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This study explores the potential efficacy of chlorogenic acid (CGA) in mitigating lipopolysaccharide (LPS)-induced cystitis in a mice model. C57BL/6J mice were divided into four groups: normal control (NC), LPS, LPS + low CGA, and LPS + high CGA. Evaluation methods included cystometrogram (CMG), histopathological, western blot, and immunohistological analysis. In the LPS group, CMG revealed abnormal voiding behavior with increased micturition pressure, voided volume (VV), and decreased voided frequency. Low CGA treatment in LPS mice demonstrated improved micturition pressure and inter-contraction intervals (ICI). However, high CGA treatment exhibited prolonged ICI and increased VV, suggesting potential adverse effects. Histological analysis of LPS-treated mice displayed bladder inflammation and interstitial edema. Low CGA treatment reduced interstitial edema and bladder inflammation, confirmed by Masson’s trichrome staining. Western blotting revealed increased cytokeratin 20 (K20) expression in the low CGA group, indicating structural abnormalities in the bladder umbrella layer after LPS administration. In conclusion, low CGA treatment positively impacted voiding behavior and decreased bladder edema and inflammation in the LPS-induced cystitis mice model, suggesting its potential as a supplement for inflammation cystitis prevention. However, high CGA treatment exhibited adverse effects, emphasizing the importance of dosage considerations in therapeutic applications.

Background: The intracavernosal (IC) injection of chitosan activated platelet rich plasma (cPRP) has shown to improve the erectile dysfunction in cavernous nerve injury rat model. However, the action target of PRP in improving neurogenic erectile dysfunction remains unclear. We aimed to determine the effect of cPRP action at early stage that further mediates its effect on erectile function (EF) recovery in the bilateral cavernous nerve crushing (BCNC) injury rat model. Methods: Fifty-four rats were randomly divided into two equal groups: intracavernosal ( IC) injection of saline after BCNC (group 1) and IC injection of cPRP after BCNC (group 2). Five animals in each group were euthanized at 3, 7 and 14 day (d) post-injection, and the tissues were harvested to conduct transmission electron microscopy and histological assays. Six animals in each group were used to determine the recovery of EF at 14 and 28 d post-injury. Results: IC injections of cPRP increased all EF parameters at 28 d and 14 d post-injury (p

PurposeTaiwan has a high incidence of upper tract urothelial carcinoma (UTUC). This study aimed to compare the surgical outcomes following transperitoneal hand-assisted laparoscopic nephroureterectomy (TP-HALNU) and transperitoneal pure laparoscopic nephroureterectomy (TP-LNU) from the Taiwan nationwide UTUC collaboration database using different parameters, including surgical volumes.Materials and methodsThe nationwide UTUC collaboration database includes 14 hospitals in Taiwan from the Taiwan Cancer Registry. We retrospectively reviewed the records of 622 patients who underwent laparoscopic nephroureterectomy between July 1988 and September 2020. In total, 322 patients who received TP-LNU or TP-HALNU were included in the final analysis. Clinical and pathological data and oncological outcomes were compared.ResultsOf the 322 patients, 181 and 141 received TP-LNU and TP-HALNU, respectively. There were no differences in clinical and histopathological data between the two groups. No differences were observed in perioperative and postoperative complications. There were no significant differences in oncological outcomes between the two surgical approaches. In the multivariate analysis, the cohort showed that age ≥70 years, positive pathological lymph node metastasis, tumors located in the upper ureter, and male sex were predictive factors associated with an increased risk of adverse oncological outcomes. A surgical volume of ≥20 cases showed a trend toward favorable outcomes on cancer-specific survival [hazard ratio (HR) 0.154, p = 0.052] and marginal benefit for overall survival (HR 0.326, p = 0.019) in the multivariate analysis.ConclusionAlthough different approaches to transperitoneal laparoscopic nephroureterectomy showed no significant differences in surgical outcomes, age, sex, lymph node metastasis, and tumor in the upper ureter in the following period were predictive factors for oncological outcomes. Higher surgical volume did not impact disease-free survival and bladder recurrence-free survival but was associated with improved overall survival and cancer-specific survival. Exploration of unknown influencing factors is warranted.

