Effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis based on large randomized trials: A systematic review and network meta-analysis.

OBJECTIVE: To quantify the effectiveness and safety of intra-articular interventions for knee and hip osteoarthritis (OA) through a systematic review and Bayesian random-effects network meta-analysis. DESIGN: We searched CENTRAL and regulatory agency websites (inception-2023) for large, English-language, randomized controlled trials (RCTs) (≥100 patients/group) examining any intra-articular intervention. PRIMARY OUTCOME: pain intensity. SECONDARY OUTCOMES: physical function and safety outcomes. Pain and function outcomes were analyzed at 2,6,12,24, and 52 weeks post-randomization, and presented as standardized mean differences (SMDs) (95% credible intervals, 95%CrI). The prespecified minimal clinically important between-group difference (MID) was -0.37 SMD. Safety outcomes were presented as odds ratios (OR) (95%CrI). FINDINGS: Among 57 RCTs (22,795 participants) examining 18 intra-articular interventions, usual care or placebo, treatment effects were larger in high-risk-of-bias trials (n = 35) than low/unclear-risk-of-bias trials (n = 22). In the main analysis (excluding high-risk-of-bias trials), triamcinolone had the highest probabilities of reaching the MID at weeks 2-6 (75.3% and 90%, respectively) with corresponding SMDs of -0.48 (95%CrI,-0.85 to -0.10) and -0.53 (95%CrI,-0.79 to -0.27) compared to placebo. Tr14/Ze14 homeopathic product showed therapeutic potential at week 6 compared to placebo (SMD:-0.42, 95%CrI,-0.71 to -0.11, 63.5% probability of reaching the MID). Hyaluronic acid had higher risk of dropouts due to adverse events (OR:2.01, 95%CrI,1.08 to 3.77) and serious adverse events (OR:1.86, 95%CrI,1.16 to 3.03) than placebo. CONCLUSION: Triamcinolone had the highest probabilities to have a treatment effect beyond the MID at weeks 2-6. Large RCTs with lower risk of bias do not support the notion that 16 other intra-articular interventions assessed improve pain or function beyond placebo effects in knee or hip OA. Lack of evidence of long-term effectiveness underscores the need for further research beyond 24-52 weeks.

ChatGPT v4 outperforming v3.5 on cancer treatment recommendations in quality, clinical guideline, and expert opinion concordance.

Objectives: To assess the quality and alignment of ChatGPT's cancer treatment recommendations (RECs) with National Comprehensive Cancer Network (NCCN) guidelines and expert opinions. Methods: Three urologists performed quantitative and qualitative assessments in October 2023 analyzing responses from ChatGPT-4 and ChatGPT-3.5 to 108 prostate, kidney, and bladder cancer prompts using two zero-shot prompt templates. Performance evaluation involved calculating five ratios: expert-approved/expert-disagreed and NCCN-aligned RECs against total ChatGPT RECs plus coverage and adherence rates to NCCN. Experts rated the response's quality on a 1-5 scale considering correctness, comprehensiveness, specificity, and appropriateness. Results: ChatGPT-4 outperformed ChatGPT-3.5 in prostate cancer inquiries, with an average word count of 317.3 versus 124.4 (p < 0.001) and 6.1 versus 3.9 RECs (p < 0.001). Its rater-approved REC ratio (96.1% vs. 89.4%) and alignment with NCCN guidelines (76.8% vs. 49.1%, p = 0.001) were superior and scored significantly better on all quality dimensions. Across 108 prompts covering three cancers, ChatGPT-4 produced an average of 6.0 RECs per case, with an 88.5% approval rate from raters, 86.7% NCCN concordance, and only a 9.5% disagreement rate. It achieved high marks in correctness (4.5), comprehensiveness (4.4), specificity (4.0), and appropriateness (4.4). Subgroup analyses across cancer types, disease statuses, and different prompt templates were reported. Conclusions: ChatGPT-4 demonstrated significant improvement in providing accurate and detailed treatment recommendations for urological cancers in line with clinical guidelines and expert opinion. However, it is vital to recognize that AI tools are not without flaws and should be utilized with caution. ChatGPT could supplement, but not replace, personalized advice from healthcare professionals.

