Endoscopic papillectomy for synchronous adenoma of the major and minor duodenal papilla.

OBJECTIVES: Synchronous adenomas of the major and minor duodenal papilla are seldom reported. The aim of this study was to describe the characteristics of synchronous major and minor papilla adenomas and to evaluate the safety and efficacy of endoscopic papillectomy (EP) for the management of the disease. METHODS: Consecutive patients who underwent endoscopy for synchronous major and minor papilla adenomas from January 1, 2013 to August 31, 2023 were analyzed retrospectively. Patients' characteristics, clinical manifestations, laboratory, imaging and endoscopic findings were collected. RESULTS: The nine patients with synchronous major and minor papilla adenomas had an average age of 50.78 ± 10.70 years. The diameter of major and minor papilla adenomas was 12.11 ± 3.41 mm and 6.11 ± 1.05 mm, respectively. Most major papilla adenomas had R0 horizontal margins (n = 8), while R0 vertical margins were achieved in all patients. While minor papilla adenomas were resected with both R0 horizontal and vertical margins in all patients. Post-EP bleeding was observed in one patient, which was classified as mild. Post-EP hyperamylasemia and pancreatitis was observed in two and four patients, respectively; the latter consisted of three with mild pancreatitis and one with severe pancreatitis. No perforation was observed. The mean follow-up duration was 9.22 ± 5.99 months. Histologically confirmed recurrence at the resection site was detected in one patient at 3 months after the procedure. CONCLUSIONS: Synchronous major and minor papilla adenomas may not be as rare as previously speculated. EP may be an effective and safe alternative modality for their management.

Arthroscopic Linear Chain Fixation for the Treatment of Medial Meniscus Posterior Root Tear: A Case Study.

BACKGROUND: The repair and reconstruction of medial meniscus posterior root tears (MMPRTs) is an important issue in the field of orthopedic sports medicine. This study reports the first application of arthroscopic linear chain fixation for the treatment of MMPRTs. CASE PRESENTATION: A 78-year-old female patient presented with a 1.5-month history of right knee pain accompanied by a locked facet joint. The patient underwent surgery with the new linear chain fixation method. In this method, the suture and the loop part of the buckle-strap titanium plate were combined into a linear chain mechanical complex, and the tension of the posterior root stump was gradually increased by pulling on the two attachment lines at the external mouth of the tibial tunnel. The postoperative Lysholm score was 89, and the visual analogue scale score was 0.9, indicating a significant improvement in knee joint function. At the 7-month and 1-year post-surgery follow-up, physical and MRI examinations confirmed satisfactory healing of the MMPRTs. CONCLUSION: This surgical approach offers several benefits, including a simplified instrumentation setup, preservation of natural anatomical structures, and reliable residual stump fixation. It has the potential for clinical implementation.

Effect of VEGF on neurological impairment and prognosis of acute cerebral infarction patients: A retrospective case-control study.

OBJECTIVE: Due to the complex pathological mechanism of acute cerebral infarction, the role of vascular endothelial growth factor (VEGF) on the disease is not clear. Therefore, a retrospective case-control study was performed to explore the effect of VEGF on neurological impairment and prognosis of acute cerebral infarction patients. METHOD: A total of 100 patients with acute cerebral infarction admitted to our hospital from April 2021 to April 2022 were selected. Blood samples from all patients would be routinely collected to detect the expression of serum VEGF. Pearson chi-square, Spearman correlation and univariate Logistic regression were used to analyze the clinical data to explore the relationship between VEGF expression and basic information, stroke degree, quality of life, and prognosis of patients. To determine whether VEGF can provide relevant basis for the early prevention and prognostic treatment of acute cerebral infarction. And multivariate logistic regression was used to calculate the odds ratio between each variable and VEGF expression. RESULTS: Pearson chi-square test and Spearman correlation coefficient showed that sex, degree of stroke, limb convulsions, loss of consciousness, hemiplegia, aphasia, mental functioning score, overall quality of life score, and short-term prognosis were significantly correlated with VEGF expression in 100 patients. Univariate logistic regression was used to describe the ORs and 95% confidence interval of subjects at the univariate level, and the degree of stroke (OR = 83.333, P < 0.001), tic of limbs (OR = 26.316, P < 0.001), loss of consciousness (OR = 23.256, P < 0.001), hemiplegia (OR = 62.500, P < 0.001), aphasia (OR = 76.923, P < 0.001), mental functioning score (OR = 7.937, P < 0.001), overall quality of life score (OR = 5.464, P < 0.001), short-term prognosis (OR = 37.037, P < 0.001) was significantly correlated with the high expression of VEGF. CONCLUSIONS: The level of serum VEGF was positively correlated with neurological impairment degree and prognosis in patients with acute cerebral infarction, the more severe the degree of stroke and the worse the prognosis.

