DNA Hyper-methylation Associated With Schizophrenia May Lead to Increased Levels of Autoantibodies.

Background and Hypothesis: Environmental stressors may influence immune surveillance in B lymphocytes and stimulate autoimmune responses via epigenetic DNA methylation modifications in schizophrenia (SCZ). Study Design: A total of 2722, Chinese Han origin subjects were recruited in this study (2005-2011), which included a discovery follow-up cohort with 40 remitters of SCZ (RSCZ), 40 nonremitters of SCZ (NRSCZ), and 40 controls (CTL), and a replication follow-up cohort (64 RSCZ, 16 NRSCZ, and 84 CTL), as well as a case-control validation cohort (1230 SCZ and 1208 CTL). Genomic DNA methylation, target gene mRNA transcripts, and plasma autoantibody levels were measured across cohorts. Study Results: We found extensive differences in global DNA methylation profiles between RSCZ and NRSCZ groups, wherein differential methylation sites (DMS) were enriched with immune cell maturation and activation in the RSCZ group. Out of 2722 participants, the foremost DMS cg14341177 was hyper-methylated in the SCZ group and it inhibited the alternative splicing of its target gene BICD2 and may have increased its autoantigen exposure, leading to an increase in plasma anti-BICD2 IgG antibody levels. The levels of cg14341177 methylation and anti-BICD2 IgG decreased significantly in RSCZ endpoint samples but not in NRSCZ endpoint samples. There are strong positive correlations between cg14341177 methylation, anti-BICD2 IgG, and positive and negative syndrome scale (PANSS) scores in the RSCZ groups, but not in the NRSCZ groups. Conclusions: These data suggest that abnormal DNA methylation could affect autoreactive responses in SCZ, and that cg14341177 methylation and anti-BICD2 IgG levels may potentially serve as useful biomarkers.

The impact of family function on post-traumatic reactions of Chinese adolescents infected with COVID-19: a latent profile study.

Background: Since the end of 2019, Corona Virus Disease 2019, also known as COVID-19, has broken out in various countries. However, the change of China's COVID-19 prevention and control policy and the sharp increase in the number of infected people are making the teenagers have post-traumatic reactions. Negative post-traumatic reactions include: post-traumatic stress disorder (PTSD), depression, anxiety. Positive post-traumatic reaction mainly refers to post-traumatic growth (PTG). The purpose of this study is to explore the post-traumatic reaction, which refers to PTSD, depression, anxiety and the co-occurrence pattern of growth after trauma and to further explore the influence of family function on different categories of Post-traumatic Reactions. Methods: Latent profile analysis (LPA) was used to explore the co-occurrence of PTSD, depression, anxiety, and PTG. Multiple logistics regression was used to analyze the influence of family function on different categories of post-traumatic response. Results: There were three categories of post-traumatic reactions in adolescents infected with COVID-19 adolescents infected with COVID-19, namely: growth class, struggling class, and pain class. Multivariate Logistic regression showed that the growth class and struggling class were affected by problem solving and behavior control in family function, while the growth class and pain class were affected by problem solving, roles, behavior control, and general functioning. Multiple logistic regression showed that the growth class and struggling class were affected by problem solving and roles. Conclusions: The findings of this study provide evidence for the identification of high-risk individuals and the provision of effective interventions in clinical practice, as well as the influence of family functioning on the different categories of PTSD among adolescents infected with COVID-19.

Corrigendum to "Giant squamous cell carcinoma of penis with rapid progression" [Urol. Case Rep. 34 (2021) 101496].

[This corrects the article DOI: 10.1016/j.eucr.2020.101496.].

Corrigendum to "Basal cell carcinoma arising from the scrotum: An understated entity" [Urol Case Rep 33 (2020) 101332].

[This corrects the article DOI: 10.1016/j.eucr.2020.101332.].

The SFT2D2 gene is associated with the autoimmune pathology of schizophrenia in a Chinese population.

Background: The relative risk of GWAS-confirmed loci strongly associated with schizophrenia may be underestimated due to the decay of linkage disequilibrium between index SNPs and causal variants. This study is aimed to investigate schizophrenia-associated signals detected in the 1q24-25 region in order to identify a causal variant in LD with GWAS index SNPs, and the potential biological functions of the risk gene. Methods: Re-genotyping analysis was performed in the 1q24-25 region that harbors three GWAS index SNPs associated with schizophrenia (rs10489202, rs11586522, and rs6670165) in total of 9801 case-control subjects of Chinese Han origin. Circulating autoantibody levels were assessed using an in-house ELISA against a protein derived fragment encoded by SFT2D2 in total of 682 plasma samples. Results: A rare variant (rs532193193) in the SFT2D2 locus was identified to be strongly associated with schizophrenia. Compared with control subjects, patients with schizophrenia showed increased anti-SFT2D2 IgG levels. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.803 with sensitivity of 28.57% against specificity of 95% for the anti-SFT2D2 IgG assay. Discussion: Our findings indicate that SFT2D2 is a novel gene for risk of schizophrenia, while endogenous anti-SFT2D2 IgG may underlie the pathophysiology of the immunological aspects of schizophrenia.

