Applications of Biosensors in Bladder Cancer.

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

Nuclear matrix protein 22 in bladder cancer.

Bladder cancer (BC) is ranked as the ninth most common malignancy worldwide, with approximately 570,000 new cases reported annually and over 200,000 deaths. Cystoscopy remains the gold standard for the diagnosis of BC, however, its invasiveness, cost, and discomfort have driven the demand for the development of non-invasive, cost-effective alternatives. Nuclear matrix protein 22 (NMP22) is a promising non-invasive diagnostic tool, having received FDA approval. Traditional methods for detecting NMP22 require a laboratory environment equipped with specialized equipment and trained personnel, thus, the development of NMP22 detection devices holds substantial potential for application. In this review, we evaluate the NMP22 sensors developed over the past decade, including electrochemical, colorimetric, and fluorescence biosensors. These sensors have enhanced detection sensitivity and overcome the limitations of existing diagnostic methods. However, many emerging devices exhibit deficiencies that limit their potential clinical use, therefore, we propose how sensor design can be optimized to enhance the likelihood of clinical translation and discuss the future applications of NMP22 as a legacy biomarker, providing insights for the design of new sensors.

Application of digital guide plate with drill-hole sharing technique in the mandible reconstruction.

Background/purpose: With the development of computer-assisted surgery, digital guide plate was widely used in vascularized bone flap grafts for mandibular reconstruction. The purpose of this study was to design and manufacture a digital guide plate with drill-hole sharing for mandibular reconstruction and assess for surgical accuracy. Materials and methods: 17 patients that required mandibular reconstruction using fibula free flap or iliac crest free flap were included in the study. The computed tomography (CT) data of the patient's mandible and pelvis or fibula were acquired preoperatively. A surgical simulation was then performed using computer-aided surgical simulation (CASS) technology based on above date, which allowed the design of two cutting guide and a repositioning guide for mandibular reconstruction. After surgery, the accuracy of reconstruction was evaluated by superimposing the postoperative image onto the preoperative image of mandible, recording the linear and angular deviation of landmarks, measuring the differences between the planned and actual outcomes. Results: The osteotomy and repositioning of fibula or iliac crest segments were successfully performed as planned using surgical guides. The digital guide plate with drill-hole sharing showed excellent accuracy, When the iliac crest or the fibula free flap were used for mandibular reconstruction, the largest mean differences between the preoperative and postoperative were 1.11 mm and 2.8° or 1.3 mm and 3.87°. Conclusion: The digital guide plate with drill-hole sharing designed preoperatively provides a reliable method of for the mandibular reconstruction. This can assist surgeons in accurately performing osteotomy and repositioning fibula or iliac crest segments during the mandibular reconstruction.

Comparison and evaluation of different deep learning models of synthetic CT generation from CBCT for nasopharynx cancer adaptive proton therapy.

BACKGROUND: Cone-beam computed tomography (CBCT) scanning is used for patient setup in image-guided radiotherapy. However, its inaccurate CT numbers limit its applicability in dose calculation and treatment planning. PURPOSE: This study compares four deep learning methods for generating synthetic CT (sCT) to determine which method is more appropriate and offers potential for further clinical exploration in adaptive proton therapy for nasopharynx cancer. METHODS: CBCTs and deformed planning CT (dCT) from 75 patients (60/5/10 for training, validation and testing) were used to compare cycle-consistent Generative Adversarial Network (cycleGAN), Unet, Unet+cycleGAN and conditionalGenerative Adversarial Network (cGAN) for sCT generation. The sCT images generated by each method were evaluated against dCT images using mean absolute error (MAE), structural similarity (SSIM), peak signal-to-noise ratio (PSNR), spatial non-uniformity (SNU) and radial averaging in the frequency domain. In addition, dosimetric accuracy was assessed through gamma analysis, differences in water equivalent thickness (WET), and dose-volume histogram metrics. RESULTS: The cGAN model has demonstrated optimal performance in the four models across various indicators. In terms of image quality under global condition, the average MAE has been reduced to 16.39HU, SSIM has increased to 95.24%, and PSNR has increased to 28.98. Regarding dosimetric accuracy, the gamma passing rate (2%/2 mm) has reached 99.02%, and the WET difference is only 1.28 mm. The D95 value of CTVs coverage and Dmax value of spinal cord, brainstem show no significant differences between dCT and sCT generated by cGAN model. CONCLUSIONS: The cGAN model has been shown to be a more suitable approach for generating sCT using CBCT, considering its characteristics and concepts. The resulting sCT has the potential for application in adaptive proton therapy.