Berberine-mediated REDD1 down-regulation ameliorates senescence of retinal pigment epithelium by interrupting the ROS-DDR positive feedback loop.

BACKGROUND: Accumulation of age-associated senescent cells accompanied with increased reactive oxygen species (ROS) and inflammatory factors contributes to the progression of age-related macular degeneration (AMD), the main cause of blindness in the elderly. Berberine (BBR) has shown efficacy in the treatment of age-related diseases including diabetes and obesity by decreasing ROS. However, the pharmacological effect of BBR on alleviating retinal aging remains largely unknown. PURPOSE: Our study aimed to investigate the pharmacological effect of BBR as an anti-aging agent in retinal aging and its further molecular mechanisms. METHODS: D-galactose (DG)-induced ARPE-19 cell senescence and retinal aging were employed to evaluate the anti-aging effect of BBR in vivo and in vitro. The siRNA transfection, Western-Blot analyses, SA-ß-Gal assay and immunofluorescence were performed to investigate the potential mechanisms of BBR on anti-aging of RPE. RESULTS: In RPE-choroid of both natural aged and DG-induced accelerated aged mice, oxidative stress was increased along with the up-regulation of p21 expression, which was ameliorated by BBR treatment. BBR down-regulated the expression of REDD1 to decrease intracellular ROS content, attenuating DG-induced senescence in vitro and in vivo. Furthermore, p53 instead of HIF-1α was identified as the transcriptional regulator of REDD1 in DG-induced premature senescence. Importantly, NAC and BBR reversed the expression of p53 and the content of 8-OHdG, indicating that the positive feedback loop of ROS-DNA damage response (DDR) was formed, and BBR interrupted this feedback loop to alleviate DG-induced premature senescence by reducing REDD1 expression. In addition, BBR restored DG-damaged autophagy flux by up-regulating TFEB-mediated lysosomal biosynthesis by inhibiting REDD1 expression, thereby attenuating cellular senescence. CONCLUSION: BBR down-regulates REDD1 expression to interrupt the ROS-DDR positive feedback loop and restore autophagic flux, thereby reducing premature senescence of RPE. Our findings elucidate the promising effects of REDD1 on cellular senescence and the great potential of BBR as a therapeutic approach.

Vaginal enterocele after cystectomy: A case report.

BACKGROUND: After undergoing radical cystectomy combined with hysterectomy, female patients may suffer from pelvic organ prolapse due to the destruction of pelvic structures, which mainly manifests as the prolapse of tissues of the vulva to varying degrees and can be accompanied by symptoms, such as bleeding and inflammation. Once this complication is present, surgical intervention is needed to resolve it. Therefore, preventing and managing this complication is especially important. CASE SUMMARY: The postoperative occurrence of acute enterocele is rare, and a case of acute small bowel vaginosis 2 mo after radical cystectomy with hysterectomy is reported. When the patient was admitted, physical examination revealed that the small bowel was displaced approximately 20 cm because of vaginocele. A team of gynecological, general surgery, and urological surgeons was employed to return the small bowel and repair the lacerated vaginal wall during the emergency operation. Eventually, the patient recovered, and no recurrence was seen in the half year of follow-up. CONCLUSION: We review the surgical approach for such patients, analyze high-risk factors for the disease and suggest corresponding preventive measures.

