Konjac glucomannan-assisted fabrication of stable emulsion-based oleogels constructed with pea protein isolate and its application in surimi gels.

Konjac glucomannan (KGM) is widely used as a stabilizer for the structuring of highly unsaturated oils. This study aimed to investigate the changes in structure and functional properties of soybean oil - based oleogels (emulsion template method) prepared with different amounts of KGM-modified pea isolate protein (PPI). The findings revealed that the oleogels formed three - dimensional networks through van der Waals interactions and hydrogen bonding between the stretched PPI and KGM. As the amount of KGM increased, the oil droplets were more uniformly dispersed within the continuous PPI - KGM rigid network, especially when the ratio of PPI to KGM was 4:1. This formulation also showed the highest thixotropy (73.2 %) and the best oil binding capacity (94 %). Cryo - SEM revealed that the oleogel - prepared surimi gels successfully enclosed oil droplets in a dense matrix through a dual stabilization mechanism. Additionally, the incorporation of oleogels significantly improved the textural properties of surimi in comparison to directly adding oil.

Antarctic krill (Euphausia superba) oil high internal phase emulsions improved the lipid quality and gel properties of surimi gel.

In the study, high internal phase emulsions (HIPEs) prepared from Antarctic krill oil (AKO) were added into surimi and the effects on gel properties, lipid quality and stability were investigated. It is found that HIPEs-added groups exhibited higher gel strength and lower cooking loss than Oil-added counterparts. HIPEs-added groups had higher proportion of capillary water, and microstructure of HIPEs-added gels showed fewer large voids and small size droplets. HIPEs-added groups also showed less pronounced myosin heavy chain band. HIPEs- and Oil-added gels showed > 3500 mg/kg EPA + DHA and 0.4-0.8 mg/kg astaxanthin, and most HIPEs-added groups had higher levels of them but lower TBARS values. Results suggest AKO-HIPEs could reduce the intervention by lipids on myosin crosslinking during gelation, and protect fatty acids and asxtanthin from oxidation due to oxygen-isolation led by their high accumulation. Thus, AKO-HIPEs can be applied to fortify ω-3 PUFA and maintain good gel properties in surimi product.

Effects of gene silencing of indoleamine 2,3-dioxygenase 1 combined with rosmarinic acid on tumor immune microenvironment in H22 tumor-bearing mice.

Rosmarinic acid (RA) is a natural polyphenolic compound with several pharmacological activities, including immunomodulation and anti-tumor effect. Indoleamine 2,3-dioxygenase-1 (IDO1), the rate-limiting enzyme that metabolizes tryptophan into kynurenine, is an important negative immune regulator. This study aimed to explore the effect of combined action of IDO1 gene silencing and RA on tumor immune microenvironment. H22 tumor-bearing mice were treated with combination therapy with RA and IDO1-shRNA. The percentages and apoptosis of T-cells and subsets of splenic regulatory T-cells (Tregs) were detected by flow cytometry. Levels of tumor necrosis factor (TNF-α), Interferon-γ (IFN-γ), interleukin-2 (IL-2) and interleukin-10 (IL-10) were measured by enzyme linked immunosorbent assay (ELISA). Treatment with RA + IDO1-shRNA significantly increased the percentage of CD4+ T cells, ratio of CD4+/CD8+ and the levels of IFN-γ and IL-2, while decreased CD8+ apoptosis, the proportion of splenic Tregs and the levels of TNF-α and IL-10. The present study demonstrated that combination therapy with RA and IDO1-shRNA had anti-tumor effects on HCC. The mechanism might be related to regulating immune response and immunocytokines, as well as alleviating immunosuppression induced by Tregs in the tumor immune microenvironment.

Feasibilities and outcomes of patients treated with simultaneous prostate biopsy and general urological surgeries.