The preoperative platelet to neutrophil ratio and lymphocyte to monocyte ratio are superior prognostic indicators compared with other inflammatory biomarkers in ovarian cancer.

Background: Previous studies have suggested that the ratios of immune-inflammatory cells could serve as prognostic indicators in ovarian cancer. However, which of these is the superior prognostic indicator in ovarian cancer remains unknown. In addition, studies on the prognostic value of the platelet to neutrophil ratio (PNR) in ovarian cancer are still limited. Methods: A cohort of 991 ovarian cancer patients was analyzed in the present study. Receiver operator characteristic (ROC) curves were utilized to choose the optimal cut-off values of inflammatory biomarkers such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and PNR. The correlation of inflammatory biomarkers with overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier methods and log-rank test, followed by Cox regression analyses. Results: Kaplan-Meier curves suggested that LMR<3.39, PLR≥181.46, and PNR≥49.20 had obvious associations with worse RFS (P<0.001, P=0.018, P<0.001). Multivariate analysis suggested that LMR (≥3.39 vs. <3.39) (P=0.042, HR=0.810, 95% CI=0.661-0.992) and PNR (≥49.20 vs. <49.20) (P=0.004, HR=1.351, 95% CI=1.103-1.656) were independent prognostic indicators of poor RFS. In addition, Kaplan-Meier curves indicated that PLR≥182.23 was significantly correlated with worse OS (P=0.039). Conclusion: Taken together, PNR and LMR are superior prognostic indicators compared with NLR, PLR, and SII in patients with ovarian cancer.

Niche stiffness sustains cancer stemness via TAZ and NANOG phase separation.

Emerging evidence shows that the biomechanical environment is required to support cancer stem cells (CSCs), which play a crucial role in drug resistance. However, how mechanotransduction signals regulate CSCs and its clinical significance has remained unclear. Using clinical-practice ultrasound elastography for patients' lesions and atomic force microscopy for surgical samples, we reveal that increased matrix stiffness is associated with poor responses to neoadjuvant chemotherapy, worse prognosis, and CSC enrichment in patients with breast cancer. Mechanically, TAZ activated by biomechanics enhances CSC properties via phase separation with NANOG. TAZ-NANOG phase separation, which is dependent on acidic residues in the N-terminal activation domain of NANOG, promotes the transcription of SOX2 and OCT4. Therapeutically, targeting NANOG or TAZ reduces CSCs and enhances the chemosensitivity in vivo. Collectively, this study demonstrated that the phase separation of a pluripotency transcription factor links mechanical cues in the niche to the fate of CSCs.

Tumor Cell-Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid ß-Oxidation.

Targeting CD96 that originates in immune cells has shown potential for cancer therapy. However, the role of intrinsic CD96 in solid tumor cells remains unknown. Here, it is found that CD96 is frequently expressed in tumor cells from clinical breast cancer samples and is correlated with poor long-term prognosis in these patients. The CD96+ cancer cell subpopulations exhibit features of both breast cancer stem cells and chemoresistance. In vivo inhibition of cancer cell-intrinsic CD96 enhances the chemotherapeutic response in a patient-derived tumor xenograft model. Mechanistically, CD96 enhances mitochondrial fatty acid ß-oxidation via the CD155-CD96-Src-Stat3-Opa1 pathway, which subsequently promotes chemoresistance in breast cancer stem cells. A previously unknown role is identified for tumor cell-intrinsic CD96 and an attractive target in improving the chemotherapeutic response.

Concurrence of novel mutations causing Gilbert's and Dubin-Johnson syndrome with poor clinical outcomes in a Han Chinese family.

