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Background and Aims: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare, with limited evidence regarding endoscopic treatment. This study investigated the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluated long-term outcomes, including local recurrence and metastasis., Methods: Seventy-eight patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. Clinicopathologic characteristics and treatment outcomes were collected and analyzed., Results: En-bloc resection was achieved for 74 tumors (94.9%) and R0 resection for 68 tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥10 mm, and muscularis propria invasion as risk factors for noncurative resection. Two patients with R1 resection (vertical margin involvement) and 2 patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including 2 cases of delayed bleeding and 2 cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in 1 patient with R1 resection 3 months after the original procedure., Conclusions: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided by grants from the National Natural Science Foundation of China (82000623), Major Project of Shanghai Municipal Science and Technology Committee (23ZR1445500), Yangfan Program of Shanghai Municipal Science and Technology Committee (21YF1440100), and Outstanding Youth Foundation of Zhongshan Hospital, Fudan University (202ZSYQ12)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the value of predicting shunt-dependent hydrocephalus (SDHC) in patients with aneurysmal subarachnoid hemorrhage (aSAH) based on whole brain CT perfusion(CTP) and clinical data within 24 hours at admission. Methods: The clinical and imaging data of aSAH patients who received interventional embolization in our hospital were retrospectively collected from March 2018 to August 2022. All patients underwent one-stop whole brain CT examination within 24 hours after symptom onset, and the qualitative and quantitative CTP parameters were obtained after post-processing. Follow-up was conducted once every 2 months by consulting electronic medical records or by telephone for 6 months. According to whether SDHC occurred or not, the patients were divided into SDHC group and non-SDHC group. The differences between the two groups were compared. Logistic regression model was used to analyze and determine the predictive factors of SDHC, and the SDHC predictive model was established. The effectiveness of the predictive model was evaluated by drawing the receiver operating characteristic (ROC) curve of the subjects. Results: A total of 414 patients were included, including 132 males and 282 females, aged (59±11) years. 17.6%(73/414) patients had SDHC. There were significant differences in the occurrence of acute hydrocephalus, the World Neurosurgical League Scale (WFNS), the Hunt-Hess scale, the modified Fisher score (mFS), and the qualitative and quantitative parameters of CTP between the two groups (both P <0.001). Multivariate logistic regression analysis showed that acute hydrocephalus ( OR =8.621, 95% CI : 4.237-17.542),old age ( OR =1.107, 95% CI : 1.068-1.148), high mFS and high Hunt-Hess classification ( OR =3.740, 95% CI : 1.352-10.342) were the risk factors of SDHC in aSAH patients, and high mean cerebral blood flow (mCBF) ( OR =0.931, 95% CI : 0.885-0.980) was a protective factor of SDHC.The area under ROC curve (AUC) of the prediction model constructed by these five variables was 0.923(95% CI : 0.89-0.95), with 84.5% sensitivity and 87.7% specificity. Conclusion: The mCBF and acute hydrocephalus, age, mFS and Hunt-Hess classification within 24 hours at admission can be used to predict SDHC for aSAH patients.

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.

Objective: To evaluate the utility of computed tomography perfusion (CTP) both at admission and during delayed cerebral ischemia time-window (DCITW) in the detection of delayed cerebral ischemia (DCI) and the change in CTP parameters from admission to DCITW following aneurysmal subarachnoid hemorrhage., Methods: Eighty patients underwent CTP at admission and during DCITW. The mean and extreme values of all CTP parameters at admission and during DCITW were compared between the DCI group and non-DCI group, and comparisons were also made between admission and DCITW within each group. The qualitative color-coded perfusion maps were recorded. Finally, the relationship between CTP parameters and DCI was assessed by receiver operating characteristic (ROC) analyses., Results: With the exception of cerebral blood volume (P=0.295, admission; P=0.682, DCITW), there were significant differences in the mean quantitative CTP parameters between DCI and non-DCI patients both at admission and during DCITW. In the DCI group, the extreme parameters were significantly different between admission and DCITW. The DCI group also showed a deteriorative trend in the qualitative color-coded perfusion maps. For the detection of DCI, mean transit time to the center of the impulse response function (Tmax) at admission and mean time to start (TTS) during DCITW had the largest area under curve (AUC), 0.698 and 0.789, respectively., Conclusion: Whole-brain CTP can predict the occurrence of DCI at admission and diagnose DCI during DCITW. The extreme quantitative parameters and qualitative color-coded perfusion maps can better reflect the perfusion changes of patients with DCI from admission to DCITW., (© 2023. Huazhong University of Science and Technology.)