PLC-Based Polymer/Silica Hybrid Inverted Ridge LP11 Mode Rotator.

The mode rotator is an important component in a PLC-based mode-division multiplexing (MDM) system, which is used to implement high-order modes with vertical intensity peaks, such as LP11b mode conversions from LP11a in PLC chips. In this paper, an LP11 mode rotator based on a polymer/silica hybrid inverted ridge waveguide is demonstrated. The proposed mode rotator is composed of an asymmetrical waveguide with a trench. According to the simulation results, the broadband conversion efficiency between the LP11a and LP11b modes is greater than 98.5%, covering the C-band after optimization. The highest mode conversion efficiency (MCE) is 99.2% at 1550 nm. The large fabrication tolerance of the proposed rotator enables its wide application in on-chip MDM systems.

Performance of ChatGPT on the Taiwan urology board examination: insights into current strengths and shortcomings.

PURPOSE: To compare ChatGPT-4 and ChatGPT-3.5's performance on Taiwan urology board examination (TUBE), focusing on answer accuracy, explanation consistency, and uncertainty management tactics to minimize score penalties from incorrect responses across 12 urology domains. METHODS: 450 multiple-choice questions from TUBE(2020-2022) were presented to two models. Three urologists assessed correctness and consistency of each response. Accuracy quantifies correct answers; consistency assesses logic and coherence in explanations out of total responses, alongside a penalty reduction experiment with prompt variations. Univariate logistic regression was applied for subgroup comparison. RESULTS: ChatGPT-4 showed strengths in urology, achieved an overall accuracy of 57.8%, with annual accuracies of 64.7% (2020), 58.0% (2021), and 50.7% (2022), significantly surpassing ChatGPT-3.5 (33.8%, OR = 2.68, 95% CI [2.05-3.52]). It could have passed the TUBE written exams if solely based on accuracy but failed in the final score due to penalties. ChatGPT-4 displayed a declining accuracy trend over time. Variability in accuracy across 12 urological domains was noted, with more frequently updated knowledge domains showing lower accuracy (53.2% vs. 62.2%, OR = 0.69, p = 0.05). A high consistency rate of 91.6% in explanations across all domains indicates reliable delivery of coherent and logical information. The simple prompt outperformed strategy-based prompts in accuracy (60% vs. 40%, p = 0.016), highlighting ChatGPT's limitations in its inability to accurately self-assess uncertainty and a tendency towards overconfidence, which may hinder medical decision-making. CONCLUSIONS: ChatGPT-4's high accuracy and consistent explanations in urology board examination demonstrate its potential in medical information processing. However, its limitations in self-assessment and overconfidence necessitate caution in its application, especially for inexperienced users. These insights call for ongoing advancements of urology-specific AI tools.

Lung abscess with chronic cough secondary to xanthogranulomatous pyelonephritis: A rare case report.

RATIONALE: Xanthogranulomatous pyelonephritis (XGPN) is a form of chronic pyelonephritis caused by chronic calculus obstruction and bacterial infection, leading to the destruction of the renal parenchyma and calyces. Conservative treatment is usually not sufficient, and surgical intervention is still the main curative approach. XGPN with transdiaphragmatic extension and lung abscess formation is a rare condition. PATIENT CONCERNS: We report a 64-year-old woman who presented with persistent productive cough. DIAGNOSES: Lung abscess secondary to XPGN. Both nephrostomy urine and sputum cultures showed Proteus mirabilis infection with the same antibiotic sensitivity spectrum, but blood culture was negative. INTERVENTIONS: Laparoscopic radical nephrectomy and prolonged antibiotic treatment. OUTCOMES: The lung abscess and cough gradually resolved in 1 month after nephrectomy. CONCLUSION: Lung abscess secondary to transdiaphragmatic extension of XGPN is rare but should be considered in patients with lower lung infections that are unresponsive to treatment, especially infections due to unusual respiratory pathogens such as P mirabilis.