STING up-regulates VEGF expression in oxidative stress-induced senescence of retinal pigment epithelium via NF-κB/HIF-1α pathway.

AIM: Aging-related dysfunction of retinal pigment epithelium (RPE) is the main pathogenic factors for pathological angiogenesis due to dysregulated vascular endothelial growth factor (VEGF) in retinal vascular diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). However, the molecular mechanism behind the up-regulation of VEGF in senescent RPE is still blurred. MATERIALS AND METHODS: As oxidative damage is the key cause of RPE dysfunction, we employed a model of oxidative stress-induced premature senescence of ARPE-19 to explore the effect of senescent RPE on VEGF. KEY FINDINGS: We reported that senescent ARPE-19 up-regulated VEGF expression under both short-term and prolonged H2O2 treatment, accompanying with increased HIF-1α, the key mediator of VEGF. STING signaling, which could be activated by oxidative stress-damaged DNA, was also observed to be increased in senescent ARPE-19 treated with H2O2. And the inhibition of STING significantly reduced HIF-1α expression to alleviate the up-regulation of VEGF. NF-κB was also shown to be involved in the regulation of VEGF in senescent ARPE-19 in response to STING signaling. Furthermore, oxidative stress impaired the lysosomal clearance of damaged DNA to enhance STING signaling, thereby up-regulating VEGF expression in senescent RPE. SIGNIFICANCE: Our data provide evidence that STING plays an important role in VEGF regulation in senescent RPE induced by oxidative stress.

PAX9 functions as a tumor suppressor gene for cervical cancer via modulating cell proliferation and apoptosis.

To investigate the effect of PAX9 on the progression of cervical cancer (CC). PAX9 expression was quantified in CC tissues and adjacent normal tissues, as well as human CC cell lines and human cervical epithelial cells (HCerEpiC). PAX9-overexpression lentiviral vectors were transfected into CC cell lines, followed by the measurement of proliferation and apoptosis and the quantification of apoptosis-related proteins. In vivo, mice were subcutaneously injected with CaSki cells transfected with PAX9-overexpression lentiviral vectors and control vectors. Then, the volume and weight of tumors were measured followed by hematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemistry. PAX9 expression in the CC tissues was lower than that in the adjacent normal tissues, which was correlated with the FIGO stage, tumor size, infiltration depth, parametrium invasion, lympho-vascular space invasion tumor-positive lymph nodes, and prognosis. Furthermore, PAX9 in CC cell lines was also lower than in HCerEpiC. PAX9 inhibits the CC cell proliferation and promotes the apoptosis, with the up-regulations of caspase-3, poly(ADP-ribose) polymerase (PARP), and Bax and the down-regulation of Bcl-2. In vivo experiments demonstrated that in the PAX9 group, the tumor weight and volume were lower than those in the vector group accompanying the decreased Ki-67, cleaved-caspase-3, and Bax expressions and the increased TUNEL and Bcl-2 expression. PAX9 was lowly expressed in the CC tissues and associated with the clinicopathological characteristics and prognosis. PAX9 could inhibit proliferation of CC cell lines and promote the apoptosis, thus suppressing the tumor growth in vivo, indicating its potential therapeutic role for CC treatment.

Activation of TLR4 induces severe acute pancreatitis-associated spleen injury via ROS-disrupted mitophagy pathway.

