Glutathione (GSH) depletion can inhibit glutathione peroxidase 4 (GPX4) activity, leading to the accumulation of lipid peroxides and the induction of ferroptosis. However, achieving efficient GSH depletion under the hypoxic conditions typical of tumor microenvironments using non-precious metal-based materials remains a significant challenge for effective cancer therapy. Methods:We synthesized a two-dimensional birnessite-type nanosheet-like manganese oxide nanozyme (CMO). The multienzymatic activity and GSH consumption capacity of CMO were evaluated. Density functional theory calculations and material characterizations were utilized to investigate the mechanism of GSH oxidation under varying oxygen levels. In vitro and in vivo experiments using 4T1 tumor models were conducted to assess the nanozyme's ability to induce cytotoxicity, corresponding mechanism, and function as a magnetic resonance imaging contrast agent. Results:CMO demonstrated ultrafast GSH depletion, consuming GSH within 1 minute at a concentration of 20 μg/mL. Importantly, this rapid depletion capacity was not suppressed under hypoxic conditions. Theoretical and experimental analyses revealed that GSH oxidation was driven by the reduction of Mn and the sacrificing of lattice oxygen, which generated oxygen vacancies and a rougher material surface. In vitro and in vivo studies confirmed that CMO induced ferroptosis and immunogenic cell death in 4T1 cells. This process promoted dendritic cell maturation and T-cell infiltration, successfully eliciting a robust systemic antitumor immune response. Furthermore, CMO exhibited significant magnetic resonance imaging capabilities, validating its theranostic potential. Conclusions:The study presents a non-precious metal-based birnessite-type manganese oxide nanozyme capable of ultrafast GSH consumption under hypoxia. This platform effectively activates immunogenic ferroptosis and offers strong potential for magnetic resonance imaging-guided cancer immunotherapy.

Objective:The current study aimed to compare clinical outcomes and postoperative complications of two endoscopic treatments (endoscopic isolated papillary small balloon dilation [EIPSBD] and endoscopic sphincterotomy [EST]) with endoscopic papillary balloon dilation (EPBD) in patients with choledocholithiasis. Methods:A total of 316 patients diagnosed with and treated for choledocholithiasis from January 2014 to December 2024 were enrolled in this nonrandomized study. The patients were divided into EIPSBD (n = 178) and EST + EPBD groups (n = 138). Postoperative morbidities, including pancreatitis, cholangitis, bleeding, and hyperamylasemia, were assessed at 3 and 24 hours. Stone clearance was also evaluated. Results:The incidence of pancreatitis was 9.55% in the EIPSBD group and 7.97% in the EST + EPBD group (P = .5). Hyperamylasemia occurred in 41.57% of the patients in the EIPSBD group and 42.03% in the EST + EPBD group (P = .9). The incidence of cholangitis, bleeding, and stone clearance was not significantly different between the two groups. The incidence of pancreatitis in female patients was greater than male patients (χ2 = 5.12, P = .025). The total complication rate was 10.67% and 10.14% in the EIPSBD and EST ± EPBD groups, respectively, and was not significantly different (P = .9). Conclusion:EIPSBD and EST ± EPBD were shown to be equally effective in the treatment of choledocholithiasis with comparable postoperative complication rates. EIPSBD may be an acceptable alternative to traditional EST for stones ≤10 mm in size. Follow-up studies of longer duration will be helpful to assess long-term outcomes.

