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Background Cancer therapy has evolved from non-specific cytotoxic agents to a selective, mechanism-based approach that includes targeted agents and immunotherapy. Although the response to targeted therapies for unresectable hepatocellular carcinoma (HCC) is acceptable with the improved survival, the high tumor recurrence rate and drug-related side effects continue to be problematic. Given that immune checkpoint inhibitor alone are not robust enough to improve survival in unresectable HCC, growing evidence supports the combination of targeted therapy and immunotherapy with synergistic effect. Methods Online databases including PubMed, EMBASE, Cochrane Library, and Web of Science were searched for the studies that compared targeted monotherapy with the combination therapy of targeted drug and checkpoint inhibitors in unresectable HCC patients. Eligibility criteria were the presence of at least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (version 1.1) for unresectable HCC patients, an Eastern Cooperative Oncology Group performance status of 0–2, and a Child–Pugh score ≤ 7. Outcome measurements include overall survival (OS), progression-free survival (PFS), and treatment-related adverse event (TRAE). Results Three phase II/III randomized controlled trials were included in this study. The pooled results showed that combination therapy significantly improved survival than targeted monotherapy, in terms of OS (hazard ratio (HR) = 0.67; 95% confidence interval [CI]: 0.50–0.91) and PFS (HR = 0.58; 95% CI: 0.51–0.67), respectively. In the incidence of grade 3–5 TRAEs, the combination therapy was significantly higher than targeted monotherapy (odds ratio = 1.98; 95% CI: 1.13–3.48). Conclusion For unresectable HCC, combined targeted drug and immunotherapy significantly improved survival compared with targeted monotherapy. However, the incidences of AEs of combinational therapy were higher than targeted monotherapy.

Lung adenocarcinoma (LUAD) is the most common histologic type of lung cancer. Mutations of the

In Taiwan, the outcomes of acute limb ischemia have yet to be investigated in a standardized manner. In this study, we compared the safety, feasibility and outcomes of acute limb ischemia after surgical embolectomy or catheter-directed therapy in Taiwan. This study used data collected from the Taiwan’s National Health Insurance Database (NHID) and Cause of Death Data between the years 2000 and 2015. The rate ratio of all-cause in-hospital mortality and risk of amputation during the same period of hospital stay were estimated using Generalized linear models (GLM). There was no significant difference in mortality risk between CDT and surgical intervention (9.5% vs. 10.68%, adjusted rate ratio (95% CI): regression 1.0 [0.79–1.27], PS matching 0.92 [0.69–1.23]). The risk of amputation was also comparable between the two groups. (13.59% vs. 14.81%, adjusted rate ratio (95% CI): regression 0.84 [0.68–1.02], PS matching 0.92 [0.72–1.17]). Age (p p = 0.01) were associated with higher mortality risks. Heart failure (p = 0.03) and chronic or end-stage renal disease (p = 0.03) were associated with higher amputation risks. Prior antithrombotic agent use (p = 0.03) was associated with a reduced risk of amputation. Both surgical intervention and CDT are effective and feasible procedures for patients with ALI in Taiwan.

Background Sleeve gastrectomy (SG) is the most common surgery for severe obesity. Patients lose weight post SG and regain some weight in the following years. Early weight loss predicts weight loss after SG. However, etiologies of weight loss and regain after SG remain unclear. Objectives To investigate the effects of early weight loss on medium-term weight regain post SG. Setting Two university hospitals in Taiwan. Methods Patients with records within 1 and at 3 years after SG were enrolled retrospectively. Preoperative clinical variables and percentage of total weight loss (%TWL) were analyzed. Weight regain was defined as a weight increase from 1 year postoperatively of >25% of the lost weight. Linear and multiple logistic regression were applied to examine the associations of early weight loss, weight loss, and weight regain. Results A total of 363 patients were included. Body mass indexes before and 1, 3, 6, 12, and 36 months postoperatively were 40.7 ± 6.8 kg/m2, 36.6 ± 6.2 kg/m2, 33.5 ± 5.8 kg/m2, 30.9 ± 5.5 kg/m2, 28.4 ± 5.2, and 29.3 ± 5.4 kg/m2, respectively. At 3 years after SG, 73 patients (20.1%) had weight regain. In multivariate linear analyses, initial age, waist circumference, type 2 diabetes, and %TWL at 1 or 3 months were associated with either 1-year or 3-year %TWL. Multiple logistic regression revealed %TWL at 3 months to be a predictor for 3-year weight regain after SG (odds ratio, .927; P = .02). Conclusion Early weight loss predicted weight loss and regain 3 years after SG. Early lifestyle and behavioral interventions are suggested in patients at high risk of poor weight loss and weight regain outcomes after SG.

Background Morbidly obese patients often suffer from gastroesophageal reflux disease (GERD). High-resolution impedance manometry (HRIM) allows a comprehensive evaluation of esophageal motility and esophagogastric junction (EGJ) morphology and helps to clarify GERD pathophysiology. Objective To evaluate the esophageal function and EGJ anatomy in morbid obesity by HRIM. Setting University Hospital, Taiwan. Methods We consecutively enrolled 57 morbidly obese patients planning to undergo bariatric surgery and 58 healthy volunteers in this prospective study. All patients responded to validated symptom questionnaires and underwent fasting blood tests, HRIM, and esophagogastroduodenoscopy. We compared anthropometric and HRIM parameters between the 2 groups, and analyzed correlations between the GERD symptom scores and clinical variables in the obese patients. Results The obese patients, comprising 30 males (53%), had a median age of 35 years and body mass index of 40.5 kg/m2. The 4-second integrated relaxation pressure in the lower esophageal sphincter was significantly higher in the patients than the volunteers (median: 10.8 versus 5.6 mm Hg; P Conclusions The obese patients had a higher lower esophageal sphincter 4-second integrated relaxation pressure and higher prevalence of EGJ outflow obstruction and m-HH than the healthy volunteers. The presence of m-HH was strongly associated with erosive esophagitis. The absence of GERD symptoms in morbid obesity was not necessarily suggestive of negative esophagogastroduodenoscopy and HRIM findings, and the discrepancy existed between esophagogastroduodenoscopy and HRIM for diagnosing HH. A comprehensive evaluation of the EGJ anatomy and esophageal function may be considered before bariatric surgery.

Single crystal metal-free halide perovskites have received great attention in recent years owing to their excellent piezoelectric and ferroelectric properties. However, the nanotoxicity and piezoelectricity within the nanoscale of such materials have yet been reported for the demonstration of practical applications. In this work, the observation of intrinsic piezoelectricity in metal-free perovskite (MDABCO-NH

Irreversible electroporation (IRE) is a modality that utilizes high electric voltage to cause cell apoptosis. IRE has been used to treat locally advanced pancreatic cancer (LAPC). However, studies of IRE via surgical approaches for LAPC are limited. This study aims to analyse the outcomes and related prognostic factors of IRE for Asian patients with LAPC.From 2012 to 2017, this prospective trial for using IRE through surgical approaches for LAPC was conducted in 11 medical centres in Asia. All related and treatment outcomes were analysed from a prospective database.Seventy-four patients were enrolled. Thirty complications occurred in thirteen (17.6%) patients without mortality. The electrode placement direction (anteroposterior vs. craniocaudal, HR = 14.2, p 0.01) and gastrointestinal invasion (HR = 15.7, p 0.01) were significant factors for complications. The progression-free survival (PFS) rate in one year, three years, and five years were 69.1%, 48.7%, and 28.8%, and the overall survival (OS) rate in one year, three years, and five years were 97.2%, 53%, and 31.2%. In univariate analysis, the chemotherapy regimen, local tumour recurrence, axial tumour length, tumour volume, and serum carbohydrate antigen 19-9 levels were all significantly associated with PFS and OS. In multivariate analysis, the chemotherapy regimen was the only significant factor associated with PFS and OS. TS-1 (Tegafur, gimeracil, and oteracil) group has superior survival outcome than gemcitabine group.This study showed that combined induction chemotherapy and surgical IRE for LAPC is safe. For well-selected patients, IRE can achieve encouraging survival outcomes.

