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SARM1, an executioner in axon degeneration, is an autoinhibitory NAD-consuming enzyme, composed of multiple domains. NMN and its analogs, CZ-48 and VMN, are the only known activators, which can release the inhibitory ARM domain from the enzymatic TIR domain. Here, we document that acid can also activate SARM1, even more efficiently than NMN, possibly via the protonation of the negative residues. Systematic mutagenesis revealed that a single mutation, E689Q in TIR, led to the constitutive activation of SARM1. It forms a salt bridge with R216 in the neighboring ARM, maintaining the autoinhibitory structure. Using this 'acid activation' protocol, mutation K597E was found to inhibit activation, while H685A eliminated SARM1 catalytic activity, revealing two distinct inhibitory mechanisms. The protocol has also been applied to differentiate two classes of chemical inhibitors. NAD, dHNN, disulfiram, CHAPS, and TRX-100 mainly inhibited the activation process, while nicotinamide and Tweens mainly inhibited SARM1 catalysis. Taken together, we demonstrate a new mechanism for SARM1 activation and decipher two distinct inhibitory mechanisms of SARM1.

BACKGROUND: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated. METHODS: The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo. RESULTS: The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo. CONCLUSION: TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

Objectives To evaluate the efficacy of 12-week pelvic floor muscle training (PFMT) using bio-assisted surface electromyography (EMG) feedback in women with complex pelvic floor dysfunction (PFD); to further differentiate the effect of exercise adherence from the biofeedback per se; and to assess and compare the severities of overactive bladder (OAB) symptoms, stress urinary incontinence (SUI), and stage of prolapse with the women’s perception of symptom cure or improvement following the program. Study design This prospective observational study was conducted between December 2015 and November 2018 at a medical center in Taiwan. It included 83 women with PFD, manifesting solely as either OAB or SUI with (group 1) or without (group 2) concomitant stages I and II pelvic organ prolapse (POP). All women underwent a 12-week bio-assisted PFMT. The main outcome was the electromyographic activity of the pelvic floor muscles (PFMs). The severities of OAB symptoms, SUI, and stage of POP were assessed both subjectively and objectively before and after the intervention. Results A notable improvement of PFM function was identified after 12 weeks of training in all women with PFD. The number of effective PFM contractions achieved during bio-assisted PFMT was positively correlated with the improvement of PFM function in both groups of women in different body positions, except in the standing position in group 2. Exercise adherence, however, had no significant impact on the efficacy of the training. There was a significant improvement over time and high consistency between subjective and objective improvements of OAB symptoms and SUI severity after the completion of PFMT. Nonetheless, only the Ba point of the POP-Quantification system in women with POP showed a significant improvement after the intervention. Conclusion PFMT using surface EMG biofeedback significantly improves PFM function in women with complex PFD, and thus, has a significant therapeutic effect on OAB, SUI, and bladder prolapse.

Background With the recent emergence of immune checkpoint inhibitors, microsatellite instability (MSI) status has become an important biomarker for immune checkpoint blockade therapy. There are growing technical demands for the integration of different genomic alterations profiling including MSI analysis in a single assay for full use of the limited tissues. Methods Tumor and paired control samples from 64 patients with primary colorectal cancer were enrolled in this study, including 14 MSI-high (MSI-H) cases and 50 microsatellite stable (MSS) cases determined by MSI-PCR. All the samples were sequenced by a customized NGS panel covering 2.2 MB. A training dataset of 28 samples was used for selection of microsatellite loci and a novel NGS-based MSI status classifier, USCI-msi, was developed. NGS-based MSI status, single nucleotide variant (SNV) and tumor mutation burden (TMB) were detected for all patients. Most of the patients were also independently detected by immunohistochemistry (IHC) staining. Results A 9-loci model for detecting microsatellite instability was able to correctly predict MSI status with 100% sensitivity and specificity compared with MSI-PCR, and 84.3% overall concordance with IHC staining. Mutations in cancer driver genes (APC, TP53, and KRAS) were dispersed in MSI-H and MSS cases, while BRAF p.V600E and frameshifts in TCF7L2 gene occurred only in MSI-H cases. Mismatch repair (MMR)-related genes are highly mutated in MSI-H samples. Conclusion We established a new NGS-based MSI classifier, USCI-msi, with as few as 9 microsatellite loci for detecting MSI status in CRC cases. This approach possesses 100% sensitivity and specificity, and performed robustly in samples with low tumor purity.

Evidence indicates that age-related macular degeneration (AMD) is associated with the prior presence of allergic diseases; however, large-scale studies in the literature are limited. A case–control study was conducted to describe the relationship between premorbid allergic diseases and AMD using Taiwan’s National Health Insurance database. Eligibility criteria for inclusion of new adult AMD cases from 2000 to 2013 were set up. We defined the year of diagnosis as the index year. Age-, gender-, index year- matched controls who were drawn from the same database. The case control ratio was 1:4. For all participants, all premorbid conditions staring 1996 to index year were documented. Binary logistic regression was used to describe factors related to AMD occurrence. The AMD group consisted of 10,911 patients, and the comparison group consisted of 43,644 individuals. Patients with AMD showed significant associations with premorbid allergic diseases (aOR 1.54, 95% CI 1.47–1.61), specifically with allergic conjunctivitis (aOR 2.07, 95% CI 1.94–2.20), allergic rhinitis (aOR 1.32, 95% CI 1.25–1.39), asthma (aOR 0.99, 95% CI 0.93–1.06), and atopic dermatitis (aOR 1.04, 95% CI 0.94–1.17). Further analyses indicated that patients with more concurrent allergic diseases have higher associations with AMD than those with fewer concurrent diseases. Patients with more annual medical visits for their allergic diseases also showed higher associations with AMD than those with fewer visits. AMD is significantly associated with premorbid allergic diseases. The underlying mechanisms must be further investigated.

Study Objective To identify factors predictive of persistent ectopic pregnancy (PEP) in women who have undergone laparoscopic salpingostomy or salpingotomy for tubal pregnancy. Design Retrospective cohort study (Canadian Task Force classification II-2). Setting Tertiary referral center. Patients Ninety-nine women who underwent laparoscopic tubal preservation surgery for ectopic pregnancy. Interventions Seventy women underwent laparoscopic salpingostomy, and the remaining 29 women underwent laparoscopic salpingotomy. Measurements and Main Results Factors predicting PEP were evaluated. The change in serum beta human chorionic gonadotropin (β-hCG) levels from baseline observed between postoperative days 5 and 10 (ChCGD5-10) was a predictor of PEP (odds ratio [OR], 0.80; p = .01). Based on receiver operating characteristic (ROC) curve analysis, a cutoff value of 93.1% was determined, with an area under the ROC curve of 0.95 (sensitivity, 85.7%; specificity, 100%). Nonetheless, when considering perioperative variables only, body mass index (BMI) was identified as a predictor of PEP (OR, 0.71; p = .03). Based on the ROC analysis, a BMI cutoff value of ≤22 kg/m 2 was determined, with an ROC area of 0.73 (sensitivity, 43.2%; specificity, 100%). In addition, a higher baseline β-hCG level (hazard ratio [HR], 1.0002; p = .009) and left tubal pregnancy (HR, 6.46; p = .03) were predictive of recurrent ectopic pregnancy. There were no differences in the perioperative outcomes, PEP rates, or subsequent intrauterine pregnancy rates between the salpingostomy and salpingotomy groups. In addition, surgical method was not a predictor of recurrent ectopic pregnancy. Conclusions ChCGD5-10 was identified as a predictor for PEP, suggesting that it might be more clinically useful for the follow-up of PEP. When considering perioperative variables only, BMI was a predictor for PEP. In addition, there was no significant difference in clinical outcomes between the salpingostomy and salpingotomy groups.

