Bladder Neck Contracture with Hem-o-Lok Clips Migration after Robotic-Assisted Radical Prostatectomy: A Case Report and Literature Review.

Hem-o-lok clips are widely used in robotic-assisted radical prostatectomy (RARP). However, clips-related complications have been reported, including intravesical migration. Here, we share a 60-year-old male case with newly diagnosed prostatic adenocarcinoma. With an unfavorable intermediate risk, he was admitted for RARP. He was discharged from hospital without any immediate complications. However, he reported progressive dysuria and slow urine stream 6 months after surgery. Cystoscopy showed severe bladder neck contracture (BNC), and 2 Hem-o-lok clips were found intravesically and removed during bladder neck incision. Subsequently, fiberocystoscopy revealed another 2 clips near the bladder neck with mild BNC after another 6 months. These 2 clips were also removed during bladder neck dilatation. His urination status then improved without further obstruction. Clip migration after RARP is uncommon; however, clinicians must keep this in mind when patients present with new complaints such as lower urinary tract symptoms, hematuria, and recurrent urinary tract infections.

Analysis of risk factors of bladder neck contracture following transurethral surgery of prostate.

BACKGROUNDS: The aim of the present study was to investigate the perioperative parameters associated with bladder neck contracture (BNC) after transurethral surgery of the prostate and to compare the incidence of BNC after transurethral resection of the prostate (TURP) or Thulium vaporesection (resection group) versus Thulium vapoenucleation or enucleation of the prostate (enucleation group). METHODS: Between March 2008 and March 2020, 2363 patients received TURP and 1656 patients received transurethral surgery of the prostate with Thulium laser (ThuP) at Mackay Memorial Hospital. A total of 62 patients developed BNC. These BNC patients were age-and operation-matched to 124 randomly sampled TURP/ThuP controls without BNC. A 1:1 propensity score matching model was used to evaluate the difference in incidence of BNC. RESULTS: Our study demonstrated that a greater proportion of BNC patients had history of cerebrovascular accidents (11/62 vs. 7/124, p = 0.009), coronary artery disease (14/48 vs. 16/108, p = 0.03), chronic kidney disease (14/62 vs. 11/124, p = 0.01), and two or more comorbidities (29/62 vs. 27/124, p = 0.001) compared with NBNC patients. Multivariate analysis showed that smaller prostate volume (OR 0.96 (0.94-0.99), p = 0.008) and recatherization (OR 5.6 (1.02-30.6), p = 0.047) were significantly associated with BNC. A ROC curve predicted that a prostate volume < 42.9 cm3 was associated with a notably higher rate of BNC. The propensity score matching model reported there was no difference in incidence between resection and enucleation groups. CONCLUSION: This study demonstrated that incidence of BNC was the same in different surgical techniques and that low prostate volume, recatherization and ≥ 2 comorbidities were positively correlated with the development of BNC after TURP or ThuP.

The relationship between androgen deprivation therapy and depression symptoms in patients with prostate cancer.

AIM: In this study, we administered a questionnaire to consecutive prostate cancer patients who received androgen deprivation therapy (ADT) for understanding the prevalence of depression symptoms. MATERIALS AND METHODS: We retrospectively identified patients with prostate adenocarcinoma who received ADT between January 2015 and February 2018 at Mackay Memorial Hospital. The patients were then asked to complete the Chinese version of the Patient Health Questionnaire-9 (PHQ-9) during an interview. The patients were divided into two groups according to PHQ-9 score: those with depression symptoms (PHQ-9 ≥ 6, depression group), and those without depression symptoms (PHQ-9 < 6, non-depression group). Two groups were compared using t-tests and correlation coefficients, as appropriate. Statistical significance was set at p < .05. RESULTS: There were no significant correlations between PHQ-9 scores and any of the parameters in the patients overall. In subgroup analysis, a positive correlation was found between the duration of ADT and PHQ-9 score in the patients with depression symptoms (p = .03). In addition, univariate analysis showed a positive association between the duration of ADT and PHQ-9 score, and a longer duration of ADT was further independently associated with increased PHQ-9 score in multivariate analysis in the patients with depression symptoms. CONCLUSION: This study demonstrated that in patients with prostate cancer and depression symptoms, the severity of the depression symptoms was positively correlated with the duration of ADT. In contrast, this association was not found in patients without depression symptoms.

