Contrast-enhanced ultrasound to predict malignant upgrading of atypical ductal hyperplasia.

BACKGROUND: A malignancy might be found at surgery in cases of atypical ductal hyperplasia (ADH) diagnosed via US-guided core needle biopsy (CNB). The objective of this study was to investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in predicting ADH diagnosed by US-guided CNB that was upgraded to malignancy after surgery. METHODS: In this retrospective study, 110 CNB-diagnosed ADH lesions in 109 consecutive women who underwent US, CEUS, and surgery between June 2018 and June 2023 were included. CEUS was incorporated into US BI-RADS and yielded a CEUS-adjusted BI-RADS. The diagnostic performance of US BI-RADS and CEUS-adjusted BI-RADS for ADH were analyzed and compared. RESULTS: The mean age of the 109 women was 49.7 years ± 11.6 (SD). The upgrade rate of ADH at CNB was 48.2% (53 of 110). The sensitivity, specificity, positive predictive value, and negative predictive value of CEUS for identification of malignant upgrading were 96.2%, 66.7%,72.9%, and 95.0%, respectively, based on BI-RADS category 4B threshold. The two false-negative cases were low-grade ductal carcinoma in situ. Compared with the US, CEUS-adjusted BI-RADS had better specificity for lesions smaller than 2 cm (76.7% vs. 96.7%, P = 0.031). After CEUS, 16 (10 malignant and 6 nonmalignant) of the 45 original US BI-RADS category 4A lesions were up-classified to BI-RADS 4B, and 3 (1 malignant and 2 nonmalignant) of the 41 original US BI-RADS category 4B lesions were down-classified to BI-RADS 4A. CONCLUSIONS: CEUS is helpful in predicting malignant upgrading of ADH, especially for lesions smaller than 2 cm and those classified as BI-RADS 4A and 4B on ultrasound.

Three new griseofulvin derivatives from Aureobasidium pullulans.

Three new griseofulvin derivatives, griseofulvinoside A-C (1-3), were isolated from the ethyl acetate extract of the solid fermentation product of Aureobasidium pullulans. Their structures were elucidated based on extensive spectroscopic data analysis of MS, 1D and 2D NMR. The antifungal activities of new compounds were evaluated against four phytopathogenic fungi in vitro, and all test compounds demonstrated inhibitory effects. Among them, compound 2 exhibited the most potent activities against the four selected phytopathogenic fungi with inhibitory rates ranging from 40.2 to 75.8% at 0.2 mg/mL.

Combination of Breast Ultrasound With Magnetic Resonance Imaging in the Diagnosis of Non-mass-like Breast Lesions Detected on Ultrasound: A New Integrated Strategy to Improve Diagnostic Performance.

OBJECTIVE: The aim of the work described here was to evaluate the diagnostic performance of a new integrated strategy using breast ultrasound (US) combined with magnetic resonance imaging (MRI) to differentiate benign and malignant breast non-mass-like lesions (NMLs) detected on US. METHODS: From October 2017 to January 2021, 183 NMLs detected on US that had undergone MRI examinations were included in this respective study. Pathological results were used as the reference standard. The integrated diagnostic strategy of breast US combined with MRI based on a combination of MRI Breast Imaging Reporting and Data System (BI-RADS) with discriminant sonographic indicators highly associated with malignancy was established and validated in a cohort of 61 women. The diagnostic performances of US, MRI and the combined method were calculated and compared. RESULTS: In the training set, the area under the receiver operating characteristic curve (AUC), sensitivity and specificity of US, MRI and the integrated diagnostic strategy using US combined with MRI for NMLs were 0.730, 93.7% and 52.3%; 0.849, 94.7% and 75.0%; and 0.901, 92.6% and 87.5%, respectively. Compared with US or MRI alone, the integrated diagnostic strategy significantly increased the AUC (p < 0.001, p = 0.007) and specificity (p < 0.001, p = 0.034) while maintaining high sensitivity (p = 0.774, p = 0.551). In the validation set, the integrated strategy of US combined with MRI (AUC = 0.899) also had good performance compared with US (AUC = 0.728) or MRI (AUC = 0.838). CONCLUSION: The integrated diagnostic strategy of US combined with MRI exhibited good performance for breast NMLs compared with either modality used alone, which can improve the diagnostic specificity while maintaining high sensitivity.

