Amelanotic primary cervical malignant melanoma: A case report and review of literature.

BACKGROUND: Primary malignant melanoma of the cervix (PMMC) is an extremely rare disease that originates from primary cervical malignant melanoma and frequently represents a challenge in disease diagnosis due to unclarified clinical and histological presentations, particularly those without melanin. CASE SUMMARY: Here, we report a case of amelanotic PMMC, with a history of breast cancer and thyroid carcinoma. The patient was finally diagnosed by immunohistochemical staining and staged as IB2 based on the International Federation of Gynecology and Obstetrics with reference to National Comprehensive Cancer Network guidelines and was treated with radical hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy. She then received combination therapy consisting of immunotherapy with tislelizumab and radiofrequency hyperthermia. She has remained free of disease for more than 1 year. CONCLUSION: The differential diagnosis process reenforced the notion that immunohistochemical staining is the most reliable approach for amelanotic PMMC diagnosis. Due to the lack of established therapeutic guidelines, empirical information from limited available studies does not provide the rationale for treatment-decision making. By integrating 'omics' technologies and patient-derived xenografts or mini-patient-derived xenograft models this will help to identify selective therapeutic window(s) and screen the appropriate therapeutics for targeted therapies, immune checkpoint blockade or combination therapy strategies effectively and precisely that will ultimately improve patient survival.

Interface Modulation for the Heterointegration of Diamond on Si.

Along with the increasing integration density and decreased feature size of current semiconductor technology, heterointegration of the Si-based devices with diamond has acted as a promising strategy to relieve the existing heat dissipation problem. As one of the heterointegration methods, the microwave plasma chemical vapor deposition (MPCVD) method is utilized to synthesize large-scale diamond films on a Si substrate, while distinct structures appear at the Si-diamond interface. Investigation of the formation mechanisms and modulation strategies of the interface is crucial to optimize the heat dissipation behaviors. By taking advantage of electron microscopy, the formation of the epitaxial ß-SiC interlayer is found to be caused by the interaction between the anisotropically sputtered Si and the deposited amorphous carbon. Compared with the randomly oriented ß-SiC interlayer, larger diamond grain sizes can be obtained on the epitaxial ß-SiC interlayer under the same synthesis condition. Moreover, due to the competitive interfacial reactions, the epitaxial ß-SiC interlayer thickness can be reduced by increasing the CH4/H2 ratio (from 3% to 10%), while further increase in the ratio (to 20%) can lead to the broken of the epitaxial relationship. The above findings are expected to provide interfacial design strategies for multiple large-scale diamond applications.

Solar-Blind Photodetector Arrays Fabricated by Weaving Strategy.

The quest for solar-blind photodetectors (SBPDs) with exceptional optoelectronic properties for imaging applications has prompted the investigation of SBPD arrays. Ga2O3, characterized by its ultrawide bandgap and low growth cost, has emerged as a promising material for solar-blind detection. In this study, SBPD arrays were fabricated by weaving Sn-doped ß-Ga2O3 microbelts (MBs). These MBs, which have a conductive core surrounded by a high-resistivity depletion surface layer resulting from the segregation of Sn and oxygen, are woven into a grid structure. Each intersection of the MBs functions as a photodetector pixel, with the intersecting MBs serving as the output electrodes of the pixel. This design simplifies the readout circuit for the photodetector array. The solar-blind photodetector array demonstrates superior solar-blind detection performance, including a dark current of 0.5 pA, a response time of 38.8 µs, a light/dark current ratio of 108, and a responsivity of 300 A/W. This research may provide a feasible strategy for the fabrication of photodetector arrays, thus pushing forward the application of photodetectors in imaging.

Long-term outcomes of anatomic vs. non-anatomic resection in intrahepatic cholangiocarcinoma with hepatolithiasis: A multicenter retrospective study.