OBJECTIVES:The Node Reporting and Data System (Node-RADS) offers a reliable framework for lymph node assessment, but its prognostic significance remains unexplored. This study aims to investigate the added prognostic value of Node-RADS in patients with locally advanced gastric cancer (LAGC) undergoing neoadjuvant chemotherapy (NAC) followed by gastrectomy. MATERIALS AND METHODS:This single-center retrospective study included 118 patients with LAGC underwent NAC and gastrectomy. The maximum Node-RADS score and the number of metastatic lymph node stations (defined as LNM-Station) were evaluated on pretreatment CT. The pretreatment Node-RADS-CT and Node-RADS-integrated models were developed using Cox regression to predict overall survival (OS) and disease-free survival (DFS). The pretreatment cN-CT models, cN-integrated models, as well as post-NAC pathological models were also developed in comparison. The performance of the models was assessed in terms of discrimination, calibration and clinical applicability. RESULTS:The LNM-Station was significantly associated with OS and DFS (all p < 0.05). The Node-RADS-CT model showed higher Harrell's consistency index (C-index) than cN-CT model (0.755 vs. 0.693 for OS, p = 0.017; 0.759 vs. 0.706 for DFS, p = 0.018). The Node-RADS-integrated model also achieved higher C-index than cN-integrated model (0.771 vs. 0.731 for OS, p = 0.091; 0.773 vs. 0.733 for DFS, p = 0.053). The net reclassification improvement (NRI) of the Node-RADS-integrated model at 5 years was 0.379 for OS and 0.364 for DFS (all p < 0.05). The integrated discrimination improvement (IDI) of the Node-RADS-integrated model was 0.103 for OS and 0.107 for DFS (all p < 0.05). The C-indices (OS: 0.745; DFS: 0.746) of pathological models were slightly lower than those of Node-RADS-based models (all p > 0.05). CONCLUSION:The baseline Node-RADS score and LNM-Station were effective prognostic indicators for LAGC. The pretreatment CT Node-RADS-based models can offer added prognostic value for LAGC, compared with clinical N stage.

Background: Accurate diagnosis of patients with ulcerative colitis (UC) can reduce their risk of developing colorectal cancer. This study intended to explore whether moxifloxacin, an agent with fluorescence potential, could promote two-photon microscopy (TPM) diagnosis for mice with dextran sodium sulfate (DSS)-induced colitis, which could imitate human UC. Methods: 32 Balb/c mice were randomly divided into 4 groups: control, acute colitis, remission colitis and chronic colitis. Fluorescence parameters, imaging performance, and tissue features of different mouse models were compared under moxifloxacin-assisted TPM and label-free TPM. Results: Excitation wavelength of 720 nm and moxifloxacin labeling time of 2 min was optimal for moxifloxacin-assisted TPM. With moxifloxacin labeling for colonic tissues, excitation power was decreased to 1/10 of that without labeling while fluorescence intensity was increased to 10-fold of that without labeling. Photobleaching was negligible after moxifloxacin labeling and moxifloxacin fluorescence kept stable within 2 h. Compared with the control group, moxifloxacin fluorescence was reduced in the three colitis groups (P < 0.05). Meanwhile, the proportion of enhanced moxifloxacin fluorescence regions was (22.4 ± 1.6)%, (7.7 ± 1.0)%, (13.5 ± 1.7)% and (5.0 ± 1.3)% in the control, acute, remission and chronic groups respectively, with significant reduction in the three colitis groups (P < 0.05). Besides, variant tissue features of experimental colitis models were presented under moxifloxacin-assisted TPM, such as crypt opening, glandular structure, adjacent glandular space and moxifloxacin distribution. Conclusions: With unique biological interaction between moxifloxacin and colonic mucosa, moxifloxacin-assisted TPM imaging is feasible and effective for accurate diagnosis of different stages of experimental colitis.

Endoscopic submucosal dissection (ESD) is a popular technique for resecting duodenal tumors. However, there is a risk of losing resected specimens during the procedure, particularly for lesions in the descending part of the duodenum. This study aims to introduce a simple and effective method for specimen collection after descending duodenal ESD using a self-made balloon occluder. The balloon occluder, made from a spray pipe and sterile rubber glove, is utilized to prevent the loss of resected specimens. The balloon is inflated under endoscopic visualization, occluding the descending lumen. With careful timing, the resected specimen can be safely collected by grasping it from the balloon using foreign forceps. This method has been successfully applied in several cases, demonstrating its practicality and efficacy. Further evaluation and validation of this technique in a larger patient population are warranted to establish its wider application in clinical practice.

