Facilitating safe and sustained submucosal lift through an endoscopically injectable shear-thinning carboxymethyl starch sodium hydrogel.

Traditional submucosal filling materials frequently show insufficient lifting height and duration during clinical procedures. Here, the anionic polysaccharide polymer sodium carboxymethyl starch and cationic Laponite to prepare a hydrogel with excellent shear-thinning ability through physical cross-linking, so that it can achieve continuous improvement of the mucosal cushion through endoscopic injection. The results showed that the hydrogel (56.54 kPa) had a lower injection pressure compared to MucoUp (68.56 kPa). The height of submucosal lifting height produced by hydrogel was higher than MucoUp, and the height maintenance ability after 2 h was 3.20 times that of MucoUp. At the same time, the hydrogel also showed satisfactory degradability and biosafety, completely degrading within 200 h. The hemolysis rate is as low as 0.76 %, and the cell survival rate > 80 %. Subcutaneous implantation experiments confirmed that the hydrogel showed no obvious systemic toxicity. Animal experiments clearly demonstrated the in vivo feasibility of using hydrogels for submucosal uplift. Furthermore, successful endoscopic submucosal dissection was executed on a live pig stomach, affirming the capacity of hydrogel to safely and effectively facilitate submucosal dissection and mitigate adverse events, such as bleeding. These results indicate that shear-thinning hydrogels have a wide range applications as submucosal injection materials.

Metal-Organic Framework Glass Catalysts from Melting Glass-Forming Cobalt-Based Zeolitic Imidazolate Framework for Boosting Photoelectrochemical Water Oxidation.

Sluggish oxygen evolution kinetics and serious charge recombination restrict the development of photoelectrochemical (PEC) water splitting. The advancement of novel metal-organic frameworks (MOFs) catalysts bears practical significance for improving PEC water splitting performance. Herein, a MOF glass catalyst through melting glass-forming cobalt-based zeolitic imidazolate framework (Co-ag ZIF-62) was introduced on various metal oxide (MO: Fe2 O3 , WO3 and BiVO4 ) semiconductor substrates coupled with NiO hole transport layer, constructing the integrated Co-ag ZIF-62/NiO/MO photoanodes. Owing to the excellent conductivity, stability and open active sites of MOF glass, Co-ag ZIF-62/NiO/MO photoanodes exhibit a significantly enhanced photoelectrochemical water oxidation activity and stability in comparison to pristine MO photoanodes. From experimental analyses and density functional theory calculations, Co-ag ZIF-62 can effectively promote charge transfer and separation, improve carrier mobility, accelerate the kinetics of oxygen evolution reaction (OER), and thus improve PEC performance. This MOF glass not only serves as an excellent OER cocatalyst on tunable photoelectrodes, but also enables promising opportunities for PEC devices for solar energy conversion.

Conductive Hydrogel Patches with High Elasticity and Fatigue Resistance for Cardiac Microenvironment Remodeling.

Remodeling the conductive zone to assist normal myocardial contraction and relaxation during myocardial fibrosis has become the primary concern of myocardial infarction (MI) regeneration. Herein, we report an unbreakable and self-recoverable hyaluronic acid conductive cardiac patch for MI treatment, which can maintain structural integrity under mechanical load and integrate mechanical and electrical conduction and biological cues to restore cardiac electrical conduction and diastolic contraction function. Using the free carboxyl groups and aldehyde groups in the hydrogel system, excellent adhesion properties are achieved in the interface between the myocardial patch and the tissue, which can be closely integrated with the rabbit myocardial tissue, reducing the need for suture. Interestingly, the hydrogel patch exhibits sensitive conductivity (ΔR/R0 ≈ 2.5) for 100 cycles and mechanical stability for 500 continuous loading cycles without collapse, which allows the patch to withstand mechanical damage caused by sustained contraction and relaxation of the myocardial tissue. Moreover, considering the oxidative stress state caused by excessive ROS in the MI area, we incorporated Rg1 into the hydrogel to improve the abnormal myocardial microenvironment, which achieved more than 80% free radicalscavenging efficiency in the local infarcted region and promoted myocardial reconstruction. Overall, these Rg1-loaded conductive hydrogels with highly elastic fatigue resistance have great potential in restoring the abnormal electrical conduction pathway and promoting the myocardial microenvironment, thereby repairing the heart and improving the cardiac function.

