Endoscopic ultrasound-guided versus surgical pancreatic duct drainage after failed endoscopic retrograde pancreatography: a pilot comparative study.

BACKGROUND: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis. METHODS: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention. RESULTS: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group. CONCLUSION: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy.

Comparative Performance of Endoscopic Ultrasound-Based Techniques in Patients With Pancreatic Cystic Lesions: A Network Meta-Analysis.

INTRODUCTION: Evidence on the comparative diagnostic performance of endoscopic ultrasound (EUS)-based techniques for pancreatic cystic lesions (PCLs) is limited. This network meta-analysis comprehensively compared EUS-based techniques for PCL diagnosis. METHODS: A comprehensive literature search was performed for all comparative studies assessing the accuracy of 2 or more modalities for PCL diagnosis. The primary outcome was the diagnostic efficacy for mucinous PCLs. Secondary outcomes were the diagnostic efficacy for malignant PCLs, diagnostic success rate, and adverse event rate. A network meta-analysis was conducted using the ANOVA model to assess the diagnostic accuracy of each index. RESULTS: Forty studies comprising 3,641 patients were identified. The network ranking of the superiority index for EUS-guided needle-based confocal laser endomicroscopy (EUS-nCLE) and EUS-guided through-the-needle biopsy (EUS-TTNB) were significantly higher than other techniques for differentiating mucinous PCLs; besides, EUS-TTNB was also the optimal technique in identifying malignant PCLs. The evidence was inadequate for EUS-nCLE diagnosing malignant PCLs and contrast-enhanced harmonic EUS diagnosing both mucinous and malignant PCLs. Glucose showed a high sensitivity but low specificity, and molecular analysis (KRAS, GNAS, and KRAS + GNAS mutations) showed a high specificity but low sensitivity for diagnosing mucinous PCLs. Satisfactory results were not obtained during the evaluation of the efficiency of pancreatic cyst fluid (PCF) biomarkers in detecting malignant PCLs. DISCUSSION: For centers with relevant expertise and facilities, EUS-TTNB and EUS-nCLE were better choices for the diagnosis of PCLs. Further studies are urgently required for further improving PCF biomarkers and validating the diagnostic performance of the index techniques.

New Insights into the Understanding of Mechanisms of Radiation-Induced Heart Disease.

OPINION STATEMENT: Cancer patients who receive high-dose thoracic radiotherapy may develop radiation-induced heart disease (RIHD). The clinical presentation of RIHD comprises coronary artery atherosclerosis, valvular disease, pericarditis, cardiomyopathy, and conduction defects. These complications have significantly reduced due to the improved radiotherapy techniques. However, such methods still could not avoid heart radiation exposure. Furthermore, people who received relatively low-dose radiation exposures have exhibited significantly elevated RIHD risks in cohort studies of atomic bomb survivors and occupational exposures. The increased potential in exposure to natural and artificial ionizing radiation sources has emphasized the necessity to understand the development of RIHD. The pathological processes of RIHD include endothelial dysfunction, inflammation, fibrosis, and hypertrophy. The underlying mechanisms may involve the changes in oxidative stress, DNA damage response, telomere erosion, mitochondrial dysfunction, epigenetic regulation, circulation factors, protein post-translational modification, and metabolites. This review will discuss the recent advances in the mechanisms of RIHD at cellular and molecular levels.

Nursing Cooperation Pattern for Patients With Advanced Pancreatic Cancer and Abdominal Pain Undergoing Endoscopic Ultrasound-guided Celiac Plexus Neurolysis.

Context: Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasound-guided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective: The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients' pain, decrease operation times, increase operational efficiency, and increase nurses' satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design: The research team designed a retrospective controlled study. Setting: The study took place at the Shenzhen People's Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants: Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention: Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People's Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures: The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn't satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results: The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P > .05), while a significant difference occurred in the nurses' operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses' satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient's rehabilitation and increase nurses' satisfaction. Conclusions: The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses' satisfaction.

Automatic synthesis of 18F-AV-45 and its clinical application in Alzheimer's disease.