The punch tool is a swift and practical instrument in the facial pigmented melanocytic nevus. However, few studies have evaluated the efficacy of the method for facial pigmented nevus. The aim of this study was to evaluate the practicability and effectiveness of removing facial pigmented nevus by punch biopsy technique. This was an observational study of patients with facial pigmented nevus in the Hospital of Plastic Surgery, Weifang Medical University. The ages of patients ranged from 15 to 36 years (average, 25 y). The outcome evaluations included Vancouver Scar Scale (VSS) score, esthetic appearance, and patient satisfaction. Following standard procedures, preoperative surgical excision was performed with safety margins. Anatomopathologic analysis of the surgical specimen was used as the gold standard to evaluate the accuracy of diagnosis by punch biopsy. From January 2019 to January 2020, this punch technique was carried out on 96 patients (151 pigmented nevus) with 35 melanocytic nevus on the forehead, 39 on the cheek, 21 on the eyelid, and 45 on the nose, whereas 11 were on nasolabial folds. The diameters of pigmented nevus are 0.5 to 10 mm on the face. All patients were evaluated at a follow-up visit ranging from 6 to 20 months (average, 11±1.5 mo) and healed with no complication. The histopathological examinations of the skin lesions showed benign outcomes. The mean Vancouver Scar Scale were 1.1±0.4. Ideal cosmetic and functional outcomes were achieved in 94 patients (97.9%). All patients achieved complete satisfaction except 2 patients with partial satisfaction. No recurrences and complications were recorded. This study demonstrated that the punch technique is an effective method to remove facial pigmented melanocytic nevus with acceptable functional and esthetic outcomes without relapse., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Biodiesel consists of various fatty acid methyl esters (FAMEs) that are mainly produced through transesterification of plant oil or animal fat. It is essential for biodiesel to be purified utmostly to meet its product standard before being traded, while the universal purification method has been water washing. However, water washing inevitably causes the residual of FAMEs in wastewater, which represents a loss of industrial profits. For the purpose of determination and monitoring of the FAME profile in wastewater, there is a necessity to develop a fast and reliable approach with small volume of sample in need. Hence, in this study, a combination of dispersive liquid-liquid microextraction (DLLME) and microwave demulsification is applied for the enrichment of residual FAMEs in water, followed by qualitative and quantitative analyses using gas chromatography-mass spectrometry. The results indicate that the optimal extractant in DLLME approach is toluene. And the optimal parameters are 20 mL of water sample, 80 μL of toluene as the extractant, 60 s of ultrasonic irradiation duration, 200 W of microwave power and 2 min of microwave irradiation duration. The standard curves and linear equations obtained with these conditions are used for the quantitative analysis of biodiesel wastewater, which reveals that there was 50.35 mg·L-1 of the total FAME residuals in wastewater. To the best of our knowledge, it is for the first time that the combined technique of DLLME and microwave demulsification is applied in determination of residual FAMEs in water samples. The proposed method corresponds to small volumes of sample and extractant and short analytical period. It also has the potential to be extended to the analysis of other water pollutants., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Surface water samples were collected in the middle reaches of the Yellow River (Weinan-Zhengzhou section) and all 28 perfluoroalkyl and polyfluoroalkyl substance (PFAS) levels were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The results show that the levels of PFASs in the water and particle phase are 18.4-56.9 ng·L -1 and 26.8-164 ng·g -1 , respectively. Perfluorohexanoic acid (PFHxA) in the water and particle phases is the main pollutant, accounting for 27% and 16% of the total concentrations, respectively, and 3H-perfluoro-3-[(3-methoxy-propoxy)-propanoate] acid (ADONA) and chlorinated polyfluorinated ethersulfonic acids (6:2 and 8:2 Cl-PFESA) were detected in the particle phase, indicating that the use of PFAS alternatives gradually increases. The lg K d of PFASs between the water and particle phase ranges from 2.95±0.553 (PFPeA) to 3.85±0.237 (8:2 FTUCA)and the adsorption of fluorotelomer carboxylic acids (FTCAs) and fluorotelomer unsaturated carboxylic acids (FTUCAs) on particulate matter increases with increasing of carbon chain length. Perfluoroalkane sulfonic acids (PFSAs) are more easily adsorbed by particulate matter than perfluoroalkyl carboxylic acids (PFCAs). The fluxes of PFASs in the Weinan-Zhengzhou section of the Yellow River show a decrease at first and then increase, indicating that this section receives pollution inputs from the upstream and tributaries. In addition, the results show that the fluxes of PFASs in the water phase are greater than those in the particle phase.