Effectiveness of intraoperative peritoneal lavage with saline in patient with intra-abdominal infections: a systematic review and meta-analysis.

BACKGROUND: Intraoperative peritoneal lavage (IOPL) with saline has been widely used in surgical practice. However, the effectiveness of IOPL with saline in patients with intra-abdominal infections (IAIs) remains controversial. This study aims to systematically review randomized controlled trials (RCTs) evaluating the effectiveness of IOPL in patients with IAIs. METHODS: The databases of PubMed, Embase, Web of Science, Cochrane library, CNKI, WanFang, and CBM databases were searched from inception to December 31, 2022. Random-effects models were used to calculate the risk ratio (RR), mean difference, and standardized mean difference. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the quality of the evidence. RESULTS: Ten RCTs with 1318 participants were included, of which eight studies on appendicitis and two studies on peritonitis. Moderate-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (0% vs. 1.1%; RR, 0.31 [95% CI, 0.02-6.39]), intra-abdominal abscess (12.3% vs. 11.8%; RR, 1.02 [95% CI, 0.70-1.48]; I2 = 24%), incisional surgical site infections (3.3% vs. 3.8%; RR, 0.72 [95% CI, 0.18-2.86]; I2 = 50%), postoperative complication (11.0% vs. 13.2%; RR, 0.74 [95% CI, 0.39-1.41]; I2 = 64%), reoperation (2.9% vs. 1.7%; RR,1.71 [95% CI, 0.74-3.93]; I2 = 0%) and readmission (5.2% vs. 6.6%; RR, 0.95 [95% CI, 0.48-1.87]; I2 = 7%) in patients with appendicitis when compared to non-IOPL. Low-quality evidence showed that the use of IOPL with saline was not associated with a reduced risk of mortality (22.7% vs. 23.3%; RR, 0.97 [95% CI, 0.45-2.09], I2 = 0%) and intra-abdominal abscess (5.1% vs. 5.0%; RR, 1.05 [95% CI, 0.16-6.98], I2 = 0%) in patients with peritonitis when compared to non-IOPL. CONCLUSION: IOPL with saline use in patients with appendicitis was not associated with significantly decreased risk of mortality, intra-abdominal abscess, incisional surgical site infection, postoperative complication, reoperation, and readmission compared with non-IOPL. These findings do not support the routine use of IOPL with saline in patients with appendicitis. The benefits of IOPL for IAI caused by other types of abdominal infections need to be investigated.

Enzyme-regulated NO programmed to release from hydrogel-forming microneedles with endogenous/photodynamic synergistic antibacterial for diabetic wound healing.

The infection-prone wound pathology microenvironment leads to ulceration and difficult healing of diabetic wounds, which seriously affects the quality of survival of patients. In this study, natural polymer materials gelatin and polylysine were used as substrates. By introducing iron/tannic acid (FeIIITA) composite nanoparticles with excellent photothermal properties into the system, the glutamine residues of gelatin were crosslinked with the primary ammonia of polylysine by glutamine aminotransferase. A nanocomposite hydrogel with excellent antibacterial ability and NO production was constructed it was used to improve the clinical problems of diabetes wounds that were difficult to vascularize and easy to be infected. Under the premise of maintaining its structural stability, the hydrogel can be customized to meet the needs of different mechanical strengths by adjusting the ratios to match different diabetic wounds. Meanwhile, the photothermal effect of FeIIITA nanoparticles can synergize with the endogenous antibacterial ability of polylysine to improve the antibacterial efficacy of hydrogels. The potential of hydrogel to promote intracellular NO production was confirmed by fluorescent staining. Microneedle patches prepared from hydrogel can be applied to diabetic wounds, which can achieve NO deep release. Its anti-inflammatory and angiogenic abilities are also useful in achieving effective healing of diabetic wounds.

Mental health and self-management in glaucoma patients during the COVID-19 pandemic: a cross-sectional study in China.

