In vitro modulation the Notch pathway by piperine: A therapeutic strategy for docetaxel-resistant and non-resistant prostate cancer.

Docetaxel (DTX) resistance poses a significant challenge in the treatment of prostate cancer (PCa), often leading to chemotherapy failure. This study investigates the ability of piperine, a compound derived from black pepper, to enhance the sensitivity of PCa cells to DTX and elucidates its underlying mechanism. We established a DTX-resistant PCa cell line, DU145/DTX, to conduct our experiments. Through a series of assays, including MTT for cell viability, flow cytometry for apoptosis, Transwell for cell migration and invasion, and western blot for protein expression analysis, we assessed the effects of piperine on these cellular functions and on the Notch signaling pathway components. Our results demonstrated that we successfully established the DTX-resistant PCa cell line DU145/DTX. Piperine effectively decreased the viability of both DU145 and its DTX-resistant counterpart, DU145/DTX, in a concentration and time-dependent manner when used alone and in combination with DTX. Notably, piperine also induced apoptosis and reduced the migration and invasion capabilities of these cells. At the molecular level, piperine down-regulated the Notch pathway by inhibiting Notch1 and Jagged1 signaling, as well as reducing the expression of downstream effectors Hey1 and hes family bHLH transcription factor 1. The study concludes that piperine's ability to modulate the Notch signaling pathway and induce apoptosis highlights its potential as a complementary treatment for DTX-resistant PCa, paving the way for the use of traditional Chinese medicinal compounds in modern oncology treatment strategies.

Nitrogen-doped carbon-coated Cu0 activates molecular oxygen for norfloxacin degradation over a wide pH range.

The Fenton-like activated molecular oxygen technology demonstrates significant potential in the treatment of refractory organic pollutants in wastewater, offering promising development prospects. We prepared a N-doped C-coated copper-based catalyst Cu0/NC3-600 through the pyrolysis of Mel-modified Cu-based metal-organic framework (MOF). The results indicate that the degradation of 20 mg/L norfloxacin (NOR) was achieved using 1.0 g/L Cu0/NC3-600 across a wide pH range, with a removal rate exceeding 95 % and total organic carbon (TOC) removals approaching 70 % after 60 min at pH 5-11. The nitrogen doping enhances the electronic structure of the carbon material, facilitating the adsorption of molecular oxygen. Additionally, the formed carbon layer effectively prevent copper leaching,contributing to increased stability to a certain extent. Subsequently, we propose the catalytic reaction mechanism for the Cu0/NC/air system. Under acidic conditions, Cu0/NC3-600 activates molecular oxygen to produce the •O2-, which serves as the primary active species for NOR degradation. While in alkaline conditions, the high-valent copper species Cu3+ is generated in conjunction with •O2-, both working simultaneously for NOR degradation. Furthermore, based on the LC-MS results, we deduced four possible degradation pathways. This work offers a novel perspective on expanding the pH range of copper-based catalysts with excellent ability to activate molecular oxygen for environmental water treatment.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, and its development comprises a multistep process from intraepithelial neoplasia (IN) to carcinoma (CA). However, the critical regulators and underlying molecular mechanisms remain largely unknown. AIM: To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention. METHODS: A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide (4NQO) to C57BL/6 mice. Moreover, we established a control group without 4NQO treatment of mice. Then, transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses, including low-grade IN (LGIN), high-grade IN (HGIN), and CA, and controlled normal tissue (NOR) samples. Differentially expressed genes (DEGs) were identified in the LGIN, HGIN, and CA groups, and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The CIBERSORT algorithm was used to detect the pattern of immune cell infiltration. Immunohistochemistry (IHC) was also conducted to validate our results. Finally, the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice. RESULTS: Compared with those in the NOR group, a total of 681541, and 840 DEGs were obtained in the LGIN, HGIN, and CA groups, respectively. Using the intersection of the three sets of DEGs, we identified 86 genes as key genes involved in the development of ESCC. Enrichment analysis revealed that these genes were enriched mainly in the keratinization, epidermal cell differentiation, and interleukin (IL)-17 signaling pathways. CIBERSORT analysis revealed that, compared with those in the NOR group, M0 and M1 macrophages in the 4NQO group showed stronger infiltration, which was validated by IHC. Serum cytokine analysis revealed that, compared with those in the NOR group, IL-1ß and IL-6 were upregulated, while IL-10 was downregulated in the LGIN, HGIN, and CA groups. Moreover, the expression of the representative key genes, such as S100a8 and Krt6b, was verified in external human samples, and the results of immunohistochemical staining were consistent with the findings in mice. CONCLUSION: We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions. In addition, we found that macrophage infiltration and abnormal alterations in the levels of inflammation-associated cytokines, such as IL-1ß, IL-6, and IL-10, in the peripheral blood may be closely associated with the development of ESCC.