Dual-hereditary jaundice (Dubin-Johnson syndrome (DJS) and Gilbert's syndrome (GS)) is a rare clinical entity resulting from defects of the ATP binding cassette subfamily C member 2 (ABCC2) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genes with autosomal recessive inheritance. In this study, we aimed to investigate the mutation profiles and characterize the phenotypes in a Han Chinese family with DJS and GS. Genetic screening for variants in the ABCC2 and UGT1A1, immunohistochemistry for expression of ABCC2, and histopathological examination were carried out. The proband and his brother had unconjugated and conjugated hyperbilirubinemia after birth. The proband's sister had only conjugated hyperbilirubinemia after birth. The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. Hepatocellular carcinoma occurred in the proband's brother at age 46. Seven compound defects of the ABCC2 gene [c.2414delG, p.(Ile1489Gly), p.(Thr1490Pro), and p.(Ile1491Gln)] and the UGT1A1 gene (c.-3279T>G, p.(Gly71Arg), and p.(Pro451Leu)) were identified in family members. Accumulation of pigment in hepatocytes characteristic of that in DJS was present in the proband and his brother. Expression of ABCC2 protein was markedly diminished in the patient's liver. Our results show a different genetic profile of DJS and GS in a Han Chinese family, indicating a more complex pattern of dual-hereditary jaundice among different populations. The present study illuminates the underpinnings of DJS and GS and extends the mutation profiles and phenotypes of these two syndromes in dual-hereditary jaundice.

Paradoxical phenomena of bullous pemphigoid induced and treated by identical biologics.

Objective: This study aimed to investigate the clinical features of biologics-induced bullous pemphigoid (BP) and the therapeutic effects of those agents for BP, exploring the underlying pathophysiological mechanisms. Methods: We searched PubMed, Web of Science, and Elsevier for studies involving pemphigoid patients treated with or induced by identical biologics published in English from January 2009 to April 2022. Results: Seventeen cases of drug-induced BP associated with anti-tumor necrosis factor (aTNF)-α therapies, one with interleukin (IL)-17 inhibitors, and seven with IL-12/IL-23 or IL-23 inhibitors were enrolled. Time to cutaneous toxicity varied among different types of agents, and the characteristics of clinical examinations were similar to idiopathic BP. Discontinuation of the culprit drugs and initiation of topical or systemic corticosteroids were adequate in most cases. Several monoclonal antibodies above have also been reported for the treatment of refractory or recurrent BP, especially concurrent with psoriasis. Conclusion: Biologics for immune-related diseases, including TNF-α, IL-17, and IL-12/IL-23 or IL-23 inhibitors, can both induce and treat BP, which might be associated with a helper T cells Th1/Th2 imbalance, complicated inflammatory networks, and a specific individual microenvironment, suggestive of a new perspective on the therapeutic algorithms of BP. There have been numerous reports about biologics inducing or treating BP. We have taken note of this phenomenon and focused on biologics with both pathogenetic and therapeutic effects on BP. Our review summarized the clinical characteristics of associated cases, trying to figure out the underlying mechanisms of this paradoxical phenomenon and to provide an integrated perspective and new therapeutic alternatives for BP.

Insight into the role of p62 in the cisplatin resistant mechanisms of ovarian cancer.

Cisplatin is a platinum-based first-line drug for treating ovarian cancer. However, chemotherapy tolerance has limited the efficacy of cisplatin for ovarian cancer patients. Research has demonstrated that cisplatin causes changes in cell survival and death signaling pathways through its interaction with macromolecules and organelles, which indicates that investigation into the DNA off-target effects of cisplatin may provide critical insights into the mechanisms underlying drug resistance. The multifunctional protein p62 works as a signaling hub in the regulation of pro-survival transcriptional factors NF-κB and Nrf2 and connects autophagy and apoptotic signals, which play important roles in maintaining cell homeostasis. In this review, we discuss the role of p62 in cisplatin resistance by exploring p62-associated signaling pathways based on current studies and our work. Insights into these resistance mechanisms may lead to more effective therapeutic strategies for ovarian cancer by targeting p62.

The LINC00365/SCGB2A1 (Mammaglobin B) Axis Down-Regulates NF-κB Signaling and Is Associated with the Progression of Gastric Cancer.