Giant squamous cell carcinoma of penis with rapid progression.

A 65-year-old man presented with a giant ulcerative and malodorous genital mass rapidly growing for 5 months. On first presentation, he noticed a 3 cm × 2 cm cauliflower-like mass located in the penile dorsal shaft. But, he rejected any operation. Unfortunately, the lesion became aggressive and eventually destroyed the entire penile shaft and urethra within a five-month period. He underwent a radical penectomy, scrotal extended resection, formation of a perineal urethrostomy and left inguinal lymph node biopsy. Pathology revealed poor-differentiated invasive squamous cell carcinoma. The patient had an uneventful recovery.

Basal cell carcinoma arising from the scrotum: An understated entity.

Basal cell carcinoma (BCC) is the most commonly occurring carcinoma among humans. Reports of this lesion on nonexposed areas, such as the scrotum, soles, vulva, groin, pubic region, and axilla, are relatively uncommon. We present the case of a male patient with BCC located in the scrotum with a duration of 12 years who was successfully treated by local excision. Histopathology revealed infiltration by BCC. Our objective of this report is to remind specialists like urologists of the possibility of scrotal BCC when encountering scrotal lesions of unknown origin or not responding to topical treatments in a reasonable time frame.

miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke.

Stroke is a leading cause of death and disability worldwide. The purpose of this study was to investigate the possible role of the microRNA (miRNA or miR) miR-137 in ischemic stroke. miRNAs are very stable in the blood and may serve as potential diagnostic and therapeutic markers. Wild-type, Src-/- and miR-137-/- mice were treated with p38 siRNA or Erk2 siRNA to identify their roles in the inflammatory response, oxidative stress, neuronal injury and cognitive impairment in brain tissues of mice following middle cerebral artery occlusion (MCAO) operation. We evaluated several factors including; inflammatory responses, oxidative stress, viability and apoptosis of astrocytes in order to identify the functions of miR-137 and Src in ischemic stroke. miR-137 alleviated the inflammatory response, oxidative stress, neuronal injury and cognitive impairment, and restricted apoptosis via targeting Src and inactivating the MAPK signaling pathway. Furthermore, up-regulation of miR-137 or inhibition of Src inhibited the secretion of inflammatory factors, suppressed oxidative stress, and reduced apoptosis of astrocytes. In conclusion, our work suggests that, in mice, miR-137 confers neuroprotective effects against ischemic stroke via attenuation of oxidative, apoptotic, and inflammatory pathways through inhibiting Src-dependent MAPK signaling pathway.

Correction to: Overexpression of Shrm4 promotes proliferation and differentiation of neural stem cells through activation of GABA signaling pathway.

The original publication of the article includes an error in Fig. 2. The correct version of the Fig. 2 is provided in this correction.

Downregulation of MicroRNA-494 inhibits the TGF-ß1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.

BACKGROUND: Hypospadias, as a congenital disorder of the urethra, is the second most common birth abnormality of the male reproductive system. This study primarily investigates the effects of microRNA-494 (miR-494) on the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway and on the development of hypospadias by binding to neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4L). METHODS: We induced a mouse model of hypospadias through di-(2-ethylhexyl) phthalate treatment. The underlying regulatory mechanisms of miR-494 in this model were analyzed upon treatment of miR-494 mimic, miR-494 inhibitor, or small interfering RNA against Nedd4L in urethral epithelial cells isolated from mice with hypospadias. We then verified the binding site between miR-494 and Nedd4L and applied a gain- and loss-of-function approach to determine the effects of miR-494 on cell proliferation, cycle distribution, and apoptosis. RESULTS: Male mice with hypospadias exhibited significantly higher miR-494 expression and lower Nedd4L expression in urethral tissues than normal male mice. Nedd4L was verified as a target gene of miR-494. Treatment with miR-494 inhibitor suppressed the activation of the TGF-ß1/Smads signaling pathway, whereas down-regulation of miR-494 exerted protective effects on urethral epithelial cells by impeding cell proliferation and inducing cell apoptosis. CONCLUSIONS: The study indicates that downregulation of miR-494 inhibits the TGF-ß1/Smads signaling pathway and prevents the development of hypospadias through upregulating Nedd4L.