Development of a Multi-Parametric ultrasonography nomogram for prediction of invasiveness in ductal carcinoma in situ.

OBJECTIVE: To investigate the independent risk variables associated with the potential invasiveness of ductal carcinoma in situ (DCIS) on multi-parametric ultrasonography, and further construct a nomogram for risk assessment. METHODS: Consecutive patients from January 2017 to December 2022 who were suspected of having ductal carcinoma in situ (DCIS) based on magnetic resonance imaging or mammography were prospectively enrolled. Histopathological findings after surgical resection served as the gold standard. Grayscale ultrasound, Doppler ultrasound, shear wave elastography (SWE), and contrast-enhanced ultrasound (CEUS) examinations were preoperative performed. Binary logistic regression was used for multifactorial analysis to identify independent risk factors from multi-parametric ultrasonography. The correlation between independent risk factors and pathological prognostic markers was analyzed. The predictive efficacy of DCIS associated with invasiveness was assessed by logistic analysis, and a nomogram was established. RESULTS: A total of 250 DCIS lesions were enrolled from 249 patients, comprising 85 pure DCIS and 165 DCIS with invasion (DCIS-IDC), of which 41 exhibited micro-invasion. The multivariate analysis identified independent risk factors for DCIS with invasion on multi-parametric ultrasonography, including image size (>2cm), Doppler ultrasound RI (≥0.72), SWE's Emax (≥66.4 kPa), hyper-enhancement, centripetal enhancement, increased surrounding vessel, and no contrast agent retention on CEUS. These factors correlated with histological grade, Ki-67, and human epidermal growth factor receptor 2 (HER2) (P < 0.1). The multi-parametric ultrasound approach demonstrated good predictive performance (sensitivity 89.7 %, specificity 73.8 %, AUC 0.903), surpassing single US modality or combinations with SWE or CEUS modalities. Utilizing these factors, a predictive nomogram achieved a respectable performance (AUC of 0.889) for predicting DCIS with invasion. Additionally, a separate nomogram for predicting DCIS with micro-invasion, incorporating independent risk factors such as RI (≥0.72), SWE's Emax (≥65.2 kPa), and centripetal enhancement, demonstrated an AUC of 0.867. CONCLUSION: Multi-parametric ultrasonography demonstrates good discriminatory ability in predicting both DCIS with invasion and micro-invasion through the analysis of lesion morphology, stiffness, neovascular architecture, and perfusion. The use of a nomogram based on ultrasonographic images offers an intuitive and effective method for assessing the risk of invasion in DCIS. Although the nomogram is not currently considered a clinically applicable diagnostic tool due to its AUC being below the threshold of 0.9, further research and development are anticipated to yield positive outcomes and enhance its viability for clinical utilization.

Preoperative glucose-to-lymphocyte ratio predicts survival in cancer.