Selective Defluoroalkylation and Hydrodefluorination of Trifluoromethyl Groups Photocatalyzed by Dihydroacridine Derivatives.

The selective functionalization of trifluoromethyl groups through C-F cleavage poses a significant challenge due to the high bond energy of the C(sp3)-F bonds. Herein, we present dihydroacridine derivatives as photocatalysts that can functionalize the C-F bond of trifluoromethyl groups with various alkenes under mild conditions. Mechanistic studies and DFT calculations revealed that upon irradiation, the dihydroacridine derivatives exhibit high reducibility and function as photocatalysts for reductive defluorination. This process involves a sequential single-electron transfer mechanism. This research provides valuable insights into the properties of dihydroacridine derivatives as photocatalysts, highlighting the importance of maintaining a planar conformation and a large conjugated system for optimal catalytic activity. These findings facilitate the efficient catalytic reduction of inert chemical bonds.

Benign Phyllodes Tumors: Comparison of Prognosis among Three Different Surgical Approaches.

Purpose: To evaluate the prognosis of patients with benign phyllodes tumors (PTs) treated by different surgical methods and to explore the influencing factors of local recurrence. Methods: We retrospectively analyzed 215 benign PTs from 193 patients who underwent surgery at Chinese PLA General Hospital between October 2008 and December 2020. We stratified our analysis according to surgical factors and explored the clinicopathological factors to influence local recurrence. Results: Among 193 patients, a total of 17 (8.8%, 17/193) recurred during follow-up. There were 89 patients in the US-VAE group, of whom 6 (6.7%) recurred; 8 of 57 patients (14%) in the local lumpectomy group recurred, while 3 of 47 patients (6.4%) in the extended lumpectomy group recurred (P=0.252). Multivariate logistic regression analysis showed that tumor diameter, mitosis, and history of breast myoma were independent risk factors for tumor recurrence (P=0.005, P=0.006, and P=0.004, respectively). The intraoperative blood loss, operation time, and scar length of the US-VAE group were shorter than those of the other two groups (P < 0.05). Conclusion: Negative surgical margins of benign PTs can obtain similar prognosis as negative surgical margins >10 mm. Therefore, we recommend that a follow-up observation policy be adopted for patients with unexpected benign PTs, rather than unnecessary open surgical resection. Patients' maximum tumor diameter, mitosis, and fibroadenoma history were independent predictors for recurrence of benign PTs.

Conventional ultrasound combined with contrast-enhanced ultrasound: could it be helpful for the diagnosis of thoracic wall recurrence after mastectomy?

OBJECTIVES: To develop a predictive model using conventional ultrasound combined with CEUS to identify thoracic wall recurrence after mastectomy. METHODS: A total of 162 women with pathologically confirmed thoracic wall lesions (benign 79, malignant 83; median size 1.9 cm, ranging 0.3-8.0 cm) underwent a mastectomy and were checked by both conventional ultrasound and CEUS and were retrospectively included. Logistic regression models of B-mode ultrasound (US) and color Doppler flow imaging (CDFI) with or without CEUS were established to assess the thoracic wall recurrence after mastectomy. The established models were validated by bootstrap resampling. The models were evaluated using calibration curve. The clinical benefit of models were assessed using decision curve analysis. RESULTS: The area under the receiver characteristic was 0.823 (95% CI: 0.76, 0.88) for model using US alone, 0.898 (95% CI: 0.84, 0.94) for model using US combined with CDFI, and 0.959 (95% CI: 0.92, 0.98) for model using US combined with both CDFI and CEUS. The diagnostic performance of the US combined with CDFI was significantly higher than that of the US alone (0.823 vs 0.898, p = 0.002) but significantly lower than that of the US combined with both CDFI and CEUS (0.959 vs 0.898, p < 0.001). Moreover, the unnecessary biopsy rate of the US combined with both CDFI and CEUS was significantly lower than that of the US combined with CDFI (p = 0.037). CONCLUSIONS: Compared to B-mode ultrasound and CDFI, CEUS improves the diagnostic performance to evaluate thoracic wall recurrence after mastectomy. KEY POINTS: • CUES is an effective supplementary method for US in the diagnosis of thoracic wall recurrence after mastectomy. • CEUS combined with both US and CDFI can significantly improve the accuracy of diagnosis of thoracic wall recurrence after mastectomy. • CEUS combined with both US and CDFI can reduce the rate of unnecessary biopsy of thoracic wall lesions after mastectomy.

