Evaluation of the diagnostic performance of the EFSUMB CEUS Pancreatic Applications guidelines (2017 version): a retrospective single-center analysis of 455 solid pancreatic masses.

OBJECTIVES: To explore the diagnostic performance of EFSUMB CEUS Pancreatic Applications guidelines (version 2017) before and after the addition of iso-enhancement and very fast/fast washout as supplementary diagnostic criteria for PDAC. METHODS: In this retrospective study, patients diagnosed with solid pancreatic lesions from January 2017 to December 2020 were evaluated. Pancreatic ductal adenocarcinoma (PDAC) is reported to show hypo-enhancement in all phases according to the EFSUMB guidelines. First, based on this definition, all lesions were categorized as PDAC and non-PDAC. Then, iso-enhancement and very fast/fast washout were added as supplementary diagnostic criteria, and all lesions were recategorized. The diagnostic performance was assessed in terms of the accuracy (ACC), sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and negative predictive value (NPV). The reference standard consisted of histologic evaluation or composite imaging and clinical follow-up findings. RESULTS: A total of 455 nodules in 450 patients (median age, 58.37 years; 250 men) were included. The diagnostic performance using the EFSUMB CEUS guidelines for PDAC had an ACC of 69.5%, SEN of 65.4%, SPE of 84%, PPV of 93.5%, NPV of 40.6%, and ROC of 0.747. After recategorization according to the supplementary diagnostic criteria, the diagnostic performance for PDAC had an ACC of 95.8%, SEN of 99.2%, SPE of 84%, PPV of 95.7%, NPV of 96.6%, and ROC of 0.916. CONCLUSION: The EFSUMB guidelines and recommendations for pancreatic lesions can effectively identify PDAC via hypo-enhancement on CEUS. However, the diagnostic performance may be further improved by the reclassification of PDAC lesions after adding iso-enhancement and very fast/fast washout mode. KEY POINTS: • In the EFSUMB guidelines, the only diagnostic criterion for PDAC is hypo-enhancement, to which iso-enhancement and very fast/fast washout mode were added in our research. • Using hypo-enhancement/iso-enhancement with very fast/fast washout patterns as the diagnostic criteria for PDAC for solid pancreatic masses on CEUS has high diagnostic accuracy. • The blood supply pattern of PDAC can provide important information, and CEUS has unique advantages in this respect due to its real-time dynamic attenuation ability.

Microplastics contamination in groundwater of a drinking-water source area, northern China.

Although the contamination of microplastics (MPs) in groundwater has been anticipated, their occurrence, distribution, and composition require further understanding. In this study, the occurrence and distributions of MPs were investigated in shallow groundwater from an important water source district in Tianjin city of northern China. The abundance, the physical morphology, the chemical composition, and the potential correlations of the determined MPs with human activities were thoroughly characterized. MPs were determined from all ten sampling sites with the abundance ranged between 17.0 ± 2.16 to 44.0 ± 1.63 n/L, revealing the ubiquitous existed MPs contamination. Based on the physical categorization, fiber (44.74%) was the most abundant shape, while blue (31.02%) and transparent (26.09%) were the most prevalent colors. The dominant size of MPs was smaller than 200 µm which accounted for 73.10%. A total of seven types of MPs were determined with polyethylene, polyethylene terephthalate, and polystyrene as the main types, of which, polypropylene showed strong positive correlations with polystyrene, indicating the possible similar sources of them. Besides, the determined MPs in groundwater were greater in areas with the high population density and strong population activity, indicating their high correlation with human activity. The study highlighted the presence of MPs in groundwater of drinking water source in northern China and provided useful information for evaluating the potential ecological effects on water quality safety and human health brought by MPs.

Noninvasive imaging of c(RGD)2 -9R as a potential delivery carrier for transfection of siRNA in malignant tumors.

The purpose of our study was to develop and evaluate a novel integrin αv ß3 -specific delivery carrier for transfection of siRNA in malignant tumors. We adopted arginine-glycine-aspartate (RGD) motif as a tissue target for specific recognition of integrin αν ß3 . A chimaeric peptide was synthesized by adding nonamer arginine residues (9-arginine [9R]) at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD)2 -9R, to enable small interfering RNA (siRNA) binding. To test the applicability of the delivery carrier in vivo, c(RGD)2 -9R was labeled with radionuclide of technetium-99m. Biodistribution and γ-camera imaging studies were performed in HepG2 xenograft-bearing nude mice. As results, an optimal 10:1 molar ratio of 99m Tc-c(RGD)2 -9R to siRNA was indicated by the electrophoresis on agarose gels. 99m Tc-c(RGD)2 -9R/siRNA remained stable under a set of conditions in vitro. For in vivo study, tumor radioactivity uptake of 99m Tc-c(RGD)2 -9R/siRNA in nude mice bearing HepG2 xenografts was significantly higher than that of control probe (P < .05). The xenografts were clearly visualized at 4 hours till 6 hours noninvasively after intravenous injection of 99m Tc-c(RGD)2 -9R/siRNA, while the xenografts were not visualized at any time after injection of control probe. It was concluded that c(RGD)2 -9R could be an effective siRNA delivery carrier. Technetium-99m radiolabeled-delivery carrier represents a potential imaging strategy for RNAi-based therapy.