Background: The benefits of anatomic resection (AR) vs. non-anatomic resection (NAR) in patients with primary intrahepatic cholangiocarcinoma (ICC) with hepatolithiasis (HICC) are unclear. This study aimed to compare the long-term outcomes of AR vs. NAR in patients with HICC. Methods: A total of 147 consecutive patients with HICC who underwent R0 hepatectomy were included. Overall survival (OS) and recurrence-free survival (RFS) following AR vs. NARs were compared using a 1:1 propensity score matching (PSM) analysis. A subgroup analysis was also conducted according to whether there are lymph node metastases (LNM). Results: In a multivariate analysis, CA 19-9 (>39 U/L), microvascular invasion, LNM, and NAR were independent risk factors for poor RFS and OS rates, whereas multiple tumors were independent risk factors for OS. AR had better 1-, 3-, and 5-year RFS and OS rates than NAR (OS: 78.7, 58.9, and 28.5%, respectively, vs. 61.2, 25.4, and 8.8%, respectively; RFS: 59.5, 36.5, and 20.5%, respectively, vs. 38.2, 12.1, and 6.9%, respectively). After PSM, 100 patients were enrolled. The NAR group also had significantly poorer OS and RFS (OS: 0.016; RFS: p = 0.010) than the AR group. The subgroup analysis demonstrated that in HICC without LNM, OS and RFS were significantly poorer in the NAR group than the AR group, while no significant differences were observed in HICC with LNM before or after PSM. Conclusion: Anatomic resection was associated with better long-term survival outcomes than NAR in patients with HICC, except for patients with LNM.

Morphological Risk Factors for Posterior Cruciate Ligament Tear and Tibial Avulsion Injuries of the Tibial Plateau and Femoral Condyle.

BACKGROUND: Identification of morphological risk factors associated with the knee that threaten ligaments is important for understanding injury mechanisms and prevention. However, the morphological risk factors for posterior cruciate ligament (PCL) lesions are not clearly understood. PURPOSE: To investigate whether the medial tibial depth (MTD), medial and lateral posterior tibial slope, asymmetry of the medial and lateral slopes, radius of the sagittal plane medial femoral condyle, coronal tibial slope, and notch width index (NWI) were risk factors for PCL intrasubstance tearing (PCLIT) and tibial avulsion fractures (PCLAF). STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Between January 2015 and March 2022, 82 patients with isolated PCLIT, 68 patients with isolated PCLAF, and 82 controls without any ligamentous or meniscal pathologic findings as determined via physical examination and magnetic resonance imaging were included. Values were compared among the 3 groups. Logistic regression analysis was performed to confirm the risk factors. Receiver operating characteristic curves were defined for the morphological indicators and combination of risk factors. RESULTS: Logistic regression analysis revealed (1) MTD, lateral minus medial posterior tibial slope, radius of the posterior circle of the medial femoral condyle, and NWI as significant independent predictors for PCLIT and (2) MTD and NWI for PCLAF. The areas under the curve combining the 4 indicators for PCLIT and noncontact PCLIT were 0.79 (95% CI, 0.72-0.86) and 0.90 (95% CI, 0.85-0.96), respectively. The area under the curve for the combination of MTD and NWI for PCLAF was 0.78 (95% CI, 0.70-0.86). CONCLUSION: Decreased MTD and NWI were associated with an increased incidence of PCLIT and PCLAF. Increased asymmetry of the medial and lateral slopes and the radius of the posterior circle of the medial femoral condyle were associated with the presence of PCLIT. In addition, the model of a combination of risk factors showed good predictive ability for noncontact PCLIT. These findings may aid clinicians in identifying patients at risk for PCL lesions. Further studies are warranted for identifying the effect of these factors on biomechanical mechanisms.

Intercondylar notch volume in patients with posterior cruciate ligament tears and tibial avulsion injuries: a study applying computed tomography.