Breast cancer is the most common cancer and the leading cause of cancer-related deaths in women. The estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the important biomarkers in the prognosis of breast cancer, and their expression is used to categorize breast cancer into subtypes. We aimed to analyze the concordance among ER, PR, and HER2 expression levels and breast cancer subtyping results obtained by immunohistochemistry (IHC, for protein) and reverse transcriptase-polymerase chain reaction (RT-PCR, for mRNA) and to assess the recurrence-free survival (RFS) of the different subtypes as determined by the two methods. We compared biomarker expression by IHC and RT-PCR in 397 operable breast cancer patients and categorized all patients into luminal, HER2, and triple-negative (TN) subtypes. The concordance of biomarker expression between the two methods was 81.6% (κ = 0.4075) for ER, 87.2% (κ = 0.5647) for PR, and 79.1% (κ = 0.2767) for HER2. The κ-statistic was 0.3624 for the resulting luminal, HER2, and TN subtypes. The probability of 5-year RFS was 0.78 for the luminal subtype versus 0.77 for HER2 and 0.51 for TN, when determined by IHC (P=0.007); and 0.80, 0.71, and 0.61, respectively, when determined by the RT-PCR method (P=0.008). Based on the current evidence, subtyping by RT-PCR performs similar to conventional IHC with regard to the 5-year prognosis. The PCR method may thus provide a complementary means of subtyping when IHC results are ambiguous.

Background To evaluate the correction differences between vertebra and tumor matching as cone‐beam computed tomography (CBCT)‐guided setup strategies in lung stereotactic body radiation therapy (SBRT), and the correlations with tumor characteristics such as size, mobility, and location. Methods The manual registrations for 33 lung tumors treated with SBRT were retrospectively performed by matching thoracic vertebrae for vertebra matching and then by matching CBCT‐visualized tumors within the internal target volume obtained from a four‐dimensional CT dataset for tumor matching. Results The mean correction difference between the two matching methods during the SBRT fractions was larger in the anterior‐posterior direction (2.7 mm) than in the superior‐inferior (2.1 mm) and left‐right (1.4 mm) directions, with differences of less than 5 mm in 90% of the total 134 CBCT fractions. The X‐axis and direct distances from the central axis to the tumor had significant correlations with the correction differences in all three directions, while the mobility‐related parameters were correlated only in the superior‐inferior direction. The absolute differences in lung‐dose parameters after applying the margins (3.4–6.5 mm) required for the setup errors from vertebra matching relative to tumor matching were mild, with values of 1.95 Gy for the mean lung dose and 3.9% for V20. Conclusion The setup differences between vertebra and tumor matching in the CBCT‐guided setup without rotation correction were increased in tumors located long distances from the central axis. The additional safety margins of 3.4–6.5 mm were required for the setup errors from vertebra matching. Key points Significant findings of the study The correction difference between the vertebra and tumor matching as CBCT‐guided setup strategies was the largest in the anterior‐posterior direction and significantly correlated with the X‐axis and direct distances from the central axis to the tumor. What this study adds Setup differences between vertebra and tumor matching in the CBCT‐guided setup were increased in tumors located long distances from the central axis. The additional safety margins of 3.4–6.5 mm were required for the setup errors from vertebra matching.

Background Heart sound measurement is crucial for analyzing and diagnosing patients with heart diseases. This study employed phonocardiogram signals as the input signal for heart disease analysis due to the accessibility of the respective method. This study referenced preprocessing techniques proposed by other researchers for the conversion of phonocardiogram signals into characteristic images composed using frequency subband. Image recognition was then conducted through the use of convolutional neural networks (CNNs), in order to classify the predicted of phonocardiogram signals as normal or abnormal. However, CNN requires the tuning of multiple hyperparameters, which entails an optimization problem for the hyperparameters in the model. To maximize CNN robustness, the uniform experiment design method and a science-based methodical experiment design were used to optimize CNN hyperparameters in this study. Results An artificial intelligence prediction model was constructed using CNN, and the uniform experiment design method was proposed to acquire hyperparameters for optimal CNN robustness. The results indicate Filters ($${X}_{1}$$ X 1 ), Stride ($${X}_{3}$$ X 3 ), Activation functions ($${X}_{6}$$ X 6 ), and Dropout ($${X}_{7}$$ X 7 ) to be significant factors considerably influencing the ability of CNN to distinguish among heart sound states. Finally, the confirmation experiment was conducted, and the hyperparameter combination for optimal model robustness was Filters ($${X}_{1}$$ X 1 ) = 32, Kernel Size ($${X}_{2})$$ X 2 ) = 3 × 3, Stride ($${X}_{3}$$ X 3 ) = (1,1), Padding ($${X}_{4})$$ X 4 ) as same, Optimizer ($${X}_{5})$$ X 5 ) as the stochastic gradient descent, Activation functions ($${X}_{6}$$ X 6 ) as relu, and Dropout ($${X}_{7}$$ X 7 ) = 0.544. With this combination of parameters, the model had an average prediction accuracy rate of 0.787 and standard deviation of 0. Conclusion In this study, phonocardiogram signals were used for the early prediction of heart diseases. The science-based and methodical uniform experiment design was used for the optimization of CNN hyperparameters to construct a CNN with optimal robustness. The results revealed that the constructed model exhibited robustness and an acceptable accuracy rate. Other literature has failed to address hyperparameter optimization problems in CNN; a method is subsequently proposed for robust CNN optimization, thereby solving this problem.

Background The prevalence of chronic disease is growing in aging societies, and artificial-intelligence–assisted interpretation of macular degeneration images is a topic that merits research. This study proposes a residual neural network (ResNet) model constructed using uniform design. The ResNet model is an artificial intelligence model that classifies macular degeneration images and can assist medical professionals in related tests and classification tasks, enhance confidence in making diagnoses, and reassure patients. However, the various hyperparameters in a ResNet lead to the problem of hyperparameter optimization in the model. This study employed uniform design—a systematic, scientific experimental design—to optimize the hyperparameters of the ResNet and establish a ResNet with optimal robustness. Results An open dataset of macular degeneration images (https://data.mendeley.com/datasets/rscbjbr9sj/3) was divided into training, validation, and test datasets. According to accuracy, false negative rate, and signal-to-noise ratio, this study used uniform design to determine the optimal combination of ResNet hyperparameters. The ResNet model was tested and the results compared with results obtained in a previous study using the same dataset. The ResNet model achieved higher optimal accuracy (0.9907), higher mean accuracy (0.9848), and a lower mean false negative rate (0.015) than did the model previously reported. The optimal ResNet hyperparameter combination identified using the uniform design method exhibited excellent performance. Conclusion The high stability of the ResNet model established using uniform design is attributable to the study’s strict focus on achieving both high accuracy and low standard deviation. This study optimized the hyperparameters of the ResNet model by using uniform design because the design features uniform distribution of experimental points and facilitates effective determination of the representative parameter combination, reducing the time required for parameter design and fulfilling the requirements of a systematic parameter design process.