PURPOSE: A lack of early diagnostic biomarkers and therapeutic targets has led to poor prognosis for gastric cancer patients. However, the analysis of cancer-associated genomic data has been shown to be effective in identifying potential markers. Recently, the long non-coding RNA LINC00365 and SCGB2A1 gene (as known as mammaglobin B) were predicted to be co-expressed in gastric cancer based on the Gene Expression Omnibus database. However, their precise role in gastric cancer tumors is still not clear. METHODS: The expressions of LINC00365 and SCGB2A1 in gastric cancer tissues were investigated using qPCR and their expressions were detected in a gastric cancer tissue microarray by in situ hybridization and immunohistochemical staining. The functions of LINC00365 in BGC-823 and MGC-803 gastric cancer cells were tested using the MTT assay, flow cytometry, colony formation assay, EDU staining, immunofluorescence and luciferase assay. RESULTS: We found that LINC00365 and SCGB2A1 mRNA were both expressed at low levels in 30 cases of gastric cancer. Gastric cancer tissue microarray analysis indicated that LINC00365 and SCGB2A1 were expressed at low levels in tumor tissue, and low expression of both factors correlated with shorter survival time. Functional studies showed that LINC00365 overexpression significantly inhibited gastric cancer cell viability through the impairment of proliferation rather than the promotion of apoptosis. Furthermore, overexpressed LINC00365 upregulated SCGB2A1 in gastric cancer cell lines. Immuno-fluorescence and luciferase assay analysis indicated that LINC00365 overexpression inhibited the NF-κB pro-survival signaling pathway. Consistent with the effects of LINC00365, SCGB2A1 upregulation also reduced cell survival and inactivated NF-κB. CONCLUSION: Collectively, our findings revealed that SCGB2A1 may be the target coding protein regulated by LINC00365 in gastric cancer. LINC00365 and SCGB2A1 may function as tumor suppressors and may serve as potential prognostic and therapeutic markers in gastric cancer treatment.

PET-MR Imaging and MR Texture Analysis in the Diagnosis of Pancreatic Cysts: A Prospective Preliminary Study.

RATIONALE AND OBJECTIVES: Our aim was to evaluate the capability of textural and metabolic parameters measured at pretreatment 18F-fluorodeoxyglucose Positron emission tomography (PET)-MR in differentiating malignant from benign pancreatic cystic lesions. MATERIALS AND METHOD: Forty consecutive patients were prospectively enrolled in this study. They underwent simultaneous PET-MR for the diagnosis of pancreatic cysts. Thirty texture parameters were extracted from manually contoured axial T2-weighted imaging with fat suppression (T2FS) and apparent diffusion coefficient images, respectively. Maximal and mean standardized uptake values (SUVmax and SUVmean, respectively) of pancreatic cysts were measured at PET-MR imaging. The Mann-Whitney test was used to compare both textural and metabolic parameters between benign and malignant group. RESULTS: FDG uptake was significantly higher in patients with malignant pancreatic cysts (SUVmaxp = 0.002, SUVmeanp < 0.001). Malignant cysts showed significantly lower standard deviation for spatial scaling factor at 3-6mm on T2FS images and lower skewness for spatial scaling factor at 2-4mm on apparent diffusion coefficient images (p < 0.01). SUVmean had the highest Area under the curve of 0.892 on receiver-operating characteristic analysis with a sensitivity, specificity, and accuracy of 88.9%, 87.1%, and 87.6%, respectively. When metabolic and textural features were combined into a single diagnostic model, the AUC increased to 0.961, with a sensitivity, specificity, and accuracy of 88.9%, 96.8%, and 95.0%, respectively. CONCLUSION: Our study implied that PET-MR showed no obvious advantages over traditional PET-related imaging in differentiating malignant from benign pancreatic cystic lesions. Diagnostic model based on the combination of metabolic and textural parameters showed satisfactory performance.

The B1 defective type of bifurcated right upper lobe bronchus.

BACKGROUND: As the more application of high-resolution computed tomography (HRCT), a great number of ground glass opacity (GGO) is identified. Video-assisted thoracoscopic surgery (VATS) segmentectomy is technically more difficult than lobectomy because of the anatomical complexity. Three-dimensional computed tomography bronchography angiography (3D-CTBA) is a powerful tool for thoracic surgeons to analyze pulmonary anatomy, allowing a better understanding of the pulmonary anatomy in each patient. Here we encountered seven cases of bifurcated right upper bronchus (B1 defective). The variation in vascular pattern of these patients is analyzed. METHODS: Between October 2018 and December 2018, a consecutive 162 patients with pulmonary lesions were admitted and underwent 3D-CTB prior to surgery. A total of seven cases of bifurcated right upper bronchus (B1 Defective) were identified. Then 3D-CTBA reconstruction was performed by Syngo MultiModality Workplace (Software: Syngo MMWP, Version: VF40A). Radiology colleagues processed all 3D images and thoracic surgeons confirmed the validity of all reconstructions. RESULTS: The mean age of the seven patients (3 females and 4 males) is 54 years. According to the branches of artery, they are divided into two types: "Tr. sup + A. asc" (2/7, 28.6%) and "Tr. sup + Tr. inf + A. asc" (5/7, 71.4%). According to the branches of A2 asc, another two types can be divided: type A, two branches of A2a asc + A2b asc (4/7, 57.1%) and type B, only one branch of A2b asc (3/7, 42.9%). Types can also be divided according to the branches of A2 rec: A, no A2 rec (4/7, 57.1%); B, one branch of A2a rec (2/7, 28.6%); C, two branches of A2a rec + A2b rec (1/7, 14.3%). According to the origins of A3, three types can be divided: A, A3 origins from Tr. inf (1/7, 14.3%); B, A3 origins from Tr. sup (2/7, 28.6%); C, A3 origins from both Tr. sup and Tr. inf (4/7, 57.1%). CONCLUSIONS: The "defective B1" type of bifurcated right upper lobe (RUL) bronchus is relatively rare. A pre-operative understanding of its anatomical features, especially the vascular variation patterns, may be helpful for completing a satisfactory segmentectomy. 3D-CTBA is a powerful tool, allowing a better understanding of the pulmonary anatomy in each patient before and during surgical procedures.