Severe acute pancreatitis (SAP) is complicated by systemic inflammatory response syndrome and multiple organ dysfunction, the disease will eventually result in death in almost half of the case. The spleen, as the largest immune organ adjacent to the pancreas, is prone to damage in SAP, thereby aggravating the damage of other organs and increasing mortality. However, to date, the research on the mechanism and treatment of spleen injury caused by SAP is still in its infancy. Herein, we investigated the mechanism of spleen injury, and explored the application potential of tuftsin for relieving spleen damage in SAP mice. Firstly, SAP mice model was constructed via the retrograde infusion of 3.5 % sodium taurocholate into the biliopancreatic duct. Then, we proved that the up-regulation of Toll-like receptor 4 (TLR4) in spleen would lead to the accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction under SAP conditions. The splenic ROS and mitochondrial dysfunction could be improved by N-acetylcysteine (NAC) treatment or knocking out TLR4 in SAP mice. Meanwhile, we found that NAC treatment could also improve the autophagy of spleen tissue, suggesting that splenic ROS may affect impaired autophagy, causing the accumulation of damaged mitochondria, aggravating spleen damage. Furthermore, we verified the mechanism of spleen injury is caused by splenic ROS affecting PI3K/p-AKT/mTOR pathway-mediated autophagy. In addition, we detected the spleen injury caused by SAP could decrease the concentration of tuftsin in the serum of mice. Whereas, exogenous supplementation of tuftsin ameliorated the pathological damage, ROS accumulation, impaired autophagy, inflammation expression and apoptosis in damaged spleen. In summary, we verified the new mechanism of SAP-caused spleen damage that TLR4-induced ROS provoked mitophagy impairment and mitochondrial dysfunction in spleen via PI3K/p-AKT mTOR signaling, and the application potential of tuftsin in treating spleen injury, which might expand novel ideas and methods for the treatment of pancreatitis.

Vitamin B12 Attenuates Acute Pancreatitis by Suppressing Oxidative Stress and Improving Mitochondria Dysfunction via CBS/SIRT1 Pathway.

Acute pancreatitis is an inflammatory disorder of the pancreas associated with substantial morbidity and mortality, which is characterized by a rapid depletion of glutathione (GSH). Cysthionine-ß-synthase (CBS) is a key coenzyme in GSH synthesis, and its deficiency is related to a variety of clinical diseases. However, whether CBS is involved in the pathogenesis of acute pancreatitis remains unclear. First, we found that CBS was downregulated in both in vivo and in vitro AP models. The pancreatic damage and acinar cell necrosis related to CBS deficiency were significantly improved by VB 12, which stimulated clearance of reactive oxygen species (ROS) by conserving GSH. Furthermore, EX-527 (a specific inhibitor of SIRT1) exposure counteracted the protective effect of VB 12 by promoting oxidative stress and aggravating mitochondrial damage without influencing CBS, indicating that vitamin B12 regulates SIRT1 to improve pancreatical damage by activating CBS. In conclusion, we found that VB 12 protected acute pancreatitis associated with oxidative stress via CBS/SIRT1 pathway.

Feasibility of Brain Imaging Using a Digital Surround Technology Body Coil: A Study Based on SRGAN-VGG Convolutional Neural Networks.

Brain imaging using conventional head coils presents several problems in routine magnetic resonance (MR) examination, such as anxiety and claustrophobic reactions during scanning with a head coil, photon attenuation caused by the MRI head coil in positron emission tomography (PET)/MRI, and coil constraints in intraoperative MRI or MRI-guided radiotherapy. In this paper, we propose a super resolution generative adversarial (SRGAN-VGG) network-based approach to enhance low-quality brain images scanned with body coils. Two types of T1 fluid-attenuated inversion recovery (FLAIR) images scanned with different coils were obtained in this study: joint images of the head-neck coil and digital surround technology body coil (H+B images) and body coil images (B images). The deep learning (DL) model was trained using images acquired from 36 subjects and tested in 4 subjects. Both quantitative and qualitative image quality assessment methods were performed during evaluation. Wilcoxon signed-rank tests were used for statistical analysis. Quantitative image quality assessment showed an improved structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR) in gray matter and cerebrospinal fluid (CSF) tissues for DL images compared with B images (P <.01), while the mean square error (MSE) was significantly decreased (P <.05). The analysis also showed that the natural image quality evaluator (NIQE) and blind image quality index (BIQI) were significantly lower for DL images than for B images (P <.0001). Qualitative scoring results indicated that DL images showed an improved SNR, image contrast and sharpness (P<.0001). The outcomes of this study preliminarily indicate that body coils can be used in brain imaging, making it possible to expand the application of MR-based brain imaging.

