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BACKGROUND Focal liver lesions (FLLs) are abnormal masses that are distinguishable from the surrounding liver parenchyma, solid or cystic and may be benign or malignant. They are usually detected incidentally on abdominal examinations. The classification of FLLs is very important as it directly determines the diagnosis and treatment of patients. CASE SUMMARY A 46-year-old male patient was admitted into the hospital with tarry stool, during the investigation of this issue an incidental FLL was detected. Upon further investigation of this “incidentaloma” computerized tomography and magnetic resonance imaging reached contradictory conclusions. The lesion was then further investigated using contrast-enhanced ultrasound (CEUS) with an initial diagnosis of idiopathic FLL was acquired and observation of the FLL over time need for final diagnosis, however in the follow up the FLL disappeared spontaneously. CONCLUSION CEUSs value for characterization of FLLs is undeniable, especially when other methods produce inconsistent results, is undeniable but with its limitations. Why and how the FLL disappeared is not known, and can be only hypothesized it was a pseudolesion.

We propose a new concept that utilizes the difference in Poisson's ratio between component materials as a strengthening mechanism that increases the effectiveness of the sacrificial bond toughening mechanism in macroscale double-network (Macro-DN) materials. These Macro-DN composites consist of a macroscopic skeleton imbedded within a soft elastic matrix. We varied the Poisson's ratio of the reinforcing skeleton by introducing auxetic or honeycomb functional structures that results in Poisson’s ratio mismatch between the skeleton and matrix. During uniaxial tensile experiments, high strength and toughness were achieved due to two events: (1) multiple internal bond fractures of the skeleton (like sacrificial bonds in classic DN gels) and (2) significant, biaxial deformation of the matrix imposed by the functional skeleton. The Macro-DN composite with auxetic skeleton exhibits up to 4.2 times higher stiffness and 4.4 times higher yield force than the sum of the component materials. The significant improvement in mechanical performance is correlated to the large mismatch in Poisson's ratio between component materials, and the enhancement is especially noticeable in the low-stretch regime. The strengthening mechanism reported here based on Poisson's ratio mismatch can be widely used for soft materials regardless of chemical composition and will improve the mechanical properties of elastomer and hydrogel systems.

Macromolecular crowding (MMC) in cells is a hot topic in biology; therefore, well-characterized measurement standards for the evaluation of the nano-environment in MMC solutions are necessary. We propose to use polarization-dependent fluorescence correlation spectroscopy (Pol-FCS) for evaluation of macromolecular crowding in solutions. Pol-FCS can simultaneously measure the relaxation times of rotational and translational diffusion of fluorescent molecules at the same position, even in living cells with low damage. In this report, the differences in the nano-environment among solutions of small molecules, gels, and MMC solutions were evaluated by comparing their rotational and translational diffusion using Pol-FCS. Moreover, this method could distinguish the phase shift in the polyethylene glycol solution. Finally, we separately evaluated the nano-environment in the cytosol and nucleus of living cells in different cell lines and cell cycles. We expect this evaluation method to be useful in characterizing the nano-environment in MMC studies. In addition, the proposed method may be useful for other nano-environments such as liquid–liquid phase separation.

The high water content of hydrogels makes them important as synthetic biomaterials, and tuning the mechanical properties of hydrogels to match those of natural tissues without changing chemistry is usually difficult. In this study, we have developed a series of hydrogels with varied stiffness, strength, and toughness based on a combination of poly(2-acrylamido-2-methylpropane sulfonic acid) (PAMPS), a strong acidic polyelectrolyte, and poly-N-(carboxymethyl)-N,N-dimethyl-2-(methacryloyloxy) ethanaminium) (PCDME), a polyzwitterion with a weak acidic moiety. We demonstrate that modifying the true molar ratio, R, of PCDME to PAMPS results in four unique categories of hydrogels with different swelling ratios and Young's moduli. When R 6.5, a tough and stiff double-network gel (DN) is formed. Both the PEC and DN gels exhibit high toughness and fracture stress, up to 1.8 and 1.5 MPa, respectively. Importantly, the PEC gels exhibit strong recovery properties along with high toughness, distinguishing them from DN gels. Without requiring a change in chemistry, we can tune the mechanical response of hydrogels over a wide spectrum, making this a useful system of soft and hydrated biomaterials.

Polyelectrolyte gels exhibit intrinsic salt-sensitive swelling behaviour, which causes size instability in ionic environments. Thus, polyelectrolyte gels that show salt-insensitive swelling have been anticipated for applications in ionic environments, such as medical materials used in vivo. We found that double-network (DN) gels consisting of both a polyelectrolyte network and a non-ionic network are resistant to salt-sensitive swelling. This resistance is attributed to their lower osmotic pressure originating from mobile ions relative to the osmotic pressure of mixing at swelling equilibrium. Our investigation indicated that the two contrasting network structures within the DN gels are vital for achieving these properties, where the structures include a highly prestretched and sparse polyelectrolyte network and a coiled and dense non-ionic network. The salt-insensitivity of the DN gels will lead to their unique applications in ionic environments.

Recently, we have developed a hydroxyapatite (HAp)-hybridized double-network (DN) hydrogel (HAp/DN gel), which can robustly bond to the bone tissue in the living body. The purpose of this study is to clarify whether the HAp/DN gel surface can differentiate the bone marrow-derived mesenchymal stem cells (MSCs) to osteogenic cells. We used the MSCs which were harvested from the rabbit bone marrow and cultured on the polystyrene (PS) dish using the autogenous serum-supplemented medium. First, we confirmed the properties of MSCs by evaluating colony forming unit capacity, expression of MSC markers using flow cytometry, and multidifferential capacity. Secondly, polymerase chain reaction analysis demonstrated that the HAp/DN gel surface significantly enhanced mRNA expression of the eight osteogenic markers (TGF-β1, BMP-2, Runx2, Col-1, ALP, OPN, BSP, and OCN) in the cultured MSCs at 7 days than the PS surfaces (p < 0.0001), while the DN gel and HAp surfaces provided no or only a slight effect on the expression of these markers except for Runx2. Additionally, the alkaline phosphatase activity was significantly higher in the cells cultured on the HAp/DN gel surface than in the other three material surfaces (p < 0.0001). Thirdly, when the HAp/DN gel plug was implanted into the rabbit bone marrow, MSC marker-positive cells were recruited in the tissue generated around the plug at 3 days, and Runx2 and OCN were highly expressed in these cells. In conclusion, this study demonstrated that the HAp/DN gel surface can differentiate the MSCs into osteogenic cells.