Abstract Aims A recent guideline presented by the ESC Congress in 2022 had indicated a novel therapy targeted at pulmonary artery hypertension, known as pulmonary artery denervation (PADN), which get inspired from a laboratorial trial that could lowering the pulmonary artery pressure through the intervention on the animals. Our aim is to conduct a network meta‐analysis to compare the efficacy and safety of PADN from six aspects with the current conventional therapies. Methods and results According to the PRISMA guidance, databases including Ovid, ClinicalTrials.gov, Medline, Embase, and PubMed were searched from inception to 22 August 2023, along with a full assessment of the previous five meta‐analyses. Data were extracted and curated for Bayesian network meta‐analysis. The primary outcome was the change in the 6‐min walking distance (6MWD) from baseline with a secondary outcome called change in mean pulmonary artery pressure (mPAP) from baseline. The four safety outcomes included risk of clinical worsening, hospitalization, mortality and severe adverse events (SAEs). The comparison is structured on a contrast model based on 65 randomized controlled trials (RCTs) on PADN and the other conventional mainstream drugs. PADN had a better effect in improving 6MWD than Placebo (−77.76 m, 95% CI: −102.04 to −54.34 m), Macitentan (−65.32 m, 95% CI: −95.34 to −36.1 m), Bosentan (−64.5 m, 95% CI: −94.7 to −35.07 m), Iloprost (−62.66 m, 95% CI: −99.48 to −27.13 m), Oxygen (−62.42 m, 95% CI: −100.01 to −25.78 m), Treprostinil (−62.01 m, 95% CI: −89.04 to −35.61 m), Riociguat (−60.59 m, 95% CI: −86.11 to −35.98 m), Selexipag (−47.2 m, 95% CI: −85.61 to −10.19 m), Sildenafil (−44.92 m, 95% CI: −74.43 to −16.15 m), or Sitaxsentan (−39.53 m, 95% CI: −78.99 to −0.76 m). PADN had a better antihypertensive effect than placebo and showed statistical significant lower risks to induce clinical worsening and re‐hospitalization than treprostinil, riociguat, and placebo groups. No statistically significant difference in risk of mortality and severe adverse events was observed between PADN versus the other interventions. Conclusions Compared with 16 types of conventional therapies and Placebo, PADN has advantage over nine single therapies and Placebo in improving 6MWD and appears to be better than two types of dual‐drug combined therapies while with no statistical significance. PADN shows a favourable antihypertensive effect on mPAP and has a lower risk to trigger clinical worsening or hospitalization, while its risk on mortality and severe adverse events is still inconclusive.

Non-small-cell lung cancer (NSCLC) predominates lung cancer with a striking percentage of 85%. Eupafolin is documented to possess anti-tumor efficacy, which prompts efforts to uncover its impacts on the pathology of diseases including cancers. Focal adhesion kinase (FAK)-mediated phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) has been found to be associated with several carcinomas. Nevertheless, how eupafolin exerts its effects in NSCLC and whether FAK/PI3K/AKT is related to the corresponding mechanism remain unclear. Thus, the relevant experiments were carried out with NSCLC cells treated with eupafolin and/or LY294002 at first. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, wound healing, and transwell assays were used to assess cell viability, proliferation, migration, and invasion, respectively. Western blot assay was performed to measure the relative protein expressions of phosphorylated (p)-FAK/FAK, p-PI3K/ PI3K, p-AKT/AKT, matrix metalloproteinase 9 (MMP9), and ras homolog gene family member A (RhoA), and to determine transfection efficiency. From experimental results, it was found that eupafolin inhibited the viability, proliferation, migration, and invasion of NSCLC cells, and inactivated the FAK/PI3K/AKT pathway by downregulating the ratios of p-FAK/FAK, p-PI3K/PI3K, and p-AKT/AKTand the expressions of MMP9 and RhoA. On the contrary, overexpressed FAK upregulated the expressions of FAK, MMP9, and RhoA and the ratios of p-PI3K/ PI3K and p-AKT/AKT, and promoted cell proliferation, migration, and invasion. LY294002, conversely, could partly reverse the effects of FAK on the aforementioned aspects of NSCLC cells. Collectively, it was verified in our study that eupafolin regulates the proliferation, migration, and invasion of NSCLC cells by downregulating MMP9 and RhoA expressions via the FAK/PI3K/AKT axis, which may provide a promising avenue for cancer therapy.

