percentages of good and excellent ( P > .05) among the 3 groups. CONCLUSION: DBTSs, which retain the native tendon structure and bioactive factors, had the ability to remodel and integrate into the rabbit AT and improve the healing process. CLINICAL RELEVANCE: DBTSs could serve as an effective bioscaffold to reconstruct AT defects.

Improvements to the gastric cancer tumor-node-metastasis staging system based on computer-aided unsupervised clustering.

BACKGROUND: The Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) classification is a key gastric cancer prognosis system. This study aimed to create a new TNM system to provide a reference for the clinical diagnosis and treatment of gastric cancer. METHODS: A review of gastric cancer patients' records was conducted in The First Hospital of China Medical University and the Liaoning Cancer Hospital and Institute. Based on patients' prognoses data, computer-aided unsupervised clustering was performed for all possible TNM staging situations to create a new staging division system. RESULTS: The primary outcome measure was 5-year survival, analyzed according to TNM classifications. Computer-aided unsupervised clustering for all TNM staging situations was used to create TNM division criteria that were more consistent with clinical situations. Furthermore, unsupervised clustering for the number of lymph node metastasis in the N stage led to the formulation of a classification method that differs from the existing N stage criteria, and unsupervised clustering for tumor size provided an additional reference for prognosis estimates. CONCLUSIONS: Finally, we developed a TNM staging system based on the computer-aided unsupervised clustering method; this system was more in line with clinical prognosis data when compared with the 7th edition of UICC gastric cancer TNM classification.

Meloxicam increases epidermal growth factor receptor expression improving survival after hepatic resection in diet-induced obese mice.

BACKGROUND: Patients with fatty liver have delayed regenerative responses, increased hepatocellular injury, and increased risk for perioperative mortality. Currently, no clinical therapy exists to prevent liver failure or improve regeneration in patients with fatty liver. Previously we demonstrated that obese mice have markedly reduced levels of epidermal growth factor receptor in liver. We sought to identify pharmacologic agents to increase epidermal growth factor receptor expression to improve hepatic regeneration in the setting of fatty liver resection. METHODS: Lean (20% calories from fat) and diet-induced obese mice (60% calories from fat) were subjected to 70% or 80% hepatectomy. RESULTS: Using the BaseSpace Correlation Engine of deposited gene arrays we identified agents that increased hepatic epidermal growth factor receptor. Meloxicam was identified as inducing epidermal growth factor receptor expression across species. Meloxicam improved hepatic steatosis in diet-induced obese mice both grossly and histologically. Immunohistochemistry and Western blot analysis demonstrated that meloxicam pretreatment of diet-induced obese mice dramatically increased epidermal growth factor receptor protein expression in hepatocytes. After 70% hepatectomy, meloxicam pretreatment ameliorated liver injury and significantly accelerated mitotic rates of hepatocytes in obese mice. Recovery of liver mass was accelerated in obese mice pretreated with meloxicam (by 26% at 24 hours and 38% at 48 hours, respectively). After 80% hepatectomy, survival was dramatically increased with meloxicam treatment. CONCLUSION: Low epidermal growth factor receptor expression is a common feature of fatty liver disease. Meloxicam restores epidermal growth factor receptor expression in steatotic hepatocytes. Meloxicam pretreatment may be applied to improve outcome after fatty liver resection or transplantation with steatotic graft.

Predicting level 2 axillary lymph node metastasis in a Chinese breast cancer population post-neoadjuvant chemotherapy: development and assessment of a new predictive nomogram.

BACKGROUND: We aimed to develop a new nomogram to predict the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in breast cancer (BC) patients treated with neoadjuvant chemotherapy (NAC). METHODS: Data were collected from 709 patients who received neoadjuvant chemotherapy and then underwent axillary lymph node (ALN) dissection between May 2009 and December 2015 at the Liaoning Cancer Hospital. The level 2 axillary lymph node metastasis (L-2-ALNM ) nomogram was created from the logistic regression model. An additional set of 141 consecutive patients treated at the same institution between January 2015 and December 2015 were enrolled as the validation group. The predictive accuracy of the L-2-ALNM nomogram was measured by calculating the area under the receiver operating characteristic curve (AUC). RESULTS: In multivariate analysis, age, tumor size, histological grade, skin invasion, and response to neoadjuvant chemotherapy were identified as independent predictors of L-2-ALNM. The new model was accurate and discriminating for both the modeling and validation groups (AUC: 0.819 vs 0.849). The false-negative rates of the L-2-ALNM nomogram were 4.44% and 7.69% for the predicted probability cut-off points of 10% and 20%. CONCLUSION: The L-2-ALNM nomogram shows reasonable accuracy for making clinical decisions. The omission of level 2 axillary lymph node dissection after neoadjuvant chemotherapy might be possible if the probability of level 2 lymph node involvement was < 10% or < 20% in accordance with the acceptable risk determined by medical staff and patients.