Effects of Fecal Occult Blood Immunoassay Screening for Colorectal Cancer-Experience from a Hospital in Central Taiwan.

Background and Objectives: In 2004, the Health Administration of Taiwan began to promote a hospital-based cancer screening quality improvement program, under the principle that "prevention is better than therapy". The aim of this study was to evaluate the effectiveness of colorectal cancer (CRC) screening in patients who received a fecal immunochemical test (FIT) at a hospital in central Taiwan. Materials and Methods: This was a retrospective study. Results: Fecal occult blood immunoassays for CRC screening were conducted in 58,891 participants, of whom 6533 were positive (positive detection rate 11.10%). The positive patients then underwent colonoscopy, and the detection rates of polyps and CRC accounted for 53.6% and 2.4% of all colonoscopy-confirmed diagnoses (3607), respectively. We further enrolled data from patients diagnosed with CRC at our hospital from 2010 to 2018. The patients with CRC were divided into two groups according to whether or not they had received fecal occult blood screening. Among the 88 patients with CRC by screening, 54 had detailed medical records including cancer stage. Of these 54 patients, 1 (1.8%) had pre-stage, 11 (20.4%) had stage I, 24 (44.4%) had stage II, 10 (18.5%) had stage III, and 8 (14.8%) had stage IV CRC. The early cancer detection rates of the screening and non-screening groups were 66.7% and 52.7%, respectively, and the difference was significant (p = 0.00130). Conclusions: In this study, screening with FIT significantly increased the early detection of CRC. The main advantage of FIT is the non-invasiveness and low cost. It is hoped that the further adoption of early screening can increase the detection rates of colorectal polyps or early cancer to improve survival, reduce the high cost of subsequent cancer treatment, and reduce the burden on the patient and healthcare system.

Association between the Severity of Nonalcoholic Fatty Liver Disease and the Risk of Coronary Artery Calcification.

Background and Objectives: There are limited data on the association between severity of non-alcoholic fatty liver disease (NAFLD) and coronary artery calcification. This study investigated sonographic diagnosed NAFLD and coronary artery calcium score (CAC) as detected by cardiac multidetector computed tomography in general populations. Materials and Methods: A total of 545 patients were enrolled in this study. NAFLD was diagnosed by ultrasonography examination and CAC score were evaluated by cardiac multidetector computed tomography. The association between NAFLD and artery calcium score stage was determined by logistic regression analysis and Spearman correlation coefficient analysis. Results: Of all the participants, 437 (80.2%) had ultrasonography-diagnosed NAFLD and 242 (44%) had coronary artery calcification (CAC > 0). After adjustment for cardiovascular risk factors, the risk of developing coronary artery calcification was 1.36-fold greater in the patients with different severity of NAFLD compared to those without NAFLD (OR = 1.36, 95% CI = 1.07-1.77, p = 0.016). The highest OR for separate coronary artery calcification was 1.98 (OR = 1.98, 95% CI = 1.37-2.87, p < 0.001) in the left main artery, and the risk was still 1.71-fold greater after adjustments (OR = 1.71, 95% CI = 1.16-2.54, p = 0.007). Conclusions: This cross-sectional study demonstrated that the severity of NAFLD was associated with the presence of significant coronary artery calcification, especially in the left main coronary artery, suggesting increasing the cardiovascular risk.

Characterization, Phylogeny, and Genome Analyses of Nonpathogenic Xanthomonas campestris Strains Isolated from Brassica Seeds.