Zonal adjusted PSA density improves prostate cancer detection rates compared with PSA in Taiwanese males with PSA < 20 ng/ml.

BACKGROUND: The current study aimed to compare the efficacy of transition zone PSA density (TZPSAD) with traditional PSA and PSA density (PSAD), for the diagnosis of prostate cancer (PCa) in Taiwanese males. METHODS: Men with PSA between 4.0 and 20.0 ng/ml who underwent a transrectal ultrasound (TRUS) guided prostate biopsy between the studied period were retrospectively identified. The demographic data, PSAD and TZPSAD were calculated in all patients. Receiver operating characteristic (ROC) curves were used to analyze the accuracy of a positive PCa diagnosis. RESULTS: The area under the ROC (AUC) was 0.615, 0.748 and 0.746 for PSA, PSAD and TZPSAD, respectively. The best cut-off of value for TZPSAD in predicting PCa in men with a PSA of 4.0-10.0 ng/ml was 0.367 ng/ml/ml with a sensitivity of 50% and a specificity of 77.5%. In men with a PSA of 10.1-20.0 ng/ml, the best cut-off value was 0.454 ng/ml, with a sensitivity of 74.8% and specificity of 70.9%. CONCLUSION: The use of TZPSAD can improve the efficiency and specificity of PSA for the diagnosis of PCa in Taiwanese men with PSA 4.0-20.0 ng/ml. TZPSAD efficiency was similar to PSAD but TZPSAD had better cancer specificity.

Comparison of ultrasound-assisted and pure fluoroscopy-guided extracorporeal shockwave lithotripsy for renal stones.

BACKGROUND: In this study, we aimed to compare the efficacy and clinical outcomes of shock wave lithotripsy (SWL) for patients with renal stones using pure fluoroscopy (FS) or ultrasound-assisted (USa) localization with two lithotripters. METHODS: We retrospectively identified 425 patients with renal calculi who underwent SWL with either a LiteMed LM-9200 ELMA lithotripter (209 cases), which combined ultrasound and fluoroscopic stone targeting or a Medispec EM-1000 lithotripter machine (216 cases), which used fluoroscopy for stone localization and tracking. The patient demographic data, stone-free rates, stone disintegration rates, retreatment rates and complication rates were analyzed. RESULTS: The USa group had a significantly higher overall stone-free rate (43.6 vs. 28.2%, p < 0.001) and stone disintegration rate (85.6 vs. 64.3%, p < 0.001), as well as a significantly lower retreatment rate (14.8 vs. 35.6%, p < 0.001) and complication rate (1.9 vs. 5.5%, p = 0.031) compared with the FS group. This superiority remained significant in the stone size < 1 cm stratified group. In the stone size > 1 cm group, the stone-free rate (32.4 vs. 17.8%, p = 0.028), disintegration rate (89.2 vs. 54.8%, p = 0.031) and retreatment rate (21.6 vs. 53.4%, p < 0.001) were still significantly better in the USa group, however there was no significant difference in the complication rate. The most common complication was post-SWL-related flank pain. CONCLUSION: SWL is a safe and non-invasive way of treating renal stones. This study compared two electromagnetic shock wave machines with different stone tracking systems. LiteMed LM-9200 ELMA lithotripter, which combined ultrasound and fluoroscopic stone targeting outperformed Medispec EM-1000 lithotripter, which used fluoroscopy for stone localization and tracking, with better stone-free rates and disintegration rates, as well as lower retreatment rates and complications with possible reduced radiation exposure.

Comparison of electrohydraulic and electromagnetic extracorporeal shock wave lithotriptors for upper urinary tract stones in a single center.