Efficacy of transcatheter arterial chemoembolization combined with sirolimus for treating Kasabach-Merritt phenomenon in infants, a retrospective study.

OBJECTIVE: This retrospective study aimed to observe the efficacy of transcatheter arterial chemoembolization (TACE) combined with sirolimus in the treatment of haemangioma combined with the Kasabach-Merritt phenomenon (KMP). METHODS: A total of 11 infants with KMP who were treated at our hospital from January 2016 to September 2021 were selected and treated with arteriosclerosis embolotherapy using a microsphere emulsion formed by bleomycin + ultra-fluid lipiodol + dexamethasone + contrast agent or bleomycin mixed microspheres as the embolising agent. The patients were administered sirolimus orally after TACE. The clinical efficacy and examination indicators before and after treatment were observed and compared. RESULTS: The 11 infants underwent TACE treatment by arteriosclerosis embolotherapy a total of 21 times; of these cases, 10 were cured, and 1 showed a moderate response. There were no cases of non-response or death. The platelet count rose from 10.0 (7.0, 18.0) x 109/L before TACE to 236.0 (188.0, 275.0) x 109/L six months after the first TACE, and the tumour size decreased from 49.0 (43.0, 111.7) cm3 before TACE to 7.0 (3.5, 17.0) cm3 six months after the first TACE. The differences were statistically significant (the Z values were -2.943 and -2.934, respectively, p < 0.05). CONCLUSION: The combination of TACE and sirolimus has significant efficacy on critical children with KMP.

Identification of Spodoptera frugiperda (Lepidoptera: Noctuidae) and its two host strains in China by PCR-RFLP.

The fall armyworm (FAW) Spodoptera frugiperda was first found in China in 2018. In other countries, FAW has evolved corn and rice strain biotypes. It is not possible to identify these strains based on morphology. In addition, FAW is very similar in appearance to several other common pests. These situations bring great challenges to the population management of FAW. In this study, we developed a rapid identification method based on PCR-RFLP to distinguish the two FAW strains and the FAW from other lepidopteran pests. A 697 bp mitochondrial cytochrome c oxidase I (COI) was cloned and sequenced from FAW, Spodoptera litura, Spodoptera exigua, and Mythimna separata. The COI fragments of these species revealed unique digestion patterns created by three enzymes (Tail, AlWN I, and BstY II). Thus, these four species can be distinguished from each other. The enzyme Ban I recognized a unique SNP site on a 638 bp triosephosphate isomerase (Tpi) fragment of the corn strain FAW. The Tpi fragment of the corn strain was cut into two bands. However, the rice strain could not be digested. Using this method, all 28 FAW samples collected from different host plants and locations in China were identified as the corn strain. This suggests that the rice strain has not yet invaded China. This method allows discrimination of FAW from other Lepidopteran pests and distinguishes the two FAW host strains.

Novel Antifungal and Antifeedant Metabolites from Penicillium chrysogenum Co-Cultured with Nemania primolutea and Aspergillus fumigatus.