Xanthomonads were detected by using the Xan-D(CCF) medium from the brassica seeds, and their pathogenicity was determined by plant inoculation tests. It was found that some seed lots were infested with Xanthomonas campestris pv. campestris, some with X. campestris pv. raphani, and some with nonpathogenic xanthomonads. The nonpathogenic xanthomonad strains were identified as X. campestris, and the multilocus sequence analysis showed that the nonpathogenic X. campestris strains were grouped together with pathogenic X. campestris, but not with nonpathogenic strains of X. arboricola. In addition, all isolated X. campestris pv. campestris and X. campestris pv. raphani strains were positive in the hrpF-PCR, but the nonpathogenic strains were negative. It was further found that nonpathogenic X. campestris strain nE1 does not contain the entire pathogenicity island (hrp gene cluster; type III secretion system) and all type III effector protein genes based on the whole genome sequence analyses. The nonpathogenic X. campestris strain nE1 could acquire the entire pathogenicity island from the endemic X. campestris pv. campestris and X. campestris pv. raphani strains by conjugation, but type III effector genes were not cotransferred. The studies showed that the nonpathogenic X. campestris strains indeed exist on the brassica seeds, but it could be differentiated by the PCR assays on the hrp and type III effector genes. Nevertheless, the nonpathogenic X. campestris strains cannot be ignored because they may be potential gene resources to increase genetic diversity in the endemic pathogenic X. campestris pv. campestris and X. campestris pv. raphani strains.

Swimming Pool-Associated Vittaforma-Like Microsporidia Linked to Microsporidial Keratoconjunctivitis Outbreak, Taiwan.

We analyzed 2 batches of environmental samples after a microsporidial keratoconjunctivitis outbreak in Taiwan. Results indicated a transmission route from a parking lot to a foot washing pool to a swimming pool and suggested that accumulation of mud in the foot washing pool during the rainy season might be a risk factor.

What is the impact of metabolic syndrome and its components on reflux esophagitis? A cross-sectional study.

BACKGROUND: The prevalence rate of reflux esophagitis (RE) in Asia, including Taiwan, has increased dramatically in recent years. However, few studies have discussed on its relationship with metabolic syndrome (MetS). This study aimed to evaluate the correlation between RE and MetS and its components. METHODS: We conducted a cross-sectional study during 2013 to 2014 in Taiwan. A total of 4895 subjects who completed upper gastrointestinal endoscopy at the Health Examination Center of Changhua Christian Hospital were enrolled. RE was defined according to the upper gastrointestinal endoscopic findings and MetS was defined according to the Taiwanese criteria. Univariate and multivariate logistic regression analyses were applied to calculate odds ratios and 95% confidence intervals for each variable to assess the associated features for RE. We analyzed the relationship between the number of MetS components and the severity of RE using the chi-square test for trend. RESULTS: The prevalence rates of MetS and RE were respectively 28.5 and 59.6%. According to univariate logistic regression analysis, MetS was significantly associated with RE and remained a positive association in multivariate logistic regression analysis (adjusted ORß = 1.251; 95% CI = 1.071-1.462; p = 0.005). Furthermore, among the five MetS components, elevated blood pressure (adjusted ORγ = 1.163; 95% CI = 1.023-1.323; p = 0.021), abdominal obesity (adjusted ORγ = 1.173; 95% CI = 1.020-1.349; p = 0.026) and hyperglycemia (adjusted ORγ = 1.306; 95% CI = 1.142-1.495; p < 0.001) were positively associated with the presence of RE. A weak association was also found between elevated triglycerides and RE after adjusting for age and gender (adjusted ORα = 1.171; 95% CI = 1.022-1.343; p = 0.023). Reduced high-density lipoprotein cholesterol showed no significant difference between groups with and without RE. Older age (≥65 years), male gender, higher body mass index, higher uric acid, smoking, alcohol drinking, and hiatal hernia were found to be significant associated factors for RE. In addition, a dose-response relation between the number of MetS components and the presence of RE was demonstrated in the multivariate analysis. Furthermore, we performed a trend analysis and found the severity of RE got worse as the number of MetS components increased (p < 0.001). CONCLUSION: This study suggests that MetS is significantly related to the presence and the severity of RE.

Tuning Semiconductor Performance of Nickel Complexes through Crystal Transformation.