PURPOSE: To compare the efficacy and outcomes of shock wave lithotripsy (SWL) for upper urinary tract stones with an electrohydraulic (EH) and an electromagnetic (EM) lithotriptor in a single center. METHODS: The medical records of 272 patients with upper urinary tract stones ≤ 2 cm in size who underwent SWL with either the Medispec E3000 EH lithotriptor (179 cases) or the Medispec EM1000 EM lithotriptor (93 cases) were reviewed. The demographic data, stone parameters, stone-free rates, and retreatment rates were analyzed. RESULTS: The EH group had a higher stone-free rate (53.6 vs. 30.1%, p < 0.001) and a lower retreatment rate (32.4 vs. 61.2%, p < 0.001) for renal and upper third ureteral stones than the EM group. The stone-free rates for renal stones < 1 cm (55.5 vs. 32.2%, p = 0.045), ureteral stones < 1 cm (64.5 vs. 42.1%, p = 0.028), and renal stones ≥ 1 cm (43.1 vs. 0%, p = 0.03) were higher in the EH group. Two patients in the EH group had a renal hematoma needing hospitalization after SWL. There were no complications in the EM group. CONCLUSIONS: The Medispec E3000 EH lithotriptor had higher stone-free rates and lower retreatment rates than the Medispec EM1000 EM lithotriptor for renal stones < 2 cm and ureteral stones < 1 cm. Complications were rare.

Spontaneous regression of adrenal metastasis from renal cell carcinoma after sunitinib withdrawal: case report and literature review.

BACKGROUND: The spontaneous regression of metastatic renal cell carcinoma is a rare phenomenon, with an estimated incidence of < 1%. We report a case of post-nephrectomy renal cell carcinoma adrenal metastasis, followed by the spontaneous regression of the metastasis after withdrawal of sunitinib. CASE PRESENTATION: The patient was a 55-year-old male with clear cell type renal cell carcinoma who previously underwent a left laparoscopic radical nephrectomy. After 51 months of follow up, a recurrence in the left renal fossa was observed and subsequently excised. Four months after excision, an abdominal Computerized tomography (CT) identified an adrenal metastasis of 1.6 cm. The patient was treated with sunitinib. However, the treatment was discontinued because of gastrointestinal side effects and fatigue. Eleven months after the discontinuation of sunitinib treatment, a progression in the adrenal metastasis growth (5.7 cm) was observed, whereas 16 months after the discontinuation, a regression of the adrenal metastasis growth (3.4 cm) was observed. During subsequent follow-ups, a gradual reduction in the size of the adrenal metastasis (1.8 cm) was observed. After 44 months from the discontinuation of sunitinib treatment, the patient was still alive and followed up in the outpatient department. CONCLUSIONS: Sunitinib is a multi-targeted inhibitor of vascular endothelial growth factor (VEGF) receptors. This compound reduces tumor angiogenesis and has been approved worldwide for the treatment of advanced renal cell carcinoma. To our knowledge, this is the fourth case of the spontaneous regression of metastatic renal cell carcinoma after the discontinuation of sunitinib treatment.

Investigation of Interactive Activity of Electro-Acupuncture on Pharmacokinetics of Sildenafil and Their Synergistic Effect on Penile Blood Flow in Rats.

Erectile dysfunction (ED) is a disorder found in males throughout the world, which negatively affects relationships with partners with advancing age. Hence, in this study, we tested a combined novel treatment of electro-acupuncture (EA) and sildenafil citrate against ED. In addition to EA therapy, the sildenafil citrate, a phosphodiesterase 5 inhibitor, is a widely recognized drug that has achieved considerable success in the treatment of ED. However, the combined effect of both the EA and sildenafil has not yet been investigated. Hence, we aimed to examine the effect of EA on the pharmacokinetics and pharmacodynamics of sildenafil in rat plasma. The pharmacokinetic parameters were determined using ultra performance liquid chromatography (UPLC) after EA and sildenafil administration (10 mg/Kg). Following this, the pharmacodynamics was studied via blood flow pattern using developing Doppler images of the lower body and penis. The pharmacokinetic studies demonstrated that sildenafil significantly increases by administration of low-frequency EA. Further, the pharmacodynamic studies using Doppler imaging revealed an elevated blood flow in rat penis compared with lower body during combined treatment of sildenafil and low-frequency EA. These data indicate a synergistic therapeutic effect of EA and sildenafil for the treatment of ED.

FTY720 inhibits germ cell apoptosis in testicular torsion/detorsion.

