Gelatin nanofiber-reinforced decellularized amniotic membrane promotes axon regeneration and functional recovery in the surgical treatment of peripheral nerve injury.

Effective recovery of peripheral nerve injury (PNI) after surgical treatment relies on promoting axon regeneration and minimizing the fibrotic response. Decellularized amniotic membrane (dAM) has unique features as a natural matrix for promoting PNI repair due to its pro-regenerative extracellular matrix (ECM) structure and anti-inflammatory properties. However, the fragile nature and rapid degradation rate of dAM limit its widespread use in PNI surgery. Here we report an engineered composite membrane for PNI repair by combining dAM with gelatin (Gel) nanofiber membrane to construct a Gel nanofiber-dAM composite membrane (Gel-dAM) through interfacial bonding. The Gel-dAM showed enhanced mechanical properties and reduced degradation rate, while retaining maximal bioactivity and biocompatibility of dAM. These factors led to improved axon regeneration, reduced fibrotic response, and better functional recovery in PNI repair. As a fully natural materials-derived off-the-shelf matrix, Gel-dAM exhibits superior clinical translational potential for the surgical treatment of PNI.

Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence and Oxygen Self-Supply.

Photodynamic therapy (PDT) is a promising strategy for cancer treatment. However, its efficiency is hindered by three key parameters, namely, limited penetration depth of external light, tumor hypoxia, and self-aggregation of photosensitizers. Herein, we fabricated a novel "all-in-one" chemiluminescence-PDT nanosystem through the integration of an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) in hierarchically engineered mesoporous porphyrinic metal-organic framework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescence of Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and then absorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescence resonance energy transfer. The excited porphyrins then sensitize oxygen supplied by Hb to produce sufficient reactive oxygen species that kill cancer cells. The MOF-based nanocomposite demonstrates excellent anticancer activity both in vitro and in vivo, with eventually a 68.1% tumor inhibition rate after intravenous injections without external light irradiation. This self-illuminating, oxygen-self-supplying nanosystem integrates all essential components of PDT into one simple nanoplatform, demonstrating great potential for the selective phototherapy of deep-seated cancer.

Development and validation of a deep learning-based approach to predict the Mayo endoscopic score of ulcerative colitis.

Background: The ulcerative colitis (UC) Mayo endoscopy score is a useful tool for evaluating the severity of UC in patients in clinical practice. Objectives: We aimed to develop and validate a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. Design: A multicenter, diagnostic retrospective study. Methods: We collected 15120 colonoscopy images of 768 UC patients from two hospitals in China and developed a deep model based on a vision transformer named the UC-former. The performance of the UC-former was compared with that of six endoscopists on the internal test set. Furthermore, multicenter validation from three hospitals was also carried out to evaluate UC-former's generalization performance. Results: On the internal test set, the areas under the curve of Mayo 0, Mayo 1, Mayo 2, and Mayo 3 achieved by the UC-former were 0.998, 0.984, 0.973, and 0.990, respectively. The accuracy (ACC) achieved by the UC-former was 90.8%, which is higher than that achieved by the best senior endoscopist. For three multicenter external validations, the ACC was 82.4%, 85.0%, and 83.6%, respectively. Conclusions: The developed UC-former could achieve high ACC, fidelity, and stability to evaluate the severity of UC, which may provide potential application in clinical practice. Registration: This clinical trial was registered at the ClinicalTrials.gov (trial registration number: NCT05336773).

Why was this study done? The development of an auxiliary diagnostic tool can reduce the workload of endoscopists and achieve rapid assessment of ulcerative colitis (UC) severity. What did the researchers do? We developed and validated a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. What did the researchers find? The model that was developed in this study achieved high accuracy, fidelity, and stability, and demonstrated potential application in clinical practice. What do the findings mean? Deep learning could effectively assist endoscopists in evaluating the severity of UC in patients using endoscopic images.

Graphical education and appropriate time before elective colonoscopy make better bowel preparation.