Nonalcoholic fatty liver disease (NAFLD) is the second major chronic liver disease world-wide and growing. Current medical treatment of NAFLD is not effective, and there is an urgent need to find new effective drugs. Liraglutide is now the first-line treatment for type 2 diabetes mellitus (T2DM) with promise, according to recent reports, to mitigate the fatty degeneration of the liver. The investigators of the current study discern if liraglutide reduces non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet using mice via modulating Kupffer cells M2 polarization in the liver. The mice underwent four weeks of intraperitoneal injections of liraglutide (0.6 mg/kg body weight). In the NAFLD model used in this study, the liver index, the body weight, and the serum levels of ALT, AST, total cholesterol, and triglycerides were meaningfully improved. In sections using H&E and Oil Red O staining, hepatic steatosis was significantly improved. Liraglutide decreased liver inflammation and the inflammatory properties of Kupffer cells in the NAFLD mouse model and there was a higher ratio of M2/M1 Kupffer cells. In vitro studies found that Liraglutide treatment modulates Kupffer cells to M2-like activation via the cAMP-PKA-STAT3 signaling pathway. The perilous effects of a high-fat diet were alleviated by liraglutide, including hepatic steatosis, by modulating Kupffer cells M2 polarization via the cAMP-PKA-STAT3 signaling pathway. Liraglutide can indeed reverse the negative effects of NAFLD.

Background: Ultrapurified alginate (UPAL) gel implantation has been demonstrated as effective in cartilage repair for osteochondral defects; however, cell transplantation within UPAL gels would be required to treat larger defects. Hypothesis: The combination of UPAL gel and bone marrow aspirate concentrate (BMAC) would enhance cartilage repair and subchondral bone repair for large osteochondral defects. Study Design: Controlled laboratory study. Methods: A total of 104 osteochondral defects (1 defect per knee) of 52 rabbits were randomly divided into 4 groups (26 defects per group): defects without any treatment (Defect group), defects treated using UPAL gel alone (UPAL group), defects treated using UPAL gel containing allogenic bone marrow mesenchymal stromal cells (UPAL-MSC group), and defects treated using UPAL gel containing BMAC (UPAL-BMAC group). At 4 and 16 weeks postoperatively, macroscopic and histologic evaluations and measurements of repaired subchondral bone volumes of reparative tissues were performed. Collagen orientation and mechanical properties of the reparative tissue were assessed at 16 weeks. Results: The defects in the UPAL-BMAC group were repaired with hyaline-like cartilage with well-organized collagen structures. The histologic scores at 4 weeks were significantly higher in the UPAL-BMAC group (16.9 ± 2.0) than in the Defect group (4.7 ± 1.9; P < .05), the UPAL group (10.0 ± 3.3; P < .05), and the UPAL-MSC group (12.2 ± 2.9; P < .05). At 16 weeks, the score in the UPAL-BMAC group (24.4 ± 1.7) was significantly higher than those in the Defect group (9.0 ± 3.7; P < .05), the UPAL group (14.2 ± 3.9; P < .05), and the UPAL-MSC group (16.3 ± 3.6; P < .05). At 4 and 16 weeks, the macroscopic evaluations were significantly superior in the UPAL-BMAC group compared with the other groups, and the values of repaired subchondral bone volumes in the UPAL-BMAC group were significantly higher than those in the Defect and UPAL groups. The mechanical properties of the reparative tissues were significantly better in the UPAL-BMAC group than in the other groups. Conclusion: The implantation of UPAL gel containing BMAC-enhanced hyaline-like cartilage repair and subchondral bone repair of osteochondral defects in a rabbit knee model. Clinical Relevance: These data support the potential clinical application of 1-step treatment for large osteochondral defects using biomaterial implantation with cell transplantation.

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that ~10%–19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%–27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.

Background and aim Hepatocellular carcinoma (HCC) urgently needs a marker for early diagnosis and targeted treatment. C2orf40 has been identified as a tumor suppressor gene in many cancers. However, the precise role and regulatory mechanism by C2orf40 contribute to HCC remain elusive and merit exploration. Methods Reverse-transcription PCR, quantitative real-time PCR, and methylation-specific PCR were used to detect expression and methylation of C2orf40 in HCC cell lines or tissues. The effects of C2orf40 in liver cancer cells were examined via colony formation, CCK8, transwell, and flow cytometric assays. The effect of C2orf40 on tumorigenesis in vivo was determined by xenografts and immunohistochemical analysis. Western blot, indirect immunofluorescence, Co-IP, and cycloheximide (CHX) were used to further investigate the potential mechanism of C2orf40. Results The down-regulation of C2orf40 in hepatocellular cancer tissue samples is often related to the degree of methylation of its promoter CpG. The recovery of C2orf40 expression in HCC cell lines can induce G0/G1 phase arrest and apoptosis and also inhibit cell migration and invasion by reversing the epithelial-mesenchymal transition (EMT) process, both in vivo and in vitro. In addition, C2orf40 can increase the expression of p21 through interaction with UBR5. Conclusions Low expression levels of C2orf40 are related to the hypermethylation of its promoter. C2orf40 can inhibit HCC through UBR5-dependent or p53-independent mechanisms. C2orf40 may be a diagnostic biomarker and a potential therapeutic target in HCC.

The double network (DN) gel is a rigid, tough, and safe hydrogel; however, like all hydrogels and existing particle embolization materials composed of a polymer, they lack X-ray visibility. Thus, it is not possible to locate the embolization material in the body. In this study, we successfully developed an X-ray-visible embolization material, a tough DN gel incorporated with biocompatible heavy metal powder. The DN gel particles, composed of poly(N,N'-dimethylacrylamide) and poly(2-acrylamido-2-methylpropanesulfonic acid) with tantalum powder, were synthesized via two-step suspension radical polymerization. The characteristics of the DN particles were evaluated by comparing them with Embosphere®, an existing embolization material. Furthermore, we used a rat carotid artery embolic model to evaluate the material’s X-ray computed tomography visibility in vivo. The developed embolization material was visible in X-ray computed tomography scans and safe for use in the body. Moreover, as it remained in the vessels for a long time, it is expected to be more effective than Embosphere®. Thus, the developed material is a promising DN particle embolization material with X-ray computed tomography visibility.