The outbreak of the novel coronavirus, COVID-19, has become one of the most severe pandemics in human history. In this paper, we propose to leverage social media users as social sensors to simultaneously predict the pandemic trends and suggest potential risk factors for public health experts to understand spread situations and recommend proper interventions. More precisely, we develop novel deep learning models to recognize important entities and their relations over time, thereby establishing dynamic heterogeneous graphs to describe the observations of social media users. A dynamic graph neural network model can then forecast the trends (e.g. newly diagnosed cases and death rates) and identify high-risk events from social media. Based on the proposed computational method, we also develop a web-based system for domain experts without any computer science background to easily interact with. We conduct extensive experiments on large-scale datasets of COVID-19 related tweets provided by Twitter, which show that our method can precisely predict the new cases and death rates. We also demonstrate the robustness of our web-based pandemic surveillance system and its ability to retrieve essential knowledge and derive accurate predictions across a variety of circumstances. Our system is also available athttp://scaiweb.cs.ucla.edu/covidsurveiller/.This article is part of the theme issue ‘Data science approachs to infectious disease surveillance’.

This study aims to compare the efficacy, tolerability and patient satisfaction between aqueous subcutaneous progesterone (Prolutex, 25 mg/vial; IBSA) and vaginal progesterone (Crinone, 90 mg/tube; Merck) as luteal support for fresh embryo transfers in in-vitro fertilization (IVF).In this prospective randomized study, 65 patients who underwent IVF were recruited and randomly assigned to either the Prolutex (25 mg daily, n = 33) or Crinone (90 mg daily, n = 32) group. The luteal support regimens were given daily, starting from two days after oocyte pickup. If the serum pregnancy test was positive, luteal support was continued until 7 weeks of gestation. Primary outcomes were clinical pregnancy rate and serum progesterone level at the mid-luteal phase and at 4 weeks of gestation. Secondary outcomes were drug tolerability and patient satisfaction assessed by questionnaire.There were no significant differences in clinical pregnancy rates (Prolutex 25.0% versus Crinone 33.3%, p = 0.699), serum progesterone levels and patient satisfaction between Prolutex and Crinone group. Although the patients that had received Prolutex complained of more local pain at the injection sites, they also had less annoying vaginal discharges and vulvar discomforts.Prolutex is of comparable efficacy and patient satisfaction to Crinone, and its availability means patients have more options in regards to the routes of progesterone administration as luteal phase support during IVF.

Background/Purpose Various microRNAs (miRs) have been found to be associated with the development of the precancerous condition of the oral cavity, oral submucous fibrosis (OSF). The expression of miR-29c is dysregulated in oral cancer, but its role in OSF has not been investigated. The purpose of the study is to investigate the functional role of miR-29c and its target in OSF. Methods The expression levels of miR-29c in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were assessed using next-generation sequencing and real-time Polymerase Chain Reaction (PCR) analysis. MiR-29c mimic and inhibitors were employed to examine its functional role of myofibroblast transdifferentiation. In addition, several myofibroblast phenotypes, such as collagen gel contraction and migration were tested, and a luciferase reporter assay was conducted to confirm the relationship between miR-29c and its predicted target, tropomyosin-1 (TPM1). Results We observed that miR-29c expression was downregulated in fBMFs. fBMFs transfected with miR-29c mimics exhibited reduced migration ability and collagen gel contractility, whereas inhibition of miR-29c in normal BMFs induced the myofibroblast phenotypes. Results from the luciferase reporter assay showed that TPM1 was a direct target of miR-29c and the expression of TPM1 was suppressed in the fBMFs transfected with miR-29c mimics. Besides, we confirmed that the expression of miR-29c was indeed downregulated in OSF specimens. Conclusion MiR-29c seems to exert an inhibitory effect on myofibroblast activation, such as collagen gel contractility and migration ability, via suppressing TPM1. These results suggested that approaches to upregulate miR-29c may be able to ameliorate the progression of OSF.

Background Limited studies have focused on diabetes relapse after metabolic surgery, especially among Asians. Objectives To identify the predictors of diabetes relapse following initial postoperative remission in Asia. Setting Four tertiary hospitals Methods We assessed 342 patients (age, 41.0±10.8 years; body mass index (BMI), 39.6±7.3 kg/m2) with complete diabetes data before and 1 and 3 years after metabolic surgery. A total of 290 (84.8%) and 277 (81.0%) patients had diabetes remission at 1 and 3 years after surgery. Logistic regressions were performed to identify the independent predictors of diabetes relapse. Two published predictive models for diabetes remission were also tested for relapse. Results Of the 290 patients with 1-year diabetes remission, 29 (10%) experienced a relapse at 3 years after surgery. The area under the receiver operating characteristic curve of the ABCD score in predicting 1-year remission, 3-year remission, and 3-year relapse were 0.814, 0.793, and 0.795, while those of the DiaRem2 score were 0.823, 0.774, and 0.701, respectively. The baseline age, BMI, and insulin use were independent predictors for relapse. The most powerful predictive model for relapse was composed of preoperative insulin use, 1-year A1c, and a change in BMI between the first and third year (C-statistic: 0.919). Conclusions The ABCD score predicted both mid-term postoperative diabetes remission and relapse in Asians. Initial older age, lower BMI, insulin use, higher 1-year A1c, and weight regain were independent predictors of relapse. Personalized strategies should be proposed for those at risk of relapse to optimize diabetes outcomes after surgery.

To assess the relationship between gene expressions of the magnesium transporters and glucose parameters in pregnant women.A cohort of women without ongoing or prior medical illnesses was recruited at the start of an early singleton pregnancy. Expression levels of the magnesium transporters-SLC41A1, CNNM2, MAGT1, TRPM6, and TRPM7-were assessed in the peripheral leukocytes, while total calcium and magnesium were assessed in the serum between 10 and 13 weeks gestation. Glucose parameters were assessed between 24 and 28 weeks gestation using the 75 g oral glucose tolerance test.A total of 208 patients were included in the study. The expressions of the magnesium transports were generally unrelated to age, body mass index (BMI), or serum levels of calcium and magnesium. The magnesium transporters were correlated with each other at baseline (correlation coefficients: 0.31 to 0.51). BMI was a strong predictor of fasting glucose levels, while both BMI and age were strong predictors of post-load glucose levels. The expression of TRPM7 was found to be predictive of 1-h post-load blood glucose after accounting for the effects of age and BMI (β = -0.196, p = 0.020).The increased maternal expression of the magnesium transporter TRPM7 may be associated with decreased glucose tolerance in pregnant women. In particular, the association between TRPM7 and 1-h post-load glucose levels was found to be independent of the effects of age and BMI. Future studies are needed to determine whether a mechanistic relationship can be demonstrated between TRPM7 and glucose metabolism.

