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Peyronie's Disease (PD) is clinically characterized by the development of localized fibrous plaques, primarily on the tunica albuginea, especially on the dorsal area of the penis. These plaques are the hallmark feature of this condition, resulting in penile curvature, deformity, and painful erections for affected individuals. Although various nonsurgical treatment options exist, their overall effectiveness is limited. As a result, surgical intervention has become the ultimate choice for patients with severe penile curvature deformities and associated erectile dysfunction. Our research team has successfully employed a combined approach involving microscopic electric rotary grinding of the fibrous plaques and the use of tunica vaginalis or bovine pericardium as graft materials for the repairing of the defects of tunica albuginea in the treatment of PD. This approach has consistently yielded highly satisfactory results regarding the restoration of penile shape, with excellent cosmetic results and significantly improved sexual satisfaction. This protocol aims to present a comprehensive surgical management strategy utilizing electric rotary grinding of the plaques and repairing the defects of tunica albuginea by using the tunica vaginalis, which represents an optimal surgical strategy for treating PD.

Introduction: Early diagnosis of sepsis and discrimination from SIRS is crucial for clinicians to provide appropriate care, management and treatment to critically ill patients. We describe identification of mRNA biomarkers from peripheral blood leukocytes, able to identify severe, systemic inflammation (irrespective of origin) and differentiate Sepsis from SIRS, in adult patients within a multi-center clinical study., Methods: Participants were recruited in Intensive Care Units (ICUs) from multiple UK hospitals, including fifty-nine patients with abdominal sepsis, eighty-four patients with pulmonary sepsis, forty-two SIRS patients with Out-of-Hospital Cardiac Arrest (OOHCA), sampled at four time points, in addition to thirty healthy control donors. Multiple clinical parameters were measured, including SOFA score, with many differences observed between SIRS and sepsis groups. Differential gene expression analyses were performed using microarray hybridization and data analyzed using a combination of parametric and non-parametric statistical tools., Results: Nineteen high-performance, differentially expressed mRNA biomarkers were identified between control and combined SIRS/Sepsis groups (FC>20.0, p<0.05), termed 'indicators of inflammation' (I°I), including CD177, FAM20A and OLAH. Best-performing minimal signatures e.g. FAM20A/OLAH showed good accuracy for determination of severe, systemic inflammation (AUC>0.99). Twenty entities, termed 'SIRS or Sepsis' (S°S) biomarkers, were differentially expressed between sepsis and SIRS (FC>2·0, p-value<0.05)., Discussion: The best performing signature for discriminating sepsis from SIRS was CMTM5/CETP/PLA2G7/MIA/MPP3 (AUC=0.9758). The I°I and S°S signatures performed variably in other independent gene expression datasets, this may be due to technical variation in the study/assay platform., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Szakmany, Fitzgerald, Garlant, Whitehouse, Molnar, Shah, Tong, Hall, Ball and Kempsell.)

