Mesenchymal stem cells derived from CHIR99021 and TGF­ß induction remained on the colicomentum and improved cardiac function of a rat model of acute myocardium infarction.

Human induced pluripotent stem cells (hiPSCs) have been regarded as a potential stem cell source for cell therapy. However, the production of cells with mesenchymal potential from hiPSCs through spontaneous differentiation is time consuming and laborious. In the present study, the combined use of the GSK-3 inhibitor CHIR99021 and TGF-ß was used to obtain mesenchymal stem cell (MSC)-like cells from hiPSCs. During the induction process, the transcription of epithelial-mesenchymal transition (EMT)-related genes N-cadherin and Vimentin in the transformed cells was upregulated, whereas the transcription of E-cadherin and pluripotency-related transcription factors SOX2, OCT4 and NANOG did not change significantly. This indicated that whilst cells were pluripotent, EMT was initiated by the upregulation of transcription of EMT promoting genes. Both SMAD-dependent and independent signalling pathways were significantly activated by the combined induction treatment compared with the single factor induction. The hiPSC-derived MSC-like cells (hiPSC-MSCs) expressed MSC-related markers and acquired osteogenic, chondrogenic and adipogenic differentiation potentials. After being injected into the peritoneal cavity of rats, the hiPSC-MSCs secreted angiogenic and immune-regulatory factors and remained on the colicomentum for 3 weeks. Within an 11-week period, four intraperitoneal hiPSC-MSC injections (1x107 cells/injection) into acute myocardial infarction (AMI) model rats significantly increased the left ventricular ejection fraction, left ventricular fractional shortening and angiogenesis and significantly reduced scar size and the extent of apoptosis in the infarcted area compared with that of the control PBS injection. Symptoms of hiPSC-MSC-induced immune reaction or tumour formation were not observed over the course of the experiment in the hiSPC-MSC treated rats. In conclusion, the CHIR99021 and TGF-ß combined induction was a rapid and effective method to obtain MSC-like cells from hiPSCs and multiple high dose intraperitoneal injections of hiPSC-derived MSCs were safe and effective at restoring cardiac function in an AMI rat model.

Identifying IDH-mutant and 1p/19q noncodeleted astrocytomas from nonenhancing gliomas: Manual recognition followed by artificial intelligence recognition.

Background: The T2-FLAIR mismatch sign (T2FM) has nearly 100% specificity for predicting IDH-mutant and 1p/19q noncodeleted astrocytomas (astrocytomas). However, only 18.2%-56.0% of astrocytomas demonstrate a positive T2FM. Methods must be considered for distinguishing astrocytomas from negative T2FM gliomas. In this study, positive T2FM gliomas were manually distinguished from nonenhancing gliomas, and then a support vector machine (SVM) classification model was used to distinguish astrocytomas from negative T2FM gliomas. Methods: Nonenhancing gliomas (regardless of pathological type or grade) diagnosed between January 2022 and October 2022 (N = 300) and November 2022 and March 2023 (N = 196) will comprise the training and validation sets, respectively. Our method for distinguishing astrocytomas from nonenhancing gliomas was examined and validated using the training set and validation set. Results: The specificity of T2FM for predicting astrocytomas was 100% in both the training and validation sets, while the sensitivity was 42.75% and 67.22%, respectively. Using a classification model of SVM based on radiomics features, among negative T2FM gliomas, the accuracy was above 85% when the prediction score was greater than 0.70 in identifying astrocytomas and above 95% when the prediction score was less than 0.30 in identifying nonastrocytomas. Conclusions: Manual screening of positive T2FM gliomas, followed by the SVM classification model to differentiate astrocytomas from negative T2FM gliomas, may be a more effective method for identifying astrocytomas in nonenhancing gliomas.

Distinguishing Tumor Cell Infiltration and Vasogenic Edema in the Peritumoral Region of Glioblastoma at the Voxel Level via Conventional MRI Sequences.