[Inhibitory Effect of Ascorbic Acid on Myelodysplastic Syndrome Cells and Its Mechanism].

OBJECTIVE: To investigate the inhibitory effect of ascorbic acid single or combination of decitabine on tumor cells of myelodysplastic syndrome (MDS) and explore its related mechanism. METHODS: The human MDS cell lines SKM-1 and MUTZ-1 were treated with different concentrations of ascorbic acid, and the cell proliferation activity was detected by the CCK-8 assay. The reactive oxygen species (ROS) level, labile iron pool (LIP), cell cycle, and apoptosis of SKM-1 and MUTZ-1 cells were detected by flow cytometry. The control group, ascorbic acid monotherapy group, decitabine monotherapy group, and combination group of ascorbic acid and decitabine were set up, the cell proliferation activity and apoptosis were detected in each group. RESULTS: High-dose ascorbic acid could reduce the cell proliferation activity of SKM-1 (R=0.886, p=0.000) and MUTZ-1 (R=0.880, p=0.000). With the increase of ascorbic acid concentration, the ROS level in SKM-1 and MUTZ-1 cells increased (r=0.816, r=0.942), the proportion of cells stagnation in G2 phase increased (r=0.970, p=0.000; r=0.962, p=0.000), the proportion of surviving cells decreased (r=-0.966, p=0.000; r=-0.952, p=0.000), and the apoptosis cells significantly increased (r=0.966, p=0.000; r=0.958, p=0.000). Nevertheless, the level of LIP showed no significant changes. After the combined application of ascorbic acid and decitabine, MDS tumor cells showed decreased proliferative activity and increased apoptosis compared with single-agent ascorbic acid and decitabine group. CONCLUSION: High-dose ascorbic acid shows a cytotoxic effect on MDS tumor cells, inhibiting cell proliferation and increasing apoptosis. Ascorbic acid combined decitabine have a synergistic effect of anti-MDS tumor cells.

Columbamine-Mediated PTEN/AKT Signal Pathway Regulates the Progression of Glioma.

PURPOSE: At present, comprehensive therapy has been widely used in the treatment of glioma, but the curative effect is not good, and the survival rate of patients is low. Therefore, it is crucial to explore further the regulatory mechanism of the occurrence and development of glioma and find potential therapeutic targets. We aimed to investigate the columbamine (a tetrahydroisoquinoline alkaloid derived from the rhizome of Chinese herbal medicine Rhizoma Coptidis) on glioma progression. METHODS: MTT, clone formation assay, wound healing assay, and transwell assay were performed to detect the cell viability, proliferation, migration, and invasion ability. Flow cytometry, TUNEL, and Western blot were used to identify the apoptosis level in glioma cells. PTEN inhibitor (SF1670) and AKT activator (SC79) were used to explore the mechanism of columbamine on glioma cell progression. RESULTS: Columbamine inhibits proliferation, migration, invasion, and induces apoptosis in glioma cell lines (SHG44 and U251). Columbamine prevents phosphorylation of AKT and promotes the expression of PTEN. Blocking PTEN level or inducing phosphorylation of AKT attenuates columbamine function on SHG44 cells proliferation, metastasis, and apoptosis. CONCLUSION: In this research, we find that columbamine could inhibit proliferation and metastasis of glioma cell lines, and promote apoptosis of glioma cell lines via regulating PTEN/AKT signal pathway. It provides a new theoretical basis for the development of anti-glioma drugs.

A pH-Sensitive Prodrug Nanocarrier Based on Diosgenin for Doxorubicin Delivery to Efficiently Inhibit Tumor Metastasis.

BACKGROUND: The metastasis, one of the biggest barriers in cancer therapy, is the leading cause of tumor deterioration and recurrence. The anti.-metastasis has been considered as a feasible strategy for clinical cancer management. It is well known that diosgenin could inhibit tumor metastasis and doxorubicin (DOX) could induce tumor apoptosis. However, their efficient delivery remains challenging. PURPOSE: To address these issues, a novel pH-sensitive polymer-prodrug based on diosgenin nanoparticles (NPs) platform was developed to enhance the efficiency of DOX delivery (DOX/NPs) for synergistic therapy of cutaneous melanoma, the most lethal form of skin cancer with high malignancy, early metastasis and high mortality. METHODS AND RESULTS: The inhibitory effect of DOX/NPs on tumor proliferation and migration was superior to that of NPs or free DOX. What is more, DOX/NPs could combine mitochondria-associated metastasis and apoptosis with unique internalization pathway of carrier to fight tumors. In addition, biodistribution experiments proved that DOX/NPs could efficiently accumulate in tumor sites through enhancing permeation and retention (EPR) effect compared with free DOX. Importantly, the data from in vivo experiment revealed that DOX/NPs without heart toxicity significantly inhibited tumor metastasis by exerting synergistic therapeutic effect, and reduced tumor volume and weight by inducing apoptosis. CONCLUSION: The nanocarrier DOX/NPs with satisfying pharmaceutical characteristics based on the establishment of two different functional agents is a promising strategy for synergistically enhancing effects of cancer therapy.

Toxoplasma gondii infection in patients with lung diseases in Shandong province, eastern China.

Toxoplasma gondii, an intracellular protozoan parasite, can induce various clinical symptoms. T. gondii has been considered to play an important role in the pathogenesis of lung diseases. This survey was conducted to explore the correlation between T. gondii infection and lung diseases through a case-control study carried out in Shandong province, eastern China. In the present survey, T. gondii IgG antibodies were found in 76/398 (19.10%) of patients with lung diseases, which was significantly higher (P < 0.001) than the level found in the control subjects (35/398; 8.79%) through serological diagnosis. Patients with lung cancer have the highest T. gondii seroprevalence (26.19%), followed by Pulmonary cyst (25.00%), Tuberculosis (17.07%), Pneumonia (16.33%) and chronic obstructive pulmonary disease (COPD) (16.05%). Moreover, a semi-nest PCR targeted T. gondii B1 gene was employed to detect the T. gondii DNA in the blood samples. T. gondii DNA was detected in 5.53% blood samples of patients with lung diseases and 2.51% control subjects, respectively. The present study firstly shows that T. gondii has a high probability to infect the patients with lung diseases. Thus, the potential presence of T. gondii in patients with lung diseases should be appreciated during in the course of treatment and safeguard procedures should be implemented to protect vulnerable patients with lung diseases.

Diagnostic Performance of 68Gallium Labelled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging for Staging the Prostate Cancer with Intermediate or High Risk Prior to Radical Prostatectomy: A Systematic Review and Meta-analysis.

PURPOSE: To compare the diagnostic efficiency of 68Gallium labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA PET) and magnetic resonance imaging (MRI) for staging the lymph node metastases (LNMs) in the prostate cancer. MATERIALS AND METHODS: A broad search of scientific databases including PubMed, EMBASE, Web of Science, Cochrane Database, and Chinese Biomedicine Literature Database (updated prior to November 1st, 2018) was conducted systematically by two reviewers. In this paper, we evaluated the methodological quality of each included article independently and performed a systematic review and meta-analysis to reveal the summary of the diagnostic performance of 68Ga-PSMA PET and MRI in properly identifying LNMs of intermediate- and/or high-risk prostate cancer. RESULTS: Thirteen eligible articles comprising 1,597 patients were included. For LNMs detection, the pooled sensitivity and specificity of 68Ga-PSMA PET were 0.65 (95% confidence interval [CI]: 0.49-0.79) and 0.94 (95% CI: 0.88-0.97), respectively, while the corresponding values of MRI were 0.41 (95% CI: 0.26-0.57) and 0.92 (95% CI: 0.86-0.95). The area under the symmetric receiver-operating characteristic (SROC) curve for 68Ga-PSMA PET and MRI were 0.92 and 0.83, respectively. CONCLUSIONS: In intermediate- or high-risk pre-treatment prostate cancer, 68Ga-PSMA PET had a higher sensitivity and a slightly different specificity in probing the LNMs when comparing with MRI. Moreover, the area under the SROC curve indicated that 68Ga-PSMA PET was a more effective weapon for predicting the LNMs prior to radical surgery.