BACKGROUND: Two relatively common forms of injury exist in the posterior cruciate ligament (PCL) after the onset of trauma: PCL tear and tibial avulsion fracture. The mechanism for the occurrence of these different forms of injury is not known. Herein, we aimed to investigate this mechanism by comparing the intercondylar notch parameters between patients with PCL tears and those with PCL avulsion fractures of the tibial insertion. METHODS: Fifty-three patients with PCL tears (37 male, 16 female: median age of 37 years: range 18-54 years) and 46 patients with avulsion fractures of tibial insertion (33 male, 13 female: median age of 33 years: range 18-55 years) were included in this study. Three-dimensional computed tomography (CT) was applied to measure the intercondylar notch width index and intercondylar notch volume. The intercondylar notch volume was simulated as the truncated-pyramid shape. Measurements of the top and bottom areas of this model were conducted on the slice containing the most proximal (S1) and most distal (S2) levels of Blumensaat's line. Femoral condyle height (h) was defined as the vertical distance between two parallel planes, and the volume was calculated as h(S1 + S2 + √(S1S2))/3. The values of S1, S2, h, notch volume, the body mass index (BMI), intercondylar notch width (NW), femoral condylar width (FW) and notch width index (NWI) were compared among the PCL tear and avulsion-fracture groups. RESULTS: The results show a significant difference in the S2 and normalized intercondylar notch volumes among patients with PCL tears and tibial avulsion injuries. Patients with PCL tears have smaller S2 and intercondylar notch volumes than those with tibial avulsion. There were no significant differences between the two groups in S1 or the 2D notch measurement parameters, such as the NW, FW and NWI. In addition, logistic regression analysis revealed notch volume and body mass index (BMI) as two significant independent predictors for PCL tears. CONCLUSION: Decreased intercondylar notch volume and increased BMI are associated with an increased incidence of PCL tears. The occurrence of PCL tears and tibial avulsion injuries is influenced by the femoral intercondylar notch volume, and the measurement of the notch volume could be useful for identifying patients at risk for PCL tears.

68Ga-PSMA ligand PET/CT integrating indocyanine green-guided salvage lymph node dissection for lymph node metastasis after radical prostatectomy.

To efficiently remove all recurrent lymph nodes (rLNs) and minimize complications, we developed a combination approach that consisted of 68Gallium prostate-specific membrane antigen (PSMA) ligand positron emission tomography (PET)/computed tomography (CT) and integrated indocyanine green (ICG)-guided salvage lymph node dissection (sLND) for rLNs after radical prostatectomy (RP). Nineteen patients were enrolled to receive such treatment. 68Ga-PSMA ligand PET/CT was used to identify rLNs, and 5 mg of ICG was injected into the space between the rectum and bladder before surgery. Fluorescent laparoscopy was used to perform sLND. While extensive LN dissection was performed at level I, another 5 mg of ICG was injected via the intravenous route to intensify the fluorescent signal, and laparoscopy was introduced to intensively target stained LNs along levels I and II, specifically around suspicious LNs, with 68Ga-PSMA ligand PET/CT. Next, both lateral peritonea were exposed longitudinally to facilitate the removal of fluorescently stained LNs at levels III and IV. In total, pathological analysis confirmed that 42 nodes were rLNs. Among 145 positive LNs stained with ICG, 24 suspicious LNs identified with 68Ga-PSMA ligand PET/CT were included. The sensitivity and specificity of 68Ga-PSMA ligand PET/CT for detecting rLNs were 42.9% and 96.6%, respectively. For ICG, the sensitivity was 92.8% and the specificity was 39.1%. At a median follow-up of 15 (interquartile range [IQR]: 6-31) months, 15 patients experienced complete biochemical remission (BR, prostate-specific antigen [PSA] <0.2 ng ml-1), and 4 patients had a decline in the PSA level, but it remained >0.2 ng ml-1. Therefore, 68Ga-PSMA ligand PET/CT integrating ICG-guided sLND provides efficient sLND with few complications for patients with rLNs after RP.

A Sagittal Patellar Angle Linear Equation Reflecting Patellofemoral Kinematics: Evaluation of Patellar Height at any Degree of Knee Flexion Angle.