Objective: MiRNAs are important regulators of translation and have been described as biomarkers of a number of cardiovascular diseases, including stroke. The purpose of the study was to determine expression levels of serum miR-1297 in patients with aneurysmal subarachnoid hemorrhage (aSAH), and to assess whether miR-1297 was the prognostic indicator of aSAH. Methods: We treated 128 aSAH patients with endovascular coiling. The World Federation of Neurological Surgeons (WFNS) grades, Hunt-Hess grades, and modified Fisher scores were used to assess aSAH severity. Neurologic outcome was assessed using the Modified Rankin Scale (mRS) at 1-year post-aSAH. Serum was taken at various time points (24, 72, and 168 h, and 14 days). Serum samples from aSAH patients and healthy controls were subjected to reverse transcription (RT) quantitative real-time PCR (RT-qPCR). Results: A poor outcome at 1 year was associated with significantly higher levels of miR-1297 value at the four time points, higher WFNS grade, higher Hunt-Hess grade, and higher Fisher score. Serum miR-1297 levels were significantly higher in patients, compared with healthy controls. There were significant correlations of miR-1297 concentrations in serum with severity in aSAH. The AUCs of miR-1297 at the four time points for distinguishing the aSAH patients from healthy controls were 0.80, 0.94, 0.77, and 0.59, respectively. After multivariate logistic regression analysis, only miR-1297 at 24 and 72 h enabled prediction of neurological outcome at 1 year. Conclusion: Serum was an independent predictive factor of poor outcome at 1 year following aSAH. This result supports the use of miR-1297 in aSAH to aid determination of prognosis., (© 2018 The Author(s).)

Aims: Inflammation plays a crucial role in aneurysm wall remodeling, which could lead to the rupture of intracranial aneurysms. Stromal cell-derived factor 1α (SDF-1α), a vital inflammation cytokine, is also related to aneurysm pathogenesis. However, the characteristics of SDF-1α expression and its role in aneurysm remodeling remain largely unknown. In this study, we aimed to investigate the expression dynamics of SDF-1α and its correlation with aneurysm remodeling., Methods: Saccular aneurysms were induced by porcine pancreatic elastase in New Zealand White rabbits. Aneurysm size was measured by digital subtraction angiography. Endothelial-like cells on the aneurysm wall were assessed on postoperative days 1, 3, 7, 14, 21, and 30. SDF-1α levels in the aneurysmal wall and serum were examined at several follow-up time points. Adherent molecule expression was examined, and migration assays were performed in vitro. After SDF-1α stimulation, the mobilization of endothelial-lineage cells and its role in the reendothelialization of the aneurysm wall were investigated in a saccular aneurysm rabbit model., Results: After the creation of saccular aneurysms in rabbits, the aneurysm sacs were filled with acute thrombosis within 3days, followed by a significant enlargement on day 14 and maturation on day 21. Serum SDF-1α levels increased in a bimodal fashion on day 1 and day 14, whereas SDF-1α expression in the aneurysm wall reached its maximum on day 14. VE-cadherin was up-regulated after SDF-1α stimulation and down-regulated by the SDF-1α ligand blocker AMD3100. Endothelial progenitor cell migration was enhanced by SDF-1α and blocked by AMD3100. The in vivo administration of SDF-α to rabbits with saccular aneurysms promoted endothelial-lineage cell mobilization into the peripheral blood and reendothelialization of the aneurysm wall., Conclusions: The SDF-1α expression level in the peripheral blood and local aneurysm wall correlated with the aneurysm remodeling process in rabbits with elastase-induced saccular aneurysms. We conclude that SDF-1α may facilitate aneurysm wall remodeling by up-regulating VE-cadherin expression and mobilizing endothelial-lineage cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