The present single-center retrospective clinical real-world study aimed to assess the feasibility and outcomes of patients who underwent simultaneous prostate biopsy and general urological surgeries. The medical records of 49 patients who underwent prostate biopsy and general urological surgeries simultaneously from October 2016 to June 2019 were retrospectively reviewed. Patients' outcomes were evaluated 3 days, 1 month and 6 months after biopsy. Of the 49 biopsy cases, 41 were treated by transurethral prostatectomy, two by ureteroscopic lithotripsy, two by laparoscopic renal cyst decortication, two by cystostomy and two by ureteral stent extraction. The overall detection rate of clinically significant prostate cancer was 22.4%. The rate in patients with a prostate imaging reporting and data system (PI-RADS) score of 4-5 was 100%, while in cases with a PI-RADS score of <3 it was 7.1%. Postoperative complications within 3 days included hematuria in 39 (79.6%) cases, fever in three (6.1%) cases and hematochezia in two (4.1%) cases. There was no significant difference in the incidence of hematuria between the transrectal and transperineal approaches; however, the overall incidence of complications was significantly reduced after switching from a transrectal approach to a transperineal approach. No complications were observed after 1 or 6 months. In summary, combining simultaneous prostate biopsy to general urological surgeries is a safe and feasible approach. The transperineal approach has a lower incidence of complications. This method may benefit certain patients who are concurrently undergoing general urological surgeries and are under suspicion of prostate cancer in real-world clinical practice.

Case report: Complete response of a bladder cancer patient with multiple hepatic and pelvic metastases treated by nab-paclitaxel combined with sintilimab.

This article described a patient with metastatic bladder cancer (mBC) who was successfully treated with nab-paclitaxel plus sintilimab. Localized muscle-invasive bladder cancer (MIBC) was discovered in a 56-year-old man who received radical cystectomy and platinum-based adjuvant chemotherapy. Eleven months after cystectomy, this patient developed numerous hepatic and pelvic metastases and progressed to mBC. The patient was given an anti-PD-1 antibody (sintilimab 200mg, q3w) in combination with Nab-paclitaxel (100mg, qw) for mBC. Complete remission (CR) was achieved after nine cycles of therapy, and the patient had no severe side effects during the treatment. The disease remained in CR after 41 months of follow-up. This case suggests that nab-paclitaxel combined with sintilimab is a safe and effective option in treatment of mBC.

Pathological characteristics and predictive factors of prostate biopsy in patients with serum PSA levels between 0 and 4.0 ng/ml.

Background: This study aimed to analyze the pathological characteristics and predictive factors of prostate biopsy in men with PSA levels below 4.0 ng/ml. Patients and methods: We retrospectively analyzed 158 patients who underwent prostate biopsy with PSA levels below 4.0 ng/ml. Pathological results were statistically analyzed. The logistic regression analysis was used to determine the predictive factors for malignant outcomes. Subgroup analysis was performed on patients who received surgery and the postoperative pathological upgrading was counted. Results: A total of 143 patients were enrolled. The tumor detection rate was 20.3%. Among these patients, most of them (79.3%) had prostate adenocarcinoma, but rare malignant tumors also accounted for 20.7%. Logistic regression analysis indicated that the only independent predictive factor for a positive prostate biopsy was the PI-RADS score. For prostate adenocarcinoma cases, 95.7% of them were organ localized and 47.8% of cases were clinically significant. Subgroup analysis was performed on 14 patients who received surgical treatment. 28.6% of patients were upgraded to clinically significant prostate cancer, while 64.3% of patients had an upgrade in tumor stage. Conclusion: Our study indicated that 20.3% of men with PSA levels between 0 and 4.0 ng/ml were diagnosed with prostate malignancies. Among these patients, most of them (79.3%) were diagnosed with prostate adenocarcinoma, and several uncommon types of malignancies were also detected in 20.7% of patients. The only risk factor for a positive biopsy in patients with a low PSA concentration was the PI-RADS score. It should be emphasized that the invasiveness of PCa patients diagnosed by biopsy may be underestimated as more than half of patients will upgrade their Gleason score or clinical stages after surgery. Thus, clinicians should pay more attention to patients with PSA levels between 0 and 4.0 ng/ml.