Background This study was designed to explore the prognostic and diagnostic value of Sex-Determining Region Y-Box 9 (SOX9) in cirrhotic hepatocellular carcinoma HCC (CHCC) and noncirrhotic hepatocellular carcinoma (NCHCC). Methods SOX9 tissue expression was detected using data from The Cancer Genome Atlas (TCGA) database and our cohort. The Kaplan-Meier method was used to analyze differences in survival between high/low SOX9 expression groups. Univariate analysis and multivariate analysis were used to identify independent risk factors associated with overall survival (OS). Receiver operating characteristic (ROC) curve and area under the curve (AUC) were utilized for evaluation of the diagnostic efficacy of SOX9. Results SOX9 was found to exhibit differential expression between HCC and adjacent normal tissues but not between CHCC and NCHCC, which was confirmed by RNA sequencing, quantitative real-time polymerase chain reaction and immunohistochemical staining. Kaplan-Meier survival analysis and multivariate analysis revealed that high SOX9 expression was closely related to the OS in NCHCC but not that in CHCC. In CHCC and NCHCC, SOX9 expression was positively associated with serum α-fetoprotein levels. The AUC of SOX9 in differentiating HCC and adjacent normal tissues in CHCC and NCHCC was 0.77 and 0.78, respectively, and no significant difference was found between them. Conclusions High SOX9 expression may aid prognostic evaluation in NCHCC but not in CHCC. SOX9 expression was not different between CHCC and NCHCC, but it has reliable and comparable diagnostic value in both CHCC and NCHCC.

Introduction: though endoscopic and percutaneous drainage have emerged as the most common minimally invasive treatments for pancreatic fluid collections (PFCs), estimates of therapeutic superiority for either treatment have yielded inconsistent results. Methods: we retrieved studies comparing the efficacy and safety of these two approaches in PubMed, Embase, and the Cochrane Library. Primary outcomes were differences in technical success, clinical success, and adverse events, and secondary outcomes included differences in reintervention, need for surgical intervention, mortality, recurrence rate, and length of hospital stay. Results: there were nonsignificant differences in technical success rate (OR 0.54; CI: 0.15-1.86), clinical success rate (OR 1.39; CI: 0.82-2.37), adverse events rate (OR 1.21; CI: 0.70-2.11), mortality rate (OR 0.81; CI: 0.30-2.16), and recurrence rate (OR 1.94; CI 0.74-5.07) between the two groups. Reintervention rate (OR 0.19; CI: 0.08-0.45) and percentage of need for surgical intervention (OR 0.08; CI: 0.02-0.39) in the endoscopic drainage group were much lower than in the percutaneous drainage group. Total length of hospital stay (standard mean difference [SMD] -0.60; CI: -0.84 to -0.36) in the endoscopic drainage group was shorter; however, there was a nonsignificant difference in the length of post-procedure hospital stay (SMD: -0.30; CI: -1.05-0.44) between the two groups. Conclusion: endoscopic drainage is effective for PFCs, and superior in terms of lower reintervention and need for surgery rates over traditional percutaneous drainage, despite a similar clinical efficacy and safety compared with traditional percutaneous drainage.

BackgroundCurrently, although Inula nervosa Wall is substantially investigated, little is understood about blossoms of Inula nervosa Wall (BINW).ObjectiveIn this work, we systematically investigated the antioxidant activity of the extract from BINW by various standard assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical ability, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) di-ammonium salt radical cation (ABTS), and ferric reducing antioxidant potential (FRAP).MethodsChemical compounds were tentatively identified through an UHPLC-QTOF-MS system. Furthermore, the contents of nine compounds were detected with UHPLC method coupled with photodiode array (PDA) detector. By carefully analyzing the quantitative data via clusters analysis and principal component analysis (PCA).ResultsForty-six compounds were tentatively identified, and our results showed that nine compound samples in 21 batches of BINW collected from different areas could be differentiated and analyzed by a heatmap visualization. In addition, the contents of nine compounds (flavonoids, phenolic acids) exhibited a total of higher amounts and better antioxidant activities from Yunnan than those from the other three origins.ConclusionsOur study not only developed a powerful platform to explain the difference between traditional Chinese medicines species that are closely related through the chemometric and chemical profiling, but also presented a useful method to establish quality criteria of BINW with multiple origins.HighlightsTo characterize the BINW in detail, we not only performed DPPH, FRAP, and ABTS assays to investigate its antioxidant activity, but also established UHPLC-QTOF-MS/MS- and UHPLC-PDA-based methods to comprehensively identify and qualitatively analyze its components.

Background: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT. Hypothesis: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity. Study Design: Controlled laboratory study. Methods: Seventy-five osteochondral defects in rabbits were divided into 3 groups: osteochondral defects with OAT alone, defects with OAT augmented by UPAL gel (combined group), and defects without intervention as controls. Macroscopic and histological evaluations of the reparative tissues were performed at 4 and 12 weeks postoperatively. Histological evaluation of graft cartilage degradation was also performed. To evaluate the effects of UPAL gel on graft healing, repaired bone volumes and osseointegration of the graft were evaluated. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were also evaluated qualitatively. Results: The macroscopic and histological evaluations of the combined group were significantly superior to the other groups at 12 weeks postoperatively. Regarding degenerative change of the graft, the histological scores of the combined group were significantly higher than those of the OAT-alone group. The values of repaired subchondral bone volumes and osseointegration of the graft were almost identical in both groups. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were significantly better in the combined group than in the other groups. Conclusion: Administration of UPAL gel in OAT enhanced cartilage repair and protected graft cartilage without inhibiting subchondral bone repair and graft survival. Clinical Relevance: OAT augmented by UPAL gel decreases the number and/or size of osteochondral grafts, minimizing the risk of donor site morbidity. This combination technique has the potential to improve clinical outcomes and expand the surgical indications for OAT.

Negatively charged synthetic hydrogels have been known to facilitate various cellular responses including cell adhesion, proliferation, and differentiation; however, the molecular mechanism of hydrogel-dependent control of cell behavior remains unclear. Recently, we reported that negatively charged poly(2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel induces chondrogenic differentiation of ATDC5 cells via novel protein reservoir function. In this study, we identified the cell adhesion molecules binding to PAMPS gels that act as mechanoreceptors. First, we performed a pull-down assay by particle gels using cell membrane proteins of ATDC5, and found that multiple membrane proteins bound to the PAMPS gel, whereas the uncharged poly(N,N'-dimethylacrylamide) gel as control did not bind to any membrane proteins. Western blot analysis indicated differential binding of integrin (ITG) isoforms to the PAMPS gel, in which the α4 isoform, but not α5 and αv, efficiently bound to the PAMPS gel. ITG α4 knockdown decreased cell spreading of ATDC5 on PAMPS gels, whereas the enhanced expression increased the behavior. Furthermore, ITG α4 depletion suppressed PAMPS gel-induced expression of bone morphogenic protein (BMP) 4 contributing to chondrogenic differentiation, in concordance with the reduction of ERK activation. These results demonstrated that membrane protein binding to PAMPS gels occurred in a charge-dependent manner, and that ITG α4 plays a crucial role in cell spreading on PAMPS gels and acts as a mechanoreceptor triggering cellular signaling leads to chondrogenic differentiation.

