Efficacy and Safety of Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors Originating from the Muscularis Propria.

BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.

Enhancing the Spermidine Synthase-Based Polyamine Biosynthetic Pathway to Boost Rapid Growth in Marine Diatom Phaeodactylum tricornutum.

Diatoms, efficient carbon capture organisms, contribute to 20% of global carbon fixation and 40% of ocean primary productivity, garnering significant attention to their growth. Despite their significance, the synthesis mechanism of polyamines (PAs), especially spermidine (Spd), which are crucial for growth in various organisms, remains unexplored in diatoms. This study reveals the vital role of Spd, synthesized through the spermidine synthase (SDS)-based pathway, in the growth of the diatom Phaeodactylum tricornutum. PtSDS1 and PtSDS2 in the P. tricornutum genome were confirmed as SDS enzymes through enzyme-substrate selectivity assays. Their distinct activities are governed primarily by the Y79 active site. Overexpression of a singular gene revealed that PtSDS1, PtSDS2, and PtSAMDC from the SDS-based synthesis pathway are all situated in the cytoplasm, with no significant impact on PA content or diatom growth. Co-overexpression of PtSDS1 and PtSAMDC proved essential for elevating Spd levels, indicating multifactorial regulation. Elevated Spd content promotes diatom growth, providing a foundation for exploring PA functions and regulation in diatoms.

Enhanced Electrical Conductivity and Mechanical Properties of Stretchable Thermoelectric Generators Formed by Doped Semiconducting Polymer/Elastomer Blends.

Recent research efforts have concentrated on the development of flexible and stretchable thermoelectric (TE) materials. However, significant challenges have emerged, including increased resistance and reduced electrical conductivity when subjected to strain. To address these issues, rigid semiconducting polymers and elastic insulating polymers have been incorporated and nanoconfinement effects have been exploited to enhance the charge mobility. Herein, a feasible approach is presented for fabricating stretchable TE materials by using a doped semiconducting polymer blend consisting of either poly(3-hexylthiophene) (P3HT) or poly(3,6-dithiophen-2-yl-2,5-di(2-decyltetradecyl)-pyrrolo[3,4-c]pyrrole-1,4-dione-alt-thienylenevinylene-2,5-yl) (PDVT-10) as the rigid polymer with styrene-ethylene-butylene-styrene (SEBS) as the elastic polymer. In particular, the blend composition is optimized to achieve a continuous network structure with SEBS, thereby improving the stretchability. The optimized polymer films exhibit well-ordered microstructural aggregates, indicative of good miscibility with FeCl3 and enhanced doping efficiency. Notably, a lower activation energy and higher charge-carrier concentration contribute to an improved electrical conductivity under high tensile strain, with a maximum output power of 1.39 nW at a ΔT of 22.4 K. These findings offer valuable insights and serve as guidelines for the development of stretchable p-n junction thermoelectric generators based on doped semiconducting polymer blends with potential applications in wearable electronics and energy harvesting.

[Multisystem inflammatory syndrome in children in the context of coronavirus disease 2019 pandemic]. / æ–°åž‹å† çŠ¶ç— æ¯’æ„ŸæŸ“æµè¡ŒèƒŒæ™¯ä¸‹çš„å„¿ç«¥å¤šç³»ç»Ÿç‚Žç—‡ç»¼åˆå¾.

Multisystem inflammatory syndrome in children (MIS-C) is a complex syndrome characterized by multi-organ involvement that has emerged in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. The clinical presentation of MIS-C is similar to Kawasaki disease but predominantly presents with fever and gastrointestinal symptoms, and severe cases can involve toxic shock and cardiac dysfunction. Epidemiological findings indicate that the majority of MIS-C patients test positive for SARS-CoV-2 antibodies. The pathogenesis and pathophysiology of MIS-C remain unclear, though immune dysregulation following SARS-CoV-2 infection is considered a major contributing factor. Current treatment approaches for MIS-C primarily involve intravenous immunoglobulin therapy and symptomatic supportive care. This review article provides a comprehensive overview of the definition, epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of MIS-C.

Magnetic Microbead-Based Herringbone Chip for Sensitive Detection of Human Immunodeficiency Virus.