BackgroundDifficult biliary cannulation and unintended pancreatic cannulation exist in biliary interventions during endoscopic retrograde cholangiopancreatography. Wire-guided cannulation over a pancreatic stent (PS-WGC) and needle-knife precut over a pancreatic stent (PS-NKP) may facilitate biliary cannulation. This study aimed to compare the outcomes of PS-NKP and PS-WGC following guidewire passage into the pancreatic duct.MethodsA total of 304 patients who inserted a pancreatic stent and continued cannulation using wire-guided (PS-WGC) or needle-knife precut (PS-NKP) from October 2018 to November 2021 in three centers were ultimately enrolled in this study. The success rate of cannulation and incidence of complications were compared between the two groups.ResultsResults of the success rate of cannulation in the PS-NKP (n = 98) group were significantly higher compared with the PS-WGC (n = 206) group (96.9% vs. 89.8%; P < 0.05). The overall adverse events were 10.2% (31/304), and PS-NKP had lower (PEP) rates compared with the PS-WGC (3.1% vs. 10.7%, P < 0.05).ConclusionThe PS-NKP group is superior to the PS-WGC group in terms of the effectiveness and safety of continued cannulation. Using needle-knife precut, especially early use, over the pancreatic stent to continue cannulation reduced PEP compared with PS-WGC.

Since two-photon microscopy (TPM) can obtain high-resolution images at cellular and subcellular level and moxifloxacin has multiphoton fluorescence characteristic, our study aimed to explore the feasibility and diagnostic value of moxifloxacin-assisted TPM in different human colorectal diseases, including low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN) and cancer tissues. Excitation power for TPM imaging with and without moxifloxacin was (2.74 ± 0.16) mW and (0.28 ± 0.02) mW, respectively (p < 0.05). Whether labeled with moxifloxacin or not, images of normal, LGIN, HGIN and cancer tissues all reached the strongest signal at 30 μm from the mucosa. Normalized fluorescence intensity of TPM images with moxifloxacin was approximately 10 times stronger than that without moxifloxacin. Fluorescence signal was differed significantly in normal, LGIN, HGIN and cancer tissues with or without moxifloxacin (p < 0.05). Besides, moxifloxacin-assisted TPM could present variant tissue features with different colorectal diseases, such as the crypt opening, glandular structure, adjacent glandular space and fluorescence distribution.

Background: This research explored the effects of vinorelbine combined with oxaliplatin on non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC cells were treated with vinorelbine, oxaliplatin, and insulin-like growth factor-1 (IGF-1; phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway activator), and transfected with ATP-binding cassette subfamily G member 2 (ABCG2) overexpression plasmid and silenced ABCG2 (siABCG2). Cell viability was detected by cell counting kit-8 assay, cell migration and invasion by the transwell assay, and cell apoptosis by flow cytometry. Levels of ABCG2, PI3K, phosphorylation (p)-PI3K, AKT, and p-AKT were evaluated through qRT-PCR and western blot. Results: Co-treatment with vinorelbine and oxaliplatin exerted synergistic effects in suppressing the proliferation, migration, invasion, and the phosphorylation of PI3K and AKT, and inhibiting ABCG2 expression while inducing apoptosis in NSCLC cells. Overexpression of ABCG2 reversed these effects on proliferation, migration, invasion, and apoptosis, while not affecting the PI3K/AKT pathway in NSCLC cells. IGF-1 inhibited the synergistic effect of vinorelbine and oxaliplatin on the NSCLC cells. Moreover, siABCG2 reversed the effects of IGF-1 on ABCG2 expression, and other cellular functions mentioned above in NSCLC cells receiving the co-treatment. Conclusion: A combination of vinorelbine with oxaliplatin represses the proliferation, migration, and invasion of NSCLC cells, and facilitates apoptosis via inhibition of the PI3K/AKT/ABCG2 axis.