Chinese medicine (CM) has become a popular interventional treatment for rheumatoid arthritis (RA). However, limited knowledge about general characteristics and long-term clinical outcomes hampers the development of CM for RA.The main objectives of the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) were to describe the population of RA patients receiving CM treatment in multiple centers in China using different variables and compare these findings with internationally reported data.The CERTAIN is a prospective, multicenter, observational disease registry.Adult RA patients who fulfilled the 2010 American College of Rheumatology/ European League Against Rheumatism classification criteria for RA and received CM treatment were recruited into the CERTAIN by rheumatologists from 145 hospitals across 30 provinces in China. Data on demographics, disease characteristics, comorbidities, treatments, and adverse events, with a 2-year follow-up, were collected and documented using a predefined protocol.In the 2 years since the study began in September 2019, 11,764 patients have been enrolled (enrolment is ongoing), and 13.10% of participants have completed the 6-month follow-up. We present the baseline characteristics of the first 11,764 enrollees.The CERTAIN is the first nationwide registry to document comprehensive data on CM treatment in patients with RA. The development of the CERTAIN resource is a significant step forward for Chinese RA patients, herbal medicine users, and research communities and will deepen our understanding of CM for RA.The study was registered at ClinicalTrials.gov (NCT05219214).

Objective To evaluate the feasibility and effectiveness of robotic/laparoscopic repair of cesarean scar defects or cesarean scar pregnancies with a uterine sound. Materials and methods All consecutive women with cesarean scar defects or cesarean scar pregnancies who underwent robotic/laparoscopic repair with a bent uterine sound guidance were reviewed. Subjective changes in symptoms and objective changes in the depth and width of cesarean scar defects after surgery were reviewed. Results A total of 20 women underwent robotic (n = 3) or conventional laparoscopic (n = 17) repair of cesarean scar defects, which included postmenstrual vaginal bleeding associated with cesarean scar defects (n = 15), cesarean scar pregnancies (n = 3), accumulated pus in the cesarean scar defect (n = 1) and an incomplete abortion incarcerated in the cesarean scar defect (n = 1). Bladder perforation occurred in one woman during robotic adhesiolysis. All women with cesarean scar defects (n = 15) reported an improvement in postmenstrual vaginal bleeding after surgery. Follow-up sonography showed a decrease in the depth and width of the cesarean scar defect and an increase in the residual myometrial thickness. Conclusion Robotic or laparoscopic repair with a uterine sound guidance seems to be a feasible and effective method in the treatment of cesarean scar defect or cesarean scar pregnancy.

Parent education programs, offered via family–school partnerships, offer an effective means for promoting the mental health and educational functioning of children and adolescents at a whole-school level. However, these programs often have a low uptake. This study aimed to identify strategies for increasing the uptake of parent education programs within preschool and school settings. A three-round Delphi procedure was employed to obtain expert consensus on strategies that are important and feasible in educational settings. First, thirty experts rated statements identified from the literature and a stakeholder forum. Next, experts re-appraised statements, including new statements generated from the first round. Ninety statements were endorsed by ≥80% of the experts. Primary themes include strategies for program selection, strategies for increasing the accessibility of programs and the understanding of educational staff on parent engagement and child mental health, strategies for program development, promotion and delivery, as well as strategies for increasing parent and community engagement. This study offers a set of consensus strategies for improving the uptake of parent education programs within family–school partnership.

Background Despite considerable evidence on parenting risk and protective factors for child anxiety and depressive disorders, the development of interventions based on this evidence is still lagging behind. To address this gap, the web-based Parenting Resilient Kids (PaRK) program was developed to target these risk and protective factors. This study evaluated the effects of the program at 12-month follow-up. Methods A randomized controlled trial was conducted with a community sample of 355 parents and 342 children (Mchild age = 9.79). Parents randomized into the web-based PaRK intervention condition received a personalized feedback report about their parenting and were recommended a tailored course of up to 12 interactive modules. Parents in the control condition received a standard set of web-based educational factsheets. Results Parents in the intervention group demonstrated significantly greater improvement in self-reported parenting compared to control group parents from baseline to 12-month follow-up, d = 0.24, 95% CI [0.03, 0.45]. Both groups showed reductions in child anxiety and depressive symptoms, parental psychological control and unhealthy family functioning; and improvements in parental acceptance, child- and parent- health-related quality of life. Limitations The PaRK intervention was tailored based on the parents’ own report of their parenting behaviors. There was an over-representation of highly-educated mothers and only one parent-child dyad was included per family. Conclusions PaRK improved parenting for up to 12 months, but had no superior effect on children's mental health outcomes compared with an educational-factsheet intervention. Further follow-up is needed to assess longer-term effects.

Metastasis is the most frequent cause of death in cancer patients. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGFβ) signaling pathway is a major driver of EMT. Increasing evidence demonstrates that metabolic reprogramming is a hallmark of cancer and extensive metabolic changes are observed during EMT. The aim of this review is to summarize and interconnect recent findings that illustrate how changes in glycolysis, mitochondrial, lipid and choline metabolism coincide and functionally contribute to TGFβ-induced EMT. We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. Combined we illustrate that a better understanding of the mechanistic links between TGFβ signaling, cancer metabolism and EMT holds promising strategies for cancer therapy, some of which are already actively being explored in the clinic.

Background: to elucidate the predictors of progression-free survival (PFS) and overall survival (OS) in high-risk endometrial cancer patients. Methods: the medical records of all consecutivewomen with high-risk endometrial cancer were reviewed. Results: among 92 high-risk endometrial cancer patients, 30 women experienced recurrence, and 21 women died. The 5-year PFS and OS probabilities were 65.3% and 75.9%, respectively. Multivariable Cox regression revealed that body mass index (hazard ratio (HR) = 1.11), paraaortic lymph node metastasis (HR = 11.11), lymphovascular space invasion (HR = 5.61), and sandwich chemoradiotherapy (HR = 0.15) were independently predictors of PFS. Body mass index (HR = 1.31), paraaortic lymph node metastasis (HR = 32.74), non-endometrioid cell type (HR = 11.31), and sandwich chemoradiotherapy (HR = 0.07) were independently predictors of OS. Among 51 women who underwent sandwich (n = 35) or concurrent (n = 16) chemoradiotherapy, the use of sandwich chemoradiotherapy were associated with better PFS (adjusted HR = 0.26, 95% CI = 0.08&ndash, 0.87, p = 0.03) and OS (adjusted HR = 0.11, 95% CI = 0.02&ndash, 0.71, p = 0.02) compared with concurrent chemoradiotherapy. Conclusion: compared with concurrent chemoradiotherapy, sandwich chemoradiotherapy was associated with better PFS and OS in high-risk endometrial cancer patients. In addition, high body mass index, paraaortic lymph node metastasis, and non-endometrioid cell type were also predictors of poor OS in high-risk endometrial cancer patients.