The microfluidic chip-based nucleic acid detection method significantly improves the sensitivity since it precisely controls the microfluidic flow in microchannels. Nonetheless, significant challenges still exist in improving the detection efficiency to meet the demand for rapid detection of trace substances. This work provides a novel magnetic herringbone (M-HB) structure in a microfluidic chip, and its advantage in rapid and sensitive detection is verified by taking complementary DNA (cDNA) sequences of human immunodeficiency virus (HIV) detection as an example. The M-HB structure is designed based on controlling the magnetic field distribution in the micrometer scale and is formed by accumulation of magnetic microbeads (MMBs). Hence, M-HB is similar to a nanopore microstructure, which has a higher contact area and probe density. All of the above is conducive to improving sensitivity in microfluidic chips. The M-HB chip is stable and easy to form, which can linearly detect cDNA sequences of HIV quantitatively ranging from 1 to 20 nM with a detection limit of 0.073 nM. Compared to the traditional herringbone structure, this structure is easier to form and release by controlling the magnetic field, which is flexible and helps in further study. Results show that this chip can sensitively detect the cDNA sequences of HIV in blood samples, demonstrating that it is a powerful platform to rapidly and sensitively detect multiple nucleic acid-related viruses of infectious diseases.

Gastric schwannoma: A retrospective analysis of clinical characteristics, treatments, and outcomes.

BACKGROUND: This study aimed to investigate the clinical characteristics, treatment options, and prognosis of patients with gastric schwannoma (GS). METHODS: Patients who were pathologically diagnosed with GS between April 2011 and October 2022 were enrolled. The data of clinical characteristics, pathological features, treatment options, and clinical outcomes were collected and compared between GS patients who underwent endoscopic resection (ER) and surgical resection (SR). RESULTS: Of the 32 cases, 23 underwent SR and nine underwent ER. The median tumor size was significantly smaller in ER group than in SR group (12.0 vs. 40.0 mm, P < 0.001), while patients in SR group were older than those in ER group (54.5 ± 10.6 vs. 45.3 ± 10.9 years, P = 0.036). Moreover, tumors in ER group were more likely to exhibit an intraluminal pattern (100% vs. 26.1%, P < 0.001). Patients in ER group had significantly lower hospitalization cost (25859.2 ± 8623.9 vs. 44953.0 ± 13083.8 RMB, P = 0.011) than those in SR group. No differences were found between the two groups in terms of R0 resection rate, operative time, estimated blood loss, adverse events, and recurrence rate. All patients were followed up for 4-96 months (mean: 35 months; median: 23 months), during which no evidence of recurrence or metastasis was observed. CONCLUSIONS: Both ER and SR are safe and effective treatment modalities for the management of GS, with ER being associated with lower medical costs compared to SR. The majority of GS are benign and do not recur, with little possibility of malignant transformation.

1,25(OH)2D3 alleviates oxidative stress and inflammation through up-regulating HMGCS2 in DSS-induced colitis.

BACKGROUND: Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS: HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS: Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION: 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.

Mixed Ionic-Electronic Conducting Hydrogels with Carboxylated Carbon Nanotubes for High Performance Wearable Thermoelectric Harvesters.

Mixed ionic-electronic conducting (MIEC) thermoelectric (TE) materials offer higher ionic conductivity and ionic Seebeck coefficient compared to those of purely ionic-conducting TE materials. These characteristics make them suitable for direct use in thermoelectric generators (TEGs) as the charge carriers can be effectively transported from one electrode to the other via the external circuit. In the present study, MIEC hydrogels are fabricated via the chemical cross-linking of polyacrylamide (PAAM) and polydopamine (PDA) to form a double network. In addition, electrically conducting carboxylated carbon nanotubes (CNT-COOH) are dispersed evenly within the hydrogel via sonication and interaction with the PDA. Moreover, the electrical properties of the hydrogel are further improved via the in situ polymerization of polyaniline (PANI). The presence of CNT-COOH facilitates the ionic conductivity and enhances the ionic Seebeck coefficient via ionic-electronic interactions between sodium ions and carboxyl groups on CNT-COOH, which can be observed in X-ray photoelectron spectroscopy results, thereby promoting the charge transport properties. As a result, the optimum device exhibits a remarkable ionic conductivity of 175.3 mS cm-1 and a high ionic Seebeck coefficient of 18.6 mV K-1, giving an ionic power factor (PFi) of 6.06 mW m-1 K-2 with a correspondingly impressive ionic figure of merit (ZTi) of 2.65. These values represent significant achievements within the field of gel-state organic TE materials. Finally, a wearable module is fabricated by embedding the PAAM/PDA/CNT-COOH/PANI hydrogel into a poly(dimethylsiloxane) mold. This configuration yields a high power density of 171.4 mW m-2, thus highlighting the considerable potential for manufacturing TEGs for wearable devices capable of harnessing waste heat.