p62 aggregates mediated Caspase 8 activation is responsible for progression of ovarian cancer.

Increasing evidence suggests that p62/SQSTM1 functions as a signalling centre in cancer. However, the role of p62 in tumour development depends on the interacting factors it recruits and its precise regulatory mechanism remains unclear. In this study, we investigated the pro-death signalling recruitment of p62 with the goal of improving anti-tumour drug effects in ovarian cancer treatment. We found that p62 with Caspase 8 high expression is correlated with longer survival time compared with cases of low Caspase 8 expression in ovarian cancer. In vivo experiments suggested that insoluble p62 and ubiquitinated protein accumulation induced by autophagy impairment promoted the activation of Caspase 8 and increased cell sensitivity to cisplatin. Furthermore, p62 functional domain UBA and LIR mutants regulated autophagic flux and attenuated Caspase 8 activation, which indicates that autophagic degradation is involved in p62-mediated activation of Caspase 8 in ovarian cancer cells. Collectively, our study demonstrates that p62 promotes Caspase 8 activation through autophagy flux blockage with cisplatin treatment. We have provided evidence that autophagy induction followed by its blockade increases cell sensitivity to chemotherapy which is dependent on p62-Caspase 8 mediated apoptosis signalling. p62 exhibits pro-death functions through its interaction with Caspase 8. p62 and Caspase 8 may become novel prognostic biomarkers and oncotargets for ovarian cancer treatment.

Unresectable pancreatic ductal adenocarcinoma: Role of CT quantitative imaging biomarkers for predicting outcomes of patients treated with chemotherapy.

OBJECTIVES: The primary aim of this study was to determine if computed tomographic (CT) texture analysis measurements of the tumor are independently associated with progression-free survival (PFS) and overall survival (OS) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC), including both unresectable locally advanced and metastatic PDAC, who were treated with chemotherapy. METHODS: After an institutional review board waiver was obtained, contrast material-enhanced CT studies in 41 patients with unresectable PDAC who underwent contrast-enhanced CT before chemotherapy between 2014 and 2017 were analyzed in terms of tumor texture, with quantification of mean gray-level intensity (Mean), entropy, mean of positive pixels (MPP), kurtosis, standard deviation (SD), and skewness for fine to coarse textures (spatial scaling factor (SSF) 0-6, respectively). The association between pretreatment and posttreatment texture parameters, as well as Δ value (difference between posttreatment and pretreatment texture parameters), and survival time was assessed by using Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: Findings from the multivariate Cox model indicated that tumor size, tumor SD (HR, 0.942; 95% CI: 0.898, 0.988) and skewness (HR, 0.407; 95% CI: 0.172, 0.962) measurements with SSF = 3, and tumor SD (HR, 0.958; 95% CI: 0.92, 0.997) measurements with SSF = 4 were significantly and independently associated with PFS, while tumor size and tumor SD (HR, 0.928; 95% CI: 0.882, 0.976) measurements with SSF = 3 were significantly and independently associated with OS. None of the post-therapy texture parameters or Δ value had a significant association with OS or PFS in multivariate Cox regression models. Medium SD (SSF = 3) of more than 38.38 and coarse SD (SSF = 4) of more than 40.67 were associated with longer PFS after chemotherapy (for SSF = 3, median PFS was 10.0 vs 6.0 months [P = 0.024], and for SSF = 4, median PFS was 12.0 vs 6.0 months [P = 0.003]). SD of 38.38 or greater (SSF = 3) as a dichotomized variable was a significant positive prognostic factor for OS (median OS, 20.0 vs 9.0 months [P = 0.04]). Survival models that included a combination of pretreatment SD (SSF = 3) with tumor size, had the potential to perform better than SD alone, while having no statistical significance in this study (area under the ROC curve, 0.756 vs 0.715 [P = 0.066]). CONCLUSIONS: Pretreatment CT quantitative imaging biomarkers from texture analysis are associated with PFS and OS in patients with unresectable PDAC who were treated with chemotherapy, and the combination of pretreatment texture parameters and tumor size have the potential to perform better in survival models than imaging biomarker alone.