OBJECTIVE: To confirm whether a novel sagittal patellar angle linear equation used for evaluating patellar height by calculating expected sagittal patellar angle (SPA) at any degree of knee flexion angle is suitable for patients older than 17 years and its reliability compared with other commonly used methods. METHODS: From September 2016 to September 2019, a total number of 202 consecutive outpatients' knee lateral X-ray radiographs were retrospectively measured and evaluated using a recently proposed linear equation Y = 1.94 + 0.74 × knee flexion(KF) angle. Patients were divided by ages into ayounger group, whose ages were between 17-49 years, and an older group, whose ages were older than 49 years, which has not been validated in the original study. Parameters such as KF, SPA, patella and patella tendon length and so on were measured on computer with picture archiving and communication system by two independent observers at an interval of 1 month. Insall-Salvati (IS) index, Caton-Deschamps (CD) index and Y value, correlation coefficients were calculated and compared using SPSS 22.0 software. RESULTS: In the younger group, 143 patients (165 knees) were included, ages were 17-49 (31.62 ± 11.38) years, males/females were 70 (48.95%)/73 (51.05%), left knees/right knees were 83 (50.30%)/82 (49.70%), mean value of Y was 31.50° ± 10.07°, and SPA was 34.38° ± 12.38°, mean value of IS was 1.06 ± 0.17, mean value of CD was 1.04 ± 0.18. While in older group, 59 patients (78 knees) were included, ages were 50-60 (mean 54.61 ± 2.99) years, there were 32 males (54.24%) and 27 females (45.76%), 42 knees were left (53.85%) and 36 knees were right (46.15%), mean values of Y and SPA were 25.90° ± 11.55° and 29.36° ± 14.22°, mean IS index in older group was 1.06 ± 0.18, mean CD index was 1.00 ± 0.16. Intra- and inter-observer reliabilities of Y in younger and older groups were 0.999, 0.999, 1.000 and 0.999, meaning high reliability and reproducibility, but low Pearson's correlation coefficients with IS and CD index were showed as -0.213 and - 0.216 in younger group and - 0.113 and - 0.316 in older group. CONCLUSIONS: In patients older than 17 years, the linear equation Y = 1.94 + 0.74 × KF is a reliable and practical method to evaluate SPA regardless of age and knee flexion angle, but has weak correlation coefficients with the IS and CD index.

The Effects of Acarbose on Non-Diabetic Overweight and Obese Patients: A Meta-Analysis.

INTRODUCTION: This systematic review aims to verify the efficacy of acarbose monotherapy in treating obese or overweight patients without diabetes. METHODS: In the study, we conducted a systematic search of the Pub-Med, EMBASE, Cochrane and Science Citation Index Expanded databases in search of clinical trials on acarbose treatment, overweight and obesity. The crucial inclusion criteria were as follows: (1) patients were diagnosed as overweight or obese (BMI ≥ 25 kg/m2); (2) randomized controlled trials (RCTs); (3) patients had undergone acarbose monotherapy or placebo control; (4) acarbose treatment had been carried out for at least 3 months. Exclusion criteria were as follows: (1) patients diagnosed with diabetes mellitus (DM); (2) patients had received a weight loss medication or surgery in the past 3 months; (3) papers not published in English; (4) repeated research results of the same experiment or repeated published documents. RESULTS: A total of 7 studies involving 132 in the acarbose group and 137 in placebo group, 269 subjects in total, were included in this meta-analysis. From the selected seven papers, we extracted the following clinical parameters: systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), body mass index (BMI), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density cholesterol (HDL) and fasting plasma glucose (FPG). An important finding of our research is that TG was the only significantly reduced parameter in the acarbose group. Weight mean difference (WMD) was - 0.21 (95% CI - 0.33, - 0.09) mmol/l between acarbose (P = 0.0006) and placebo patients. Reduction of BMI was also greater for acarbose than placebo subjects, although the discrepancy was not statistically significant (P = 0.56). Moreover, no hypoglycemia occurred in either the acarbose group or placebo group. A few subjects experienced gastrointestinal reactions, but these were mild and improved over time. Acarbose has no obvious influence on other metabolic indexes. CONCLUSION: Acarbose monotherapy is beneficial in reducing TG levels in obese or overweight patients and will not result in hypoglycemia during medication. The side effects of acarbose are mild.

