Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression.

Background: Epidemiologic studies suggested the association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and disorders of sex development (DSD), adult male disorders, and reproductive aging. Inhibiting testosterone synthesis by interfering with steroidogenic gene expression induces testicular toxicity, however, whether prenatal DEHP exposure induces testicular toxicity through this mechanism remains uncertain. Methods: C57BL/6JGpt male mice underwent different doses (0, 100, 500, 1,000 mg/kg) of prenatal DEHP exposure during gestational day 10 to delivery day, the testicular toxicity (genital development, testosterone, semen quality, and morphology of testis tissue) in the neonatal, post-puberal and middle-aged stages was observed, and the steroidogenic gene (Lhcgr, Star, Cyp11a1, Cyp17a1, Hsd17b3, and Hsd3b2) expression was analyzed by quantitative polymerase chain reaction (qPCR) and Western blot (WB). The interference of steroidogenic gene expression in TM3 cells after mono-(2-ethylhexyl) phthalate (MEHP) exposure was also explored for verification. Results: Prenatal DEHP exposure induced immediate testicular injury in the neonatal stage [reduced anogenital distance (AGD) and intratesticular testosterone], DSD in the post-puberal stage (poor genital development), and reproductive aging in the middle-aged stage (obesity, reduced testosterone and semen quality, and atrophic seminiferous tubules), especially in the high dose. Prenatal DEHP exposure continuously interfered with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. MEHP inhibited testosterone synthesis of TM3 cells by interfering with steroidogenic gene expression (Hsd3b2, Hsd17b3) in RNA and protein levels. Conclusions: Prenatal DEHP exposure induces lifelong testicular toxicity by continuously interfering with steroidogenic gene expression, thus indicating the association between prenatal exposure and DSD, adult male disorders, and reproductive aging.

Di-(2-ethylhexyl) phthalate exposure induces premature testicular senescence by disrupting mitochondrial respiratory chain through STAT5B-mitoSTAT3 in Leydig cell.

Di-(2-ethylhexyl) phthalate (DEHP), a prevalent plasticizer, is known to have endocrine-disrupting effects on males and cause reproductive toxicity. There were causal effects of DEHP on testosterone levels in the real world by Mendelian randomization analysis. Exposure to DEHP during the preadult stage might lead to premature testicular senescence, but the mechanisms responsible for this have yet to be determined. In this study, we administered DEHP (300 mg/kg/day) to male C57BL/6 mice from postnatal days 21 to 49. The mice were kept for 6 months without DEHP. RNA sequencing was conducted on testicular tissue at PNM6. The results indicated that DEHP hindered testicular development, lowered serum testosterone levels in male mice, and induced premature testicular senescence. TM3 Leydig cells were exposed to 300 µM of mono(2-ethylhexyl) phthalate (MEHP), the bioactive metabolite of DEHP, for 72 h. The results also found that DEHP/MEHP induced senescence in vivo and in vitro. The mitochondrial respiratory chain was disrupted in Leydig cells. The expression and stability of STAT5B were elevated by MEHP treatment in TM3 cells. Furthermore, p-ERK1/2 was significantly decreased by STAT5B, and mitochondria-STAT3 (p-STAT3 ser727) was significantly decreased due to the decrease of p-ERK1/2. Additionally, the senescence level of TM3 cells was decreased and treated with 5 mM NAC for 1 h after MEHP treatment. In conclusion, these findings provided a novel mechanistic understanding of Leydig cells by disrupting the mitochondrial respiratory chain through STAT5B-mitoSTAT3.