Background: We aimed to compare the clinical outcomes between intraperitoneal chemotherapy and dose-dense chemotherapy for the frontline treatment of advanced ovarian, fallopian tube and primary peritoneal cancer in women not receiving bevacizumab. Methods: All consecutive women with stage II~IV cancer treated with either frontline intraperitoneal or dose-dense platinum/paclitaxel chemotherapy and not receiving bevacizumab between March 2006 and June 2019 were reviewed. Results: A total of 50 women (intraperitoneal group, n = 22, dose-dense group, n = 28) were reviewed. Median progression-free survival (32.6 months versus 14.2 months, adjusted hazard ratio = 0.38, 95% CI = 0.16 to 0.90, p = 0.03) and overall survival (not reached versus 30.7 months, adjusted hazard ratio = 0.23, 95% CI = 0.07 to 0.79, p = 0.02) were significantly higher in the intraperitoneal group than in the dose-dense group. A multivariable Cox proportional-hazards model also indicated that the number of frontline chemotherapy cycles (adjusted hazard ratio = 0.66, 95% CI 0.47 to 0.94, p = 0.02) was a predictor of better overall survival. Nausea/vomiting and nephrotoxicity occurred more frequently in the intraperitoneal group (p = 0.02 and &lt, 0.0001, respectively). Conclusions: Intraperitoneal chemotherapy seems to be superior in progression free survival and overall survival to dose-dense chemotherapy in the frontline treatment of women with optimally resected advanced ovarian, fallopian tube or primary peritoneal cancer and not receiving bevacizumab.

Voxel-based morphometry (VBM) is a popular non-invasive magnetic resonance imaging technique to investigate brain gray matter (GM) differences between groups. Recently, two VBM studies in migraine have been published in The Journal of Headache and Pain. Reviewing the two and those previous published VBM studies, we found considerable variations of the results. Spatially diverse brain regions with decreased and increased GM alterations and null findings have been reported. It is interesting to know whether there is a reliable brain morphological signature for migraine. Coordinate-based meta-analysis (CBMA) is increasingly used to quantitatively pool individual neuroimaging studies to identify consistent and reliable findings. Several CBMA have been conducted, however, their results were inconsistent. The algorithms for CBMA have evolved and more eligible VBM studies in migraine have been published. We therefore conducted an updated CBMA using the latest algorithms for CBMA, seed-based d mapping with permutation of subject images (SDM-PSI). The present CBMA of 32 VBM studies (41 datasets comprising 1252 patients and 1025 healthy controls) found no evidence of consistent GM alterations in migraine. Sensitivity analysis, subgroup meta-analyses, and meta-regression analyses revealed that the result was robust. This negative result indicates that there is no reliable brain morphological signature for migraine. VBM investigations in migraine remain a heterogeneous field. Many potential confounding factors, such as underpowered sample sizes, variations in demographic and clinical characteristics, and differences in MRI scanners, head coils, scanning parameters, preprocessing procedures, and statistical strategies may cause the inconsistences of the results. Future VBM studies are warranted to enroll well-characterized and homogeneous subtype samples with appropriate sample sizes, comprehensively assess comorbidities and medication status, and use well-validated and standardized imaging protocols and processing and analysis pipelines to produce robust and replicable results in migraine.

Background In order to detect glaucomatous optic nerve damages early on and evaluate the severity of glaucoma, a previously developed analytic method based on photographic retinal nerve fiber layer (RNFL) angle defect was proposed. However, the correlation between these defective angles and the severity of visual field defect has not been verified. This study aimed to confirm the correlation described above. Methods We reviewed a total of 227 glaucomatous eyes (38 enrolled, 189 excluded) during an interval of 5 years. The angles of all eyes were measured on RNFL photograph, of which angle α is the angular width between the macula center and the proximity of RNFL defect, and angle β (+c) is the sum of angular width(s) of localized RNFL defect. The severity of visual field defect was determined by mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). Correlation analysis was performed on angle α and angle β (+c) with the presence of central scotoma and visual field defect parameters, respectively. Results Angle β (+c) showed significant correlation with MD (P = 0.007), PSD (P = 0.02), VFI (P = 0.03), and average RNFL thickness (P = 0.03). No correlation was found between angle α and the presence of central scotoma. Conclusions In conclusion, measuring the angular width of localized RNFL defect is a viable method for determining the severity of visual field defect.

In Taiwan, the prevalence of myopia in children between 6 and 18 years old is over 80%, and high myopia accounts for over 20%, which turned out to be in the leading place worldwide. Orthokeratology and low-dose atropine are proven treatments to reduce myopia progression, though the potential corneal disturbances remain an issue in young populations. The alteration of the tear film is widely discussed but there is no consensus to date, so we aim to investigate the tear film spatial instability in children with myopia control using atropine or orthokeratology. Thirty-eight treatment-naïve participants and 126 myopic children under treatments were enrolled. The ocular surface homeostasis, spatial distribution of tear break-up, and high-order aberrations (HOAs) of the corneal surface were assessed. We found out that myopic children treated with either atropine or orthokeratology showed ocular surface homeostasis similar to that in treatment-naïve children. Nevertheless, children treated with orthokeratology presented higher HOAs (p p = 0.04). This unique spatial instability of the tear film associated with myopia treatment might provide a more focused way of monitoring the pediatric tear film instability.

OBJECTIVE Photoplethysmogram (PPG) signals have been widely used to estimate blood pressure (BP) cufflessly and continuously. A number of different PPG features have been proposed and extracted from PPG signals with the aim of accurately estimating BP. However, the underlying physiological mechanisms of PPG-based BP estimation still remain unclear, particularly those corresponding to various PPG features. In this study, the physiological mechanisms of PPG features for BP estimation were investigated, which may provide further insight. APPROACH Experiments with cold stimuli and an exercise trial were designed to change the total peripheral vascular resistance (TPR) and cardiac output (CO), respectively. Instantaneous BP and continuous PPG signals from 12 healthy subjects were recorded throughout the experiments. A total of 65 PPG features were extracted from the original, the first derivative, and the second derivative waves of PPG. The significance of the change of PPG features in the cold stimuli phase and in the early exercise recovery period was compared with that in the baseline phase. MAIN RESULTS Intensity-specific PPG features changed significantly (p < 0.05) in the cold stimuli phase compared with the baseline phase, demonstrating that they were TPR-correlated. Time-specific PPG features changed significantly (p < 0.05) in the early exercise recovery period compared with the baseline phase, suggesting they were CO-correlated. Most of the PPG features associated with slope and area changed obviously both in the cold stimuli phase and in the early exercise recovery period, indicating that they should be TPR-correlated and CO-correlated. SIGNIFICANCE The findings of this study explained the intrinsic physiological mechanisms underlying PPG features used for BP estimation, and provided insights for exploring more diagnostic applications of the PPG features.