Acute pulmonary embolism and severe post thrombolysis renal bleeding, two deadly complications following mini-percutaneous nephrolithotomy: a rare case report.

BACKGROUND: Acute pulmonary embolism and severe renal bleeding are two lethal postoperative complications, but there has been no report that involves both of them after mini-percutaneous nephrolithotomy. CASE PRESENTATION: A 62-year-old woman was admitted to our hospital with extremely severe hydronephrosis and multiple right renal calculi. After thorough examination, she received prone-position mini-percutaneous nephrolithotomy under spinal anaesthesia. Three days postoperatively, the patient complained of chest pain and dyspnea. Computed tomography pulmonary angiogram (CTPA) showed multiple embolisms in the left pulmonary artery and its branches. Symptoms were relieved after anticoagulant and thrombolysis therapy. On the 6th postoperative day, the patient developed shortness of breath, computed tomography angiography (CTA) showed massive hemorrhage in the right kidney, diffused contrast medium in the middle and lower part of the right kidney was seen during digital substraction angiography (DSA). Superselective right renal artery embolization (SRAE) was then applied using coil to occlude the responsible artery. The patient generally recovered under conscientious care and was approved to be discharged 26 days postoperatively. CONCLUSIONS: This is the first case that involved both acute pulmonary embolism and severe post thrombolysis renal bleeding. The importance of D-dimer in the prediction and early detection of pulmonary embolism should be noted. For post thrombolysis renal bleeding, SRAE is considered as a reliable treatment.

The Use of High-Intensity Focused Ultrasound (HIFU) Plus 150mg Bicalutamide as First Line Salvage Therapy for Local Recurrent Prostate Cancer.

Patients with localized prostate cancer (PCa) are often treated with radical prostatectomy (RP). However, more than 30% of such patients have high risk of recurrence. Salvage radiotherapy (SRT), androgen deprivation therapy (ADT) and combination of radiotherapy and ADT are the standard care for recurrent PCa. Recently, high intensity focused ultrasound (HIFU) has gradually applied in the treatment of recurrent PCa. Here, we proposed a hypothesis that combined HIFU and bicalutamide 150mg as first line salvage therapy to treat patients with local recurrent PCa with visible lesions due to the following advantages: (1) HIFU is effective in reducing local tumor load, and bicalutamide 150mg is a feasible and safety option to combine with HIFU. (2) Compared with radiotherapy, HIFU plus 150mg bicalutamide is minimal invasiveness with fewer adverse effects and better quality of life(QOL); (3) Radiotherapy can be preserved as the second-line salvage method in the cases who are failure to HIFU and 150mg bicalutamide combination. More clinical trials are warranted to confirm this hypothesis in treatment with recurrent PCa.

Modified Predictive Model and Nomogram by Incorporating Prebiopsy Biparametric Magnetic Resonance Imaging With Clinical Indicators for Prostate Biopsy Decision Making.