Ningmitai capsules have anti-inflammatory and pain-relieving effects in the chronic prostatitis/chronic pelvic pain syndrome mouse model through systemic immunity.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects the physical and mental health of approximately 90% of males. Due to its complex and unclear etiology, the treatment methods that are currently available for chronic prostatitis/chronic pelvic pain syndrome are controversial, and their efficacy is unsatisfactory. At present, most researchers believe that this kind of prostatitis is caused by autoimmune inflammation. Chinese herbs, which are the essence of traditional Chinese medicine (TCM), are emerging treatment options for inflammation and immune diseases. In this experiment, we investigated the effect of Ningmitai capsules (a kind of traditional Chinese medicine widely used to treat lower urinary tract inflammation and pain in males) on chronic prostatitis/chronic pelvic pain syndrome in a non-obese diabetes-experimental autoimmune prostatitis (NOD-EAP) mouse model. First, by using bioinformatics analysis of data from the Encyclopedia of Traditional Chinese Medicine (ETCM) database, we found that quercetin, which is one of the main components of Ningmitai capsules, could reduce the secretion of CCL2 by inhibiting the MAPK pathway. In animal experiments, it was found that after Ningmitai treatment, the inflammation in mouse prostates was alleviated, the expression of CCL2, which is related to pain, and MAPK pathway components were downregulated, and the activation of the inflammatory NF-κB and STAT3 pathways was reduced. Pelvic pain and inflammation were relieved in mice with EAP. Due to the presence of the blood-prostate barrier, the drug may not completely reach the prostate directly and take effect locally. However, we found that after Ningmitai treatment, the proportions of proinflammatory CD11b+Ly6Chigh immune cells in the spleen, bloodstream (systemic immunity), and prostate (local immunity) were reduced. The infiltration of CD11b+ immune cells into the spleen and prostate was decreased. These findings suggested that Ningmitai can treat chronic prostatitis/chronic pelvic pain syndrome by affecting systemic and local immunities through the CCL2-MAPK pathway.

46,XY disorders of sex development: the use of NGS for prevalent variants.

46,XY disorders of sex development (DSD) present with diverse phenotypes and complicated genetic causes. Precise genetic diagnosis contributes to accurate management, and targeted next-generation sequencing (NGS) and whole-exome sequencing are powerful tools for investigating DSD. However, the prevalent variants resulting in 46,XY DSD remain unclear, especially those associated with mild forms, such as isolated hypospadias, inguinal cryptorchidism, and micropenis. From 2019 to 2021, 74 patients with 46,XY DSD (48 typical and 26 mild) from the First Affiliated Hospital of Sun Yat-sen University were enrolled in our cohort study for targeted NGS or whole-exome sequencing. Our targeted 46,XY DSD panel included 108 genes involved in disorders of gonadal development and differentiation, steroid hormone synthesis and activation, persistent Müllerian duct syndrome, idiopathic hypogonadotropic hypogonadism, syndromic disorder, and others. Variants were classified as pathogenic, likely pathogenic, variant of uncertain significance, likely benign, or benign following the American College of Medical Genetics guidelines. As a result, 28 of 74 (37.8%) patients with pathogenic and/or likely pathogenic variants acquired genetic diagnoses. The Mild DSD patients acquired a diagnosis rate of 30.7%. We detected 44 variants in 28 DSD genes from 31 patients, including 33 novel and 11 reported variants. Heterozygous (65%) and missense (70.5%) variants were the most common. Variants associated with steroid hormone synthesis and activation were the main genetic causes of 46,XY DSD. In conclusion, 46,XY DSD manifests as a series of complicated polygenetic diseases. NGS reveals prevalent variants and improves the genetic diagnoses of 46,XY DSD, regardless of severity.

Salvage 125I brachytherapy for liver metastases of colorectal cancer in anatomically challenging locations after failure of systemic chemotherapy-A retrospective study.

PURPSOE: Colorectal cancer liver metastasis (CCLM) in anatomically challenging locations is difficult to treat. This retrospective study aimed to evaluate the effectiveness and safety of permanent 125I seeds implantation (ISI) for treatment of CCLM in anatomically challenging locations after failure of systemic chemotherapy. METHODS AND MATERIALS: A total of 31 liver metastases (in 25 patients) were treated by ISI under computerized tomography guidance from January 2011 to December 2017. Post-treatment follow-up was for 40 months. Adverse events were classified using the National Cancer Institute's Common Terminology Criteria for Adverse Events. Tumor response was evaluated by the mRECIST criteria. Objective response rate, overall survival rate, and complications were retrospectively analyzed. RESULTS: All ISI procedures were performed successfully. Most patients only complained of fatigue and mild pain after ISI. Only one patient had liver rupture during the procedure. Serum alanine aminotransferase and aspartate aminotransferase levels at 1 month after ISI were not significantly different from pre-procedure levels (p > 0.05). Computed tomography at 6 months after ISI treatment showed completed response in 11 (11/31, 35.5%) lesions, partial response in 14 (14/31, 45.2%) lesions, stable disease in 4 (4/31, 12.9%) lesions, and disease progression in 2 (2/31, 6.5%) lesions; thus, the objective response rate was 80.6%. Median survival was for 12 months. The 1 and 2 year overall survival rates were 52.0% and 20.0%, respectively. CONCLUSIONS: 125I seeds implantation for CCLM in anatomically challenging locations is safe and effective. Survival benefit is limited in the salvage setting where patients have high intrahepatic tumor load after failed systemic chemotherapy.

