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Objective: The first Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor, olaparib, was approved by Taiwan Food and Drug Administration in June 2018, which was available under a compassionate use program since 2015. This study aims to report the early experience of the effectiveness and adverse effects of olaparib in recurrent ovarian cancer patients in Taiwan. Materials and methods: This retrospective study enrolled patients with recurrent epithelial ovarian and peritoneal cancer who received olaparib as maintenance therapy or salvage therapy between December, 2015 and October, 2019. We observed response rates in the salvage therapy group, and progression-free interval (PFI) in both groups. Results: A total of 20 patients (10 in maintenance and 10 in salvage groups) were enrolled. BRCA status was checked in 18 patients by blood or tumor samples, and 83.3% were mutated (n = 15), including pathological/probable pathological variants in BRCA1 (n = 11), BRCA2 (n = 2), or both BRCA1/BRCA2 (n = 2). In the salvage group, there were two partial responses and two stable diseases, adding up to a clinical benefit rate at 40%. In the maintenance group, median PFI was 20.1 months (range, 1.0–33.1). The median PFI of those with chemotherapy-free interval >12 months was not reached, which was significantly better than those ≤12 months, with median PFI 3.1 months (p = 0.022). The most common grade 3/4 adverse effects in patient with olaparib as monotherapy were neutropenia (30.8%) and fatigue (7.7%). Anemia of grade 1/2 was noted in 76.9%. Conclusion: This real-world experience of olaparib for recurrent ovarian cancer in Taiwan showed efficacy and safety similar to the results of previous clinical trial.

Candida albicans is the most common pathogen causing clinical Candida infections. Neutrophils are a key member of the host innate immunity that plays an essential role in clearing invading C. albicans. In addition to the well-known defensive approaches such as phagocytosis, degranulation, and reactive oxygen species production, the formation of neutrophil extracellular traps (NETs) has also become an important way for neutrophils to defend against various pathogens. C. albicans has been reported to be capable of activating neutrophils to release NETs that subsequently kill fungi. The induction of NETs is affected by both the morphology and virulence factors of C. albicans, which also develops specific strategies to respond to the attack by NETs. Our review specifically focuses on the mechanisms by which C. albicans triggers NET formation and their subsequent interactions, which might provide meaningful insight into the innate immunity against C. albicans infection.

Cutting fluids are the most effective method to lower the cutting temperature and decrease the cutting tool wear. At the same time, the cutting fluids influence the corrosion resistance property of the machined surface. In this study, chlorinated paraffin (CP), which is a common additive in the cutting fluid, was selected as the research objective to study its corrosion resistance property. The passivation effect of CP with different concentrations on the machined surface of stainless steel was studied. Electrochemical measurements and surface morphology investigation were used to characterize the passivation effect of CP with different concentrations. The test results showed that the corrosion resistance of stainless steel in the cutting fluid was enhanced with the increase in CP additive. This reason is that the charge transfer resistance increases and the corrosion current density decreases with the increase in CP additive. The X-ray photoelectron spectroscopy (XPS) results show that the proportion of metal oxides on the processed surface of the stainless steel sample was increased from 20.4% to 22.0%, 32.9%, 26.6%, and 31.1% after adding 1 mL, 2 mL, 4 mL and 6 mL CP in the cutting fluid with a total volume of 500 mL, respectively. The oxidation reaction between CP and the stainless steel sample resulted in an increase in metal oxides proportion, which prevented the stainless steel sample from corrosion in cutting fluid.

Abstract Despite wide application of high frequency oscillatory ventilation (HFOV) in neonates with respiratory distress, little has been reported about its rescue use in preterm infants. We aimed to evaluate the therapeutic effects of HFOV in preterm neonates with refractory respiratory failure and investigate the independent risk factors of in-hospital mortality. We retrospectively analyzed data collected prospectively (January 2011–December 2018) in four neonatal intensive care units of two tertiary-level medical centers in Taiwan. All premature infants (gestational age 24–34 weeks) receiving HFOV as rescue therapy for refractory respiratory failure were included. A total of 668 preterm neonates with refractory respiratory failure were enrolled. The median (IQR) gestational age and birth weight were 27.3 (25.3–31.0) weeks and 915.0 (710.0–1380.0) g, respectively. Pre-HFOV use of cardiac inotropic agents and inhaled nitric oxide were 70.5% and 23.4%, respectively. The oxygenation index (OI), FiO2, and AaDO2 were markedly increased after HFOV initiation (all p

