A multicenter study on surgical procedure selection and risk factor analysis of postoperative complications after TIP and Duckett hypospadias repair.

BACKGROUND: Hypospadias is a common congenital malformation in pediatric urology with surgery being the only curative treatment. Although there are hundreds of surgical methods for hypospadias, no single method can treat all types, and there are still high rates of postoperative complications. We performed this study to investigate surgical procedure selection and perform risk factor analysis of postoperative complications in hypospadias repair. METHODS: Retrospective analysis was performed of complete clinical and follow-up data of children with hypospadias who were treated and followed up at 15 children's clinical centers in Mainland China from December 2018 to December 2019. Children were divided into groups according to Barcat classification and surgical methods in order to analyze the surgical choice for different types of hypospadias and the influencing factors of different surgical methods for complications. RESULTS: In total, 1011 patients were followed up for 26 months. According to Barcat classification, there were 248 cases of distal type hypospadias, 214 of intermediate, and 549 of proximal type. Transverse preputial island flap urethroplasty (Duckett) and tubularized incised plate urethroplasty (TIP) were performed in 375 (37.1%) and 336 cases (33.2%), respectively. The postoperative complication rate of distal hypospadias was 23.4% (15.8-57.1%), mid shaft 29.0% (22.7-40.0%), and proximal 43.7% (30.2-52.9%). Among the 375 patients in Duckett group, 192 had complications. Multivariate logistic analysis showed that the length of prepuce island flap (OR = 3.506, 95% CI: 2.258-5.442) was an independent risk factor for complications after Duckett operation (P < 0.001). In TIP group, there were 336 cases with 84 complications. Multivariate logistic analysis showed that the width of urethral plate after longitudinal resection (OR = 0.836, 95% CI: 0.742-0.942) and glans width (OR = 0.851, 95% CI: 0.749-0.965) were independent risk factors for postoperative complications after TIP (P = 0.003, P = 0.012). CONCLUSION: Several anatomical features play a role during the selection process among the different surgical approaches, including glans size, urethral plate width, and the meatal position. The width of the urethral plate and glans width were risk factors for postoperative complications after TIP. The length of prepuce island flap was a risk factor for complications after Duckett operation.

Emergency Management of Acute Late-Presenting Congenital Diaphragmatic Hernia in Infants and Children.

OBJECTIVES: Acute late-presenting congenital diaphragmatic hernia (CDH) might result in mediastinal shift away from the lesion and even sudden cardiopulmonary arrest. This study aimed to discuss the prompt and effective emergency management of acute late-presenting CDH. METHODS: A retrospective review of acute late-presenting CDH cases in West China Hospital of Sichuan University and Guizhou Provincial People's Hospital from October 2010 to June 2016 was conducted. RESULTS: A total of 22 patients were included in this study. All the patients presented with respiratory symptoms. Chest x-ray revealed swollen stomach and mediastinal shift. After nasogastric tube placement, fluid infusion, and nasal oxygen breathing, the symptoms in 8 patients ameliorated, and 14 patients had no signs of obvious relief. Three patients underwent the bedside percutaneous puncture of distensible stomach, and 1 patient died in the process of emergent management for critical condition. The remaining 21 patients underwent emergency surgery. Five thoracotomies and 16 thoracoscopies were performed. Five thoracoscopies that were converted to thoracotomies were required for the difficult reduction of herniated stomach. At follow-up, all patients improved their condition. CONCLUSIONS: Acute late-presenting CDH is a clinical emergency that can be fatal. The sudden and progressive expansion of the stomach is mainly responsible for this emergent condition. The prompt and effective management is key to decrease the mortality and achieve favorable prognosis.

CXCR4-SF1 bifunctional adipose-derived stem cells benefit for the treatment of Leydig cell dysfunction-related diseases.