Background: Systemic inflammation and glucose metabolism have been closely related to the survival of cancer patients. Therefore, we aimed to evaluate whether preoperative glucose-to-lymphocyte ratio (GLR) can be used to predict the survival of cancer patients. Methods: We retrospectively examined 2172 cancer patients who underwent surgery from January 1, 2014, to December 31, 2016. There were 240 patients with non-small cell lung cancer (NSCLC), 378 patients with colorectal cancer (CRC), 221 patients with breast cancer (BC), 335 patients with gastric cancer (GC), 270 patients with liver cancer, 233 patients with esophageal cancer (EC), 295 patients with renal cancer, and 200 patients with melanoma. The formula for preoperative GLR calculation was as follows: GLR=glucose/lymphocyte count. The overall survival (OS) was estimated using the Kaplan-Meier method. The predictive factors for OS were determined using multivariate analysis. Results: The Kaplan-Meier analysis showed that the median survival time in the high-GLR group was much shorter than that of those in the low-GLR group for different cancers. Cox multivariate regression analysis reveals that preoperative GLR was an independent factor for predicting overall survival in different tumor types. Conclusion: Elevated preoperative GLR was remarkably associated with a poorer prognosis in patients with NSCLC, CRC, breast cancer, gastric cancer, kidney cancer, liver cancer, esophageal cancer, and melanoma. Preoperative GLR promises to be an essential predictor of survival for cancer patients.

Predictive value of contrast-enhanced ultrasonography and ultrasound elastography for management of BI-RADS category 4 nonpalpable breast masses.

PURPOSE: The objective of this study was to investigate the independent risk factors and associated predictive values of contrast-enhanced ultrasound (CEUS), shear wave elastography (SWE), and strain elastography (SE) for high-risk lesions (HRL) and malignant tumors (MT) among nonpalpable breast masses classified as BI-RADS category 4 on conventional ultrasound. METHODS: This prospective study involved consecutively admitted patients with breast tumors from January 2018, aiming to explore the management of BI-RADS category 4 breast tumors using CEUS and elastography. We conducted a retrospective review of patient data, focusing on those with a history of a nonpalpable mass as the primary complaint. Pathologic findings after surgical resection served as the gold standard. The CEUS arterial-phase indices were analyzed using contrast agent arrival-time parametric imaging processing mode, while quantitative and qualitative indices were examined on ES images. Independent risk factors were identified through binary logistic regression multifactorial analysis. The predictive efficacy of different modalities was compared using a receiver operating characteristics curve. Subsequently, a nomogram for predicting the risk of HRL/MT was established based on a multifactorial logistic regression model. RESULTS: A total of 146 breast masses from 146 patients were included, comprising 80 benign tumors, 12 HRLs, and 54 MTs based on the final pathology. There was no significant difference in pathologic size between the benign and HRL/MT groups [8.00(6.25,10.00) vs. 9.00(6.00,10.00), P = 0.506]. The diagnostic efficacy of US plus CEUS exceeded that of US plus SWE/SE for BI-RADS 4 nonpalpable masses, with an AUC of 0.954 compared to 0.798/0.741 (P ï¼œ 0.001). Further stratified analysis revealed a more pronounced improvement for reclassification of BI-RADS 4a masses (AUC: 0.943 vs. 0.762/0.675, P ï¼œ 0.001) than BI-RADS 4b (AUC:0.950 vs. 0.885/0.796, P＞0.05) with the assistance of CEUS than SWE/SE. Employing downgrade CEUS strategies resulted in negative predictive values ranging from 95.2 % to 100.0 % for BI-RADS 4a and 4b masses. Conversely, using upgrade nomogram strategies, which included the independent predictive risk factors of irregular enhanced shape, poor defined enhanced margin, earlier enhanced time, increased surrounding vessels, and presence of contrast agent retention, the diagnostic performance achieved an AUC of 0.947 with good calibration. CONCLUSION: After investigating the potential of CEUS and ES in improving risk assessment and diagnostic accuracy for nonpalpable BI-RADS category 4 breast masses, it is evident that CEUS has a more significant impact on enhancing classification compared to ES, particularly for BI-RADS 4a subgroup masses. This finding suggests that CEUS may offer greater benefits in improving risk assessment and diagnostic accuracy for this specific subgroup of breast masses.

Red blood cell distribution width is associated with sarcopenia risk in early-stage non-small cell lung cancer.

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.

Subcutaneous fat predicts bone metastasis in breast cancer: A novel multimodality-based deep learning model.