OBJECTIVE: To investigate the automatic synthesis of ß-amyloid (Aß) positron emission tomography (PET) imaging agent (E) -4- (2- (6- (2- (2-18F fluoroethoxy) ethoxy) ethoxy) pyridine-3-yl) vinyl) - N-methylaniline (18F-AV-45) for the diagnosis of Alzheimer's disease (AD) and its clinical application in AD patients. MATERIALS AND METHODS: Fluorine-18-AV-45 was synthesized with AV-105 as the precursor, and the factors affecting the synthesis efficiency, such as the amount of precursor, nucleophilic reaction temperature were studied. At the same time, 18F-AV-45 PET/computed tomography (CT) brain scanning was performed in 15 patients with dementia to determine whether AD was the cause of the dementia. RESULTS: After optimizing the parameters, it was discovered that the highest synthesis efficiency was achieved with a AV-105 dosage of 2mg, a reaction temperature of 130oC, and 1mL of DMSO. The radiochemical yield (RCP) was greater than 98, and the uncorrected synthesis efficiency was about 31.0%±2.8%. Ten of the 15 patients with dementia showed positive Aß protein deposition, and the main deposition site of the imaging agent was the gray matter area of the brain, which was consistent with AD diagnosis, while the other 5 patients showed negative Aß protein deposition, suggesting non-AD dementia. CONCLUSION: ß-amyloid protein 18F-AV-45 imaging agent can be easily and quickly prepared by the All in One radiochemical synthesis module. Our preliminary results offer hope that it can effectively detect ß-amyloid deposition in the brain of AD patients in order to determine the etiology of dementia.

Enhanced autophagy promotes radiosensitivity by mediating Sirt1 downregulation in RM-1 prostate cancer cells.

Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC.

Altered diversity and composition of gut microbiota in Chinese patients with chronic pancreatitis.

BACKGROUND/OBJECTIVES: Gut microbiota alterations in chronic pancreatitis (CP) are seldomly described systematically. It is unknown whether pancreatic exocrine insufficiency (PEI) and different etiologies in patients with CP are associated with gut microbiota dysbiosis. METHODS: The fecal microbiota of 69 healthy controls (HCs) and 71 patients with CP were compared to investigate gut microbiome alterations in CP and the relationship among gut microbiome dysbiosis, PEI and different etiologies. Fecal microbiomes were analyzed through 16S ribosomal RNA gene profiling, based on next-generation sequencing. Pancreatic exocrine function was evaluated by determining fecal elastase 1 activity. RESULTS: Patients with CP showed gut microbiota dysbiosis with decreased diversity and richness, and taxa-composition changes. On the phylum level, the gut microbiome of the CP group showed lower Firmicutes and Actinobacteria abundances than the HC group and higher Proteobacteria abundances. The abundances of Escherichia-Shigella and other genera were high in gut microbiomes in the CP group, whereas that of Faecalibacterium was low. Kyoto Encyclopedia of Genes and Genomes pathways (lipopolysaccharide biosynthesis and bacterial invasion of epithelial cells) were predicted to be enriched in the CP group. Among the top 5 phyla and 8 genera (in terms of abundance), only Fusobacteria and Eubacterium rectale group showed significant differences between CP patients, with or without PEI. Correlation analysis showed that Bifidobacterium and Lachnoclostridium correlated positively with fecal elastase 1 (r = 0.2616 and 0.2486, respectively, P < 0.05). CONCLUSIONS: The current findings indicate that patients with CP have gut microbiota dysbiosis that is partly affected by pancreatic exocrine function.

Comparison of smear cytology and liquid-based cytology in EUS-guided FNA of pancreatic lesions: experience from a large tertiary center.

BACKGROUND AND AIMS: Studies comparing the diagnostic efficacy of liquid-based cytology (LBC) and smear cytology (SC) of pancreatic tissue sampling obtained via EUS-guided FNA (EUS-FNA) are still insufficient, mainly because results were controversial. We compared the diagnostic efficiency of LBC and SC of EUS-FNA of pancreatic lesions in one of the largest tertiary hospitals in China. METHODS: A retrospective database search (January 2015 to January 2019) was performed for patients who underwent EUS-FNA with both LBC and SC. Demographic, cytologic, and endosonographic data were collected from 819 patients; 514 cases met the inclusion criteria. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were compared. Rapid on-site evaluation was not available in all cases. RESULTS: Three hundred eighty-five cases (74.90%) had confirmed malignancy, and 40 cases (7.78%) confirmed benign neoplasm. Adequate tissue sampling rates showed no significant difference between the 2 groups. The sensitivity, accuracy, and negative predictive value (NPV) of LBC were higher than those of SC with statistical significance (71.4% vs 55.1%, 76.1% vs 61.6%, and 40.6% vs 27.7%, respectively). The sensitivity, accuracy, and NPV of combined SC and LBC were higher than those of LBC alone with statistical significance (83.9% vs 71.4%, 86.5% vs 76.1%, and 56.8% vs 40.6%, respectively). Multivariate analysis revealed that pancreatic neck/body/tail lesions (P = .003), solid lesions (P < .001), 22-gauge needle size (P < .001), and number of needle passage >3 (P = .041) were associated with higher diagnostic sensitivity in all participants using LBC, whereas number of needle passage >3 (P = .017) was associated with higher diagnostic sensitivity using SC. CONCLUSIONS: LBC was more accurate and sensitive than SC in EUS-FNA of pancreatic lesions with higher NPV when rapid on-site evaluation is unavailable. Pancreatic neck/body/tail lesions, solid lesions, 22-gauge needle, and more than 3 passes were associated with higher sensitivity when using LBC. Performing more than 3 passes is associated with higher sensitivity when using SC.

