Diagnostic value of contrast-enhanced ultrasound and shear-wave elastography for small breast nodules.

Background: The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods: This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results: The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion: The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.

Dual-Emitting Mixed-Lanthanide Metal-Organic Framework for Ratiometric and Quantitative Visual Detection of 2,6-Pyridine Dicarboxylic Acid.

The detection of the major biomarker of Bacillus anthracis, 2,6-dipicolinic acid (DPA), has attracted great interest in recent years. In this work, mixed-lanthanide metal-organic frameworks (M'LnMOFs), TbxEu1-x-cppa (cppa = 5-(5-carboxypyridin-3-yl)isophthalic acid), with different Tb/Eu ratios, were solvothermally synthesized. The results reveal that ratiometric fluorescent probe [Tb0.533Eu0.467-(Hcppa)1.5(H2O)(DMF)]·3H2O is water and acid-base stable and exhibits excellent sensitivity (LOD = 2.286 µM), high selectivity, and fast response (<2 min) for the detection of DPA. Due to the blocked energy transfer from Tb3+ to Eu3+ and the inner filter effect upon the addition of DPA, the fluorescent probe shows a distinct color change from orange-red to green. Furthermore, the visual detection of DPA was realized by identifying the RGB values of MOF-based agarose hydrogel films via a smartphone, highlighting the practical application of the fluorescent probe for DPA detection under aqueous solution conditions.

A Nomogram for Predicting Delayed Viral Shedding in Non-Severe SARS-CoV-2 Omicron Infection.

Purpose: The Omicron variant of SARS-CoV-2 has emerged as a significant global concern, characterized by its rapid transmission and resistance to existing treatments and vaccines. However, the specific hematological and biochemical factors that may impact the clearance of Omicron variant infection remain unclear. The present study aimed to identify easily accessible laboratory markers that are associated with prolonged virus shedding in non-severe patients with COVID-19 caused by the Omicron variant. Patients and Methods: A retrospective cohort study was conducted on 882 non-severe COVID-19 patients who were diagnosed with the Omicron variant in Shanghai between March and June 2022. The least absolute shrinkage and selection operator regression model was used for feature selection and dimensional reduction, and multivariate logistic regression analysis was performed to construct a nomogram for predicting the risk of prolonged SARS-CoV-2 RNA positivity lasting for more than 7 days. The receiver operating characteristic (ROC) curve and calibration curves were used to assess predictive discrimination and accuracy, with bootstrap validation. Results: Patients were randomly divided into derivation (70%, n = 618) and validation (30%, n = 264) cohorts. Optimal independent markers for prolonged viral shedding time (VST) over 7 days were identified as Age, C-reactive protein (CRP), platelet count, leukocyte count, lymphocyte count, and eosinophil count. These factors were subsequently incorporated into the nomogram utilizing bootstrap validation. The area under the curve (AUC) in the derivation (0.761) and validation (0.756) cohorts indicated good discriminative ability. The calibration curve showed good agreement between the nomogram-predicted and actual patients with VST over 7 days. Conclusion: Our study confirmed six factors associated with delayed VST in non-severe SARS-CoV-2 Omicron infection and constructed a Nomogram which may assist non-severely affected patients to better estimate the appropriate length of self-isolation and optimize their self-management strategies.

Clinical value of radiography after transnasal ileus intubation for the surgical timing of small bowel obstruction.

OBJECTIVE: To explore the guiding value of radiography after transnasal ileus intubation for the treatment of small bowel obstruction and the selection of surgical timing. METHODS: This retrospective study analyzed the clinical data of 133 patients with small bowel obstruction who were admitted to Gongli Hospital from January 2013 to December 2020. The patients were included in a nasogastric intubation group (n=65) or a transnasal ileus intubation + radiography group (n=68), according to different treatment methods. The response rate of non-surgical treatment, bowel function, observation time before surgery, postoperative complications and the recurrence rate were observed in both groups. RESULTS: There was no significant difference in the response rate of non-surgical treatment and the incidence of postoperative complications between the two groups (P=0.257 and P=0.959, respectively). The observation time before surgery was shorter and the recurrence rate of obstruction was lower in the transnasal ileus intubation + radiography group than those in the nasogastric intubation group. The pain relief time, first flatus time and hospital stay were shorter in the transnasal ileus intubation + radiography group than those in the nasogastric intubation group, with statistically significant differences (all P<0.05). It was found that ascites and observation time before surgery were the influencing factors of surgical timing in patients with small bowel obstruction. CONCLUSION: Transnasal ileus intubation is an effective treatment for small bowel obstruction. Radiography after transnasal ileus intubation is helpful to determine the optimal surgical timing for small bowel obstruction, shorten the postoperative recovery time and reduce the recurrence rate in patients, so it is recommended in clinical practice.