PURPOSE: The purpose of this study is to explore the value of combining bpMRI and clinical indicators in the diagnosis of clinically significant prostate cancer (csPCa), and developing a prediction model and Nomogram to guide clinical decision-making. METHODS: We retrospectively analyzed 530 patients who underwent prostate biopsy due to elevated serum prostate specific antigen (PSA) levels and/or suspicious digital rectal examination (DRE). Enrolled patients were randomly assigned to the training group (n = 371, 70%) and validation group (n = 159, 30%). All patients underwent prostate bpMRI examination, and T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences were collected before biopsy and were scored, which were respectively named T2WI score and DWI score according to Prostate Imaging Reporting and Data System version 2 (PI-RADS v.2) scoring protocol, and then PI-RADS scoring was performed. We defined a new bpMRI-based parameter named Total score (Total score = T2WI score + DWI score). PI-RADS score and Total score were separately included in the multivariate analysis of the training group to determine independent predictors for csPCa and establish prediction models. Then, prediction models and clinical indicators were compared by analyzing the area under the curve (AUC) and decision curves. A Nomogram for predicting csPCa was established using data from the training group. RESULTS: In the training group, 160 (43.1%) patients had prostate cancer (PCa), including 128 (34.5%) with csPCa. Multivariate regression analysis showed that the PI-RADS score, Total score, f/tPSA, and PSA density (PSAD) were independent predictors of csPCa. The prediction model that was defined by Total score, f/tPSA, and PSAD had the highest discriminatory power of csPCa (AUC = 0.931), and the diagnostic sensitivity and specificity were 85.1% and 87.5%, respectively. Decision curve analysis (DCA) showed that the prediction model achieved an optimal overall net benefit in both the training group and the validation group. In addition, the Nomogram predicted csPCa revealed good estimation when compared with clinical indicators. CONCLUSION: The prediction model and Nomogram based on bpMRI and clinical indicators exhibit a satisfactory predictive value and improved risk stratification for csPCa, which could be used for clinical biopsy decision-making.

Case Report: Anlotinib Combined With Sintilimab as Third-Line Treatment in a Metastatic Urothelial Bladder Carcinoma Patient With FGFR3 Mutation.

We report on a case of metastatic urothelial bladder carcinoma (mUBC) treated with anlotinib combined with sintilimab. A 69-year-old male was diagnosed with non-muscle invasive bladder cancer (NMIBC). He received transurethral resection of bladder tumor (TURBT) and intravesical gemcitabine chemotherapy. After the patients' cancer progressed to mUBC, cisplatin-based chemotherapy (gemcitabine combined with cisplatin, GC) was performed to this patient as first line therapy for four cycles. However, the disease progressed again within 6 months. Local radiotherapy was performed on the metastatic lesions, and after radiotherapy, the patient received anti-PD-1 antibody (sintilimab 200 mg, q3w)combined with Albumin-bound (Nab)-paclitaxel (100 mg, qw) as the second-line therapy, but the patient's cancer was still observed to be progressing. Molecular characterization confirmed the presence of FGFR3 mutations in the patient. Anlotinib was recommended to this patient. After the patient was fully informed and he was aware of off-label use of the drug, then, Nab-paclitaxel was replaced by anlotinib (10 mg D1-14, q3w) and sintilimab infusions were maintained for every 3 weeks. Partial response (PR) was observed through imaging examinations and stable disease (SD) was observed for more than 11 months; the patient's quality of life also improved. This case suggested that anlotinib combined with sintilimab may be a safe and effective choice in the treatment of mUBC in patients with FGFR3 mutations.

Maintenance Long-Term Multiple Cycles Treatment with Docetaxel in Metastatic Castration-Resistant Prostate Cancer: A Report of Three Cases.

Prostate cancer (PCa) is one of the most common types of malignancy, most patients with PCa will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), which has a poor prognosis. Since 2004, chemotherapy has been approved by the FDA as the first-line treatment for mCRPC, and docetaxel-based regimens have been shown to improve both the patients' symptoms and overall survival (OS). 10 cycles of docetaxel therapy are usually given to patients with mCPRC, but there is still no consensus on the optimal number of treatment cycles. Here, we present three cases of mCRPC patients that received maintenance long-term multiple-cycles docetaxel treatment. We believe that this new treatment strategy may benefit carefully selected mCRPC patients and provide several key advantages such as maximum exposure to drugs, improvements in drug efficacy, and reduce the risk of developing drug resistance.

Post-mortem quality changes of common carp (Cyprinus carpio) during chilled storage from two culture systems.