RATIONALE AND OBJECTIVES: The peritumoral region of glioblastoma (GBM) is composed of infiltrating tumor cells and vasogenic edema, which are difficult to distinguish manually on MRI. To distinguish tumor cell infiltration and vasogenic edema in GBM peritumoral regions, it is crucial to develop a method that is precise, effective, and widely applicable. MATERIALS AND METHODS: We retrieved the image characteristics of 379,730 voxels (marker of tumor infiltration) from 28 non-enhanced gliomas and 365,262 voxels (marker of edema) from the peritumoral edema region of 14 meningiomas on conventional MRI sequences (T1-weighted image, the contrast-enhancing T1-weighted image, the T2-weighted image, the T2-fluid attenuated inversion recovery image, and the apparent diffusion coefficient map). Using the SVM classifier, a model for predicting tumor cell infiltration and vasogenic edema at the voxel level was developed. The accuracy of the model's predictions was then evaluated using 15 GBM patients who underwent stereotactic biopsies. RESULTS: The area under the curve (AUC), accuracy, sensitivity, and specificity of the prediction model were 0.93, 0.84, 0.83, and 0.85 in the training set, and 0.90, 0.82, 0.83, and 0.83 in the test set (704,992 voxels), respectively. The pathology verification of 28 biopsy points with an accuracy of 0.79. CONCLUSION: At the voxel level, it seems possible to forecast tumor cell infiltration and vasogenic edema in the peritumoral region of GBM based on conventional MRI sequences.

Comparative studies on the chemical composition and pharmacological effects of vinegar-processed antler glue modified from Lei Gong Pao Zhi Lun and traditional water-processed antler glue.

ETHNOPHARMACOLOGICAL RELEVANCE: Antler glue is a classic medicinal to enhance sexual function in traditional Chinese medicine (TCM), which was first recorded in Shen Nong Ben Cao Jing (Shennong's Classic of the Materia Medica). Vinegar-processing is a classic method of processing traditional Chinese medicine. The method of preparing antler glue by boiling antlers in vinegar and then concentrating them is recorded in Lei Gong Pao Zhi Lun (Master Lei's Discourse on Medicinal Processing). In modern times, the typical processing method of antler glue is water extraction and concentration. However, it is not clear whether there is a difference in the effect of these two processing methods on the chemical composition and pharmacological activity of antler glue. AIM OF THE STUDY: The Chinese Pharmacopoeia (2020) records that the processing method of antler glue is water extraction and concentration. But Lei Gong Pao Zhi Lun differs in Chinese Pharmacopoeia (2020), which records the processing method of vinegar extraction and concentration. The effect of the two processing methods on antler glue's chemical composition and pharmacological activity is unknown. So this study aimed to elucidate the difference between different processing methods on the chemical composition and the treatment effect on oligoasthenospermia of antler glue. MATERIALS AND METHODS: So the automatic amino acid analyzer is used to determine the amino acid content of two different processing methods of antler glue. Proteomics was performed to detect the protein components of two different processing methods of antler glue and analyze them. Cyclophosphamide-induced mice models of oligoasthenospermia were used to study the different pharmacological effects of antler glue in two different processing methods. An automatic sperm analyzer observed the quantity and quality of sperm in mice epididymis. Serum sex hormone testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in mice were tested using the enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin-eosin (H&E) staining was used to analyze pathological alterations in mouse testicular tissue. The transcriptome has been used to reveal the potential mechanism of antler glue in treating oligoasthenospermia. Mitochondrial complex activity assay kits were used to assay the activity of mitochondrial respiratory chain complex I-V in mouse testicular tissue. Western blot was used to determine the expression of related proteins in mouse testicular tissue. RESULTS: Vinegar-processing can increase the alanine, proline, and glycine content in antler glue, reduce the length of protein peptides in antler glue, and produce a variety of unique proteins. Vinegar-processed antler glue (VAG) increased sperm density, sperm survival, sperm viability, and serum sex hormone levels in oligozoospermic mice. It reversed testicular damage caused by cyclophosphamide, and the effects were differently superior to those of water-processed antler glue (WAG). In addition, transcriptomics and related experiments have shown that VAG can increase the expression of Ndufa2, Uqcr11, Cox6b1, and Atp5i genes and proteins in mouse testis, thus promoting adenosine diphosphate (ATP) synthesis by increasing the activity of mitochondrial respiratory chain complexes I, III, IV and V. By promoting the oxidative phosphorylation process to produce more ATP, VAG can achieve the therapeutic effect of oligoasthenospermia. CONCLUSION: Vinegar-processing method can increase the content of active ingredients in antler glue. VAG increases ATP levels in the testes by promoting the process of oxidative phosphorylation to treat oligozoospermia.