The endophyte Nemania primolutea, inhibited the growth of Penicillium chrysogenum in the coculture system. Four new compounds, nemmolutines A-B (1-2), and penigenumin (3) from N. primolutea, penemin (4) from P. chrysogenum were isolated from the coculture. On the other hand, P. chrysogenum inhibited the Aspergillus fumigatus in the coculture. Induced metabolites (13-16) with monasone naphthoquinone scaffolds including a new one from P. chrysogenum were produced by the coculture of P. chrysogenum, and A. fumigatus. Interesting, cryptic metabolites penicichrins A-B isolated from wild P. chrysogenum induced by host Ziziphus jujuba medium were also found in induced P. chrysogenum cultured in PDB ordinary medium. So the induction of penicichrin production by supplementing with host extract occurred in the fungus P. chrysogenum not the host medium. The productions of penicichrins were the spontaneous metabolism, and the metabolites (13-16) were the culture driven. Compounds 4, 6, 8, 10, 11, 14, and 15 showed significant antifungal activities against the phytopathogen Alternaria alternata with MICS of 1-8 µg/mL, and compounds 7, 9, and 12 indicated significant antifeedant activities against silkworms with feeding deterrence indexes (FDIs) of 92 %, 66 %, and 64 %. The carboxy group in 4-(2-hydroxybutynoxy)benzoic acid derivatives, and xylabisboeins; the hydroxy group in mellein derivatives; and the quinoid in monasone naphthoquinone increased the antifungal activities.

Endoscopic management of pancreatic fluid collections with disconnected pancreatic duct syndrome.

Disconnected pancreatic duct syndrome (DPDS) is an important and common complication of acute necrotizing pancreatitis. Endoscopic approach has been established as the first-line treatment for pancreatic fluid collections (PFCs) with less invasion and satisfactory outcome. However, the presence of DPDS significantly complicates the management of PFC; besides, there is no standardized treatment for DPDS. The diagnosis of DPDS presents the first step of management, which can be preliminarily established by imaging methods including contrast-enhanced computed tomography, ERCP, magnetic resonance cholangiopancreatography (MRCP), and EUS. Historically, ERCP is considered as the gold standard for the diagnosis of DPDS, and secretin-enhanced MRCP is recommended as an appropriate diagnostic method in existing guidelines. With the development of endoscopic techniques and accessories, the endoscopic approach, mainly including transpapillary and transmural drainage, has been developed as the preferred treatment over percutaneous drainage and surgery for the management of PFC with DPDS. Many studies concerning various endoscopic treatment strategies have been published, especially in the recent 5 years. Nonetheless, existing current literature has reported inconsistent and confusing results. In this article, the latest evidence is summarized to explore the optimal endoscopic management of PFC with DPDS.

Determining whether the diagnostic value of B-ultrasound combined with contrast-enhanced ultrasound and shear wave elastography in breast mass-like and non-mass-like lesions differs: a diagnostic test.

Background: Mass-like (ML) and non-mass-like (NML) are two manifestations of breast lesions on ultrasound. Contrast-enhanced ultrasound (CEUS) can make up for the limitation of B-ultrasound (US) in the observation of focal blood flow, and shear wave elastography (SWE) can supplement the hardness information of the lesion. The present study aimed to analyze the characteristic manifestations of US, CEUS, and SWE in NML and ML breast and evaluate whether the diagnostic performance of these three ultrasound techniques differs in terms of differentiating between benign and malignant breast lesions. Methods: From January to August 2021, 382 patients (417 breast lesions) underwent US, CEUS, and SWE examinations. Of these, 204 women (218 breast lesions) were included in our study due to subsequent biopsy or surgery with pathological findings. The patients were divided into ML and NML groups according to the ultrasound characteristics, and the differences in multimodal ultrasound performance between benign and malignant NML and benign and malignant ML breast lesions were compared. The diagnostic performance of US, US + CEUS, US + SWE, US + CEUS + SWE for ML, NML and all breast lesions was evaluated by analyzing sensitivity, specificity and area under receiver operating characteristic (ROC) curve (AUC). Results: Pathologically, the 218 lesions included 96 malignant and 122 benign breast lesions. The sensitivity and specificity of US + CEUS + SWE in all lesion groups, ML group and NML group were 92.7% and 90.2%, 95.9% and 90.3%, 91.3% and 79.3%, respectively. In all breast group, AUCs of US + CEUS, US + SWE, US + CEUS + SWE were statistically different from AUC of US (P=0.0010, 0.0001, 0.0001). In the ML group, the AUC of US + CEUS, US + SWE, US + CEUS + SWE were statistically different from that of US (P=0.0120, 0.0008, 0.0002). In the NML group, there was a statistical difference between US + SWE and US AUC (P=0.0149). Conclusions: US, CEUS, and SWE have an important diagnostic value for benign and malignant ML and NML breast lesions. Multimodal ultrasound combined with US, CEUS, and SWE can improve the diagnostic efficacy in distinguishing between benign and malignant ML and NML lesions.