miRNAs are important regulators of translation and have been associated with the pathogenesis of a number of cardiovascular diseases including stroke and may be possible prognostic biomarkers. The purpose of the present study was to determine the expression levels of miRNAs in the sera of subarachnoid haemorrhage (SAH) patients and to evaluate their relationships with the severity and clinical outcome of SAH. Serum samples on day 3 after the onset of SAH were subjected to microarray analysis with Exqion miRCURY TM LNA array and quantitative PCR analysis. Serum samples from SAH patients ( n =60) and healthy controls ( n =10) were subjected to quantitative PCR analysis. The severities and clinical outcomes of the SAH patients were evaluated with the WFNS grade and the Modified Rankin Scale (mRS). Three miRNAs, miR-502-5p , miR-1297 and miR-4320 were significantly up-regulated in the sera of SAH patients when compared with the healthy controls. The serum miR-502-5p and miR-1297 levels were significantly higher in the patients with severe SAH and a poor outcome than in those with mild SAH and a good outcome ( P <0.05). The areas under the receiver operating characteristic (ROC) curves (AUCs) of miR-502-5p , miR-1297 and miR-4320 to distinguish the SAH patients from the healthy controls were 0.958 ( P <0.001), 0.950 ( P <0.001) and 0.843 ( P <0.001) respectively. Taken together, these results indicate that miR-502-5p and miR-1297 are potentially valuable indicators of the diagnosis, severity and prognosis of SAH, and miR-4320 was a potentially valuable indicator of the diagnosis of SAH., (© 2017 The Author(s).)

Background: MicroRNA-210 (miR-210) is an oncogenic miRNA previously associated with prognosis in human gliomas, an incurable tumour type of the central nervous system. Here miR-210 was investigated as a potential serum biomarker in the diagnosis and prognosis of glioma., Methods: Serum was immediately prepared from blood samples collected from patients with glioma grades I-IV at primary diagnosis (n=136) and healthy controls (n=50) from February 2007 to March 2014 in the Department of Neurosurgery of the First Affiliated Hospital of Wannan Medical College (Wuhu, China). Total RNA was isolated from serum. cDNA was synthesised with primers specific for miR-210 and miR-16-1 (internal control), and quantitative real-time RT-PCR was performed. Results were statistically analysed to determine the role of miR-210 in the diagnosis and prognosis of human glioma patients., Results: An approximately seven-fold increase in miR-210 expression was detected in serum samples from glioblastoma patients relative to healthy controls. A threshold expression value (2.259) was chosen from receiver operator characteristic curves (ROC), and the low and high miR-210 expression groups were analysed by multivariate Cox proportional hazard regression and Kaplan-Meier analyses. Results revealed an association of high serum miR-210 expression with tumour grade and poor patient outcome (P-values <0.001)., Conclusions: Serum miR-210 is a promising diagnostic and prognostic biomarker that can be detected in the peripheral blood of patients with glioma.

Aims: Endothelial progenitor cells (EPCs) are involved in vascular repair and homeostasis after vascular injuries. In this study, we aimed to explore whether bone marrow (BM)-derived EPCs contribute to neointima formation and reendothelialization in rabbit elastase-induced aneurysm after flow diverter treatment., Methods: Elastase-induced aneurysms were created in New Zealand male rabbits. Three weeks after model creation, flow diverter was implanted to cover the induced aneurysm neck. Autologous EPCs were isolated from bone marrow, expanded ex vivo, double labeled with Hoechst 33,342 and CFSE(carboxyfluorescein diacetate succinimidyl ester), and transplanted transvenously into the rabbits. The rabbits were assigned into three groups. The first group received autologous transfusion of double-labeled EPCs from the first day after stent implantation, and the second group received transfusion from the fifteenth day. The autologous transfusion was given at a 3-day interval and continued for 2 weeks. Fluorescence-labeled cells were tracked under fluorescence microscope at the aneurysm neck and parent artery in the two groups. The third group was established as control group without EPCs transplantation. Scanning electron microscope was used to investigate the reendothelialization rate between the former two groups and the control group., Results: In the first group, double-positive EPCs were found in 3/5 rabbits and mainly located in the subendothelial space and around the stent struts. In the second group, double-positive EPCs were found in 2/5 rabbits and mainly located on the surface of neointima. More endothelial-like cells were observed on the neointima of aneurysm neck and stented parent artery in the groups with EPCs transplantation than control group without EPCs transplantation, but the difference on the number of these cells did not reach statistical significance., Conclusions: BM-derived EPCs participate in neointima formation and reendothelialization in elastase-induced aneurysm after flow diverter treatment. The EPCs may differentiate into different cell types according to the stages of neointima formation in vivo., (© 2013 Blackwell Publishing Ltd.)