Factors associated with diagnostic accuracy, technical success and adverse events of endoscopic ultrasound-guided fine-needle biopsy: A systematic review and meta-analysis.

BACKGROUND AND AIM: Endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) is used to diagnose lesions within or adjacent to the digestive tract. However, there is no report on the overall diagnostic accuracy, technical success, and adverse events of FNB. The aims of this study were to conduct a systematic review and meta-analysis to comprehensively assess the diagnostic accuracy, technical success, and adverse events of FNB. METHODS: Pubmed, Embase, and Cochrane Library databases were searched for relevant articles published in English from January 1998 to May 2019 (No. CRD42019141647). Primary outcomes were EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate. RESULTS: A total of 51 articles including 5330 patients met our criteria. The overall EUS-FNB related diagnostic accuracy rate, technical success rate, and adverse event rate was 90.82% [95% confidence interval (CI) 88.69-92.76%], 99.71% [95% CI 99.35-99.93%], and 0.59% [95% CI 0.29-1.0%], respectively. Biopsy with 22G needle could increase the diagnostic accuracy rate and technical success rate to 92.17% [95% CI 89.32-94.61%] and 99.88% [95% CI 99.64-99.99%], respectively, and decrease the adverse event to 0.37% [95% CI 0.08-0.87%]. Moreover, it showed that 22G needle was an independent factor associated with a higher diagnostic accuracy rate and technical success rate and a lower adverse event rate (P = 0.04, P < 0.001, and P = 0.04, respectively) by univariate and multivariate meta-regression analyses. CONCLUSION: Endoscopic ultrasound-guided fine-needle biopsy is a feasible and safe procedure for lesions within or adjacent to the digestive tract. Biopsy using 22G needle could increase the diagnostic accuracy rate and technical success rate and decrease adverse event rate during the FNB procedure.

Spliceosomal Protein Gene BmSPX Regulates Reproductive Organ Development in Bombyx mori.

Sex determination and differentiation are nearly universal to all eukaryotic organisms, encompassing diverse systems and mechanisms. Here, we identified a spliceosomal protein gene BmSPX involved in sex determination of the lepidopeteran insect, Bombyx mori. In a transgenic silkworm line that overexpressed the BmSPX gene, transgenic silkworm males exhibited differences in their external genitalia compared to wild-type males, but normal internal genitalia. Additionally, transgenic silkworm females exhibited a developmental disorder of the reproductive organs. Upregulation of BmSPX significantly increased the expression levels of sex-determining genes (BmMasc and BmIMP) and reduced the female-type splice isoform of Bmdsx, which is a key switch gene downstream of the sex-determination pathway. Additionally, co-immunoprecipitation assays confirmed an interaction between the BmSPX protein and BmPSI, an upstream regulatory factor of Bmdsx. Quantitative real-time PCR showed that BmSPX over-expression upregulated the expression of the Hox gene abdominal-B (Adb-B), which is required for specification of the posterior abdomen, external genitalia, and gonads of insects, as well as the genes in the Receptor Tyrosine Kinase (RTK) signaling pathway. In conclusion, our study suggested the involvement of BmSPX, identified as a novel regulatory factor, in the sex-determination pathway and regulation of reproductive organ development in silkworms.

P-element Somatic Inhibitor Protein Binding a Target Sequence in dsx Pre-mRNA Conserved in Bombyx mori and Spodoptera litura.