This study explores the relationship between China's reproductive health policy and the rate of return on urban education by using fixed-effect, mediating-effect, and breakpoint regression models. The authors study the impact of China's reproductive health policy on individual years of education, income, return on education, the impact of reproductive health policy on population health, and overall human development. The empirical results show that the implementation of China's reproductive health policy can improve the rate of return on urban education and increase the average length of education of urban residents by 0.29 years. Under the breakpoint regression model, the educational return rate of urban residents is approximately 12.2% higher than the ordinary least squares (OLS) estimate. China's reproductive health policy has significantly promoted the return rate of residents' education and simultaneously effectively promoted the income of urban residents. With the development of the economy, the government should properly adjust reproductive health policies and improve the population health rate so that the adjustment of reproductive health policies can comprehensively promote the health of residents of all ages. The overall relaxation of family restrictions on children's human capital investment will likely reduce the negative impact of the overall relaxation of family planning, not only improving the health of the population but also contributing to sustainable economic development.

Two-dimensional generalized XY spin model on a triangular lattice is studied by means of Monte-Carlo simulations. The critical temperatures of Berezinskii-Kosterlitz-Thouless (BKT) phase transition are obtained by the method of helicity modulus. It is found that the results are consistent with those obtained by other methods. The vortex density and the vortex-antivortex pair formation energy are also obtained. The result shows that the critical temperature decreases with the increase of the generalization parameter q. While the vortex-antivortex pair formation energy increases with the increase of q when q>1.

Background/Purpose: We sought to compare the diagnostic performances of 68Ga-PSMA-11 PET/CT and prostate/whole-abdomen multiparametric magnetic resonance imaging (PWAmpMRI) in Taiwanese patients with biochemically recurrent prostate cancer following robot-assisted radical prostatectomy. Methods: Between June 2017 and December 2018, we prospectively enrolled 34 patients. Upon review of all available clinical and imaging data, a best valuable comparator (BVC) was defined on an individual basis in the light of a consensus reached by a multidisciplinary tumor board. Diagnostic positivity was investigated in relation to the different lesion types. Results: On a patient-based analysis, 68Ga-PSMA-11 PET/CT and PWAmpMRI showed a moderate agreement (kappa coefficient = 0.62). 68Ga-PSMA-11 PET/CT identified local recurrences, regional, and non-regional lymph node metastases, and bone metastases in 15, 10, 1, and 5 patients, respectively. Conversely, PWAmpMRI detected these lesions in 26, 8, 1, and 4 patients, respectively. When the BVC was used as reference standard, the positive diagnostic rates for local recurrences, regional lymph node metastases, non-regional lymph node metastases, and bone metastases were 57.7%, 90.9%, 100%, and 100%, respectively for 68Ga-PSMA-11 PET/CT, and 100%, 72.7%, 100%, and 80% for PWAmpMRI, respectively. The use of both PWAmpMRI and 68Ga-PSMA-11 PET/CT showed a complete diagnostic yield for detecting both local recurrence and systemic failure when PSA levels reached 0.5 ng/mL. Conclusion: Due to urine radioactivity, 68Ga-PSMA-11 PET/CT performs less than PWAmpMRI on local recurrences. However, it can have a complementary diagnostic role in the detection of lymph node metastases and in identifying non-axial bone metastases beyond the PWAmpMRI scanning field.

Abstract Background To evaluate the use of a human fibrin glue (Tisseel) for minor bleeding control and approximation of ovarian defect during transvaginal natural orifice ovarian cystectomy (TNOOC) of benign and non-endometriotic ovarian tumors. Methods A total of 125 women with benign and non-endometriotic ovarian tumors who underwent TNOOC between May 2011 and January 2020: 54 with the aid of Tisseel and 71 with traditional suture for hemostasis and approximation of ovarian defect. Surgical outcomes such as length of surgery, operative blood loss, postoperative pain score, and postoperative hospital stay were recorded. Before and immediately (10 days) and at 6 months after the procedure, serum anti-Müllerian hormone (AMH) levels were also determined. Results Complete hemostasis and approximation of ovarian defect were achieved in all cases. No significant difference was noted in the operating time, operative blood loss, postoperative pain scores after 12, 24 and 48 h, length of postoperative stay, and baseline AMH levels between the two groups. The operation did not have a negative effect on the immediate and 6-month postoperative AMH levels in the suture group. However, the decline in the AMH levels was significant immediately after surgery in the Tisseel group, nevertheless, no significant difference was noted in the AMH levels at 6 months (3.3 vs. 1.7 mg/mL; p = 0.042, adjusted p = 0.210). Conclusion The use of Tisseel in TNOOC of benign and non-endometriotic ovarian tumors without suturing the ovarian tissue is clinically safe and feasible.