Background The information of Oncotype DX applied in Asian breast cancer patients is limited. A recurrence index for distant recurrence (RI-DR) has been developed for early-stage breast cancer (EBC) from tumor samples in Chinese patients. In this study, we compared the prognostic performance of the Oncotype DX (ODx) recurrence score (RS) with the RI-DR for any recurrence risk type. Materials and methods One hundred thirty-eight (138) patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative EBC who were previously tested with ODx were included for testing with the RI-DR. The cutoff score to partition the low- and high-risk patients was 26 for RS and 36 for RI-DR. The primary endpoint was recurrence-free survival (RFS). Results The concordance between the RI-DR and RS was 83% in N0 patients and 81% in node-positive patients when the RS score cutoff was set at 26. With a median follow-up interval of 36.8 months, the 4-year RFS for the high- and low-risk groups categorized by the RS were 61.9% and 95.0%, respectively (hazard ratio: 10.6, 95.0% confidence interval [CI]: 1.8–62.9). The 4-year RFS in the high- and low-risk groups categorized by the RI-DR were 72.6% and 98.5%, respectively (hazard ratio: 18.9, 95% CI: 1.8–138.8). Conclusion This paper illustrated the performance of RI-DR and ODx RS in breast cancer women in Taiwan. There was high concordance between the RI-DR and RS. The RI-DR is not inferior to the RS in predicting RFS in EBC patients. This study will fill the gap between the current and best practice in Chinese patients., Utilization of Oncotype DX is uncommon in Asia due to lack of clinical data. We compare a clinical-genomic model, developed from Taiwan, to Oncotype 21-gene panel in Chinese patients.

Background/purpose: Oral submucous fibrosis (OSF) is a precancerous condition of oral cancer with a complex etiology. Our previous work has demonstrated that non-coding RNA miR-1246 contributes to the cancer stemness of oral cancer. In the current study, we sought to investigate the effect of the inhibition of miR-1246 on the oral fibrogenesis. Methods: The expression levels of miR-1246 in OSF tissues and fibrotic buccal mucosal fibroblasts (fBMFs) were examined by qRT-PCR. Collagen gel contraction and migration assays were conducted to evaluate the myofibroblast activities. The relationship between miR-1246 and type I collagen was assessed and the protein expression of type I collagen was determined by Western blot. Results: MiR-1246 expression was upregulated in both OSF specimen and fBMFs compared to the normal counterparts. Inhibition of miR-1246 successfully suppressed the myofibroblast activities, including collagen gel contractility and migration capacity. Moreover, the expression of miR-1246 was positively correlated with type I collagen and the expression of type I collagen was abrogated by repression of miR-1246. Conclusion: MiR-1246 is not only critical to the maintenance of oral stemness but also important to the activation of myofibroblasts. Our results showed that miR-1246 is positively associated with the type I collagen, which may be a downstream effector of miR-1246 and responsible for the fibrosis effect on fBMFs. Keywords: Oral submucous fibrosis, MicroRNA-1246, Type I collagen, Buccal mucosal fibroblasts

Bloodstream infections (BSI) are an important source of postoperative mortality in hepatobiliary–pancreatic surgery (HBPS) patients, and no prediction model has been analyzed before. Using big data from the electronic medical records of the administrative and culture databases of MacKay Memorial Hospital, we identified the potential risk factors for community-acquired and healthcare-associated BSI and mortality of patients who received HBPS. Subsequently, we analyzed the microorganisms’ profiles and antimicrobial susceptibility patterns for these BSI. BSI were found in 6.3% patients (349 of 5513 HBPS patients), and hospital mortality was 1.48% (82 of 5513). Dividing patients into low-, intermediate-, and high-risk groups on the basis of sex, age, status of comorbidity (renal failure, peptic ulcer disease, fluid and electrolyte disorders, and acute cholecystitis), a predictive BSI risk score model was developed. According to this model, BSI risk ranged from 1.43% to 11.95%; AUROC to predict BSI risk was 0.72 (95% CI 0.69–0.75). From this retrospective study, Enterobacteriaceae were the most common microorganisms that were isolated from BSI. For both community-acquired and healthcare-associated BSI, imipenem and colistin are the most successful. This novel model can be useful to predict who is at risk of BSI after HBPS, and new prophylactic protocols for these patients are needed.

Background: Detection of intrauterine lesions is important for infertile women, as the uterine cavity is the site for embryo growth. This study aims to investigate factors that increase the detection rate of intrauterine lesions on office hysteroscopy in infertile women with sonographically normal uterine cavities. Methods: We retrospectively enrolled 1726 infertile women who had normal uterine cavities on two-dimensional transvaginal sonography. Office hysteroscopy was performed in the early proliferative phase of the menstrual cycle. Results: Intrauterine lesions were detected in 260 (15.1%) of the 1726 women. In women who suffered from abnormal uterine bleeding (AUB), hypomenorrhea or had a history of dilation and curettage (D&C), the detection rates of intrauterine lesions on office hysteroscopy were 41.4%, 22.2% and 19.4%, respectively. The predictive rate of abnormal hysteroscopic finding was 22.4% in women with at least one of these three clinical features, while it was 9.6% in those without. Conclusion: AUB, hypomenorrhea, and previous D&C are the three factors that increase the detection rate of intrauterine lesions on office hysteroscopy in infertile women with sonographically normal uterine cavities. Keywords: Hysteroscopy, Infertility, Intrauterine lesion, Sonography

The progression of metabolic dysfunction associated fatty liver disease (MAFLD) leads to steatohepatitis, liver fibrosis and hepatocellular carcinoma. Thus far, there have been no FDA-approved medications for MAFLD. Bariatric surgery (BS) has been found to improve insulin resistance, steatohepatitis and liver fibrosis but is not recommended for treating MAFLD due to its invasiveness. Recent studies suggest the improved glucose metabolism after BS is a result of, at least partly, alterations to the gut microbiota and its associated metabolites, including short chain fatty acids and bile acids. It makes sense the improved steatohepatitis and fibrosis after BS are also induced by the gut microbiota that involves in host metabolic modulation, for example, through altering bile acids composition. Given that the gut–liver axis is a path that may harbor unexplored mechanisms behind MAFLD, we review current literatures about disentangling the metabolic benefits of MAFLD after BS, with a focus on gut microbiota. Some useful research tools including the rodent BS model, the multiomics approach, and the human microbiota associated (HMA) mice are presented and discussed. We believe, by taking advantage of these modern translational tools, researchers will uncover microbiota related pathways to serve as potential therapeutic targets for treating MAFLD.

There have been reports of improved pregnancy rates after performing intentional endometrial injuries, also known as endometrial scratching, in patients with recurrent implantation failure. In our previous study on intentional endometrial injury, we found an increased expression of matrix metalloproteinase (MMP)-3 following induced injuries to the mice endometrium. In the current study, we further examine whether the rise in MMP-3 could contribute to increased angiogenesis. Female C57B1/6 mice were obtained at 12 weeks of age, and intentional endometrial injuries were induced mechanically in the left uterine horns. Using the appropriate media, uterine-washes were performed on the injured and uninjured (control) horns of the harvested uteri. The uterine tissues were further processed for tissue lysates, histopathology and immunohistochemistry. The results show that intentional endometrial injuries caused an increase in secreted LPA in the injured horns, which were detected in the uterine-washes. In addition, LPA induced increased production of TNF-α in human endometrial epithelial cells (hEEpCs). Furthermore, TNF-α appeared to induce differential and cell-specific upregulation of the MMPs: MMP-3 was upregulated in the epithelial (hEEpCs), while MMP-9 was upregulated in the endothelial cells (human endometrial endothelial cells; hEEnCs). The upregulation of MMP-3 appeared to be necessary for the activation of MMP-9, whose active form stimulated the formation of vessel-like structure by the hEEnCs. The results of this study suggest that there may be enhanced angiogenesis following intentional endometrial injuries, which is mediated in part by TNF-α-induced and MMP-3-activated MMP-9 production.