OBJECTIVES: This study explores a deep learning (DL) approach to predicting bone metastases in breast cancer (BC) patients using clinical information, such as the fat index, and features like Computed Tomography (CT) images. METHODS: CT imaging data and clinical information were collected from 431 BC patients who underwent radical surgical resection at Harbin Medical University Cancer Hospital. The area of muscle and adipose tissue was obtained from CT images at the level of the eleventh thoracic vertebra. The corresponding histograms of oriented gradients (HOG) and local binary pattern (LBP) features were extracted from the CT images, and the network features were derived from the LBP and HOG features as well as the CT images through deep learning (DL). The combination of network features with clinical information was utilized to predict bone metastases in BC patients using the Gradient Boosting Decision Tree (GBDT) algorithm. Regularized Cox regression models were employed to identify independent prognostic factors for bone metastasis. RESULTS: The combination of clinical information and network features extracted from LBP features, HOG features, and CT images using a convolutional neural network (CNN) yielded the best performance, achieving an AUC of 0.922 (95% confidence interval [CI]: 0.843-0.964, P< 0.01). Regularized Cox regression results indicated that the subcutaneous fat index was an independent prognostic factor for bone metastasis in breast cancer (BC). CONCLUSION: Subcutaneous fat index could predict bone metastasis in BC patients. Deep learning multimodal algorithm demonstrates superior performance in assessing bone metastases in BC patients.

Albumin-bilirubin score predicts trastuzumab resistance in HER2-positive breast cancer.

BACKGROUND: The albumin-bilirubin (ALBI) score is a novel indicator of liver function. Some studies showed that the ALBI score was a predictive marker for the prognosis and efficacy of drug therapy in malignancies. We aimed to assess the predicted role of ALBI score in the sensitivity to therapy with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer (BC). The clinical data of 226 HER2-positive BC patients at the Harbin Medical University Cancer Hospital from January 2017 and December 2018 were retrospectively collected. The ALBI score was calculated with serum albumin and bilirubin before diagnosis. The associations between ALBI score and trastuzumab resistance were analyzed by logistic regression analyses. The patients with trastuzumab resistance had higher ALBI scores compared with the patients without trastuzumab resistance. Moreover, there were weak correlations between the ALBI score and lymph node status (P= 0.093). In addition, multivariate analysis revealed that the ALBI score was an independent prognostic factor for trastuzumab resistance in HER2-positive BC. High ALBI score is associated with trastuzumab resistance in HER2-positive BC. Future studies are needed.

Preoperative small airway dysfunction is associated with skeletal muscle loss in early-stage non-small cell lung cancer.

BACKGROUND: Postoperative skeletal muscle loss (SM loss) was reported to be associated with a poor prognosis in early-stage non-small cell lung cancer (NSCLC). Small airway dysfunction (SAD) is a common but neglected respiratory abnormality. Little information is known about the association between preoperative SAD and postoperative SM loss in early-stage NSCLC. Therefore, this study aimed to investigate the correlation between preoperative SAD and SM loss after surgery in early-stage NSCLC patients. METHODS: There were 348 NSCLC patients with stages I-IIIA in this study from January 2017 to December 2020. All CT images were contrast-enhanced scans, and the skeletal muscle index (SMI) was measured using CT images. A 10.0% decrease in SMI over 12 months was determined as the cut-off value to define excessive SM loss. Logistic regression analyses were used to examine the relationship between SAD and SM loss. RESULTS: This study included 348 subjects who underwent pulmonary operation (159 males and 189 females; mean age: 57.5 ± 8.8 years). 152 (43.7%) patients were identified as having SAD before surgery, and 179 patients (51.4%) were identified as having SM loss after 1 year. Moreover, a higher incidence of SAD was found in the SM loss group compared with that in the non-SM loss group (52.0% vs. 34.9%, p = 0.001). The patients with SAD were older, had larger tumor size, and had lower albumin levels. Furthermore, there were significant correlations between the lung function parameters manifesting SAD and the percentage change in SMI (for the forced expiratory flow when 75% of forced vital capacity has been exhaled (FEF75%), Pearson r=-0.107, p = 0.046; for FEF50%, r = -0.142, p = 0.008; and for FEF25-75%, r=-0.124, p = 0.021; respectively). However, no significant correlations were found between SMI and the lung function parameters reflecting proximal airway obstruction (p > 0.05). Logistic regression analysis revealed that preoperative SAD (HR, 2.465; 95% CI, 1.256-4.838; p = 0.009) was independent risk factor for postoperative SM loss in early-stage NSCLC. In addition, multivariable analysis revealed that SAD (HR, 1.816; 95% CI, 1.025-3.216, P = 0.041) were associated with postoperative complications. CONCLUSION: Preoperative SAD is significantly associated with postoperative complications and SM loss in early NSCLC patients. Our results suggest that preoperative assessment of SAD may be useful for risk stratification of surgical candidates with potential for targeted interventions.