Post-operative chemotherapy improves the survival of patients with well differentiated widespread metastatic appendiceal non-mucinous adenocarcinomas.

BACKGROUND: Appendiceal adenocarcinoma is a very rare type of tumor, often asymptomatic in the early stages of development. Surgical resection is the most preferred intervention against appendiceal non-mucinous adenocarcinoma, but the efficacy of post-operative adjuvant chemotherapy is still unclear because the cancer is rare. Accordingly, we sought to characterize appendiceal non-mucinous adenocarcinoma profile that confers a better survival advantage for post-operative chemotherapy. METHODS: We analyzed patients with appendiceal non-mucinous adenocarcinoma in the Surveillance, Epidemiology and End Results database, histologically diagnosed for the cancer between 2004 and 2015. Nearly half of the patients first underwent surgery and thereafter received post-operative chemotherapy. Logistic regression, Kaplan-Meier, univariate and multivariate Cox analysis were performed to evaluate the odds ratio for the propensity of patients underweening chemotherapy, whereas hazard ratios were used to evaluate the overall as well as cancer-specific survival. RESULTS: Of the 724 patients with appendiceal non-mucinous adenocarcinoma who underwent surgery, 301 (41.6%) received post-operative chemotherapy. Notably, patients with metastatic appendiceal non-mucinous adenocarcinoma were more likely to receive chemotherapy (OR =7.42, 95% CI: 5.34-10.39, P<0.001), similar to those with poor pathologically differentiated cancer types (OR =2.10, 95% CI: 1.49-3.00, P<0.001). However, univariate and multivariable Cox regression analyses found no significant overall survival and cancer-specific survival advantage for patients put on postoperative post-operative chemotherapy. In the disease stage and pathological differentiation groups, only patients with widespread metastatic (Stage IV) but well differentiated tumors displayed better 3-year (11.9% in overall survival, 11.5% in cancer-specific survival) and 5-year survival rate (7.8% in overall survival, 6.8% in cancer-specific survival) to post-operative chemotherapy. CONCLUSIONS: Staging and grading of appendiceal non-mucinous adenocarcinoma is invaluable in guiding the rationale of post-operative chemotherapy. Findings of this research support the view that only patients with both of widespread metastatic but well differentiated appendiceal non-mucinous adenocarcinoma should be considered for post-operative chemotherapy. Nonetheless, further prospective multidisciplinary clinical trials are necessary to further discern the use chemotherapy after surgery in appendiceal non-mucinous adenocarcinoma patients.

Binimetinib Is a Potent Reversible and Time-Dependent Inhibitor of Cytochrome P450 1A2.

Binimetinib is a selective MEK1/2 inhibitor, which is indicative of melanoma. We aimed to investigate the inhibitory effect of binimetinib on cytochrome P450 using human liver microsomes. Binimetinib was demonstrated to display reversible and time-dependent inhibitory effects on human CYP1A2. Binimetinib can inhibit the activity of phenacetin deethylation with IC50 of 5.6 µM. A 30 min preincubation of binimetinib with NADPH-supplemented human liver microsomes raised a significant left IC50 shift (6.5-fold), from 5.69-0.88 µM. The inactivation parameters Kinact and KI were 0.063 min-1 and 15.47 µM, and the half-life of inactivation was 11 min. Glutathione (GSH) and catalase/superoxide exhibited minor or no protective effect on binimetinib-induced enzyme inactivation. Trapping experiment by GSH induced a detection of GSH adduct, of which the formation was believed to be through the oxidation of electron-rich 1,4-benzenediamine to reactive 1,4-diiminoquinone species. Cytochrome P450 3A4, 2C9, and 2D6 were involved in the bioactivation of binimetinib. In conclusion, binimetinib was proven to display reversible and time-dependent inhibitory effect on CYP1A2, which may have implications for the toxicity of binimetinib.

In vitro metabolism of ibrutinib in rat, dog and human hepatocytes using liquid chromatography combined with diode-array detection and Q-Exactive Orbitrap tandem mass spectrometry.