PURPOSE: To investigate mental health and self-management in glaucoma patients during the COVID-19 pandemic in China and to describe the correlation between anxiety, depression, glaucoma, and self-management. METHODS: This cross-sectional study included glaucoma patients who enrolled in the case management platform and completed an online survey. The survey included the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and Glaucoma Self-Management Questionnaire (GSMQ). RESULTS: Among 109 glaucoma patients enrolled in this study, the proportions of patients suffering from depression and anxiety during the COVID-19 pandemic were 26.6% and 20.2%, respectively. A statistical association was found between depression and self-management behaviour in these glaucoma patients (r = -0.247, P = 0.010). The self-management scores in patients less than 35 years were lower than those in patients aged 35-60 years (P = 0.046). The scores of body function promotion in men were lower than those in women (P = 0.048). Patients with primary school education and below had lower scores in the medical management of disease than those with either middle school education (P = 0.032) or community college education or higher (P = 0.022). CONCLUSION: A high proportion of anxiety and depression was found in glaucoma patients during the COVID-19 pandemic. Better self-management behaviour was associated with stronger mental health regulation. It is important to help glaucoma patients improve their self-management behaviours, especially for young men with low educational levels.

Thyroid eye disease or Graves' orbitopathy: What name to use, and why it matters.

There is currently no universally accepted name for inflammatory disease of the eye and orbit associated with thyroid autoimmune disease. Variability in terminology impedes the evaluation of scientific literature and clinical collaboration and can affect patients' understanding of a disease process. The goals of this perspective article are 1. To compare the frequency of different terms used for eye disease associated with autoimmune thyroid disease in the scientific literature between 2000, 2010 and 2020 publications; 2. To investigate potential associations of terminology with author and journal specialty, and multidisciplinary vs. mono-disciplinary author teams; 3. To determine preferential terms used by professional societies; and 4. To propose standardized terminology based on our data analysis. The methods for this study included review of all English language articles listed in PubMed, with publication dates in the years 2000, 2010 and 2020, that included one of 6 terms currently used to describe eye disease associated with autoimmune thyroid disease. Characteristics pertaining to authors, journals, and article type were recorded. Results showed that the most used term in the 2000 literature was Graves' Ophthalmopathy (61%). In the 2010 literature, Graves' Orbitopathy (31%) became most common, followed by Graves' Ophthalmopathy (30%). Between 2010 and 2020, thyroid eye disease (37%) became the most common term, followed by Graves' Orbitopathy (35%). This perspective article proposes "thyroid eye disease" (TED) as the preferred name for this entity and discusses supporting terminology patterns and trends over time in scientific literature and in professional societies.

An Artificial-Intelligence-Based Automated Grading and Lesions Segmentation System for Myopic Maculopathy Based on Color Fundus Photographs.

Purpose: To develop deep learning models based on color fundus photographs that can automatically grade myopic maculopathy, diagnose pathologic myopia, and identify and segment myopia-related lesions. Methods: Photographs were graded and annotated by four ophthalmologists and were then divided into a high-consistency subgroup or a low-consistency subgroup according to the consistency between the results of the graders. ResNet-50 network was used to develop the classification model, and DeepLabv3+ network was used to develop the segmentation model for lesion identification. The two models were then combined to develop the classification-and-segmentation-based co-decision model. Results: This study included 1395 color fundus photographs from 895 patients. The grading accuracy of the co-decision model was 0.9370, and the quadratic-weighted κ coefficient was 0.9651; the co-decision model achieved an area under the receiver operating characteristic curve of 0.9980 in diagnosing pathologic myopia. The photograph-level F1 values of the segmentation model identifying optic disc, peripapillary atrophy, diffuse atrophy, patchy atrophy, and macular atrophy were all >0.95; the pixel-level F1 values for segmenting optic disc and peripapillary atrophy were both >0.9; the pixel-level F1 values for segmenting diffuse atrophy, patchy atrophy, and macular atrophy were all >0.8; and the photograph-level recall/sensitivity for detecting lacquer cracks was 0.9230. Conclusions: The models could accurately and automatically grade myopic maculopathy, diagnose pathologic myopia, and identify and monitor progression of the lesions. Translational Relevance: The models can potentially help with the diagnosis, screening, and follow-up for pathologic myopic in clinical practice.

Vision-related quality of life in patients with glaucoma: the role of illness perceptions.