[Expression of interleukin-17A in serum of children with intravenous immunoglobulin-resistant Kawasaki disease and its clinical significance]. / é™è„‰æ³¨å°„å ç–«çƒè›‹ç™½æ— ååº”åž‹å·å´Žç— æ‚£å„¿è¡€æ¸ ç™½ç»†èƒžä»‹ç´ -17A的表达及临床意义.

OBJECTIVES: To study the expression of interleukin-17A (IL-17A) in the serum of children with intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) and its clinical significance. METHODS: A total of 143 children with KD who were hospitalized in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2021 to June 2022 were enrolled in this prospective study, among whom 115 had IVIG-sensitive KD and 28 had IVIG-resistant KD. After matching for sex and age, 110 children with acute respiratory infectious diseases (fever time ≥5 days but without KD) were enrolled as the control group. The enzyme-linked immunosorbent assay was used to measure the serum level of IL-17A. The levels of white blood cell count (WBC), neutrophil count (NE), platelet count, erythrocyte sedimentation rate, and C-reactive protein (CRP) were measured. The receiver operating characteristic curve was plotted to analyze the value of WBC, NE, CRP, and IL-17A in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis was used to evaluate the predictive factors for resistance to IVIG in children with KD. RESULTS: Before IVIG treatment, the KD group had a significantly higher serum level of IL-17A than the control group (P<0.05), and the children with IVIG-resistant KD had a significantly higher serum level of IL-17A than those with IVIG-sensitive KD (P<0.05). The receiver operating characteristic curve analysis showed that WBC, NE, CRP, and IL-17A had an area under the curve of 0.718, 0.741, 0.627, and 0.840, respectively, in the prediction of IVIG-resistant KD. With serum IL-17A ≥44.06 pg/mL as the cut-off value, IL-17A had a sensitivity of 84% and a specificity of 81% in the prediction of IVIG-resistant KD. The multivariate logistic regression analysis showed that a high serum level of IL-17A was a predictive factor for resistance to IVIG in children with KD (OR=1.161, P=0.001). CONCLUSIONS: Serum IL-17A levels are elevated in children with IVIG-resistant KD, and serum IL-17A level (≥44.06 pg/mL) may have a predictive value for resistance to IVIG in children with KD.

Proteomics comparison between mass-like and non-mass-like breast lesions.

Background: The proteomic differences between mass-like (ML) breast lesions and non-mass-like (NML) breast lesions were compared to explore the formation mechanism of NML ultrasonic morphological characteristics. Methods: From January to August 2021, tissue samples were collected from 10 patients with malignant ML (MML), 10 patients with malignant NML (MNML), 10 patients with benign ML (BML), and seven patients with benign NML (BNML). The proteomic differences between the BML and BNML groups and the MML and MNML groups were compared by data-independent acquisition (DIA) quantitative mass spectrometry. The differentially expressed proteins were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks analyses. Results: We identified a total of 623 significantly differentially expressed proteins in the MML/MNML group, and 167 significantly differentially expressed proteins in the BML/BNML group, with relative ratios >1.2 or <-0.83. The up-regulated differential proteins were more abundant in the tumor necrosis factor (TNF) signaling pathway in both the MML/MNML and BML/BNML groups, suggesting that the TNF signaling pathway may be related to the ultrasonic morphological characteristics of breast lesions. Dual specificity mitogen-activated protein kinase 3 (MP2K3), a protein factor in the TNF signaling pathway, exhibited significant upregulation in both the malignant and BML groups. Conclusions: The TNF signaling pathway may be associated with the ultrasonic morphological characteristics of breast lesions. MP2K3 is the up-regulated differential expression protein in the MML/MNML and BML/BNML groups, which may be related to the ultrasonic morphological characteristics of breast lesions.