Newly diagnosed pancreatic cancer increases year by year, while the prognosis of pancreatic cancer has not been very good. Statin drugs were found to have protective effects against a variety of cancers, but their association with pancreatic cancer remains to be clarified. This study used different pancreatic cancer cell lines and in different animal models to confirm the relationship between simvastatin and pancreatic cancer. Flow cytometry and luciferase-based bioluminescent images were used to investigate the cell cycle and tumor growth changes under simvastatin treatment. Simvastatin decreased the MIA PaCa-2 cells, PANC-1 cells, and BxPC-3 cell viability significantly and may arrest the cell cycle in the G0 phase. During in vivo study, subcutaneously implanted simvastatin pre-treated pancreatic cancer cells and intraperitoneally treated simvastatin continuously demonstrated a slower tumor growth rate and decreased the tumor/body weight ratio significantly. In intravenous implant models, implanted simvastatin-pre-treated BxPC-3 cells and cells treated along with simvastatin significantly decreased the tumor growth curve. Implanting the simvastatin-pre-treated pancreatic cells in the subcutaneous model showed better growth inhibition than the intravenous model. These results suggest simvastatin treatment may relate to different signaling pathways in local growth and metastasis. Pancreatic cancer cells presented different growth patterns in different animal-induced models, which could be important for clinical reference when it comes to the relationship of long-term statin use and pancreatic cancer.

Congenital bilateral absence of vas deferens (CBAVD) is a special entity in obstructive azoospermia. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are involved in Taiwanese CBAVD but most heterozygous 5T variant. The solute carrier family 9 isoform 3 (SLC9A3) is the Na+/H+ exchanger, which interacts with CFTR and regulates the Ca2+ homeostasis. Loss of SLC9A3 decreases CFTR protein and causes obstructive azoospermia in mice. It also causes mal-reabsorption by the efferent tubules, which leads to the obstructive phenomenon and eventually results in testicular atrophy. In 6-month old SLC9A3 deficiency mice, the atrophy of their vas deferens and seminal vesicles become more prominent. Decreases of CFTR expression in the reproductive organ in the SLC9A3 deficient (−/−) mice prove the interaction between CFTR and SLC9A3 in the reproductive tract. Most of Taiwanese CBAVD have at least one variant of SLC9A3 deletion and CFTR IVS8-5T, which co-contribute to Taiwanese CBAVD. The report indicates SLC9A3 deficiency can reverse the pathological changes in the gastrointestinal tract of CF mice. Further research can explore the definite mechanism of SLC9A3 and its role interacting with CFTR in different organ systems, which can contribute to novel treatment for the patients with cystic fibrosis and CBAVD. Keywords: Congenital bilateral absence of vas deferens, Cystic fibrosis transmembrane conductance regulator, Solute carrier family 9 isoform 3

Abstract Background Disparities in prostate cancer (PCa) outcomes and their links to socioeconomic status (SES) have been intensively studied. A relatively low incidence rate and a high proportion of late-stage diagnosis have been documented in studies of Asian populations. For the past 20 years, the trend in the growth of PCa cases in Taiwan was opposite to that of Western countries. However, there is a striking paucity of local studies on these important issues. To mitigate this gap in knowledge, we exploited two population databases to investigate the impact of SES on PCa incidence rate and stage at diagnosis. Particularly, we sought to explore the discriminating capabilities of various indexes of SES on two diagnostic outcome indicators. Method We conducted a population-based, follow-up, observational study. Data of study populations and newly diagnosed PCa cases between 2011 and 2013 were collected from the National Health Insurance Research Database and the Taiwan Cancer Registry. We retrieved 50–79 old male subjects who were classified as government employee, enterprise employee, or labor class. People with a diagnosis of any type of cancer before January 1, 2011, were excluded. The influences of four independent variables, i.e., age, beneficiary’s insurance status, occupation and income, were analyzed. We used Cox proportional hazard models to calculate the hazard ratios of PCa and used logistic regression models to analyze the odds ratios (ORs) of late-stage PCa diagnosis. Results The low crude PCa incidence rate (112 per 100,000 person-years) and the high percentage of late-stage presentation (44%) were similar to those found in previous studies of old Asian men. Unsurprisingly, age was consistently revealed to be the most determinant factor in PCa diagnosis, while the insurance status of the beneficiaries showed no significant difference. Significant socioeconomic disparities in PCa diagnosis were demonstrated by occupation and income indexes, individually or in combination. However, occupation and income showed varied capabilities in discriminating disparities between different outcome indicators. Conclusion Our study supported the findings of extant works showing that advantaged populations have a higher PCa incidence rate and a lower percentage of late-stage diagnosis. The discriminating capabilities of health disparity by occupation and/or income were contingent on the choice of health outcome indicators. The relatively high percentage of late-stage presentation is a critical public health challenge, and a tailored coping strategy is urgently needed. For more effective health policy-making, local socioeconomic effects on the other outcome indicators of PCa, such as incidence to mortality ratio, warrant further investigation.