Suppression of CCDC6 sensitizes tumor to oncolytic virus M1.

Oncolytic virus is an effective therapeutic strategy for cancer treatment, which exploits natural or manipulated viruses to selectively target and kill cancer cells. However, the innate antiviral system of cancer cells may resistant to the treatment of oncolytic virus. M1 virus is a newly identified oncolytic virus belonging to alphavirus species, but the molecular mechanisms underlying its anticancer activity are largely unknown. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. RNA seq analysis was used to analyze the gene alternation after M1 virus infection. Small interfering RNAs transfection for gene knockdown was used for gene functional tests. Caspase-3/7 activity was detected by Caspase-Glo Assay Systems. A mice model of orthotopic bladder tumor was established to determine the oncolytic effectiveness of the M1 virus. The expression of cleaved-Caspase 3 as well as Ki-67 in tumor cells were detected by immunohistochemical analysis. To further define the molecular factors involved in M1 virus-mediated biological function, we knocked down genes related to alphavirus' activity and found that CCDC6 plays an important role in the oncolytic activity of M1 virus. Moreover, knocked down of CCDC6 augments the reproduction of M1 virus and resulted in endoplasmic reticulum (ER) stress-induced cell apoptosis in vitro as well as in vivo orthotopic bladder cancer model. Our research provides a rational new target for developing new compounds to promote the efficacy of oncolytic virus therapy.

Late Pennsylvanian carbonate platform facies and coral reef: new insights from southern China (Guizhou Province).

The Pennsylvanian is characterized by intense paleoenvironmental changes related to glacio-eustatic sea-level fluctuations and major tectonic events, which affected the evolution of biocommunities. Most known Pennsylvanian tropical reefs and mounds are predominantly composed of calcareous algae (e.g. phylloid algae, Archaeolithophyllum), calcareous sponges, fenestrate bryozoans, Tubiphytes, and microbialites. However, in Houchang (southern China), the Late Pennsylvanian carbonate platform records a large coral reef lacking any analogs in age (Gzhelian), size (80-100 m thick) and composition (high biodiversity). The large coral reef developed at the border of the Luodian intraplatform basin. The intraplatform basin is characterized by the deposition of green algal grainstone, coated grain grainstone and bioclastic packstone, grainstone, floatstone and rudstone in shallow-waters. In the deep-water shelf, lithofacies are composed of burrowed bioclastic wackestone, microbioclastic peloidal packstone, grainstone, and fine-grained burrowed wackestone and packstone. In this context, the coral reef developed on a deep-shelf margin, in a moderate to low energy depositional environment, below the FWWB. The scarcity of Pennsylvanian coral reefs suggests global unfavorable conditions, which can be attributed to a complex pattern of several environmental factors, including seawater chemistry (aragonite seas), paleoclimatic cooling related to continental glaciation, and the biological competition with the more opportunistic and adaptive phylloid algal community that occupied similar platform margin paleoenvironments. The existence of the large Bianping coral reef in southern China, as well as a few additional examples of Pennsylvanian coralliferous bioconstructions, provides evidence that coral communities were able to endure the Late Paleozoic fluctuating paleoenvironmental conditions in specific settings. One of such settings appears to have been the deep shelf margin, where low light levels decreased competition with the phylloid algal community.

Impact of breath-hold level on positional error aligned by stent/Lipiodol in Hepatobiliary radiotherapy with breath-hold respiratory control.