BACKGROUND: Testicular torsion/detorsion (T/D) can induce germ cells apoptosis, which may lead to impairment of spermatogenesis. FTY720, an agonist of the sphingosine-1-phosphate receptor 1 (S1PR1), inhibits apoptosis in ischemic stroke. We examined whether FTY720 could mitigate germ cell apoptosis in testicular T/D rats. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were allocated to receive testicular T/D (the T/D group), T/D plus FTY720 (the T/D-FTY group), or T/D plus FTY720 plus the potent S1PR1 antagonist VPC23019 (the T/D-FTY-VPC group; n = 6 in each group). Sham control groups were run simultaneously. At 24 h after detorsion, rats were euthanized. RESULTS: Our data revealed that, in the ipsilateral twisted testes, sperm counts and expression of the S1PR1 of the T/D and the T/D-FTY-VPC groups were significantly lower than those of the T/D-FTY group (all P < 0.001). In contrast, signals of apoptotic cells stained by terminal deoxynucleotidyl transferase dUTP nick end labeling and the proapoptotic protein cleaved caspase-3 of the T/D, and the T/D-FTY-VPC groups were significantly stronger than those of the T/D-FTY group. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end labeling signals mainly localized to germ cells. CONCLUSIONS: FTY720 could mitigate testicular T/D-induced germ cell apoptosis, and the mechanisms may involve the S1PR1.

Role of Mitochondrial DNA Copy Number Alteration in Human Renal Cell Carcinoma.

We investigated the role of mitochondrial DNA (mtDNA) copy number alteration in human renal cell carcinoma (RCC). The mtDNA copy numbers of paired cancer and non-cancer parts from five resected RCC kidneys after radical nephrectomy were determined by quantitative polymerase chain reaction (Q-PCR). An RCC cell line, 786-O, was infected by lentiviral particles to knock down mitochondrial transcriptional factor A (TFAM). Null target (NT) and TFAM-knockdown (TFAM-KD) represented the control and knockdown 786-O clones, respectively. Protein or mRNA expression levels of TFAM; mtDNA-encoded NADH dehydrogenase subunit 1 (ND1), ND6 and cytochrome c oxidase subunit 2 (COX-2); nuclear DNA (nDNA)-encoded succinate dehydrogenase subunit A (SDHA); v-akt murine thymoma viral oncogene homolog 1 gene (AKT)-encoded AKT and v-myc myelocytomatosis viral oncogene homolog gene (c-MYC)-encoded MYC; glycolytic enzymes including hexokinase II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), and lactate dehydrogenase subunit A (LDHA); and hypoxia-inducible factors the HIF-1α and HIF-2α, pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase E1 component α subunit (PDHA1) were analyzed by Western blot or Q-PCR. Bioenergetic parameters of cellular metabolism, basal mitochondrial oxygen consumption rate (mOCRB) and basal extracellular acidification rate (ECARB), were measured by a Seahorse XF(e)-24 analyzer. Cell invasiveness was evaluated by a trans-well migration assay and vimentin expression. Doxorubicin was used as a chemotherapeutic agent. The results showed a decrease of mtDNA copy numbers in resected RCC tissues (p = 0.043). The TFAM-KD clone expressed lower mtDNA copy number (p = 0.034), lower mRNA levels of TFAM (p = 0.008), ND1 (p = 0.007), and ND6 (p = 0.017), and lower protein levels of TFAM and COX-2 than did the NT clone. By contrast, the protein levels of HIF-2α, HK-II, PFK, LDHA, AKT, MYC and vimentin; trans-well migration activity (p = 0.007); and drug resistance to doxorubicin (p = 0.008) of the TFAM-KD clone were significantly higher than those of the NT clone. Bioenergetically, the TFAM-KD clone expressed lower mOCRB (p = 0.009) but higher ECARB (p = 0.037) than did the NT clone. We conclude that a reduction of mtDNA copy number and decrease of respiratory function of mitochondria in RCC might be compensated for by an increase of enzymes and factors that are involved in the upregulation of glycolysis to confer RCC more invasive and a drug-resistant phenotype in vitro.

FTY720 mitigates torsion/detorsion-induced testicular injury in rats.