Objectives: The surge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron infections has affected most Chinese residents at the end of 2022, including a number of patients with systemic autoimmune rheumatic diseases (SARDs)., Methods: To investigate the antibody level of the Omicron variant in SARD patients after SARS-CoV-2 Omicron infection, we tested BA.5.2 and BF.7 Omicron variant IgG antibody levels using ELISA on blood samples collected from 102 SARD patients and 19 healthy controls (HCs). The type of SARD, demographics, concurrent treatment, doses of SARS-CoV-2 vaccines and outcomes were also recorded., Results: A total of 102 SARD patients (mean age: 40.3 years; 89.2% female), including 60 SLE, 32 RA and 10 other SARDs, were identified. Of these, 87 (85.3%) were infected with SARS-CoV-2. We found that the BA.5.2 and BF.7 antibody levels of infected SARD patients were lower than those of HCs ( P  <   0.05). Sixty-five (63.7%) patients had at least one dose of a SARS-CoV-2 vaccine. SARD patients with at least two doses of SARS-CoV-2 vaccine had a higher level of BA.5.2 and BF.7 antibodies than the unvaccinated group ( P  <   0.05). There was no evidence for a significant inhibitory effect of glucocorticoids (GCs) on the BA.5.2 and BF.7 Omicron variant antibody levels in SARD patients. SLE patients using biologic DMARDs had a lower BA.5.2 Omicron variant antibody level than patients using GCs and/or HCQ., Conclusion: These data suggest that patients with SARDs had a lower antibody response than HCs after Omicron infection., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS) of non-infectious origin. Sepsis presents with a range of pathophysiological and genetic features which make clinical differentiation from SIRS very challenging. This may reflect a poor understanding of the key gene inter-activities and/or pathway associations underlying these disease processes. Improved understanding is critical for early differential recognition of sepsis and SIRS and to improve patient management and clinical outcomes. Judicious selection of gene biomarkers suitable for development of diagnostic tests/testing could make differentiation of sepsis and SIRS feasible. Here we describe a methodologic framework for the identification and validation of biomarkers in SIRS, sepsis and septic shock patients, using a 2-tier gene screening, artificial neural network (ANN) data mining technique, using previously published gene expression datasets. Eight key hub markers have been identified which may delineate distinct, core disease processes and which show potential for informing underlying immunological and pathological processes and thus patient stratification and treatment. These do not show sufficient fold change differences between the different disease states to be useful as primary diagnostic biomarkers, but are instrumental in identifying candidate pathways and other associated biomarkers for further exploration., (Copyright © 2020 Tong, Kempsell, Szakmany and Ball.)

Accumulated genetic evidences indicate that the contactin associated protein-like (CNTNAP) family is implicated in autism spectrum disorders (ASD). In this study, we identified genetic mutations in the CNTNAP3 gene from Chinese Han ASD cohorts and Simons Simplex Collections. We found that CNTNAP3 interacted with synaptic adhesion proteins Neuroligin1 and Neuroligin2, as well as scaffolding proteins PSD95 and Gephyrin. Significantly, we found that CNTNAP3 played an opposite role in controlling the development of excitatory and inhibitory synapses in vitro and in vivo, in which ASD mutants exhibited loss-of-function effects. In this study, we showed that the male Cntnap3-null mice exhibited deficits in social interaction， spatial learning and prominent repetitive behaviors. These evidences elucidate the pivotal role of CNTNAP3 in synapse development and social behaviors, providing mechanistic insights into ASD., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To investigate the effects of glucose metabolism, insulin resistance, and inflammatory factors on International Prostatic Symptom Score (IPSS) of patients with benign prostatic hyperplasia (BPH), to explore their correlations and evaluate the clinical significance., Patients and Methods: 90 patients with BPH were selected and divided into normal blood glucose group and abnormal blood glucose group. The changes of indexes related to prostate function, prostate volume (PV), prostate-specific antigen (PSA), and IPSS in two groups were evaluated. The fasting blood glucose (FBS), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR) index and inflammatory factors interleukin-8 (IL-8) and cyclooxygenase 2 (COX-2) levels in expressed prostatic secretion (EPS) were compared. The correlations of glucose metabolism, insulin resistance and inflammatory factors with IPSS were analyzed by Logistic regression. The changes of these indexes after treatment of BPH were observed., Results: The FBS, FINS, HOMA-IR, and inflammatory factors IL-8 and COX-2 levels were significantly different between high IPSS group and low IPSS group of patients with BPH. Moreover, the PV and PSA were higher in high IPSS group than those in low IPSS group. The FBS, FINS and inflammatory factors IL-8 and COX-2 levels were positively correlated with IPSS (p<0.05). All the indexes above of BPH patients were decreased after treatment., Conclusions: The FBS, FINS, and inflammatory factors IL-8 and COX-2 levels are closely correlated with IPSS, which can reflect the severity and prognosis of BPH. It can effectively postpone the progression of BPH by lowering blood glucose, improving insulin resistance, and controlling the expressions of inflammatory factors in serum through a healthy lifestyle and clinical comprehensive treatment.

Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development. Importantly, two autism-associated truncations, R205X and E239X, were shown to be Dyrk1a loss-of-function mutants. Studies of the truncated Dyrk1a mutants may provide new insights into the role of Dyrk1a in brain development, as well as the role of Dyrk1a loss of function in the pathophysiology of autism.

Batch experiments were conducted to investigate the effect of soluble and insoluble decomposing products (decomposed for 1 day and 120 day; noted by DP1 and DP120, respectively) from immobilized carriers (corncob) on the desorption of pyrene in PAH-contaminated soil (120 d ageing, 20 mg x kg(-1)). It was found that (1) adding decomposing products of immobilized carriers could not only increase the rapidly desorbing fraction, but also improve the desorption rate of pyrene. The desorption rates of pyrene increased from 20% to 81.8% and 84.5% because of adding insoluble DP1 and DP120, and from 40% to 89.6% and 88.5% because of adding soluble DP1 and DP120. (2) The sorption amounts of pyrene by insoluble DP1 and.DP120 were 9. 4 and 16. 6 times higher than that by natural corncob, respectively. The sorption amounts of XAD-2 resins were increased by 1.5 and 3.1 times due to the added soluble DP1 and DP120, respectively. These results indicated that decomposing products of immobilized carries could improve the desorption of pyrene by sorption or activation in contaminated soil.

The dramatic increase in the complexity of flow cytometric datasets requires new computational approaches that can maximize the amount of information derived and overcome the limitations of traditional gating strategies. Herein, we present a multivariate computational analysis of the HIV-infected flow cytometry datasets that were provided as part of the FlowCAP-IV Challenge using unsupervised and supervised learning techniques. Out of 383 samples (stimulated and unstimulated), 191 samples were used as a training set (34 individuals whose disease did not progress, and 157 individuals whose disease did progress). Using the results from the training set, the participants in the Challenge were then asked to predict the condition and progression time of the remaining individuals (45 "nonprogressors" and 147 "progressors"). To achieve this, we first scaled down data resolution and then excluded doublet cells from the analysis using Expectation Maximization approaches. We then standardized all samples into histograms and used Genetic Algorithm-Neural Network to extract feature sets from the datasets, the reliability of which were examined using WEKA-implemented classifiers. The selected feature set resulted in a high sensitivity and specificity for the discrimination of progressors and nonprogressors in the training set (average True Positive Rate = 1.00 and average False Positive Rate = 0.033). The capacity of the feature set to predict real-time survival time was better when using data from the "unstimulated" training set (r = 0.825). The P-values and 95% confidence interval log-rank ratios between actual and predicted survival time in the test set were 0.682 and 0.9542 ± 0.24 for the unstimulated dataset, and 0.4451 and 0.9173 ± 0.23 for the stimulated dataset. Our analytic strategy has demonstrated a promising capacity to extract useful information from complex flow cytometry datasets, despite a significance imbalance and variation between the training and test sets., (© 2015 International Society for Advancement of Cytometry.)

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI)., Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model., Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing's sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen., Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas.

Background: Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood., Results: Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically., Conclusions: Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models.