Simultaneous detection of multiple influenza virus subtypes based on microbead-encoded microfluidic chip.

Influenza virus, existing many subtypes, causes a huge risk of people health and life. Different subtypes bring a huge challenge for detection and treatment, thus simultaneous detection of multiple influenza virus subtypes plays a key role in fight against this disease. In this work, three kinds of influenza virus subtypes are one-step detection based on microbead-encoded microfluidic chip. HIN1, H3N2 and H7N3 were simultaneously captured only by microbeads of different magnetism and sizes, and they were further treated by magnetic separation and enriched through the magnetism and size-dependent microfluidic structure. Different subtypes of influenza virus could be linearly encoded in different detection zones of microfluidic chip according to microbeads of magnetism and size differences. With the high-brightness quantum dots (QDs) as label, the enriched fluorescence detection signals were further read online from linearly encoded strips, obtaining high sensitivity with detection limit of HIN1, H3N2, H7N3 about 2.2 ng/mL, 3.4 ng/mL and 2.9 ng/mL. Moreover, a visual operation interface, microcontroller unit and two-way syringe pump were consisted of a miniaturized detection device, improving the detection process automation. And this assay showed strong specificity. This method improves a new way of multiple pathogens detection using microbead-encoded technologies in the microfluidic chip.

Continuous magnetic separation microfluidic chip for tumor cell in vivo detection.

Continuously recording the dynamic changes of circulating tumor cells (CTCs) is crucial for tumor metastasis. This paper creates a continuous magnetic separation microfluidic chip that enables rapid and continuous in vivo cell detection. The chip shows its potential to study tumor cell circulation in the blood, offering a new platform for studying the cellular mechanism of tumor metastasis.

Inhibition of oxidative stress-induced epithelial-mesenchymal transition in retinal pigment epithelial cells of age-related macular degeneration model by suppressing ERK activation.

INTRODUCTION: Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is related to the pathogenesis of various retinopathies including age-related macular degeneration (AMD). Oxidative stress is the major factor that induces degeneration of RPE cells associated with the etiology of AMD. OBJECTIVES: Sodium iodate (NaIO3) generates intracellular reactive oxygen species (ROS) and is widely used to establish a model of AMD due to the selective induction of retinal degeneration. This study was performed to clarify the effects of multiple NaIO3-stimulated signaling pathways on EMT in RPE cells. METHODS: The EMT characteristics in NaIO3-treated human ARPE-19 cells and RPE cells of the mouse eyes were analyzed. Multiple oxidative stress-induced modulators were investigated and the effects of pre-treatment with Ca2+ chelator, extracellular signal-related kinase (ERK) inhibitor, or epidermal growth factor receptor (EGFR) inhibitor on NaIO3-induced EMT were determined. The efficacy of post-treatment with ERK inhibitor on the regulation of NaIO3-induced signaling pathways was dissected and its role in retinal thickness and morphology was evaluated by using histological cross-sections and spectral domain optical coherence tomography. RESULTS: We found that NaIO3 induced EMT in ARPE-19 cells and in RPE cells of the mouse eyes. The intracellular ROS, Ca2+, endoplasmic reticulum (ER) stress marker, phospho-ERK, and phospho-EGFR were increased in NaIO3-stimulated cells. Our results showed that pre-treatment with Ca2+ chelator, ERK inhibitor, or EGFR inhibitor decreased NaIO3-induced EMT, interestingly, the inhibition of ERK displayed the most prominent effect. Furthermore, post-treatment with FR180204, a specific ERK inhibitor, reduced intracellular ROS and Ca2+ levels, downregulated phospho-EGFR and ER stress marker, attenuated EMT of RPE cells, and prevented structural disorder of the retina induced by NaIO3. CONCLUSIONS: ERK is a crucial regulator of multiple NaIO3-induced signaling pathways that coordinate EMT program in RPE cells. Inhibition of ERK may be a potential therapeutic strategy for the treatment of AMD.