Stem cell transplantation is a candidate method for the treatment of Leydig cell dysfunction-related diseases. However, there are still many problems that limit its clinical application. Here, we report the establishment of CXCR4-SF1 bifunctional adipose-derived stem cells (CXCR4-SF1-ADSCs) and their reparative effect on Leydig cell dysfunction. CD29+ CD44+ CD34- CD45- ADSCs were isolated from adipose tissue and purified by fluorescence-activated cell sorting (FACS). Infection with lentiviruses carrying the CXCR4 and SF1 genes was applied to construct CXCR4-SF1-ADSCs. The CXCR4-SF1-ADSCs exhibited enhanced migration and had the ability to differentiate into Leydig-like cells in vitro. Furthermore, the bifunctional ADSCs were injected into BPA-mediated Leydig cell damage model mice via the tail vein. We found that the CXCR4-SF1-ADSCs were capable of homing to the injured testes, differentiating into Leydig-like cells and repairing the deficiency in reproductive function caused by Leydig cell dysfunction. Moreover, we investigated the mechanism underlying SF1-mediated differentiation and testosterone synthesis in Leydig cells, and the B-box and SPRY Domain Containing Protein (BSPRY) gene was proposed to be involved in this process. This study provides insight into the treatment of Leydig cell dysfunction-related diseases.

Hyperleptinemia directly affects testicular maturation at different sexual stages in mice, and suppressor of cytokine signaling 3 is involved in this process.

BACKGROUND: Leptin plays an important role in reproductive function, and the mechanism of this phenomenon primarily focuses on the hypothalamic-pituitary-gonadal axis. However, until now, the direct effects of leptin on the testes during development from infancy to adulthood remained unclear. The aim of the present study was to explore the effects and molecular mechanisms that underlie leptin's action in the testes during sexual maturation. METHODS: We used a monosodium glutamate (MSG)-treated mouse model to assess the effects of endogenous hyperleptinemia on the development of the testes from infancy to adulthood. Then, a variety of reproductive parameters were measured, including the concentration of testosterone, the weight and volume of the testicles, the diameter of the seminiferous tubules, and numbers of spermatogonia, spermatocytes, sperm, Leydig cells and offspring. In addition, we assessed the direct role of leptin and suppressor of cytokine signalling 3 (SOCS3)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3) on the testes in vitro. RESULTS: Testosterone secretion exhibited a diverse response: a low concentration of leptin induced testosterone secretion, and a high concentration inhibited testosterone secretion both in vivo and in vitro. A variety of reproductive parameters decreased in hyperleptinemic mice, including the weight and volume of the testicles, the diameter of the seminiferous tubules, and the numbers of spermatocytes, sperm, Leydig cells and offspring. The amount of spermatogonia was also elevated. The development of the testes was partially recovered after hyperleptinemia withdrawal. A high concentration of leptin induced SOCS3 expression and inhibited pSTAT3 expression in the testes. CONCLUSIONS: The results indicated that MSG-induced hyperleptinemia directly affects testicular structure and function and that SOCS3/pSTAT3 played an important role in this process. These results also indicated the importance of monitoring and controlling leptin levels in obese male children. SOCS3 is a potential therapeutic target for leptin-induced dysgenesis.

Foetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia--a systemic review and meta-analysis of randomized controlled trials.

To evaluate and analyze the effect of foetal endocsopic tracheal occlusion (FETO) therapy on survival rates of neonatal with congenital diaphragmatic hernia and maternal complications. We performed a systemic review and meta-analysis of three randomized controlled trials (RCTs). The combined data on neonatal survival rates, length of gestational age and rates of premature rupture of membrane from these studies were retrieved and analysed. Pooled data of these three RCTs revealed that FETO provided neonates with severe congenital diaphragmatic hernia a significantly higher survival rate: 27/48 VS 12/52. The odds ratio was 5.95 (95% CI: 2.11 - 16.79, p < 0.0008). The gestational age (week) of FETO group was shorter than postnatal standard therapy group. The mean difference was -3.43 (95% CI: -6.82 - -0.04, p < 0.05). FETO group also had a significantly greater rate of premature rupture of membranes than control group with the odds ratio of 3.35 (95% CI: 2.11 - 16.79, p < 0.0008). Foetal endoscopic tracheal occlusion improved neonatal survival rate but also increased major maternal complications including preterm delivery and premature rupture of membranes.

Interleukin 23 regulates proliferation of lung cancer cells in a concentration-dependent way in association with the interleukin-23 receptor.