Lung adenocarcinoma (LADC) is the most common subtype of lung cancer worldwide and the epidermal growth factor receptor (EGFR) has a great influence on its clinical course, mainly due to the influence of different phenotypes. The Aurora kinase A (AURKA) would influence the progression of several solid malignancies. However, whether the interaction between EGFR phenotypes and AURKA would influence the clinical characteristics of LADC remains unknown. Herein, this study aimed to explore the effects of single-nucleotide polymorphisms (SNPs) of AURKA and EGFR phenotypes on the clinicopathological characteristics of LADC. Four loci of AURKA SNPs (rs1047972, rs2273535, rs6024836, and rs2064863) were genotyped using TaqMan allelic discrimination in 105 wild-type EGFR individuals and 167 LADC patients with EGFR mutations. After the statistical analysis, patients with LADC who had CT heterozygotes of AURKA rs1047972 had a lower risk of EGFR mutations than patients with wild-type homozygotes. Moreover, female and nonsmoking patients who carried the CT genotype of AURKA rs1047972 had a lower risk of EGFR mutation (p = 0.008 and p = 0.004, respectively). Moreover, in patients with EGFR mutations, AURKA SNP rs6024836 G allele (AG + GG) carriers had a lower risk of developing advanced-stage LADC (stage III or IV, odds ratio = 0.423, 95% confidence interval: 0.203&ndash, 0.879, p = 0.019) than patients with AA homozygotes. Our results suggested that AURKA rs1047972 variants are significantly associated with EGFR mutations among patients with LADC, particularly in female and nonsmoking patients. AURKA variants may contribute to the pathological development of LADC.

Prostate cancer is one of the major cancers of the genitourinary tract. High-mobility group box 1 (HMGB1) was suggested as a promising therapeutic target for prostate cancer. In this study, we aim to elucidate the associations of HMGB1 single nucleotide polymorphisms (SNPs) with prostate cancer susceptibility and clinicopathological characteristics. The HMGB1 SNPs rs1412125, rs2249825, rs1045411, and rs1360485 in 579 prostate cancer patients and 579 cancer-free controls were analyzed with real-time polymerase chain reactions (real-time PCR). All of the data were evaluated with SAS statistical software. Our results showed that the HMGB1 rs1045411 T allele genotype was significantly associated with advanced pathologic T stage (odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.021–2.012; p = 0.037) and pathologic N1 stage (OR = 2.091, 95% CI = 1.160–3.767; p = 0.012), and the rs1360485 polymorphic CT + TT genotype was associated with pathologic Gleason grade group (4 + 5) (OR = 1.583, 95% CI = 1.017–2.462; p = 0.041), pathologic T stage (3 + 4) (OR = 1.482, 95% CI = 1.061–2.070; p = 0.021), and pathologic N1 stage (OR = 2.131, 95% CI = 1.178–3.852; p = 0.011) compared with their wild-type carriers. In conclusion, our results revealed that the HMGB1 SNPs were associated with the clinical status of prostate cancer. The HMGB1 SNPs may have the potential to predict prostate cancer disease progression.

Fibroblast growth factor receptor 4 (FGFR4) is involved in multiple physiological and pathological processes. Several genetic variants of FGFR4 have been shown to be associated with tumor progression in many cancers. However, its association, such as genetic variants and expression levels, with lung cancer is controversial. The present study examined the relationship between four single-nucleotide polymorphisms (SNPs, rs2011077 T/C, rs351855 G/A, rs7708357 G/A, and rs1966265 A/G) of FGFR4 and the risk of lung adenocarcinoma with the epidermal growth factor receptor (EGFR) mutation status in a Taiwanese cohort. The results demonstrated that FGFR4 rs2011077 (odds ratio (OR) = 0.348, 95% confidence interval (CI) = 0.136&ndash, 0.891, p = 0.024), and rs351855 (OR = 0.296, 95% CI = 0.116&ndash, 0.751, p = 0.008) showed an inverse association with distant metastasis in wild-type EGFR lung adenocarcinoma. Furthermore, a database analysis using The Cancer Genome Atlas revealed that the higher FGFR4 expression level was correlated with poor survival rates in wild-type EGFR lung adenocarcinoma. In conclusion, the data suggest that FGFR4 SNPs may help in identifying patient subgroups at low-risk for tumor metastasis, among carriers of lung adenocarcinoma bearing wild-type EGFR.

Background Patients with polycystic ovarian syndrome (PCOS) are associated with known alterations in mitochondria DNA copy number (mtDNA-CN). The aim of this study is to study the change in mtDNA-CN in patients with PCOS who were treated with metformin. Methods This is a prospective cohort of patients with PCOS, who received metformin for one year. From 2009 to 2015, 88 women diagnosed with PCOS, based on the Rotterdam criteria, were enrolled. Serial measurements of mtDNA-CN, 8-hydroxydeoxyguanosine (8-OHdG), anthropometric, metabolic, endocrine, and inflammatory markers were obtained before and after 3, 6, and 12 months of treatment. Results A significant decrease in mtDNA-CN was seen over the course of one year. Other markers, including 8-OHdG, testosterone, free androgen index, blood pressure and liver enzymes, also decreased in the same interval. On regression analysis, there was a significant association between the change in mtDNA-CN and serum total testosterone, and no association between mtDNA-CN and metabolic factors. Conclusions Treatment with metformin is associated with a time-dependent decrease in mtDNA-CN in patients with PCOS who are treated over the course of one year. This may signify a reduction in mitochondria dysfunction. The change in mtDNA-CN corresponds to a similar change in serum total testosterone, and suggests a possible relationship between mtDNA-CN and testosterone. Trial registration ClinicalTrials.gov, NCT00172523. Registered September 15, 2005

There are several debates on the association between gastric anatomy and weight loss after laparoscopic sleeve gastrectomy (LSG). There is a paucity of data on the impact of gastric wall volume (GWV) on weight loss. This study therefore aimed to investigate the effect of GWV on weight loss response after LSG.Thirty-two patients with body mass index (BMI) of ≧ 40 kg/mThe mean preoperative GWV was 216.9 ± 47.7 ml in the SGWV group, versus 336.3 ± 24.1 ml in the LGWV group. Patients with LGWV had significantly lower 1-year %TWL (34.9.1% versus 27.9%, p = 0.0439). Multilinear regression identified LGWV as a significant prognostic factor after adjusting for BMI and early weight loss response. Repeated measure mixed effect model showed that the LGWV group had a significantly slower %TWL change, particularly after 3 months postoperatively. No association was found between 1-year %TWL and preoperative and postoperative gastric luminal volume or resected gastric volume.3D-CT disclosed GWV, but not other gastric anatomical characteristics, was an independent predictor of %TWL after 1-year post LSG.

Irreversible electroporation (IRE) is a non-thermal ablation modality that has been shown to be safe and effective in its application to tumors that are close to risky areas. This study aims to assess the safety and efficacy of IRE for unresectable hilar cholangiocarcinoma. Nine patients from two medical centers in Asia received IRE treatment between June 2015 and July 2017. Before IRE treatment, percutaneous biliary decompressions had been performed on eight patients, and internal stenting had been performed on one patient. All patients tolerated the procedure well without high-grade complications. The ablated tumors had constant size without contrast enhancement for more than three months in eight patients and the level of CA19-9 decreased significantly in all patients. The percutaneous biliary drainage tube was removed from two patients with recanalization of the bile duct. The internal stent in one patient was removed without further stenting. The median overall survival period was 26 months, and the progression-free survival was 18 months. Bile ducts remained narrow in the majority (2/3) of the treated patients. Nevertheless, IRE ablation of unresectable hilar cholangiocarcinoma involving vital structures is a safe and feasible primary treatment for local tumor control and is effective in prolonging survival.