Application of the Mathieu combined tunnel technique for repairing glans dehiscence after failed hypospadias repair.

Repairing glans dehiscence after failed hypospadias repair is challenging for pediatric surgeons. Here, we introduced and evaluated a newly modified Mathieu technique, Mathieu combined tunnel (MCT), which involves multiple custom-designed flaps for the shortage of flap source material after repeated operations; we also constructed a tunnel to avoid the glans incision that may carry new risks of dehiscence. This retrospective study included 26 patients who were consecutively admitted to the First Affiliated Hospital of Sun Yat-Sen University (Guangzhou, China) for glans dehiscence repair after failed hypospadias repair from October 2014 to October 2020; sixteen patients underwent surgery using the MCT (MCT group) and ten patients underwent surgery using the tubularized incised plate (TIP) technique (TIP group). The operative time, blood loss, postoperative complications, normal urethral meatus rate, success rate, and Hypospadias Objective Penile Evaluation (HOPE) score were compared between the two groups. The MCT group achieved an overall satisfactory penile appearance and voiding function, with a higher rate of normal urethral meatus (15/16, 93.8%) and a lower rate of glans dehiscence (1/16, 6.2%), compared with the TIP group (70.0% and 30.0%, respectively). However, these differences were not statistically significant, possibly because of the limited number of patients (all P > 0.05). Mean postoperative HOPE scores were similar in the MCT group (mean ± standard deviation: 8.83 ± 0. 89) and TIP group (8.94 ± 0.57) (P > 0.05). No significant differences were found between the two groups in terms of blood loss and success rate, nor in the rates of various complications (e.g., fistula, urethral stricture, and glans dehiscence). In conclusion, the MCT technique appears to be feasible and reliable for repairing glans dehiscence after failed hypospadias repair.

Iodine-125 seed implantation treatment of lung metastases < 2.5 cm using 5-ml syringe as a guide.

PURPOSE: Small lung metastases change their location with respiration, making difficult to localize, therefore, increasing the number of punctures. Accurate puncture can reduce trauma to lung tissue and accelerate patient's recovery. The aim of the study was to present our experience with the technique of using local anesthesia 5-ml syringe as a guide for computerized tomography-guided iodine-125 seed implantation (CT-ISI). MATERIAL AND METHODS: This was a retrospective study, including patients with small metastatic tumors in the lung, treated with CT-ISI between December 2013 and March 2018 at the Affiliated Hospital of the University. The patients were divided according to whether a 5-ml syringe was used as a guide during CT-ISI or not. The final follow-up was on March 31st, 2018. Implantation success and complications were examined. RESULTS: Nineteen patients were included. A total of 840 seeds were used, with 44.2 ±33.6 (range, 10-160) seeds per patient. The mean D90 for CT-ISI was 134.5 ±7.5 Gy. Treatment intervention for eleven patients was performed using a 5-ml syringe as a guide during CT-ISI. There were no differences in total dose and number of implanted seeds between the two groups, but the number of punctures per lesion was lower in the syringe group than in the no-syringe group (1.9 ±0.5 vs. 2.9 ±0.6, p < 0.001), suggesting a higher puncture accuracy. The total number of SMTIL was 50 (median, 2; range, 1-10), and the median size was 1.9 cm (range, 0.8-2.4 cm). All SMTIL were well-controlled at 6-months follow-up (response rate [RR] = 100%). One patient in the no-syringe group experienced grade 2 chest tightness, chest pain, intraoperative needle tract bleeding, and post-operative blood in sputum. CONCLUSIONS: Puncture with a 5-ml syringe as a guide during CT-ISI seems to be a more accurate option for patients with small (< 2.5 cm) lung metastasis.