Fungal infections pose a serious challenge to human health due to the limited paucity of antifungal treatments. Starting as a hit compound screened from our compound library, a series of nicotinamide derivatives have been successfully synthesized via a facile one-step coupling reaction of aromatic carboxylic acid and amine. The synthesized compounds were evaluated for their antifungal activity against Candida albicans SC5314. Among the 37 nicotinamide derivatives screened, compound 16g was found to be the most active against C. albicans SC5314, with an MIC value of 0.25 μg/mL and without significant cytotoxicity. The rudimentary structure-activity relationships study revealed that the position of the amino and isopropyl groups of 16g was critical for its antifungal activity. In particular, compound 16g showed potent activity against six fluconazole-resistant C. albicans strains with MIC values ranging from 0.125–1 μg/mL and showed moderate activity against the other seven species of Candida, three strains of Cryptococcus neoformans, and three strains of Trichophyton. Furthermore, compound 16g showed fungicidal, anti-hyphal, and anti-biofilm activities in vitro, which were related to its ability to disrupt the cell wall of C. albicans. Taken together, 16g is a promising compound that is fungal-specific by targeting the cell wall and could be used as a lead compound for further investigation.

Reactive species (RS) are the key factors of plasma‐activated solutions (PAS) against cancer. However, the specific contribution of each RS in inducing cancer cell death remain unclear. Therefore, this study aimed to evaluate the anticancer potential and mechanism of plasma‐activated medium (PAM) and plasma‐activated phosphate buffer saline (PA‐PBS) in vitro using colorectal cancer cells HCT116. Results showed that PAM and PA‐PBS effectively inhibited the growth and proliferation of HCT116 cells, with PA‐PBS exhibiting greater potency. H2O2, intracellular reactive oxygen species, and pH (H+) were essential mediators of cell death, and ONOO− exhibited cytotoxicity only after reaching a specific concentration. Additionly, PAS induced cell death through the exogenous apoptotic pathway. [ABSTRACT FROM AUTHOR]

Significance: Monitoring blood glucose levels is crucial for individuals with diabetes. Noninvasive methods for measuring serum glucose levels have been explored to aid in blood glucose control for diabetes management. Aim: We introduced a noncontact optical glucometer (NCGM) for measuring glucose levels in the aqueous humor of the human eye. We also investigated the correlation between glucose levels in the NCGM and the aqueous humor, blood samples, and self-monitoring blood glucose devices. Approach: The optical system used in this study measured both the near-infrared absorption and polarized rotatory distribution of glucose molecules in the human aqueous humor. This prospective study’s outcomes were eye aqueous glucose level, preoperative blood glucose level, intraoperative blood glucose level, and NCGM reading of patients in a single center in Taiwan. Results: The NCGM’s measurements showed a strong correlation with blood glucose levels (intra-class correlation [ICC]: 0.95 to 0.98) and aqueous humor glucose levels (ICC: 0.76), indicating its ability to noninvasively measure blood glucose levels in human subjects. Conclusions: This NCGM may offer a convenient, pain-free, and rapid tool for measuring blood glucose levels in diabetic patients. The device could represent a significant advancement in noncontact hybrid optical glucose measurement systems. [ABSTRACT FROM AUTHOR]