Characteristics of Microstructural Changes Associated with Glioma Related Epilepsy: A Diffusion Tensor Imaging (DTI) Study.

(1) Background: Glioma is the most common primary tumor in the central nervous system, and glioma-related epilepsy (GRE) is one of its common symptoms. The abnormalities of white matter fiber tracts are involved in attributing changes in patients with epilepsy (Rudà, R, 2012).This study aimed to assess frontal lobe gliomas' effects on the cerebral white matter fiber tracts. (2) Methods: Thirty patients with frontal lobe glioma were enrolled and divided into two groups (Ep and nEep). Among them, five patients were excluded due to apparent insular or temporal involvement. A set of 14 age and gender-matched healthy controls were also included. All the enrolled subjects underwent preoperative conventional magnetic resonance images (MRI) and diffusion tensor imaging (DTI). Furthermore, we used tract-based spatial statistics to analyze the characteristics of the white matter fiber tracts. (3) Results: The two patient groups showed similar patterns of mean diffusivity (MD) elevations in most regions; however, in the ipsilateral inferior fronto-occipital fasciculus (IFOF), superior longitudinal fasciculus (SLF), and superior corona radiata, the significant voxels of the EP group were more apparent than in the nEP group. No significant fractional anisotropy (FA) elevations or MD degenerations were found in the current study. (4) Conclusions: Gliomas grow and invade along white matter fiber tracts. This study assessed the effects of GRE on the white matter fiber bundle skeleton by TBSS, and we found that the changes in the white matter skeleton of the frontal lobe tumor-related epilepsy were mainly concentrated in the IFOF, SLF, and superior corona radiata. This reveals that GRE significantly affects the white matter fiber microstructure of the tumor.

Image-Based Differentiation of Intracranial Metastasis From Glioblastoma Using Automated Machine Learning.

Purpose: The majority of solitary brain metastases appear similar to glioblastomas (GBMs) on magnetic resonance imaging (MRI). This study aimed to develop and validate an MRI-based model to differentiate intracranial metastases from GBMs using automated machine learning. Materials and Methods: Radiomics features from 354 patients with brain metastases and 354 with GBMs were used to build prediction algorithms based on T2-weighted images, contrast-enhanced (CE) T1-weighted images, or both. The data of these subjects were subjected to a nested 10-fold split in the training and testing groups to build the best algorithms using the tree-based pipeline optimization tool (TPOT). The algorithms were independently validated using data from 124 institutional patients with solitary brain metastases and 103 patients with GBMs from the cancer genome atlas. Results: Three groups of models were developed. The average areas under the receiver operating characteristic curve (AUCs) were 0.856 for CE T1-weighted images, 0.976 for T2-weighted images, and 0.988 for a combination in the testing groups, and the AUCs of the groups of models in the independent validation were 0.687, 0.831, and 0.867, respectively. A total of 149 radiomics features were considered as the most valuable features for the differential diagnosis of GBMs and metastases. Conclusion: The models established by TPOT can distinguish glioblastoma from solitary brain metastases well, and its non-invasiveness, convenience, and robustness make it potentially useful for clinical applications.

Development and validation of a novel survival prediction model for newly diagnosed lower-grade gliomas.