Background: Inadequate bowel preparation leads to lower polyp detection rates, longer procedure times and lower cecal intubation rates. However, there is no consensus about high-quality bowel preparation, so our study evaluated graphical education and appropriate time before elective colonoscopy. Patients and Methods: We performed a secondary analysis of a national colorectal cancer screening programme of 738 patients. The patients were divided into a group given a graphical information manual (n = 242) or a word-only one (n = 496). They were also divided into groups according to the interval between bowel preparation and colonoscopy: 6-8 h (Group 1, n = 106), 9-12 h (Group 2, n = 228) and 13-17 h (Group 3, n = 402). All patients were scored according to the Boston Bowel Preparation Scale (BBPS) during the examination. Results: The bowel preparation of the graphical group was significantly better than the text group (P < 0.001). After adjustment, the bowel preparation score of Group 1 and Group 2 were both significantly higher than that of Group 3 (P = 0.012 and P = 0.032). Maximum BBPS was 6.31 when the interval time was 6.52 h (95% confidence interval: 5.95-6.66), and when the interval was <10 h, the BBPS was ≥6. Conclusion: High-quality bowel preparation was linked to graphical education and appropriate time before colonoscopy. We suggest that the interval between taking the first laxative and colonoscopy should be <10 h, preferably 6.5 h. Prospective multicentre research is needed to give more evidence of high-quality bowel preparation methods.

Development and Validation of a Deep Neural Network for Accurate Identification of Endoscopic Images From Patients With Ulcerative Colitis and Crohn's Disease.

Background and Aim: The identification of ulcerative colitis (UC) and Crohn's disease (CD) is a key element interfering with therapeutic response, but it is often difficult for less experienced endoscopists to identify UC and CD. Therefore, we aimed to develop and validate a deep learning diagnostic system trained on a large number of colonoscopy images to distinguish UC and CD. Methods: This multicenter, diagnostic study was performed in 5 hospitals in China. Normal individuals and active patients with inflammatory bowel disease (IBD) were enrolled. A dataset of 1,772 participants with 49,154 colonoscopy images was obtained between January 2018 and November 2020. We developed a deep learning model based on a deep convolutional neural network (CNN) in the examination. To generalize the applicability of the deep learning model in clinical practice, we compared the deep model with 10 endoscopists and applied it in 3 hospitals across China. Results: The identification accuracy obtained by the deep model was superior to that of experienced endoscopists per patient (deep model vs. trainee endoscopist, 99.1% vs. 78.0%; deep model vs. competent endoscopist, 99.1% vs. 92.2%, P < 0.001) and per lesion (deep model vs. trainee endoscopist, 90.4% vs. 59.7%; deep model vs. competent endoscopist 90.4% vs. 69.9%, P < 0.001). In addition, the mean reading time was reduced by the deep model (deep model vs. endoscopists, 6.20 s vs. 2,425.00 s, P < 0.001). Conclusion: We developed a deep model to assist with the clinical diagnosis of IBD. This provides a diagnostic device for medical education and clinicians to improve the efficiency of diagnosis and treatment.

Twelve-week peptide-based formula therapy may be effective in inducing remission of active Crohn disease among women who are pregnant or preparing for pregnancy.

BACKGROUND: Conventional treatment for Crohn disease (CD) in pregnancy includes mesalamine, thiopurine, and anti-tumor necrosis factor (TNF)-α agents. However, women may abstain because of complications, nonresponse, or potential adverse outcomes. Peptide-based formula therapy, through oral or nasogastric feeding without other food intake, is an effective and safe therapy for active CD. Herein, We confirmed the effectiveness and safety of peptide-based formula therapy for active CD in pregnant women or those preparing for pregnancy. METHOD: Outcomes of peptide-based formula therapy to induce CD remission during pregnancy preparation and the conception period were evaluated retrospectively among 14 women. Efficacy was evaluated as the change in serum indices and inflammatory markers after 12-week treatment. Pregnancy outcomes were compared between 14 women treated with nutrition therapy and eight women using conventional CD drugs. RESULTS: After 12 weeks, 85.7% (12 of 14) of patients treated with peptide-based formula achieved remission with a significant decrease in the CD activity index (P < .001) and high-sensitivity C-reactive protein level (P = .004). There were no effects of peptide-based formula therapy on pregnancy outcomes compared with conventional CD treatment (P > .05). Among the 12 patients who achieved CD remission with exclusive peptide-based formula therapy, 10 selected to continue total or partial peptide-based formula treatment to maintain CD remission throughout pregnancy. CONCLUSION: Peptide-based formula therapy, without other food intake, may provide a safe and effective alternative to conventional CD drugs to induce disease remission among women during conception and pregnancy.