A proinflammatory cytokine, interleukin 23 (IL-23), plays a role in tumor progression by inducing inflammation in the tumor microenvironment, although there is debate about its role in carcinogenesis. Direct effects of IL-23 on tumor cells have been reported rarely, and contradictory effects have been observed. Here, we studied such effects of IL-23 in lung cancer cells in vitro and in vivo and explored the underlying mechanism. We found IL-23 receptor expression in tissues from lung adenocarcinoma and small cell carcinoma but not in lung squamous cell carcinoma tissue. Interestingly, different concentrations of IL-23 had opposite effects in the same types of cells. We confirmed that the different effects could be explained by differences in binding to the IL-23 receptor (subunits IL-23r and IL-12Rß1). Low concentrations of IL-23 promoted the proliferation of IL-23 receptor-positive A549 and SPCA-1 lung cancer cells by binding to IL-23r, whereas high concentrations of IL-23 inhibited proliferation of these cells by binding to both IL-23r and IL-12Rß1. In contrast, IL-23 had no effect on IL-23 receptor-negative SK-MES-1 cells. IL-23 regulated the growth of human lung cancer cells through its effects on STAT3 expression and phosphorylation in a concentration-dependent way; the Ki-67 gene was involved in these processes. Our findings demonstrate for the first time that IL-23 affects the proliferation of IL-23 receptor-positive lung cancer cells and that this effect is dependent on the IL-23 concentration. This can explain at least part of the inconsistent reports on the role of IL-23 in the progression of carcinogenesis.

Cytoplasmic expression, antibody production, and characterization of the novel zinc finger protein 637.

Zinc finger protein 637 (zfp637), belonging to the Kruppel-like protein family, comprises one atypical C(2)H(2) and six consecutive typical zinc finger motifs. Based on the structural characterization of zfp637 and its location in the cell nucleus, we predict that zfp637 might function as a DNA-binding protein to regulate gene transcription. However, the absence of both a purified zfp637 protein and any commercial antibody for detecting it in cells and tissues has limited functional studies of zfp637 to date. Here, we developed and optimized an expression system by fusing zfp637 with glutathione S-transferase (GST) to achieve a maximal yield of soluble GST-zfp637 fusion protein in Escherichia coli BL21(DE3) cells. The yield was about 10 mg/l of the original bacterial culture. The recombinant GST-zfp637 fusion protein was purified and used for polyclonal antibody production in rabbits. In addition, we developed a method to remove the anti-GST antibody component and obtained a highly purified anti-zfp637 antibody, as demonstrated by an enzyme-linked immunosorbent assay. Western blotting showed that the anti-zfp637 antibody recognized not only the recombinant zfp637 protein but also endogenous zfp637 in several cell lines. The protein was localized mainly in the cell nucleus by immunofluorescence and immunohistochemistry. The expression levels of zfp637 mRNA and protein were significantly increased in NIH3T3 cells treated with 200 µM of H(2)O(2) in a time-dependent manner. The recombinant GST-zfp637 fusion protein and our purified anti-zfp637 antibody will help in elucidating the function of zfp637.

[Effects of ethane dimethane sulfonate on fetal Leydig cells in neonatal rats].

OBJECTIVE: To investigate the effects of ethane dimethane sulfonate (EDS) on fetal Leydig cells (FLCs) in neonatal rats. METHODS: In the study, 40 male neonatal SD rats were divided into control group and experimental groups. The rats in the experimental groups aged 3 days (PND3) were intraperitoneally injected with one single EDS (75, 100 and 125 mg/kg). The samples were collected on PND7. The body and testes was weighed, and the serum level of testosterone was detected. One testis was for histological analysis (3ß-hydroxysteroid dehydrogenase stainining), and the other was frozen in refrigerator for molecular determination (RT-PCR, Western blot). RESULTS: Compared with the control group, on day 4 after EDS treatment, significant decrease of serum testosterone was observed in the 75, 100 and 125 mg/kg experimental groups [(0.542 ± 0.117) µg/L, (0.124 ± 0.021) µg/L, (0.113 ± 0.015) µg/L, vs. (0.834 ± 0.172) µg/L, P<0.05]. Meanwhile, fetal Leydig cells in clusters disappeared with a lower expression level of Hsd3b1 and Cyp17a1 after EDS treatment in the testes of neonatal male rats in EDS (100 mg/kg)-treatment group (P<0.001). CONCLUSION: Ethane dimethane sulfonate can specifically deplete the fetal Leydig cells in testes of neonatal rats. Thus we could establish the FLCs' depletion model to know more about these testicular interstitial cells.

[Clinical characteristics of pediatric victims in the Lushan and Wenchuan earthquakes and experience of medical rescue].