OBJECTIVE: Diffuse gliomas are the most common primary gliomas with a poor prognosis. This study aimed to develop and validate prognostic models for predicting the survival probability in newly diagnosed lower-grade glioma (LGG) patients. METHODS: Detailed data were obtained for newly diagnosed LGG from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) cohorts. Survival was assessed using Cox proportional hazards regression with adjustment for known prognostic factors. The model was established using the TCGA cohort, and independently validated using the CGGA cohort, to predict the 3-, 5-, and 10-year survival probabilities of patients. RESULTS: Data from 293 patients with newly diagnosed LGG from the TCGA cohort were used to establish a prognostic model, and from 232 patients with primary LGG in the CGGA cohort to validate the model. Age, tumor grade, molecular subtype, tumor resection, and preoperative neurological deficits were included in the prediction model. The Cox regression model had a satisfactory corrected concordance index of 0.8508, 0.8510, and 0.8516 in the internal bootstrap validation at 3, 5, and 10 years, respectively. The calibration plots demonstrated high consistency of the predicted and observed outcomes. The CGGA cohort was used for external validation and showed satisfactory discrimination of 0.7776, 0.7682, and 0.7051 at 3, 5, and 10 years, respectively. The calibration plots demonstrated an acceptable calibration capability in the external validation. CONCLUSIONS: This study established and validated a prognostic model to predict the survival probability of patients with newly diagnosed LGG. The model performed well in discrimination and calibration with ease of use, speed, accessibility, interpretability, and generalizability. An easily used nomogram based on the Cox model was established for clinical application. Moreover, a free, easy-to-use software interface based on the nomogram is provided online.

Management of central nervous system Rosai-Dorfman disease: A single center treatment experience.

Rosai-Dorfman disease (RDD) is an idiopathic histiocytic proliferation disease with various clinical manifestations. A retrospective study of patients with pathological diagnosed RDD primarily involved in the central nervous system was conducted from January 2011 to December 2020 at a tertiary center. The clinical profile, imaging, and treatment data were collected. There were 16 male and 5 female patients with RDD-CNS. The patients were aged from 6 to 68 years with a median of 37 years. Of these 21 patients, 15 presented with intracranial RDD and 6 with spinal RDD. The main symptoms of RDD-CNS included headache, epilepsy, and neurological deficits. 76.19% (16/21) of the patients showed dura-based, homogeneous enhancement lesion on magnetic resonance imaging (MRI). Twenty patients received surgery as first treatment, and one patient received biopsy after steroid therapy. Total lesion resection was achieved in 42.9% (9/21) of the patients, subtotal resection in 47.6% (10/21), and biopsy in 0.9% (2/21). The symptoms were alleviated or stayed stable. Some RDDs (80%, 4/5) in the skull base had some complications. The patients were followed up for 11-108 months with a median duration of 47 months. Lesion progression or recurrence was found in two patients. The various clinical manifestations, as well as the dura-based and homogenous enhancement imaging profiles of RDD-CNS patients pose a great diagnostic challenge for clinicians. Surgery is effective for RDD-CNS requiring treatment. Medical therapy and radiotherapy would be feasible as noninvasive treatments, varying degrees of efficacy. The overall prognosis of RDD-CNS is acceptable. Periodic long-term follow-up is necessary.

The utility of intraoperative ECoG in tumor-related epilepsy: Systematic review.

OBJECT: Epilepsy is one of the most common clinical manifestations of primary brain tumors. Intraoperative electrocorticography (ECoG) has been widely used in tumor resection. We aim to describe the indication and utility of ECoG during brain tumor surgery. METHODS: We performed a systematic review of the literature on the prognosis of tumor-related epilepsy surgery guided by intraoperative ECoG. The published studies were searched in PubMed, Embase, and Web of Science using the keyword 'seizure' or 'epilepsy' and 'electrocorticography' or 'ECoG'. Two reviewer authors screened studies and extracted data independently. RESULTS: Thirteen studies included 569 patients were finally selected, of which eight investigated medically intractable epilepsy. Three publications described temporal tumor-related epilepsy. All included studies were retrospective, and the age of all patients ranged from 1 to 71 years. The duration of epilepsy ranged from 1 month to 30 years. Patients with tumor-related epilepsy underwent surgical treatment with Engel I outcomes ranging from 56.5%-100%. CONCLUSION: Intraoperative ECoG is generally considered a useful technique in delineating epileptogenic areas and improving the prognosis of surgical treatment of tumor-related epilepsy. However, large-scale randomized control trials are still needed to verify these findings and formulate appropriate surgical strategies.