Crystal transformation between two polymorphs (green, 1-G, and red, 1-R) of the square-planar nickel complex NiL2 (L = 2-ethoxy-6-( N-methyliminomethyl)phenolate) and their tuning effect to semiconductor properties were studied both experimentally and theoretically. When 1-G is heated to 413 K, it converts to 1-R, whereas soaking 1-R in several kinds of solvents causes it to revert to 1-G. Crystallographic and PXRD studies reveal the dramatic changes in crystal dimensions due to the changes of packing models. Heating device made from 1-G (D-1-G(298)) at 413 K significantly increases the electrical conductivity from 6.55 × 10-4 S cm-1 for D-1-G(298) to 1.11 × 10-3 S cm-1 for D-1-G(413), showing significant crystal form dependence. Heat-treating D-1-G and D-1-R devices at different temperatures clearly reveals the reason for the conductivity tuning. Thus, the conductivity of NiL2-based devices could be well tuned through crystal transformation by heating or by soaking in solvent. Theoretical calculations clearly revealed the reason for such conductivity changes and also predicted that both polymorphs are good p-type semiconductors with hole mobilities of 1.63 × 10-2 (1-G) and 2.11 × 10-1 cm2 V-1 s-1 (1-R).

Stepwise Assembly of MII7 Clusters Revealed by Mass Spectrometry, EXAFS, and Crystallography.

The square-planar monomer NiL2 (Ni1 ), L=2-ethoxy-6-(N-methyl-iminomethyl)phenolate, reacts with M(H2 O)6 (ClO4 )2 , M=Ni or Co, to form heptanuclear disks [Cox Ni7-x (OH)6 (L)6 ](ClO4 )2 ⋅2 CH3 CN (Cox Ni7-x , x=0-7) and the co-crystal [Cox Ni7-x (OH)6 L6 ][NiL2 ](ClO4 )2 ⋅2 CH3 CN (Cox Ni7-x -Ni1 ) under ambient conditions. It has proved possible to explore the bottom-up assembly process of Cox Ni7-x and Cox Ni7-x -Ni1 in real time. The final products have been characterized by thermogravimetric analysis, IR, elemental analysis, ICP-MS, and single-crystal X-ray diffraction. Time-dependent mass spectrometry (MS) revealed the following reaction steps: Ni1 →[M2 L3 ]+ →[M4 (OH)2 L4 ]2+ →[M7 (OH)6 L6 ]2+ . In contrast, the reaction of Ni1 with Zn2+ only reaches halfway, and crystallographic evidence indicates a butterfly structure for [Zn2 Ni2 (OH)2 Cl2 ] (Zn2 Ni2 ), an intermediate that is difficult to isolate in the above Ni-Co series. A summation method has been used to analyze the MS of bimetallic clusters with very similar atomic masses, as is the case for Co and Ni. The results provide ample information on the distribution of Co and Ni within each cluster and their statistical distribution within selected crystals.

Association Between Serratia marcescens Contamination and Hygiene Compliance in Orthokeratology.

BACKGROUND/AIM: Given the characteristics of Serratia marcescens (S. marcescens), this study aimed at investigating its presence in the hands and contact lens cases of orthokeratology wearers, along with the status of bacterial contamination. PATIENTS AND METHODS: The 39 patients received the questionnaires about the background of orthokeratology and hygiene habits. A total of 39 contact lens cases and 39 hand samples from the patients were collected at Show Chwan Memorial Hospital from June to August in 2020 and sent to National Chung Cheng University for DNA extraction and PCR identification. RESULTS: The results indicated a detection rate of 5.13% for S. marcescens in the contact lens cases and 12.82% in the hand samples. Additionally, 66.67% of contact lens case samples and 30.77% of hand samples found positive for 16s bacterial amplicons. The relationship between hand contamination and the duration of contact lens usage were revealed for both S. marcescens (p=0.021) and 16s bacterial amplicons (p=0.048). CONCLUSION: The results indicated that hand hygiene is more critical than focusing on contact lens hygiene when it comes to preventing S. marcescens infections. Nevertheless, both proper hand and contact lens hygiene practices can reduce the detection of bacterial eye pathogens, especially a common intestinal bacterium.