Preoperative hydronephrosis is an independent protective factor of renal function decline after nephroureterectomy for upper tract urothelial carcinoma.

Objectives: To evaluate the predictive role of pre-nephroureterectomy (NU) hydronephrosis on post-NU renal function (RF) change and preserved eligibility rate for adjuvant therapy in patients with upper tract urothelial carcinoma (UTUC). Patients and methods: This retrospective study collected data of 1018 patients from the Taiwan UTUC Collaboration Group registry of 26 institutions. The patients were divided into two groups based on the absence or presence of pre-NU hydronephrosis. Estimated glomerular filtration rate (eGFR) was calculated pre- and post-NU respectively. The one month post-NU RF change, chronic kidney disease (CKD) progression, and the preserved eligibility rate for adjuvant therapy were compared for each CKD stage. Results: 404 (39.2%) patients without and 614 (60.8%) patients with pre-NU hydronephrosis were enrolled. The median post-NU change in the eGFR was significantly lower in the hydronephrosis group (-3.84 versus -12.88, p<0.001). Pre-NU hydronephrosis was associated with a lower post-NU CKD progression rate (33.1% versus 50.7%, p< 0.001) and was an independent protective factor for RF decline after covariate adjustment (OR=0.46, p<0.001). Patients with pre-NU hydronephrosis had a higher preserved eligibility rate for either adjuvant cisplatin-based chemotherapy (OR=3.09, 95%CI 1.95-4.69) or immune-oncology therapy (OR=2.31, 95%CI 1.23-4.34). Conclusion: Pre-NU hydronephrosis is an independent protective predictor for post-NU RF decline, CKD progression, and eligibility for adjuvant therapy. With cautious selection for those unfavorably prognostic, non-metastatic UTUC patients with preoperative hydronephrosis, adjuvant rather than neoadjuvant therapy could be considered due to higher chance of preserving eligibility.

Orf Infection on the Scalp of a Taiwanese Woman: A Case Report and Literature Review.

BACKGROUND: Orf, or ecthyma contagiosum, is a zoonosis caused by Parapoxvirus that infects sheep and goats. Human transmission typically occurs in persons in contact with the infected animals or contaminated fomites and environment. In humans, it generally occurs as solitary or multiple skin lesions on the hands or fingers. Involvement of the head region has rarely been reported. CASE PRESENTATION: We report an unusual case with multiple orf lesions on the scalp of a middle-aged woman, along with a review of previously reported Orf cases on the head region. CONCLUSIONS: Although Orf infection rarely happens on the head region, it should be considered in the differential diagnosis of cases with relevant animal exposure.

Repeated vertebral compression fractures in young adult may imply functional adrenal tumor.

BACKGROUND: Patients with adrenal Cushing's syndrome (ACS) typically present with central obesity, hirsutism, hypertension, or glucose intolerance, which can be easily identified by a clinical physician. However, recognizing those with subclinical CS or those with less common symptoms and signs is challenging to the subspecialist, which can lead to delayed diagnosis and treatment. We report a case who presented with repeated vertebral fractures in 6 months. Typical physical appearance of CS was not shown so that suspicions were not raised until severe osteoporosis was demonstrated from bone marrow density study. From our case report, endocrine tests and image survey should always be considered in young patients with repeat vertebral fractures. CASE PRESENTATION: A 48-year-old man presented with severe back pain for 3 months. Second and fifth lumbar spine (L2 and L5) vertebral compression fractures were noted from X-ray and magnetic resonance imaging (MRI), and vertebroplasty was performed by orthopedic surgeons. After 1 month, a newly developed compression fracture of the ninth to twelfth thoracic spine and L4-L5 were noted. Severe osteoporosis was noted from the hip bone mineral density test, and he was referred to an endocrinologist for analysis. Serial endocrine tests confirmed hypercortisolism, and subsequent abdomen MRI showed a left adrenal tumor. ACS was diagnosed. Left laparoscopic adrenalectomy was performed, and the patient received cortisol supplement for 12 months. Thereafter, no new fractures were identified. CONCLUSIONS: ACS should be considered and carefully verified in middle-aged adults who present with severe osteoporosis and repeated vertebral compression fracture.

