The Alzheimer's disease-associated gene TREML2 modulates inflammation by regulating microglia polarization and NLRP3 inflammasome activation

Triggering receptor expressed on myeloid cells-like 2(TREML2)is a newly identified susceptibility gene for Alzheimer's disease(AD).It encodes a microglial inflammation-associated receptor.To date,the potential role of mic roglial TREML2 in neuroinflammation in the context of AD remains unclear.In this study,APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression.In addition,lipopolysaccharide(LPS)stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD.Our res ults show that TREML2 levels gradually increased in the brains of AP P/PS1 mice during disease progression.LPS stimulation of primary microglia led to the release of inflammato ry cytokines including interleukin-1β,inte rleukin-6,and tumor necrosis factor-a in the culture medium.The LPS-induced mic roglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knoc kdown.LPS increased the levels of mic roglial M1-type polarization marker inducible nitric oxide synthase.This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown.Furthermore,the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown.LPS stimulation increased the levels of NLRP3 in primary microglia.The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown.In summary,this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation.These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

Psychological burden prediction based on demographic variables among infertile men with sexual dysfunction

There has been increasing interest in the psycho-socio-relational and sexual disorders of infertility,as the risk of psychological burden among in fertile men with sexual dysf un ctio ns is sign ifica nt.The purpose of this study was to develop and to validate a predictive model to estimate in dividual psychological burde n among in fertile men with sexual dysf unction and study the associati on betwee n them.Comprehe nsive data were collected for in fertile men(n=480)who sought treatme nt for infertility in a reproductive medici ne center between June 2012 and December 2013.Using independent predictors of psychological burden from the least absolute shrinkage and selection operator,univariable and multivariable analyses were developed into two models.Predictive accuracy was compared between the models.We explored the association between sexual dysfunction and psychological burden.A total of 480 patie nts were an a lyzed using 10-fold cross-validatio n.In depende nt predictors of psychological burde n were incorporated into a model to measure anxiety(corrected-area under curve(AUC):77.3%)and a model to measure depression(corrected-AUC:70.2%).Anxiety and depression were both associated with erectile dysfunction(P<0.05),with anxiety demonstrating the strongest association.Only anxiety was associated with premature ejaculation(P>0.05).Premature ejaculation was not found to be associated with depression(P>0.05).Predictive models for psychological burden among infertile men with sexual dysfunction are presented,and we found that there is an association between psychological burden and sexual dysfunction.According to the models,proper counseling and treatment of sexual dysfunction in infertile men may reduce the psychological burden,help attain natural pregnancy,and improve the quality of life.

An alternative surgical technique for varicoceles:a preliminary experience of the microsurgical spermatic(distal end)-inferior or superficial epigastric vein anastomosis in symptomatic varicoceles associated with perineal pain

Many therapies are effective in treating varicoceles,including dilation of the pampiniform plexus in males.The most common method of treatment is varicocelectomy.We aimed to assess an alternative technique(microsurgical spermatic[distal end]-superficial or inferior epigastric vein anastomosis)that preserves the normal blood flow pattern for varicocele treatment.We retrospectively analyzed 27 men with varicocele between October 2019 and July 2020.All patients underwent microsurgical spermatic(distal end)-superficial or inferior epigastric vein anastomosis.The prognosis was reviewed retrospectively with an additional survey conducted 3 months after surgery.The mean±standard deviation of the age was 26.1±7.3 years in patients with microsurgical spermatic(distal end)-superficial or inferior epigastric vein anastomosis.The maximum diameter of the varicocele vein,perineal pain score,sperm density,and forward movement of sperm improved over 3 months after surgery.Microsurgical spermatic(distal end)-superficial or inferior epigastric vein anastomosis is a safe and efficient surgical treatment for varicoceles.