The underlying changes and predicting role of peripheral blood inflammatory cells in severe COVID-19 patients: A sentinel?

BACKGROUND: The underlying changes of peripheral blood inflammatory cells (PBICs) in COVID-19 patients are little known. Moreover, the risk factors for the underlying changes of PBICs and their predicting role in severe COVID-19 patients remain uncertain. MATERIAL AND METHODS: This retrospective study including two cohorts: the main cohort enrolling 45 patients of severe type serving as study group, and the secondary cohort enrolling 12 patients of no-severe type serving as control group. The PBICs analysis was based on blood routine and lymphocyte subsets. The inflammatory cell levels were compared among patients according to clinical classifications, disease-associated phases, as well as one-month outcomes. RESULTS: Compared with patients of non-severe type, the patients of severe type suffered from significantly decreased counts of lymphocytes, eosinophils, basophils, but increased counts of neutrophils. These PBICs alterations got improved in recovery phase, but persisted or got worse in aggravated phase. Compared with patients in discharged group, the patients in un-discharged/died group suffered from decreased counts of total T lymphocytes, CD4 + T lymphocytes, CD8 + T lymphocytes, as well as NK cells at 2 weeks after treatment. Clinical classification-critically severe was the independently risk factor for lymphopenia (OR = 7.701, 95%CI:1.265-46.893, P = 0.027), eosinopenia (OR = 5.595, 95%CI:1.008-31.054, P = 0.049), and worse one-month outcome (OR = 8.984; 95%CI:1.021-79.061, P = 0.048). CONCLUSION: Lymphopenia and eosinopenia may serve as predictors of disease severity and disease progression in COVID-19 patients, and enhancing the cellular immunity may contribute to COVID-19 treatment. Thus, PBICs might become a sentinel of COVID-19, and it deserves attention during COVID-19 treatment.

Overexpression of Shrm4 promotes proliferation and differentiation of neural stem cells through activation of GABA signaling pathway.

Shrm4 is a protein that is exclusively expressed in polarized tissues. The physiological function of Shrm4 in the brain was required to be elucidated. Thus, we aimed to explore how the Shrm4-mediated gamma-aminobutyric acid (GABA) pathway affected neural stem cells (NSCs). At first, the Nestin expression in cultured NSCs was identified. After determination of the interaction of Shrm4 and GABAB1, a series of in vitro experiment were performed to detect cell proliferation, the ability of cell colony formation, degree that NSCs differentiated into neurons, the apoptosis rate, and cell cycle. The levels of Shrm4, GABAB1, Bcl-2-associated protein x (Bax), B cell lymphoma 2 (Bcl-2), cleaved Caspase-3, microtubule-associated protein 2 (MAP-2) as well as suppressor of cytokine signaling 2 (SOCS2) were detected to further assess the role of Shrm4 and GABA pathway in NSCs. Initially, we found that Shrm4 could bind to GABAB1, and overexpression of Shrm4 or activation of GABAB1 increased the number of positive cells, and promoted cell viability, colony formation rate and differentiation of NSCs. After overexpression of Shrm4 or activation of GABAB1, cells in the G1 phase were decreased, while those in the S phase were increased with an inhibited cell apoptosis rate in the NSCs. Besides, the overexpression of Shrm4 or activation of GABAB1 upregulated the levels of Shrm4, GABAB1, Bcl-2, MAP-2 and SOCS2, while downregulated Bax and cleaved Caspase-3 in NSCs. Overall, overexpression of Shrm4 activated GABAB1 to stimulate the proliferation and differentiation of NSCs. Thus, Shrm4 might be considered as a novel target for promoting the proliferation and differentiation of NSCs.

Reducing PRLR expression and JAK2 activity results in an increase in BDNF expression and inhibits the apoptosis of CA3 hippocampal neurons in a chronic mild stress model of depression.