Short- and Long-Term Effects of Repetitive Transcranial Magnetic Stimulation on Poststroke Visuospatial Neglect: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis aimed to assess the effects of repetitive transcranial magnetic stimulation and select a suitable protocol for poststroke visuospatial neglect. DESIGN: PubMed, Cochrane Library, and Embase databases were searched for relevant studies from the inception date to October 31, 2021. The inclusion criteria were (1) randomized controlled trials, (2) people with visuospatial neglect, (3) treatment with different repetitive transcranial magnetic stimulation protocols, (4) comparison with sham or blank control, and (5) reports of performance measurements. RESULTS: Data were obtained from 11 randomized controlled trials. The effects of immediate and 1-mo postintervention were measured using line bisection test, cancellation test, and Catherine Bergego Scale. Results showed statistically significant improvement when applying low-frequency (0.5-1 Hz) repetitive transcranial magnetic stimulation or continuous theta burst stimulation to the left hemisphere on short- and long-term line bisection test (standardized mean difference = -1.10, 95% confidence interval = -1.84 to -0.37; standardized mean difference = -1.25, 95% confidence interval = -2.11 to -0.39) and cancellation test (standardized mean difference = 1.08, 95% confidence interval = 0.45 to 1.71; standardized mean difference = 1.45, 95% confidence interval = 0.42, 2.47). CONCLUSIONS: Repetitive transcranial magnetic stimulation may be considered a treatment option for poststroke visuospatial neglect. This review proves that a decrease in neuronal excitation in the left hemisphere, which restores the interhemispheric balance, benefits poststroke visuospatial neglect.

Rapid automatic naming and phonological awareness deficits in preschool children with probable developmental coordination disorder.

Children with developmental coordination disorder (DCD) have been reported to have a higher risk of dyslexia than children with typical development (TD). Phonological awareness (PA) and rapid automatic naming (RAN) are known to be predictive of children's reading development. The present study examined PA and RAN in preschool children with and without probable DCD in Taiwan. In total, 704 children aged 5-6 years old from 25 preschools in Taichung City were included as participants. The probable DCD children performed more poorly than the children with TD on the PA and the RAN tests. Put in deficit terms, 22% of the children with TD, but 48% of the probable DCD children, had a single or dual PA/RAN deficit. Furthermore, it was manual dexterity that bore the unique relationship with RAN. Automatic visual perceptual-motor coordination may be the common processing component that underlies RAN and probable DCD. The early visual perceptual-motor profile of probable DCD children has not been well recognized before.

Urinating in the standing position: a feasible alternative for elderly women with knee osteoarthritis.

PURPOSE: Urinating while standing is a possible alternative for elderly women with knee osteoarthritis when a sitting toilet is unavailable. We evaluated uroflowmetric characteristics and post-void residual urine volume in elderly women with knee osteoarthritis who urinated while standing. MATERIALS AND METHODS: We recruited 21 women with a mean±SD age of 65.0±4.6 years who had a knee osteoarthritis Lequesne index score of at least 6 points and were unable to maintain or found it difficult to stand up from a squat or crouch. Participants used a homemade auxiliary appliance to collect urine and drain it forward while stand voiding. Uroflowmetric data, including voided volume, and maximal and average flow rates, were recorded. Post-void residual urine volume was detected using an ultrasound bladder scanner. Participants completed a questionnaire to evaluate their attitude toward stand voiding and using the auxiliary device. RESULTS: Maximal and average flow rates, and voided and post-void residual urine volumes were not statistically different while sitting and standing. No learning curve was noted for stand voiding. Uroflowmetry patterns while standing were smooth. Of the 21 participants 17 (81%) experienced no difficulty while stand voiding. All expressed willingness to urinate while standing position if they did not have access to a satisfactorily clean toilet seat. CONCLUSIONS: Urinating while standing is a feasible option for elderly women with knee osteoarthritis who have difficulty crouching or squatting to void in public restrooms.

Overexpression of urokinase-type plasminogen activator in pterygia and pterygium fibroblasts.