Interfacial adsorption behavior of the Aspergillus oryzae lipase-chitosan complex and stability evaluation of the resultant Pickering emulsion.

To prompt the application of the chitosan (CS)-Aspergillus oryzae lipase (AOL) complex in the construction of novel biphasic catalysis medium, its Pickering emulsion stabilization ability as well as adsorption behavior in the oil-water interface were investigated and the stability of resultant emulsion was evaluated. The results indicated that the CS-AOL complex assembled in mass ratio 1:5 was an effective Pickering stabilizer and up to 90 % AOL could be retained in the emulsion interface. Quartz crystal microbalance with dissipation monitoring suggested that the CS-AOL complex spontaneously absorbed to oil-water interface; absorption dynamics analysis revealed that the adsorption was driven by diffusion accompanied by rapid structural rearrangement; while interfacial dilatational rheology demonstrated the formation of an elastic film in the oil-water interface. The Pickering emulsions were pseudoplastic and that in oil fraction 0.6 exhibited the elastic behavior in contrast to the viscous behavior in oil fractions 0.2 and 0.4. The Pickering emulsion exhibited excellent stability against storage for up to 28 d, pHs 2.0-12.0, heating at 25-90 °C, and up to 500 mmol/L NaCl, and the corresponding interfacial AOL retentions exceeded 80 % during exposure to these conditions. Hence, the CS-AOL complex could be used as a stabilizer to construct Pickering emulsion-based biphasic catalysis systems.

Poly-hydroxylated bile acids and their prognostic roles in Alagille syndrome.

BACKGROUND: The liver manifestations of Alagille syndrome (ALGS) are highly variable, and factors affecting its prognosis are poorly understood. We asked whether the composition of bile acids in ALGS patients with good clinical outcomes differs from that in patients with poor outcomes and whether bile acids could be used as prognostic biomarkers. METHODS: Blood for bile acid profiling was collected from genetically confirmed JAG1-associated ALGS patients before one year of age. A good prognosis was defined as survival with native liver and total bilirubin (TB) < 85.5 µmol/L, while a poor prognosis was defined as either liver transplantation, death from liver failure, or TB ≥ 85.5 µmol/L at the last follow-up. RESULTS: We found that the concentrations of two poly-hydroxylated bile acids, tauro-2ß,3α,7α,12α-tetrahydroxylated bile acid (THBA) and glyco-hyocholic acid (GHCA), were significantly increased in patients with good prognosis compared to those with poor prognosis [area under curve (AUC) = 0.836 and 0.782, respectively] in the discovery cohort. The same trend was also observed in the molar ratios of GHCA to glyco- chenodeoxycholic acid (GCDCA) and tetrahydroxylated bile acid (THCA) to tauro-chenodeoxycholic acid (TCDCA) (both AUC = 0.836). A validation cohort confirmed these findings. Notably, tauro-2ß,3α,7α,12α-THBA achieved the highest prediction accuracy of 88.00% (92.31% sensitivity and 83.33% specificity); GHCA at > 607.69 nmol/L was associated with native liver survival [hazard ratio: 13.03, 95% confidence interval (CI): (2.662-63.753), P = 0.002]. CONCLUSIONS: We identified two poly-hydroxylated bile acids as liver prognostic biomarkers of ALGS patients. Enhanced hydroxylation of bile acids may result in better clinical outcomes.

Clinicopathological Features of Sessile Serrated Polyps in China: A Retrospective Study of a Tertiary Hospital.

BACKGROUND: Serrated polyps have been recognized as the important premalignant lesions. In this study, we aimed to analyze the clinicopathological features of sessile serrated polyps and determine the association between sessile serrated polyps and synchronous advanced adenomas. METHODS: Consecutive patients undergoing diagnostic or therapeutic colonoscopies (including 156 681 diagnostic colonoscopies) from 2011 to 2019 were included. RESULTS: A total of 958 patients, including 699 (73%) males, were detected with at least 1 sessile serrated polyp, and 65.9% (n = 658) of sessile serrated polyps were located in the distal colon. Advanced serrated lesions accounted for 9.1% (n = 91) of all the sessile serrated polyp (n = 999). The types of SSP included flat type (953/999, 95.4%) and sub-pedunculated or pedunculated type (46/999, 4.6%). Meanwhile, there was no obvious evidence supporting the association between advanced adenomas and characteristics of advanced serrated lesions or sessile serrated polyps. CONCLUSION: Sessile serrated polyps seem to be more frequently seen in the distal colon of men in this study. However, more evidence is required to confirm the actual distribution of sessile serrated polyp in colon among Chinese people. There is still much room for improvement of sessile serrated polyp detection rate, and more importance should be attached to sessile serrated polyp both for pathologists and endoscopists.