Preoperative Radiomics Analysis of 1p/19q Status in WHO Grade II Gliomas.

PURPOSE: The present study aimed to preoperatively predict the status of 1p/19q based on radiomics analysis in patients with World Health Organization (WHO) grade II gliomas. METHODS: This retrospective study enrolled 157 patients with WHO grade II gliomas (76 patients with astrocytomas with mutant IDH, 16 patients with astrocytomas with wild-type IDH, and 65 patients with oligodendrogliomas with mutant IDH and 1p/19q codeletion). Radiomic features were extracted from magnetic resonance images, including T1-weighted, T2-weighted, and contrast T1-weighted images. Elastic net and support vector machines with radial basis function kernel were applied in nested 10-fold cross-validation loops to predict the 1p/19q status. Receiver operating characteristic analysis and precision-recall analysis were used to evaluate the model performance. Student's t-tests were then used to compare the posterior probabilities of 1p/19q co-deletion prediction in the group with different 1p/19q status. RESULTS: Six valuable radiomic features, along with age, were selected with the nested 10-fold cross-validation loops. Five features showed significant difference in patients with different 1p/19q status. The area under curve and accuracy of the predictive model were 0.8079 (95% confidence interval, 0.733-0.8755) and 0.758 (0.6879-0.8217), respectively, and the F1-score of the precision-recall curve achieved 0.6667 (0.5201-0.7705). The posterior probabilities in the 1p/19q co-deletion group were significantly different from the non-deletion group. CONCLUSION: Combined radiomics analysis and machine learning showed potential clinical utility in the preoperative prediction of 1p/19q status, which can aid in making customized neurosurgery plans and glioma management strategies before postoperative pathology.

Ischemic Infarction of Pituitary Apoplexy: A Retrospective Study of 46 Cases From a Single Tertiary Center.

OBJECTIVE: Ischemic infarction of pituitary apoplexy (PA) is a rare type of pituitary apoplexy. This study aims to characterize ischemic PA via clinical presentations, imaging data, histopathological manifestations, and focus on the management and prognosis of the disease. METHODS: This study retrospectively identified 46 patients with ischemic PA confirmed using histopathology at a single institution from January 2013 to December 2020. The clinical presentations, imaging data, laboratory examination, management, and outcomes were collected. We then summarized the clinical presentations, imaging features, intraoperative findings, and histopathological manifestations, and compared the outcomes based on the timing of surgical intervention. RESULTS: Headache was the most common initial symptom (95.65%, 44/46), followed by visual disturbance (89.13%, 41/46), and nausea and vomiting (58.70%, 27/46). 91.3% of the patients had at least one pituitary dysfunction, with hypogonadism being the most common endocrine dysfunction (84.78%, 39/46). Cortisol dysfunction occurred in 24 (52.17%) patients and thyroid dysfunction occurred in 17 (36.96%). Typical rim enhancement and thickening of the sphenoid sinus on MRI were seen in 35 (85.37%) and 26 (56.52%) patients, respectively. Except for one patient with asymptomatic apoplexy, the remaining patients underwent early (≤ 1 week, 12 patients) and delayed (> 1 week, 33 patients) transsphenoidal surgery. Total tumor resection was achieved in 27 patients and subtotal tumor resection in 19 patients. At surgery, cottage cheese-like necrosis was observed in 50% (23/46) of the patients. At the last follow-up of 5.5 ± 2.7 years, 92.68% (38/41) of the patients had gained a significant improvement in visual disturbance regardless of surgical timing, and 65% of the patients were still receiving long-term hormone replacement therapy. CONCLUSION: Patients with ischemic PA can be accurately diagnosed by typical imaging characteristics preoperatively. The timing of surgical intervention does not significantly affect the resolution of neurological and endocrinological dysfunctions. Preoperative endocrine dysfunctions are common and usually appear to be poor after surgical intervention.

Radiomics Features Predict Telomerase Reverse Transcriptase Promoter Mutations in World Health Organization Grade II Gliomas via a Machine-Learning Approach.