BACKGROUND: FTY720, a sphingosine-1-phosphate (S1P) receptor agonist, possesses potent anti-inflammation capacity. We evaluated the therapeutic potentials of FTY720 against testicular injury induced by testicular torsion and/or detorsion (T/D). MATERIALS AND METHODS: Young adult male Sprague-Dawley rats were allocated to receive T/D (the T/D group) and T/D plus FTY720 (4 mg/kg, the T/D-FTY group, n = 6 in each group). To investigate the possible roles of the S1P receptors, another group of rats received T/D plus FTY720 plus the potent S1P receptor antagonist VPC23019 (1 mg/kg, the T/D-FTY-VPC group, n = 6). FTY720 was administered immediately before testicular detorsion, and VPC23019 was administered 30 min before FTY720. Another set of rats that received sham operation, immediately followed by injection of normal saline, FTY720, or FTY720 plus VPC23019, served as control groups. Sham control groups were run simultaneously. After euthanization, levels of testicular injury were measured. RESULTS: Histologic findings revealed severe testicular injury changes in both the T/D and T/D-FTY-VPC groups and moderate testicular injury changes in the T/D-FTY group. In addition, malondialdehyde activity (oxidative status), concentration of interleukin-1ß (inflammation index), myeloperoxidase activity (neutrophil infiltration index), and wet-to-dry weight ratio (tissue edema index) of both the T/D and T/D-FTY-VPC groups were significantly higher than those of the T/D-FTY group. These data confirmed the protective effects of FTY720 against testicular T/D. Moreover, antagonizing the S1P receptors could reverse the protective effects of FTY720. CONCLUSIONS: FTY720 significantly mitigated testicular injury induced by testicular T/D. The mechanisms may involve activating the S1P receptors.

Study design, rationale and methods for a population-based study of myopia in schoolchildren: the Myopia Investigation study in Taipei.

BACKGROUND: To describe the study design, rationale and methodology of the Myopia Investigation Study in Taipei (MIT). DESIGN: The MIT was a city-wide, population-based cohort study. PARTICIPANTS: Participants were grade 2 students (Fall 2013) of all 153 elementary schools in Taipei City. METHODS: The baseline data on the risk factors for myopia development was collected by parent-administered questionnaire surveys covering demographics, medical history, parental myopia, time spent on near work and outdoor activities, reading habits and eye care-seeking behaviour. Ocular examinations focused on the measurement of visual acuity (unaided and best-corrected) and refractive status (before and after cycloplegia), which will be carried out for the eligible schoolchildren biannually for 3 years consecutively. Once myopic children are identified, case manager-led telecoaching for health-care instructions and reminders will be delivered to parents or caregivers. MAIN OUTCOME MEASURES: To build a comprehensive database for prevalence, incidence and risk factors of early childhood myopia over a 3-year follow-up period. RESULTS: Of all 19 374 eight-year-old schoolchildren (10 210 [52.7%] boys) eligible for the MIT, 16 486 (85.1%) responded to the questionnaire, 12 019 (62.0%) were examined during the third quarter of 2013 and 11 590 (59.8%) (6267 [52.9%] boys) completed cycloplegic autorefraction on both eyes and were enrolled for further data analysis. There was no significant difference in terms of demographics between the analysed participants and all grade 2 students in Taipei City. CONCLUSIONS: Data from the MIT will provide population-based information concerning the prevalence, incidence and risk factors for myopia development among young schoolchildren in a metropolitan area of Taiwan.

Butein inhibits metastatic behavior in mouse melanoma cells through VEGF expression and translation-dependent signaling pathway regulation.

BACKGROUND: Melanoma is an aggressive skin cancer and a predominant cause of skin cancer-related deaths. A previous study has demonstrated the ability of butein to inhibit tumor proliferation and invasion. However, the anti-metastatic mechanisms and in vivo effects of butein have not been fully elucidated. METHODS: MTT cell viability assays were used to evaluate the antitumor effects of butein in vitro. Cytotoxic effects of butein were measured by lactate dehydrogenase assay. Anti-migratory effects of butein were evaluated by two-dimensional scratch and transwell migration assays. Signaling transduction and VEGF-releasing assays were measured by Western blotting and ELISA. We also conducted an experimental analysis of the metastatic potential of tumor cells injected into the tail vein of C57BL/6 mice. RESULTS: We first demonstrated the effect of butein on cell viability at non-cytotoxic concentrations (1, 3, and 10 µM). In vitro, butein was found to inhibit the migration of B16F10 cells in a concentration-dependent manner using transwell and scratch assays. Butein had a dose-dependent effect on focal adhesion kinase, Akt, and ERK phosphorylation in B16F10 cells. Butein efficiently inhibited the mTOR/p70S6K translational inhibition machinery and decreased the production of VEGF in B16F10 cells. Furthermore, the in vivo antitumor effects of butein were demonstrated using a pulmonary metastasis model. CONCLUSION: The results of the present study indicate the potential utility of butein in the treatment of melanoma.