In this work, we intended to investigate the relationship between the swelling ratio Q and Young's modulus E of hydrogels from their contracted state to extreme swelling state and elucidate the underlining molecular mechanism. For this purpose, we used tetra-poly(ethylene glycol) (tetra-PEG) gel, whose network parameters are well known, as the polymer backbone, and we succeeded in tuning the swelling of the gel by a factor of 1500 times while maintaining the topological structure of the network unchanged, using an approach combining a molecular stent method and a PEG dehydration method. A master curve of Q-E, independent of the method of obtaining Q, was obtained. Using the worm-like chain model, the experimentally determined master curve can be well reproduced. We also observed that the uniaxial stress-strain curve of the hydrogel can be well predicted by the worm-like chain model using the structure parameters determined from the fitting of the Q-E experimental curve.

Novel, supramolecular, anisotropic hydrogels (called MC-PDGI gels) are presented in this study. These MC-PDGI gels consist of multi-cylindrical lipid bilayers aligned in a uniaxial manner and embedded in a soft hydrogel matrix. The bilayers and the hydrogel interact weakly due to hydrogen bonding. These MC-PDGI gels swell after exposure to water, which causes their volume and diameter to increase while simultaneously causing their length to decrease. This anisotropic swelling-induced contraction behavior is the result of competition between the isotropic elasticity of the hydrogel matrix and the interfacial tension of the lipid bilayers. Moreover, the MC-PDGI gels exhibit unique quasi one-dimensional diffusion behavior owing to the difficulty of molecular penetration through the multi-layered lipid bilayers. These materials would be useful for prolonged drug release or as an actuator.

Objective This study investigates operative techniques, treatment, and precaution for common complications of orthotopic liver transplantation (OLT) in rats. Methods OLT was performed in 110 rats through modified two-cuff method. Operative techniques were concluded, and causes, treatment, and precaution of common complications were analyzed. Results In operation phase, main causes for rat death included anesthesia, airway obstruction, pneumothorax, hemorrhagic shock, long anhepatic time, and air embolism. After surgery, main causes for rat death were as follows: stoma bleeding, infection, obstruction, and necrosis of biliary tract and poor hepatic function restoration. Conclusion Improving operative techniques, modifying operative methods, and familiarizing with common complications can reduce occurrence of complications, heighten operative successful rate, and establish more stable models of OLT in rats.

This meta-analysis aimed to explore the effectiveness of partial spleen arterial embolization (PSAE) in the treatment of hypersplenism secondary to hepatic cirrhosis. PubMed, Embase, Cochrane Library, Wan Fang, CNKI, Vip, and CBM databases were searched for randomized controlled trials, cohort studies, and case–control studies that compared PSAE with splenectomy in the treatment of hypersplenism secondary to hepatic cirrhosis from their inception to July 25, 2015. Statistical analysis was conducted in Cochrane Network RevMan v5.3. Primary outcomes included the pre- and postoperative platelet and leukocyte counts and hemoglobin levels. Secondary outcomes were operative time, intraoperative volume of bleeding, and length of hospital stay. Mean and standard deviation were obtained from each study and then pooled using fixed- or random-effects models to calculate the mean difference. Ten original studies investigating 737 patients were included. Both the PSAE group and the splenectomy group yielded higher postoperative platelet and leukocyte counts and hemoglobin levels than the preoperative. The difference of platelet and leukocyte counts and hemoglobin levels between postoperative and preoperative levels in the PSAE group was smaller than that in the splenectomy group. Besides, compared with the splenectomy group, the PSAE group exhibited shorter operative time, less intraoperative bleeding, and shorter length of stay. PSAE is a mini-invasive therapy, which can be applied to treat hypersplenism secondary to hepatic cirrhosis effectively, particularly for patients with a poor overall condition. However, further high-quality studies should be conducted because this meta-analysis is limited by the quality of studies and the large statistical heterogeneity.

Inspired by the toughening mechanism of double-network (DN) gels, tough hydrogel composites with a sandwich structure were fabricated from photoresponsive polymers. By copolymerization of hydrophilic monomers, 2-ureidoethyl methacrylate (UM), and photoresponsive hydrophobic monomers, (2-nitrobenzyloxycarbonylaminoethyl methacrylate (NBOC)) at high concentrations, physical hydrogels that are soft and highly stretchable are formed due to the hydrophobic associations of NBOC, serving as dynamic crosslinkers. By UV irradiation, the physical crosslinking switches into chemical crosslinking, and the soft physical hydrogels transform into rigid and less stretchable chemical hydrogels. By UV curing the surface layers of the physical hydrogels, we prepared hydrogel composites having a sandwiched structure with two rigid outer layers and a soft inner layer. The molecular-level continuous interfaces and matched swelling ratios between the layers ensure the macroscale hydrogel composites’ high strength and toughness with a DN gel effect. The outer layers fracture preferentially at deformation, playing a role like the first network of a DN gel, while the inner layer maintains the integrity, playing a role resembling the second network. The evolution of the fracture morphology of the rigid layers gives useful insight into the internal fracture process of DN gels.