Variation of body regional responses to Ustekinumab and Secukinumab in psoriasis patients: A real-world retrospective study and literature review.

Psoriasis in different body regions displays varying therapeutic responses to biologics, whereas currently relevant studies remain scarce. We retrospectively reviewed the treatment responses of patients with moderate-to-severe psoriasis, who completed the two-year reimbursed ustekinumab or secukinumab treatment in two medical centers in Southern Taiwan. Demographic profiles and body regional PASI scores (head/neck, trunk, upper and lower limbs) along the treatment course were recorded. The proportions of patients attaining PASI 75, 90, 100 and the extent of body regional PASI score improvements were compared in biologic naïve or experienced patients. A total of 57 and 67 patients receiving ustekinumab and secukinumab injections, respectively, were included. Overall, patients receiving secukinumab showed higher degrees of PASI score improvements along the two-year treatment course. The lower limbs had the highest, and the upper extremities and head/neck had the lowest post-treatment PASI scores regardless of prior biologic use in the groups of ustekinumab and secukinumab. The upper limbs showed the highest, while the lower limbs had the lowest complete remission rate (regional specific PASI 100) in response to ustekinumab (upper limbs 48.7%, lower limbs 25.6%) and secukinumab (upper limbs 77.1%, lower limbs 42.8%) in biologic naïve groups. Our study demonstrated that lower limbs were the most treatment-refractory area in response to ustekinumab and secukinumab injections, while the upper limbs and head/neck region had a better response.

Surgical outcome predictor analysis following hand-assisted or pure laparoscopic transperitoneal nephroureterectomy using the Taiwan upper urinary tract urothelial carcinoma database.

Purpose: Taiwan 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 methods: The 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. Results: Of 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. Conclusion: Although 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.

Diffused bladder wall calcification in a survivor with severe coronavirus disease 2019: A case report.

RATIONALE: Bladder calcification is a rare presentation that was first interpreted to be related to a urea-splitting bacterial infection. Aside from infection, other hypotheses such as schistosomiasis, tuberculosis, cancer, and cytokine-induced inflammatory processes have also been reported. Severe coronavirus disease 2019 (COVID-19) is known for its provoking cytokine storm and uninhibited systematic inflammation, and calcification over the coronary artery or lung has been reported as a long-term complication. PATIENT CONCERNS: We presented a 68 years old man who had persistent lower urinary tract symptoms after recovery from severe COVID-19. No urea-splitting bacteria were identified from urine culture. DIAGNOSIS: Cystoscopy examination revealed diffuse bladder mucosal and submucosa calcification. INTERVENTIONS: Transurethral removal of the mucosal calcification with lithotripsy. OUTCOMES: The patient's lower urinary tract symptoms improved, and stone analysis showed 98% calcium phosphate and 2% calcium oxalate. No newly formed calcifications were found at serial follow-up. CONCLUSION: Diffuse bladder calcification may be a urinary tract sequela of COVID-19 infection. Patients with de novo lower urinary tract symptoms after severe COVID-19 should be further investigated.

Oncologic impact of delay between diagnosis and radical nephroureterectomy.

