Increased susceptibility of human limbal aniridia fibroblasts to oxidative stress.

Aniridia-associated keratopathy originates from a haploinsufficiency of the transcription factor PAX6 (PAX6+/-). In the corneal epithelium of PAX6+/- mice, a significant increase in oxidized proteins was observed, accompanied by impaired compensation for elevated oxidative stress (OS). The extent to which limbal fibroblast cells (LFCs) are affected by an increased susceptibility to OS in cases of congenital aniridia (AN) has not been determined, yet. Our aim was to examine the impact of OS on antioxidant enzyme expression in normal and AN-LFCs. Following isolation and culture of primary LFCs (n = 8) and AN-LFCs (n = 8), cells were treated with cobalt chloride for 48 h to chemically induce hypoxic conditions and OS. Subsequently, HIF-1α/-2α, PHD1/2, Nrf2, CAT, SOD1, PRDX6, and GPX1 gene expression was examined by qPCR. SOD1, PRDX6, and GPX1 protein levels were assessed from the cell lysate by Western blot. The induction of hypoxia led to reduced HIF-1α gene expression in both fibroblast groups (p≤0.008), while the decrease in PHD1 was limited to AN-LFCs (p = 0.0007). On the other hand, under hypoxic conditions, PHD2 showed higher mRNA expression in AN-LFCs compared to normal LFCs (p = 0.013). As a result of OS, the mRNA levels of Nrf2 (p<0.0001) and the antioxidant enzymes CAT (p = 0.005), SOD1 (p = 0.005), GPX1 (p = 0.002) decreased in AN-LFCs. This was accompanied by an increased protein expression of SOD1 (p = 0.019) and PRDX6 (p=0.0009). In the normal LFC group, the induced extent of OS had no impact on the gene (p≥0.151) and protein expression (p ≥ 0.629) of antioxidant enzymes, except for the GPX1 mRNA level (p = 0.027). AN-LFCs exhibit higher susceptibility to OS than normal LFCs. Therefore, in AN-LFCs, there are sustained alterations in gene and protein expression of antioxidative enzymes even after 48 h of CoCl2 treatment.

Effect of Ritanserin and Duloxetine on the Gene Expression of Primary Aniridia and Healthy Human Limbal Stromal Cells, In Vitro.

INTRODUCTION: In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro. METHODS: Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-ß1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7. RESULTS: In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-ß1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-ß1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039). CONCLUSIONS: The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-ß1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media.

Expression of matrix metalloproteinases and their inhibitors in corneal stromal fibroblasts and keratocytes from healthy and keratoconus corneas.

PURPOSE: To examine the in-vitro expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in corneal stromal cells by distinguishing between fibroblasts and keratocytes of healthy and keratoconus (KC) corneas. METHODS: Stromal cells were isolated from healthy and KC corneas (n = 8). A normal-glucose, serum-containing cell culture medium (NGSC-medium) was used for cultivation of healthy human corneal fibroblasts (HCFs) and KC human corneal fibroblasts (KC-HCFs). In order to obtain a keratocyte phenotype, the initial cultivation with NGSC-medium was changed to a low-glucose, serum-free cell culture medium for healthy (Keratocytes) and KC cells (KC-Keratocytes). Gene and protein expression of MMP-1, -2, -3, -7, -9 and TIMP-1, -2, -3 were measured by quantitative PCR and Enzyme-Linked Immunosorbent Assay (ELISA) from the cell culture supernatant. RESULTS: KC-HCFs demonstrated a lower mRNA gene expression for MMP-2 compared to HCFs. In contrast to their respective fibroblast groups (either HCFs or KC-HCFs), Keratocytes showed a higher mRNA gene expression of TIMP-3, whereas TIMP-1 mRNA gene expression was lower in Keratocytes and KC-Keratocytes. Protein analysis of the cell culture supernatant revealed lower concentrations of MMP-1 in KC-HCFs compared to HCFs. Compared to Keratocytes, TIMP-1 concentrations was lower in the cell culture supernatant of KC-Keratocytes. In HCFs and KC-HCFs, protein levels of MMP-1 and TIMP-1 were higher and MMP-2 was lower compared to Keratocytes and KC-Keratocytes, respectively. CONCLUSION: This study indicates an imbalance in MMP and TIMP expression between healthy and diseased cells. Furthermore, differences in the expression of MMPs and TIMPs exist between corneal fibroblasts and keratocytes, which could influence the specific proteolytic metabolism in-vivo and contribute to the progression of KC.