BACKGROUND:Lung adenocarcinoma is the leading cause of cancer death worldwide. Recently, ubiquitin C-terminal hydrolase L1 (UCHL1) has been demonstrated to be highly expressed in many tumors and plays the role of an oncogene. However, the functional mechanism of UCHL1 is unclear in lung adenocarcinoma progression.METHODS:We analyzed the differential expression of the UCHL1 gene in lung adenocarcinoma and normal lung tissues, and the correlation between the UCHL1 gene and prognosis was also analyzed by the bioinformatics database TCGA. Meanwhile, we detected and analyzed the expression of UCHL1 and Ki-67 protein in a tissue microarray (TMA) containing 150 patients with lung adenocarcinoma by immunohistochemistry (IHC) and clinicopathological characteristics by TCGA database. In vitro experiments, we knocked down the UCHL1 gene of A549 cells and detected the changes in cell migration, invasion, and apoptosis. At the same time, we analyzed the effect of UCHL1 on anti-tumor drug sensitivity of lung adenocarcinoma by a bioinformatics database. In terms of the detection rate of lung adenocarcinoma indicators, we analyzed the impact of UCHL1 combined with common clinical indicators on the detection rate of lung adenocarcinoma through a bioinformatics database.RESULTS:In this study, the analysis of UCHL1 protein expression in lung adenocarcinoma proved that obviously higher UCHL1 protein level was discovered in lung adenocarcinoma tissues. The expression of UCHL1 was closely related to poor clinical outcomes. Interestingly, a significantly positive correlation between the expression of UCHL1 and Ki-67-indicated UCHL1 was associated with tumor migration and invasion. Through executing loss of function tests, we affirmed that silencing of UCHL1 expression significantly inhibited migration and invasion of lung adenocarcinoma cells in vitro. Furthermore, lung adenocarcinoma cells with silenced UCHL1 showed a higher probability of apoptosis. In terms of the detection rate of lung adenocarcinoma indicators, we discovered UCHL1 could improve the detection rate of clinical lung adenocarcinoma and affect drug sensitivity.CONCLUSION:In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma. In addition, UCHL1 can improve the detection rate of clinical lung adenocarcinoma. Above all, UCHL1 may be a new marker for the diagnosis of lung adenocarcinoma and provide a new target for the treatment of clinical diseases.

BACKGROUND Left bundle branch pacing (LBBP) is the most rapidly growing conduction system pacing technique that is capable of correcting intrinsic left bundle branch block (LBBB). As such, it is potentially an optimal alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BiVP).OBJECTIVES The authors sought to compare the efficacy of LBBP-CRT with BiVP-CRT in patients with heart failure and reduced left ventricular ejection fraction (LVEF).METHODS This is a prospective, randomized trial of patients with nonischemic cardiomyopathy and LBBB with 6-month preplanned follow-up. Crossovers were allowed if LBBP or BiVP were unsuccessful. The primary endpoint was the dif-ference in LVEF improvement between 2 groups. The secondary endpoints included changes in echocardiographic measurements, N-terminal pro-B-type natriuretic peptide (NT-proBNP), New York Heart Association functional class, 6-minute walk distance, QRS duration, and CRT response.RESULTS The study included 40 consecutive patients (20 males, mean age 63.7 years, LVEF 29.7% +/- 5.6%). Cross-overs occurred in 10% of LBBP-CRT and 20% of BiVP-CRT. All patients completed follow-up. Intention-to-treat analysis showed significantly higher LVEF improvement at 6 months after LBBP-CRT than BiVP-CRT (mean difference: 5.6%; 95% CI: 0.3-10.9; P = 0.039). LBBP-CRT also appeared to have greater reductions in left ventricular end-systolic volume (-24.97 mL; 95% CI: -49.58 to -0.36 mL) and NT-proBNP (-1,071.80 pg/mL; 95% CI: -2,099.40 to -44.20 pg/mL), and comparable changes in New York Heart Association functional class, 6-minute walk distance, QRS duration, and rates of CRT response compared with BiVP-CRT.CONCLUSIONS LBBP-CRT demonstrated greater LVEF improvement than BiVP-CRT in heart failure patients with nonischemic cardiomyopathy and LBBB. (Left Bundle Branch Pacing Versus Biventricular Pacing for Cardiac Resynchro-nization Therapy [LBBP-RESYNC]; NCT04110431) (J Am Coll Cardiol 2022;80:1205-1216) (c) 2022 by the American College of Cardiology Foundation.