Purpose: This study aimed to evaluate the oncological outcome of delayed surgical wait time from the diagnosis of upper tract urothelial carcinoma (UTUC) to radical nephroureterectomy (RNU). Methods: In this multicenter retrospective study, medical records were collected between 1988 and 2021 from 18 participating Taiwanese hospitals under the Taiwan UTUC Collaboration Group. Patients were dichotomized into the early (≤90 days) and late (>90 days) surgical wait-time groups. Overall survival, disease-free survival, and bladder recurrence-free survival were calculated using the Kaplan-Meier method and multivariate Cox regression analysis. Multivariate analysis was performed using stepwise linear regression. Results: Of the 1251 patients, 1181 (94.4%) were classifed into the early surgical wait-time group and 70 (5.6%) into the late surgical wait-time group. The median surgical wait time was 21 days, and the median follow-up was 59.5 months. Our study showed delay-time more than 90 days appeared to be associated with worse overall survival (hazard ratio [HR] 1.974, 95% confidence interval [CI] 1.166-3.343, p = 0.011), and disease-free survival (HR 1.997, 95% CI 1.137-3.507, p = 0.016). This remained as an independent prognostic factor after other confounding factors were adjusted. Age, ECOG performance status, Charlson Comorbidity Index (CCI), surgical margin, tumor location and adjuvant systemic therapy were independent prognostic factors for overall survival. Tumor location and adjuvant systemic therapy were also independent prognostic factors for disease-free survival. Conclusions: For patients with UTUC undergoing RNU, the surgical wait time should be minimized to less than 90 days. Prolonged delay times may be associated with poor overall and disease-free survival.

Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: network meta-analysis.

OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose. DESIGN: Systematic review and network meta-analysis of randomised trials. DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis. OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed. REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo. RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%). CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.

Comparative analysis of patients with upper urinary tract urothelial carcinoma in black-foot disease endemic and non-endemic area.

BACKGROUND: A high incidence of upper urinary tract urothelial carcinoma has been reported in the southwestern area of Taiwan, where arsenic water contamination was considered the main cause. However, there is no definite proof to show a correlation between arsenic water contamination and upper urinary tract urothelial carcinoma. To investigate the clinical and epidemiological features of patients with upper urinary tract urothelial carcinoma between arsenic water endemic and non-endemic areas, we analyzed patients in terms of characteristics, stratified overall survival, disease-free survival, and cancer-specific survival. METHODS: The records of a total of 1194 patients diagnosed with upper urinary tract urothelial carcinoma were retrospectively reviewed. Clinical data and current medical status were collected from the medical records. Statistical analyses were performed to determine the clinical variables and stratified survival curves between endemic and non-endemic groups. RESULTS: Female predominance was revealed in both endemic and non-endemic groups (male:female ratio = 1:1.2-1.4). No statistical differences were found in histological types, staging, and tumor size between the two groups. Nonetheless, patients with characteristics of aging and having end-stage renal disease were outnumbered in the non-endemic group, while a higher prevalence of previous bladder tumors and more ureteral tumors were found in the endemic group. Adjusted stratified cumulative survival curves suggested a poorer prognosis in endemic patients, especially in disease-free survival of early stage disease. CONCLUSIONS: A higher mortality rate with more previous bladder cancer history and ureteral tumors was seen in patients with upper urinary tract urothelial carcinoma residing in the arsenic water contamination area. This may be attributed to the long-term carcinogenic effect of arsenic underground water.

Digit Force Controls and Corresponding Brain Activities in Finger Pressing Performance: A Comparison Between Older Adults and Young Individuals.

This study aims toward an investigation and comparison of the digital force control and the brain activities of older adults and young groups during digital pressing tasks. A total of 15 young and 15 older adults were asked to perform force ramp tasks at different force levels with a custom pressing system. Near-infrared spectroscopy was used to collect the brain activities in the prefrontal cortex and primary motor area. The results showed that the force independence and hand function of the older adults were worse than that of the young adults. The cortical activations in the older adults were higher than those in the young group during the tasks. A significant hemodynamic between-group response and mild negative correlations between brain activation and force independence ability were found. Older adults showed poor force independence ability and manual dexterity and required additional brain activity to compensate for the degeneration.

Growth of Polystyrene Pillars in Electric Field.