RATIONALE: Ibrutinib is a potent Bruton's tyrosine kinase inhibitor which has shown promising efficacy against various B-cell malignancies. Its metabolic profiles have not been disclosed. The aim of this study was to investigate the metabolism of ibrutinib in the hepatocytes of rat, dog and human. METHODS: Ibrutinib was incubated with hepatocytes at 37°C for 2 h, after which the samples were analyzed using ultrahigh-performance liquid chromatography with diode-array detection and Q-Exactive Orbitrap tandem mass spectrometry (UHPLC/DAD-Q-Exactive-Orbitrap-MS). The acquired data were processed using MetWorks™ software. RESULTS: A total of 20 metabolites were structurally identified by their MS and MS2 data. M1 and M5 were unambiguously identified using authentic standards. The biotransformation of ibrutinib involved hydroxylation, hydration, oxygenation, epoxide hydrolysis, dehydrogenation, dealkylation and GSH conjugation. CONCLUSIONS: Humans have a relatively low capability for metabolizing ibrutinib. Compared with rat, dog had closer metabolic profiles to humans and would be more suitable for toxicity studies. This study provides more valuable information with respect to the in vitro disposition of ibrutinib.

LncRNA LINC00668 promotes the progression of breast cancer by inhibiting apoptosis and accelerating cell cycle.

Objective: To elucidate how lncRNA 00668 (LINC00668) influences the development of breast cancer (BC). Materials and methods: Genome-wide expression profile of BC and paracancerous tissues were downloaded from The Cancer Genome Atlas (TCGA) and BC tissues and paracancerous tissues enrolled from our hospital for analyzing the expression level of LINC00668 and its correlation with prognosis. GSEA was conducted to analyze the potential functions of LINC00668. By transfection of sh-LINC00668 in BC cells, proliferation, apoptosis, cell cycle and colony formation of BC cells were accessed. Western blot was conducted to detect protein expressions of Ki-67, CDK4, Bcl-2, p21 and genes in AKT/mTOR pathways after LINC00668 knockdown in BC cells. Finally, tumor-bearing nude mice were administrated with BC cells. We compared the proliferative rate in mice with different administrations. Immunohistochemistry was carried out to access expression levels of Ki-67, CDK4, Bcl-2 and P21 in mice. Results: Both TCGA data and BC tissues harvested from our hospital indicated the higher expression of LINC00668 in BC tissues. LINC00668 expression was negatively correlated to prognosis of BC patients. GSEA pointed out that LINC00668 is enriched in regulations of cell cycle and apoptosis. By transfection of sh-LINC00668 in MDA-MB-231 and MDA-MB-436 cells, the proliferative and colony formation abilities of BC cells decreased. Besides, LINC00668 knockdown in BC cells induced apoptosis and arrested cell cycle. LINC00668 knockdown downregulated Ki-67, CDK4 and Bcl-2, but upregulated p21. The AKT/mTOR pathway was inhibited after LINC00668 silenced. In vivo experiments demonstrated the decreased proliferative rate in tumor-bearing mice administrated with sh-LINC00668 transfected BC cells. Consistently, immunohistochemical results showed lower positive expressions of Ki-67, CDK4 and Bcl-2, but higher positive expression of p21 in sh-LINC00668 group. Conclusion: LINC00668 is highly expressed in BC tissues and can promote the progression of BC by inhibiting apoptosis and accelerating cell cycle progression.

Circular RNA circBACH2 plays a role in papillary thyroid carcinoma by sponging miR-139-5p and regulating LMO4 expression.

Circular RNAs (circRNAs) are a class of non-coding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. They are structurally stable and tissue-specific. However, the function of human circRNAs and the role of circRNAs in papillary thyroid carcinoma (PTC) remain to be determined. Herein, the function of circRNA circBACH2 was investigated in human PTC cells. First, we detected the expression of circBACH2 in PTC tissues and PTC cell lines by RT-PCR. FISH was used to confirm the subcellular localization of circBACH2. A luciferase reporter assay and AGO2-RIP was used to confirm the relationship between circBACH2 and miR-139-5p. PTC cells were stably transfected with siRNA against circBACH2 and cell proliferation, migration and invasion were detected to evaluate the effect of circBACH2 in PTC, while tumorigenesis was assayed in nude mice. We found that circBACH2 was highly expressed in PTC tissues and PTC cell lines. Mechanistically, we confirmed that circBACH2 could directly bind to miR-139-5p and relieve suppression of the target LMO4. Functionally, we found that inhibiting circBACH2 expression decreased cell proliferation, migration, and invasion. Finally, down-regulating circBACH2 suppressed the growth of PTC xenografts in nude mice. Our findings indicate that circBACH2 acts as a novel oncogenic RNA that sponges miR-139-5p and can be used as a tumor biomarker of PTC. What's more, these results revealed that the circBACH2/miR-139-5p/LMO4 axis could be targeted as a potential treatment strategy for PTC.

High expression of CD39 in gastric cancer reduces patient outcome following radical resection.

Ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also known as cluster of differentiation (CD)39, is the rate-limiting enzyme in the generation of immunosuppressive adenosine and is important in tumor progression. The present study evaluated the expression of CD39+ and CD39+ forkhead box P3 (FoxP3)+ regulatory T (Treg) cells in gastric cancer (GC), and determined their prognostic roles in patients with GC following radical resection. It was observed that CD39 was expressed at significantly higher rates in tumor tissues as compared with paired peritumoral tissues. Overexpression of tumor CD39 was correlated with overall survival (OS). Furthermore, CD39 expression in GC tissues exhibited a prognostic role in OS. The CD39+ FoxP3+/FoxP3+ ratio in tumor tissues was higher than that in paired peritumoral tissues, and CD39+ FoxP3+ Treg cells were a better prognostic indicator than FoxP3+ Treg cells for OS. Collectively, our study indicates that overexpression of CD39 in GC is a predictor of poor outcome for GC patients following radical resection. CD39+ FoxP3+ Treg cells are a potential target for cancer immunotherapy.

The Value of Performing Early Non-enhanced CT in Developing Strategies for Treating Acute Gallstone Pancreatitis.

BACKGROUND: The purpose of this study is to assess the value of early abdominal non-enhanced computed tomography (NECT) in developing strategies for treating acute gallstone pancreatitis (AGP). METHODS: AGP patients underwent NECT within 48 h after symptom onset to determine the presence of peripancreatic fluid collection, gallstones, and common bile duct stones. Patients with mild AGP who had neither organ failure by clinical data nor peripancreatic fluid collection by NECT (classified as grade A, B, or C based on the Balthazar CT grading system) were randomized to undergo an early laparoscopic cholecystomy (ELC; LC performed within 7 days after a pancreatitis attack, without waiting for symptom resolution) or late laparoscopic cholecystomy (LLC; LC performed ≥ 7 days following an attack, with the patient being completely free of AGP symptoms). RESULTS: The study enrolled 102 patients with mild AGP defined by clinical data and NECT. NECT was 89.2 % and 87.8 % accurate in detecting gallbladder stones and CBD stones, respectively. Totals of 49 and 53 patients were assigned to an ELC and LLC group, respectively. All patients in both groups were cured, no LC-related complications occurred, and no case of AGP increased in severity following LC. The mean lengths of hospital stay and LC operation time were significantly shorter in the ELC group than the LLC group (P < 0.05). CONCLUSIONS: NECT can accurately detect peripancreatic fluid collection and biliary obstructions; thus, early abdominal NECT is valuable when developing strategies for treating AGP. Patients with mild AGP without organ failure or peripancreatic fluid collection can safely undergo ELC without waiting for complete resolution of their pancreatitis.

Overexpression of CD39 and high tumoral CD39⁺/CD8⁺ ratio are associated with adverse prognosis in resectable gastric cancer.

CD39/ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1) is a cell surface-located, rate-limiting enzyme in the generation of adenosine, and plays a crucial role in tumor development. We examined co-expression of CD39 and CD8in gastric cancer (GC) and showed that the expression of CD39 and CD8 increased significantly in tumor tissues compared to paired peritumor tissues. The expression of tumoral CD39 (tCD39), but not tumoral CD8 (tCD8), was related to overall survival. Furthermore, the CD39(+)/CD8(+) ratio was associated with poor prognosis in resected GC patients. Taken together, our data indicate that highCD39 expression and high tCD39(+)/CD8(+) ratio in GC is a predictor of poor prognosis for GC patients after radical resection. Moreover, CD39 could serve as a potential target for cancer immunotherapy.

Optimization of thermosensitive chitosan hydrogels for the sustained delivery of venlafaxine hydrochloride.

Chitosan/glycerophosphate disodium (GP) thermosensitive hydrogels were prepared for the sustained delivery of venlafaxine hydrochloride (VH) and optimization of this formulation was mainly studied. Release mechanism was investigated by applying various mathematical models to the in vitro release profiles. Overall, drug release from the hydrogels showed best fit in first-order model and drug release mechanism was diffusion-controlled release. Optimization of VH chitosan/GP thermosensitive hydrogels was conducted by using a three-level three-factorial Box-Behnken experimental design to evaluate the effects of considered variables, the strength of the formulation, chitosan concentration and GP amount, on the selected responses: cumulative percentage drug release in 1h, 24h and the rate constant. It presented that higher strength and GP concentration resulted in higher initial release and rate constant, which supported the hypothesis that the kinetic gelation mechanism of this system was nucleation and growth. Drug release profiles illustrated that controlled drug delivery could be obtained over 24h, which confirmed the validity of optimization. In vivo pharmacokinetic study was investigated and it demonstrated that compared with VH solution, chitosan/GP thermosensitive hydrogels had a better sustained delivery of VH.