Rose Bengal Photodynamic Therapy (RB-PDT) Modulates the Inflammatory Response in LPS-Stimulated Human Corneal Fibroblasts By Influencing NF-κB and p38 MAPK Signaling Pathways.

PURPOSE: To investigate the effect of rose bengal photodynamic therapy on lipopolysaccharide-induced inflammation in human corneal fibroblasts. Furthermore, to analyze potential involvement of the mitogen-activated protein kinase and nuclear factor kappa B signaling pathways in this process. METHODS: Human corneal fibroblast cultures underwent 0-2.0 µg/mL lipopolysaccharide treatment, and 24 h later rose bengal photodynamic therapy (0.001% RB, 565 nm wavelength illumination, 0.17 J/cm2 fluence). Interleukin-6, interleukin-8, intercellular adhesion molecule-1, interferon regulatory factor-3, interferon α2, and interferon ß1 gene expressions were determined by quantitative PCR. Interleukin-6, interleukin-8, and C-C motif chemokine ligand-4 concentrations in the cell culture supernatant were measured by enzyme-linked immunosorbent assays and intercellular adhesion molecule-1 protein level in human corneal fibroblasts by western blot. In addition, the nuclear factor kappa B and mitogen-activated protein kinase signaling pathways were investigated by quantitative PCR and phosphorylation of nuclear factor kappa B p65 and p38 mitogen-activated protein kinase by western blot. RESULTS: Rose bengal photodynamic therapy in 2.0 µg/mL lipopolysaccharide-stimulated human corneal fibroblasts triggered interleukin-6 and interleukin-8 mRNA (p < .0001) and interleukin-6 protein increase (p < .0001), and downregulated intercellular adhesion molecule-1 expression (p < .001). C-C motif chemokine ligand-4, interferon regulatory factor-3, interferon α2, and interferon ß1 expressions remained unchanged (p ≥ .2). Rose bengal photodynamic therapy increased IκB kinase subunit beta, nuclear factor kappa B p65, extracellular signal-regulated kinases-2, c-Jun amino terminal kinase, and p38 transcription (p ≤ .01), and triggered nuclear factor kappa B p65 and p38 mitogen-activated protein kinase phosphorylation (p ≤ .04) in lipopolysaccharide treated human corneal fibroblasts. CONCLUSION: Rose bengal photodynamic therapy of lipopolysaccharide-stimulated human corneal fibroblasts can modify the inflammatory response by inducing interleukin-6 and interleukin-8 expression, and decreasing intercellular adhesion molecule-1 production. C-C motif chemokine ligand-4, interferon regulatory factor-3, and interferon α and ß expressions are not affected by rose bengal photodynamic therapy in these cells. The underlying mechanisms may be associated with nuclear factor kappa B and p38 mitogen-activated protein kinase pathway activation.

Plastic film mulching application improves potato yields, reduces ammonia emissions, but boosts the greenhouse gas emissions in China.