Benign anastomotic stricture is a frequent complication after rectal surgery. This study investigated the feasibility of endoscopic dilation combined with bleomycin injection for benign anastomotic stricture after rectal surgery. 31 patients who diagnosed with benign anastomotic stricture after rectal surgery were included in this study. 15 patients received simple endoscopic dilation (dilation group) and 16 patients received endoscopic dilation combined with bleomycin injection (bleomycin group). The clinical effect and adverse events were compared in the 2 groups. The strictures were managed successfully and the obstruction symptoms were relieved immediately. There were 2 minor complications in dilation group and 3 minor complications in bleomycin group. The difference was not significant between the 2 groups (P > .05). During the follow-up, the mean reintervention interval was 4.97 +/- 1.00 months in dilation group and 7.60 +/- 1.36 months in bleomycin group. The median treatment times was 4 (range 3-5) in dilation group and 2 (range 2-3) in bleomycin group. The differences in the 2 groups were significant (P < .05). Compared with endoscopic dilation, endoscopic dilation combined with bleomycin injection may reduce the treatment times and prolong the reintervention interval, which is a safe and effective endoscopic management for benign anastomotic stricture after rectal surgery.

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe 3 O 4 core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe 3 O 4 @SiO 2 -QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn 2+ was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn 2+ with a 22-fold fluorescence emission enhancement in the presence of 10 μM Zn 2+ . Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM −1 S −1 based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivo experiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging.

Dental anatomy is an integrated, core fundamental dental course, which prepares students for all future clinical dental courses. This study aimed to build up an online dental learning platform of micro-computed tomography-based three-dimensional (3D) tooth models with pulp cavity, and to further evaluate its effectiveness for dental anatomy education using a cohort study. First, ninety-six extracted permanent teeth were scanned by micro-computed tomography and the enamel, dentine, and pulp cavity of each was distinguished by different grey-scale intensities using Mimics software. Three-dimensional images allowed further discrimination and insights into permanent three-rooted premolars, central tip, and dental diseases including deep caries and wedge-shaped defects. Furthermore, a second mesiobuccal canal (MB2) in maxillary permanent molar teeth and Vertucci type III root canal configuration in mandibular anterior teeth could be detected using the 3D analytical tool. A digitized 3D tooth model learning platform was implemented. Last, two groups of dental students were assessed to evaluate the effect of 3D models on dental anatomy education. Participants in the Digital group were allowed to use the online dental learning platform freely after class, while the participants in the Traditional group were not. Assessment quizzes showed that participants' scores improved in the Digital group with the use of the learning platform compared with scores in the Traditional group. A questionnaire survey indicated that the participants had a positive attitude toward the 3D models. Thus, adding digital 3D resources to a traditional curriculum may have a positive effect on academic achievements.