Mitochondrial damage plays an important role in mediating postburn cardiac injury. To elucidate the pivotal mitochondrial proteins and pathways underlying postburn cardiac injury, mitochondria were purified from control and postburn rat hearts. 2-dimensional gel electrophoresis (2-DE) and HPLC-chip-MS/MS analyses revealed 9 differentially expressed proteins, 3 of which were further validated by Western blotting. The differential expression of these mitochondrial proteins was accompanied by increased levels of oxidative cardiac damage and decreased levels of cardiac output. One of the differentially expressed proteins, mitochondria translation elongation factor Tu (EF-Tumt), was hypothesized to contribute crucially to postburn oxidative cardiac damage. The small interfering RNA (siRNA)-mediated downregulation of EF-Tumt in cultured rat cardiomyocytes increased reactive oxygen species (ROS) generation and protein carbonyl levels, and led to cell damage. The potential pathway of this process was associated with respiratory chain complex I deficiency. Together, these results demonstrate the mitochondrial responses to severe burn, and indicate a pathway by which decreased EF-Tumt expression mediates oxidative damage in postburn myocardium., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To retrospectively analyze the effect of restrictive fluid management strategy (RFMS) on the early pulmonary function and the prognosis of patients with extremely severe and extensive burn., Methods: Thirteen patients with extremely severe burn hospitalized from June 2010 to November 2011, being treated with RFMS in the fluid reabsorption stage, were enrolled as treatment group. Twenty-six patients with extremely severe burn hospitalized from March 2008 to November 2011, being treated with normal fluid therapy in the fluid reabsorption stage, were enrolled as control group. The match proportion between treatment group and control group was 1:2. Fluid intake, fluid output, fluid balance (the difference between fluid intake and output), and plasma albumin level from post burn day (PBD) 3 to 10, pulmonary oxygenation index on PBD 3, 5, 7, 10, and 14, occurrence of lung and blood stream infections from PBD 7 to 14, and occurrence of acute respiratory distress syndrome (ARDS), occurrence of other organ complications, and mortality within 2 weeks post burn (PBW) were recorded and compared. Measurement data were processed with t test and randomized blocks analysis of variance, enumeration data were processed with Fisher's exact test., Results: Daily fluid intake of patients showed a tendency of decrease in both groups from PBD 3 to 10. Except for that of PBD 4, there was no statistically significant difference between two groups in fluid intake (with F values from 0.072 to 1.939, P values all above 0.05). Daily fluid output of patients showed a tendency of increase in both groups from PBD 3 to 10. It peaked on PBD 10 in control group and PBD 6 in treatment group. The mean daily fluid output was higher in treatment group than in control group from PBD 4 to 9, but without statistically significant difference (with F values from 0.001 to 3.026, P values all above 0.05). Fluid balance lowered in both groups, and it was the lowest on PBD 10 in control group and PBD 6 in treatment group. Fluid balance was lower in treatment group than in control group from PBD 3 to 7, and it showed statistically significant differences on PBD 4, 5, and 6 (with F values from 4.799 to 8.031, P values below 0.05). Plasma albumin level was higher in treatment group than in control group from PBD 3 to 10, with statistically significant differences observed on PBD 4, 9, and 10 (with F values from 5.691 to 10.551, P < 0.05 or P < 0.01). Pulmonary oxygenation index was higher in treatment group than in control group from PBD 3 to 14, with statistically significant differences observed on PBD 7 (respectively 372 ± 78 in treatment group and 291 ± 92 in control group, F = 5.184, P < 0.05) and 14 (respectively 354 ± 39 in treatment group and 283 ± 72 in control group, F = 8.683, P < 0.05). Lung infection and blood stream infection were respectively observed in 1 and 4 patient (s) in treatment group, and 9 and 11 patients in control group from PBD 7 to 14. Occurrence of ARDS, occurrence of other organ complications, and mortality were fewer in treatment group than in control group within PBW 2, though the differences were not statistically significant (P values all above 0.05)., Conclusions: RFMS is a useful strategy in improving early pulmonary oxygenation of patients with extremely severe and extensive burn by promoting the process of fluid reabsorption and rebalance. This strategy may be also beneficial for the prevention of organ complications as well as a better prognosis in severely burned patients.

Previous studies on heart growth and development have elucidated important gene- and cellular-level changes. The development of improved biochemical, mathematical, and computational methods has enabled more accurate elaboration of the structural and functional processes of the heart. Systematic analyses of heart complexity have revealed the differences between normal and pathological growth and development in terms of self-organizational ability, energy balance, clock regulation, and heart rate variability. The present study summarizes what is known about cardiac behaviors and characteristics during heart growth and development. The results indicate that the heart demonstrates systematic complexity, and suggest that new characteristic analyses and treatments of heart diseases can be expected in the future.