BACKGROUND: Omega-3 common carp (OCC) raised by patented culture systems have higher level of n-3 fatty acids and n-3/n-6 ratio than normal common carps (NCCs) from traditional culture system. Whether the patented farming system and modified fatty acid profile will influence OCC storage stability is unclear. This study aimed to expose the differences of post-mortem quality changes between NCC and OCC. RESULTS: NCC and OCC have similar rigor mortis patterns, only a higher level of lactic acid was observed in NCC after 96 h. Adenosine triphosphate (ATP) related compounds had no major differences, but slightly higher inosine monophosphate in OCC was found at 36 h. The K-value, Ki-value and Hx-index demonstrated high cohesiveness (Pearsons two-tailed, r = 0.968-0.984, P < 0.05) during storage, with statistically comparable (P > 0.05) temporal progress of change in NCC and OCC. The indices were lower in OCC than in NCC. Attenuation of myosin heavy chain in OCC was not as distinct as in NCC, coincided with its higher salt-soluble protein level at 144 h. Before 96 h, thiobarbituric acid value (TBA), total viable count (TVC), cooking loss (CL), drip loss (DL), and hardness in NCC and OCC were similar. However, at 144 h, higher TBA, TVC, CL and DL while lower hardness in NCC than in OCC were observed. Principle component analysis showed good separation of NCC and OCC in biplot at 0 and 144 h. CONCLUSION: Patented culture system has a slightly positive influence on post-mortem quality of common carp. It can be used for producing OCC without compromising storage stability. © 2020 Society of Chemical Industry.

Gene silencing of indoleamine 2,3-dioxygenase hinders tumor growth through angiogenesis inhibition.

The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in various types of tumors, but the relationship between IDO1 and tumor angiogenesis needs further delineation. We aimed to clarify the relationship between tumor angiogenesis and IDO1 expression, and to explore the possibility of IDO1-targeting molecular therapy for lung cancer. For the first time, we found that silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro cancer cell invasion and migration. We further demonstrated that knockdown of IDO1 decreased the formation of vasculogenic mimicry. In addition to these in vitro findings, we also demonstrated that in vivo IDO1 gene silencing using short hairpin RNA (shRNA) delayed tumor onset and inhibited tumor growth in the mouse model. Immunostaining showed that IDO1 gene silencing inhibited tumor angiogenesis. Moreover, the expression of IDO1 was associated with microvessel density (MVD) labeled by CD34 and CD146. These findings indicate that IDO1 has the potential to participate in or contribute to the formation of new capillaries, supporting the applicability of IDO1-targeting molecular therapy in lung cancer.

Retrospective study of hepatocellular adenomas based on the phenotypic classification system: A report from China.

A molecular and pathological classification system for hepatocellular adenomas (HCAs) was recently introduced in Europe, resulting in four major identified subgroups. Asian countries have a considerably lower incidence of HCA as well as a different etiology. We aimed to characterize HCAs in a Chinese population based on this new classification system. A series of 30 patients with HCA were analyzed based on the phenotypic classification system using immunohistochemical analysis. Investigated antigens included liver-fatty acid binding protein (L-FABP), glutamine synthetase (GS), ß-catenin, serum amyloid A (SAA), and C-reactive protein (CRP). Of the 30 cases (20 female) included in this study, only one had a history of oral contraceptive use. We identified 9 (30%) hepatocyte nuclear factor (HNF)-1α-inactivated HCAs, 3 (10%) ß-catenin-activated HCAs, 11 (36.7%) inflammatory HCAs, and 7 (23.3%) unclassified HCAs. In the inflammatory HCA group, 2 cases demonstrated concurrent ß-catenin-activation. Homogeneous steatosis (6/9) and microadenomas (2/9) were more frequently observed in HNF1α-inactivated HCAs. A body mass index (BMI) of greater than 25 (5/11), alcohol use (4/11), and steatosis in background liver (3/11) were more frequent in inflammatory HCAs. ß-catenin-activated HCAs were larger than those of other subgroups. Despite obvious differences in etiology and gender proportion compared with Western countries, the clinical and pathological characteristics of HCA subgroups in China are similar to those in Europe. The phenotypic classification system could be reliably applied to Chinese patients as a meaningful tool for HCA management.