Iodine-125 seed implantation for residual hepatocellular carcinoma or cholangiocellular carcinoma in challenging locations after transcatheter arterial chemoembolization: Initial experience and findings.

PURPOSE: To evaluate the clinical efficacy and safety of computed tomography (CT)-guided iodine-125 (125I) seed implantation (ISI) for hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) lesions in challenging locations after transcatheter arterial chemoembolization (TACE). MATERIAL AND METHODS: A retrospective single-center review of 24 patients with HCC or CCC tumors in challenging locations (hepatic dome or close to the heart/diaphragm/hepatic hilum) was conducted. Patients who underwent CT-guided 125I implantation from May 2014 to January 2019 were recruited. Patients' demographics and details including technical success, treatment response, patient survival, and complication rate were also evaluated. RESULTS: Treated tumors were located in the hepatic dome (n = 10; 41.7%), subcapsularly (n = 6; 25%), close to the heart (n = 3; 12.5%), and in the liver hilum (n = 5; 20.8%). The mean maximum diameter of tumors in challenging locations was 40.08 ±11.34 mm (range, 25-68 mm). TACE (2 ±1, 1-4 times) was applied before ISI. There were 27 ISI treatments administered (3 patients also received supplemental ISI). The total number of implanted seeds was 1,160, with mean 48 ±16 seed per patient (range, 30-90 seeds). The mean D90 value for ISI was 125 Gy. Technical success rate was 100%, while a complete response + partial response (CR + PR) was documented in 70.83%, 79.17%, 83.33%, and 79.17% of patients at 3, 6, 12, and 24 months post-ISI, respectively. There were no major complications, although 2 cases experienced 125I seed transfer to the diaphragm, and 1 case experienced transfer to the heart cavity. CONCLUSIONS: CT-guided ISI for HCC or CCC lesions in challenging locations after TACE is both highly effective and safe.

NLGN3 promotes neuroblastoma cell proliferation and growth through activating PI3K/AKT pathway.

Neuroblastoma is the most common extracranial solid tumor of childhood, previous studies show synaptic protein neuroligin-3 (NLGN3) promotes glioma proliferation and growth, However, no investigation about the role of NLGN3 in neuroblastoma was reported. Here, we found NGLGN3 was significantly upregulated in neuroblastoma cells and tissues, its overexpression significantly promoted neuroblastoma cell proliferation and growth determined by MTT analysis, colony formation assay, cell cycle progression analysis, BrdU incorporation assay and animal model, while its knockdown inhibited cell proliferation and growth. Then we found NLGN3 could increase the phosphorylation level of AKT and the transcription activity of FOXO family, suggesting NLGN3 activated PI3K/AKT pathway, inhibition of PI3K/AKT pathway in NLGN3 overexpressing cells inhibited cell proliferation, confirming NLGN3 promoted neuroblastoma proliferation through activating PI3K/AKT pathway. In summary, we found NLGN3 promoted neuroblastoma cell proliferation and growth through activating PI3K/AKT pathway and providing a new target for neuroblastoma therapy.

How many times 125I seed implantation brachytherapy can be repeated for pulmonary metastases: clinical efficacy and complications.