Bombyx mori doublesex (Bmdsx) functions as a double-switch gene in the final step of the sex-determination cascade in the silkworm Bombyx mori. The P-element somatic inhibitor (PSI) protein in B. mori interacts with Bmdsx pre-mRNA in CE1 as an exonic splicing silencer to promote male-specific splicing of Bmdsx. However, the character of the interaction between BmPSI and Bmdsx pre-mRNA remains unclear. Electrophoretic mobility shift assay (EMSA) results showed that the four KH_1 motifs in BmPSI are all essential for the binding, especially the former two KH_1 motifs. Three active sites (I116, L127, and IGGI) in the KH_1 motif were found to be necessary for the binding through EMSA, circular dichroism (CD) spectroscopy, and isothermal titration calorimetry (ITC). The PSI homologous protein in S. litura (SlPSI) was purified and the binding of SlPSI and CE1 was verified. Compared with BmPSI, the mutant SlPSI proteins of I116 and IGGI lost their ability to bind to CE1. In conclusion, the binding of PSI and dsx pre-mRNA are generally conserved in both B. mori and S. litura. These findings provide clues for sex determination in Lepidoptera.

Clinical efficacy of EUS-guided celiac plexus neurolysis versus EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.

Background and Objective: To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (125I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer. Methods: We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-125I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups. Results: EUS-CPN and 125I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-125I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-125I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure. Conclusions: Both EUS-CPN and EUS-125I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-125I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.

Cross-sectional evaluation of gut microbial-host cometabolites in patients with chronic pancreatitis.

OBJECTIVES: Gut bacteria facilitate nutrient metabolism and generate small molecules that form part of the broader "metabolome". It is unclear whether these metabolites are disturbed in chronic pancreatitis (CP). This study aimed to evaluate the gut microbial-host cometabolites and their relationship in patients with CP. METHODS: Fecal samples were collected from 40 patients with CP and 38 healthy family members. Each sample was examined with 16S rRNA gene profiling and gas chromatography time-of-flight mass spectrometry to estimate the relative abundances of specific bacterial taxa between the two groups and to profile any changes in the metabolome, respectively. Correlation analysis was used to evaluate the differences in metabolites and gut microbiota between the two groups. RESULTS: The abundance of Actinobacteria was lower at the phylum level, and that of Bifidobacterium was lower at the genus level in the CP group. Eighteen metabolites had significantly different abundances and the concentrations of 13 metabolites were significantly different between the two groups. Oxoadipic acid and citric acid levels were positively correlated with Bifidobacterium abundance (r = 0.306 and 0.330, respectively, both P < 0.05), while the 3-methylindole concentration was negatively correlated with Bifidobacterium abundance (r = -0.252, P = 0.026) in CP. CONCLUSIONS: Gut microbiome and host microbiome metabolic products might be altered in patients with CP. Evaluating gastrointestinal metabolite levels may further enhance our understanding of the pathogenesis and/or progression of CP.

EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain control in pancreatic carcinoma: a prospective pilot study.

BACKGROUND: Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 ((125)I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. OBJECTIVE: To evaluate the safety and efficacy of direct celiac ganglion irradiation with (125)I seeds for the relief of moderate to severe pain secondary to unresectable PC. DESIGN: Prospective study. SETTING: Single, tertiary care referral center. PATIENTS: This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. INTERVENTION: All patients underwent EUS-guided direct celiac ganglion irradiation with (125)I seeds. Follow-up was conducted at least once weekly until death. MAIN OUTCOME MEASUREMENTS: Blood parameters, Visual Analog Scale (VAS) score, mean analgesic (MS Contin [morphine sulfate]) consumption, and complications were evaluated during follow-up. RESULTS: Twenty-three patients with unresectable PC underwent the procedure. The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6). Immediately after the procedure, pain relief and analgesic consumption showed no significant changes compared with preoperative values. Six patients (26%) reported pain exacerbation. Two weeks later, the VAS score and mean analgesic consumption were significantly less than preoperative values. No procedure-related deaths or major complications occurred. LIMITATIONS: Uncontrolled study. CONCLUSIONS: EUS-guided direct celiac ganglion irradiation with (125)I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Long Non-Coding RNA Bmdsx-AS1 Effects on Male External Genital Development in Silkworm.