BACKGROUND: Respiratory motion management with breath hold for patients with hepatobiliary cancers remain a challenge in the precise positioning for radiotherapy. We compared different image-guided alignment markers for estimating positional errors, and investigated the factors associated with positional errors under breath-hold control. METHODS: Spirometric motion management system (SDX) for breath holds was used in 44 patients with hepatobiliary tumor. Among them, 28 patients had a stent or embolized materials (lipiodol) as alignment markers. Cone-beam computed tomography (CBCT) and kV-orthogonal images were compared for accuracy between different alignment references. Breath-hold level (BHL) was practiced, and BHL variation (ΔBHL) was defined as the standard deviation in differences between actual BHLs and baseline BHL. Mean BHL, ΔBHL, and body-related factors were analyzed for the association with positional errors. RESULTS: Using the reference CBCT, the correlations of positional errors were significantly higher in those with stent/lipiodol than when the vertebral bone was used for alignment in three dimensions. Patients with mean BHL > 1.4 L were significantly taller (167.6 cm vs. 161.6 cm, p = 0.03) and heavier (67.1 kg vs. 57.4 kg, p = 0.02), and had different positional error in the craniocaudal direction (- 0.26 cm [caudally] vs. + 0.09 cm [cranially], p = 0.01) than those with mean BHL < 1.4 L. Positional errors were similar for patients with ΔBHL< 0.03 L and > 0.03 L. CONCLUSION: Under rigorous breath-hold respiratory control, BHL correlated with body weight and height. With more accurate alignment reference by stent/lipiodol, actual BHL but not breath-hold variation was associated with craniocaudal positional errors.

A water stable layered Tb(iii) polycarboxylate with high proton conductivity over 10-2 S cm-1 in a wide temperature range.

An unprecedented Tb(iii) polycarboxylate, {[Tb4(TTHA)2(H2O)4]·7H2O}n (1), has been synthesized. It possesses an efficient proton transfer pathway formed by water molecules and carboxyl groups, which exhibits proton conductivity over 10-2 S cm-1 at 295-358 K and 98% relative humidity.

Intravenous injections of the oncolytic virus M1 as a novel therapy for muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is associated with low survival and high recurrence rates even in cases in which patients receive systemic treatments, such as surgery and chemotherapy. Here, we found that a naturally existing alphavirus, namely, M1, selectively kills bladder cancer cells but not normal cells, findings supported by our observations of changes in viral replication and MIBC and patient-derived MIBC cell apoptosis. Transcriptome analysis revealed that interferon-stimulated genes (ISGs) are expressed at low levels in sensitive bladder cancer cells and high levels in resistant cells. Knocking down ZC3HAV1 (ZAP), an antiviral factor in ISGs, restores M1 virus reactivity in resistant cells, and overexpressing ZAP partially reverses M1 virus-induced decreases in cell viability in sensitive cells. In orthotopic MIBC mice, tail vein injections of M1 significant inhibit tumor growth and prolong survival period, antitumor effects of M1 are stronger than those of the first-line chemotherapy agent cisplatin (CDDP). Treated tumors display enhanced cleaved-caspase-3 signals, which are representative of cell apoptosis, and decreased Ki-67 signals, which are representative of cell proliferation. Moreover, tissue microarray (TMA) analyses of clinical tumor specimens revealed that up to 45.6% of cases of MIBC presented with low ZAP expression, a finding that is prevalent in advanced MIBC. Our results indicate that the oncolytic virus M1 is a novel agent capable of functioning as a precise and effective therapy for MIBC.

Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.

Association between three VEGF polymorphisms and renal cell carcinoma susceptibility: a meta-analysis.

Several studies have reported an association between vascular endothelial growth factor (VEGF) gene polymorphisms rs2010963, rs3025039 and rs699947 and renal cell carcinoma (RCC). However, the results remain inconclusive and controversial. We therefore conducted a meta-analysis to evaluate this association. Electronic databases were searched for relevant case-control studies up to November 2016. RevMan 5.2 software and STATA version 12.0 were used for statistical analysis in our meta-analysis. Heterogeneity was assessed using the I2 value. Nine eligible studies were retrieved for detailed evaluation. The pooled estimates indicated that the GG genotype of VEGF rs2010963 polymorphism significantly decreased RCC risk [GG vs. GC+CC; GG vs. GC]. There was also a significant association between VEGF rs3025039 polymorphism and RCC susceptibility [CC+CT vs. TT; CC vs. TT]. Furthermore, a significant association between VEGF rs699947 polymorphism and RCC susceptibility was detected [A vs. C; AA+AC vs. CC; AA vs. AC+CC; AA vs. CC; AA vs. AC; AC vs. CC]. Subgroup analysis revealed that these associations held true especially for Asians. Our meta-analysis suggested that there may be a relationship between the VEGF rs2010963, rs3025039 and rs699947 polymorphisms and RCC susceptibility.