Objective: To explore the factors influencing the trends in incidence and cost for female inpatient urinary incontinence (UI) surgery from 1997 to 2011. Materials and methods: A dataset of one million individuals was randomly drawn from the nationwide National Health Insurance claim database covering Taiwan's population from 1997 to 2011. The participants consisted of women aged ≥20 years who underwent UI surgery. We evaluated the trends of inpatient UI incidence, the medical cost of UI surgery, and the number of UI surgeries performed from 1997 to 2011. Results: A total of 1517 women underwent inpatient UI surgery from 1997 to 2011. Among these patients, the age-standardized incidence of UI surgery gradually trended upward from 1997 to 2010 but decreased in 2011. The trends were similar for medical costs, including annual inpatient cost, total medical service cost, and surgery fees. The annual inpatient cost had doubled in 2011 compared with that in 1997. However, physician visit fees, ward fees, and anesthesia fees started decreasing from 2005. The length of hospital stay and medication fees decreased during the 15-year study period. Surgeries by doctor specialty, hospital accreditation level, and patient age were stable for the study period. Conclusion: The trends of age-standardized incidence of UI surgery, annual inpatient cost, total inpatient cost, and surgery fees increased significantly from 1997 to 2009, and abruptly decreased from 2010 to 2011. Long-term observation evaluating the impact of Diagnosis-Related Group payment system in Taiwan is warranted to verify in the future.

Traditional bladder volume measurement from B-mode (two-dimensional) ultrasound has been found to produce inaccurate results, and thus in this work we aim to improve the accuracy of measurement from B-mode ultrasound. A total of 75 electronic medical records including ultrasonic images were reviewed retrospectively from 64 patients. We put forward a novel bladder volume measurement method, in which a three-dimensional (3D) reconstruction model was established from conventional two-dimensional (2D) ultrasonic images to estimate the bladder volume. The differences and relationships were analyzed among the actual volume, the traditional estimated volume, and the new reconstruction model estimated volume. We also compared the data in different volume groups from small volume to high volume. The mean actual volume is 531.8 mL and the standard deviation is 268.7 mL; the mean percentage error of traditional estimation is −28%. In our new bladder measurement method, the mean percentage error is −10.18% (N = 2), −4.72% (N = 3), −0.33% (N = 4), and 2.58% (N = 5). There is no significant difference between the actual volume and our new bladder measurement method (N = 4) in all data or the divided four groups. The estimated volumes from the traditional method or our new method are highly correlated with the actual volume. Our data show that the three-dimensional bladder reconstruction model provides an accurate measurement from conventional B-mode ultrasonic images compared with the traditional method. The accuracy is seen across different groups of volume, and thus we can conclude that this is a reliable and economical volume measurement model that can be applied in general software or in apps on mobile devices.

This study aimed to determine the mechanism of ketamine-induced cystitis without metabolism. A total of 24 adult male Sprague-Dawley rats were separated into control, ketamine, and norketamine groups. To induce cystitis, rats in the ketamine and norketamine groups were treated with intravesical instillation of ketamine and norketamine by mini-osmotic pump, which was placed in subcutaneous space, daily for 24 h for 4 weeks. After 4 weeks, all rats were subjected to bladder functional tests. The bladders were collected for histological and pathological evaluation. Compared to control, ketamine treatment demonstrated an increase in the bladder weight, high bladder/body coefficient, contractive pressure, voiding volume, collagen deposition, reduced smooth muscle content, damaged glycosaminoglycan layer, and low bladder compliance. Compared to ketamine, norketamine treatment showed more severe collagen deposition, smooth muscle loss, damaged glycosaminoglycan layer, and increased residual urine. Intravesical administration of ketamine and norketamine induced cystitis with different urodynamic characteristics. Norketamine treatment caused more severe bladder dysfunction than ketamine treatment. Direct treatment of the bladder with norketamine induced symptoms more consistent with those of bladder outlet obstruction than ketamine cystitis. Detailed studies of cellular mechanisms are required to determine the pathogenesis of ketamine cystitis.

Objective: To evaluate the benefits of antibiotic-impregnated inflatable penile prosthesis (IPP; InhibiZone®) in patients at high risk of infection in Taiwan. Materials and methods: From 2004 to 2008, 39 patients diagnosed with uncorrectable erectile dysfunction received an IPP implantation at our hospitals. Based on the underlying diseases, the patients were divided into groups. The results of the two study groups were compared with a control group, which received a conventional IPP implantation. The control group was also divided into two groups based on underlying diseases, similar to that of the study groups. Single-tailed Student t test was performed to determine the difference between each group and to compare the data of our patients with our previously published results. Results: Surgical outcome analysis showed that the postoperative infection rate is lower in the InhibiZone group (2.6% overall, 5.6% in the high-risk group, and 8.3% in revision surgeries) compared with the conventional (control) IPP group (9.6% overall, 25% in the high-risk group, and 33.3% in revision surgeries). The postoperative infection rate is obviously higher in the high-risk group, irrespective of whether the patient received InhibiZone prostheses or the conventional ones. Furthermore, for patients prone to a high risk of prosthesis infection, InhibiZone penile prosthesis was used instead of the conventional prosthesis, and this was found to reduce the infection rate (from 25% to 5.6%); furthermore, the overall infection rate (from 9.6% to 2.6%) was found to be reduced in the group that received InhibiZone prostheses and in patients with common etiologies (from 5% to 0%), both of which were prominent and statistically significant. Conclusion: An antibiotic-impregnated IPP (InhibiZone®) definitely increases the success rate of reimplantation surgery, and can be indicated for patients at a high risk of postoperative infection.