Prognostic value of caveolin-1 in genitourinary cancer: a meta-analysis.

We aimed to obtain the most comprehensive picture to date of the prognostic value of caveolin-1 (Cav-1) in genitourinary carcinoma by meta-analyzing all eligible studies in PubMed and EMBASE. Data on patient clinical characteristics, cancer-specific survival (CSS) and recurrence-free survival (RFS) were extracted. The meta-analysis included 6 articles on prostate cancer, 5 on renal cancer, 1 on bladder cancer and 1 on transition cell carcinoma of the upper urinary tract. Two studies examining the association of ELISA-measured Cav-1 levels in serum with RFS in 621 patients with prostate cancer gave a combined hazard ratio (HR) of 1.25 (95% CI 0.36 to 4.36). The other 4 studies on prostate cancer examined the association of immunohistochemically determined Cav-1 levels in cancerous tissue with RFS and gave a combined HR of 1.83 (95% CI 1.36 to 2.47). Three studies on renal cancer examining the association of Cav-1 levels with CSS gave a multivariate HR of 1.98 (95% CI 1.35 to 2.90). The single studies on bladder carcinoma and upper urinary tract carcinoma gave, respectively, a multivariate HR of 2.28 (95% CI 1.09 to 4.74) for the relationship of Cav-1 levels to DFS, and a multivariate HR of 5.08 (95% CI 1.799 to 14.342) for the relationship of Cav-1 levels to CSS. This meta-analysis of available evidence suggests that elevated Cav-1 levels in serum can predict poor survival in patients with genitourinary cancer, which may help identify high-risk patients earlier and guide clinical decision-making.

Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis.

Microvessel density (MVD), an indicator of angiogenesis, has been proposed to predict prognosis of patients with renal cell carcinoma (RCC), but its ability to predict survival of patients with RCC remains controversial. The present study sought to address this question rigorously by systematically reviewing the literature on MVD and RCC prognosis. We identified relevant studies in PubMed, EMBASE and the Cochrane Library, and two reviewers independently assessed study quality and extracted relevant data to compare survival based on MVD stratification in patients with RCC. We identified 15 studies that satisfied the inclusion criteria; eight studies assessed MVD in surgical samples by immunohistochemistry to label factor VIII; four studies, by immunohistochemistry to label CD34; two studies, CD31; and one study, CD105. Survival meta-analysis was performed using data pooled from 10 studies: five based on factor VIII, two based on CD34, two based on CD31 and one based on CD105. The overall survival hazard ratio describing the relationship between MVD and survival in all 10 pooled studies was 0.964 (95% CI: 0.873-1.065), while the individual hazard ratios for pooled studies based on factor VIII were 1.673 (95% CI: 0.860-3.252); CD34, 0.903 (95% CI: 0.853-0.956); and CD31, 0.926 (95% CI: 0.868-0.989). The corresponding result for the sole trial based on CD105 was 0.1759 (95% CI: 0.036-0.856). These findings suggest that MVD is not reliably associated with survival time of patients with RCC, which may reflect the need to take into account whether the microvasculature is differentiated or not. MVD as currently calculated may not be an ideal prognostic factor for patients with RCC.

[Circumcision with no-flip Shang Ring technique for adult males: analysis of 168 cases].