Background: Knowledge of the clinical outcome of women with non-gastric gastrointestinal stromal tumors (GISTs) is important for preoperative and postoperative consultation, especially for gynecologic oncologist. The aim of this study is to elucidate the factors affecting the clinical outcome of women with non-gastric GISTs.Methods: Between January 2000 and October 2019, all consecutive women with non-gastric GIST who underwent surgeries in a tertiary referral center were reviewed.Results: Among 26 women with non-gastric GISTs, eight (31%) women had recurrence or metastasis. Common clinical presentations included abdominal pain/fullness (n=12, 46%) and tarry/bloody stool (n=7, 27%). The primary locations of the tumors included the intestines (n=24) and an undetermined origin (n=2). Five (19%) women were initially admitted to the gynecologic department. Twenty-four (92%) patients underwent laparotomic tumor resection, and 2 (8%) patients underwent laparoscopic tumor resection. The probabilities of recurrence-free survival (RFS) at 60 and 120 months were 65.2% and 55.9%, respectively. Death occurred in seven (26.9%) women. The probabilities of overall survival (OS) at 60 and 120 months were 71.1% and 63.9%, respectively. Cancer stage was the only independent predictor for RFS (hazard ratio=6.00, p=0.007) and OS (hazard ratio=3.88, p=0.04). However, excluding cancer stage, metastasis (hazard ratio=8.74 for RFS, 6.03 for OS) and tumor size (hazard ratio=1.20 for OS) were independent predictors. Tumor size ≥ 13.9 cm was the optimum cut-off value to predict death and had an area under the receiver operating characteristic curve of 0.75 (95% confidence interval=0.53 to 0.98).Conclusions: Non-gastric GIST may mimic gynecologic adnexal tumors. In addition to cancer stage, metastasis and tumor size (especially ≥ 13.9 cm for OS) remain independent predictors for RFS and OS in women with non-gastric GIST. The above findings may be used for consultation.Trial registration: ClinicalTrials.gov NCT04256226

Both in Taiwan and around the world, lung cancer is a primary cause of cancer-related deaths. In Taiwan, the most prevalent form of lung cancer is lung adenocarcinoma, a type of non-small-cell lung carcinoma. Although numerous lung cancer therapies are available, their clinical outcomes are unsatisfactory. Natural products, including fungal metabolites, are excellent sources of pharmaceutical compounds used in cancer treatment. We employed in vitro cell invasion, cell proliferation, cell migration, cell viability, and colony formation assays with the aim of evaluating the effects of coriloxin, isolated from fermented broths of Nectria balsamea YMJ94052402, on human lung adenocarcinoma CL1-5 and/or A549 cells. The potential targets regulated by coriloxin were examined through Western blot analysis. The cytotoxic effect of coriloxin was more efficiently exerted on lung adenocarcinoma cells than on bronchial epithelial cells. Moreover, low-concentration coriloxin significantly suppressed adenocarcinoma cells’ proliferative, migratory, and clonogenic abilities. These inhibitory effects were achieved through ERK/AKT inactivation, epithelial–mesenchymal transition regulation, and HLJ1 expression. Our findings suggest that coriloxin can be used as a multitarget anticancer agent. Further investigations of the application of coriloxin as an adjuvant therapy in lung cancer treatment are warranted.

Although parents’ engagement in parenting programmes has frequently been posited to influence the efficacy and dissemination of these programmes, its relationship with intervention outcomes in parenting programmes is understudied. This study examined the predictive value of parental engagement on preventive parenting outcomes in a tailored online parenting programme aimed at enhancing parental protective factors and reducing risk factors for child depression and anxiety disorders. The present study also explored the associations between parental engagement and other parent, child and family outcomes. Data were collected from a community sample of 177 parents who received a tailored online parenting programme (‘Parenting Resilient Kids’; PaRK) and their children as part of a randomised controlled trial. Participants completed measures on parenting, child anxiety and depressive symptoms, health-related quality of life and family functioning on three occasions. Multiple regressions showed that parental engagement explained additional variance in preventive parenting (most proximal outcomes) at post-intervention and 12-month follow-up. Indicators of higher levels of parental engagement, operationalised by greater proportions of recommended programme modules and intended goals completed, uniquely predicted higher levels of preventing parenting. Higher levels of parental engagement also predicted higher levels of parental acceptance and parental psychosocial health-related quality of life, lower levels of parental psychological control and lower levels of impairments in child health-related quality of life. However, parental engagement did not explain additional variance in parent or child reported anxiety or depressive symptoms. This study provides support for the role of parental engagement in facilitating parenting changes in parenting-focused interventions.

We examined the bathtub drowning mortality among older adults in Japan. Mortality data from Japan and 30 other Organization for Economic Co-operation and Development (OECD) countries were extracted from World Health Organization Cause of Death Query Online. During 2012-2014, unintentional drowning mortality rates in Japan were 9.5, 28.2 and 39.7 per 100,000 population for adults aged 65-74, 75-84 and ≥85 years, respectively-rates highest among the 31 OECD countries. In total, 6377 older adults aged ≥65 years died from unintentional drowning in 2014, of which 4857 (76%) deaths involved bathtubs. During 1995-2014, the bathtub drowning mortality rate for adults aged ≥65 years was stable in Japan. During 2011-2014, approximately 4800 older adults died from bathtub drowning annually. Death predominantly occurred 'while in a bathtub', rather than 'following a fall into a bathtub'. In 2014, 95% and 87% of bathtub drowning deaths among older women and men aged ≥65 years, respectively, occurred at home. In conclusion, bathtub drowning deaths at home is an important public health problem among older adults Japanese and efforts are needed to reduce these preventable deaths.

For better treatment outcomes, dentists usually use a set of parameters for orthodontic evaluation. In this study, a new method is proposed to assist dentists in obtaining reliable assessment of these parameters. The proposed method is based on dental panoramic radiographs and can be divided into four stages: image preprocessing, model training, tooth segmentation, and assessment of orthodontic parameters. The image is first normalized and enhanced. Then, the model training stage consists of shape and image model training, energy function training, and weight training. Next, we automatically segment the tooth contours in an energy-minimized manner. Finally, the automatic assessment of orthodontic parameters is carried out. The experimental results show that the average of absolute distance, the Dice similarity coefficient, and the average qualitative score ranged between 4.17 and 6.03, 0.87 and 0.90, as well as 2.58 and 3.12, respectively. The orthodontic assessment also is close to the evaluation of orthodontists. It has been shown that the proposed method can obtain accurate and consistent measurement in helping dentists to obtain an objective treatment evaluation.

Probiotics are defined as microorganisms with beneficial health effects when consumed by humans, being applied mainly to improve allergic or intestinal diseases. Due to the increasing resistance of pathogens to antibiotics, the abuse of antibiotics becomes inefficient in the skin and in systemic infections, and probiotics may also provide the protective effect for repairing the healing of infected cutaneous wounds. Here we selected two Lactobacillus strains, L. plantarum GMNL-6 and L. paracasei GMNL-653, in heat-killed format to examine the beneficial effect in skin wound repair through the selection by promoting collagen synthesis in Hs68 fibroblast cells. The coverage of gels containing heat-killed GMNL-6 or GMNL-653 on the mouse tail with experimental wounds displayed healing promoting effects with promoting of metalloproteinase-1 expression at the early phase and reduced excessive fibrosis accumulation and deposition in the later tail-skin recovery stage. More importantly, lipoteichoic acid, the major component of Lactobacillus cell wall, from GMNL-6/GMNL-653 could achieve the anti-fibrogenic benefit similar to the heat-killed bacteria cells in the TGF-β stimulated Hs68 fibroblast cell model. Our study offers a new therapeutic potential of the heat-killed format of Lactobacillus as an alternative approach to treating skin healing disorders.