To evaluate the effectiveness and safety of high-power 120W Greenlight HPS laser (HPS) and compare the results to transurethral resection of the prostate (TURP), and define a subgroup of patients who had better symptom score improvement after HPS. Methods: One hundred and twenty-five patients who underwent surgery for benign prostatic hyperplasia (BPH) (61 HPS and 64 TURP) were retrospectively followed. Improvements of International Prostate Symptom Score (IPSS), quality of life score (QoL), maximum flow rate (Qmax) and post-void residual (PVR) were assessed at 4 weeks after the procedures. Potential covariates including age, body mass index (BMI), prostate volume (PV) and serum prostate-specific antigen (PSA) were defined and further subgroup analyses were utilized. Results: The HPS group had a significantly higher education level, annual household income and larger prostate size. Compared with TURP, HPS resulted in comparable IPSS, QoL, Qmax and PVR improvements, but shorter hospitalization duration, serum hemoglobin loss and blood transfusion rate. Subgroup analyses showed that men in the HPS group were younger (age

We conducted a retrospective study to compare the cost and effectiveness between two different running models for extracorporeal shock wave lithotripsy (SWL), including the outsourcing cooperation model (OC) and the rental cooperation model (RC). Methods: Between January 1999 and December 2005, we implemented OC for the SWL, and from January 2006 to October 2011, RC was utilized. With OC, the cooperative company provided a machine and shared a variable payment with the hospital, according to treatment sessions. With RC, the cooperative company provided a machine and received a fixed rent from the hospital. We calculated the cost of each treatment session, and evaluated the break-even point to estimate the lowest number of treatment sessions to make the balance between revenue and cost every month. Effectiveness parameters, including the stone-free rate, the retreatment rate, the rate of additional procedures and complications, were evaluated. Results: Compared with OC there were significantly less treatment sessions for RC every month (42.6±7.8 vs. 36.8±6.5, p=0.01). The cost of each treatment session was significantly higher for OC than for RC (751.6±20.0 USD vs. 684.7±16.7 USD, p=0.01). The break-even point for the hospital was 27.5 treatment sessions/month for OC, when the hospital obtained 40% of the payment, and it could be reduced if the hospital got a greater percentage. The break-even point for the hospital was 27.3 treatment sessions/month for RC. No significant differences were noticed for the stone-free rate, the retreatment rate, the rate of additional procedures and complications. Conclusion: Our study revealed that RC had a lower cost for every treatment session, and fewer treatment sessions of SWL/month than OC. The study might provide a managerial implication for healthcare organization managers, when they face a situation of high price equipment investment.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene cause cystic fibrosis (CF) and are associated with congenital bilateral absence of the vas deferens (CBAVD), which is the major cause of infertility in male patients with CF. However, most Taiwanese patients with CBAVD do not carry major CFTR mutations. Some patients have a single copy deletion of the solute carrier family 9 isoform 3 (SLC9A3) gene. SLC9A3 is a Na+/H+ exchanger, and depleted Slc9a3 in male mice causes infertility due to the abnormal dilated lumen of the rete testis and efferent ductules. Furthermore, SLC9A3 interacts with CFTR in the pancreatic duct and functions as a genetic modifier of CF. However, SLC9A3 function and its relation to CFTR expression in the male reproductive tract in vivo remain elusive. In the present study, we found that CFTR expression was dramatically decreased in the epididymis and vas deferens of Slc9a3 knockout mice. Adult Slc9a3-/- mice showed not only significantly decreased epididymis and vas deferens weight but also increased testis weight. Furthermore, Slc9a3-/- mice developed obstructive azoospermia because of abnormal abundant secretions and calcification in the lumen of the reproductive tract. Ultrastructural analysis of the epithelium in Slc9a3-/-epididymis and vas deferens displayed disorganized and reduced number of stereocilia and numerous secretory apparatuses. Our data revealed that interdependence between SLC9A3 and CFTR is critical for maintaining a precise microenvironment in the epithelial cytoarchitecture of the male reproductive tract. The Slc9a3-deficient mice with impaired male excurrent ducts in this study provide proof for our clinical findings that some Taiwanese of CBAVD carry SLC9A3 deletion but without major CFTR mutations.