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.

Hepatocyte-derived MANF mitigates ethanol-induced liver steatosis in mice via enhancing ASS1 activity and activating AMPK pathway.

Hepatic steatosis plays a detrimental role in the onset and progression of alcohol-associated liver disease (ALD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an evolutionarily conserved protein related to the unfolded protein response. Recent studies have demonstrated that MANF plays an important role in liver diseases. In this study, we investigated the role of MANF in ethanol-induced steatosis and the underlying mechanisms. We showed that the hepatic MANF expression was markedly upregulated in mouse model of ALD by chronic-plus-single-binge ethanol feeding. Moreover, after chronic-plus-binge ethanol feeding, hepatocyte-specific MANF knockout (HKO) mice displayed more severe hepatic steatosis and liver injury than wild-type (WT) control mice. Immunoprecipitation-coupled MS proteomic analysis revealed that arginosuccinate synthase 1 (ASS1), a rate-limiting enzyme in the urea cycle, resided in the same immunoprecipitated complex with MANF. Hepatocyte-specific MANF knockout led to decreased ASS1 activity, whereas overexpression of MANF contributed to enhanced ASS1 activity in vitro. In addition, HKO mice displayed unique urea cycle metabolite patterns in the liver with elevated ammonia accumulation after ethanol feeding. ASS1 is known to activate AMPK by generating an intracellular pool of AMP from the urea cycle. We also found that MANF supplementation significantly ameliorated ethanol-induced steatosis in vivo and in vitro by activating the AMPK signaling pathway, which was partly ASS1 dependent. This study demonstrates a new mechanism in which MANF acts as a key molecule in maintaining hepatic lipid homeostasis by enhancing ASS1 activity and uncovers an interesting link between lipid metabolism and the hepatic urea cycle under excessive alcohol exposure.

Optimal sampling technique for EUS-guided fine-needle biopsy of solid pancreatic lesions using a 25-gauge ProCore needle: A multicenter randomized crossover superiority study.

Background and Objectives: It remains unclear whether the use of the stylet slow-pull (SP) and wet suction (WS) can improve the yield of endoscopic ultrasound-guided fine-needle biopsy compared to standard suction (SS). The aim of this study was to compare the diagnostic efficacy of the three sampling techniques when using 25G ProCore needles for solid pancreatic lesions. Materials and Methods: This multicenter single-blind randomized crossover superiority trial enrolled patients with solid pancreatic lesions (n = 300) from four digestive endoscopic centers in China. All three sampling techniques were performed on each patient using a 25G ProCore needle in a randomized sequence. The diagnostic efficacy, the specimen yield, and quality of each technique, the overall technical success rate and diagnostic yield of the 25G ProCore needle, and rate of adverse events were evaluated. Results: A total of 291 patients were analyzed. No significant difference was found in diagnostic efficiency among the three techniques (sensitivity, 82.14% vs. 75.00% vs. 77.86, P = 0.1186; accuracy, 82.82% vs. 75.95% vs. 78.69%, P = 0.1212). The SP had an inferior tissue integrity compared to the SS and WS techniques (71.82% vs. 62.55% vs. 69.76%, P = 0.0096). There was no significant difference in the degree of blood contamination among the three groups (P = 0.2079). After three passes, the overall sensitivity was 93.93%, and the accuracy was 94.16%. Conclusions: SS and WS techniques are better choices than SP technique for 25G ProCore needle, for they could provide higher specimen adequacy without increasing the amount of blood contamination. The 25G ProCore needle can provide a satisfactory diagnostic yield for solid pancreatic lesions.