With global population growth and climate change, food security and global warming have emerged as two major challenges to agricultural development. Plastic film mulching (PM) has long been used to improve yields in rain-fed agricultural systems, but few studies have focused on soil gas emissions from mulched rainfed potatoes on a long-term and regional scale. This study integrated field data with the Denitrification-Decomposition (DNDC) model to evaluate the impacts of PM on potato yields, greenhouse gas (GHG) and ammonia (NH3) emissions in rainfed agricultural systems in China. We found that PM increased potato yield by 39.7 % (1505 kg ha-1), carbon dioxide (CO2) emissions by 15.4 % (123 kg CO2 eq ha-1), nitrous oxide (N2O) emissions by 47.8 % (1016 kg CO2 eq ha-1), and global warming potential (GWP) by 38.9 % (1030 kg CO2 eq ha-1), while NH3 volatilization decreased by 33.9 % (8.4 kg NH3 ha-1), and methane (CH4) emissions were little changed compared to CK. Specifically, the yield after PM significantly increased in South China (SC), North China (NC), and Northwest China (NWC), with increases of 66.1 % (2429 kg ha-1), 44.1 % (1173 kg ha-1), and 43.6 % (956 kg ha-1) compared to CK, respectively. The increase in GWP and greenhouse gas emission intensity (GHGI) under PM was more pronounced in the Northeast China (NEC) and NWC regions, with respective increases of 57.1 % and 60.2 % in GWP, 16.9 % and 10.3 % in GHGI. While in the Middle and Lower reaches of the Yangtze River (MLYR) and SC, PM decreased GHGI with 10.2 % and 31.1 %, respectively. PM significantly reduced NH3 emissions in all regions and these reductions were most significant in Southwest China (SWC), SCand MLYR, which were 41 %, 38.0 %, and 38.0 % lower than CK, respectively. In addition, climatic and edaphic variables were the main contributors to GHG and NH3 emissions. In conclusion, it is appropriate to promote the use of PM in the MLYR and SC regions, because of the ability to increase yields while reducing environmental impacts (lower GHGI and NH3 emissions). The findings provide a theoretical basis for sustainable agricultural production of PM potatoes.

In Situ Exfoliation Growth Strategy Realizing Controlled Synthesis of 3D to 2D MOF Materials as High-Performance Electrochemical Biosensors.

Two-dimensional (2D) metal-organic framework (MOF) nanosheets with large surface area, ultrathin thickness, and highly accessible active sites have attracted great research attention. Developing efficient approaches to realize the controllable synthesis of well-defined 2D MOFs with a specific composition and morphology is critical. However, it is still a significant challenge to construct thin and uniform 2D MOF nanosheets and resolve the reagglomeration as well as poor stability of target 2D MOF products. Here, an "in situ exfoliation growth" strategy is proposed, where a one-step synthetic process can realize the successful fabrication of PBA/MIL-53(NiFe)/NF nanosheets on the surface of nickel foam (NF) via in situ conversion and exfoliation growth strategies. The PBA/MIL-53(NiFe)/NF nanosheets combine the individual advantages of MOFs, Prussian blue analogues (PBAs), and 2D materials. As expected, the resulting PBA/MIL-53(NiFe)/NF as a glucose electrode exhibits an extremely high sensitivity of 25.74 mA mM-1 cm-2 in a very wide concentration range of 180 nM to 4.8 µM. The present exciting work provides a simple and effective strategy for the construction of high-performance nonenzymatic glucose electrochemical biosensors.

Short-Term Effect of Rose Bengal Photodynamic Therapy (RB-PDT) on Collagen I, Collagen V, NF-κB, LOX, TGF-ß and IL-6 Expression of Human Corneal Fibroblasts, In Vitro.

PURPOSE: To investigate collagen I, collagen V, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), lysyl oxidase (LOX), transforming growth factor ß1 (TGF-ß1) and interleukin-6 (IL-6) expression in healthy and keratoconus human corneal fibroblasts (HCFs and KC-HCFs), 24 h after Rose Bengal photodynamic therapy (RB-PDT). METHODS: HCFs were isolated from healthy human corneal donors (n = 5) and KC-HCFs from elective penetrating keratoplasties (n = 5). Both cell cultures underwent RB-PDT (0.001% RB concentration, 0.17 J/cm2 fluence) and 24 h later collagen I, collagen V, NF-κB, LOX, TGF-ß1 and IL-6 mRNA and protein expression have been determined using qPCR and Western blot, IL-6 concentration in the cell culture supernatant by ELISA. RESULTS: TGF-ß1 mRNA expression was significantly lower (p = 0.02) and IL-6 mRNA expression was significantly higher in RB-PDT treated HCFs (p = 0.01), than in HCF controls. COL1A1, COL5A1 and TGF-ß1 mRNA expression was significantly lower (p = 0.04; p = 0.02 and p = 0.003) and IL-6 mRNA expression was significantly higher (p = 0.02) in treated KC-HCFs, than in KC-HCF controls. TGF-ß1 protein expression in treated HCFs was significantly higher than in HCF controls (p = 0.04). IL-6 protein concentration in the HCF and KC-HCF culture supernatant after RB-PDT was significantly higher than in controls (p = 0.02; p = 0.01). No other analyzed mRNA and protein expression differed significantly between the RB-PDT treated and untreated groups. CONCLUSIONS: Our study demonstrates that RB-PDT reduces collagen I, collagen V and TGF-ß1 mRNA expression, while increasing IL-6 mRNA and protein expression in KC-HCFs. In HCFs, RB-PDT increases TGF-ß1 and IL-6 protein level after 24 h.