Patients suffering from depression most commonly present with symptoms associated with the autonomic nervous system. Despite the satisfactory results achieved following treatment with vagus nerve stimulation and drug treatment, recurrence is a common occurrence in many patients. As described in numerous studies, prolactin receptor (PRLR) has been identified as an anxiolytic and anti-depressant factor in depression. However, the effect of PRLR on chronic mild stress (CMS)-induced depression remains to be thoroughly demonstrated. Therefore, the present study was conducted on the effect of PRLR gene on brain derived neurotrophic factor (BDNF) expression and hippocampal neuron apoptosis through the establishment of CMS-induced depression mouse models, with aims of providing a new and effective therapeutic option for depression. Microarray-based analysis was initially used to retrieve depression-related expression dataset and PRLR-related signaling pathway. Lentiviral vectors overexpressing PRLR or expressing PRLR-specific shRNA were used to up- or down-regulated the expression of PRLR in mice. Subsequently, the effects of PRLR on hippocampal neurons and pyramidal cells in CA1 and CA3 regions, and ultrastructure in hippocampal region were evaluated. Serum BDNF level and the positive rate of cleaved-Caspase-3 in hippocampal CA3 region were determined. Next, the regulatory mechanism by which PRLR gene silencing influences hippocampal neuron apoptosis via the JAK2-STAT5 signaling pathway was detected. PRLR gene was assumed to participate in the development of depression by regulating the JAK-STAT signaling pathway. Our results found that the mice with CMS-induced depression exhibited locomotion activity and anhedonia. In addition, a decrease in the number of pyramidal cells was observed in the hippocampus while that of apoptotic cells was increased. In addition, serum BDNF level was increased, and the expression of Caspase-3 and Bax in hippocampal neurons and the JAK2-STAT5 signaling pathway was decreased in response to PRLR silencing, along with increased expression of BDNF and Bcl-2. From the aforementioned findings, we concluded that PRLR gene silencing results in the inhibition of hippocampal neuron apoptosis and alleviation of CMS-induced depression by inactivating the JAK2-STAT5 signaling pathway and elevating BDNF expression, providing a new insight for the treatment of depression.

Embryonal rhabdomyosarcoma of the epididymis presenting as epididymitis: A case report.

Paratesticular rhabdomyosarcoma (RMS) is an extremely rare malignancy in adults, accounting for 7% of all RMS cases and 6% of all non-germinal intrascrotal tumors. The clinical signs are similar to those of a hydrocele or testicular tumor, typically presenting as a unilateral, painless mass in the inguinal canal or scrotum. No specific serum markers are currently available for this tumor. RMS of the epididymis is extremely rare. Particularly when it is associated with epididymitis, this malignancy is usually overlooked. We herein present a case of epididymal embryonal RMS, manifesting an painful scrotal edema, misdiagnosed as epididymitis. The patient received 3 cycles of adjuvant chemotherapy postoperatively and remained disease-free after 4 years of follow-up.

[Relationship of MTHFR gene polymorphisms with infertility].

The folate metabolic pathway plays important roles in cellular physiology by participating in nucleotide synthesis, DNA repair and methylation, and maintenance and stability of the genome. Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme involved in folate metabolism. Polymorphisms of MTHFR may change the level of homocysteine and affect DNA synthesis and methylation, leading to an increased oxidative stress and disturbed methylation reactions and consequently affecting reproductive function. This article presents an overview on MTHFR gene polymorphisms, proposing that multicentered, large-sample and long-term prospective studies are needed to reveal the relationship between MTHFR gene polymorphisms and infertility.

Adenomatoid Tumor of the Tunica Albuginea in a Boy: A Case Report and Literature Review.

Adenomatoid tumors (AT) are the most common paratesticular neoplasms and account for approximately 30% of all paratesticular masses. Most of them occur in the third or fourth decade and present as well-defined firm and painless masses. We report here a case of adenomatoid tumor from tunica albuginea. This patient is a 12-year-old boy with left testicular pain for 6 months. Scrotal ultrasonography revealed a solid mass of paratesticular origin. The histology and immunohistochemistry confirmed the final diagnosis. A right tumor resection was performed. Because of its rarity, the clinical and histopathologic appearance is seldom illustrated. Here we present a case report and a comprehensive literature review with the objective of providing useful information on this entity.

A rare case of bilateral sequential spermatocytic seminoma.

Spermatocytic seminoma (SS) is a rare testicular neoplasm characterized by a palpable, painless, slowly enlarging mass in the testis. Even more rare is a synchronous bilateral presentation. Only eight cases of bilateral SS have been reported in the literature, of which three cases were present with synchronous testis enlargement, and five were sequential. Here, we report an additional case of synchronous bilateral SS and present a comprehensive relevant literature review concerning clinical features, histopathology, and treatment.

Liposarcoma of the spermatic cord mimicking a left inguinal hernia: a case report and literature review.

Liposarcoma of the spermatic cord (LSC) is a rare condition characterized by a painless inguinal or scrotal mass. To our knowledge, only about 200 cases have been previously reported in the literature. These tumors are often mistaken for common scrotal swellings, such as hydroceles and hernias. We present a LSC case in which a definitive diagnosis was obtained upon histological examination. We also provide a literature review of other cases that have been reported.