Maternal tobacco exposure during pregnancy and allergic rhinitis in offspring: A systematic review and meta-analysis.

BACKGROUND: Maternal tobacco exposure during pregnancy is known to cause a potential hazard to the offspring's health. So far, published studies have shown no consistent results with whether tobacco exposure in utero is causally linked to the development of allergic rhinitis in offspring. The aim of this study was to comprehensively evaluate the association between maternal tobacco exposure during pregnancy and allergic rhinitis in offspring by meta-analysis and to provide reference for clinical work. METHODS: Literatures were searched in CNKI, Wanfang Data, VIP, SinoMed, PubMed, Web of science and Embase up to September 30,2020. Screening, inclusion, quality assessment, data extraction and data analysis of the literatures were conducted. Meta-analysis was performed with Revman 5.3 and State15.1 software. Odds ratio (OR) and 95%CI were used as observation indicators. RESULTS: We had retrieved 16 articles with 22 independent datasets and 11,49,879 sample size. When all the studies were analyzed together, the results showed that maternal smoking exposure during pregnancy would increase the risk of allergic rhinitis in offspring (OR = 1.13, 95%CI:1.02-1.26), especially maternal passive smoking during pregnancy (OR = 1.39, 95%CI:1.05-1.84). But subgroup analysis showed that maternal active smoking during pregnancy was only significantly associated with offspring allergic rhinitis in cross-sectional studies (OR = 1.24, 95%CI:1.07-1.45) and study done in America study (OR = 1.22, 95%CI:1.05-1.42). CONCLUSIONS: Tobacco exposure during pregnancy could increase the risk of allergic rhinitis in offspring. The importance of avoiding prenatal tobacco exposure should be emphasized more for the health of next generation in the public.

[Sagittal Balance Parameters Correlate with Resorption of the Lumbar Disc Extrusion: Results of a Retrospective Study].

OBJECTIVE: A retrospective study was designed to explore the relationship between the satittal spinopelvic alignment in patients with lumbar disc extrusion and spontaneous resorption. METHODS: From May 2010 to March 2019, referring to NASS evidence-based clinical guidelines, patients with lumbar disc extrusion were enrolled in this retrospective study, according to the degree of herniation size during the follow-up, the patients were divided into two groups: resorption (group R: the herniated disc completely disappeared or the herniation size was grade 1 according to Michgan State University (MSU) classification) and nonresorption (group N: the herniated disc remain unchanged or the herniation size overpass grade 1), spinopelvic parameters (including the pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL)) were determined on standing profile radiographs of the lumbar spine and pelvis, and mean values were compared using the multi-factor analysis of variance. RESULTS: This study included 67 patients with lumbar disc extrusion. There were 37 in group R (the average age was 42.6 years), 21 males and 16 females, 13 cases at L 4-5 level and 24 cases at L 5-S 1 level, follow-up 22 months, and 30 in group N (the average age was 40.8 years), 19 males and 11 females, 12 cases at L 4-5 level and 18 cases at L 5-S 1 level, follow-up 21 months, at the follow up time, there symptoms were all satisfactorily relieved. There were no signifcant differences in age, gender, smoking history, chronic medical history, prominent segmnet, MSU classification, follow up time and other baseline conditions between two groups ( P>0.05). At the follow-up, in group R, all 30 cases of sagittal displaced disc disappeared, the herniated disc changed from the initial MSU classification of grade 2 in 19 cases and grade 3 in 18 cases to the post-absorption residual disc, which were limited to grade 1; in group N, 20 cases of sagittal displaced disc reduced to 14 cases, the herniated disc changed from the initial MSU classification of grade 2 in 21 cases and grade 3 in 9 cases to grade 2 in 27 cases and grade 3 in 3 cases. There was no significant difference in spinopelvic parameters between the two groups before the treatment ( P>0.05). At the follow-up, there was no significant difference in PI between the two groups ( P>0.05); the SS and LL in group R were bigger than those in group N, the PT in group R was smaller than that in group N, and the difference was statistically significant ( P<0.05). Compared within the same group, before treatment and follow-up, there were no significant differences in PI, SS and PT in group R, but a bigger LL ( P<0.05); no significant differences in all the parameters in group N were found. CONCLUSION: Resorption may result in pinopelvic parameter changes, which suggest that the lumbar spine is better at cushioning against load, reducing the disc pressure, and leading to resorption of the herniated disc.