Human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium.

PURPOSE: To investigate human corneal epithelial cell and fibroblast migration and growth factor secretion after rose bengal photodynamic therapy (RB-PDT) and the effect of conditioned medium (CM). METHODS: A human corneal epithelial cell line (HCE-T), human corneal fibroblasts (HCF) and keratoconus fibroblasts (KC-HCF) have been used. Twenty-four hours after RB-PDT (0.001% RB concentration, 565 nm wavelength illumination, 0.17 J/cm2 fluence) cell migration rate using scratch assay and growth factor concentrations in the cell culture supernatant using ELISA have been determined. In addition, the effect of CM has been observed. RESULTS: RB-PDT significantly reduced migration rate in all cell types, compared to controls (p≤0.02). Migration rate of HCE-T cultures without RB-PDT (untreated) was significantly higher using HCF CM after RB-PDT, than using HCF CM without RB-PDT (p<0.01). Similarly, untreated HCF displayed a significantly increased migration rate with HCE-T CM after RB-PDT, compared to HCE-T CM without treatment (p<0.01). Furthermore, illumination alone and RB-PDT significantly decreased keratinocyte growth factor (KGF) concentration in HCF and KC-HCF supernatant, and RB-PDT significantly decreased soluble N-Cadherin (SN-Cad) concentration in HCF supernatant, compared to controls (p<0.01 for all). In HCE-T CM, RB-PDT increased hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGFb) concentration (p≤0.02), while decreasing transforming growth factor ß (TGF-ß) concentration (p<0.01). FGFb concentration increased (p<0.0001) and TGF-ß concentration decreased (p<0.0001) in HCF CM, by RB-PDT. Epidermal growth factor (EGF), HGF, and TGF-ß concentration decreased (p≤0.03) and FGFb concentration increased (p<0.01) in KC-HCF CM, using RB-PDT. CONCLUSIONS: HCE-T, HCF and KC-HCF migration rate is reduced 24 hours after RB-PDT. In contrast, HCE-T migration is enhanced using HCF CM after RB-PDT, and HCF migration rate is increased through HCE-T CM following RB-PDT. Modulation of EGF, KGF, HGF, FGFb, TGF-ß and N-Cadherin secretion through RB-PDT may play an important role in corneal wound healing.

Endoscopic resection of gastrointestinal stromal tumors.

Surgical resection is regarded as the main modality for the treatment of gastrointestinal stromal tumors (GISTs). With the advancement of endoscopic techniques and the introduction of super minimally invasive surgery (SMIS), endoscopic resection has been an alternative option to surgery. Recently, various endoscopic resection techniques have been used for the treatment of GISTs, including endoscopic submucosal dissection (ESD), endoscopic submucosal excavation (ESE), endoscopic full-thickness resection (EFR), submucosal tunneling endoscopic resection (STER), and laparoscopic and endoscopic cooperative surgery (LECS). Studies on the safety and efficacy of the endoscopic treatment of GISTs have emerged in recent years. Endoscopic resection techniques have demonstrated to be effective and safe for the treatment of GISTs. However, there is currently no consensus on the optimal follow-up strategy and the appropriate cut-off value of tumor size for endoscopic resection. In this review we discussed the indications, preoperative preparation, procedures, efficacy, safety, postoperative evaluation, follow-up, and perspectives of endoscopic resection modalities for GISTs.

(FeMnCe)-co-doped MOF-74 with significantly improved performance for overall water splitting.