OBJECTIVE: To observe the clinical effects of the no-flip procedure with the Chinese Shang Ring when circumcising adult males with redundant prepuce or phimosis, and to discuss its advantages and disadvantages. METHODS: Using the no-flip Shang Ring technique, we performed circumcision for 167 adult males aged 18 -72 (mean 27.8) years with redundant prepuce or phimosis, and analyzed the clinical data, including the operation time, postoperative complications, ring-removal time, and postoperative appearance of the penis. RESULTS: Complete follow-up data of 94 cases (56.29%) were obtained. The mean operation time was (5.03 +/- 0.71) minutes and the average ring-removal time was (18.83 +/- 6.70) days. The primary postoperative complications were edema (35 cases [37.23%] at 2 weeks and 9 cases [9.57%] at 4 weeks), including 2 severe cases (2.13%), and infection (3 cases [3.19%]). The pain scores were 2.01 +/- 2.46 during the procedure and 4.52 +/- 2.53 at 24 hours postoperatively. Slipping of the outer ring occurred in 1 case, and delayed removal of the ring in 30 cases (31.91%). CONCLUSION: Adult male circumcision with the no-flip Shang Ring technique is recommended for its short operation time, simple procedure, fewer postoperative complications, less pain, and better incision appearance.

[Drug delivery systems of baicalin, baicalin-phospholipid complex and self-microemulsifying drug across Caco-2 cell model].

OBJECTIVE: To study the absorption of baicalin (BA), baicalin-phospholipid complex (BA-PC), and two kinds of self-microemulsifying drug delivery system (SMEDDS) of BA-PC (BA-PC-NE-SMEDDS with natural emulsifier and BA-PC-NS-SMEDDS with nonionic surfactants) and predict the ability of improving bioavailability through changing the formulation of BA. METHODS: Transmembrane transports of each formulation were studied by Caco-2 cell model and the concentration of BA was determined by HPLC. RESULTS: With the increasing concentration of BA, the transport rate and apparent permeability coefficient (Papp) of BA was increased,indicating the passive absorption mechanism of BA. While with the increase of transport time, the transport rate and Papp of BA was decreased slowly, most likely due to the biological transformation of BA during the permeation process as reported in other people's paper. When coupled with P-gp inhibitor (Verapamil), the efflux rate (ER) of BA decreased from 2.07 to 0.48, indicating it was the substrate of P-gp. Compared with BA,the cumulative permeate quantity of BA-PC and BA-PC-SMEDDS were with no significant increase before 90 min (P > 0.05), but increased obviously after 90 min (P < 0.05). Three hours later, the cumulative permeate quantity and Papp showed significant differences (P < 0.05) among each formulation and were arranged in the following order: BA-PC-NS-SMEDDS > BA-PC-NE-SMEDDS > BA-PC > BA. Furthermore, the Papp of BA-PC and BA-PC-SMEDDS was significantly greater than that of BA coupled with Verapamil (P < 0.05). CONCLUSION: PC promotes the permeation of BA; PC-SMEDDS further accelerates its permeation bases on BA-PC; And BA-PC-NS-SMEDDS shows the better effect than BA-PC-NE-SMEDDS to promote the permeation of BA.

Prognostic value of vascular endothelial growth factor expression in resected gastric cancer.

BACKGROUND AND AIMS: Vascular endothelial growth factor (VEGF) is a potential prognostic biomarker for patients with resected gastric cancer. However, its role remains controversial. The objective of this study was to conduct a systematic review and meta-analysis of published literature. METHODS: Relevant literature was identified using Medline and survival data from published studies were collected following a methodological assessment. Quality assessment of eligible studies and meta-analysis of hazard ratio (HR) were performed to review the correlation of VEGF overexpression with survival and recurrence in patients with gastric cancer. RESULTS: Our meta-analysis included 44 published studies with 4,794 resected patients. VEGF subtype for the prediction of overall survival (OS) included tissue VEGF (HR=2.13, 95% CI 1.71-2.65), circulating VEGF (HR=4.22, 95% CI 2.47-7.18), tissue VEGF-C (HR=2.21, 95% CI 1.58-3.09), tissue VEGF-D (HR=1.73, 95% CI 1.25-2.40). Subgroup analysis showed that HRs of tissue VEGF for OS were, 1.78 (95% CI 0.90-3.51) and 2.31 (95% CI 1.82-2.93) in non-Asians and Asians, respectively. The meta-analysis was also conducted for disease free survival (DFS) and disease specific survival (DSS). CONCLUSION: Positive expression of tissue VEGF, circulating VEGF, VEGF-C and VEGF-D were all associated with poor prognosis in resected gastric cancer. However, VEGF demonstrated no significant prognostic value for non-Asian populations. Circulating VEGF may be better than tissue VEGF in predicting prognosis.