Long non-coding RNAs (lncRNAs) have been suggested to play important roles in some biological processes. However, the detailed mechanisms are not fully understood. We previously identified an antisense lncRNA, Bmdsx-AS1, that is involved in pre-mRNA splicing of the sex-determining gene Bmdsx in the silkworm. In this study, we analyzed the changes in the male external genitalia of transgenic overexpressed Bmdsx-AS1 silkworm lines and analyzed downstream and upstream responses. We found that Bmdsx-AS1 transgenic silkworms, compared with wild type, showed more claspers in the male external genitalia. Quantitative real-time PCR (qPCR) results indicated that overexpression of Bmdsx-AS1 decreased the expression of genes in the EGFR signaling pathway. Knockdown of Bmdsx-AS1 increased the activity of the EGFR pathway. Through promoter prediction, promoter truncation and electrophoretic mobility shift assay (EMSA) analyses, we found that the protein encoded by the Hox gene BmAbd-B specifically binds to the promoter of Bmdsx-AS1. Moreover, overexpression of BmAbd-B in the silkworm BmE cell line indicated that BmAbd-B negatively regulates the mRNA expression of Bmdsx-AS1. Our study provides insights into the regulatory mechanism of the lncRNA in the silkworm.

Efficient and automatic synthesis of TSPO PET ligand [18F]-GE-180 and its application in rheumatoid arthritis model.

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic synovial inflammation, which ultimately leads to joint deformity and dysfunction. [18F]-GE-180 is a specific PET tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of inflammation. Our study addresses the need to streamline the automatic synthesis of [18F]-GE-180 to make it more accessible for routine production and widespread clinical evaluation and application. The nucleophilic radiofluorination was performed on an AllinOne synthesis module by SPE purification method, and the formulated [18F]-GE-180 was obtained in non-decay corrected radiochemical yields of 69 ± 1.8% in 32 min. PET/CT imaging in animal model showed that [18F]-GE-180 highly concentrated in joints from RA rats. This methodology facilitates efficient synthesis of [18F]-GE-180 in a commercially available synthesis module and shows potential diagnosis performance in RA models.

Momordica. charantia-Derived Extracellular Vesicles-Like Nanovesicles Protect Cardiomyocytes Against Radiation Injury via Attenuating DNA Damage and Mitochondria Dysfunction.

Thoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of Momordica. charantia-derived EVs-like nanovesicles (MCELNs) against RIHD. Using density gradient centrifugation, we successfully isolated MCELNs with similar shape, size, and markers as EVs. Confocal imaging revealed that rat cardiomyocytes H9C2 cells internalized PKH67 labeled MCELNs time-dependently. In vitro assay identified that MCELNs promoted cell proliferation, suppressed cell apoptosis, and alleviated the DNA damage in irradiated (16 Gy, X-ray) H9C2 cells. Moreover, elevated mitochondria ROS in irradiated H9C2 cells were scavenged by MCELNs, protecting mitochondria function with re-balanced mitochondria membrane potential. Furthermore, the phosphorylation of ROS-related proteins was recovered with increased ratios of p-AKT/AKT and p-ERK/ERK in MCELNs treated irradiated H9C2 cells. Last, intraperitoneal administration of MCELNs mitigated myocardial injury and fibrosis in a thoracic radiation mice model. Our data demonstrated the potential protective effects of MCELNs against RIHD. The MCELNs shed light on preventive regime development for radiation-related toxicity.

Independent risk factors for true malignancy in atypical cytologic diagnostic category in EUS-FNA/FNB of the pancreas: A novel prediction model.

Background and Objects: An atypical cytologic diagnosis arises from inflammation or early neoplastic process. It is commonly found in EUS-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) tissue sampling of pancreatic malignancies. The aims of this study were to evaluate the diagnostic performance of EUS-FNA/FNB in patients with cytologic diagnosis of atypical cells and to develop a prediction model for malignant tumors of the pancreas in the atypical cytologic diagnostic category. Methods: Two hundred and twenty-six patients in the atypical cytologic diagnostic category were analyzed. Multivariate logistic regression analyses were performed to determine predictive factors for pancreatic malignancies. The final diagnoses were confirmed by repeat biopsy; surgical pathology, or clinical follow-up for at least 6 months. Results: The atypical cytologic diagnosis using EUS-FNA/FNB was associated with an absolute risk of malignancy (82.3%). Multivariate logistic regression analyses revealed that older age, long axis of the mass, and increased carbohydrate antigen 19-9 (CA19-9) were independent risk factors for true malignant pancreatic tumors among patients in the atypical cytologic diagnostic category. The calibration curve had a slope of 0.96, and a regression coefficient (R2) of 0.91. The area under the receiver operating characteristic curve of the validation group was 0.803. Conclusions: Atypical lesions of EUS-FNA/FNB have a higher risk of malignancy. Older age, the long axis of the mass, and elevated serum CA19-9 level were identified as independent risk factors for true malignant pancreatic tumors among patients in the atypical cytologic diagnostic category.