Objective: To assess the associated risk factors and the prevalence of urinary incontinence (UI) among women with hypertension (H/T) aged 60 or over in Taiwan. Materials and Methods: A total of 2410 women aged 60 or over were selected by a multistage random sampling method and a total of 1519 women completed the face-to-face interviews. Only women who answered “yes” to the question “Do you have H/T?” were included in the H/T sample. The factors were assessed by frequency and Pearson's χ2 test using a significance level of p

XX male is a rare sex chromosomal disorder in infertile men. The purpose of this study was to distinguish the clinical and genetic features of the 46,XX male syndrome from other more frequent, testicular-origin azoospermic causes of male infertility. Methods: To study 46,XX male syndrome, we compared clinical and endocrinological parameters to other groups with testicular-origin azoospermia, and to an age-matched group of healthy males and females as normal control. Fluorescent in situ hybridization for detection and localization of the sex-determining region of the Y gene (SRY), array-based comparative genomic hybridization screening, and real-time qualitative polymerase chain reaction of FGF9, WT1, NR5A1, and SPRY2 genes were performed in this genetic investigation. Results: Our three patients with 46,XX male syndrome had a much higher follicular-stimulating hormone level, lower body height, lower testosterone level, and ambiguous external genitalia. One of the three patients with 46,XX male syndrome was SRY-negative. A further genetic study, including a comparative genomic hybridization array and real-time polymerase chain reaction, showed a gain of FGF9 copy numbers only in the SRY-negative 46,XX male. The genetic copy number of the FGF9 gene was duplicated in that case compared to the normal female control and was significantly lower than that of the normal male control. No such genomic gain was observed in the case of the two SRY-positive 46,XX males. Conclusion: Similar to clinical manifestations of 46,XX male syndrome, genetic evidence in this study suggests that FGF9 may contribute to sex reversal, but additional confirmation with more cases is still needed.

Benign prostatic hyperplasia (BPH) is the most common urologic disease among elderly men. A well-established in vitro cell model is required to determine the therapeutic mechanism of BPH inflammation. In this study, we attempted to establish an immortalized human prostate stromal cell line by transfecting with HPV-16 E6/E7 and designated as ihPSC. No significant difference was found in fibroblast-like morphology between primary hPSC and ihPSC. The ihPSC possessed a significantly higher cell proliferation rate than primary hPSC. The prostate-specific markers and proteins including cytoskeleton (α-SMA and vimentin) and smooth muscle (calponin), especially the androgen receptor (AR) were also examined in ihPSC, almost identical to the primary hPSC. To create an in vitro model featuring chronic prostatic inflammation, ihPSC was stimulated with IFN-γ+IL-17 and then treated with the high molecular weight hyaluronic acid hylan G-F 20 as an alternative strategy for inhibiting BPH inflammation. Hylan G-F 20 could dose-dependently diminish the inflammation-induced proliferation in ihPSC. The enhanced expressions of inflammatory molecules including IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), inducible nitrogen oxide synthase (iNOS), and Toll-like receptor 4 (TLR4) were all abolished by hylan G-F 20. For inflammatory signaling, hylan G-F 20 can also diminish the IFN-γ+IL-17-increased expression of iNOS and p65 in ihPSC. These findings suggest that ihPSC could provide a mechanism-based platform for investigating prostate inflammation. The hylan G-F 20 showed strong anti-inflammatory effects by decreasing inflammatory cytokines and signalings in the ihPSC, indicating its therapeutic potentials in BPH treatment in the future.

Interstitial cystitis (IC) has been described as a chronic debilitating sterile inflammatory multifactorial bladder syndrome of unknown etiology. IC is characterized by bladder pain (or suprapubic pain) associated with urgency, urinary frequency, and nocturia. Because the pathogenesis of IC remains unclear, it is still an enigma and represents a diagnostic and therapeutic challenge. The diagnosis of IC remains unclear and is based on exclusion of other diseases. Consequently, IC has usually been underdiagnosed, and the consensus on best available treatment for the disease is lacking. The current goal for the treatment of IC is usually symptomatic relief, and treatment protocols are based on empiricism. Multiple forms of therapy are available, and most patients can be managed conservatively. Nevertheless, the efficacy of most treatments is short term. This review article gives an overview of the available treatments for IC.