PURPOSE: The aim of the study was to determine how many times iodine-125 (125I) seed brachytherapy (ISB) for recurrent pulmonary metastases (RPM) can be done, and the clinical efficacy and complications of repeated ISB in RPM treatment. MATERIAL AND METHODS: Between September 2013 and August 2018, 18 patients with RPM, after conventional chemotherapy, radiotherapy, and trans-arterial chemoembolization, received CT-guided repeated ISB. Patients were followed up, and local control, survival, and post-operative complications were analyzed retrospectively. The Kaplan-Meier method was used for survival analyses. RESULTS: Eighty-two metastases in 18 patients were treated with ISB, with 71 implantations (mean number of implantations per patient, 4; range, 3-8). The total number of implanted 125I seeds was 1,220 (mean number per patient, 68; minimum, 40; maximum, 110). The mean value of D90 for ISB was 138 Gy. Local control was 91.46%, 90.24%, and 89.02% at 1, 3, and 6 months after ISB, respectively. After repeated ISB, good local control was achieved, and all patients were discharged from hospital within 3 days. One month after, six metastases of large diameter were treated with ISB; computed tomography revealed level 1 radioactive injury to the lungs, but special treatment was not administered. Post-operative renal, hepatic, and vascular functions were normal. CONCLUSIONS: ISB for RPM is safe and efficacious. RPM treatment seems not to be limited by number of times ISB could be repeated; at least up to 8 times for different sites of lung.

GDNF family receptor alpha 2 promotes neuroblastoma cell proliferation by interacting with PTEN.

Neuroblastoma is a childhood tumor, and high-stage neuroblastoma has a poor prognosis. The regulatory mechanisms for neuroblastoma progression are poorly understood. In present study, we found that GDNF family receptor alpha 2 (GFRA2) was upregulated in neuroblastoma cells and tissues, and its overexpression promoted neuroblastoma cell proliferation, as revealed using colony formation, soft agar growth, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays Tumor suppressor phosphatase and tensin homolog (PTEN) is an inhibitor of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway that interacts with GFRA2. A luciferase activity assay showed GFRA2 inhibits the transcriptional activity of the forkhead box O (FOXO) family proteins, which suggested that GFRA2 activated the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway in GFRA2 overexpressing cells decreased cell proliferation, confirming that GFRA2 promoted neuroblastoma cell proliferation by activating the PI3K/AKT pathway. In summary, cell proliferation via the GFRA2-PTEN-PI3K/AKT axis may represent new target to develop treatments for neuroblastoma.

125I seeds implantation for treating residual hepatocellular carcinoma located beneath the diaphragm after transcatheter arterial chemoembolization.

PURPOSE: The effect of 125I seed implantation for the treatment of local residual tumor of hepatocellular carcinoma located beneath the diaphragm (HCC-LBD) after transcatheter arterial chemoembolization (TACE) has not yet been reported. This retrospective study was performed to evaluate the safety and efficacy of 125I seeds implantation (ISI) for the treatment of residual HCC-LBD after TACE. METHODS AND MATERIALS: A total of 18 patients treated with ISI between August 2012 and March 2018 for residual HCC-LBD after single or multiple TACE were enrolled. Local control, survival, and postoperative complications were analyzed retrospectively. Overall followup time was displayed by survival curves. RESULTS: The 18 patients received a total of 20 ISI treatments. The total number of seeds implanted was 650, with a mean of 36 ± 13 seeds per patients (range, 20-70). Mean D90 was 123 Gy. Complete response + partial response (CR + PR) was documented in 14, 16, and 16 of patients at 3, 6, and 12 months after implantation, respectively. In four patients, seeds implantation was performed through the diaphragm; two of these patients developed small pneumothoraces. Pulmonary compression of pneumothorax is less than 30% combined with a little blood in sputum, no chest tightness, shortness of breath, all symptoms subsided without interventions, and the patients were discharged after observation for 2 days. After the procedure, routine blood examination and liver and kidney function were normal. CONCLUSION: The combination of TACE with ISI appears to be a safe and efficient treatment for residual HCC-BLD. IMPLICATIONS FOR PRACTICE: This study evaluated the feasibility, safety, and short-term efficacy of ISI for local residual tumor of hepatocellular carcinoma located beneath the diaphragm (HCC-LBD) after TACE. Results suggest that residual tumor of HCC after TACE located in the posterosuperior part of the liver (segments seven and eight), laparoscopic liver resection, and alblation is difficult to perform and that as a supplement treatment, 125I seeds implantation is safe and easy accessible. TACE combined with 125I seeds has excellent local control effectiveness, and long-term efficacy and survival benefit still need to be more comprehensively evaluated.

Impact of 3D printing technology on the comprehension of surgical liver anatomy.