Bifunctional magnetic/fluorescent core-shell silica nanospheres (MNPs) encapsulated with the magnetic Fe 3 O 4 core and a derivate of 8-amimoquinoline (N-(quinolin-8-yl)-2-(3-(triethoxysilyl) propylamino) acetamide) (QTEPA) into the shell were synthesized. These functional MNPs were prepared with a modified stöber method and the formed Fe 3 O 4 @SiO 2 -QTEPA core-shell nanocomposites are biocompatible, water-dispersible, and stable. These prepared nanoparticles were characterized by X-ray power diffraction (XRD), transmission electron microscopy (TEM), thermoelectric plasma Quad II inductively coupled plasma mass spectrometry (ICP-MS), superconducting quantum interference device (SQUID), TG/DTA thermal analyzer (TGA) and Fourier transform infrared spectroscopy (FTIR). Further application of the nanoparticles in detecting Zn 2+ was confirmed by the fluorescence experiment: the nanosensor shows high selectivity and sensitivity to Zn 2+ with a 22-fold fluorescence emission enhancement in the presence of 10 μM Zn 2+ . Moreover, the transverse relaxivity measurements show that the core-shell MNPs have T2 relaxivity (r2) of 155.05 mM −1 S −1 based on Fe concentration on the 3.0 T scanner, suggesting that the compound can be used as a negative contrast agent for MRI. Further in vivo experiments showed that these MNPs could be used as MRI contrast agent. Therefore, the new nanosensor provides the dual modality of magnetic resonance imaging and optical imaging. Keywords nanosensor , Fe , O , nanoparticles , magnetic resonance imaging , core-shell silica nanospheres , ZnII fluorescent sensing

Mineral smectite granules have traditionally been used for diarrhea and gastrointestinal bleeding; however, the wound healing ability of mineral smectite granules has not been investigated in detail. Therefore, the present study explored the efficacy and safety of mineral smectite granules on wound healing. An excision wound rat model was established. The experimental group was treated with smectite granules, the positive control group was treated with starch and the blank control group was left untreated. Wound closure rates, wound healing times and histopathological analysis were compared among the three groups. The mechanism underlying the effects of mineral smectite granules on wound healing was assessed by performing picrosirius red staining and immunohistochemical staining and measuring hydroxyproline content. Based on wound closure rates, wound healing times and histopathological analysis, the results indicated that rats treated with smectite granules displayed increased wound healing efficacy compared with the other two groups. Investigation of the underlying mechanism suggested that mineral smectite granules could promote wound healing by inducing collagen fiber synthesis and increasing the number of neovessels. The present study indicated the efficacy and safety of mineral smectite granules on wound healing and provided a theoretical basis for its application in a clinical setting.

目的 目前临床上使用的黏膜下注射剂品种繁多但各有优劣,使用何种黏膜下注射剂效果更佳仍待探索.文章旨在研究一种新型可注射剪切变稀水凝胶,并评估其用于内镜胃部黏膜下注射和辅助电刀剥离的可行性、有效性,为临床应用提供实验依据.方法 通过将不同体积的laponite粉末加入0.2％海藻酸钠水溶液中合成不同浓度的水凝胶,观察其可注射性及流变性能.对新鲜离体猪胃(离体时间<12 h)进行黏膜下注射,观察对比注射2 mL不同浓度水凝胶、等渗盐水和0.4％透明质酸钠的黏膜隆起高度和随时间变化情况;新鲜离体猪胃,用等渗盐水、0.4％透明质酸钠及水凝胶隆起相同面积(3 cm)的黏膜,随后用高频电刀模拟内镜下黏膜下剥离术(ESD)进行隆起黏膜完整剥离,比较分析操作时间.结果 流变性实验证明,合成了稳定的水凝胶.该水凝胶具有较好的剪切变稀性,且通过改变laponite的浓度,可以方便地调节其流变行为.不同浓度的水凝胶均可顺利通过23G内镜下注射针注射.离体猪胃黏膜下注射2 mL不同黏膜下注射剂,2％～5％浓度水凝胶的隆起高度[(8.70±0.57)、(9.60±0.89)、(10.10±0.74)、(9.50±1.41)mm]均大于等渗盐水[(5.20±0.76)mm]和透明质酸钠[(7.40±0.74)mm],差异有统计学意义(P<0.05).注射水凝胶黏膜隆起高度随时间变化最为稳定、缓慢.在60 min时,等渗盐水处理的隆起高度维持率不足25％,透明质酸钠处理的隆起高度维持率约为46％,而不同浓度水凝胶(2％～5％)的隆起维持率高达72％～83％.注射4％水凝胶后隆起的平均剥离时间最短为[(3.09±0.70)min],明显低于等渗盐水组[(7.97±0.42)min]和透明质酸钠处理[(6.92±0.39)min],差异有统计学意义(P<0.01).结论 该水凝胶具有良好的流变性及可注射性,可有效且持久稳定地维持胃黏膜下隆起高度,降低电刀剥离操作时间,有望成为一种新型的黏膜下注射剂.