Objective: To assess the efficacy of hydrodistention (HD) followed by bladder training (BT) versus HD alone in patients with interstitial cystitis (IC). Methods: A total of 70 patients with IC were included and randomly assigned to two groups: one treated with HD (HD group) and the other treated with HD plus BT (HD plus BT group). Each patient was followed up using a weekly diary for 8 weeks after HD and monthly thereafter for 6 months after HD. Evaluation parameters included age, duration of IC in years, how many doctors visited before treatment, urgency, bladder pain, daytime voided volume per void, nocturnal volume per void, daytime voids per day, and nocturia per day. Results: Age, duration of IC in years, doctors visited before treatment, and voiding profiles of patients before treatments between the two groups did not show statistical significance. However, at 24 weeks after HD, the proportions of urgency, and bladder pain of the HD group versus the HD plus BT group were 43.48% versus 10.71% (p = 0.008), and 34.78% versus 14.29% (p = 0.086), respectively. Concurrently, the mean ± standard deviation of daytime voided volume per void, nocturnal volume per void, daytime voids per day, and nocturia per day of the HD group and HD plus BT group are 212.2 ± 114.2 mL and 300.1 ± 90.2 mL (p = 0.005), 276.8 ± 113.0 mL and 360.0 ± 129.6 mL (p = 0.018), 8.2 ± 3.2 and 6.2 ± 1.4 (p = 0.010), and 2.2 ± 1.2 and 1.5 ± 0.7 (p = 0.019), respectively. Conclusion: HD followed by BT produced a statistically significantly better effect than HD alone in the treatment of patients with IC.

Umbilical cord blood is rich in primitive natural killer (NK) cells, which are activated by interleukin (IL)-12. It was previously reported that a novel IL-12 family cytokine, IL-27 comprised of EBI3 and p28, was elevated in maternal serum during normal pregnancy. Thus, we compared the immune regulatory functions of IL-27 and IL-12 on mononuclear cells derived from cord blood and adult peripheral blood. Methods: After stimulation with IL-27, IL-12, and IL-27 combined with IL-12, the cytotoxicity against BJAB lymphoma cells by blood mononuclear cells was performed. Then immunofluorescence staining, reverse transcriptase-polymerase chain reaction and Western blotting were used to detect the effects of IL-27 and IL-12 in isolated NK cells. Results: IL-27, IL-12, and IL-27 combined with IL-12 enhanced the cytotoxicity of adult peripheral blood cells and cord blood cells, but the proliferation of distinct subpopulations of cells was not evident. Similar results were also obtained with purified cord blood NK cells. Interestingly, distinct from IL-12, IL-27 could induce aggregation and morphological changes of umbilical cord blood cells. Finally, IL-27 combined with IL-12 could stimulate increased IL-27 receptor (gp130 and WSX-1) transcripts in purified cord blood NK cells. However, the activation of signal transducer and activator of transcription 3 (STAT3) in NK cells was only detected in the presence of IL-27, but not IL-12 alone. Conclusion: From previous results, we summarize our current understanding of the augmentation of distinct regulation of NK cells by IL-27 and IL-12.

Objective: To assess the associated risk factors for daytime urinary frequency among Taiwanese women aged = 60 years. Materials and Methods: Daytime urinary frequency, defined by the International Continence Society, and its associated problems were evaluated, and medical history and sociodemographic variables were recorded. A total of 2,410 women were selected by a multistage random sampling method. The factors were assessed by frequency and Pearson's ?2 test using a significance level of < 0.05. Results: A total of 621 women of those initially selected in the study died before completion of this study. Face-to-face interviews with 1,521 women were completed, producing a response rate of 85.0% (1,521/1,789 women). The prevalence of daytime urinary frequency was significantly related to body mass index (p = 0.018), diabetes mellitus (p = 0.017), hypertension (p = 0.015), previous drug allergy (p = 0.003), smoking (p = 0.005), hormone therapy (p = 0.019), parity (p = 0.019), and urinary incontinence (p = 0.000). However, there was no association between urinary frequency and previous gynecologic surgery, hysterectomy, alcohol consumption, marital status, childbirth, and age of menopause. Conclusion: The results of this study showed a relatively high risk of urinary frequency development in patients with urinary incontinence, diabetes mellitus, hypertension, obesity, and smoking that are preventable, modifiable, or controllable. Better quality of health education for these women, drawing their attention to the associated factors, may have an impact on the prevalence of urinary frequency.