BACKGROUND AND AIMS: Surgical planning in liver resection depends on the precise understanding of the three-dimensional (3D) relation of tumors to the intrahepatic vascular trees. This study aimed to investigate the impact of 3D printing (3DP) technology on the understanding of surgical liver anatomy. METHODS: We selected four hepatic tumors that were previously resected. For each tumor, a virtual 3D reconstruction (VIR) model was created from multi-detector computed tomography (MDCT) and was prototyped using a 3D printer. Forty-five surgical residents were evenly assigned to each group (3DP, VIR, and MDCT groups). After evaluation of the MDCT scans, VIR model, or 3DP model of each tumor, surgical residents were asked to assign hepatic tumor locations and state surgical resection proposals. The time used to specify the tumor location was recorded. The correct responses and time spent were compared between the three groups. RESULTS: The assignment of tumor location improved steadily from MDCT, to VIR, and to 3DP, with a mean score of 34.50, 55.25, and 80.92, respectively. These scores were out of 100 points. The 3DP group had significantly higher scores compared with other groups (p < 0.001). Furthermore, 3DP significantly improved the accuracy of surgical resection proposal (p < 0.001). The mean accuracy of the surgical resection proposal for 3DP, VIR, and MDCT was 57, 25, and 25%, respectively. The 3DP group took significantly less time, compared with other groups (p < 0.005). The mean time spent on assessing the tumor location for 3DP, VIR, and MDCT groups was 93, 223, and 286 s, respectively. CONCLUSIONS: 3D printing improves the understanding of surgical liver anatomy for surgical residents. The improved comprehension of liver anatomy may facilitate laparoscopy or open liver resection.

Comparison of clinical efficacy and complications of 125I seed brachytherapy and stereotactic body radiation therapy for recurrent pulmonary metastases from colorectal carcinoma.

PURPOSE: To evaluate the efficacies of 125I seed implantation and stereotactic body radiation therapy (SBRT) in treatment of recurrent lung metastases from colorectal cancer, to compare the tolerance of lung tissue to both forms of radiotherapy, and to analyze the factors that affect the prognosis. MATERIAL AND METHODS: According to treatment received, thirty colorectal cancer patients with post-operative lung metastases were separated into two groups: 125I seed implantation group (group A; n = 16) and SBRT group (group B; n = 14). Patients were followed up, and local control rate, survival, and post-operative complications were analyzed retrospectively. Kaplan-Meier method was used for survival analysis. Cox proportional hazards model was used to identify the independent predictors of poor prognosis. RESULTS: Survival was significantly different between group A and group B (median survival, 15 months and 11.5 months, respectively; p = 0.015). Local control rates at the first, third, sixth, and twelfth months after treatment were all > 80%, with no significant difference between the two groups (p = 0.829). Significant differences were seen between the two groups in the number of treatments received (p = 0.009) and the incidence of radiation pneumonitis (p < 0.001) as well as radiation-induced pulmonary fibrosis (p = 0.005). On multivariate regression analysis radiation pneumonitis was an independent predictor of poor prognosis (HR = 3.356, 95% CI: 1.518-7.421; p = 0.003). CONCLUSIONS: 125I seeds brachytherapy and SBRT are both effective for control of lung metastases but the former causes milder lung tissue damage. It can be repeated after short intervals, and appears to be a safe and efficient treatment for lung metastases.

Computed tomography-guided implantation of 125I seeds brachytherapy for recurrent multiple pulmonary oligometastases: initial experience and results.