Developing inexpensive electrocatalysts with high activity and stability is of great value for overall water splitting. In this work, we designed a series of 3d-4f (FeMnCe)-trimetallic MOF-74 with different ratios of 3d- and 4f-metal centers. Among them, FeMn6Ce0.5-MOF-74/NF exhibited the best electrocatalytic performance for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) in an alkaline solution. It only requires a low overpotential of 281 mV@100 mA cm-2 for OER and 186 mV@-10 mA cm-2 for HER in 1 M KOH. With FeMn6Ce0.5-MOF-74/NF as the anode and cathode in the overall water splitting system, only 1.65 V is needed to deliver a current density of 10 mA cm-2. In particular, for the as-fabricated FeMn6Ce0.5-MOF-74/NF||Pt/C cell unit, only 1.40 V is needed to achieve 10 mA cm-2. Therefore, the successful design of 3d-4f mixed-metallic MOF-74 provides a new viewpoint to develop highly efficient non-precious metal electrocatalysts.

SGK3 overexpression correlates with a poor prognosis in endoscopically resected superficial esophageal squamous cell neoplasia: A long-term study.

BACKGROUND: The expression status of serum and glucocorticoid-induced protein kinase 3 (SGK3) in superficial esophageal squamous cell neoplasia (ESCN) remains unknown. AIM: To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection. METHODS: A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled. Immunohistochemistry was used to evaluate SGK3 expression. RESULTS: SGK3 was overexpressed in 55 (59.8%) patients with ESCN. SGK3 overexpression showed a significant correlation with death (P = 0.031). Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group (P = 0.013 and P = 0.004, respectively). Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients (hazard ratio 4.729; 95% confidence interval: 1.042-21.458). CONCLUSION: SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival. Thus, it might be a new prognostic factor for ESCN.

Plasma exosomal hsa_circ_0079439 as a novel biomarker for early detection of gastric cancer.

BACKGROUND: Due to the poor prognosis of gastric cancer (GC), early detection methods are urgently needed. Plasma exosomal circular RNAs (circRNAs) have been suggested as novel biomarkers for GC. AIM: To identify a novel biomarker for early detection of GC. METHODS: Healthy donors (HDs) and GC patients diagnosed by pathology were recruited. Nine GC patients and three HDs were selected for exosomal whole-transcriptome RNA sequencing. The expression profiles of circRNAs were analyzed by bioinformatics methods and validated by droplet digital polymerase chain reaction. The expression levels and area under receiver operating characteristic curve values of plasma exosomal circRNAs and standard serum biomarkers were used to compare their diagnostic efficiency. RESULTS: There were 303 participants, including 240 GC patients and 63 HDs, involved in the study. The expression levels of exosomal hsa_circ_0079439 were significantly higher in GC patients than in HDs (P < 0.0001). However, the levels of standard serum biomarkers were similar between the two groups. The area under the curve value of exosomal hsa_circ_0079439 was higher than those of standard biomarkers, including carcinoembryonic antigen, carbohydrate antigen (CA)19-9, CA72-4, alpha-fetoprotein, and CA125 (0.8595 vs 0.5862, 0.5660, 0.5360, 0.5082, and 0.5018, respectively). The expression levels of exosomal hsa_circ_0079439 were significantly decreased after treatment (P < 0.05). Moreover, the expression levels of exosomal hsa_circ_0079439 were obviously higher in early GC (EGC) patients than in HDs (P < 0.0001). CONCLUSION: Our results suggest that plasma exosomal hsa_circ_0079439 is upregulated in GC patients. Moreover, the levels of exosomal hsa_circ_0079439 could distinguish EGC and advanced GC patients from HDs. Therefore, plasma exosomal hsa_circ_0079439 might be a potential biomarker for the diagnosis of GC during both the early and late stages.

Per-oral endoscopic myotomy is safe and effective for pediatric patients with achalasia: A long-term follow-up study.