An X-chromosomal association study identifies a susceptibility locus at Xq22.1 for hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND OBJECTIVE: Genetic epidemiological data in hepatocellular carcinoma (HCC) pedigrees indicate a pattern of X-linked recessive inheritance of HCC susceptibility genes. This study is designed to test the hypothesis that there are genes conferring susceptibility to HCC located on the X-chromosome. METHODS: An X-chromosomal association study was conducted among Chinese men recruited from an area with a high prevalence of HCC. The candidate gene was further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: By analyzing 5454 X-chromosome single nucleotide polymorphisms (SNPs) in 50 HCC patients and 50 controls, we found two promising regions in which the associated SNPs clustered, located at Xq22.1 and Xq26.2. We further selected 35 tag SNPs (tSNPs) from these two regions for additional genotyping analysis in another independent set of 290 cases and 242 controls. Notably, SNP rs5945919 at Xq22.1 exhibited a significant association with HBV-related HCC (odds ratio [OR]=2.22, 95% confidence interval [CI]=1.15-4.30, P=0.016). The expressions of the three genes near the rs5945919 locus, RAB40AL, BEX1, and NXF3, were analyzed by qRT-PCR between another 24 HCC tissues and paired peritumoral liver tissues. The results indicated that NXF3, rather than RAB40AL and BEX1, mRNA level was found to be more abundant in HCC tissue than in peritumoral liver tissue. CONCLUSIONS: Our findings implicated Xq22.1 as a novel susceptibility locus for HCC and NXF3 as a candidate risk factor for relevant HCC.

IL-17 induces AKT-dependent IL-6/JAK2/STAT3 activation and tumor progression in hepatocellular carcinoma.

BACKGROUND: The Th17 subset and IL-17 have been found in increased frequencies within certain tumors. However, their relevance in cancer biology remains controversial. This study aimed to clarify the biological action of IL-17 on hepatocellular carcinoma (HCC). METHODS: Effects and underlying molecular mechanisms of IL-17 on human HCC were explored in vitro using exogenous IL-17 stimulation and in nude mice by implanting IL-17 overexpressed HCC cells. The clinical significance of IL-17 was investigated in tissue microarrays containing HCC tissues from 323 patients following hepatectomy using immunohistochemistry. RESULTS: Although exogenous IL-17 showed no direct effect on the growth rate of HCC cells in vitro, PCR and ELISA showed that IL-17 selectively augmented the secretion of diverse proinvasive factors and transwell showed a direct promotion of invasion of HCC cells by IL-17. Furthermore, transfection of IL-17 into HCC cells significantly promoted neoangiogenesis, neutrophil recruitment and tumor growth in vivo. Using siRNA mediated knockdown of AKT and STAT3, we suggested that the effects of IL-17 were operated through activation of the AKT signaling in HCC, which resulted in IL-6 production. Then, IL-6 in turn activated JAK2/STAT3 signaling and subsequently up-regulated its downstream targets IL-8, MMP2, and VEGF. Supporting these findings, in human HCC tissues, immunostaining indicated that IL-17 expression was significantly and positively associated with STAT3 phosphorylation, neutrophil infiltration and increased tumor vascularity. The clinical significance of IL-17 was authenticated by revealing that the combination of intratumoral IL-17+ cells and phospho-STAT3 served as a better prognosticator for postoperative tumor recurrence than either marker alone. CONCLUSIONS: IL-17 mediated tumor-promoting role involves a direct effect on HCC cells through IL-6/JAK2/STAT3 induction by activating the AKT pathway.

Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3.

AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC). METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model. RESULTS: Sorafenib decreased STAT3 phosphorylation at the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phospha-tase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib significantly inhibited STAT3 activity, reducing tumor growth and metastasis. CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation.