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.

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.

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.

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.

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.

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.

[Correlation of human papillomavirus (HPV) and HPV vaccines with male reproductive health].

HPV is a very common virus worldwide spread by direct contact and involved in male reproductive health-related diseases such as infertility, condyloma acuminatum, and penile cancer. The development of HPV vaccines has contributed to the effective prevention of various subtypes of HPV and protection of males from HPV infection, especially the partners of HPV-positive females, the men who have sex with men, and those with a psychological fear of HPV infection. Therefore, HPV vaccines play an important role in the protection of males.

Association between the sonographer's experience and diagnostic performance of IOTA simple rules.

BACKGROUND: To validate the clinical value of simple rules in distinguishing malignant adnexal masses from benign ones and to explore the effect of simple rules for experienced and less-experienced sonographers. METHODS: Patients with persistent adnexal masses were enrolled between November 2013 and December 2015. All masses were proven through histological examinations. Five sets of diagnoses were made and compared with one another. Diagnosis 1 was made, according to the simple rules, by a trainee with little clinical diagnostic experience. Diagnoses 2 and 3 were made by experienced and less-experienced sonographers, respectively, according to their clinical experiences. With diagnosis 1 as a reference, the two sonographers were asked to provide a second diagnosis, which were diagnoses 4 and 5. The efficiency of the five sets of diagnoses was compared using ROC curves. RESULTS: In total, 75 malignant (37.7%) and 124 benign lesions (62.3%) were enrolled in this study. The mean diameter of the benign masses was obviously smaller than that of the malignant ones (6.8 ± 3.4 cm vs. 9.3 ± 4.9 cm, p < 0.01). The malignant ratio in postmenopausal women was much higher (66.1%) than that in the premenopausal population (25.7%) (p < 0.0001). Totally, 156 of the 199 cases (79.4%) resulted in conclusive diagnoses. Sensitivity and specificity were 98.4% and 73.9%, respectively, among the conclusive cases. The area under the ROC curve (Az) for the simple rule diagnosis was significantly lower than that for the experienced sonographer diagnosis (0.85 vs. 0.96, p < 0.0001); compared with the less-experienced sonographer, this difference was not significant (0.85 vs. 0.86, p = 0.9776). No significant difference was found in the comparison between the diagnoses made by the experienced sonographer before and after referencing the simple rule diagnosis (Az, 0.96 vs. 0.97, p = 0.2055). Using diagnosis 1 as a reference, the diagnostic performance of the less-experienced sonographer increased (from 0.86 to 0.92, p = 0.012); however, it was still lower than that of the experienced sonographer (Az, 96% vs. 92%, p = 0.0241). CONCLUSIONS: The simple rules was an appealing method for discriminating malignant masses from benign ones, particularly for a less-experienced sonographer.

CRM1, a novel independent prognostic factor overexpressed in invasive breast carcinoma of poor prognosis.

Breast cancer (BC) is the most commonly diagnosed cancer in females globally and is more aggressive at later stages. Chromosome region maintenance 1 (CRM1) is involved in the nuclear export of proteins and RNAs and has been associated with a number of malignancies. However, the clinicopathological significance of its expression in BC remains to be elucidated therefore this was investigated in the present study. CRM1 expression in 280 breast cancer tissues and 60 normal tissues was retrospectively analyzed using immunohistochemistry (IHC) and western blotting. IHC investigation demonstrated that CRM1 expression was significantly increased in BC compared with the normal breast epithelium (P<0.0001). Overexpression of CRM1 was markedly associated with poor prognostic characteristics, including larger tumor size (P=0.024), positive lymph node metastasis (P=0.032), invasive histological type (P=0.004) and distant metastasis (P=0.026). Significant associations were also observed between increased CRM1 expression and the progesterone receptor (P=0.028) and Ki67 (P=0.019). Kaplan-Meier survival analysis demonstrated that patients with high CRM1 expression exhibited a reduced disease-free survival and overall survival compared with those with low CRM1 expression (P=0.013). In the multivariate analysis, CRM1 expression (P=0.011), tumor size (P=0.001) and lymph node metastasis (P<0.001) were independent prognostic markers of BC. In conclusion, CRM1 serves an important role in BC and may serve as a predictive and prognostic factor for a poor outcome in patients with BC.

Monocarboxylate transporters MCT1 and MCT4 are independent prognostic biomarkers for the survival of patients with clear cell renal cell carcinoma and those receiving therapy targeting angiogenesis.

BACKGROUND: Prognostic biomarkers for patients with clear cell renal cell carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis, are not well established. In this study, we examined the correlations of monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for glycolytic metabolism, with various clinicopathological parameters as well as survival of patients with ccRCC and those treated with vascular endothelial growth factor receptor (VEGFR) inhibitors. METHODS: A cohort of 150 ccRCC patients were recruited into this study. All patients underwent radical or partial nephrectomy as the first-line treatment, and 38 received targeted therapy (sorafenib or sunitinib) after the surgery. Expression levels of MCT1, MCT4, and CD34 were examined by immunohistochemistry. Correlations between MCT1 or MCT4 expression and different clinicopathological parameters or patient survival were analyzed among all as well as patients receiving targeted therapy. RESULTS: MCT1 or MCT4 expression did not significantly correlate with sex, age, tumor diameter, microvascular density, tumor staging, pathological Furmann grade, or MSKCC (P>0.05). High expression of either MCT1 or MCT4 significantly correlated with reduced overall survival (OS) and progression-free survival (PFS) among the total cohort of ccRCC patients. For patients receiving targeted therapy, high expression of either MCT1 or MCT4 significantly correlated with reduced PFS, but not OS. Both conditions were independent prognostic biomarkers for reduced PFS among all patients or those receiving targeted therapy. CONCLUSION: MCT1 and MCT4 are prognostic biomarkers for patients with ccRCC or those receiving targeted therapy. High expression of these 2 proteins predicts reduced PFS in these patients.

Distribution patterns of microcalcifications in suspected thyroid carcinoma: a classification method helpful for diagnosis.

PURPOSE: The aim of this study was to compare the distribution patterns of microcalcifications in thyroid cancers with benign cases. METHODS: In total, 358 patients having microcalcifications on ultrasonography were analysed. Microcalcifications were categorised according to the distribution patterns: (I) microcalcifications inside one (a) or more (b) suspected nodules, (II) microcalcifications not only inside but also surrounding a suspected single (a) or multiple (b) nodules, and (III) focal (a) or diffuse (b) microcalcifications in the absence of any suspected nodule. Differences in distribution patterns of microcalcifications in benign and malignant thyroid lesions were compared. RESULTS: We found that the distribution patterns of microcalcifications differed between malignant (n = 325) and benign lesions (n = 117) (X 2 = 9.926, p < 0.01). Benign lesions were classified as type Ia (66.7%), type Ib (29.1%) or type IIIa (4.3%). The specificity of type II and type IIIb in diagnosing malignant cases was 100%. Among malignant lesions, 172 locations were classified as type Ia, 106 as type Ib, 12 as type IIa, 7 as IIb, 7 as type IIIa and 19 as type IIIb. Accompanying Hashimoto thyroiditis was most frequent in type III (51.6%). CONCLUSIONS: Types II and IIIb are highly specific for cancer detection. Microcalcifications outside a nodule and those detected in the absence of any nodule should therefore be reviewed carefully in clinical practice. KEY POINTS: • A method to classify distribution patterns of thyroid microcalcifications is presented. • Distribution features of microcalcifications are useful for diagnosing thyroid cancers. • Microcalcifications outside a suspicious nodule are highly specific for thyroid cancers. • Microcalcifications without suspicious nodules should also alert the physician to thyroid cancers.

Fiber-modified adenovirus-mediated suicide gene therapy can efficiently eliminate bladder cancer cells in vitro and in vivo.

Adenovirus-mediated gene therapy is a promising strategy for bladder cancer treatment. However, the loss of the coxsackie and adenovirus receptor (CAR) in bladder cancer cells decreases the infection efficiency of the therapeutic adenovirus. In this study, we constructed an Arg-Gly-Asp (RGD)-modified adenovirus, RGDAd-UPII-TK, that carries a suicide gene called HSV-TK that is driven by a human UPII promoter. Then, we tested the bladder cancer specificity of the UPII promotor and the expression of the HSV-TK protein. Additionally, we observed a potent cytotoxic effects of RGDAd-UPII-TK and ganciclovir (GCV) on bladder cancer as demonstrated by reduced cell survival and morphology changes in vitro. Furthermore, we confirmed that RGDAd-UPII-TK in combination with a GCV injection could significantly reduce the established T24 tumor growth and increase apoptosis in vivo. Altogether, our results indicated that the recombinant adenovirus RGDAd-UPII-TK could target bladder cancer through valid gene therapy.

Targeting of MCT1 and PFKFB3 influences cell proliferation and apoptosis in bladder cancer by altering the tumor microenvironment.

Phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) and monocarboxylate transporter 1 (MCT1) play important roles in tumor endothelial cells (ECs) and several biological processes. The present study was conducted to study the effects of PFKFB3 and MCT1 on cell proliferation and apoptosis in the tumor microenvironment by co-culture of HUVECs and T24, a bladder cancer (BC) cell line, using a microfluidic device. Immunofluorescence assay showed that HUVEC activity was significantly enhanced under co-culture with T24 cells, according to the stronger fluorescence intensity of CD31 and CD105 than that in the signal­cultured cells. Quercetin treatment inhibited MCT1 expression but did not affect PFKFB3 expression. Knockdown of MCT1 or/and PFKFB3 increased the apoptosis rate of the HUVECs under single-culture and co-culture situations by staining with calcein and propidium iodide. Meanwhile, cell proliferation and lactic concentration were significantly decreased after the blocking of MCT1 or/and PFKFB3, as compared with that in the control group. No obvious differences in the effects on apoptosis, proliferation and lactic concentration were found between cells treated with quercetin and siMCT1. Thus, we concluded that the targeting of MCT1 and PFKFB3 regulated cell proliferation and apoptosis in BC cells by altering the tumor microenvironment, and quercetin exhibited a potential antitumor effect by targeting MCT1.

Adenovirus-mediated downregulation of the ubiquitin ligase RNF8 sensitizes bladder cancer to radiotherapy.

The ubiquitin ligase RNF8 promotes the DNA damage response (DDR). We observed that the expression of RNF8 was increased in bladder cancer cells and that this change in RNF8 expression could be reversed by adenovirus-mediated shRNA treatment. Moreover, we found that RNF8 knockdown sensitized bladder cancer cells to radiotherapy, as demonstrated by reduced cell survival. Additionally, the absence of RNF8 induced a high rate of apoptosis and impaired double-strand break repair signaling after radiotherapy. Furthermore, experiments on nude mice showed that combining shRNF8 treatment with radiotherapy suppressed implanted bladder tumor growth and enhanced apoptotic cell death in vivo. Altogether, our results indicated that RNF8 might be a novel target for bladder cancer treatment.

The study of energy metabolism in bladder cancer cells in co-culture conditions using a microfluidic chip.

OBJECTIVES: This study aimed to systematically analyze changes in mitochondrial-related protein expression in bladder cancer cells and tumor-associated fibroblasts and to investigate the characteristics of bladder cancer cell energy metabolism. METHODS: In this study, we utilized the following techniques to achieve the objectives: (1) a co-culture system of bladder tumor cells and fibroblasts was built using a microfluidic chip as a three-dimensional culture system; (2) the concentration of lactic acid in the medium from the different groups was determined using an automatic micro-plate reader; (3) a qualitative analysis of mitochondria-related protein expression was performed by immunofluorescent staining; and (4) a quantitative analysis of mitochondrial-associated protein expression was conducted via Western blot. SPSS software was utilized to analyze the data. RESULTS: (1) Determination of lactic acid concentration: The lactic acid concentration was determined to be highest in the experimental group, followed by the T24 cell control group and then the fibroblast control group. (2) Qualitative results: In the control group, the mitochondrial-related protein fluorescence intensity was higher in the fibroblasts compared with the cancer cells, and the fluorescence intensity of the fibroblasts was reduced compared with the experimental group. The mitochondrial-related protein fluorescence intensity of the cancer cells was higher in the experimental group compared with the control group, and the opposite results were obtained with the fibroblasts. (3) Quantitative results: The expression of mitochondria-related proteins was higher in fibroblasts compared with cancer cells in the control group, and the opposite results were obtained in the experimental group (P<0.05). The expression of mitochondria-related proteins was increased in cancer cells in the experimental group compared with the control group; the opposite results were observed for the fibroblasts (P<0.05). CONCLUSIONS: The energy metabolism of bladder tumor cells does not parallel the "Warburg effect" because even under sufficient oxygen conditions, cancer cells still undergo glycolysis. Bladder cancer cells also have an efficient oxidative phosphorylation process wherein cancer cells promote glycolysis in adjacent interstitial cells, thereby causing increased formation of nutritional precursors. These high-energy metabolites are transferred to adjacent tumor cells in a specified direction and enter the Krebs Cycle. Ultimately, oxidative phosphorylation increases, and sufficient ATP is produced.

A bladder cancer microenvironment simulation system based on a microfluidic co-culture model.

A tumor microenvironment may promote tumor metastasis and progression through the dynamic interplay between neoplastic cells and stromal cells. In this work, the most representative and significant stromal cells, fibroblasts, endothelial cells, and macrophages were used as vital component elements and combined with bladder cancer cells to construct a bladder cancer microenvironment simulation system. This is the first report to explore bladder cancer microenvironments based on 4 types of cells co-cultured simultaneously. This simulation system comprises perfusion equipment, matrigel channel units, a medium channel and four indirect contact culture chambers, allowing four types of cells to simultaneously interact through soluble biological factors and metabolites. With this system, bladder cancer cells (T24) with a tendency to form a 'reticular' structure under 3 dimensional culture conditions were observed in real time. The microenvironment characteristics of paracrine interactions and cell motility were successfully simulated in this system. The phenotype change process in stromal cells was successfully reproduced in this system by testing the macrophage effector molecule Arg-1. Arg-1 was highly expressed in the simulated tumor microenvironment group. To develop "precision medicine" in bladder cancer therapy, bladder cancer cells were treated with different clinical 'neo-adjuvant' chemotherapy schemes in this system, and their sensitivity differences were fully reflected. This work provides a preliminary foundation for neo-adjuvant chemotherapy in bladder cancer, a theoretical foundation for tumor microenvironment simulation and promotes individual therapy in bladder cancer patients.

Cardioprotective Effect of Licochalcone D against Myocardial Ischemia/Reperfusion Injury in Langendorff-Perfused Rat Hearts.

Flavonoids are important components of 'functional foods', with beneficial effects on cardiovascular function. The present study was designed to investigate whether licochalcone D (LD) could be a cardioprotective agent in ischemia/reperfusion (I/R) injury and to shed light on its possible mechanism. Compared with the I/R group, LD treatment enhanced myocardial function (increased LVDP, dp/dtmax, dp/dtmin, HR and CR) and suppressed cardiac injury (decreased LDH, CK and myocardial infarct size). Moreover, LD treatment reversed the I/R-induced cleavage of caspase-3 and PARP, resulting in a significant decrease in proinflammatory factors and an increase in antioxidant capacity in I/R myocardial tissue. The mechanisms underlying the antiapoptosis, antiinflammation and antioxidant effects were related to the activation of the AKT pathway and to the blockage of the NF-κB/p65 and p38 MAPK pathways in the I/R-injured heart. Additionally, LD treatment markedly activated endothelial nitric oxide synthase (eNOS) and reduced nitric oxide (NO) production. The findings indicated that LD had real cardioprotective potential and provided support for the use of LD in myocardial I/R injury.

Bladder Tumor Heterogeneity: The Impact on Clinical Treatment.

Bladder cancer relapse and treatment failure in most patients have often been attributed to chemoresistance in tumor cells and metastasis. Emerging evidence indicates that tumor heterogeneity may play an equally important role and extends to virtually all measurable properties of cancer cells. Although the idea of tumor heterogeneity is not new, little attention has been paid to applying it to understand and control bladder cancer progression. With the development of biotechnology, such as Gene sequencing, recent advances in understanding its generation model, original basis, consequent problems, and derived therapies provide great potential for tumor heterogeneity to be considered a new insight in the treatment of bladder cancers.