Lower subcutaneous fat index predicts bone metastasis in breast cancer.

BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer. OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients. METHODS: 517 BC patients were studied retrospectively. Patients' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models. RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05). CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.

Pectoralis muscle predicts distant metastases in breast cancer by deep learning radiomics.

BACKGROUND: Sarcopenia is associated with a poor prognosis in patients with breast cancer (BC). Currently, there are few quantitative assessments carried out between muscle biomarkers and distant metastasis using existing methods. PURPOSE: To assess the predictive value of the pectoralis muscle for BC distant metastasis, we developed a deep learning radiomics nomogram model (DLR-N) in this study. MATERIAL AND METHODS: A total of 493 patients with pathologically confirmed BC were registered. Image features were extracted from computed tomography (CT) images for each patient. Univariate and multivariate Cox regression analyses were performed to determine the independent prognostic factors for distant metastasis. The DLR-N was built based on independent prognostic factors and CT images to predict distant metastases. The model was assessed in terms of overall performance, discrimination, calibration, and clinical value. Finally, the predictive performance of the model was validated using the testing cohort. RESULTS: The developed DLR-N combined multiple radiomic features and clinicopathological factors and demonstrated excellent predictive performance. The C-index of the training cohort was 0.983 (95% confidence interval [CI] = 0.969-0.998) and the C-index of the testing cohort was 0.948 (95% CI = 0.917-0.979). Decision curve analysis (DCA) showed that patients could benefit more from incorporating multimodal radiomic features into clinicopathological models. CONCLUSIONS: DLR-N verified that there were biomarkers at the level of the fourth thoracic vertebra (T4) that affected distant metastasis. Multimodal prediction models based on deep learning could be a potential method to aid in the prediction of distant metastases in patients with BC.

Bisphenol A interferes with lncRNA Fhadlos2 and RUNX3 association in adolescent mouse ovary.

Bisphenol A (BPA) has a number of adverse effects on the reproductive development of females. In particular, the mechanism of disruption of ovarian development in adolescent mice is still unclear. Based on transcriptome sequencing results, a differentially expressed lncRNA, Fhad1os2, was detected in the ovaries of BPA-exposed pubertal mice. In our study, the lncRNA Fhad1os2, localized in the ovarian granulosa cell cytoplasm, could regulate the proliferation of mouse ovarian granulosa cells. Mechanistically, the results of RNA pull-down experiments as well as mass spectrometry analysis showed that ERα, an interfering signaling molecule of BPA, could directly bind lncRNA Fhad1os2 and decrease the transcription of lncRNA Fhad1os2 in response to the estrogen-like effect of BPA. BPA exposure also caused abnormal lncRNA Fhad1os2 pulldown protein-related signaling pathways in the ovaries of adolescent mice. Furthermore, lncRNA Fhad1os2 interacted with RUNX3, a transcription factor related to follicle development and hormone synthesis. As a negative regulator, lncRNA Fhad1os2 transactivated the expression of Runx3, which in turn induced RUNX3 to positively regulate aromatase (Cyp19a1) expression in mouse ovarian granulosa cells and promote estrogen synthesis. In conclusion, our study indicates that BPA exposure interferes with ERα-regulated lncRNA Fhad1os2 interactions with RUNX3 in pubertal mice, affecting estrogen synthesis in mouse granulosa cells and contributing to premature ovarian maturation in pubertal mice.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.