Exploring time- and frequency- dependent functional connectivity and brain networks during deception with single-trial event-related potentials.

To better characterize the cognitive processes and mechanisms that are associated with deception, wavelet coherence was employed to evaluate functional connectivity between different brain regions. Two groups of subjects were evaluated for this purpose: 32 participants were required to either tell the truth or to lie when facing certain stimuli, and their electroencephalogram signals on 12 electrodes were recorded. The experimental results revealed that deceptive responses elicited greater connectivity strength than truthful responses, particularly in the θ band on specific electrode pairs primarily involving connections between the prefrontal/frontal and central regions and between the prefrontal/frontal and left parietal regions. These results indicate that these brain regions play an important role in executing lying responses. Additionally, three time- and frequency-dependent functional connectivity networks were proposed to thoroughly reflect the functional coupling of brain regions that occurs during lying. Furthermore, the wavelet coherence values for the connections shown in the networks were extracted as features for support vector machine training. High classification accuracy suggested that the proposed network effectively characterized differences in functional connectivity between the two groups of subjects over a specific time-frequency area and hence could be a sensitive measurement for identifying deception.

Repair of urethral defects with polylactid acid fibrous membrane seeded with adipose-derived stem cells in a rabbit model.

AIM: The aim of this study is to evaluate the capacity of polylactid acid (PLA) fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells (ADSCs) to repair urethral defects in a rabbit model. MATERIALS AND METHODS: Rabbit ADSCs were harvested and phenotypically characterized. Twenty-four New Zealand male rabbits with 5-mm urethral mucosal defects were randomly divided into two groups. They underwent urethroplasty either with PLA fibrous membrane seeded with ADSCs (group A) or blank PLA fibrous membrane (group B). At 4 and 6 weeks after urethroplasty, the urethral grafts were collected and analyzed grossly and histologically. The incidence rate of urethrostenosis was measured. RESULTS: The adipose tissue-derived cells in monolayer culture showed a typical morphology of mesenchymal stem cells (MSCs). They were positive for the MSC marker CD44 but negative for lineage markers CD45 and CD105. Six weeks after surgery, the incidence rate of urethrostenosis in group A was significantly lower than that in group B (p < 0.05). In group A, the ADSC-seeded grafts showed a normal urethral architecture with a thickened muscle layer. In contrast, the newly developed urethra in group B demonstrated a fewer number of urothelial layers and scarce or no smooth muscle cells. CONCLUSION: The PLA scaffold seeded with ADSCs is effective in urethral regeneration in a rabbit model. ADSCs may represent a promising source of seed cells for urethral tissue engineering.

Manipulation of prostate cancer metastasis by locus-specific modification of the CRMP4 promoter region using chimeric TALE DNA methyltransferase and demethylase.

Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG and subsequent histone modifications. These manipulations markedly altered expression of endogenous CRMP4, a metastasis suppressor gene. Remarkably, locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 cells abolished metastasis, whereas locus-specific CpG methylation of the promoter in non-metastatic 22Rv1 cells induced metastasis. CRMP4-mediated metastasis suppression was found to require activation of Akt/Rac1 signaling and down-regulation of MMP-9 expression. This proof-of-concept study with dTALEs for locus-specific epigenomic manipulation validates the selected CpG methylation of CRMP4 gene as an independent biomarker for diagnosis and prognosis of prostate cancer metastasis and opens up a novel avenue for mechanistic research on cancer biology.