OBJECTIVE: To get a more comprehensive understanding of the clinical characteristics of pediatric victims in earthquake and to summarize the experience of medical rescue. METHODS: The clinical information was collected from the pediatric victims who were admitted to West China Hospital, Sichuan University following the Lushan earthquake in 2013 and Wenchuan earthquake in 2008. The clinical data were compared between the pediatric victims in the two earthquakes. RESULTS: Thirty-four children under 14 years of age, who were injured in the Lushan earthquake, were admitted to the West China Hospital before April 30, 2013. Compared with the data in the Wenchuan earthquake, the mean age of the pediatric victims in the Lushan earthquake was significantly lower (P<0.01), and the mean time from earthquake to hospitalization was significantly shorter (P<0.01). In the Lushan earthquake, 67.6% of the injured children had variable limb fractures; traumatic brain injury was found in 29.4% of hospitalized children, versus 9.5% in the Wenchuan earthquake (P<0.05). Among the 34 children, no amputation and death occurred, and all the 13 severe cases started to recover. CONCLUSIONS: There were higher proportions of severely injured children and children with traumatic brain injury in the Lushan earthquake than in the Wenchuan earthquake. But these cases recovered well, which was possibly due to timely on-site rescue and transfer and multi-sector, multi-institution, and multidisciplinary cooperation.

Establishment of a monoclonal antibody against a peptide of the novel zinc finger protein ZNF32 proved to be specific and sensitive for immunological measurements.

BACKGROUND: ZNF32 has been predicted to be a zinc finger protein and is involved in cell differentiation and tumor development, but its precise function is unknown. Specific monoclonal antibodies (mAbs) have been widely used in research and clinical diagnosis and treatments. Therefore, we established an anti-ZNF32 mAb to characterize this protein's function. MATERIAL/METHODS: Peptide49⁻6³, a specific small peptide of ZNF32, was chosen and the synthetic keyhole limpet hemocyanin (KLH)-peptide49⁻6³ was used as an antigen to immunize mice. A mAb against peptide49⁻6³ was generated by hybridoma technology, and hybridoma cells were screened by limiting dilution. The isoform of mAb-pZNF32-8D9 was identified by double agar diffusion. The sensitivity and specificity of the mAb and expressed levels of ZNF32 in various cells and tissues were identified by enzyme-linked immunosorbent assay (ELISA), immunocytochemistry, immunohistochemistry, and Western blotting. RESULTS: A stable anti-pZNF32-8D9 hybridoma secreting the anti-peptide49-63 mAb was established and the clone positive to the peptide49⁻6³ in supernatant was 92% in ELISA. The mAb-pZNF32-8D9 is an immunoglobulin-1 that can be used for detecting the ZNF32 protein by immunocytochemistry, immunohistochemistry, and Western blotting and is highly sensitive and specific. We also found ZNF32 expressed at high levels in Jurkat and pulmonary squamous carcinoma cells, but it was not expressed in squamous epidermis cells. CONCLUSIONS: mAb-pZNF32-8D9 can be used for the identification and expression of ZNF32. It might also provide a new tool for diagnostics or therapy for ZNF32-related diseases.

[Induced differentiation of human adipose-derived stem cells into Leydig cells in vitro].

OBJECTIVE: To explore the feasibility of inducing the differentiation of human adipose tissue-derived stem cells (ADSCs) into Leydig cells in vitro. METHODS: We isolated ADSCs by digestion with Collagenase I from the subcutaneous adipose tissue, cultured them in the DMEM/F12 medium with 10% fetal bovine serum, and detected the expression of vimentin by immunohistochemistry. We exposed the ADSCs to different concentrations of human chorionic gonadotropin (HCG) for different times, determined the expression of StAR mRNA by real-time PCR, and measured the HCG-induced proliferation of ADSCs by MTT. After a week of induction by HCG and DMSO, we conducted 3beta-HSD immunohistochemistry, and detected the testosterone level in the supernatant and lysis of the cells by radioimmunoassay. RESULTS: The ADSCs grew well with a positive expression of vimentin. The expression of the StAR gene was positively correlated with the increased concentration of HCG, reaching the peak at HCG 10 U/ml in 1 week culture. The proliferation of ADSCs was significantly increased by HCG induction. A positive expression of 3beta-HSD was observed after 1 week induction with HCG 10 U/ml and DMSO 3.2 x 10(-6)mol/L. CONCLUSION: HCG enhances the expression of the StAR gene and the proliferation of ADSCs. Induced by HCG 10 U/ml and DMSO 3.2 x 10(-6) mol/L, ADSCs tend to differentiate into Leydig cells.