PURPOSE: To retrospectively evaluate the efficacy and safety of computed tomography (CT)-guided percutaneous interstitial brachytherapy using 125I radioactive seeds for multiple pulmonary metastatic tumors. MATERIAL AND METHODS: Between September 2013 and December 2015, 22 patients with multiple pulmonary metastases, who after conventional chemotherapy and trans-arterial chemoembolization (TACE) therapy were considered unable to withstand stereotactic body radiation therapy (SBRT), received CT-guided 125I brachytherapy. Clinical data were studied retrospectively. A planning target volume of 90% (D90) was 120-160 Gy for 125I seeds with an activity of 25.9 MBq. A CT-based evaluation performed 1, 2, and 6 months' post-implantation enabled review of local control of tumors. RESULTS: Twenty-two patients with 65 pulmonary metastases successfully completed treatment. The mean value for D90 for implantation for 125I seeds was 132 Gy. Complete response (CR) + partial response (PR) was documented in 81.54%, 78.46%, and 78.46% of patients at 1, 2, and 6 months after implantation, respectively. Fourteen out of 22 patients had CR, 3 had PR, 2 had stable disease (SD), and 3 had progressive disease (PD). Most of the metastases (CR + PR + SD; 87.69% after 6 months) were controlled by implantation. CONCLUSIONS: CT-guided 125I brachytherapy is a safe and effective treatment for multiple pulmonary metastatic tumors, and can achieve good short-term local control, so long as the radiation dose is sufficient.

miR-1303 promotes the proliferation of neuroblastoma cell SH-SY5Y by targeting GSK3ß and SFRP1.

Neuroblastoma (NB) is one of the most common solid tumors in children, many microRNAs regulate progression and development of NB. Here, we found miR-1303 was upregulated in NB cells and tissues, miR-1303 overexpression promoted the proliferation of SH-SY5Y NB cell investigated by MTT assay, colony formation assay and anchorage-independent growth ability assay, while miR-1303 knockdown reduced this effect. mechanism analysis suggested glycogen synthase kinase 3 beta (GSK3ß) and secreted frizzled-related protein 1 (SFRP1) were the target of miR-1303, luciferase assay revealed miR-1303 directly bound to the 3'UTR of GSK3ß and SFRP1. miR-1303 increased expression of MYC and CyclinD1, and decreased the expression of p21 and p27, and further demonstrated miR-1303 promotes NB proliferation. Moreover, there was a negative correlation between miR-1303 expression and GSK3ß and SFRP1 expression in NB tissues, confirming GSK3ß and SFRP1 were the targets of miR-1303 in NB tissues. Collectively, our findings suggested miR-1303 promotes NB proliferation by targeting GSK3ß and SFRP1, and might be a target for NB therapy.

CT-guided implantation of (125)I seeds (permanent brachytherapy) for metastatic tumors of the hepatic portal system: Effectiveness and safety in 13 patients.

PURPOSE: To retrospectively evaluate the efficacy and safety of CT-guided implantation of (125)I seeds (permanent brachytherapy) for metastatic tumors of the hepatic portal system (HPS). METHODS AND MATERIALS: Between January 2012 and January 2015, 13 patients with metastases measuring >3.0 cm in short-axis diameter, which remained in the HPS after conventional chemotherapy and/or transcatheter arterial chemoembolization, and for which an effective therapeutic dose from external beam radiotherapy could not be delivered, received CT-guided (125)I brachytherapy. Clinical data were studied retrospectively. In terms of metrological requirements, the minimum dose to 90% of the target volume (D90) was 90-160 Gy for (125)I seeds with activity of 2.96 × 10(7)Bq. CT-based evaluation after 2, 4, and 8 weeks, as well as 6 months after implantation enabled review of local control of tumors. RESULTS: All symptoms were improved after (125)I brachytherapy. The mean value for D90 for implantation of (125)I seeds was 136 Gy. Complete response (CR) + partial response (PR) was documented in 61.5%, 69.2%, and 84.6% of patients at 2 weeks, 4 weeks, and 6 months after implantation, respectively. Four of 13 patients had complete response, 7 cases had PR, 1 patient had stable disease, and 1 case had progressive disease. All metastatic foci were controlled by implantation. No serious complications were observed. CONCLUSION: CT-guided (125)I brachytherapy is a safe and effective treatment for metastatic tumors of the HPS and can achieve good local control in the short term as long as the radiation dose is sufficient. CT-guided (125)I brachytherapy carries few complications, is simple, safe, and a good complement to cancer treatment.

[Foley catheter versus urethral stent plus gastric tube for urine drainage following urethroplasty].