BACKGROUND Severe fever with thrombocytopenia syndrome is a serious insect-borne infectious disease caused by the Huaiyangshanbanyang virus. We conducted a retrospective study to identify risk factors for neurological complications caused by the virus. MATERIAL AND METHODS We included 121 patients who had severe fever with thrombocytopenia syndrome and were admitted to our hospital from 2013 to 2020. Patients' laboratory test results and clinical data were collected. Univariate and multivariate regression were used for statistical analysis. RESULTS Patients with neurological complications had higher mortality rates and longer hospital stays and disease duration than did patients without neurological complications. The neurological symptoms with the highest incidence rates were involuntary tremors (tongue and mandible), cognitive disorder, and limb tremors. Patients with neurological complications had a higher incidence of abnormal heart rhythms. Subcutaneous bleeding, pulmonary rales, percentage of neutrophils, increased lactate dehydrogenase and C-reactive protein levels, and decreased chloride ion concentration were closely related to the occurrence of neurological complications. The significant decrease in chloride ion concentration within 1 to 5 days of disease onset may be a risk factor for predicting the occurrence of neurological complications in patients with severe fever with thrombocytopenia syndrome. CONCLUSIONS Early monitoring of subcutaneous bleeding, pulmonary rales, electrocardiogram changes, and biochemical indicators in patients with severe fever with thrombocytopenia syndrome can predict the occurrence of neurological complications.

Osteoporotic patients often suffer from bone fracture but its healing is compromised due to impaired osteogenesis potential of bone marrow-derived mesenchymal stem cells (BMSCs). Here we aimed to exploit adipose-derived stem cells from ovariectomized rats (OVX-ASCs) for bone healing. We unraveled that OVX-ASCs highly expressed miR-214 and identified 2 miR-214 targets: CTNNB1 (β-catenin) and TAB2. We demonstrated that miR-214 targeting of these two genes blocked the Wnt pathway, led to preferable adipogenesis and hindered osteogenesis. As a result, OVX-ASCs implantation into OVX rats failed to heal critical-size metaphyseal bone defects. We further engineered the OVX-ASCs with a novel Cre/loxP-based hybrid baculovirus vector that conferred prolonged expression of miR-214 sponge. Gene delivery for miR-214 sponge expression successfully downregulated miR-214 levels, activated the Wnt pathway, upregulated osteogenic factors β-catenin/Runx2, downregulated adipogenic factors PPAR-γ and C/EBP-α, shifted the differentiation propensity towards osteogenic lineage, enhanced the osteogenesis of co-cultured OVX-BMSCs, elevated BMP7/osteoprotegerin secretion and hindered exosomal miR-214/osteopontin release. Consequently, implanting the miR-214 sponge-expressing OVX-ASCs tremendously improved bone healing in OVX rats. Co-expression of miR-214 sponge and BMP2 further synergized the OVX-ASCs-mediated bone regeneration in OVX rats. This study implicates the potential of suppressing miR-214 by baculovirus-mediated gene delivery in osteoporotic ASCs for regenerative medicine.

Background: The current study followed-up site-specific cancer risks in an unique cohort with 30 years’ follow-up after long-term low-dose-rate radiation exposure in Taiwan. Methods: Six thousand two hundred and forty two Taiwanese people received extra exposure in residential and school buildings constructed with Co-60-contaminated steel from 1982 until informed and relocated in early 1990s. The additional doses received have been estimated. During 1983–2012, 300 cancer cases were identified through the national cancer registry in Taiwan, 247 cases with minimum latent periods from initial exposure. The hazard ratios (HR) of site-specific cancers were estimated with additional cumulative exposure estimated individually. Results: Dose-dependent risks were statistically significantly increased for leukaemia excluding chronic lymphocytic leukaemia (HR100mSv 1.18; 90% CI 1.04–1.28), breast cancers (HR100mSv 1.11; 90% CI 1.05–1.20), and all cancers (HR100mSv 1.05; 90% CI 1.0–1.08, P=0.04). Women with an initial age of exposure lower than 20 were shown with dose response increase in breast cancers risks (HR100mSv 1.38; 90% CI 1.14–1.60; P=0.0008). Conclusions: Radiation exposure before age 20 was associated with a significantly increased risk of breast cancer at much lower radiation exposure than observed previously.

The aim of this study was to evaluate the efficacy and feasibility of a novel pusher device for performing extracorporeal knot tying. Each of the 3 laparoscopists randomly performed 10 device-assisted double sheet bends (the device group), ten 4s modified Roeder sliding knots (the sliding group), and 10 laparoscopic traditional extracorporeal static surgeon's knots (the static group). All knots and 5 unknotted threads were measured for strength. The device group had higher knot strength, lower knotting failure rate, and shorter knotting time compared with the sliding group. The knot strengths of the successful knots in the device group were consistent with those obtained in the static group, and higher than the sliding group. Our laparoscopic novel pusher device should be an effective device in assisting knot tying with the advantages of steady and strong knot strength, lower failure rate, and shorter knotting time.

Objective Previous studies evaluating the situation-background-assessment-recommendation (SBAR) have been shown to increase effective nurse–physician communication and collaboration. The purpose of this study is to evaluate the impact of the SBAR technique on safety attitudes in the obstetrics department. Materials and Methods This study implemented the SBAR Collaborative Communication Education course and was conducted in a medical center from February 2012 to March 2015, which included an educational session on fetal heart rate monitoring, a case-based discussion, and a video demonstration on traditional and SBAR communication. The nurses in the obstetrics department were requested to report their clinical findings and recommendations using a novel SBAR list when abnormal fetal heart beat tracings occurred. All obstetric nurses were requested to complete the Chinese-version of the Safety Attitudes Questionnaire before and after the SBAR educational course. The primary outcome was to evaluate the effect of the SBAR technique on the safety attitudes of the obstetrics department. The secondary outcome was to evaluate the effect of the SBAR technique on the 5-minute Apgar score for neonates. Results Most values, including teamwork climate, safety climate, job satisfaction, and working conditions, significantly improved at both postintervention surveys compared with the preintervention survey. There were no significant differences in the number of the neonates with less than seven 5-minute Apgar scores between the pre- and postintervention periods. Conclusion The SBAR technique, which uses a novel structured handover list, is a feasible tool for nurse–obstetrician communication, and it may improve most dimensions of safety attitudes in the obstetrics department.

Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus (T2DM) in animal models and human studies. We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed (HFD) rats. In the present study, we first identified another L. reuteri strain, ADR-1, which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats. We further performed a randomized, double-blinded, placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens. Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22). Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake. There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake. With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake. Interestingly, a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri. We also observed that there was a significantly positive correlation between Bifidobacterium spp. and Lactobacillus spp. in participants with increased levels of fecal L. reuteri. In the ADR-1 intake group, the fecal Lactobacillus spp. level displayed a positive correlation with Bifidobacterium spp. but was negatively correlated with Bacteroidetes. The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes. In conclusion, L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients, and the consumption of different strains of L. reuteri may influence changes in intestinal flora, which may lead to different outcomes after probiotic intake.

Fluid overload is a potential complication of hysteroscopic procedures with the possibility of dangerous electrolyte changes. This prospective randomized controlled trial aimed to compare perioperative outcomes and changes in electrolytes after hysteroscopic procedures between the manual infusion (MI) and the pump infusion (PI) methods for distending media infusion. One hundred consecutive women who had hysteroscopic procedures between December 2013 and February 2017 were recruited and randomly allocated to either the MI or PI group. The PI group was associated with an increased volume of infused fluid and collected fluid compared with the volumes of the MI group. Almost all serum electrolyte levels differed significantly between the baseline and postoperative values in both groups; however, no significant differences were noted between the groups. The change in potassium level was positively correlated with the volume of fluid deficit (Spearman’s rho = 0.24, P = 0.03), whereas the change in calcium level was negatively correlated with the volume of fluid deficit (Spearman’s rho = −0.26, P = 0.046). With no between-group differences in the changes in the other perioperative parameters and electrolytes, the MI method can be a good alternative for delivering distending media for hysteroscopic procedures.