PURPOSE:Atherosclerosis is the leading cause of cardiovascular diseases (CVD) with high incidence rate and mortality rate. Long non-coding RNAs (lncRNAs) are important functional molecules in atherosclerosis. Present study aimed to explore the functional role and underlying mechanism of ZFAS1 in atherosclerosis. METHODS:The in-vitro cell model of atherosclerosis was established by using oxidized low-density lipoprotein (ox-LDL) to induce THP-1 macrophage-derived foam cells. qRT-PCR measured the mRNA levels of ZFAS1, miR-654-3p, ADAM10 and RAB22A. Western blot detected the protein levels of ADAM10 and RAB22A. The levels of IL-1β, IL-6 and TNF-ɑ (inflammatory biomarkers) were tested with ELISA assay. Detection of cholesterol efflux rate was experimented. The interaction between RNAs was affirmed with luciferase reporter and RNA pull-down experiments. RESULTS:The expression of ZFAS1 was significantly up-regulated in in-vitro cell model of atherosclerosis at a dose- and time-dependent manner. Knockdown of ZFAS1 impaired inflammatory responses and promoted cholesterol efflux rate. Overexpression of ZFAS1 accelerated inflammatory responses and hampered cholesterol efflux rate. Then, the cytoplasmic role of ZFAS1 was revealed. By bio-informatics analysis and mechanism assays, miR-654-3p was identified to bind with ZFAS1. Moreover, ADAM10 and RAB22A were targeted and suppressed by miR-654-3p. ZFAS1 served as a ceRNA to positively regulate ADAM10 and RAB22A expression through endogenously sponging miR-654-3p. CONCLUSION:In conclusion, ZFAS1 elevated ADAM10/RAB22A expression to reduce cholesterol efflux rate and facilitate inflammatory responses in atherosclerosis at a miR-654-3p-dependent way, suggesting a prospective treatment method for amelioration of atherosclerosis.

ABSTRACT Objective There is currently no consensus regarding the optimal management of acute suppurative thyroiditis (AST) secondary to pyriform sinus fistula (PSF). To investigate the benefits and adverse events of aspiration with or without lavage for the treatment of AST secondary to PSF. Subjects and methods This was a retrospective analysis of consecutive patients with AST secondary to PSF who were admitted at the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University between August 2012 and December 2018. Clinical information, procedural data, and imaging data were analyzed. Results Seven patients (five women; mean age, 16.9 ± 6.3 years; range, 8-26 years) were included. The patients most presented with anterior neck pain and swelling (n = 7), fever (n = 7), or odynophagia (n = 5). Six cases of AST occurred on the left side of the thyroid and 1 on the right. All patients had thyroid abscess. AST was diagnosed by ultrasound-guided needle aspiration cytology in all cases. PSF was diagnosed during the inflammatory stage in five patients and during the quiescent stage in two. All patients were treated with empiric antibiotics. Needle aspiration without lavage was performed in three cases. Needle aspiration with lavage was performed in four cases. Repeat aspiration was performed in three cases. All patients recovered completely, with no procedure-related complications. During 18.3 ± 7.8 months of follow-up, AST recurred in one case. Excision of the PSF was performed in another case. Conclusion Ultrasound-guided aspiration with or without lavage had a good treatment effect and without adverse events for the management of AST secondary to PSF.