Varicocele is associated with varicose veins: A population-based case-control study.

OBJECTIVE: To analyze the association between patients with varicocele and varicose veins in Taiwan. METHODS: Between 2001 and 2010, comprehensive data were analyzed on the characteristics of patients with varicocele and varicose veins in Taiwan through a retrospective, nationwide, population-based study. Data were obtained from the Taiwan National Health Insurance Research Database. A total of 2727 cases with varicose veins and 10 908 randomly selected controls were included in this study. Conditional logistic regression analyses were used to examine the association between varicose veins and varicocele. RESULTS: The prevalence of varicocele was 1.3% and 0.3% for cases (with varicose veins) and controls (without varicose vein), respectively (P < 0.001). Conditional logistic regression analysis showed that the odds ratio of being previously diagnosed with varicose veins for cases was 4.71 (95% confidence interval 2.87-7.89) when compared with controls after adjusting for age, diabetes, heart disease, chronic obstructive pulmonary disease, liver and kidney disease, and edema. Furthermore, the odds ratio was 5.96 (95% confidence interval 2.90-12.24), 4.76 (95% confidence interval 1.68-13.48) and 1.69 (95% confidence interval 0.30-9.55) in patients aged <50 years, 51-65 years and >65 years, respectively. In addition, the prevalence of male infertility was 15.1% for patients with varicocele and varicose veins, and 14.5% for patients with varicocele only, but no significant difference was observed. CONCLUSION: Our findings suggest an association between both varicocele and varicose veins. In addition, this association is higher in patients aged younger than 50 years. Evaluation of male patients with varicose veins for varicocele should be recommended.

TREM-1 regulates macrophage polarization in ureteral obstruction.

Chronic kidney disease (CKD) is an emerging worldwide public health problem. Inflammatory cell infiltration and activation during the early stages in injured kidneys is a common pathologic feature of CKD. Here, we determined whether an important inflammatory regulator, triggering receptor expressed on myeloid cells (TREM)-1, is upregulated in renal tissues collected from mouse ureteral obstruction-induced nephritis. TREM-1 is crucial for modulating macrophage polarization, and has a pivotal role in mediating tubular injury and interstitial collagen deposition in obstructive nephritis. Lysates from nephritic kidneys triggered a TREM-1-dependent M1 polarization ex vivo, consistent with the observation that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived M1 macrophages express higher levels of TREM-1 in comparison with M-CSF-derived cells. Moreover, agonistic TREM-1 cross-link significantly strengthens the inductions of iNOS and GM-CSF in M1 cells. These observations are validated by a strong clinical correlation between infiltrating TREM-1-expressing/iNOS-positive macrophages and renal injury in human obstructive nephropathy. Thus, TREM-1 may be a potential diagnostic and therapeutic target in human kidney disease.

Comparison of genome-wide DNA methylation in urothelial carcinomas of patients with and without arsenic exposure.