Background: Lymphoceles could represent a detrimental complication after retroperitoneal lymph node dissection. Our aim was to elucidate predictors of lymphoceles. Methods: Between 2011 and 2017, medical records of consecutive women who underwent laparotomic retroperitoneal lymph node dissection for FIGO stage I or II gynecologic cancer were reviewed. Results: A total of 204 women, including those with lymphoceles (n = 31) and symptomatic lymphoceles (n = 7), were reviewed. According to multivariable analysis, parity (odds ratio = 0.59, p = 0.003), adjuvant pelvic radiotherapy (odds ratio = 2.60, p = 0.039), and peritoneal nonclosure without pelvic drainage (odds ratio = 2.31, p = 0.048) were predictors of lymphoceles. In addition, parity (odds ratio = 0.73, p = 0.03), hypertension (odds ratio = 2.62, p = 0.02), and peritoneal partial closure with pelvic drainage (odds ratio = 0.27, p = 0.02) were predictors of complications. Conclusion: Low parity, adjuvant pelvic radiotherapy, and peritoneal nonclosure without pelvic drainage were associated with increased lymphocele formation. In addition, a lower complication rate was found in the peritoneal partial closure with pelvic drainage group, thus, peritoneal partial closure with pelvic drainage might be suggested for women who undergo laparotomic retroperitoneal lymph node dissection.

Ethnopharmacological relevance Penthorum chinense Pursh is used for promoting diuresis and alleviating “heat”-associated disorders, which were considered to be related to diabetic in Traditional Chinese Medicine (TCM). Aims of this study Here, we aimed to evaluate the ability and underlying mechanism of the ethyl acetate fraction of Penthorum chinense Pursh stems (PSE) to inhibit vascular inflammation in high glucose (HG)-induced human umbilical vein endothelial cells (HUVEC cells). Materials and methods HUVEC cells were pre-treated with PSE following HG treatment. The cell viability, mitochondrial membrane potential (MMP), lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation were analyzed. Inflammatory, and antioxidant,-related proteins were analyzed using western blotting. Molecular docking and drug affinity targeting experiments (DARTS) were utilized to analyze and verify the binding of the Keap1 protein and polyphenols of PSE. Results HG can significantly increase the activity of lactic dehydrogenase (LDH), destroy the mitochondrial membrane potential (MMP), and promote the generation of reactive oxygen species (ROS), while PSE treatment reversed these changes. Mechanistically, PSE inhibited NF-κB and inflammatory cytokines activation induced by HG through activating the expression of Nrf2 and its downstream antioxidant proteins Heme oxygenase-1 (HO-1), NAD (P)H Quinone Dehydrogenase 1 (NQO1), Glutamate cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier (GCLM). Further study indicated that PSE activated Nrf2 antioxidant pathway mainly by the binding of primary polyphenols from PSE and the Keap1 protein. Conclusion Taken together, the present data highlight the health benefits of polyphenols from Penthorum chinense Pursh. regarding diabetes, proving it to be an important source of health care products. Besides, binding of the Keap1 protein may be an effective strategy to activate Nrf2 antioxidant pathway and prevent diabetes.

Four new diarylheptanoids, (1S, 3R, 5R, 6R)-1, 5-epoxy-3, 6 dihydroxy-1-(4-hydroxy-3, 5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl) heptane (1), (1R, 3R, 5S)-1, 5-epoxy-3-acetoxy-1-(4, 5-dihydroxy-3-methoxyphenyl)-7-(3, 4- hydroxyphenyl) heptane (2), (3R, 5S, 6R, 7S)-3, 6-epoxy-7-hydroxyl-1-(4-hydroxyphenyl)-7-(3-methoxy-4-hydroxyphenyl) heptane (3), (E)-3-keto-1-(3-methoxy-4-hydroxyphenyl)-7-(4, 5-dihydroxy-3-methoxyphenyl)-4- heptene (4), were isolated from Rhizoma Zingiberis, and their structures were determined based on HR-ESI-MS and extensive spectroscopic techniques (UV, IR, 1D-NMR and 2D-NMR). Compounds 1-4 exhibited no cytotoxicity against HepG2 cell lines.

ObjectiveTo compare the drowning mortality rates and proportion of deaths of each intent among all drowning deaths in Organisation for Economic Co-operation and Development (OECD) countries in 2012–2014.DesignA population-based cross-sectional study.Setting32 OECD countries.ParticipantsIndividuals in OECD countries who died from drowning.Main outcome measuresDrowning mortality rates (deaths per 100 000 population) and proportion (%) of deaths of each intent (ie, unintentional intent, intentional self-harm, assault, undetermined intent and all intents combined) among all drowning deaths.ResultsCountries with the highest drowning mortality rates (deaths per 100 000 population) were Estonia (3.53), Japan (3.49) and Greece (2.40) for unintentional intent; Ireland (0.96), Belgium (0.96) and Korea (0.89) for intentional self-harm; Austria (0.57), Korea (0.56) and Hungary (0.44) for undetermined intent and Japan (4.35), Estonia (3.70) and Korea (2.73) for all intents combined. Korea ranked 12th and 3rd for unintentional intent and all intents combined, respectively. By contrast, Belgium ranked 2nd and 15th for intentional self-harm and all intents combined, respectively. The proportion of deaths of each intent among all drowning deaths in each country varied greatly: from 26.2% in Belgium to 96.8% in Chile for unintentional intent; 0.7% in Mexico to 57.4% in Belgium for intentional self-harm; 0.0% in nine countries to 4.9% in Mexico for assault and 0.0% in Israel and Turkey to 38.3% in Austria for undetermined intent.ConclusionsA large variation in the practice of classifying undetermined intent in drowning deaths across countries was noted and this variation hinders valid international comparisons of intent-specific (unintentional and intentional self-harm) drowning mortality rates.

Nine new gingerols, including three 6-oxo-shogaol derivatives [(Z)-6-oxo-[6]-shogaol (1), (Z)-6-oxo-[8]-shogaol (2), (Z)-6-oxo-[10]-shogaol (3)], one 6-oxoparadol derivative [6-oxo-[6]-paradol (4)], one isoshogaol derivative [(E)-[4]-isoshogaol (5)], and four paradoldiene derivatives [(4E,6Z)-[4]-paradoldiene (8), (4E,6E)-[6]-paradoldiene (9), (4E,6E)-[8]-paradoldiene (10), (4E,6Z)-[8]-paradoldiene (11)], together with eight known analogues, were isolated from the rhizoma of Zingiber officinale. Their structures were elucidated on the basis of spectroscopic data. It was noted that the isolation of 6-oxo-shogaol derivatives represents the first report of gingerols containing one 1,4-enedione motif. Their structures were elucidated on the basis of spectroscopic and HRESIMS data. All the new compounds were evaluated for their cytotoxic activities against human cancer cells (MCF-7, HepG-2, KYSE-150).