Lean body mass predicts postoperative liver failure in patients with hepatocellular carcinoma.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a severe complication of liver surgery in hepatocellular carcinoma (HCC) patients. Reduced lean body mass (LBM) decreases the immune activity and increases adverse clinical outcomes among cancer patients. OBJECTIVE: We aimed to assess the association between LBM and PHLF in HCC patients. METHODS: PHLF was defined and graded based on the International Study Group of Liver Surgery (ISGLS) criteria. Patients with Grade B or Grade C were included in PHLF ⩾ Grade B group, while others in PHLF < Grade B group. LBM was measured via preoperative computed tomography images. Binary logistic regression was applied for investigating the association between LBM and PHLF. The receiver operating characteristic curve was used to identify potential cut-off values and assess the predictive ability of the measured variables. RESULTS: The PHLF ⩾ Grade B group had significantly lower LBM levels (means ± standard deviation: 57.0 ± 14.1) than PHLF < Grade B group (67.2 ± 15.7) (p< 0.001). After controlling other variables, LBM was an independent protective factor for PHLF ⩾ Grade B (Odds Ratio: 0.406, 95% confidence interval: 0.172-0.957, p= 0.039). The prevalence of PHLF ⩾ Grade B in each quartile of LBM was 29.4% (15/51), 25.5% (13/51), 19.2% (10/52) and 4.0% (2/50), respectively (ptrend< 0.001). CONCLUSIONS: LBM might be a protective factor for PHLF in HCC patients. Our findings might help to develop a novel strategy to reduce the occurrence of hepatic dysfunction following major liver resection. Multicentric prospective studies and further molecular biologic investigation are needed.

Deep learning radiomics under multimodality explore association between muscle/fat and metastasis and survival in breast cancer patients.

Sarcopenia is correlated with poor clinical outcomes in breast cancer (BC) patients. However, there is no precise quantitative study on the correlation between body composition changes and BC metastasis and survival. The present study proposed a deep learning radiomics (DLR) approach to investigate the effects of muscle and fat on distant metastasis and death outcomes in BC patients. Image feature extraction was performed on 4th thoracic vertebra (T4) and 11th thoracic vertebra (T11) on computed tomography (CT) image levels by DLR, and image features were combined with clinical information to predict distant metastasis in BC patients. Clinical information combined with DLR significantly predicted distant metastasis in BC patients. In the test cohort, the area under the curve of model performance on clinical information combined with DLR was 0.960 (95% CI: 0.942-0.979, P < 0.001). The patients with distant metastases had a lower pectoral muscle index in T4 (PMI/T4) than in patients without metastases. PMI/T4 and visceral fat tissue area in T11 (VFA/T11) were independent prognostic factors for the overall survival in BC patients. The pectoralis muscle area in T4 (PMA/T4) and PMI/T4 is an independent prognostic factor for distant metastasis-free survival in BC patients. The current study further confirmed that muscle/fat of T4 and T11 levels have a significant effect on the distant metastasis of BC. Appending the network features of T4 and T11 to the model significantly enhances the prediction performance of distant metastasis of BC, providing a valuable biomarker for the early treatment of BC patients.

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments.

BACKGROUND: The lack of effective pharmacotherapies for nonalcoholic fatty liver disease (NAFLD) is mainly attributed to insufficient research on its pathogenesis. The pathogenesis of TM6SF2-efficient NAFLD remains unclear, resulting in a lack of therapeutic strategies for TM6SF2-deficient patients. AIM: To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency. METHODS: Liver samples collected from both NAFLD mouse models and human participants (80 cases) were used to evaluate the expression of TM6SF2 by using western blotting, immunohistochemistry, and quantitative polymerase chain reaction. RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2. Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD. MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency. RESULTS: Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models. TM6SF2 overexpression can reduce hepatic lipid accumulation, suggesting a protective role for TM6SF2 in a high-fat diet (HFD). Downregulation of TM6SF2, simulating the TM6SF2 E167K mutation condition, increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis, accompanied by impaired fatty acid oxidation. Owing to the potential effect of TM6SF2 deficiency on lipid metabolism, the application of an acetyl-CoA carboxylase inhibitor (MK-4074) could reverse the NAFLD phenotypes caused by TM6SF2 deficiency. CONCLUSION: TM6SF2 plays a protective role in the HFD condition; its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism, and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

Association between c-type lectin-like receptor 2 and microsatellite instability in colorectal cancer: a cross-sectional study.