The detection of mutations in telomerase reverse transcriptase promoter (pTERT) is important since preoperative diagnosis of pTERT status helps with evaluating prognosis and determining the surgical strategy. Here, we aimed to establish a radiomics-based machine-learning algorithm and evaluated its performance with regard to the prediction of mutations in pTERT in patients with World Health Organization (WHO) grade II gliomas. In total, 164 patients with WHO grade II gliomas were enrolled in this retrospective study. We extracted a total of 1,293 radiomics features from multi-parametric magnetic resonance imaging scans. Elastic net (used for feature selection) and support vector machine with linear kernel were applied in nested 10-fold cross-validation loops. The predictive model was evaluated by receiver operating characteristic and precision-recall analyses. We performed an unpaired t-test to compare the posterior predictive probabilities among patients with differing pTERT statuses. We selected 12 valuable radiomics features using nested 10-fold cross-validation loops. The area under the curve (AUC) was 0.8446 (95% confidence interval [CI], 0.7735-0.9065) with an optimal summed value of sensitivity of 0.9355 (95% CI, 0.8802-0.9788) and specificity of 0.6197 (95% CI, 0.5071-0.7371). The overall accuracy was 0.7988 (95% CI, 0.7378-0.8598). The F1-score was 0.8406 (95% CI, 0.7684-0.902) with an optimal precision of 0.7632 (95% CI, 0.6818-0.8364) and recall of 0.9355 (95% CI, 0.8802-0.9788). Posterior probabilities of pTERT mutations were significantly different between patients with wild-type and mutant TERT promoters. Our findings suggest that a radiomics analysis with a machine-learning algorithm can be useful for predicting pTERT status in patients with WHO grade II glioma and may aid in glioma management.

Aspirin Reduces Cardiac Interstitial Fibrosis by Inhibiting Erk1/2-Serpine2 and P-Akt Signalling Pathways.

BACKGROUND/AIMS: Cardiac interstitial fibrosis is an abnormality of various cardiovascular diseases, including myocardial infarction, hypertrophy, and atrial fibrillation, and it can ultimately lead to heart failure. However, there is a lack of practical therapeutic approaches to treat fibrosis and reverse the damage to the heart. The purpose of this study was to investigate the effect of long-term aspirin administration on pressure overload-induced cardiac fibrosis in mice and reveal the underlying mechanisms of aspirin treatment. METHODS: C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 10 mg·kg-1·day-1 of aspirin for 4 weeks. Masson staining and a collagen content assay were used to detect the effects of aspirin on cardiac fibrosis in vivo and in vitro. Western blot and qRT-PCR were applied to examine the impact of aspirin on extracellular signal-regulated kinases (Erks), p-Akt/ß-catenin, SerpinE2, collagen I, and collagen III levels in the mice heart. RESULTS: Aspirin significantly suppressed the expression of α-smooth muscle actin (α-SMA; 1.19±0.19-fold) and collagen I (0.95±0.09-fold) in TAC mice. Aspirin, at doses of 100 and 1000 µM, also significantly suppressed angiotensin II-induced α-SMA and collagen I in cultured CFs. The enhanced phosphorylation of Erk1/2 caused by TAC (p-Erk1, 1.49±0.19-fold; p-Erk2, 1.96±0.68-fold) was suppressed by aspirin (p-Erk1, 1.04±0.15-fold; p-Erk2, 0.87±0.06-fold). SerpinE2 levels were suppressed via the Erk1/2 signalling pathway following treatment with aspirin (1.36±0.12-fold for TAC; 1.06±0.07-fold for aspirin+TAC). The p-Akt and ß-catenin levels were also significantly inhibited in vivo and in vitro. CONCLUSIONS: Our study reveals a novel mechanism by which aspirin alleviates pressure overload-induced cardiac interstitial fibrosis in TAC mice by suppressing the p-Erk1/2 and p-Akt/ß-catenin signalling pathways.

Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling.