Since there is merit in noninvasive monitoring of muscular oxidative metabolism for near-infrared spectroscopy in a wide range of clinical scenarios, the present study attempted to evaluate the clinical usability for featuring the modulatory strategies of sternocleidomastoid muscular oxygenation using near-infrared spectroscopy in mild nonspecific neck pain patients. The muscular oxygenation variables of the dominant or affected sternocleidomastoid muscles of interest were extracted at 25% of the maximum voluntary isometric contraction from ten patients (5 males and 5 females, 23.6 &plusmn, 4.2 years) and asymptomatic individuals (6 males and 4 females, 24.0 &plusmn, 5.1 years) using near-infrared spectroscopy. Only a shorter half-deoxygenation time of oxygen saturation during a sternocleidomastoid isometric contraction was noted in patients compared to asymptomatic individuals (10.43 &plusmn, 1.79 s vs. 13.82 &plusmn, 1.42 s, p &lt, 0.001). Even though the lack of statically significant differences in most of the muscular oxygenation variables failed to refine the definite pathogenic mechanisms underlying nonspecific neck pain, the findings of modulatory strategies of faster deoxygenation implied that near-infrared spectroscopy appears to have practical potential to provide relevant physiological information regarding muscular oxidative metabolism and constituted convincing preliminary evidences of the adaptive manipulations rather than pathological responses of oxidative metabolism capacity of sternocleidomastoid muscles in nonspecific neck patients with mild disability.

Recent studies show brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 21 (FGF21) are neurotrophic factors associated with obesity and diabetes mellitus (DM). Laparoscopic sleeve gastrectomy (LSG) can significantly reduce weight and improve DM. In this study, we enrolled 78 patients with obesity and evaluated the change of BDNF and FGF21 6 months after LSG. At baseline, the BDNF level was similar between the preoperative DM (n = 30) (17.1 ± 7.7 ng/ml) and non-DM (n = 48) (17.0 ± 6.9 ng/ml) patients with obesity, but FGF21 was significantly higher in the DM patients (201.5 ± 204.3 versus 107.6 ± 63.8 pg/ml). At 6 months after LSG, most of the preoperative DM patients (96.7%) had DM either resolved (66.7%) or improved (30%). BDNF increased and FGF21 decreased significantly regardless of the preoperative DM status, while FGF21 decreased more prominently in the preoperative DM patients (−92.6 ± 179.8 versus −4.6 ± 63.4 pg/ml). After adjusted for age, sex, and preoperative DM status, FGF21 became significantly and positively related to C-peptide (β = 18.887), insulin (β = 2.399), and homeostasis model assessment of insulin resistance index (β = 8.566) after surgery. In conclusion, diabetic patients with obesity had higher FGF21 and similar BDNF levels compared to non-diabetic obese patients. BDNF increased and FGF21 decreased significantly after LSG. FGF21 became positively associated with several insulin-related profiles after surgery.

The optimal timing of frozen-thawed blastocyst transfer following hysteroscopic polypectomy is an important and unanswered clinical question. In this study, we conducted a retrospective survey of cases from an infertility center at an academic hospital. We reviewed the charts of all patients who received in-vitro fertilization and frozen-thawed blastocyst transfers (FBT) at the center from January 2009 to November 2019. One hundred and two patients with prior diagnosis of endometrial polyp that were treated with hysteroscopic polypectomy before received their first FBT at the center were identified as cases. Patients without prior diagnosis of endometrial polyp, and who received their first FBT at the center were defined as controls. Controls were enrolled at a 1-to-1 ratio to the cases. The cases and controls did not show differences in baseline characteristics, endometrial thickness, or the number of good blastocysts transferred. The clinical pregnancy rates and live birth rates were similar. Regarding the optimal interval between polypectomy and FBT, a cut-off of 120 days was identified from the ROC curve. A stratified analysis showed that when FBT was performed within an interval of 120 days after polypectomy, there were higher biochemical pregnancy rates (73.2%, 45.2%; OR 3.3; P = .007) and clinical pregnancy rates (64.8%, 41.9%; OR 2.54; P = .032), when compared with intervals greater than 120 days. There were no significant differences in implantation and live birth rates. In conclusion, pregnancy rates following FBT in patients who had received prior endometrial polypectomy were comparable to pregnancy rates after FBT in patients without endometrial polyp. Subgroup analysis showed that an interval greater than 120 days between hysteroscopic polypectomy and FBT was associated with decreased pregnancy rates. Patients who wish to receive embryo transfer after polypectomy should wait no longer than 120 days.

Recent reports have shown that sleeve gastrectomy (SG) accelerates gastric emptying (GE), but the etiology remains unclear. This study aimed to investigate the factors affecting GE before and after SG. We enrolled 35 normal weight healthy subjects and 23 obese patients receiving SG. The normal individuals and obese patients before and 3 months after SG received oatmeal-based scintigraphy to measure GE. Gastrointestinal symptoms and circulating levels of peptide YY (PYY) were also measured. There were no differences in the GE parameters, including simple half-time at 3 h and percentage of gastric retention at 0.5, 1, 2, and 3 h between healthy controls and pre-SG obese subjects. SG led to accelerated GE, more gastrointestinal symptoms, and increased fasting PYY levels postoperatively. Based on our previously established normal GE values, 18 (78.3%) obese patients with rapid postoperative GE had higher levels of preoperative fasting glucose and glycated hemoglobin, and homeostasis model assessment of the insulin resistance index than those with normal postoperative GE. Twelve (52.2%) obese patients had preoperative diabetes mellitus (DM), and only four (17.4%) remained diabetic after SG. The post-SG gastric retention at 0.5 and 1 h was lower in patients with preoperative DM than in those without preoperative DM. Neither severity of gastrointestinal symptoms nor fasting PYY levels were associated with postoperative GE alterations. Most of the obese patients had accelerated GE after SG. A higher preoperative glycemic profile was associated with rapid post-SG GE.

Background and objectives Irreversible electroporation (IRE) is a non-thermal focal therapy that utilizes high voltage electric pulses to permanently rupture the cellular membrane and induce cell death. In this multi-center study, we evaluated the safety and efficacy of IRE in patients with locally advanced pancreatic cancer (LAPC). Methods From 2012 to 2015, we performed laparotomic and laparoscopic IRE in a total of 70 patients with stage III LAPC. Either gemcitabine-based or TS-1 (Tegafur, Gimeracil, and Oteracil) chemotherapy was applied for at least 3 months before the IRE. Results No IRE-related deaths occurred. A median follow-up of 28.1 months showed that six patients (8.6%) experienced local recurrence and 24 (34%) experienced distant progression. The overall median survival from the time of treatment was 22.6 months, and the progression-free survival (PFS) was 15.4 months. The overall survival in the patients who used gemcitabine-based reagents was 19.1 months and that of those who used TS-1 was 28.7 months. The PFS for these two groups were 13.2 months and 26.4 months; the difference is significant. Conclusions Our study suggests that IRE is safe and effective for the control of LAPC. We surmise that the addition of IRE to a chemotherapy regimen may provide a survival advantage.

SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61-68% of papillary thyroid cancer and 41-50% of follicular thyroid cancer. The overexpression diminished in anaplastic thyroid cancer. The SPINT1 expression in normal thyroid tissues and benign thyroid lesions was low. Furthermore, we noted that the SPINT1 expression was associated with extrathyroidal invasion, lymphovascular invasion, lymph node metastasis, advanced TNM stage, and a higher risk of recurrence in differentiated thyroid cancer. The results were in accordance with our analysis of The Cancer Genome Atlas data. In conclusion, an overexpression of SPINT1 appears to be associated with an invasive phenotype in differentiated thyroid cancer.

Context The long-term effects of metformin in women with polycystic ovarian syndrome (PCOS) are inadequately studied. Objective The effects of metformin on women with PCOS during 24 months with respect to menses, hormones, and metabolic profiles are assessed. Design Prospective cohort. Setting A reproductive endocrinology clinic in a university-affiliated medical center. Patients One hundred nineteen women with PCOS, defined by the Rotterdam criteria, were enrolled. Intervention Metformin was given daily for 24 months. Main outcome measures The primary outcome was the proportion of patients with regular menstruation during treatment. Changes in anthropometric, hormonal, and metabolic parameters were also assessed. Analyses were performed using segmented regression analysis with a generalized estimating equation methodology. Outcomes are expressed as magnitude of change from the baseline. Results Both overweight (OW) and normal-weight (NW) women with PCOS had increased menstrual frequency and decreased body mass index (BMI), testosterone, and luteinizing hormone levels in the first 6 months. Further stratification showed that NW women exhibiting elevated testosterone at baseline had the largest magnitude of improvement at 6 months [odds ratio (OR), 7.21; 95% confidence interval (CI), 2.35 to 22.17], whereas OW patients with normal testosterone were most likely to achieve normal menses at 12 months (OR, 0.63; 95% CI, 0.47 to 0.77). Conclusions Metformin was associated with improvements in the menstrual cycle and most hormonal profiles in OW and NW women with PCOS during 24 months of treatment. Most parameters reached maximal response and steady-state after 6 months. Phenotypic differences in baseline BMI and testosterone level can be used as patient selection criteria or treatment prognostics.

Background: Previously we have shown that an elevated baseline neutrophil-to-lymphocyte ratio (NLR) was associated with a high risk of recurrence in patients with differentiated thyroid cancer. The clinical significance of the longitudinal changes in NLR following treatment remained unestablished. Methods: Adults patients with differentiated thyroid cancer were included in the study if the follow-up NLR data at 6 to 18 months after initial treatment were available. The response to treatment was categorized as excellent, indeterminate, biochemical incomplete, and structural incomplete as per guidelines of the American Thyroid Association. Results: Among 151 patients with thyroid cancer, a significant decrease in NLR following treatment was observed in those with stage I disease, those with low risk of recurrence, and those with an excellent response to therapy. Patients with a structural incomplete response had a significant increase in NLR at follow-up (p = 0.012). On multivariate analysis, incomplete response to therapy was associated with male sex (odds ratio [OR] = 3.35), tumor size (OR = 1.63), lymph node metastasis (OR = 4.80), distant metastasis (OR = 12.95), and increased NLR (OR = 13.68). Conclusions: An increase in systemic inflammation following treatment as measured by NLR is independently associated with an incomplete response to therapy in differentiated thyroid cancer.

Cellular senescence is the progressive impairment of function and proliferation in response to various regulators. Dihydrolipoic acid-coated gold nanoclusters (DHLA-Au NCs), which are molecular clusters with covalently linked dihydroxyl lipoic acid, preserve cellular activities for long-term incubation. DHLA-Au NC delivery was characterized, and we determined the role of growth supplements on internalization, allowing the optimization of DHLA-Au NC bioactivity. In the optimized medium, DHLA-Au NCs attenuated the levels of the senescence-associated phenotype. Molecular mechanism analysis further indicated that during DHLA-Au NC treatment, the activation of the stress signal JNK and its downstream c-Jun were impaired under LPS induction, which led to a decline in AP-1-mediated TNF-α transactivation. Confocal microscopy and subcellular fractionation analysis suggested that DHLA-Au NCs interacted with mitochondria through their lipid moiety and attenuated mitochondria-derived reactive oxygen species. With adequate treatment, DHLA-Au NCs show protection against cellular senescence and inflammation in vitro and in vivo.

Objective Obesity has been reported to have a modulatory effect on the ovulatory functions of patients with polycystic ovary syndrome. The role of adipokines in this obesity-associated ovulatory disturbance has not been extensively explored. In this study, the relationships between obesity, adipokine production from visceral fat, and ovarian folliculogenesis were explored in a mice model of induced obesity. Methods Obesity was induced in female C57BL/6 mice fed ad libitum with high-fat feed and fructose water for 4 weeks. Follicular developments in the ovaries were assessed by histopathology in these diet-induced obese mice. Changes in adipokine expression in the peri-ovarian adipose tissues were screened with an adipokine array. The adipokine with the most significant increase over time was identified. The functions of the adipokine in angiogenic processes were evaluated in a cell model of endothelial proliferation. The in vivo effects of neutralizing this adipokine using specific antibodies were assessed in the same obesity model. Results A high-fat and fructose diet induced an accumulation of early ovarian follicles and a reduction in mature follicles and corpus lutea. The number of microvessels in the early follicles also decreased. The adipokine protein array of the peri-ovarian adipose tissues identified a progressive increase in IL-10 expression with the duration of the obesogenic diet. In vitro experiments in the endothelial cell model confirmed IL-10 as a disrupter of VEGF-induced angiogenesis. Administration of anti-IL-10 antibodies prevented the histopathological changes induced by the obesogenic diet and further highlighted the role of IL-10 in disrupting folliculogenesis. Conclusions Obesity may disrupt normal folliculogenesis through increased production of IL-10 in visceral fats. This relationship may help clarify the reported association between obesity and ovulatory dysfunction, which has been found in patients with polycystic ovary syndrome. However, the duration of this study was short, which limited conclusions on the long-term reproductive outcomes., Highlights • Obesity increases IL-10 expression in visceral adipose. • IL-10 disrupts VEGF-induced angiogenesis in an endothelial cell model. • Disrupted angiogenesis is associated with disturbed folliculogenesis. • Anti-IL-10 antibody prevents the altered folliculogenesis induced by obesity. • Abnormal production of IL-10 may be a cause of dysovulation in obese individuals.

The present study elucidated mechanisms through which sulforaphane (SFN) protects retinal pigment epithelial (RPE) cells from blue light-induced impairment. SFN could activate the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and increase the expression of the heme oxygenease-1 (HO-1) gene and production of glutathione. SFN reduced blue light-induced oxidative stress, and effectively activated cytoprotective components including Nrf-2, HO-1, thioredoxin-1, and glutathione. The protective effect of SFN on blue light-induced injury was blocked by the Nrf2 inhibitor ML385, suggesting that the SFN-induced Nrf2 pathway is involved in the cytoprotective effect of SFN. SFN inhibited intercellular adhesion molecule-1 expression induced by TNF-α or blue light, suggesting the anti-inflammatory activity of SFN. The inhibitory effect of SFN was associated with the blocking of NF-κB p65 nuclear translocation in blue light-exposed RPE cells. SFN protected RPE cells from blue light-induced interruption of the mitochondrial membrane potential and reduction of the Bcl-2/Bax ratio and cleaved caspase-3 and PARP-1 expression, suggesting the antiapoptotic activity of SFN. SFN alone or together with blue light exposure increased the expression of the autophagy-related proteins LC3BII and p62. An autophagy inhibitor, 3-MA, inhibited the protective effect of SFN on blue light-induced cell damage. SFN increased sirtuin-1 (SIRT1) expression; however, treatment with blue light induced peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) expression. Our study results demonstrated that SFN exerts its protective effect under blue light exposure by maintaining the Nrf2-related redox state and upregulating SIRT1 and PGC-1α expression and autophagy.