Efficacy of color Doppler ultrasound and contrast-enhanced ultrasound in identifying vascular invasion in pancreatic ductal adenocarcinoma.

OBJECTIVES: To compare color Doppler ultrasound and contrast-enhanced ultrasound (CEUS) in evaluating vascular invasion in pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This retrospective study included 210 patients with PDAC who were evaluated by color Doppler ultrasound, CEUS, and contrast-enhanced computed tomography (CECT) at our institution between January 2017 and December 2020. Pathologic results were used as the gold standard in patients who underwent surgical and intraoperative exploration. For nonsurgical patients, CECT results were used as the reference standard. The vessels evaluated included those in the peripancreatic arterial system and venous system. The diagnostic performances of color Doppler ultrasound and CEUS for vascular invasion were compared. RESULTS: In 51 patients who underwent surgery and intraoperative exploration, color Doppler ultrasound and CEUS differed only in assessing venous system invasion in patients with PDAC of the pancreatic body and tail, with the former being superior to the latter. In 159 nonsurgical patients, there was no difference between CEUS and color Doppler ultrasound in assessing superior mesenteric arteriovenous invasion. CEUS was superior to color Doppler ultrasound in evaluating the celiac artery and its branches, with an accuracy of up to 97.8% for some vessels. Color Doppler ultrasound was ideal for evaluating the splenic and portal veins. CONCLUSION: CEUS is more suitable for the evaluation of peripancreatic arteries than color Doppler. CEUS combined with color Doppler ultrasound can be used as a potential supplement to CECT and is also expected to be used to evaluate vascular invasion of PDAC after chemotherapy. CRITICAL RELEVANCE STATEMENT: Contrast-enhanced US and color Doppler in the assessment of vascular invasion in pancreatic ductal adenocarcinoma have their respective advantages, through standardized ultrasound processes are expected to improve the efficiency of inspection. KEY POINTS: Contrast-enhanced US has unique advantages in assessing pancreatic ductal adenocarcinoma invasion of the celiac artery. Doppler imaging is of high value in assessing venous system invasion. Standardization of ultrasound imaging procedures for pancreatic ductal adenocarcinoma is expected to improve efficiency.

[The pharmacodynamic research on fuxiye, a Chinese herbal lotion for external wash].

OBJECTIVE: To observe antisepsis, anti-swelling, and therapeutic effects of Fuxiye (FXY), a Chinese medical lotion for external wash in treating vaginitis model rats. METHODS: The cervicitis rat model was induced by agar plate diffusion, ear auricle swelling induced by dimethylbenzene, and chemical stimulus. The in vitro antibiotic actions of FXY were observed. Besides, its effects on the swelling and inflammation in model rats were also observed. RESULTS: FXY at 25 mg/mL could completely inhibit the growth of Pseudomonas aeruginosa, Escherichia coli, pyogenic Streptococcus, and Streptococcus agalactiae. FXY at 50 mg/mL could completely inhibit the growth of Staphylococcus aureus and Candida albicans. It obviously restrained dimethylbenzene induced ear auricle swelling. It significantly alleviated cervicitis induced by chemical stiumli. CONCLUSION: FXY showed better effects on antisepsis, anti-inflammation, and treating cervicitis.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

CYP24A1 Involvement in Inflammatory Factor Regulation Occurs via the Wnt Signaling Pathway.

OBJECTIVE: While the upregulation of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) gene expression has been reported in colon cancer, its role in tumorigenesis remains largely unknown. In this study, we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B (NF-κB) pathway. METHODS: The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6 (IL-6) as well as tumor necrosis factor alpha (TNF-α), with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate (PDTC). Furthermore, CYP24A1 expression was subjected to knockdown via the use of small interfering RNA (siRNA). Subsequently, NF-κB pathway activation was determined by an electrophoretic mobility shift assay, and the transcriptional activity of ß-catenin was determined by a dual-luciferase reporter assay. A mouse ulcerative colitis (UC)-associated carcinogenesis model was established, wherein TNF-α and the NF-κB pathway were blocked by anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides, respectively. Then the tumor size and protein level of CYP24A1 were determined. RESULTS: IL-6 and TNF-α upregulated CYP24A1 expression and activated the NF-κB pathway in colon cancer cells. PDTC significantly inhibited this increase in CYP24A1 expression. Additionally, knockdown of CYP24A1 expression by siRNA could partially antagonize Wnt pathway activation. Upregulated CYP24A1 expression was observed in the colonic epithelial cells of UC-associated carcinoma mouse models. Anti-TNF-α monoclonal antibody and NF-κB antisense oligonucleotides decreased the tumor size and suppressed CYP24A1 expression. CONCLUSION: Taken together, this study suggests that inflammatory factors may increase CYP24A1 expression via NF-κB pathway activation, which in turn stimulates Wnt signaling.