Objective: To evaluate the prevalence of daytime urinary frequency among Taiwanese women aged 60 years and older. Materials and Methods: There were an estimated 1.25 million female residents aged 60 years and over in Taiwan in 2000. A sample of 2,410 women was selected using a multistage random sampling method. Face- to-face visits with 1,523 women were completed by trained professional interviewers within 3 months of the subjects' selection. Questions about urinary frequency and other lower urinary tract symptoms, sociodemo-graphics, reproduction, and medical and surgical histories were recorded. The factors were assessed by frequency and Pearson's χ2 test using a significance level of < 0.05. Results: The prevalence of urinary frequency in Taiwanese women aged 60 years and over was 18.8% (286/1,521). The response rate was 85.0% (1,521/1,789). For those who complained of frequency, 45.8% voided 8–15 times a day, 37.8% voided 16–23 times a day, 1.7% voided 24–31 times and a day, and 14.7% voided more than 31 times a day. The prevalence of urinary frequency was significantly associated with age (p < 0.001). Conclusion: Urinary frequency is a common symptom in menopausal women and is significantly related to age. More than half of the women interviewed experienced intervals of < 1 hour between visits to the restroom during the day.

Problem-based learning (PBL), which incorporates principles of adult learning, is an important innovation in medical education. The use of PBL in health professional curricula is becoming more widespread. The curriculum design and the ways of implementing PBL are different among schools. More evidence is needed before a full PBL curriculum can be successfully implemented in an Asian medical school. Fu Jen Medical School is the first school in Taiwan to adopt a near-full PBL approach for the 3rd and 4th year curriculum (the medical education in Taiwan is mostly a 7-year undergraduate program). Fu Jen Medical School launched the interdisciplinary case-based, small group learning and integrated curriculum in 2002. This study investigated the short-term outcomes of this PBL curriculum, evaluated from several aspects. First, the self-directed learning readiness of the medical students before and after they entered the PBL curriculum was investigated using the Self-Directed Learning Readiness Scale (SDLRS). Second, semi-structured qualitative interviews were conducted with 5th and 6th year medical students and clinical instructors to understand the impact of PBL on the learning of clinical medicine. Finally, the passing rates in the Taiwan Medical Licensure Examination were compared with those of other medical schools in Taiwan. After 1 year of PBL, medical students at Fu Jen Medical School showed significant increases in the total SDLRS score, and in the subscores for learning strategy and self-assessment. These changes persisted until the end of 2 years of PBL. Students in their clinical years claimed that they were more active in learning, and had better learning skills and confidence in self-directed learning as compared with students from lecture-based curricula. PBL helps their clinical reasoning process, self-directed learning abilities and the use of knowledge in basic science to explain the clinical problem. On the other hand, the students thought that PBL had limited breadth and depth in clinical medicine and could not give them enough confidence in facing the national licensure examination. The initial batches of medical students (students from the first three cohorts) had the highest passing rate for Part 1 (basic sciences in medicine) and students from the first two cohorts had a 100% passing rate for Part 2 (clinical medicine) of the Taiwan Medical Licensure Examination. A near-full PBL curriculum in Asian medical schools is feasible and could encourage students to improve their self-directed learning abilities, learn adequate knowledge in basic sciences, and experience positive effects on learning clinical medicine. Better preparation of students for integrated learning of basic and clinical sciences are still needed, as is an emphasis on tutor training to improve the effectiveness of tutorial discussions.

Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is one of the most common autosomal recessive diseases in Caucasians. We screened for the CFTR gene mutation in a Caucasian father with congenital bilateral absence of the vas deferens (CBAVD), a Taiwanese mother, and twins resulting from an intracytoplasmic single sperm injection (ICSI) procedure. DNA fragments that showed abnormal banding patterns on temporal temperature gradient gel electrophoresis analysis followed by analysis of DNA sequence was used. The Caucasian father with CBAVD had ΔF508 and p.L375F mutations. The two children were heterozygous for the ΔF508 and p.L375F mutations, respectively. Mutation analysis of the CFTR gene should always be recommended for infertile couples seeking ICSI. The possibility of the children resulting from ICSI being a victim or carrier of CBAVD or CF, especially when the father is Caucasian with CBAVD, should be discussed during genetic counseling.

Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end product. Elevated collagenous deposition in DN group was also attenuated through CmNo1 administration. Moreover, the enhanced levels of transforming growth factor-β1, a fibrosis-inducing protein in glomerulus were also markedly dampened. Furthermore, auxiliary risk factors in DN like serum triglycerides and cholesterol were found to be increased but were decreased by CmNo1 treatment. Conclusively, the results suggests that CmNo1 exhibit potent and efficacious renoprotective action against hyperglycemia-induced DN.