BACKGROUND: Per-oral endoscopic myotomy (POEM) is emerging as a prefer treatment option for pediatric achalasia. However, data are limited on the long-term efficacy of POEM in children and adolescents with achalasia. AIM: To evaluate the safety and long-term efficacy of POEM for pediatric patients with achalasia and compare those outcomes with adult patients. METHODS: This retrospective cohort study was conducted in patients with achalasia who underwent POEM. Patients aged under 18 years were included in the pediatric group; patients aged between 18 to 65 years who underwent POEM in the same period were assigned to the control group. For investigation of long-term follow-up, the pediatric group were matched with patients from the control group in a 1:1 ratio. The procedure-related parameters, adverse events, clinical success, gastroesophageal reflux disease (GERD) after POEM, and quality of life (QoL) were evaluated. RESULTS: From January 2012 to March 2020, POEM was performed in 1025 patients aged under 65 years old (48 in the pediatric group, 1025 in the control group). No significant differences were observed in the occurrence of POEM complications between the two groups (14.6% vs 14.6%; P = 0.99). Among the 34 pediatric patients (70.8%) who underwent follow-up for 5.7 years (range 2.6-10.6 years), clinical success was achieved in 35 patients (35/36; 97.2%). No differences were observed in post-POEM GERD occurrence (17.6% vs 35.3%; P = 0.10). QoL was significantly improved in both groups after POEM. CONCLUSION: POEM is safe and effective for pediatric patients with achalasia. It can achieve significant symptoms relief and improve QoL.

One-step synthesis of 2D@3D hollow Prussian blue analogue as a high-performance bifunctional electrochemical sensor.

Prussian blue analogues (PBAs) are a family of classic coordination polymers. They have been widely applied in various fields including electrochemical sensors. Cubic nanoparticle structure is their common morphology. It is still a great challenge to design a hollow and two-dimensional (2D) PBA material. Of course, it will be a significant surprise if a hollow cube and 2D sheet can be integrated into one material. In this work, we designed a simple one-step synthetic strategy and resolved the above difficulty, wherein a hollow cubic PBA covered by 2D ultrathin nanosheets was successfully constructed, namely hollow tremella-like PBA (HTPBA). Furthermore, Ni foam (NF) as a substrate was introduced to obtain a self-supporting HTPBA/NF-12 electrode. HTPBA/NF-12, as a bifunctional electrochemical sensor electrode, exhibited distinguished catalytic performance towards glucose and nitrite, including remarkable selectivity, reproducibility, sensitivity for glucose (21 410 µA mM-1 cm-2) and nitrite (1248 µA mM-1 cm-2), wide linear range of 2-1250 µM and 5-3380 µM, along with low detection limit of 0.056 µM and 0.38 µM, respectively. More importantly, HTPBA/NF-12 electrodes possessed good reusability and practicability even in goat serum. In this study, we developed a simple and effective strategy to fabricate 2D@3D PBA material with excellent electrocatalytic activity and provide a totally new viewpoint in the PBA sensing field.

A modified exposed endoscopic full-thickness resection: Traction-assisted resection while defect closing.

OBJECTIVES: Exposed endoscopic full-thickness resection (Eo-EFTR) has proven effective and economical for patients with gastric submucosal tumors (SMTs), showing great prospects. However, the poor operative field of view, the risk of tumors falling into the peritoneal cavity, especially the difficulties in defect closure, have limited its widespread application. Herein, we described a modified traction-assisted Eo-EFTR technique aimed at simplifying both the dissection and defect closure procedures. METHODS: Nineteen patients who underwent the modified Eo-EFTR for gastric SMTs in the Chinese People's Liberation Army General Hospital were enrolled in the study. Following a 2/3 circumferential full-thickness incision, a clip with dental floss was anchored to the resected part of the tumor surface. With the dental floss traction, the gastric defect was reshaped into a V shape, which facilitated the deployment of clips to close the defect. The defect closure and tumor dissection procedures were then performed alternately. Patients' demographics, tumor characteristics, and therapeutic outcomes were evaluated retrospectively. RESULTS: All tumors had an R0 resection. The median procedure time was 43 min (range 28-89 min). No severe perioperative adverse events occurred. Two patients experienced transient fever, and three patients complained of mild abdominal pain on the first day after the operation. All patients recovered on the next day with conservative management. No residual lesion or recurrence was reported during the follow-up period of 30.1 months. CONCLUSION: The safety and practicability of the modified technique might allow for wide clinical applications of Eo-EFTR in gastric SMTs.

Cholangioscopy-assisted extraction through novel papillary support for small-calibre and sediment-like common bile duct stones.