Prognostic significance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) in patients with primary T cell lymphomas.

OBJECTIVE: T cell lymphomas are associated with an aggressive worse prognosis. This study is designed to assess T cell lymphomas using 18F-FDG PET/CT. METHODS: Sixty-four patients with newly diagnosed T cell lymphomas underwent PET/computed tomography (PET/CT) scans, 47 cases who were fully followed up were retrospectively reviewed and analyzed. Overall survival (OS) and progression-free survival (PFS) were recorded for prognosis. We measured the maximum standardized uptake value (SUVmax) in all cases, analyzed the correlation between SUVmax and survival and other clinicopathologic parameters. Kaplan-Meier log-rank tests were then used to compare the survival of high and low PET/CT parameter groups, and multivariate Cox proportional hazards regression analysis was carried out to identify predictors of OS and PFS. RESULTS: With a median follow-up of 26.5 (range 0.7-117.5) months, the 1-, 2- and 3-year OS were 75.6, 61.7 and 49.2%, and PFS were 49.3, 39.9 and 29.9%, respectively in 47 patients. Among them, 33 cases progressed with a median time of 9.5 (0.7-115.0) months, and 26 patients died with a median survival time of 26.5 (0.7-117.5) months. Multivariate analysis showed the following independent prognostic factors for OS: age >60 years (P = 0.002), SUVmax >9.7 (P = 0.009) and extranodal involvement of more than one site (P = 0.018). In addition, lactate dehydrogenase level (P = 0.003) and B symptoms (P = 0.018) were independent risk factors for PFS. CONCLUSION: Pretherapy SUVmax may serve as an independent predictor of outcome in patients with newly diagnosed T cell lymphomas.

Influence of nitrate concentration on trichloroethylene reductive dechlorination in weak electric stimulation system.

The co-existence of volatile chlorinated hydrocarbons (VCHs) and nitrate pollution in groundwater is prominent, but how nitrate exposure affects weak-electrical stimulated bio-dechlorination activity of VCH is largely unknown. Here, by establishing weak-electrical stimulated trichloroethylene (TCE) dechlorination systems, the influence on TCE dechlorination by exposure to the different concentrations (25-100 mg L-1) of nitrate was investigated. The existence of nitrate in general decreased TCE dechlorination efficiency to varying degrees, and the higher nitrate concentration, the stronger the inhibitory effects, verified by the gradually decreased transcription levels of tceA. Although the TCE dechlorination kinetic rate constant decreased by 36% the most, under all nitrate concentration ranges, TCE could be completely removed within 32 h and no difference in generated metabolites was found, revealing the well-maintained dechlorination activity. This was due to the quickly enriched bio-denitrification activity, which removed nitrate completely within 9 h, and thus relieved the inhibition on TCE dechlorination. The obvious bacterial community structure succession was also observed, from dominating with dechlorination genera (e.g., Acetobacterium, Eubacterium) to dominating with both dechlorination and denitrification genera (e.g., Acidovorax and Brachymonas). The study proposed the great potential for the in situ simultaneous denitrification and dehalogenation in groundwater contaminated with both nitrate and VCHs.

Signal Transducer and Activator of Transcription 3 for the Differentiation of Hepatocellular Carcinoma from Cirrhosis.

BACKGROUND: Overexpression and constitutive activation of signal transducer and activator of transcription (STAT) 3 have been suggested in the tumorigenesis of many human cancers, including multiple carcinomas, melanoma, and lymphoma. The diagnosis of hepatocellular carcinoma (HCC) in lobectomy specimens is usually straightforward, but distinguishing cirrhosis from well-differentiated HCC can be challenging in core biopsies. Our aims were to investigate the expression level of STAT3 and phosphorylated STAT3 (pSTAT3) in HCC and cirrhosis, and the application of STAT3 in the differential diagnosis of HCC and cirrhosis. METHODS: Sixty cases were divided into three groups: patients with HCC only (Group 1), HCC and cirrhosis (Group 2), and cirrhosis only (Group 3). Formalin-fixed and paraffin-embedded tissue sections were stained immunohistochemically for STAT3, pSTAT3, and CD163. The values obtained from the tissue sections of each group were compared in statistical analysis. RESULTS: STAT3 showed a high level in HCC and was a significant marker for differentiating HCC from cirrhosis (P < 0.0001). The odds ratio between HCC and cirrhosis increased 34.4 times when the intensity of STAT3 increased by 1 level. Spearman's correlation and Chi-square tests also demonstrated that expression level of STAT3 did not correlate with age, gender, or the presence of a cirrhotic background. CONCLUSIONS: STAT3 staining differs significantly in HCC and cirrhosis. The findings reinforce the role of STAT3 in the tumorigenesis of HCC and provide a useful marker to differentiate HCC from cirrhosis in challenging liver biopsies.