PURPOSE: Urokinase-type plasminogen activator (uPA) is a protease involved in tissue remodeling and cell migration. Little is known about the expression of uPA in pterygium. The purpose of this study was to investigate the expression of uPA mRNA and activities in various stages of surgically excised pterygia specimens and cultured pterygium fibroblasts and to compare them with normal conjunctival tissues and fibroblasts. METHODS: The expression of uPA mRNA and activity in 15 pterygium tissues and cultured fibroblasts from pterygium were measured using quantitative RT-PCR and zymography. Five normal conjunctiva specimens and cultured conjunctival fibroblasts were tested as the controls. RESULTS: The expression of uPA mRNA and activities in pterygia and pterygium fibroblasts were significantly greater than those of the normal samples (p<0.05) and were closely related to the progression of pterygium. The amounts of uPA mRNA and activities in early, moderate, and advanced pterygia were 100%, 208%, and 311% and 100%, 157%, and 280% of the early stage specimens, respectively. The amounts of uPA mRNA and the activities in cultured pterygium fibroblasts isolated from early, moderate, and advanced pterygium specimens were 100%, 219%, and 457% and 100%, 198% and 355% of early stage fibroblasts, respectively. CONCLUSIONS: Overexpression of uPA was present in pterygium and their fibroblasts. The expression of uPA by pterygium increased significantly following the progression of the pterygium. The increased expression of uPA may covert plasminogen to plasmin, degrade extracellular matrixes, stimulate cell migration, induce angiogenesis, and plays an important role in the development and progression of pterygium.

Antrodia camphorata induces apoptosis and enhances the cytotoxic effect of paclitaxel in human ovarian cancer cells.

INTRODUCTION: Antrodia camphorata is a Chinese herb. Recently, several reports demonstrated that it had growth-inhibiting effects on some cancer cells. In this study, we investigated whether the crude extract of A. camphorata could inhibit the growth of ovarian cancer cells and examined the possible mechanisms involved. We also examined whether the cytotoxic effect of paclitaxel on ovarian cancer cells would be affected by A. camphorata. MATERIALS AND METHODS: Two human ovarian cancer cell lines, SKOV-3 and TOV-21G, were treated with A. camphorata (3-300 µg/mL). An MTT assay was used to test its cytotoxic effect. The apoptosis-related factors including the activity of caspase-3, -8, and -9 and the cytochrome c level released from mitochondria were analyzed. The expression of Bcl-2 family proteins (Bcl-2, Bcl-xL, Bax, Bim, Bad, and Bak) was examined by Western blot analysis. Cell lines were further treated with paclitaxel or paclitaxel plus A. camphorata to examine the cytotoxic efficiency. RESULTS: The MTT assay revealed that A. camphorata was cytotoxic to both the ovarian cancer cells in a dose- and time-dependent manner. Activities of caspase-3, -8, and -9 and release of mitochondrial cytochrome c increased in both ovarian cancer cell lines with increased dose of A. camphorata. Western blot analysis of Bcl-2 family proteins revealed an increased expression of Bad in SKOV-3 cells, whereas increased expression of Bim and Bak and decreased expression of Bcl-xL were noted in TOV-21G cells. In addition, the cytotoxic effect of paclitaxel on SKOV-3 and TOV-21G cells was increased significantly with the addition of A. camphorata (P < 0.01) by MTT assay. CONCLUSIONS: These in vitro results suggest that A. camphorata causes a cytotoxic effect on ovarian cancer cells through the induction of apoptosis. It may also enhance the antitumor effect of paclitaxel. Further studies with the ultimate goal of conducting clinical trials are warranted.

Impact of heavy precipitation events on pathogen occurrence in estuarine areas of the Puzi River in Taiwan.

Pathogen populations in estuarine areas are dynamic, as they are subject to multiple natural and anthropogenic challenges. Heavy rainfall events bring instability to the aquatic environment in estuaries, causing changes in pathogen populations and increased environmental sanitation and public health concerns. In this study, we investigated the effects of heavy precipitation on the occurrence of pathogens in the Puzi River estuary, which is adjacent to the largest inshore oyster farming area in Taiwan. Our results indicated that Vibrio parahaemolyticus and adenovirus were the most frequently detected pathogens in the area. There was a significant difference (Mann-Whitney U test, p < 0.01) in water quality parameters, including total coliform, Escherichia coli, water temperature, turbidity, salinity, and dissolved oxygen, between groups with and without V. parahaemolyticus. In addition, the detection rate was negatively correlated with the average daily rainfall (r2 > 0.8). There was no significant difference between water quality parameters and the presence/absence of adenovirus, but a positive correlation was observed between the average daily rainfall and the detection rate of adenovirus (r2 ≥ 0.75). We conclude that heavy precipitation changes estuarine water quality, causing variations in microbial composition, including pathogens. As extreme weather events become more frequent due to climate change, the potential impacts of severe weather events on estuarine environments require further investigation.