Background and Aim: Circular ubiquitin‐like, containing PHD and ring finger domains 1 (circUHRF1) is aberrantly upregulated in human hepatocellular carcinoma (HCC) tissues. However, the underlying molecular mechanisms remain obscure. The present study aimed at elucidating the interactive function of circUHRF1–G9a–ubiquitin‐like, containing PHD and ring finger domains 1 (UHRF1) mRNA–eukaryotic translation initiation factor 4A3 (EIF4A3)–PDZ and LIM domain 1 (PDLIM1) network in HCC. Methods: Expression of circUHRF1, mRNAs of G9a, UHRF1, PDLIM1, epithelial–mesenchymal transition (EMT)‐related proteins, and Hippo–Yap pathway components was determined by quantitative polymerase chain reaction (Q‐PCR), immunofluorescence, or Western blot analysis. Tumorigenic and metastatic capacities of HCC cells were examined by cellular assays including Cell Counting Kit‐8, colony formation, wound healing, and transwell assays. Molecular interactions between EIF4A3 and UHRF1 mRNA were detected by RNA pull‐down experiment. Complex formation between UHRF1 and PDLIM1 promoter was detected by chromatin immunoprecipitation assay. Co‐immunoprecipitation was performed to examine the binding between UHRF1 and G9a. Results: Circular ubiquitin‐like, containing PHD and ring finger domains 1, G9a, and UHRF1 were upregulated, while PDLIM1 was downregulated in HCC tissue samples and cell lines. Cellular silencing of circUHRF1 repressed HCC proliferation, invasion, migration, and EMT. G9a formed a complex with UHRF1 and inhibited PDLIM1 transcription. Conclusion: Eukaryotic translation initiation factor 4A3 regulated circUHRF1 expression by binding to UHRF1 mRNA promoter. circUHRF1 increased the stability of G9a and UHRF1 mRNAs through recruiting EIF4A3. Overexpression of circUHRF1 aggravated HCC progression through Hippo–Yap pathway and PDLIM1 inhibition. By elucidating the molecular function of circUHRF1–G9a–UHRF1 mRNA–EIF4A3–PDLIM1 network, our data shed light on the HCC pathogenesis and suggest a novel therapeutic strategy for future HCC treatment. [ABSTRACT FROM AUTHOR]

The vacuole of Candida albicans plays a significant role in many processes including homeostasis control, cellular trafficking, dimorphic switching, and stress tolerance. Thus, understanding the factors affecting vacuole function is important for the identification of new drug targets needed in response to the world’s increasing levels of invasive infections and the growing issue of fungal drug resistance. Past studies have shown that vacuolar proton-translocating ATPases (V-ATPases) play a central role in pH homeostasis and filamentation. Vacuolar protein sorting components (VPS) regulate V-ATPases assembly and at the same time affect hyphal development. As well, vacuolar calcium exchange systems like Yvc1 and Pmc1 maintain cytosolic calcium levels while being affected by V-ATPases function. All these proteins play a role in the virulence and pathogenesis of C. albicans. This review highlights the relationships among V-ATPases, VPS, and vacuolar calcium exchange proteins while summarizing their importance in C. albicans infections.

BackgroundTakayasu’s arteritis (TA) is a type of primary large vessel vasculitis. Th1, Th17, and Tfh cells have been reported to be associated with TA relapse. However, the relationship between regulatory T cells (Tregs) and TA remains unclear.ObjectiveTo analyze the levels of circulating lymphocytes, especially Treg cells (CD4+CD25+FOXP3+ T cells) and serum cytokines in TA patients and explore their relationship with their changes and TA disease activity.MethodsA total of 57 TA patients and 43 sex- and age-matched healthy controls (HCs) were enrolled. According to NIH standards, 36 patients had active disease status. Flow cytometry combined with counting was used to detect the absolute numbers and ratios of Th1, Th2, Th17, and Treg cells in the peripheral blood of all the subjects. Magnetic bead-based multiplex immunoassay was used to detect cytokines.ResultsCompared to HCs, the absolute number and proportion of peripheral Treg cells in TA patients was significantly decreased, while Th17 cells were significantly increased. Furthermore, compared to the inactive group, the TA active group had significantly increased levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α, but lower IL-10 levels. The absolute number of Th2 cells was negatively associated with platelet (PLT) and NIS scores in TA patients. The proportion of Th2 cells was negatively associated with the erythrocyte sedimentation rate in TA patients. After treatment, Treg cells were markedly increased.ConclusionThere was a Th17-Treg cell imbalance with a significant reduction in peripheral Treg cells and an increase in Th17 cells in TA patients compared to the HCs. The levels of IL-6, IL-10, IL-17, and TNF-α appeared to be related to disease activity.