Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug for fibrosis. Here, unilateral ureteral obstruction (UUO)-treated mice and a TGF-β1-treated human renal tubular epithelial cell line (HK-2 cells) were used as models of renal fibrosis. Based on the changes of mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted as a potential drug to alleviate renal fibrosis through bioinformatics. We dissolved UUO mice with MK-2206 by gastric gavage and cultured TGF-β-induced HK-2 cells with MK-2206. Histopathological examinations were performed after MK-2206 intervention, and the degree of renal fibrosis, as well as the expression of Akt/mTOR pathway-related proteins, were evaluated by immunohistochemical staining, immunofluorescence staining, and Western blot. The results showed that MK-2206 significantly improved the pathological structure of the kidney. Furthermore, MK-2206 intervention effectively inhibited UUO- and TGF-β1-induced epithelial-mesenchymal transition, fibroblast activation, and extracellular matrix deposition. Mechanistically, MK-2206 treatment attenuated the activation of the Akt/mTOR signaling pathway. Taken together, our study revealed for the first time that MK-2206 is a promising drug for the improvement of renal fibrosis.

It has been recognized that the incidence of prostatic utricle in boys is increasing and is closely associated with diseases such as hypospadias. However, the clinical features of prostatic utricle with normal external genitalia have received little attention. Based on this, a series of 22 male children with prostatic utricles has been compiled by adding our 3 patients to 19 cases reported. All children enrolled had normal external genitalia. Clinical data of the case was reviewed. Urinary tract infection, purulent urethral discharge and pyuria were the most common presenting chief complaint (41%), irritative lower urinary tract symptoms were present in 17% of cases, obstructive lower urinary tract symptoms were noted in 14%. Urinary retention has been reported in 18% and epididymitis has been reported in 14%. Relatively rare clinical symptoms are abdominal pain, hematuria, and hematospermia. A case of calculus formation and a case of neoplasia within the prostatic utricle has been reported. A cystic mass found by digital rectal examination is the most common presenting sign. A utricular lesion posterior to the bladder was revealed by imaging examination. Unilateral renal agenesis was associated in 32% of reports. Non-surgical approach was chosen in 3 cases, transrectal ultrasonography guided aspiration has been reported in 1 case. Endoscopic techniques were used in 3 cases. Open excision was used in 11 cases. The laparoscopic excision was chosen in 3 cases and Robot-assisted laparoscopy was reported in 1 case. Symptoms and signs disappeared after treatment in all children, and no recurrence occurred during follow-up. Prostate utricles without external genital anomalies are rarely reported in children, and are easily missed and misdiagnosed, often accompanied by recurrent urinary tract infections, lower urinary tract symptoms, epididymitis, dysuria and other symptoms. Imaging studies can confirm the diagnosis. Symptomatic and large utricles should be actively treated. The treatment program should be based on the age, clinical symptoms, and size and location of the utricle.

Background: Investigations regarding the association between maternal smoking and specific urogenital teratogenesis exist. However, an integrated systematic review and meta-analysis studying the relationship by encompassing the whole urogenital system is essential.Objective: Even though many studies about inborn urogenital malformations have been conducted, its etiologic factors and exact pathogenesis are still unclear. Our aim is to assess the risk of congenital urogenital malformations in offspring of smoking pregnant women.Results: The meta-analysis, covering 41 case-control and 11 cohort studies, suggested that maternal smoking was associated with an increased risk of urogenital teratogenesis (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.04–1.23, p = 0.005), cryptorchidism (OR = 1.18, 95%CI: 1.12-1.24, p = 0.0001), hypospadias (OR = 1.16, 95%CI: 1.01-1.33, p = 0.039), and kidney malformations (OR = 1.30, 95%CI: 1.14-1.48, p = 0.0001). Moreover, paternal smoking during the mother’s pregnancy was also significantly associated (OR = 1.26, 95%CI: 1.03-1.55, p = 0.028). The association between smoking > 10 cigarettes/day was evident but was not significant (OR = 1.24, 95%CI:0.81-1.88, p = 0.323).Conclusion: Our results showed that maternal smoking during pregnancy increased the risk of congenital urogenital malformations. In numerous epidemiological studies, maternal smoking during pregnancy has a significant role in fetal development. Therefore, quitting tobacco use may be an effective method for reducing the risk of congenital urogenital malformation in pregnant women.

Context: Overactive bladder is treated mainly with behavioral and drug therapy, and symptoms of urinary frequency and incontinence are challenging to eliminate. There is thus a continuous unmet need for new drugs with a substitution effect mechanism. Objective: It not known whether vitamin D deficiency can lead to overactive bladder or urinary incontinence or whether vitamin D supplementation alleviates bladder symptoms. This comprehensive systematic review with meta-analysis was conducted to determine whether overactive bladder is associated with vitamin D deficiency. Data Sources: The PubMed and Cochrane Library databases were searched systematically up to July 3, 2022. Data Extraction: Initially, 706 articles were identified in the literature search, of which 13 were included in the systematic review: 4 randomized controlled trials, 3 cohort studies, 3 cross-sectional studies, and 3 case-control studies. Data Analysis: An increased risk of overactive bladder and urinary incontinence was observed with vitamin D deficiency (odds ratio [OR] = 4.46; 95%CI, 1.03–19.33; P = 0.046 and OR = 1.30; 95%CI, 1.01–1.66; P = 0.036, respectively). Vitamin D levels were relatively low in patients with overactive bladder or urinary incontinence (SMD = −0.33; 95%CI, −0.61 to −0.06, P = 0.019). On the basis of existing data, the risk of urinary incontinence was reduced by 66% after vitamin D supplementation (OR = 0.34; 95%CI, 0.18–0.66; P = 0.001). Egger test was conducted to assess publication bias, and the results were tested for robustness using a sensitivity analysis. Conclusions: Vitamin D deficiency increases the risk of overactive bladder and urinary incontinence, and vitamin D supplementation reduces the risk of urinary incontinence. The development of new strategies to prevent or alleviate bladder symptoms is crucial. Vitamin D supplementation may be gaining recognition as an effective strategy for prevention or alleviation of bladder symptoms such as overactive bladder and incontinence. Systematic Review Registration: PROSPERO registration no. CRD42022351443.