NAXE gene mutation-related progressive encephalopathy: A case report and literature review.

RATIONALE: Progressive encephalopathy with brain edema and/or leukoencephalopathy-1 is an infantile, lethal neurometabolic disorder caused by a NAD(P)HX epimerase (NAXE) gene mutation. It is characterized by a fluctuating disease course with repeated episodes of improvement and regression. In this report, we present a rare case of NAXE gene mutation-related encephalopathy with unexpected neurological recovery and long survival time. PATIENT CONCERNS: A 20-month-old girl presented with progressively unsteady gait and bilateral hand tremors after a trivial febrile illness. Her disease rapidly progressed to consciousness disturbance, 4-limb weakness (muscle power: 1/5 on the Medical Research Council scale), and respiratory failure. The patient gradually recovered 2 months later. However, another episode of severe fever-induced encephalopathy developed 2 years after the initial presentation. DIAGNOSES: Results of laboratory investigations, including complete blood count, blood chemistry, inflammatory markers, and cerebral spinal fluid analysis were unremarkable. Electroencephalography and nerve conduction velocity studies yielded normal results. Brain magnetic resonance imaging on diffusion-weighted imaging revealed abnormal sysmmetric hyperintensity in the bilateral middle cerebellar peduncles. A genetic study using whole exome sequencing confirmed the diagnosis of NAXE gene mutation-related encephalopathy. INTERVENTIONS: Pulse therapy with methylprednisolone, intravenous immunoglobulin, coenzyme Q10, and carnitine were initially introduced. After a NAXE gene defect was detected, the vitamin B complex and coenzyme Q10 were administered. A continuous rehabilitation program was also implemented. OUTCOMES: NAXE gene mutation-related encephalopathy is usually regarded as a lethal neurometabolic disorder. However, the outcome in this case is better than that in the previous cases. She showed progressive neurological recovery and a longer survival time. The muscle power of the 4 limbs recovered to grade 4. At present (age of 5.5 years old), she can walk with an unsteady gait and go to school. LESSONS: Although NAXE gene mutation-related encephalopathy is rare, it should be considered as a differential diagnosis of early onset progressive encephalopathy.

Prevalence, virulence-gene profiles, antimicrobial resistance, and genetic diversity of human pathogenic Aeromonas spp. from shellfish and aquatic environments.

Aeromonas are found in various habitats, particularly in aquatic environments. This study examined the presence of the most common human pathogenic Aeromonas species (Aeromonas caviae, A. hydrophila, and A. veronii) in surface water, sea water, and shellfish. The detection rates in fishing harbour seawater, shellfish farming seawater, and a river basin were 33.3%, 26.4%, and 29.4%, respectively, and high prevalence was observed in summer. The detection rates in shellfish procured from a fish market and shellfish farm were 34.9% and 13.3%, respectively. The most abundant species of human pathogenic Aeromonas detected via water sampling was A. caviae, whereas that obtained via shellfish sampling was A. veronii. The prevalence of human pathogenic Aeromonas in river water was lower in fishing harbours and in the estuary shellfish farming area. Here, 25 isolates of human pathogenic Aeromonas species were isolated from 257 samples and divided among 16 virulence profiles. The high virulence gene-carrying isolates (more than six genes) belonged to A. hydrophila. The shellfish-sourced isolates had the highest detection rates of act, aerA, and fla genes than of other virulence genes, and vice versa for seawater-sourced isolates. The Aeromonas isolates showed high levels of resistance to ampicillin-sulbactam; however, none were resistant to cefepime, ciprofloxacin, or gentamicin. The incidence of multiple drug resistance (MDR) in Aeromonas isolates was 20%. In this study, phylogenetic analysis with 16S rRNA sequencing, biochemical tests and enterobacterial repetitive intergenic consensus-polymerase chain reaction fingerprinting facilitated the distinct categorisation of three species of human pathogenic Aeromonas isolates. In addition, A. veronii isolates from the same geographical area were also concentrated in the same cluster. This study provides information on the risk of infection by Aeromonas with MDR and multiple virulence genes isolated from shellfish and aquatic environments.