BACKGROUND: Arsenic is a well-documented carcinogen of human urothelial carcinoma (UC) with incompletely understood mechanisms. OBJECTIVES: This study aimed to compare the genome-wide DNA methylation profiles of arsenic-induced UC (AsUC) and non-arsenic-induced UC (Non-AsUC), and to assess associations between site-specific methylation levels and cumulative arsenic exposure. METHODS: Genome-wide DNA methylation profiles in 14 AsUC and 14 non-AsUC were analyzed by Illumina Infinium methylation27 BeadChip and validated by bisulfite pyrosequencing. Mean methylation levels (߯) in AsUC and non-AsUC were compared by their ratio (߯ ratio) and difference (Δ߯). Associations between site-specific methylation levels in UC and cumulative arsenic exposure were examined. RESULTS: Among 27,578 methylation sites analyzed, 231 sites had ߯ ratio >2 or <0.5 and 45 sites had Δ߯ >0.2 or <-0.2. There were 13 sites showing statistically significant (q<0.05) differences in ߯ between AsUC and non-AsUC including 12 hypermethylation sites in AsUC and only one hypermethylation site in non-AsUC. Significant associations between cumulative arsenic exposure and DNA methylation levels of 28 patients were observed in nine CpG sites of nine gens including PDGFD (Spearman rank correlation, 0.54), CTNNA2 (0.48), KCNK17 (0.52), PCDHB2 (0.57), ZNF132 (0.48), DCDC2 (0.48), KLK7 (0.48), FBXO39 (0.49), and NPY2R (0.45). These associations remained statistically significant for CpG sites in CTNNA2, KLK7, NPY2R, ZNF132 and KCNK17 in 20 non-smoking women after adjustment for tumor stage and age. CONCLUSIONS: Significant associations between cumulative arsenic exposure and methylation level of CTNNA2, KLK7, NPY2R, ZNF132 and KCNK17 were found in smoking-unrelated urothelial carcinoma. Arsenic exposure may cause urothelial carcinomas through the hypermethylation of genes involved in cell adhesion, proteolysis, transcriptional regulation, neuronal pathway, and ion transport. The findings of this study, which are limited by its small sample size and moderate dose-response relation, remain to be validated by further studies with large sample sizes.

Curriculum reform at Chinese medical schools: what have we learned?

INTRODUCTION: Curriculum reform at Chinese medical schools has attracted a lot of attention recently. Several leading medical schools in China have undergone exploratory reforms and in so doing, have accumulated significant experience and have made considerable progress. METHODS: An analysis of the reforms conducted by 38 Chinese medical colleges that were targeted by the government for upgrade was performed. Drawing from both domestic and international literature, we designed a questionnaire to determine what types of curricular reforms have occurred at these institutions and how they were implemented. Major questions touched upon the purpose of the reforms, curricular patterns, improvements in teaching methods post-reform, changes made to evaluation systems post-reform, intra-university reform assessment, and what difficulties the schools faced when instituting the reforms. Besides the questionnaire, relevant administrators from each medical school were also interviewed to obtain more qualitative data. RESULTS: Out of the 38 included universities, twenty-five have undergone major curricular reforms. Among them, 60.0% adopted an organ system-based curriculum model, 32.0% adopted a problem-based curriculum model, and 8.0% adopted a hybrid curriculum model. About 60.0% of the schools' reforms involved both the "pre-clinical" and the "clinical" curricula, 32.0% of the schools' reforms were limited to the "pre-clinical" curricula, and 8.0% of the schools' reforms only involved the "clinical" curricula. Following curricular reform, 60.0% of medical schools experienced an overall reduction in teaching hours, 76.0% reported an increase in their students' clinical skills, and 60.0% reported an increase in their students' research skills. DISCUSSION: Medical curricular reform is still in its infancy in China. The republic's leading medical schools have engaged in various approaches to bring innovative teaching methods to their respective institutions. However, due to limited resources and the shackle of traditional pedagogical beliefs among many faculty and administrators, progress has been significantly hindered. Despite these and other challenges, many medical schools report positive initial results from the reforms that they have enacted. Although the long term effects of such reforms remain unclear, curricular reform appears to be the inevitable solution to China's growing need for high-quality medical doctors.

A snapshot of the status of problem-based learning (PBL) in Chinese medical schools.

INTRODUCTION: In North America, where it was born, problem-based learning (PBL) has seen dips and rises in its popularity, but its inherent strengths have led to its spread to medical schools all over the world. Although its use at medical schools in some Western countries has already been examined, no one has looked at its status in many other countries, including China. The aim of this study is to determine the number of schools currently using PBL in China, the degree to which they use it, and the reasoning behind such usage. METHODS: We used survey and internet search to examine PBL usage at Chinese medical schools. We were able to collect data from 43 first-class Chinese medical schools that are geographically diverse and thus representative of medical schools all across China. RESULTS: 34 (79.1%) of the 43 medical schools use PBL in the preclinical curriculum. Of the 34, data were collected from 24 (70.6%) medical schools regarding the extent of their PBL usage. Nine (37.5%) schools use PBL for less than 10% of preclinical hours, 14 (58.3%) schools use PBL for 10-50% of preclinical hours, and one (4.2%) school uses PBL for more than 50% of preclinical hours. CONCLUSION: In our sample of Chinese medical institutions, a large majority of schools use PBL, however, most schools use it for less than 50% of total preclinical curricular hours. Our results suggest that schools are interested in increasing the number of curricular hours devoted to PBL but are constrained by resources.