Magnetic-based Microfluidic Chip: A Powerful Tool for Pathogen Detection and Affinity Reagents Selection.

The global outbreak of pathogen diseases has brought a huge risk to human lives and social development. Rapid diagnosis is the key strategy to fight against pathogen diseases. Development of detection methods and discovery of related affinity reagents are important parts of pathogen diagnosis. Conventional detection methods and affinity reagents discovery have some problems including much reagent consumption and labor intensity. Magnetic-based microfluidic chip integrates the unique advantages of magnetism and microfluidic technology, improving a powerful tool for pathogen detection and their affinity reagent discovery. This review provides a summary about the summary of pathogen detection through magnetic-based microfluidic chip, which refers to the pathogen nucleic acid detection (including extraction, amplification and signal acquisition), pathogen proteins and antibodies detection. Meanwhile, affinity reagents are served as the critical tool to specially capture pathogens. New affinity reagents are discovered to further facilitate the pathogen diagnosis. Microfluidic technology has also emerged as a powerful tool for affinity reagents discovery. Thus, this review further introduced the selection progress of aptamer as next generation affinity through the magnetic-based microfluidic technology. Using this selection technology shows great potential to improve selection performance, including integration and highly efficient selection. Finally, an outlook is given on how this field will develop on the basis of ongoing pathogen challenges.

Role of antiangiogenic agents in first-line treatment for advanced NSCLC in the era of immunotherapy.

BACKGROUND & OBJECTIVE: "Anti-angiogenetic drugs plus chemotherapy" (anti-angio-chemo) and "immune checkpoint inhibitors plus chemotherapy" (ICI-chemo) are superior to traditional chemotherapy in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, in the absence of a direct comparison of ICI-chemo with anti-angio-chemo, the superior one between them has not been decided, and the benefit of adding anti-angiogenetic agents to ICI-chemo remains controversial. This study aimed to investigate the role of antiangiogenic agents for advanced NSCLC in the era of immunotherapy. METHODS: Eligible randomized controlled trials (RCTs) comparing chemotherapy versus therapeutic regimens involving ICIs or anti-angiogenetic drugs were included. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and rate of grade 3-4 toxicity assessment. R-4.3.1 was utilized to perform the analysis. RESULTS: A total of 54 studies with a sample size of 25,046 were finally enrolled. "Atezolizumab + Bevacizumab + Chemotherapy" significantly improved the ORR compared with "Atezolizumab + Chemotherapy" (Odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.27-5.87). The trend also favored "Atezolizumab + Bevacizumab + Chemotherapy" in PFS and OS (hazard ratio (HR) = 0.71, 95% CI: 0.39-1.31; HR = 0.94, 95% CI: 0.77-1.16, respectively). In addition, "Pembrolizumab + Chemotherapy" and "Camrelizumab + Chemotherapy" significantly prolonged the PFS compared to "Bevacizumab + Chemotherapy" (HR = 0.65, 95% CI: 0.46-0.92; HR = 0.63, 95% CI: 0.41-0.97; respectively). Meanwhile, "Pembrolizumab + Chemotherapy" and "Sintilimab + Chemotherapy" yielded more OS benefits than "Bevacizumab + Chemotherapy" (HR = 0.69, 95% CI: 0.56-0.83; HR = 0.64, 95%CI: 0.46-0.91; respectively). Scheme between "Atezolizumab + Bevacizumab + Chemotherapy" and "Atezolizumab + Chemotherapy" made no significant difference (OR = 1.18, 95%CI: 0.56-2.42) concerning the rate of grade 3-4 toxicity. It seemed that ICI-chemo yielded more improvement in quality-adjusted life-year (QALY) than "Bevacizumab + Chemotherapy" in cost-effectiveness analysis. CONCLUSION: Our results suggest that ICI-chemo is associated with potentially longer survival, better cost-effectiveness outcomes, and comparable safety profiles than anti-angio-chemo. Also, adding bevacizumab to ICI-chemo seemed to provide additional therapeutic benefits without adding treatment burden. Our findings would supplement the current standard of care and help the design of future clinical trials for the first-line treatment of patients with advanced NSCLC.