BACKGROUND: To date, endoscopic retrograde cholangiopancreatography has become a well-established treatment for common bile duct (CBD) stones. However, it is not suitable for some special patients, such as pregnant women, children or those who cannot stop taking anti-coagulation/anti-platelet agents because of radiation injury and the risk of postoperative bleeding resulting from endoscopic sphincterotomy. To overcome these two problems, this study introduced cholangioscopy-assisted extraction through a novel papillary support for small-calibre and sediment-like CBD stones. AIM: To assess the feasibility and safety of cholangioscopy-assisted extraction through a novel papillary support (CEPTS) for small-calibre and sediment-like common bile duct (CBD) stones. METHODS: This Retrospective study was approved by the Ethics Committee of the Chinese PLA General Hospital. We designed a covered single dumbbell-style papillary support between 2021 and 2022. Between July 2022 and September 2022, 7 consecutive patients with small-calibre (cross diameter ≤ 1.0 cm) or sediment-like CBD stones underwent CETPS procedures in our center. The clinical characteristics and treatment outcomes of these 7 patients were extracted from a prospectively collected database. And the related data were analyzed. Informed consent was obtained from all participating patients. RESULTS: A total of 2 patients had yellow sediment-like CBD stones, and aspiration extraction was performed after the insertion of papillary support. Of the 5 patients with clumpy CBD stones (0.4-1.0 cm), 2 underwent basket extraction under direct vision for a single stone (0.5-1.0 cm, black and black grey), 1 underwent balloon plus aspiration extraction under direct vision for 5 stones (0.4-0.6 cm, brown), and 2 underwent aspiration extraction only for a single stone (0.5-0.6 cm, yellow, none). Technical success, namely, no residual stones in the CBD or left and right hepatic ducts, was achieved in all 7 cases (100%). The median operating time was 45.0 minutes (range 13.0-87.0 minutes). Postoperative pancreatitis (PEP) occurred in one case (14.3%). Hyperamylasaemia without abdominal pain was noted in 2 of 7 patients. No residual stones or cholangitis were found during the follow-up. CONCLUSION: CETPS appeared to be feasible to treat patients with small-calibre or sediment-like CBD stones. Patients, especially pregnant women and those who cannot stop anticoagulation/anti-platelet agents, could benefit from this technique.

Repeat peroral endoscopic myotomy with simultaneous submucosal and muscle dissection as a salvage option for recurrent achalasia.

BACKGROUND: For recurrent achalasia after initial peroral endoscopic myotomy (POEM) failure, repeat POEM (Re-POEM) has been reported as a treatment option. However, severe esophageal interlayer adhesions caused by previous procedures impede the successful establishment of a submucosal tunnel and lead to aborted Re-POEM procedures. Our team previously described POEM with simultaneous submucosal and muscle dissection (POEM-SSMD) as a feasible solution for achalasia with severe interlayer adhesions. AIM: To investigate the effectiveness and safety of Re-POEM with simultaneous submucosal and muscle dissection (Re-POEM-SSMD). METHODS: A total of 1049 patients with achalasia who underwent successful endoscopic myotomy at the Digestive Endoscopic Center of Chinese PLA General Hospital from December 2014 to May 2022 were reviewed. Patients with recurrent achalasia who experienced initial POEM clinical failure were retrospectively included in this study. The primary endpoint was retreatment clinical success, defined as an Eckardt score ≤ 3 during the postretreatment follow-up and no need for additional treatment. Procedure-related adverse events, changes in manometric lower esophageal sphincter (LES) pressure and reflux complications, as well as procedure-related parameters, were recorded. RESULTS: Sixteen patients underwent Re-POEM (9 patients) or Re-POEM-SSMD (7 patients) successfully at a median of 45.5 mo (range, 4-95 mo) after initial POEM. During a median follow-up period of 31 mo (range, 7-96 mo), clinical success (Eckardt score ≤ 3) was achieved in 8 (88.9%) and 6 (85.7%) patients after Re-POEM and Re-POEM-SSMD, respectively (P = 0.849). The median Eckardt score dropped from 4 (range, 3-8) at preretreatment to 1 (range, 0-5) at postretreatment in the Re-POEM group (P = 0.025) and from 5 (range, 2-8) to 2 (range, 0-4) in the Re-POEM-SSMD group (P < 0.001). The mean manometric LES pressure decreased from 23.78 ± 9.04 mmHg to 11.45 ± 5.37 mmHg after Re-POEM (P < 0.001) and from 26.80 ± 7.48 mmHg to 11.05 ± 4.38 mmHg after Re-POEM-SSMD (P < 0.001). No serious adverse events were recorded in both groups. CONCLUSION: In conclusion, Re-POEM-SSMD appears to be a safe and effective salvage therapy for recurrent achalasia with severe interlayer adhesions.