Objectives: Limited sampling strategies (LSS) have been proposed as an alternative method for estimating area under concentration-time curve (AUC) of immunosuppressive agent tacrolimus (TAC). In this study, we aimed to develop the LSS models for predicting AUC of TAC in Chinese liver transplant patients. Methods: Twenty-eight adult liver transplant patients receiving immunosuppressive regimen including TAC were enrolled. A total of 47 pharmacokinetic profiles were obtained after 1 or 3 weeks therapy. TAC concentrations were determined before dose (0 h) and at 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 h after dosing by LC-MS/MS assay. Optimal subset regression analysis was used to establish the models for estimating TAC AUC0-12. Prediction error (PE) and absolute PE were calculated. The agreement between predicted and measured AUC0-12 was investigated by Bland-Altman analysis. The obtained models were validated by bootstrap analysis. The prediction performance among various CYP3A5 and ABCB1 genotypes was compared. The models selected from previous published studies were also validated using our data. Results: Twenty-eight models including 1, 2, 3 and 4 blood time points sampling were established (r2 = 0.653-0.979). The best model for prediction of TAC AUC0-12 was 0.81 + 1.73C1 + 1.32C2 + 3.87C4 + 3.75C8 (r2 = 0.979). Forty profiles (85.1%) had estimated TAC AUC0-12 within ±15% of observed TAC AUC0-12. Model with C0-C2 (r2 = 0.880) can be used for outpatients who need monitoring to be carried out in a short period. We also found that ABCB1 genotype may be a reason of variation in the prediction performance. There was good correlation between predicted and measured AUC0-12 (r2 = 0.880-0.928) by using models from previous studies with sample collected within 4 h post dose. Conclusion: The LSS is an effective approach for estimation of full TAC AUC0-12 in Chinese liver transplant patients.

Cardiovascular disease, like hypertension, is one of the top killers of human life and early detection of cardiovascular disease is of great importance. However, traditional medical devices are often bulky and expensive, and unsuitable for home healthcare. In this paper, we proposed an easy and inexpensive technique to estimate continuous blood pressure from the heart sound signals acquired by the microphone of a smartphone. A cold-pressor experiment was performed in 32 healthy subjects, with a smartphone to acquire heart sound signals and with a commercial device to measure continuous blood pressure. The Fourier spectrum of the second heart sound and the blood pressure were regressed using a support vector machine, and the accuracy of the regression was evaluated using 10-fold cross-validation. Statistical analysis showed that the mean correlation coefficients between the predicted values from the regression model and the measured values from the commercial device were 0.707, 0.712, and 0.748 for systolic, diastolic, and mean blood pressure, respectively, and that the mean errors were less than 5 mmHg, with standard deviations less than 8 mmHg. These results suggest that this technique is of potential use for cuffless and continuous blood pressure monitoring and it has promising application in home healthcare services.

Objective Acute transverse myelitis (ATM) is a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic dysfunction. In this study, we delineate the clinical manifestations, neuroimaging characteristics, and outcome-associated risk factors in children with idiopathic ATM. Methods We retrospectively reviewed the medical charts and neuroimages in nine children aged younger than 18 years diagnosed with ATM between January 2006 and August 2014. Results The mean onset age was 5 years and 9 months. Infectious prodromes were observed in six patients. Leg weakness was observed in all patients, autonomic sphincter dysfunction was observed in seven patients, and sensory deficits on admission were observed only in four patients. The diagnosis was delayed in patients younger than 5.5 years compared with older children. The adverse outcomes cannot be predicted by the course of the disease, the laboratory findings, nor the extent of magnetic resonance imaging–detected spinal lesions; however, these outcomes can be predicted by poor early response to corticosteroids and the requirement of additional treatments ( p Conclusion The diagnosis of ATM is challenging in young children. Children with ATM who responded early to corticosteroids had more favorable outcomes than those who required additional therapies.

Transfemoral device occlusion and minimally invasive surgical repair are performed for doubly committed subarterial ventricular septal defect (dcVSD) to reduce the invasiveness of the conventional surgical repair through a median sternotomy. However, few studies have compared them in terms of effectiveness and cost. Inpatients with isolated dcVSD who had undergone transfemoral device occlusion or minimally invasive surgical repair from January 2011 to June 2014 were reviewed for a comparative investigation between the two procedures. Procedure success was achieved in 36 transfemoral (75 %) and in 36 surgical (100 %) procedures (p = 0.001). Transfemoral patients were older, with a VSD size similar to that of surgical patients (14.5 ± 11.7 vs 4.4 ± 2.9 years, p

Transfemoral and perventricular device occlusions are performed for doubly committed subarterial ventricular septal defect (dcVSD) to reduce the invasiveness of the conventional surgical repair through a median sternotomy. Few comparative studies have been conducted of these three procedures.Inpatients with isolated dcVSD who had undergone transfemoral and perventricular device occlusions or conventional surgical repair from January 2009 to June 2013 were reviewed to compare the three procedures.Procedure success was achieved in 33 transfemoral (66%), in 74 perventricular (94.9%), and in 205 repair (97.6%) procedures. The transfemoral group had the lowest success rate (p0.001), whereas the perventricular and repair groups had similar success rates (p = 0.418). Transfemoral patients were the oldest (p0.001) and had a dcVSD size similar to that of patients in other two groups (p = 0.518). The repair group required the longest hospitalization and longest stays in the intensive care unit (p0.001), required the longest operating room and mechanical ventilation times (p0.001), and had the highest rate of transfusion (p0.001). Major adverse events occurred in one transfemoral (3%), in two perventricular (2.7%), and in three repair (1.4%) procedures. Minor adverse events were absent in transfemoral (0%) and occurred in three perventricular (4%) and 14 repair (6.7%) procedures. No significant difference was noted in the rates of adverse events the three groups (p = 0.569). No grade 3 valvular regurgitation or complete atrioventricular block was observed in the studied patients.Device occlusion may be an alternative to surgical repair in selected patients with dcVSD. Perventricular occlusion was the preferred approach because it showed a higher success rate than transfemoral occlusion.

Population, the most often used denominator in calculating drowning mortality rate, might not be a good measure of risk exposure. In this study, we sought to compare the rankings of township drowning mortality according to population-based rates with those according to aquatic area-based rates in Taitung County, Taiwan. The township with the highest mortality rate using population as the denominator (deaths per 100 000 persons) was Changbin (32.3) followed by Lanyu (22.4), Donghe (19.6) and Chenggong (18.0). On the other hand, the township with the leading mortality rate using aquatic area as the denominator (deaths per 100 000 km2) was Lanyu (353) followed by Lyudao (307), Chenggong (282) and Taitung City (219). Taitung City ranked 10th according to the population-based rate, but ranked 4th according to the aquatic area-based rate. In conclusion, rankings of regional drowning mortality rates using aquatic area as the denominator differ from those using population as the denominator.