Background/aims: Nicotinamide plays a protective role in hypoxia-induced cardiomyocyte dysfunction. However, the underlying molecular mechanisms remain poorly understood. The purpose of this study was to investigate these and the effect of nicotinamide pretreatment on hypoxic cardiomyocytes., Methods: Cultured rat cardiomyocytes were pretreated with nicotinamide, subjected to hypoxia for 6 h, and then cell necrosis and apoptosis were examined. The effects of nicotinamide pretreatment on hypoxia-induced reactive oxygen species (ROS) formation, antioxidant enzyme expression, nicotinamide adenine dinucleotide (NAD(+)) and nicotinamide adenine dinucleotide phosphate (NADP(+)) levels, adenosine triphosphate (ATP) production and mitochondrial membrane potential were tested to elucidate the underlying mechanisms., Results: Based on the findings that nicotinamide treatment decreased protein expression of receptor-interacting protein (RIP; a marker for cell necrosis) and cleaved caspase-3 (CC3; a marker for cell apoptosis) in normoxic cardiomyocytes, we found that it dramatically reduced hypoxia-induced necrosis and apoptosis in cardiomyocytes. The underlying mechanisms of these effects are associated with the fact that it increased protein expression of superoxide dismutase and catalase, increased intracellular levels of NAD(+) and ATP concentration, decreased mitochondrial ROS generation and prevented the loss of mitochondrial membrane potential., Conclusion: All of these results indicate that nicotinamide pretreatment protects cardiomyocytes by improving mitochondrial stress. Our study provides a new clue for the utilization of nicotinamide in therapies for ischemic heart disease., (Copyright © 2012 S. Karger AG, Basel.)

Introduction: Raw spectral data from matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) with MS profiling techniques usually contains complex information not readily providing biological insight into disease. The association of identified features within raw data to a known peptide is extremely difficult. Data preprocessing to remove uncertainty characteristics in the data is normally required before performing any further analysis. This study proposes an alternative yet simple solution to preprocess raw MALDI-TOF-MS data for identification of candidate marker ions. Two in-house MALDI-TOF-MS data sets from two different sample sources (melanoma serum and cord blood plasma) are used in our study., Method: Raw MS spectral profiles were preprocessed using the proposed approach to identify peak regions in the spectra. The preprocessed data was then analysed using bespoke machine learning algorithms for data reduction and ion selection. Using the selected ions, an ANN-based predictive model was constructed to examine the predictive power of these ions for classification., Results: Our model identified 10 candidate marker ions for both data sets. These ion panels achieved over 90% classification accuracy on blind validation data. Receiver operating characteristics analysis was performed and the area under the curve for melanoma and cord blood classifiers was 0.991 and 0.986, respectively., Conclusion: The results suggest that our data preprocessing technique removes unwanted characteristics of the raw data, while preserving the predictive components of the data. Ion identification analysis can be carried out using MALDI-TOF-MS data with the proposed data preprocessing technique coupled with bespoke algorithms for data reduction and ion selection.

Corticotropin releasing factor (CRF) is considered as the central driving force in the stress response and plays a key role in the pathogenesis of depression. CRF neurons have been identified to locate in most regions of the prefrontal cortex (PFC), a brain region that is highly associated with the control of emotion and cognition. However, little is known on the regulation of CRF in this region. In this study, we aimed to identify the regulatory effect of acute restraint stress and glucocorticoid on PFC CRF and characterize the possible function of CRF in the PFC. We found that acute restraint stress increased and glucocorticoid decreased PFC CRF mRNA expression. The expression of glucocorticoid receptor (GR) was found to colocalize with CRF neurons in the PFC. In addition, recruitment of GR by the CRF promoter was observed in vivo. Specific attention was paid to the effect of CRF on CRF receptor 1 (CRFR1) expression in primary PFC cultures. The results showed that CRF increased CRFR1 expression through the MEK-ERK1/2 pathway. In summary, this study may contribute to the better understanding of CRF functions in the PFC., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)