[Comparison of pedicled skin flap of foreskin for phalloplasty and Sugita surgical method in treatment of complete concealed penis].

OBJECTIVE: To evaluate the effectiveness of pedicled skin flap of foreskin for phalloplasty and Sugita surgical method in the treatment of complete concealed penis. METHODS: The clinical data of 46 children with complete concealed penis between January 2016 and January 2018 were analyzed retrospectively. Among which, 25 cases were treated with pedicled skin flap of foreskin for phalloplasty (group A) and 21 cases were treated with Sugita surgical method (group B) with an average age of 4.7 years (range, 2 years and 8 months to 11 years). At 3 months after operation, the concealed penis recovery was scored from three aspects of postoperative penis length (the difference of the penis length between at 3 months after operation and before operation), penis appearance, and skin appearance (the total score was 10). And the parents evaluation of satisfaction degree of penis exposure, penis appearance, and foreskin appearance after surgical correction was collected. RESULTS: Eighteen cases (72.0%) in group A and 15 cases (71.4%) in group B were followed up with an average of 13 months (range, 3-36 months). The incisions healed well in both groups, and there was no flap dehiscence, infection, necrosis, and penile erectile dysfunction. The penile length of the two groups increased significantly at 3 months after operation ( P<0.05); there was no significant difference between the two groups in terms of penis length and increased length at 3 months after operation and score of increase penis length after operation ( P>0.05). No penile retraction occurred in the two groups. And there was no significant difference between the two groups in penis appearance score, but the penis appearance score, skin appearance score, and total score of group A were significantly better than those of group B ( P<0.05). At 3 months after operation, the satisfaction rate of penis exposure in group A and group B was 88.9% and 80.0%, respectively, with no significant difference ( χ 2=0.50, P=0.48); the satisfaction rate of penis appearance was 72.2% and 53.3%, and the satisfaction rate of foreskin appearance was 94.4% and 53.3%, respectively, and the differences were significant ( χ 2=5.13, P=0.03; χ 2=7.53, P=0.01). CONCLUSION: Both surgical methods are suitable for correction of complete concealed penis, and the penile length gets a satisfactory recovery. However, the lymphedema of the prepuce after Sugita surgical method is serious, which can easily lead to poor appearance of the penis after operation. In general, the effectiveness of pedicled skin flap of foreskin for phalloplasty is better than that of the Sugita surgical method.

Linoleic acid promotes testosterone production by activating Leydig cell GPR120/ ERK pathway and restores BPA-impaired testicular toxicity.

Bisphenol A (BPA) [2,2-bis(4-hydroxyphenyl) propane] has attracted increasing attention over the past few decades as an endocrine-disrupting chemicals that causes low testosterone levels. Linoleic acid (LA) is an essential fatty acid and GPR120 agonist. Herein, we are the first to report that LA induces the expression of GPR120 in mouse Leydig cells to directly promote testosterone production. In addition, we demonstrated that the activated GPR120 / ERK signaling pathway was involved in upregulating the expression of 3ß-HSD and StAR for testosterone production by stimulation of LA. Interestingly, although BPA failed to affect GPR120 expression, LA restored the testosterone levels decreased by BPA in Leydig cells in vitro. Furthermore, the in vivo restoration of testosterone levels and testicular structure was also observed in BPA-impaired mice fed LA. As a result, the sperm functions of BPA-impaired mice returned to normal levels. At the same time, the damaged blood-testis barrier and infertility were also resolved by LA. Our study indicates a novel and safe strategy that utilizes LA to repair reproductive damage caused by low testosterone levels through activating the GPR120/ERK pathway in Leydig cells.

[In utero exposure to dichlorvos induces apoptosis of Leydig cells in rats].