PURPOSE: To explore the predictive effects of illness perceptions on vision-related quality of life (VRQoL) in Chinese glaucoma patients. METHODS: In this cross-sectional study, 97 patients with glaucoma completed the brief illness perception questionnaire (BIPQ), the glaucoma quality of life-15 (GQL-15) questionnaire, and a questionnaire regarding sociodemographic and clinical information. A correlation analysis and hierarchical linear regression analysis were performed. RESULTS: The BIPQ total score was positively correlated with the total score of the GQL-15 questionnaire and the scores of its four dimensions. Chronic comorbidities, the type of glaucoma, the best-corrected visual acuity (BCVA), the mean defect (MD) of visual field in the better eye, and identity in the BIPQ were critical predictors of VRQoL. Illness perceptions independently accounted for 7.8% of the variance in the VRQoL of glaucoma patients. CONCLUSIONS: Patients with stronger illness perceptions and those who perceive themselves as having more glaucoma symptoms are likely to experience worse VRQoL. Illness perceptions in glaucoma patients deserve clinical attention, and further studies are needed to examine whether cognitive interventions targeting illness perceptions can improve VRQoL.

Bio-inspired hydrogel-based bandage with robust adhesive and antibacterial abilities for skin closure.

Although conventional suturing techniques are commonly used in assisting wound closure, they do pose limited conduciveness and may lead to secondary injury to wound tissues. Inspired by marine organism mussels, we designed and manufactured a bio-inspired hydrogel-based bandage with tough wet tissue adhesion to substitute traditional surgical suture, accelerate wound healing and avoid infection. Poly(γ-glutamic acid) was modified with 3,4-dihydroxyphenylalanine and glycidyl methacylate, then introduced into the acrylic acid-co-acrylamide hydrogel matrix with robust mechanical properties. The hydrogel bandage showed strong chemical linkage adhesion (70 ± 2.1 kPa), which is 2.8 times that of commercial tissue adhesive fibrin glue (25 ± 2.2 kPa). The hydrogel bandage can not only maintain the self-stability, but is also capable of self-tuning adhesive strength in the range of 14-70 kPa to achieve different adhesion effects by tuning constituent ratio. The bandage has desirable compression properties (0.7 ± 0.11 MPa) and tensile elongation (about 25 times), which ensures its resistance to damages, especially in joint spaces. Secondly, the bandage was endowed with antioxidant and endogenous broad-spectrum antibacterial properties with its catechol structure. Results also demonstrated excellent cell compatibility and blood compatibility, certifying its eligible biological safety profile. In a rat full-thickness cutaneous deficiency model, we can clearly observe that the bandage possesses the ability to promote wound healing (only need 6 days). Above all, this research provides a new strategy for the emergency treatment of liver hemostasis and myocardial repair during disaster rescue. SUPPLEMENTARY INFORMATION: Experimental details and supporting data are available in the online version of the paper10.1007/s40843-021-1724-8.

Dynamic regulable sodium alginate/poly(γ-glutamic acid) hybrid hydrogels promoted chondrogenic differentiation of stem cells.

Traditional hydrogels often fail to match the dynamic interactions between mechanical and cellular behaviors exhibited by the natural cartilage extracellular matrix. In this research, we constructed a novel hybrid hydrogels system based on sodium alginate and polyglutamic acid. By controlling the grafting rate and concentration of polymer, the gelation time and mechanical strength can be adjusted between range of 8-28 s and 60-144 kPa. By adding microcrystalline cellulose into the system, so that the degradation time was prolonged (125%) and the swelling rate was reduced (470%). Additionally, the presence of hydrazone bonds gives the system some dynamic response characteristics, and the hydrogel exhibits excellent self healing and injectable ability. It was found that the system had positive cytocompatibility (80%), which accelerated regulatory gene expression in cartilage tissue. In conclusion, this injectable hydrogel with self-healing and customizable mechanical strength will have broad application prospects in future biomedical engineering.

Gradient chondroitin sulfate/poly (γ-glutamic acid) hydrogels inducing differentiation of stem cells for cartilage tissue engineering.