Ventricular hypertrophy is a powerful and independent predictor of cardiovascular morbid events. The vascular properties of low-dose acetyl salicylic acid (aspirin) provide cardiovascular benefits through the irreversible inhibition of platelet cyclooxygenase 1; however, the possible anti-hypertrophic properties and potential mechanism of aspirin have not been investigated in detail. In this study, healthy wild-type male mice were randomly divided into three groups and subjected to transverse aortic constriction (TAC) or sham operation. The TAC-operated mice were treated with the human equivalent of low-dose aspirin (10 mg·kg(-1)·d(-1)); the remaining mice received an equal amount of phosphate buffered saline with 0.65% ethanol, which was used as a vehicle. A cardiomyocyte hypertrophy model induced by angiotensin II (10 nmol·L(-1)) was treated with the human equivalent of low (10 or 100 µmol·L(-1)) and high (1000 µmol·L(-1)) aspirin concentrations in plasma. Changes in the cardiac structure and function were assessed through echocardiography and transmission electron microscopy. Gene expression was determined through RT-PCR and western blot analysis. Results indicated that aspirin treatment abrogated the increased thickness of the left ventricular anterior and posterior walls, the swelling of mitochondria, and the increased surface area in in vivo and in vitro hypertrophy models. Aspirin also normalized the upregulated hypertrophic biomarkers, ß-myosin heavy chain (ß-MHC), atrial natriuretic peptide (ANP), and b-type natriuretic peptide (BNP). Aspirin efficiently reversed the upregulation of ß-catenin and P-Akt expression and the TAC- or ANG II-induced downregulation of GSK-3ß. Therefore, low-dose aspirin possesses significant anti-hypertrophic properties at clinically relevant concentrations for anti-thrombotic therapy. The downregulation of ß-catenin and Akt may be the underlying signaling mechanism of the effects of aspirin.

[Restoration of partial penile defect by scrotal skin flap in combination with penile lengthening].

OBJECTIVE: To evaluate the feasibility and clinical efficacy of a scrotal skin flap in combination with penile lengthening for repairing penile defects. METHODS: From 1999 to 2008, 7 cases (19 to 42 years old) of penile defects were treated by scrotal skin flap in combination with penile lengthening. The average preoperative length of stubbed penis was 2.1 cm in flaccid (range: 1.0 to 3.0 cm) and 4.8 cm in erection (range: 3.0 to 5.5 cm). All cases were treated with penile elongation. And a bilateral scrotal skin flap supplied by anterior scrotal artery (n = 3) or whole anterior scrotum flap (n = 4) was used to cover the exposed penile shaft. The scrotal incision was sutured directly. RESULTS: There was no need for urethra reconstruction. It was simple to obtain the scrotal skin flap. And the operation might be quickly performed with a lesser hemorrhage as compared with penile reconstruction. The scrotal flaps survived without any necrosis and all wounds healed primarily with an excellent contour and erectile function. When followed up for 1 - 5 years, the average preoperative penile length was 6.4 cm in flaccid (range: 5.0 to 7.5 cm) and 9.5 cm in erection (range: 8.0 to 10.5 cm). All cases had normal functions of urination, erection and gonobolia. Five cases had satisfied sexual life and one experienced a sexual life. CONCLUSIONS: The method of restoring partial penile defect with scrotal skin flaps is both simple and efficacious. Reasonable appearance and penile length are restored in most cases with better sensory and erectile functions.

[Anatomic research and clinical application of modified penile elongation: a report of 205 cases].

OBJECTIVE: To investigate the application of penile cavernous bodies elongation combined with fat flap for the treatment of micro-penis. METHODS: Anatomic study was performed to study the thickness of penile suspension ligaments and the relationship between the penile erection stability and the mobilization of cavernous bodies crus. The suspension ligaments were divided and cavernous bodies crus were partially mobilized, so as to release part of the cavernous bodies from inferior ramus of pubis. Then the penis was elongated sufficiently. Local fat flap was transposed to fill the front space of pubis to make sure the effective elongation of penis. RESULTS: 205 cases of micro-penis were treated. The average length of the penis was 4.26 cm in the static state, 8.13 cm in erectile state before operation. After operation, it increased to 8.63 cm in the static state, 12.11 cm in erectile state. CONCLUSIONS: The cavernous bodies can be elongated 1-2 cm more with the modified method, while the stability of penile erection is not affected.