OBJECTIVE: To compare the advantages and disadvantages of the Foley catheter draining method versus the urethral stent plus gastric tube draining method for urine drainage following urethroplasty for hypospadias. METHODS: We retrospectively analyzed the clinical data of 361 cases of hypospadias treated by urethroplasty. After operation, 91 of the cases received urine drainage with the Foley catheter (group A) and 270 with a urethral stent plus a gastric tube (group B). We compared the incidence rates of bladder irritation, fistula, urethral stricture, and urethral diverticulum between the two groups of patients. RESULTS: No statistically significant differences were found between groups A and B in the incidences of bladder irritation (9.89% vs 10.70%, P > 0.05) and urethral diverticulum (1.09% vs 2.22%, P > 0.05). The incidence rate of fistula was markedly higher in group A than in B (20.80% vs 13.30%, P < 0.05), and so was that of urethral stricture (10.90% vs 5.55%, P < 0.05). CONCLUSION: The urethral stent plus gastric tube draining method is more effective than the Foley catheter draining method for urine drainage following urethroplasty.

Two-stage repair with long channel technique for primary severe hypospadias.

OBJECTIVE: To introduce a 2-stage repair with long channel technique for primary severe hypospadias. PATIENTS AND METHODS: Between March 2010 and November 2013, 16 children with primary severe hypospadias underwent 2-stage repair with long channel technique. The technique applied in the first stage was almost the same as Bracka 2-stage repair. The second stage was usually performed 6 months later. A small transverse skin incision, distal to the meatal opening and about 1 cm in length, was made. Dissection was carried out deep into the surface of corpora cavernosa and a plane between the subcutaneous tissue and corpora cavernosa was reached. A long channel between the subcutaneous tissue and corpora cavernosa was created from the para-meatus incision to the apex of glans. A rectangle, pedicle scrotal septal skin flap was elevated and tubularized into neourethra around a stenting tube. The neourethra was delivered through the subcutaneous channel and fixed at the apex of glans. RESULTS: The mean operation time of the first and second stages was 65 and 55 minutes, respectively. The mean age at the first and second operation was 28 and 36 months, respectively. The mean follow-up was 10 months. No fistula, glans dehiscence, urethral stricture, and meatal stenosis were recorded. One scrotal surgical wound infection occurred after second stage and healed successfully with antibiotics treatment. The overall cosmetic and functional outcomes after second stage were excellent. CONCLUSION: Two-stage repair with long channel technique was applicable for primary severe hypospadias, with excellent short-term outcomes.

Quantitation of plasma circulating DNA using quantitative PCR for the detection of hepatocellular carcinoma.

Circulating DNA is a potential biomarker for tumor diagnosis and prognosis. This study was aimed to quantify the circulating DNA in plasma from patients with hepatocellular carcinoma (HCC) using quantitative PCR and evaluate its potential clinical value. Blood samples were collected from 72 patients with HCC, 37 with liver cirrhosis or chronic hepatitis and 41 healthy volunteers. Plasma DNA was extracted and quantified by a real-time quantitative PCR method. The diagnostic and prognostic value of plasma DNA analysis for HCC was evaluated. DNA levels in the HCC plasma (median: 173 ng/mL) were significantly higher than those in the healthy controls (9 ng/mL) or control benign patients (46 ng/mL) (P < 0.001). The area under the receiver-operation characteristic (ROC) curve (AUC) assessing plasma DNA was 0.949 for healthy controls and 0.874 for control patients. Plasma DNA detection could discriminate HCC from normal controls with 90.2% sensitivity and 90.3% specificity at the cut-off value of 18.2 ng/mL. Combined ROC analyses using plasma DNA and serum AFP revealed an elevated AUC of 0.974 with 95.1% sensitivity and 94.4% specificity in discriminating HCC from normal controls. The plasma DNA levels were positively associated with tumor size (P = 0.012), and were significantly elevated in HCC patients with intrahepatic spreading or vascular invasion (P = 0.035). The overall survival time of patients with high plasma DNA levels showed a shortened tread when compared with that of patients with low plasma DNA concentrations (P = 0.071). Plasma DNA may be a valuable noninvasive tool for the detecting and predicting the metastasis potential of HCC; and the prognostic value of plasma DNA needed further investigation.