UiO-66-Derived PBA Composite as Multifunctional Electrochemical Non-Enzymatic Sensor Realizing High-Performance Detection of Hydrogen Peroxide and Glucose.

In this work, a highly efficient multifunctional non-enzymatic electrochemical sensor is successfully fabricated based on a facile two-step synthetic strategy. It resolves two important challenges of poor stability and low reproducibility compared to conventional electrochemical enzyme-based sensors. Herein, a metal-organic framework (UiO-66) is selected as a sacrificial template to construct the corresponding Prussian blue analogue (PBA) target to improve its stability and conductivity, namely, PBA/UiO-66/NF. Target PBA/UiO-66/NF exhibits excellent electrochemical sensing performance as hydrogen peroxide (H2O2) and glucose sensors with ultrahigh sensitivity of up to 1903 µA mM-1 cm-2 for H2O2 and 22,800 µA mM-1 cm-2 for glucose, as well as a very low detection limit of 0.02 µM (S/N = 3) for H2O2 and 0.28 µM for glucose. Especially, extremely high stability can be observed, which will be beneficial for practical application.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study.

BACKGROUND: Lugol chromoendoscopy (LCE) has served as a standard screening technique in high-risk patients with esophageal cancer. Nevertheless, LCE is not suitable for general population screening given its side effects. Linked color imaging (LCI) is a novel image-enhanced endoscopic technique that can distinguish subtle diff-erences in mucosal color. AIM: To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions. METHODS: In this prospective study, we enrolled 543 patients who underwent white light imaging (WLI), LCI and LCE successively. We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions. Clinicopathological features and color analysis of lesions were assessed. RESULTS: In total, 43 patients (45 neoplastic lesions) were analyzed. Among them, 36 patients (38 neoplastic lesions) were diagnosed with LCI, and 39 patients (41 neoplastic lesions) were diagnosed with LCE. The sensitivity of LCI was similar to that of LCE (83.7% vs 90.7%, P = 0.520), whereas the specificity of LCI was greater than that of LCE (92.4% vs 87.0%, P = 0.007). The LCI procedure time in the esophageal examination was significantly shorter than that of LCE [42 (34, 50) s vs 160 (130, 189) s, P < 0.001]. The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI. However, the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer. CONCLUSION: LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions, and LCI represents a promising screening strategy for general populations.

CoOx nanoparticles loaded on carbon spheres with synergistic effects for effective inhibition of shuttle effect in Li-S batteries.

Lithium-sulfur (Li-S) batteries, as one of the new energy storage batteries, show immense potential due to their high theoretical specific capacity and theoretical energy density. However, there are still some problems to be solved, among which the shuttle effect of lithium polysulfides is one extremely serious issue with respect to the industrial application of Li-S batteries. Rational design of electrode materials with effective catalytic conversion ability is an effective route to accelerate the conversion of lithium polysulfides (LiPSs). Herein, considering the adsorption and catalysis of LiPSs, CoOx nanoparticles (NPs) loaded on carbon sphere composites (CoOx/CS) were designed and constructed as cathode materials. The CoOx NPs obtained, with ultralow weight ratio and uniform distribution, consist of CoO, Co3O4, and metallic Co. The polar CoO and Co3O4 enable chemical adsorption towards LiPSs through Co-S coordination, and the conductive metallic Co can improve electronic conductivity and reduce impedance, which is beneficial for ion diffusion at the cathode. Based on these synergistic effects, the CoOx/CS electrode exhibits accelerated redox kinetics and enhanced catalytic activity for conversion of LiPSs. Consequently, the CoOx/CS cathode delivers improved cycling performance, with an initial capacity of 980.8 mA h g-1 at 0.1C and a reversible specific capacity of 408.4 mA h g-1 after 200 cycles, along with enhanced rate performance. This work provides a facile route to construct cobalt-based catalytic electrodes for Li-S batteries, and promotes understanding of the LiPSs conversion mechanism.