International audience; experiencing solvent exchange from good to poor, a gel usually exhibits a monotonous deswelling with time if the good and poor solvents are miscible. [7-11] During this process, the good solvent easily escapes from gels driven by osmotic pressure of solvent-solvent mixing, while the poor solvent hardly enters the gel due to the demixing of polymer and poor solvent (Figure 1a). Here, we report an abnormal swelling of hydrophobic gels in water to form "hydrophobic hydrogels." We discovered that when hydrophobic gels swollen with omniphilic organic solvents are immersed in water or aqueous solutions, instead of shrinkage, the hydrophobic gels substantially swell to reach a water content as high as 99.6 wt% at most. The significant swelling of hydrophobic gels in water leads to the formation of a novel class of "hydro-phobic hydrogels" that have a unique fruit-like structure and show unique functions such as selective water absorption. To our knowledge, such abnormal swelling phenomenon of hydrophobic gels in water has never been reported before. This abnormal swelling is attributed to the rapid formation of a semipermeable skin layer on the surface of the gel by the phase separation of the hydrophobic polymer in water, which brings about a strongly asymmetrical diffusion for the organic solvent and water. The impermeable organic solvent is effectively trapped inside the gel, and thus generates a high osmotic pressure which drives the permeable Normally, a polymer network swells in a good solvent to form a gel but the gel shrinks in a poor solvent. Here, an abnormal phenomenon is reported: some hydrophobic gels significantly swell in water, reaching water content as high as 99.6 wt%. Such abnormal swelling behaviors in the nonsolvent water are observed universally for various hydrophobic organogels containing omniphilic organic solvents that have a higher affinity to water than to the hydrophobic polymers. The formation of a semipermeable skin layer due to rapid phase separation, and the asymmetric diffusion of water molecules into the gel driven by the high osmotic pressure of the organic solvent-water mixing, are found to be the reasons. As a result, the hydrophobic hydrogels have a fruit-like structure, consisting of hydrophobic skin and water-trapped micropores, to display various unique properties, such as significantly enhanced strength, surface hydrophobicity, and antidrying, despite their extremely high water content. Furthermore, the hydrophobic hydrogels exhibit selective water absorption from concentrated saline solutions and rapid water release at a small pressure like squeezing juices from fruits. These novel functions of hydrophobic hydrogels will find promising applications, e.g., as materials that can automatically take the fresh water from seawater. Polymer gels are defined as crosslinked polymer networks that are swollen in solvents. Since the last three decades, gels, especially water-based hydrogels, have embraced increasing interest for the numerous engineering and biological applications, including bioengineering, [1,2] adhesion, [3,4] soft robotics, [5] and 3D printing. [6] Ordinarily, a polymer network swells in a good solvent having a high affinity to polymer, forming a gel. When

The equilibrium swelling degree of a highly swollen charged gel has been thought to be determined by the balance between its elastic pressure and ionic osmotic pressure. However, the full experimental verification of this balance has not previously been conducted. In this study, we verified the balance between the elastic pressure and ionic osmotic pressure of charged gels using purely experimental methods. We used tetra-PEG gels created using the molecular stent method (St-tetra-PEG gels) as the highly swollen charged gels to precisely and separately control their network structure and charge density. The elastic pressure of the gels was measured through the indentation test, whereas the ionic osmotic pressure was determined by electric potential measurement without any strong assumptions or fittings. We confirmed that the two experimentally determined pressures of the St-tetra-PEG gels were well balanced at their swelling equilibrium, suggesting the validity of the aforementioned relationship. Furthermore, from single-strand level analysis, we investigated the structural requirements of the highly swollen charged gels in which the elasticity and ionic osmosis are balanced at their swelling equilibrium.

We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit osteochondral defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2 weeks, and the osteoid tissue was mineralized at 4 weeks. The push-out load of the HAp/DN gel averaged 37.54 N and 42.15 N at 4 and 12 weeks, respectively, while the push-out load of the DN gel averaged less than 5 N. The bonding area of the HAp/DN gel to the bone was above 80% by 4 weeks, and above 90% at 12 weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Statement of Significance Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage.

The purpose of this study was to clarify fundamental mechanical properties and biological responses of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. This study discovered the following facts. First, these hydrogels had high mechanical performance comparable to the native cartilage tissue, and the mechanical properties were not affected by immersion in the saline solution for 12 weeks. Secondly, the mechanical properties of the CS-DN gel were not significantly reduced at 12 weeks in vivo, while the mechanical properties of the HA-DN gel were significantly deteriorated at 6 weeks. Thirdly, the degree of inflammation around the HA-DN gel was the same as that around the negative control. The CS-DN gel showed a mild but significant foreign body reaction, which was significantly greater than the negative control and less than the positive control at 1 week, while the inflammation was reduced to the same level as the negative control at 4 and 6 weeks. Fourthly, these gels induced differentiation of the ATDC5 cells into chondrocytes in the culture with the insulin-free maintenance medium. These findings suggest that these tough hydrogels are potential biomaterials for future application to therapeutic implants such as artificial cartilage. Statement of Significance The present study reported fundamental biomaterial properties of the sodium hyaluronate-containing double network (HA-DN) gel and chondroitin sulfate-containing double network (CS-DN) gel, which were newly developed using the molecular stent method. Both the HA- and CS-DN gels had high mechanical properties comparable to the cartilage tissue and showed the ability to induce chondrogenic differentiation of ATDC5 cells in vitro. They are potential biomaterials that may meet the requirements of artificial cartilage concerning the material properties. Further, these DN gels can be also applied to the implantable inducer for cell-free cartilage regeneration therapy.

Paclitaxel has been widely used in the treatment of breast cancer. However, the development of drug resistance often increases the failure of chemotherapy. Growing evidence has reported the significant role of microRNAs (miRs) in drug resistance. The present study identified that miR-24 was significantly downregulated in paclitaxel-resistant (PR) breast cancer patients and in MCF-7/PR human breast carcinoma cells, and that overexpression of miR-24 could increase the effect of paclitaxel on drug-resistant breast carcinoma cells. Furthermore, miR-24 could directly bind to the 3'-untranslated region of ATP binding cassette B9 to downregulate its expression, thereby reducing drug transportation and improving the anti-tumor effect of paclitaxel on breast cancer cells. In vivo experiments also demonstrated that overexpression of miR-24 could increase the sensitivity of drug-resistant MCF-7 cells to paclitaxel. In conclusion, the present results suggested a novel function for miR-24 in reducing paclitaxel resistance in breast cancer, which may be of important clinical significance.

To compare the effectiveness and safety of single-port versus multi-port laparoscopic surgery for treating liver diseases. Several databases were systematically searched for randomized controlled trials, cohort studies, and case–control studies on the use of single-port versus multi-port laparoscopic surgery to treat liver diseases from their inception until March 24, 2016. The primary outcomes were the operative time, volume of intraoperative blood loss, rate of postoperative complications, median length of postoperative stay, recovery time of gastrointestinal function, volume of postoperative drainage, and postoperative drainage time. The study-specific effect sizes and their 95 % confidence interval were all combined to calculate the pooled value by using a random-effects model. A total of nine studies were included, which involved 277 patients. The total and subgroup data were combined by meta-analysis. This meta-analysis showed that single-port and multi-port laparoscopic liver surgery for treating liver diseases did not differ in terms of operative time (P = 0.48), rate of postoperative complications (P = 0.56), median length of postoperative stay (P = 0.80), and recovery time of gastrointestinal function (P = 0.54). For liver diseases, the single-port group exhibited a lower volume of intraoperative blood loss than that presented by the multi-port group (P = 0.0006). In the hepatic resection subgroup, a lower volume of intraoperative blood loss was noted in the single-port group (P

In this study, controlled amount of dangling ends is introduced to the two series of poly(ethylene glycol)-based hydrogel networks with three and four crosslinking functionality by using click chemistry. The structure of the gels with regulated defect percentage is confirmed by comparing the results of low-field NMR characterization and Monte Carlo simulation. The mechanical properties of these gels were characterized by tensile stress–strain behaviors of the gels, and the results are analyzed by Gent model and Mooney–Rivlin model. The shear modulus of the swollen gels is found to be dependent on the functionality of the network, and decreases with the defect percentage. Furthermore, the value of shear modulus well obeys the Phantom model for all the gels with varied percentage of the defects. The maximum extension ratio, obtained from the fitting of Gent model, is also found to be dependent on the functionality of the network, and does not change with the defect percentage, except at very high defect percentage. The value of the maximum extension ratio is between that predicted from Phantom model and the Affine model. This indicates that at the large deformation, the fluctuation of the crosslinking points is suppressed for some extend but still exists. Polymer volume fractions at various defect percentages obtained from prediction of Flory–Rehner model are found to be in well agreement with the swelling experiment. All these results indicate that click chemistry is a powerful method to regulate the network structure and mechanical properties of the gels. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016

Most studies on hydrogel swelling instability have been focused on a constrained boundary condition. In this paper, we studied the mechanical instability of a piece of disc-shaped hydrogel during free swelling. The fast swelling of the gel induces two swelling mismatches; a surface-inner layer mismatch and an annulus-disc mismatch, which lead to the formation of a surface crease pattern and a saddle-like bulk bending, respectively. For the first time, a stripe-like surface crease that is at a right angle on the two surfaces of the gel was observed. This stripe pattern is related to the mechanical coupling of surface instability and bulk bending, which is justified by investigating the swelling-induced surface pattern on thin hydrogel sheets fixed onto a saddle-shaped substrate prior to swelling. A theoretical mechanism based on an energy model was developed to show an anisotropic stripe-like surface crease pattern on a saddle-shaped surface. These results might be helpful to develop novel strategies for controlling crease patterns on soft and wet materials by changing their three-dimensional shape.

Liver is one of the organs with the highest injury rate, and in recent decades, the guidelines for the treatment of liver trauma have changed considerably. Now, there is a growing consensus that the most important step is diagnosis and depending upon the degree of severity, non-operative therapy is the main treatment method for hepatic trauma if conditions permit. For serious hepatic trauma patients such as those with hemodynamic instability, they should be operated upon as soon as possible. Regardless of the surgical options, doctors should control damage to patients and try to prevent complications. New therapies such as hepatic artery embolization and liver transplantation have been more and more used for the treatment of serious hepatic damage in clinics.

The purpose of this study was to establish the efficacy of a therapeutic strategy for an articular cartilage defect using a poly-(2-acrylamido-2-methylpropanesulfonic acid)/poly-(N,N'-dimethyl acrylamide) DN gel in a sheep model. Seventeen mature sheep were used in this study. We created a 6.0-mm osteochondral defect in the femoral trochlea of the patellofemoral (PF) joint and the medial condyle of the tibiofemoral (TF) joint. A cylindrical DN gel plug was implanted into the defect of the right knee so that a vacant space of the planned depths of 2.0 mm in group I, 3.0 mm in group II, and 4.0 mm in group III were left. In the left knee, we created a defect with the same depth as the right knee. The regenerated tissues were evaluated with the O'Driscoll score and real-time PCR analysis of the cartilage marker genes at 12 weeks. The DN gel implanted defect of group II in the PF and TF joints was completely filled with a sufficient volume of the proteoglycan-rich tissue stained with Safranin-O. The score showed that group II was significantly greater than groups I and III when treated with DN gel in the PF joint (p = 0.0441, p = 0.0174, respectively) and in the TF joint (p = 0.0019, p = 0.0006, respectively). This study has clarified the short-term efficacy of the cartilage regeneration strategy using the DN gel in a sheep model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2159-2165, 2016.

Background and Aim: The aim of this study was to compare the feasibility and safety of both balloon-occluded retrograde transvenous obliteration (BRTO) versus transjugular intrahepatic portosystemic shunt (TIPS) for treatment of gastric varices due to portal hypertension through the method of meta-analysis. Methods: PubMed, Embase, and Cochrane Library were searched for both randomized controlled trials and cohort studies concerning BRTO compared with TIPS in the treatment of gastric varices from their inception to April 26, 2015. The Cochrane network RevMan 5.3 software was used for statistic analysis. The primary markers that need to be evaluated contained technical success rate, hemostasis rate, incidence rate of postoperative rebleeding, incidence rate of hepatic encephalopathy, and postoperative procedure-related complication. Study-specific odds ratios (ORs) were combined to calculate pooled value by using random effects model. Results: Five original studies were included in total. Meta-analysis showed that BRTO and TIPS had no difference in aspects of technical success rate (OR, 0.19; 95% confidence interval [CI], 0.03–1.08; P = 0.06), hemostasis rate (OR, 3.41; 95% CI, 0.33–35.40; P = 0.30), and incidence rate of postoperative procedure-related complication (OR, 1.98; 95% CI, 0.44–8.84; P = 0.37). However, BRTO had a lower incidence rate of post-operative rebleeding (OR, 0.27; 95% CI, 0.09–0.81; P = 0.02) and a lower incidence rate of postoperative encephalopathy (OR, 0.05; 95% CI, 0.02–0.13; P

Oppositely charged homopolyelectrolytes were found to form strong, tough, and self-healing polyion-complex (PIC) hydrogels, similar to polyampholytes (PA) which have opposite charges randomly distributed on the same polymer chains. The excellent mechanical performances of these two novel hydrogels are the results of dynamic ionic bonds formation between entangled polymer chains. For the PIC system, only interchain bonding occurs, while for the PA system both inter- and intrachain bonding exist. In addition, the ion pairs are expected to form stronger bonding in the PIC system than those in the PA system. In this work, we performed a comparative study of PIC hydrogels with the PA hydrogels. The PIC hydrogels are synthesized by sequential homopolymerization of cationic and anionic monomers at varied formulation, and their swelling and mechanical properties are systematically studied in comparison to the PA hydrogels that were synthesized from random copolymerization of anionic monomers and cationic monomers of the similar formulation. Different from the PA system which only forms tough hydrogels around zero net charge composition without chemical cross-linking, the PIC system forms tough physical hydrogels even at weakly offbalanced charge composition. At the charge-balanced composition, the low entanglement concentration of homocharged polyelectrolyte chains leads to tough PIC hydrogels formation at much lower concentrations than that of PA hydrogels. As a result, the PIC hydrogels are much tougher than the PA hydrogels prepared at the same monomer composition. In similar to PA hydrogels, the PIC hydrogels also exhibit broad dynamic mechanical spectra, indicating the formation of ion complexes with widely ranged bond strength. The PIC hydrogels have strong viscoelasticity in comparison with PA hydrogels. However, the two systems show the similar activation energies of the dynamic mechanical spectra. The SEM microstructural observation shows that the PIC hydrogels have segregated structure while PA hydrogels are more homogeneous.

Tough double network (DN) hydrogels are promising substitutes of soft supporting tissues such as cartilage and ligaments. For such applications, it is indispensable to robustly fix the hydrogels to bones with medically feasible methods. Recently, robustly bonding the DN hydrogels to defected bones of rabbits in vivo has been proved successful. The low crystalline hydroxyapatite (HAp) of calcium-phosphate-hydroxide salt coated on the surface layer of the DN hydrogels induced spontaneous osteogenesis penetrating into the semi-permeable hydrogels to form a gel/bone composite layer. In this work, the 44 Ca isotope-doped HAp/DN hydrogel is implanted in a defect of rabbit femoral bone and the dynamic osteogenesis process at the gel/bone interface is analyzed by tracing the calcium isotope ratio using isotope microscopy. The synthetic HAp hybridized on the surface layer of DN gel dissolves rapidly in the first two weeks by inflammation, and then the immature bone with a gradient structure starts to form in the gel region, reutilizing the dissolved Ca ions. These results reveal, for the first time, that synthetic HAp is reutilized for osteogenesis. These facts help to understand the lifetime of bone absorbable materials and to elucidate the mechanism of spontaneous, non-toxic, but strong fixation of hydrogels to bones.

Mechanically robust hydrogels are promising biomaterials as artificial supportive tissue. These applications require selective and robust bonding of the hydrogels to living tissue. Recently, we achieved strong in vivo bone bonding of a tough double network (DN) hydrogel, a potential material for use as artificial cartilage and tendon, by hybridizing osteoconductive hydroxyapatite (HAp) in the gel surface layer. In this work, we report micro patterning of HAp at the surface of the DN hydrogel for selective osteoconduction. Utilizing the dissolution of HAp in an acidic environment, the soft lithography technique using an acid gel stamp was adopted to form a high-resolution HAp pattern on the gel. The HAp-patterned gel showed well-regulated migration and adhesion of cells in vitro. Moreover, the HAp-patterned gel showed selective and robust bonding to the rabbit bone tissue in vivo. This HAp soft lithography technique allows for simple and quick preparation of tailor-made osteoconductive hydrogels and can be applied to other hydrogels for selective bone bonding. STATEMENT OF SIGNIFICANCE: Hydrogels, preserving large amount of water, have been studied for next-generation artificial soft tissues. However, fixation of hydrogels to living tissue was unsolved issue for clinical application. Recently, we achieved robust bonding of a tough double network gel to bone in vivo by coating of osteoconductive hydroxyapatite in the gel surface layer. For further progress for practical use, we report the micro patterning of HAp at the surface of the DN hydrogel by using soft lithography technique, to perform selective bonding to only objective area without unnecessary coalescence. The HAp lithography technique is simple, quick and non-toxic method to prepare tailor-made osteoconductive hydrogels and has universality of species of hydrogels.

The purposes of this study were to identify signaling pathways that were specifically activated in ATDC5 cells cultured on poly (2-acrylamido-2-methylpropanesulfonic acid) (PAMPS) gel in insulin-free maintenance medium and to evaluate the significance of the determined signaling pathways in the chondrogenic differentiation induced by this gel. In this study, ATDC5 cells cultured on PAMPS gel using the maintenance medium without insulin (PAMPS Culture) were compared with cells cultured on polystyrene using the differentiation medium containing insulin (PS-I Culture). The microarray analysis, Western blot analysis, and real-time PCR analysis demonstrated that the TGF-β/BMP signaling pathway was significantly enhanced at Days 1, 2, and 3 in the PAMPS Culture when compared with the PS-I Culture. Inhibition of the BMP type-I receptor reduced the phosphorylation level of Smad1/5 and expression of type-2 collagen and aggrecan mRNA in the cells accompanied by a reduction in cell aggregation at Day 13 in the PAMPS Culture. The inhibition of the TGF-β/BMP signaling pathway significantly inhibited the chondrogenic differentiation induced by the PAMPS gel. The present study demonstrated that synthetic PAMPS gel activates the TGF-β/BMP/Smad signaling pathway in the ATDC5 cells in the absence of insulin, and that this activation plays a significant role in the chondrogenic differentiation induced by PAMPS gel. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 734-746, 2016.

Reinforcing hydrogels with a rigid scaffold is a promising method to greatly expand the mechanical and physical properties of hydrogels. One of the challenges of creating hydrogel composites is the significant stress that occurs due to swelling mismatch between the water-swollen hydrogel matrix and the rigid skeleton in aqueous media. This stress can cause physical deformation (wrinkling, buckling, or fracture), preventing the fabrication of robust composites. Here, a simple yet versatile method is introduced to create "macroscale" hydrogel composites, by utilizing a rigid reinforcing phase that can relieve stress-induced deformation. A low-melting-point alloy that can transform from a load-bearing solid state to a free-deformable liquid state at relatively low temperature is used as a reinforcing skeleton, which enables the release of any swelling mismatch, regardless of the matrix swelling degree in liquid media. This design can generally provide hydrogels with hybridized functions, including excellent mechanical properties, shape memory, and thermal healing, which are often difficult or impossible to achieve with single-component hydrogel systems. Furthermore, this technique enables controlled electrochemical reactions and channel-structure templating in hydrogel matrices. This work may play an important role in the future design of soft robots, wearable electronics, and biocompatible functional materials.

Bone tissues possess excellent mechanical properties such as compatibility between strength and flexibility and load bearing owing to the hybridization of organic/inorganic matters with anisotropic structure. To synthetically mimic such an anisotropic structure of natural organic/inorganic hybrid materials, we carried out hydroxyapatite (HAp) mineralization in stretched tough double network (DN) hydrogels. Anisotropic mineralization of HAp took place in stretched hydrogels, as revealed by high brightness synchrotron X-ray scattering and transmission electron microscopic observation. The c-axis of mineralized HAp aligned along the stretching direction, and the orientation degree S calculated from scattering profiles increased with increasing in the elongation ratio λ of the DN gel, and S at λ = 4 became comparable to that of rabbit tibial bones. The morphology of HAp polycrystal gradually changed from spherical to unidirectional rod-like shape with increased elongation ratio. A possible mechanism for the anisotropic mineralization is proposed, which would be one of the keys to develop mechanically anisotropic organic/inorganic hybrid materials.