OBJECTIVE: To observe the influence of the organophosphate insecticide dichlorvos on the apoptosis of Leydig cells in the male offspring of the SD rats exposed to dichlorvos, and to investigate the role of the changes of Leydig cells in genitourinary malformation. METHODS: Twenty-one pregnant SD rats were divided into a corn oil control group and 6 dichlorvos groups, the former given by gavage 1.0 ml corn oil daily, and the latter dichlorvos at the dose of 1, 4, 8, 16, 20 and 24 mg/kg daily from the 12th to 17th day of conception. After birth, 5 male neonates were randomly selected from each of the control and dichlorvos groups, and their testes were harvested to be analyzed by HE staining, immunohistochemistry with anti-caspase-3 antibodies and DAPI fluorescent staining. At 90 days after birth, another 5 of the male offspring were taken from each group and their testes were collected for the same analyses. RESULTS: Statistically significant differences were found in the number of both the caspase-3 positive and DAPI labeled Leydig cells in the testes of the rat offspring between the corn oil and the 4, 8, 16, 20 and 24 mg/kg dichlorvos groups (P < 0.05), but not between the control and the 1 mg/kg dichlorvos groups (P > 0.05). The apoptosis of Leydig cells was increased in the male offspring of the dichlorvos-exposed SD rats in a dose-dependent manner. CONCLUSION: Exposure of pregnant rats to dichlorvos can increase the apoptosis of Leydig cells in the male offspring, which, in turn, may reduce the number of Leydig cells, interfere with the testis function during the embryonic period, and damage the development of the genitourinary system.

Thoracoscopic Treatment of Late-Presenting Congenital Diaphragmatic Hernia in Infants and Children.

PURPOSE: Given that the application of thoracoscopic surgery to late-presenting congenital diaphragmatic hernia (CDH) in infants and children is controversial, we summarized our experiences with patients at two medical centers and aimed to discuss the safety and feasibility of thoracoscopic repair. MATERIALS AND METHODS: A retrospective review of late-presenting CDH cases involving patients who underwent thoracoscopic repair from October 2010 to June 2017 was performed. Data, including patients' demographic characteristics, manipulative details, and postoperative complications, were extracted and analyzed. RESULTS: A total of 59 cases were included in this study. Patients ranged in age from 2 months to 8 years (mean: 18 months). Twenty-five patients presented with shortness of breath and dyspnea. Furthermore, 34 cases were found occasionally. Forty-six left-sided hernias and 13 right-sided hernias were found. Operating time ranged from 30 to 100 minutes (mean: 55 minutes), and the amount of blood loss was 3-5 mL (mean: 3.8 mL). The size of the diaphragmatic defect ranged from 2 × 2 cm to 5 × 8 cm. The chest tubes were taken out within 24 hours. The average length of postoperative hospital stay was 5.2 ± 0.4 days (range: 4-6 days). The length of the follow-up period ranged from 3 months to 3 years (mean: 18 months), with no recurrences. CONCLUSION: Thoracoscopic repair of late-presenting CDH is a safe and efficacious technique. It can facilitate the procedure and decrease the recurrence rate by shifting the focus to operative details. The prognosis is excellent once the correct operative details are achieved.

ZNF32 induces anoikis resistance through maintaining redox homeostasis and activating Src/FAK signaling in hepatocellular carcinoma.

Tumor cells need to attain anoikis resistance to survive prior to metastasis making it a vital trait of malignancy. The molecular mechanism by which hepatocellular carcinoma (HCC) cells resist anoikis remains not fully understood. Here, we report that ZNF32 expression is markedly upregulated in HCC cells upon detachment. Enforced ZNF32 expression significantly promotes the anchorage-independent growth capability of HepG2 and Huh7 cells, whereas knockdown of ZNF32 results in increased apoptosis of HCC cells after detachment. Mechanistically, we demonstrate that ZNF32 overexpression suppresses the reactive oxygen species (ROS) accumulation and maintains mitochondrial membrane potential, leading to ATP, GSH and NADPH elevation and promoting HCC cell survival in response to suspension. Moreover, ZNF32 enhances the phosphorylation and activation of Src/FAK signaling. Src and FAK inhibitors effectively reverse ZNF32-induced anoikis resistance in HCC cells. Collectively, our findings not only reveal a novel and important mechanism by which ZNF32 contributes to anoikis resistance through maintaining redox homeostasis and activating Src/FAK signaling, but also suggest the potential therapeutic value of ZNF32 in HCC patients.

The tumor suppressor role of microRNA-338-3p in renal cell carcinoma.