Prenylated isoflavones with potential antiproliferative activities from Mappianthus iodoides.

A phytochemical investigation on the stems of Mappianthus iodoides led to the isolation of a new naturally occurring prenylated isoflavone, mappianthone A (1), together with seven known analogues (2-8). The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. All isolated compounds were evaluated for their antiproliferative activities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-8 showed significant antiproliferative effects against several human cancer cell lines with IC50 values ranging from 0.16 to 12.68 µM. [Formula: see text].

Monocarboxylate transporter 1 and monocarboxylate transporter 4 in cancer-endothelial co-culturing microenvironments promote proliferation, migration, and invasion of renal cancer cells.

BACKGROUND: The Warburg effect demonstrates the importance of glycolysis in the development of primary and metastatic cancers. We aimed to explore the role of monocarboxylate transporter 1 (MCT1) and MCT4, two essential transporters of lactate, in renal cancer progression during cancer-endothelial cell co-culturing. METHODS: Renal cancer cells (786-O) and human vascular endothelial cells (HUVECs) were single-cultured or co-cultured in transwell membranes in the presence or absence of a MCT-1/MCT-4 specific blocker, 7ACC1. Cell proliferation was evaluated with the CCK-8 kit, while cell migration, after a scratch and invasion in transwell chambers, was evaluated under a microscope. Real-time qPCR and western blot were employed to determine the mRNA and protein levels of MCT1 and MCT4, respectively. The concentration of lactic acid in the culture medium was quantified with an l-Lactic Acid Assay Kit. RESULTS: 786-O cells and HUVECs in the co-culturing mode exhibited significantly enhanced proliferation and migration ability, compared with the cells in the single-culturing mode. The expression of MCT1 and MCT4 was increased in both 786-O cells and HUVECs in the co-culturing mode. Co-culturing promoted the invasive ability of 786-O cells, and markedly increased extracellular lactate. Treatments with 7ACC1 attenuated cell proliferation, migration, and invasion, and down-regulated the levels of MCT1/MCT4 expression and extracellular lactate. CONCLUSIONS: The Warburg effect accompanied with high MCT1/MCT4 expression in the cancer-endothelial microenvironments contributed significantly to renal cancer progression, which sheds new light on targeting MCT1/MCT4 and glycolytic metabolism in order to effectively treat patients with renal cancers.

Dihydrodiosgenin inhibits endothelial cell-derived factor VIII and platelet-mediated hepatocellular carcinoma metastasis.