Background There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal osteochondral defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of osteochondral defects. Methods A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter osteochondral defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm osteochondral defect in Group II, and a 5.8-mm osteochondral defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. Results The present study demonstrated that all sizes of the DN gel implanted defects as well as the 2.5mm untreated defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O’Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted defects than the untreated defects at 4 and 12 weeks (p

Portal vein thrombosis (PVT) frequently occurs in patients undergoing splenectomy because of liver cirrhosis. Whether the use of postoperative anticoagulants can decrease the incidence of PVT in these subjects is inconclusive. Moreover, the safety of the use of postoperative anticoagulants in the aforementioned patients is a concern. This meta-analysis aims to explore the effectiveness and safety of the preventive anticoagulants to prevent PVT in patients undergoing splenectomy because of liver cirrhosis. Four English language databases (i.e., PubMed, Embase, Cochrane Library, and Web of Science) and four Chinese language databases (i.e., Wanfang, CNKI, Cqvip, and CBM) were searched for randomized controlled trials, cohort studies, and case-control studies on the use of preventive anticoagulants to prevent PVT in patients undergoing splenectomy because of liver cirrhosis from their inception to September 15, 2015. The primary outcome was postoperative PVT incidence. The secondary outcomes included postoperative complications and adverse reaction. Study-specific odds ratios were combined to calculate pooled value through a fixed effects model. A total of 17 original studies were included, involving 1,497 patients. This meta-analysis showed that the preventive anticoagulant group had a lower incidence of PVT than the no anticoagulant group (odds ratio, 0.31; 95% confidence interval, 0.23–0.40; P < 0.05). According to the description of limited studies, the upper gastrointestinal hemorrhage mainly occurred in the no anticoagulant group. Meanwhile, the adverse reaction was trivial in the group using anticoagulants, which could easily be released with no special management. Postoperative anticoagulants can effectively decrease PVT incidence in subjects undergoing splenectomy because of liver cirrhosis. These published studies are more prone to show that no serious negative influence of anticoagulants exists in the aspect of safety. However, further studies are still needed.

To evaluate the efficacy and safety of ustekinumab in the therapy of plaque psoriasis.Literatures published up to November 2013 were collected from Cochrane library, MEDLINE, and PubMed which were related with ustekinumab for plaque psoriasis. The efficacy was estimated using relative risk of Psoriasis Area and Severity Index (PASI) 75 response rate at the week 12 endpoint in clinical trials, and adverse effects were also analyzed. Meta-analysis was carried out by using Review Manager 5.1.Six randomized control trials consistent with the inclusion criteria were selected and reviewed. Ustekinumab 45 mg group and 90 mg group could get better therapeutic effect compared with the placebo group (all P0.00001). Furthermore, ustekinumab 90 mg group was more effective than ustekinumab 45 mg group (P=0.01). Adverse effects in the 6 trials were mentioned including headache, upper respiratory tract infection, nasopharyngtis, infection, serious infection, cardiovascular events, and malignant tumors. There were no statistically significant differences of these adverse effects among three groups (all P0.05), except that infection rate in ustekinumab 45 mg group was higher than the placebo group (P=0.02).Ustekinumab is an effective and safe therapeutic method for plaque psoriasis. However, further longer time analysis of safety is needed.

Polyelectrolyte gels are charged polymer networks with macro-ions fixed on the polymer chains. These gels have considerable potential for biological applications such as cellular scaffolds and the replacement of various biological tissues. Moreover, high strength up to several tens of megapascals can be obtained with polyelectrolyte gels by incorporating double network structure in the gel. This article gives a concise review to introduce the fundamental properties of polyelectrolyte gels and biological applications for tissue engineering using their characteristic properties. Applications of polyelectrolyte gels have been highlighted in the fields of artificial muscle, artificial corneas, artificial cartilage, scaffolds for in vitro stem cell culture, and scaffolds for in vivo cartilage regeneration. This review suggests that polyelectrolyte gels would be a useful material for the successful replacement and regeneration of damaged or diseased tissues.

Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the osteochondral defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical osteochondral defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.

In this paper, we developed several kinds of ordered structures in hydrogels with different geometries and sizes by harnessing heterogeneous swelling induced mechanical instability, i.e., surface creasing, which leads to molecular orientations along the tensile direction. These hydrogels were synthesized by polymerization of a cationic monomer, N-[3-(N,N-dimethylamino)propyl] acrylamide methyl chloride quaternary (DMAPAA-Q) and a chemical cross-linker, in the presence of a small amount of the semirigid polyanion, poly(2,2′-disulfonyl-4,4′-benzidine terephthalamide) (PBDT), as dopant. During the swelling process of as-prepared gels, surface creasing occurs and induces formation of a lattice-like periodic ordered structure, which is maintained in the swollen gels due to the formation of strong polyion complex. Besides this structure formed at the central part of gel sheets, PBDTs align parallel to the gel boundary at the edge of gels with a cuboid, disk, or ring shape. The size of the two regions with diffe...

Our recent study has revealed that neutral polyampholytes form tough physical hydrogels above a critical concentration Cm,c by forming ionic bonds of wide strength distribution. In this work, we systematically investigate the behavior of a polyampholyte system, poly(NaSS-co-DMAEA-Q), randomly copolymerized from oppositely charged monomers, sodium p-styrenesulfonate (NaSS) and acryloyloxethyltrimethylammonium chloride (DMAEA-Q) without and with a slight chemical cross-linking. A phase diagram of formulation has been constructed in the space of monomer concentration Cm and cross-linker density CMBAA. Three phases are observed for the as-synthesized samples: homogeneous solution at dilute Cm, phase separation at semi-dilute Cm, and homogenous gel at concentrated Cm. Above a critical Cm,c, the polyampholyte forms a supramolecular hydrogel with high toughness by dialysis of the mobile counter-ions, which substantially stabilizes both the intra- and inter chain ionic bonds. The presence of the chemical cross-linker (CMBAA > 0) brings about a shift of the tough gel phase to lower Cm,c. The tough polyampholyte gel, containing [similar]50 wt% water, is highly stretchable and tough, exhibits fracture stress of σb [similar] 0.4 MPa, fracture strain of εb [similar] 30, and the work of extension at fracture Wext [similar] 4 MJ m−3. These values are at the level of most tough soft materials. Owing to the reversible ion bonds, the poly(NaSS-co-DMAEA-Q) gels also exhibit complete self-recovery (100%) and high fatigue resistance upon repeated large deformation.