Based on the gradient distribution of structure and composition in biological cartilage tissue, we designed a gradient hydrogel scaffold by the moving photomask, using chondroitin sulfate and poly (γ-glutamic acid) as crude materials. The hydrogel scaffold had a gradient distribution of cross-linking density, which can be verified from the results of SEM and swelling behavior. Besides, the hydrogel exhibited great viscoelastic, toughness (70% strain), and strength properties (600 kPa). Additionally, the gradient hydrogel's superior cell compatibility was proved through the MTT, live/dead staining assays, and 3D cell culture experiments. Remarkably, the results of in vitro stem cell differentiation experiments showed that the duration of light directly affected the differentiation extent of stem cells, demonstrating that the gradient hydrogel scaffold can better simulate the function of natural cartilage than the homogeneous one. Due to these outstanding characteristics, this gradient hydrogel is a potential scaffold for cartilage tissue engineering.

Bioinspired mineral-polymeric hybrid hyaluronic acid/poly (γ-glutamic acid) hydrogels as tunable scaffolds for stem cells differentiation.

Aiming at the difficulty of integrated repair of osteochondral tissue, we designed a hybrid hydrogel scaffold that mimicked the microenvironment of osteochondral niches. Besides, the nano-hydroxyapatite (nHAP) was specially introduced into the hydrogel for its natural ability to promote bone regeneration. The hydrogel also exhibited good toughness (7500 KJ/m3), strength (1000 kPa), viscoelasticity, and in vitro cell experiments showed that hydrogels had quite good cytocompatibility (near 100 % viability). The results of the three-dimensional (3D) cell culture also proved that the survival rate of the cells in the hybrid hydrogels doped with nHAP and dispersion were the highest. In vitro RT-qPCR experiments proved that after being cultured in hydrogel scaffolds doped with nHAP, bone mesenchymal stem cells (BMSCs) could express genes related to osteoblasts and chondrocytes. As a result, this hydrogel provides a general for developing alternative materials applicable for stem cells differentiation and even osteochondral tissue engineering.

Injectable adaptive self-healing hyaluronic acid/poly (γ-glutamic acid) hydrogel for cutaneous wound healing.

The most significant challenge in designing wound dressings is to mimic the tissue microenvironment because of the pro-regenerative structural and functional properties of skin. Herein, we developed a type of bionic extracellular matrix (ECM) hydrogels based on thiol-modified poly (γ-glutamic acid) (γ-PGA-SH) and oxidized hyaluronic acid (HA-CHO). The rapid and reversible thiol-aldehyde addition reaction of thiols in γ-PGA-SH and aldehyde groups in HA-CHO provided hydrogels with a dynamic covalent network and endowed them with properties of adaptability and self-healing capability, which are conducive for initial wound coverage and for prolonging the lifespan of the dressing. Interestingly, these hydrogels also showed typical viscoelastic characteristics similar to those of natural ECM, degradation property in vitro and in vivo, and free radical scavenging capability. In addition, the gelation time, rheological behavior, mechanical property, porous structure, and degradation process of the hydrogels could be tuned by adjusting polymer content. Furthermore, the ECM-inspired hydrogels significantly enhanced the wound healing process in vivo in a full-thickness skin defect model compared to those by commercial dressing (Tegaderm™) by facilitating angiogenesis and promoting collagen deposition. The successful application of the multifunctional hydrogel as an antioxidant wound dressing for wound treatment significantly exhibited its great application potential for biomedical areas. STATEMENT OF SIGNIFICANCE: The application of tissue engineering techniques to repair full-thickness skin wounds remains a great challenge in clinical trials. Among the recent approaches used for wound healing, in situ forming injectable hydrogels have gained much attention, and few of them have shown satisfactory overall performance, such as integration into the wound bed, biodegradability, immunocompatibility, vascularization, and recapitulation of the structure and function of skin. In the present study, we designed a simple and convenient in situ forming injectable adaptable self-healing hydrogels with biodegradability and antioxidative properties, which could substantially improve wound healing quality at an affordable cost. The hydrogel-based wound dressing is expected to solve the abovementioned problems and help in promoting cutaneous wound healing.

Biomimetic poly(γ-glutamic acid) hydrogels based on iron (III) ligand coordination for cartilage tissue engineering.