Background: Our previous studies have demonstrated that diosgenin and diosgenin derivatives exhibit excellent antithrombotic activity via regulating platelet function and coagulation factor level. Platelets and blood coagulation system are highly associated with tumor hematogenous metastasis. Therefore, the purpose of this study was to evaluate whether dihydrodiosgenin (dydio) mediated-platelet inhibition or coagulation factor level modulation is involved in hepatocellular carcinoma cell (HCC) metastasis. Methods: Cell viability was examined by MTT and colony formation assays. Platelet aggregation text and morphology were used to assess dydio's role on tumor cell-induced platelet activation (TCIPA). Scratch assay, adhesion assay and Western blot were used to evaluate dydio's role on platelet-mediated metastasis. Western blot and fluorescence detection were performed to clarify dydio's role on endothelial cell (EC) function. The mice lung metastasis model was constructed to investigated dydio's function on coagulation factor and platelet-mediated metastasis. Results: This study found that pretreatment with dydio caused a significant inhibition of TCIPA. Platelets exposed to dydio significantly inhibited their adhesion to tumor cells, meanwhile, releasates of platelets that pretreated with dydio led to diminished cancer cell proliferation and migration along with the increase of epithelial markers E-cadherin and loss of mesenchymal phenotype. Additionally, ECs pretreated with dydio suppressed factor VIII (FVIII) level which in turn restrained the activation of platelets and the adhesion of cancer cells or platelets to ECs. Interestingly, our study demonstrated that FVIII could promote HCC proliferation. In vivo study revealed that mice intragastrical (i.g.) administration with dydio significantly inhibited the lung metastasis of hepal-6 cells which is highly correlated with the altered platelet function and coagulation level. Conclusion: Taken together, these results demonstrated that dydio altered platelet function and coagulation FVIII level, resulting in decreased metastatic potential of HCC. Thus, our study reveals that dydio exerts novel mechanisms of antitumor action beside its direct antitumor activity.

The relationship between human papillomavirus and penile cancer over the past decade: a systematic review and meta-analysis.

Human papillomavirus (HPV) infection appears to play an important role in the development of penile cancer (PeCa), but their relationship remains unclear. Therefore, we performed a systematic review and meta-analysis to elucidate their relationship. We systematically searched Embase, PubMed, Cochrane Library, and Web of Science for case-control studies and cross-sectional studies using polymerase chain reaction (PCR) technology on formalin-fixed paraffin-embedded (FFPE) or paraffin-embedded (PE) PeCa tissues to detect HPV (published between January 1, 2007, and December 29, 2017; no language restrictions). Twenty-two studies were identified, and 1664 cases were available for analysis. The combined HPV infectious risk of PeCa is 51.0% (95% confidence interval [CI]: 43.0%-60.0%). The three most common subtypes of HPV were HPV16 (28.5%), HPV18 (2.3%), and HPV6 (2.3%). The virus was relevantly associated with basaloid (85.5%, 95% CI: 77.2%-93.8%) and warty (50.0%, 95% CI: 35.2%-64.8%) carcinomas. The invasiveness of PeCa was not associated with HPV (χ[2] = 0.181, df = 1, P < 0.671). HPV infection in PeCa tended to be moderately differentiated (54.4%, 95% CI: 47.7%-61.1%). This study found that almost half of PeCa patients are associated with HPV. The most commonly associated genotype is HPV16, but several other genotypes were also detected. In addition to types 6 and 11, other single low-risk HPV infections have been found to contribute to PeCa to a lesser degree. HPV-positive tumors tend to exhibit warty and/or basaloid features, corresponding to a moderate histological grade. The role of HPV in PeCa should be revisited to provide evidence for the development of PeCa in the presence of HPV infection.

Villous adenoma coexistent with focal well-differentiated adenocarcinoma of female urethral orifice: A case report and review of literature.

BACKGROUND: Villous adenomas of the urinary tract are uncommon. They are morphologically similar to and difficult to differentiate from their counterpart in the colon. The histogenesis and malignant potential are uncertain. CASE SUMMARY: A 63-year-old woman was admitted to our hospital with a mass in the urethral orifice. Gross and microscopic pathological examination was suggestive of urethral villous adenoma with focal well-differentiated adenocarcinoma. The whole urethra and part of the bladder were excised. No further treatment was offered. Carcinoembryonic antigen, cytokeratin 7, cytokeratin 20, epithelial membrane antigen, and p53 protein were positive, and the ratio of Ki-67 was 60%. After follow-up at 11 mo, the patient was cured and had no recurrence. CONCLUSION: Immunohistochemistry is important for differential diagnosis of villous adenoma of the urinary system. Complete surgical resection of the urinary tract is curative.