Advantages of retrograde intrarenal incision versus laparoscopic surgery in management of pararenal cysts: a single-center experience.

PURPOSE: Renal cysts are typically a benign condition, and parapelvic cysts are a type of renal cyst that occur adjacent to the renal pelvis or renal sinus. Parapelvic cysts can increase the risk for injury to adjacent organs or urine leakage during laparoscopic surgery. Flexible ureteroscopes with laser assistance were used to make internal incisions in cysts. Perioperative outcomes of this method were compared with those of laparoscopic surgery. METHODS: Eight-three patients, who underwent surgical treatment for renal cysts at the authors' medical center between January 2019 and June 2022, were evaluated. Two patients were excluded because they originally opted for RIRS but subsequently converted to laparoscopic surgery. Patients were divided into 2 groups based on surgery type: laparoscopic; and RIRS for internal incision. Outcomes in both groups were analyzed. RESULTS: Of the 81 patients analyzed, 60 [74% (group 1)] underwent laparoscopic surgery and 21 [26% (group 2)] underwent RIRS for internal incision. The median operative durations for groups 1 and 2 were 87 and 56 min, respectively (p < 0.001). Relative to RIRS, laparoscopic surgery resulted in greater postoperative painkiller use (laparoscopic surgery versus [vs.] RIRS, 43% vs. 19%; p = 0.047). The median length of hospital stay was 2 and 1 days, respectively (p < 0.001). CONCLUSIONS: RIRS demonstrated several advantages over laparoscopic surgery for the internal incision of parapelvic cysts, including shorter operative duration, shorter hospital stay, and less postoperative pain control. These findings may guide the selection of appropriate surgical approaches for patients with renal cysts.

Causally Probing the Role of the Hippocampus in Fear Discrimination: A Precision Functional Mapping-Guided, Transcranial Magnetic Stimulation Study in Participants With Posttraumatic Stress Symptoms.

Background: Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety. A dominant model posits that hippocampal pattern separation failures drive overgeneralization. Hippocampal network-targeted transcranial magnetic stimulation (HNT-TMS) has been shown to strengthen hippocampal-dependent learning/memory processes. However, no study has examined whether HNT-TMS can alter fear learning/memory. Methods: Continuous theta burst stimulation was delivered to individualized left posterior parietal stimulation sites derived via seed-based connectivity, precision functional mapping, and electric field modeling methods. A vertex control site was also stimulated in a within-participant, randomized controlled design. Continuous theta burst stimulation was delivered prior to 2 visual discrimination tasks (1 fear based, 1 neutral). Multilevel models were used to model and test data. Participants were undergraduates with posttraumatic stress symptoms (final n = 25). Results: Main analyses did not indicate that HNT-TMS strengthened discrimination. However, multilevel interaction analyses revealed that HNT-TMS strengthened fear discrimination in participants with lower fear sensitization (indexed by responses to a control stimulus with no similarity to the conditioned fear cue) across multiple indices (anxiety ratings: ß = 0.10, 95% CI, 0.04 to 0.17, p = .001; risk ratings: ß = 0.07, 95% CI, 0.00 to 0.13, p = .037). Conclusions: Overgeneralization is an associative process that reflects deficient discrimination of the fear cue from similar cues. In contrast, sensitization reflects nonassociative responding unrelated to fear cue similarity. Our results suggest that HNT-TMS may selectively sharpen fear discrimination when associative response patterns, which putatively implicate the hippocampus, are more strongly engaged.

Fear overgeneralization is a promising pathogenic mechanism of clinical anxiety that is thought to be driven by deficient hippocampal discrimination. Using hippocampal network­targeted transcranial magnetic stimulation (HNT-TMS) in healthy participants with symptoms of posttraumatic stress, Webler et al. report that HNT-TMS did not strengthen discrimination overall, but it did strengthen fear discrimination in participants with lower fear sensitization. Sensitization reflects nonassociative fear responding unrelated to fear cue similarity and therefore is not expected to engage the hippocampal discrimination function. These results suggest that HNT-TMS may selectively sharpen fear discrimination when the hippocampal discrimination function is more strongly engaged.