Heart rate variability (HRV) is a useful clinical tool for autonomic function assessment and cardiovascular diseases diagnosis. It is traditionally calculated from a dedicated medical electrocardiograph (ECG). In this paper, we demonstrate that HRV can also be extracted from photoplethysmograms (PPG) obtained by the camera of a smartphone. Sixteen HRV parameters, including time-domain, frequency-domain, and nonlinear parameters, were calculated from PPG captured by a smartphone for 30 healthy subjects and were compared with those derived from ECG. The statistical results showed that 14 parameters (AVNN, SDNN, CV, RMSSD, SDSD, TP, VLF, LF, HF, LF/HF, nLF, nHF, SD1, and SD2) from PPG were highly correlated (r>0.7,P<0.001) with those from ECG, and 7 parameters (AVNN, TP, VLF, LF, HF, nLF, and nHF) from PPG were in good agreement with those from ECG within the acceptable limits. In addition, five different algorithms to detect the characteristic points of PPG wave were also investigated: peak point (PP), valley point (VP), maximum first derivative (M1D), maximum second derivative (M2D), and tangent intersection (TI). The results showed that M2D and TI algorithms had the best performance. These results suggest that the smartphone might be used for HRV measurement.

One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson’s test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future.

PURPOSE To investigate the meibomian gland (MG) performance in patients with glaucoma under topical intraocular pressure (IOP)-lowering medications. MATERIALS AND METHODS This was a cross-sectional case-control study. Patients with glaucoma under different dosages and instillation periods of topical IOP-lowering medications were included. A total of 30 eyes out of 30 healthy participants and 85 eyes out of 85 patients with glaucoma were analyzed. The burden of instilling antiglaucoma agents [burden of antiglaucoma (BAG)] was simply scored for each participant based on the number, formula, frequency, and duration of topical IOP-lowering medications used. All participants completed the MG and tear assessments, including Standard Patient Evaluation of Eye Dryness questionnaire, lipid layer thickness, MG secretion and dropout, Schirmer test, tear break-up time, and blinking patterns. RESULTS Patients with glaucoma had significantly lower Standard Patient Evaluation of Eye Dryness scores, thinner lipid layer thickness, worse mebium quality, and lower MG secretion compared with healthy participants. Among the patients with glaucoma, MG loss ratio (P=0.006) and meiboscale (P=0.017) were significantly correlated with the BAG score. Compared with the low BAG group (score

Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include Vascular Endothelial Growth Factor Receptors (VEGFRs), Fibroblast Growth Factor Receptors (FGFRs), Platelet-Derived Growth Factor Receptors (PDGFRs), Epidermal Growth Factor Receptors (EGFRs), Insulin-Like Growth Factor 1 Receptor (IGF-1R), Fmslike Tyrosine Kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include Checkpoint Kinases (Chks), Cyclin- Dependent Kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include Matrix Metalloproteinases (MMPs), LIM kinase (Limk), Nicotinamide Phosphoribosyltransferase (Nampt), and Histone Deacetylase (HDAC); (6) arylureas from the rational modification of natural products. This review focuses on the Structure-Activity Relationships (SARs) of these arylureas. The structural evolution and current status of some typical anti-cancer agents used in clinic and/or in clinical trials are emphasized.

The aim of the study is to compare the efficacy of an 8-week pelvic floor muscle training program with surface electromyography feedback, performed in different body positions (supine, sitting, and standing), in women with stress urinary incontinence.This is a prospective observational study performed January 2014 to May 2016.The training program was performed by 110 women with stress urinary incontinence, each completing 4 individual training sessions. The main outcome was the electromyography activity of the pelvic floor muscles and of the synergistic abdominal muscles. Outcome measures were evaluated at 4 time points, namely at baseline and at 2, 4, and 8 weeks of training.A notable effect of training was identified at week 2, which was sustained through to week 8. Training yielded a significant improvement in increased sustained voluntary contraction of the pelvic floor muscles in all 3 positions. The efficacy of training was influenced by the duration of training, age, body mass index, and history of vaginal delivery.Training of the pelvic floor muscles, with positive reinforcement by surface electromyography feedback of the pelvic floor muscles and of the synergistic abdominal muscles, was effective for the treatment of stress urinary incontinence in women and should be considered as a feasible option by healthcare providers.

To investigate the changes of TPO levels in patients with acute inflammatory response disease of different etiologies.In the case -control study, 65 patients with acute inflammatory response disease were enrolled in the case group (15 patients with acute myocardial infarction, 15 patients with acute cerebral infarction, 25 patients with acute trauma and 10 patients with acute pneumonia), and 42 healthy subjects were selected as the control group. The levels of TPO in peripheral blood and blood cell counts between the case group and the control group were compared by Student's t test for examing whether the level of TPO in acute inflammation states was higher than that in healthy people. And, by using Kruskal-Wallis H test and Nemenyi test, subsequent subgroup compaison was performed to assess whether there was a difference in TPO levels under the condition of inflammation of different etiologies and at different levels.Compared with the control group,serum TPO levels in case group were significantly higher (181.11±35.38 vs 96.13±9.7 pg/ml)(P0.001), and the white blood cell count in case group (9.64±3.43)×10In acute inflammation states, the increase of serum TPO levels does not correlate with platelet counts, but correlates with inflammation levels, and TPO may act as an acute response protein to protect the body.

Supplemental Digital Content is available in the text, Retinal arterial macroaneurysms (RAMs) develop as outpouchings of the arterial wall that is weakened by arteriosclerosis. The traditional treatment of RAMs comprises observation, focal laser photocoagulation, or surgery. Recently, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has been announced as an effective therapy for fovea-threatening RAMs and quickly improve visual acuity and central retinal thickness (CRT). In the retrospective series, medical charts and ocular images of 24 patients diagnosed as having RAM between May 2011 and November 2018 in our facility were reviewed to delineate clinical manifestations and visual prognosis in RAM patients receiving different treatment modalities. Twenty-four patients (25 eyes; 11 men and 13 women) were enrolled, and one eye with comorbidity of branch retinal vein occlusion was excluded. The mean age of the patients was 69.00 ± 13.45 years. Fourteen patients (58.33%) had a history of hypertension, and 17 patients (70.83%) were aged > 60 years. Furthermore, patients with fovea-threatening RAMs presented with either hypertension or were aged > 60 years. Eyes with fovea involvement (n = 18) were analyzed and separated into two groups according to their treatment modalities: those receiving anti-VEGF intravitreal injections (n = 13) and observation only (n = 5). The baseline visual acuity revealed no significant difference in the two groups. In patients receiving anti-VEGF intravitreal injections, a significantly better visual acuity was detected after anti-VEGF intravitreal injections than the baseline visual acuity (logMAR, 0.78 ± 0.51 vs 1.52 ± 0.48, P

After the nuclear disaster in Fukushima in Japan in 2011, a nation-wide survey using a standardized self-administered questionnaire was conducted in Taiwan, with a sample size of 2,742 individuals including the residents who live within and beyond 30 km from a nuclear power plant (NPP), to evaluate the participants’ perceived nuclear risk in comparison with their perceived risks from selected environmental hazards and human behaviors. The three leading concerns of nuclear energy were “nuclear accidents (82.2%),” “radioactive nuclear waste disposal (76.9%)” and “potential health effects (73.3%).” Respondents (77.6%) perceived a higher relative risk of cancer incidence for those who live within 30 km from an NPP than those who live outside 30 km from an NPP. All the participants had a higher risk perception of death related to “nuclear power operation and nuclear waste” than cigarette smoking, motorcycling, food poisoning, plasticizer poisoning and traveling by air. Moreover, the residents in Gongliao where the planned fourth NPP is located had a significantly higher perceived risk ratio (PRR) of cancer incidence (adjusted odd ratio (aOR) = 1.84, p value = 0.017) and perceived risk of death (aOR = 4.03, p value