Human renal cell carcinoma (RCC) is the most common type of kidney malignancy in adults accounting for 2-3% of all adult malignancies. In China, RCC accounts for ~0.5% of all cancer-associated mortalities, ranking 16th among all cancer types. For early-stage RCC, surgery is the recommended treatment. Molecularly targeted therapy is the preferred first-line treatment for clear-cell RCC. However, more potential targets are required. MicroRNA-338-3p (miR-338-3p) functions as a tumor suppressor in various cancers, but has not been studied in RCC. Accordingly, the present study investigated the role of miR-338-3p of RCC. It was demonstrated that miR-338-3p was present at low levels in RCC tissues. Also, overexpression of miR-338-3p inhibited cell proliferation and promoted cell apoptosis, and downregulation of miR-338-3p promoted cell proliferation. The 3' untranslated region of AKT serine/threonine kinase 3 was targeted by miR-338-3p. In conclusion, the data of the present study revealed the inhibitory function of miR-338-3p in RCC and suggested that miR-338-3p is novel therapeutic target for RCC, but further investigation is needed.

Chordee without hypospadias: report of 79 Chinese prepubertal patients.

A series of Chinese prepubertal patients with congenital chordee without hypospadias is presented and the clinical data described. From July 1999 to September 2006, 79 boys with congenital chordee without hypospadias were treated in the Department of Pediatric Surgery, West China Hospital of Sichuan University, China. The ages ranged from 21 months to 14 years, with a mean of 76.8 months (6.4 years). The patients were categorized according to structural defect into 4 groups, with the aid of intraoperative artificial erection. Group I included those with skin tethering (28 cases, 35.4%); group II, fascial chordee (22, 27.8%); group III, corporal disproportion (10, 12.7%); and group IV, urethral tethering (19, 24.1%). Chordee-related structural defect was considered the only criterion for classification, and urethral dysgenesis influenced the choice of surgical procedure. The chordee in group I patients was corrected with penile degloving; group II, release of dense fibrous tissue in addition; group III, dorsal-midline-plication-based correction; and group IV, longitudinal-island-flap-urethroplasty-based repair. At a mean follow-up of 14.8 months (range, 2 to 63), all patients had penile straightening except 1 group III patient with residual curvature that was managed upon reoperation. Glans dehiscence occurred in 1 group II patient who underwent a tubularized incised plate urethroplasty. Urethrocutaneous fistula and urethral stricture were found in 2 group IV patients who underwent island flap urethroplasty. With the categorization based on structural defect, chordee without hypospadias may be managed well with minimized complications.

Continuous-type splenogonadal fusion: A case report.

Splenogonadal fusion (SGF) is a rare congenital malformation. Since it lacks characteristic features, very few cases of SGF have been diagnosed preoperatively. Laparoscopy was effective in both diagnosing and surgically treating this condition. Herein, we reported left side SGF in a male patient who was diagnosed during laparoscopic exploration, and Fowler-Stephens orchidopexy was implemented at the same time. The patient was followed up for one year. At a 6-month follow-up, the left scrotum demonstrated swelling and the internal contents were hard. An ultrasound of this testicle indicated non-uniform, splenic-like organization. However, at the one-year follow-up, the volume of splenic-like organization was reduced but the testicular size did not exhibit further atrophy.

DDX17 nucleocytoplasmic shuttling promotes acquired gefitinib resistance in non-small cell lung cancer cells via activation of ß-catenin.

Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for non-small cell lung cancer (NSCLC) patients with EGFR mutations, almost all these patients will eventually develop acquired resistance to EGFR-TKI. However, the molecular mechanisms responsible for gefitinib resistance remain still not fully understood. Here, we report that elevated DDX17 levels are observed in gefitinib-resistant NSCLC cells than gefitinib-sensitive cells. Upregulation of DDX17 enhances the gefitinib resistance, whereas DDX17-silenced cells partially restore gefitinib sensitivity. Mechanistically, we demonstrate that DDX17 disassociates the E-cadherin/ß-catenin complex, resulting in ß-catenin nuclear translocation and subsequently augmenting the transcription of ß-catenin target genes. Moreover, we identify two nuclear localization signal (NLS) and four nuclear export signal (NES) sequences mediated DDX17 nucleocytoplasmic shuttling via an exportin/importin-dependent pathways. Interruption of dynamic nucleocytoplasmic shuttling of DDX17 impairs DDX17-mediating the activation of ß-catenin and acquired resistance in NSCLC cells. In conclusion, our findings reveal a novel and important mechanism by which DDX17 contributes to acquired gefitinib resistance through exportin/importin-dependent cytoplasmic shuttling and followed by activation of ß-catenin, and DDX17 inhibition may be a promising strategy to overcome acquired resistance of gefitinib in NSCLC patients.