For the problems in the research on differentiation of mesenchymal stem cells (BMSCs), such as poor differentiation tendency and low differentiation efficiency, a novel photo-crosslinked extracellular matrix (ECM) inspired double network hydrogel that composed of poly(γ-glutamic acid) (γ-PGA) hydrogel and Fe3+ ligand coordination was designed and manufactured. Compared with those traditional γ-PGA based hydrogels, the introduction of Fe3+ significantly enhanced the mechanical properties of the hydrogel and accelerated the chondrogenesis efficiency of BMSCs chondrogenesis. The experimental results confirmed that the mechanical properties of hydrogel enhanced by the introduction of metal ions Fe3+ could promote BMSCs proliferation, induce cartilage-specific gene expression, and increase secretion of hydroxyproline (HYP) and glycosaminoglycan (GAG). As a result, this method could promote chondrogenic differentiation of BMSCs, accelerate the regeneration of cartilage, and was prospective to be conducive to the research work of cartilage defect repair. Thus, the mechanically enhanced γ-PGA hydrogel scaffold by Fe3+ could mediate BMSCs differentiation and provide a scientific and theoretical basis for research and development of biomedical materials on cartilage tissue engineering field.

Marine-inspired molecular mimicry generates a drug-free, but immunogenic hydrogel adhesive protecting surgical anastomosis.

Herein, we report the synthesis of a biomimic hydrogel adhesive that addresses the poor healing of surgical anastomosis. Dopamine-conjugated xanthan gum (Da-g-Xan) is fabricated using deep insights into the molecular similarity between mussels' adhesive and dopamine as well as the structural similarity between barnacle cement proteins and xanthan gum. The hydrogel mimics marine animals' adherence to wet tissue surfaces. Upon applying this adhesive to colonic anastomosis in a rat model, protective effects were shown by significantly improving the bursting pressure. Mechanistically, the architecture of Da-g-Xan hydrogel is maintained by dynamic intermolecular hydrogen bonds that allow the quick release of Da-g-Xan. The free Da-g-Xan can regulate the inflammatory status and induce type 2 macrophage polarization (M2) by specifically interacting with mannose receptors (CD206) revealed by RNA-sequencing and molecular binding assays. Consequently, an appropriate microenvironment for tissue healing is created by the secretion of chemokines and growth factors from M2 macrophages, strengthening the fibroblast migration and proliferation, collagen synthesis and epithelial vascularization. Overall, this study demonstrates an unprecedented strategy for generating an adhesive by synergistic mimicry inspired by two marine animals, and the results show that the Da-g-Xan adhesive augments native tissue regenerative responses, thus enabling enhanced recovery following surgical anastomosis.

Early Enteral Nutrition Preserves Intestinal Barrier Function through Reducing the Formation of Neutrophil Extracellular Traps (NETs) in Critically Ill Surgical Patients.

BACKGROUND: The gut was suggested as the driver of critical illness and organ injury. Recently, excessive formation of neutrophil extracellular traps (NETs) was associated with mucosal inflammation. Direct investigation of intestinal mucosa is essential to illuminate the potential mechanism of gut barrier in critically ill patients. We hypothesized that early enteral nutrition (EN) could decrease intestinal NETs and maintain the gut barrier. METHODS: Intestinal biopsies were obtained using biopsy forceps from critically ill surgical patients complicated with enterocutaneous fistula. Expressions of tight junction (TJ) proteins, mucosal inflammation, and apoptosis were evaluated. Moreover, NET-associated proteins were evaluated in intestinal specimens of patients by Western blot and immunofluorescence analysis. RESULTS: The intestinal barrier was significantly impaired in critically ill patients receiving early total parenteral nutrition (TPN), evidenced by intestinal villi atrophy, inflammatory infiltration, increased enterocyte apoptosis, and abnormal TJ expressions. Early EN significantly alleviated these intestinal injuries. In addition, we observed increased formation of the NET structure and elevated expressions of NET-associated proteins in intestines of critically ill surgical patients. Early EN was associated with the diminished presence of NETs and reduced expression of NET-associated proteins. Mechanically, analysis of the TLR4 pathway showed a significant increase in TLR4, NFκB, and MAPK signaling in patients receiving TPN when compared to those receiving early EN. CONCLUSION: The intestinal barrier is disrupted in the human gut during critical illness. Our data suggests that an increased NET structure was showed in the gut of critically ill surgical patients, and early EN treatment was associated with the reduction of NET formation and the preservation of mucosal immunity.