Objective: To establish 2-dimensional electrophoresis (2-DE) maps of Helicobac-ter pylori in human gastritis, and gastric cancer, to identify the differentially expressed proteins,and to discuss the role of bacterial factor in pathogenesis., Methods: The total proteins of Helicobacter pylori in human gastritis and gastric cancer were separated by immobilized pH gradient-based 2-DE. The differentially expressed proteins were screened by PDQuest analysis software and identified by peptide mass fingerprint based on matrix-assisted laser desorption/ionization time of flight mass spectrometry, and searched on database., Results: A well-resolved and reproducible 2-DE pattern of Helicobacter pylori was obtained from patients with human gastritis and gastric cancer. Fourteen differentially expressed proteins were identified, including proteins related to anti-oxidation,molecular chape-rones and detoxification, enzymes related to metabolism,proteins related to cytoarchitecture,and proteins related to signal conduction., Conclusion: A well-resolved and reproducible 2-DE pattern of Helicobacter pylori in human gastritis and gastric cancer is established and differentially expressed proteins from these 2 diseases are identified. The differentiation of protein expression may play an important role in the pathogenesis of gastric cancer.

A stability-indicating, quality control analysis method was developed and validated for the diuretic drug substances hydrochlorothiazide (HCTZ) and chlorothiazide (CTZ). Micellar electrokinetic capillary chromatography employing the anionic detergent sodium dodecyl sulfate at 30 mM in 20 mM sodium borate buffer pH 9.5 was utilized to separate and quantify the active drug substance HCTZ from CTZ and the common impurity, 4-amino-6-chloro-1,3-benzenedisulfonamide (DSA). A 100 microns I.D. uncoated fused-silica capillary was necessary to provide the sensitivity, i.e. 1 microgram/ml, for quantification of the DSA impurity. In this study, the linearity, precision, selectivity, accuracy, reproducibility and limit of quantitation for the method were investigated for HCTZ, CTZ and DSA. As the first validation of a drug substance method by capillary electrophoresis in this laboratory, unusual care was taken to insure reliability and ruggedness with multiple instruments, capillaries and analysts. Precision and reproducibility in the range of 1% R.S.D. was achieved by controlling subtle injection factors. These included minimizing the time in which the capillary ends were not immersed in buffer or sample during the injection process and minimizing the number of assays for each anode or inlet buffer vial. Stacking induced by differences in ionic strength between sample and capillary buffer was reduced by using a sample buffer concentration similar to that of the capillary buffer. Although stacking accomplished by using lower sample buffer concentrations increased sensitivity, reproducibility was decreased. Achievement of the 1% R.S.D. precision level means that many quality control assays for drugs with good absorbance characteristics can be validated with HPLC reproducibility and CE efficiency. These micellar electrokinetic capillary chromatography methods conform to the USA and European Pharmacopoeial validation guidelines.

The five active drug substances and two of the excipients present in Frenadol, a cold medication, were separated. The active drug components dextromethorphan HBr monohydrate, ascorbic acid, caffeine, paracetamol and chlorpheniramine maleate were quantitatively assayed by a mixed ion pair LC method. The excipients separated were citric acid and maleic acid. The HPLC assay included dual-wavelength detection to simultaneously quantify the large concentration of paracetamol and the much lower concentration of chlorpheniramine and dextromethorphan. Both tetrabutylammonium hydrogen sulphate (TBA) and pentane sulphonic acid (PSA) were necessary for resolution of the seven compounds. The TBA was necessary to lessen peak tailing for dextromethorphan and chlorpheniramine, to retain ascorbic acid and to shorten assay time. The pentane sulphonic acid enhanced peak shape for dextromethorphan and chlorpheniramine. The assay of the active drug substances was validated for use in quality control applications. Validation studies demonstrated that the procedure was accurate, linear, precise, reproducible and rugged. The method conformed to both USP and EC validation guidelines.