Voiding dysfunctions in children with mental retardation.

AIMS: This study aims to evaluate the voiding disorder and lower urinary tract symptoms in mentally retarded children. METHODS: Fifty-one mentally retarded children (age 7.7 years) was assessed. A volunteer sample comprised of 36 typically developing children (age 6.4 years) served as the comparative group. All participants underwent uroflometric investigation, and residual urine was detected by sonography. Urological history including history of urinary tract infection, incontinence, frequency, and dysurea was collected. In addition, the mentally retarded group was classified according to IQ: severe mentally retarded group (IQ below 40) (n = 11), moderate mentally retarded group (IQ: 41 to 55) (n = 19), mild mentally retarded group (IQ: 56 to 70) (n = 21). Group comparisons were analyzed using Chi-square and Student's t-test. RESULTS: Of the 51 mentally retarded children, 18(35.2%) were found to have voiding dysfunction, which is significantly higher than the control group (8.3%). The incidence of urine incontinence and frequency is also significantly higher in the mentally retarded group. The comparison of the three mentally retarded subgroups showed that the severe mentally retarded group had the highest incidence of voiding dysfunction and urinary incontinence. Overall, the mentally retarded group had higher percentage of small bladder capacity. CONCLUSIONS: We concluded that mentally retarded children have a higher incidence of voiding dysfunction and incontinence than the control group. Early detection of voiding dysfunction in an objective, non-invasive manner is important in mentally retarded children, particularly those with severe cognitive impairment.

[Characteristics of clinical effectiveness of bloodletting and proposed ways of mechanism research].

According to the operative characteristics, the stimulated site and the curative effect-emerged site of bloodletting therapy, its clinical characteristics may be divided into three categories: a) local stimulation induced focus-local effect, b) local stimulation induced effect of the distal target organ (point-to-point distal effect), and c) special point stimulation induced broader effect of the whole body. Accordingly, the underlying mechanisms of clinical outcomes mainly involve the improvement of the local microcirculation and secondary changes of inflammatory substances for the first category (local focus). The point-to-point distal effect might mainly involve the innervation of nerve segments, while the broad effect of specific acupoint stimulation might involve multiple levels of the neuro-endocrine-immune system. The future research on the mechanisms of bloodletting should starts from its specific effects and the type of disease, which should not be generalized.

AR ubiquitination induced by the curcumin analog suppresses growth of temozolomide-resistant glioblastoma through disrupting GPX4-Mediated redox homeostasis.

Drug resistance is the main obstacle in the improvement of chemotherapeutic efficacy in glioblastoma. Previously, we showed that dehydroepiandrosterone (DHEA), one kind of androgen/neurosteroid, potentiates glioblastoma to acquire resistance through attenuating DNA damage. Androgen receptor (AR) activated by DHEA or other types of androgen was reported to promote drug resistance in prostate cancer. However, in DHEA-enriched microenvironment, the role of AR in acquiring resistance of glioblastoma remains unknown. In this study, we found that AR expression is significantly correlated with poor prognosis, and AR obviously induced the resistance to temozolomide (TMZ) treatment. Herein, we observed that ALZ003, a curcumin analog, induces FBXL2-mediated AR ubiquitination, leading to degradation. Importantly, ALZ003 significantly inhibited the survival of TMZ-sensitive and -resistant glioblastoma in vitro and in vivo. The accumulation of reactive oxygen species (ROS), lipid peroxidation and suppression of glutathione peroxidase (GPX) 4, which are characteristics of ferroptosis, were observed in glioblastoma cell after treatment of ALZ003. Furthermore, overexpression of AR prevented ferroptosis in the presence of GPX4. To evaluate the therapeutic effect in vivo, we transplanted TMZ-sensitive or -resistant U87MG cells into mouse brain followed by intravenous administration with ALZ003. In addition to inhibiting the growth of glioblastoma, ALZ003 significantly extended the survival period of transplanted mice, and significantly decreased AR expression in the tumor area. Taken together, AR potentiates TMZ resistance for glioblastoma, and ALZ003-mediated AR ubiquitination might open a new insight into therapeutic strategy for TMZ resistant glioblastoma.