Background Recurrence of papillary thyroid cancer is not uncommon, but incorporating clinicopathologic parameters to predict recurrence is suboptimal. The aim of this study was to identify systemically recurrence-associated genes using The Cancer Genome Atlas RNA sequencing database. Methods A total of 504 patients with transcriptome sequencing data of the primary neoplasm were included in this study. High and low levels of expression of each gene were defined by median splits. Differences in recurrence-free survival were compared using Kaplan-Meier curves and log-rank tests. Recurrence-associated genes were subjected to functional enrichment analyses with Kyoto Encyclopedia of Genes and Genomes annotation databases and Ingenuity Pathway Analysis. Results We found that 1,807 genes were associated with recurrence-free survival. There were 676 genes of which high expression was associated with a greater risk of recurrence. These genes were enriched in pathways involved in cell cycle regulation and DNA repair. Among 1,131 genes of which low expression was associated with recurrence, Kyoto Encyclopedia of Genes and Genomes–annotated functions were metabolism, calcium signaling, glycan biosynthesis, and the Notch signaling pathway. Canonical pathways identified by Ingenuity Pathway Analysis included RXR function, nitric oxide signaling, interleukin-8 signaling, and nutrient sensing. In addition, low expression of the majority of thyroid differentiation genes was associated with a significantly less recurrence-free survival. Conclusion Upregulation of cell cycle–regulating and DNA repair genes appears to have a negative impact on recurrence-free survival in patients with papillary thyroid cancer. Furthermore, recurrence is associated with thyroid dedifferentiation.

Star fruit (SF) is a commonly available fruit produced and eaten in tropical and subtropical countries. Since 1993, various reports have described neurotoxicity after eating SF, but this clinical condition remains unfamiliar. We aimed to describe this clinical entity, the role of renal dysfunction in this disorder, treatment strategies, and prognosis of patients with SF intoxication.We conducted a search of PubMed and Google Scholar databases from 1993 to 2016. We included reports describing patients with a clear history of SF ingestion with acute symptoms. We described the demographic characteristics, reported SF intake, treatments used, and outcomes.We reviewed totally 126 patients (male:female = 1.5:1) from 33 articles with mean age 54.4 ± 11 (range: 30-84). The most common symptom was hiccups (65%), whereas confusion and seizure were the most common symptoms associated with mortality (42% and 61%, respectively). Pre-intoxication renal function also affected mortality. While there was no mortality in patients with normal renal function (NRF), the mortality of patients among reported cases with chronic renal insufficiency and end-stage renal disease undergoing dialysis were 36% and 27%, respectively. With the inclusion of patients reported to have NRF, the overall mortality was 24%. Consistently, the number of SF consumed was substantially higher in the patients with NRF than those with renal functional impairment. The most common treatment strategy was hemodialysis (59%).Patients with impaired renal function were at higher risks of SF intoxication. Severe neurologic symptoms mandate immediate medical intervention because of the association between their occurrence and high mortalities. Toxin removal through dialysis, rather than symptomatic relief, seems to be beneficial to patient survival. Early and continuous dialysis appears to alleviate severe symptoms and prevent symptom rebounds.

On the basis of SEER data, in which most gastric cancer patients had limited lymph node dissection, node ratio-based staging system (TNrM) has been shown to have better accuracy than the AJCC TNM system. This study is to validate the result with patients from Taiwan, where D2 lymphadenectomy is routinely performed.A total of 1405 consecutive gastric cancer patients treated at National Taiwan University Hospital between 1998 and 2010 were included. To evaluate the performance of the AJCC system, each TNM stage was stratified by TNrM stages. The homogeneity of patients' survival across TNrM strata was evaluated using the log-rank test. The performance of the TNrM system was evaluated with the same approach.Five of the 7 evaluable AJCC stages (IA, IIA, IIIA, IIIB, and IIIC) contained TNrM subgroups with statistically heterogenous survival (P=0.003, 0.04, 0.002, 0.04, and0.001, respectively). Thirty-six percent of patients (506/1405) were misclassified by the AJCC TNM system. However, of the assessable 6 TNrM stages, none of the AJCC subgroups showed significantly heterogenous survivals (P0.05). About 19% of patients (264/1405) were misclassified by using the TNrM system.Lymph node ratio significantly decreases the stage migration caused by inadequate examined lymph nodes. The advantage of TNrM was validated with a patient cohort from the Eastern medical center.

// Po-Yu Yang 1, 2, 4, * , Pei-Ling Hsieh 3, * , Tong Hong Wang 5, 6, 7, * , Cheng-Chia Yu 1, 2, 3, 4, * , Ming-Yi Lu 1, 2, 3, 4 , Yi-Wen Liao 1 , Tzu-Hsin Lee 1, 2 , Chih-Yu Peng 1, 2, 3, 4 1 School of Dentistry, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4 Oral Medicine Center, Chung Shan Medical University, Taichung, Taiwan 5 Tissue Bank, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan 6 Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan 7 Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan * These authors contributed equally to this work Correspondence to: Chih-Yu Peng, email: cyp@csmu.edu.tw Keywords: oral squamous cell carcinomas, andrographolide, miR-218, cancer stemness Received: October 31, 2016 Accepted: November 23, 2016 Published: December 01, 2016 ABSTRACT Current evidence suggests that oral cancer stem cells (OCSCs) possess high tumorigenic and metastatic properties as well as chemo- and radioresistance. In this study, we demonstrated that andrographolide, the main bioactive component in the medicinal plant Andrographis, significantly reduced oncogenicity and restored radio-sensitivity of ALDH1 + CD44 + OCSCs. Mechanistic studies showed that andrographolide treatment increased the expression of microRNA-218 (miR-218), leading to the downregulation of Bmi1. We showed that knockdown of miR-218 in ALDH1 − CD44 − non-OCSCs enhanced cancer stemness, while silencing of Bmi1 significantly counteracted it. Furthermore, we found tumor growth was reduced in mice bearing xenograft tumors after andrographolide treatment via activation of miR-218/Bmi1 axis. Together, these data demonstrated that the inhibition of tumor aggressiveness in OCSCs by andrographolide was mediated through the upregulation of miR-218, thereby reducing Bmi1 expression. These findings suggest that andrographolide may be a valuable natural compound for anti-CSCs treatment of OSCC.

Double-inlet left ventricle (DILV) is a congenital heart disease that only a single left ventricle and a rudimentary right ventricle are developed. Because of lack of anatomic landmark, interpretation of Tl myocardial perfusion imaging in DILV is essentially challenging for unusual anomaly. We report the case of a 44-year-old woman with DILV who presented exertional dyspnea and tachycardia and underwent Tl SPECT. The anatomic characteristics of cardiac Tl SPECT are correlated with MRI. To obtain accurate interpretation in DILV, it is absolutely necessary to realize the anatomy relationship between perfusion imaging and anatomic imaging such as CT or MRI.