Current diagnosis and management of Crohn's disease in China: results from a multicenter prospective disease registry.

BACKGROUND: This study aimed to understand the disease characteristics and treatment outcomes of Crohn's disease (CD) in a real-world setting in China. METHODS: In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD. RESULTS: Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn's Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission. CONCLUSIONS: This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

Construction and in vitro evaluation of enzyme nanoreactors based on carboxymethyl chitosan for arginine deprivation in cancer therapy.

In this study, a pH-induced morphological transition from micelles to vesicles for an amphiphilic photo cross-linkable biocopolymer (Az-NaCMCS), synthesized by mixing azidobenzaldehyde (Az) and an aqueous solution of carboxymethyl chitosan sodium salt (NaCMCS), was used for encapsulation of l-arginine deiminase (ADI). The aqueous solution of enzyme-loaded vesicles obtained was followed by UV-irradiation to result in shell cross-linked enzyme nanoreactors. The nanoreactors were characterized by TEM and DLS. Its encapsulation efficiency and loading capacity were determined. The encapsulation process showed no effect on the activity of ADI. The cross-linked shell of nanovesicles exhibited permeability to the substrate and product. The nanoreactors are enzymatically active and stable in blood plasma at 37°C. The in vitro growth inhibitory activity against MH134 cells showed almost the same dose-response profile as that of the native ADI. The nanoreactors exhibit the potential for arginine deprivation in cancer therapy.

Clinical efficacy and safety of autologous stem cell transplantation for patients with ST-segment elevation myocardial infarction.

PURPOSE: The purpose of this study is to evaluate the therapeutic efficacy and safety of stem cells for the treatment of patients with ST-segment elevation myocardial infarction (STEMI). MATERIALS AND METHODS: We performed a systematic review and meta-analysis of relevant published clinical studies. A computerized search was conducted for randomized controlled trials of stem cell therapy for STEMI. RESULTS: Twenty-eight randomized controlled trials with a total of 1,938 STEMI patients were included in the present meta-analysis. Stem cell therapy resulted in an improvement in long-term (12 months) left ventricular ejection fraction of 3.15% (95% confidence interval 1.01-5.29, P<0.01). The 3-month to 4-month, 6-month, and 12-month left ventricular end-systolic volume showed favorable results in the stem cell therapy group compared with the control group (P≤0.05). Significant decrease was also observed in left ventricular end-diastolic volume after 3-month to 4-month and 12-month follow-up compared with controls (P<0.05). Wall mean score index was reduced significantly in stem cell therapy group when compared with the control group at 6-month and 12-month follow-up (P=0.01). Moreover, our analysis showed a significant change of 12-month infarct size decrease in STEMI patients treated with stem cells compared with controls (P<0.01). In addition, no significant difference was found between treatment group and control in adverse reactions (P>0.05). CONCLUSION: Overall, stem cell therapy is efficacious in the treatment of patients with STEMI, with low rates of adverse events compared with control group patients.

Effects of chicken extract on plasma antioxidative status and lipid oxidation in healthy rats.

Chicken extract has been consumed in oriental countries for centuries for improving body conditions such as recovery from fatigue. It is a rich source of antioxidant dipeptides. The in vivo antioxidative abilities were evaluated. Diets mixed with 4 different amounts of chicken extract were investigated for in vivo antioxidation ability using healthy male Sprague-Dawley (SD) rats. Total antioxidant status (TAS), thiobarbituric reactive substances (TBARS), iron content, superoxide dismutase (SOD) activity, glutathion peroxidase (GPx) activity and uric acid content were determined. In healthy rats, most of the indexes were not affected by intake of chicken extract significantly. However, plasma TBARS in the chicken extract-fed groups increased at the end of the experiment, which could be due to some pro-oxidative minerals in the extract. In conclusion, we found no significant or minor changes on the activities of antioxidative enzymes, antioxidant conditions, or lipid oxidation in healthy rats from consuming chicken extract, which may be the result of a balanced body condition. However, because of its high content of dipeptides, we suggest that it should have liver protecting effects if oxidative stresses are introduced.