Surface patterning on polymer films, which is a self-assembly process under the action of external and/or internal impetus, has a variety of applications, including drug delivery and flexible electronics. In this work, we study the growth of polystyrene pillars in the electric field for different combinations of annealing temperature, film thickness, and electrode separation (electric field intensity). There are five stages for the growth of the polystyrene pillars for all the configurations used in this work, including a nucleation stage, a linear growth stage, an acceleration stage in the pillar length prior to the contact between the top surface of a pillar and the upper electrode, a radial growth stage after the contact, and a stationary stage without further growth of the pillar. In the linear growth stage, there exist linear relationships between the pillar length and the annealing time and between the square of the pillar diameter and the annealing time. The activation energies for the rate processes controlling the radial growth and the length growth in the linear growth stage are 30.2 and 25.3 kJ/mol, respectively. There are two rate processes controlling the radial growth of the pillars: one is the field-induced flow of polymer through the polymer film to the roots of pillars and the other is the coalescence of pillars. The activation energy for the coalescence is 16.5 kJ/mol. The results obtained in this work offer a practical route to control the geometrical dimensions of polymer pillars through the processing parameters.

Involvement of the antioxidative property of morusin in blocking phorbol ester-induced malignant transformation of JB6 P+ mouse epidermal cells.

Chemoprevention has been acknowledged as an important and practical strategy for managing cancer. We have previously synthesized morusin, a prenylated flavonoid that exhibits anti-cancer progression activity. In the present study, we evaluated the anti-cancer promotion potential of morusin by using the mouse epidermal JB6 P+ cell model. Extensive evidence shows that tumor promotion by phorbol esters is due to the stimulation of reactive oxygen species (ROS). Therefore, the effect of morusin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ROS production was assessed. Noncytotoxic concentrations of morusin were found to dose-dependently reduce TPA-induced ROS production. Moreover, morusin inhibited TPA-induced activator protein-1 (AP-1) and nuclear factor-kappa B (NF-κB) activation, which can mediate cell proliferation and malignant transformation. Furthermore, morusin inhibited the TPA upregulation of cyclooxygenase 2 (COX-2), which may be regulated by AP-1 and NF-κB. In addition, noncytotoxic concentrations of morusin reduced the TPA-promoted cell growth of JB6 P+ cells and inhibited TPA-induced malignant properties, such as cytoskeletal rearrangement and cell migration of JB6 P+ cells. Similar to the effects of glutathione (GSH) pretreatment, morusin inhibited TPA-induced expression of N-cadeherin and vimentin, which are malignant cell surface proteins. Finally, morusin treatment dose-dependently suppressed the TPA-induced anchorage-independent cell transformation of JB6 P+ cells. In conclusion, our results evidence that morusin possesses anti-cancer promotion potential because of its antioxidant property, which mediates multiple transformation-associated gene expression.

Relationship between arsenic-containing drinking water and skin cancers in the arseniasis endemic areas in Taiwan.

Artesian well-water had high concentrations of arsenic that led to the well-known black foot disease in Taiwan around the 1950s, and the associated cancers including skin cancer, bladder cancers and lung cancers. We sought to estimate the standardized morbidity ratio (SMR) and age-standardized incidence rate (ASIR) of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in the black foot disease endemic areas (BFDEA) in Taiwan. A nationwide retrospective population-based survey was done with the data from the National Taiwan Cancer Registry Center between 1979 and 2007. Among the 29-year period, there were 11 191 cases with SCC and 13 684 cases with BCC diagnosed pathologically. The incidence rates were 4-6-fold higher for SCC and 3-4-fold higher for BCC in the BFDEA compared with the rest of Taiwan. The SMR decreased after stopping arsenic-containing well-water drinking in the 1970s. The arsenic level in the drinking water, amount of contaminated water intake, occupation and sun-exposure time were not documented. This is the first nationwide, population-based study that shows the relationship between arsenic intoxication and non-melanoma skin cancers (SCC and BCC) through comparing the data in people living in the BFDEA and non-BFDEA in Taiwan.