Construction and evaluation of early prediction model for severe acute pancreatitis complicated with acute renal injury / 中华胰腺病杂志

Objective:To establish an early prediction Nomogram model for severe acute pancreatitis(SAP) complicated with acute renal injury (AKI), and evaluate the prediction efficiency of the model.Methods:The clinical data of 295 SAP patients hospitalized in Zhejiang Rongjun Hospital from July 2017 to June 2021 were retrospectively analyzed, and the patients were divided into AKI group ( n=61) and non-AKI group ( n=234) according to whether complicated with AKI. The common characters, clinical data and laboratory examination results were compared. The risk factors for SAP complicated with AKI was analyzed by multivariate logistic regression analysis, and a nomogram prediction model was established by R software. The receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated to evaluate its prediction performance. Results:The acute physiology and chronic health assessment Ⅱ (APACHEⅡ) and Ranson score, the incidence of abdominal compartment syndrome (ACS) and systemic inflammatory response syndrome (SIRS), the cases of shock and mechanical ventilation, and the levels of blood lactic acid (BLA), blood creatinine (Scr), urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT) and cystatin C(Cys C) in peripheral blood were significantly higher in AKI group than those in non-AKI group, while the levels of blood calcium were lower than those in non-AKI group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that APACHEⅡ score ( OR=1.185, 95% CI 1.074-1.308, P=0.001), Ranson score ( OR=12.668, 95% CI 5.102-31.456, P<0.001), Scr ( OR=1.028, 95% CI 1.002-1.054, P=0.034), PCT ( OR=4.298, 95% CI 1.379-13.395, P<0.001) and Cys C ( OR=38738.38, 95% CI 43.190-347459.41, P<0.001) were independent risk factors for SAP complicated AKI. Serum calcium ( OR=0.0001, 95% 0.000-0.048, P<0.001) was an independent protective factor for SAP complicated AKI. A Nomogram prediction model based on the six factors above were established, and its AUC, sensitivity and specificity to predict AKI were 0.987, 99.0% and 98.5% in the training set, and were 0.976, 98.6% and 94.2% in the validation set. Conclusions:This study successfully established an early prediction model with high predict value for SAP complicated with AKI, which can efficiently predict the risk of SAP with concurrent AKI.

Photoelectric effect of hybrid ultraviolet-sensitized phototransistors from an n-type organic semiconductor and an all-inorganic perovskite quantum dot photosensitizer.

Low-dimensional all-inorganic perovskite quantum dots (QDs) have been increasingly developed as photo-sensing materials in the field of photodetectors because of their strong light-absorption capability and broad bandgap tunability. Here, solution-processed hybrid phototransistors built by a dithienothiophenoquinoid (DTTQ) n-type organic semiconductor transport channel mixing with a colloidal CsPbBr3 perovskite QD photosensitizer are demonstrated by manipulating the relative volume ratio from 10 : 0 to 9 : 1, 7 : 3, 5 : 5, 3 : 7, 1 : 9, and 0 : 10. This results in a significantly enhanced photodetection performance owing to the advantages of a high UV absorption cross-section based on the perovskite QDs, efficient carrier transport abilities from the DTTQ semiconductor, and the photogating effect between the bulk heterojunction photocarrier transfer interfaces. The optimized DTTQ : QD (3 : 7) hybrid phototransistor achieves a high photoresponsivity (R) of 7.1 × 105 A W-1, a photosensitivity (S) of 1.8 × 104, and a photodetectivity (D) of 3.6 × 1013 Jones at 365 nm. Such a solution-based fabrication process using a hybrid approach directly integrated into a sensitized phototransistor potentially holds promising photoelectric applications towards advanced light-stimulated photodetection.