BACKGROUND: As a transmembrane protein, C-type lectin-like receptor 2 (CLEC-2) is mainly expressed on platelets and released into plasma after platelet activation. Activated platelets participate in the regulation of innate immune cells. Patients with different microsatellite statuses have distinct immune profiles. This study aimed to investigate the association of plasma CLEC-2 levels with microsatellite status among colorectal cancer (CRC) patients. METHODS: A cross-sectional analysis of 430 CRC patients from Harbin Medical University Cancer Hospital was conducted. CLEC-2 levels were measured with fasting venous blood samples drawn from each participant before any treatment. The microsatellite status was evaluated with DNA obtained from fresh frozen tumor tissue samples. The other clinical data were collected and recorded based on the medical system records. RESULTS: CLEC-2 levels were significantly higher among patients with high microsatellite instability phenotype than the stable microsatellite group, adjusting for other confounding variables. CONCLUSIONS: The increased CLEC-2 is associated with the high microsatellite instability subtype of CRC.

Utility of mean platelet volume in differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer. HCC and ICC differ in treatment and prognosis, warranting an effective differential diagnosis between them. This study aimed to explore the clinical value of mean platelet volume (MPV) to discriminate between HCC and ICC. MATERIAL/METHODS: We performed a retrospective analysis of ICC and HCC patients who were from the Harbin Medical University Cancer Hospital, China. Logistic regression analysis was used to identify the independent factors for the differentiation of HCC and ICC. A receiver operating characteristic curve was built to evaluate the diagnostic performance of the potential model. An independent validation study was performed to validate the diagnostic ability. RESULTS: ICC patients were detected in 146 out of 348 patients in the primary cohort. MPV levels were decreased in ICC patients compared with those in HCC patients. Logistic regression analysis revealed that MPV was an independent factor in distinguishing HCC from ICC. A combination of sex, hepatitis B surface antigen, MPV, alpha-fetoprotein, and carbohydrate antigen 19-9 demonstrated a good capability to differentiate HCC from ICC. Similar results were achieved in the validation cohort. CONCLUSIONS: MPV may be a new marker to help distinguish ICC from HCC. Further validation studies are required.

Preoperative PDW levels predict pulmonary metastasis in patients with hepatocellular carcinoma.

BACKGROUND: In hepatocellular carcinoma (HCC), pulmonary metastasis (PM) after hepatectomy is associated with poor clinical outcomes. The crucial phases of tumour cell proliferation, angiogenesis, and metastasis all entail platelet activation. In HCC, platelet distribution width (PDW) suggests platelet size changes and predicts a worse prognosis. The aim of this study was to assess the association between PDW and PMs in HCC patients receiving hepatectomy. MATERIAL/METHODS: From January 2013 to December 2015, a cohort of patients who underwent hepatectomy for HCC at the Harbin Medical University Cancer Hospital in China were retrospectively evaluated. The relationship between PDW levels and clinical and demographic parameters was examined. To investigate the relationships between predicted factors and PM, a competing risk model was used. From January 2016 to December 2018, a validation cohort of 109 patients from the First Affiliated Hospital of Harbin Medical University was studied independently. RESULTS: In the primary cohort, 19 out of 214 patients had postoperative PMs. In HCC patients with PM, PDW levels were lower than in those without PM. There was a significant difference in the cumulative incidence of 2-year PM between the high-PDW and low-PDW groups after controlling for competing risk events (death prior to the development of PM) (p < 0.001). In addition, PDW was also found to be an independent predictor for PM in a multivariable competing risk analysis. The results were externally validated in another cohort. CONCLUSIONS: In HCC, preoperative PDW is significantly associated with PM. PDW could be a biomarker for post-operative PM in HCC patients.