(-)-Epicatechin-3-gallate (ECG) is a polyphenolic compound similar to (-)-epigallocatechin-3-gallate (EGCG) which is abundant in green tea. Numerous workers have proposed that EGCG protects epidermal cells against UVB-induced damage. However, little has been known about whether ECG protects keratinocytes against UVB-induced damage. We decided to investigate the protective effects and underlying mechanisms of ECG on UVB-induced damage. Cell viability was determined by the MTT assay. Activation of ERK1/2, p38 and JNK was analyzed by Western blotting. Intracellular H2O2 production and DNA content was analyzed by flow cytometry. Lipid peroxidation was assayed by colorimetry. In our study, we found that ECG dose-dependently attenuated UVB-induced keratinocyte death. Moreover, ECG markedly inhibited UVB-induced cell membrane lipid peroxidation and H2O2 generation in keratinocytes, suggesting that ECG can act as a free radical scavenger when keratinocytes were photodamaged. In parallel, H2O2-induced the activation of ERK1/2, p38 and JNK in keratinocytes could be inhibited by ECG. UVB-induced pre-G1 arrest leading to apoptotic changes of keratinocytes were blocked by ECG. Taken together, we provide here evidence that ECG protects keratinocytes from UVB-induced photodamage and H2O2-induced oxidative stress, possibly through inhibition of the activation of ERK1/2, p38 and JNK and/or scavenging of free radicals.

To estimate the age-specific prevalence rates of phimosis and circumcision in an urban sample of Taiwanese boys. Methods: A convenience sample of 1145 boys aged from 7 to 13 years was enrolled and cross-sectionally evaluated for preputial retractability and status of circumcision. Another convenience sample of 59 newborn male infants was enrolled from the infant room of a city municipal hospital. These infants were examined for preputial development at birth. Results: None of the newborn male infants had a completely retractable prepuce (i.e. type 3). The prevalence rate of type 3 prepuce increased with age from 71.7% (95% confidence interval [CI], 66.5-75.5%) for boys aged 7 years to 72.4% (95% CI, 67.3-77.0%) for boys aged 10 years and 84.1% (95% CI, 79.6-88.0%) for boys aged 13 years. In contrast, the prevalence rate of type 1 prepuce decreased with age from 83.1% (95% CI, 71.0-91.6%) for newborn infants to 0.3% (95% CI, 0.0001-1.8%) for boys aged 13 years. On the other hand, the prevalence of circumcision slightly increased with age from 7.2% (95% CI, 5.3-10.8%) for boys aged 7 years to 8.7% (95% CI, 6.5-13.3%) for boys aged 13 years. Conclusion: Nonretractability of the prepuce was very common among the Taiwanese newborns. Among the school boys, the degree of preputial separation and exposure of glans increased with age and progressed even more rapidly in adolescence. Very few boys still suffered from unretractable prepuce by the age of 13. [J Formos Med Assoc 2007;106(4):302-307]

Relatively few studies have addressed the risk factors of erectile dysfunction (ED) in Taiwanese— most have described ED and medical problems in the general population. In this study, the cardiovascular risk factors of ED among aborigines in Taiwan were investigated. However, alcohol dependence (AD) was prevalent in Taiwan’s aborigine population. So this study also focused on the relationship among AD, the cardiovascular risk factors and ED. A cross-sectional study was conducted, and data was obtained from a baseline survey of 192 aboriginal adults (35-75 years of age). The participants’ demographic data, AD, markers of endothelial function, serum testosterone, and ED status were assessed. Ninety-four (49%) of the 192 participants had a history of alcoholism and 79 (84%) of those with alcoholism had ED. The study reported that AD and hyperlipidemia, metabolic syndrome (MetS), ED, abnormality of testosterone, and high-sensitivity C-reactive protein are highly prevalent among the aborigines. Factors that may affect ED included age, AD, central obesity, diabetes mellitus, hyperlipidemia, hypertension, MetS, and testosterone. ED is highly prevalent among aborigines with the risk factors of AD, MetS, old age, and abnormal testosterone serum level. MetS, atherosclerosis, and ED are risk factors for cardiovascular diseases. Hence, an increased focus on Taiwanese aborigines with ED is necessary.

It is estimated that 10-15% of couples are infertile and male factors account for about half of these cases. With the advent of intracytoplasmic sperm injection (ICSI), many infertile men have been able to father offspring. However, teratozoospermia still remains a big challenge to tackle. Septins belong to a family of cytoskeletal proteins with GTPase activity and are involved in various biological processes e.g. morphogenesis, compartmentalization, apoptosis and cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men, is exclusively expressed in the post meiotic male germ cells. Septin12(+/+)/Septin12(+/-) chimeric mice have multiple reproductive defects including the presence of immature sperm in the semen, and sperm with bent neck (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a potential sterile gene in humans. In this study, we sequenced the entire coding region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and identified ten variants. Among them is the c.474 G>A variant within exon 5 that encodes part of the GTP binding domain. The variant creates a novel splice donor site that causes skipping of a portion of exon 5, resulting in a truncated protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for the c.474 A allele had teratozoospermia (abnormal sperm