Office hysteroscopy to guide intrauterine device hook use for the removal of a deeply embedded intrauterine device.

Office hysteroscopy is a common examination method in gynecological clinics. In most cases, it can only be examined but not treated. Here, we present our specific technique used office hysteroscope to guide intrauterine device (IUD) hook in the removal of deeply embedded IUD which provided direct visualization and sufficient force.

Uniform, Strain-Free, Large-Scale Graphene and h-BN Monolayers Enabled by Hydrogel Substrates.

Translation of the unique properties of 2D monolayers from non-scalable micron-sized samples to macroscopic scale is a longstanding challenge obstructed by the substrate-induced strains, interface nonuniformities, and sample-to-sample variations inherent to the scalable fabrication methods. So far, the most successful strategies to reduce strain in graphene are the reduction of the interface roughness and lattice mismatch by using hexagonal boron nitride (h-BN), with the drawback of limited uniformity and applicability to other 2D monolayers, and liquid water, which is not compatible with electronic devices. This work demonstrates a new class of substrates based on hydrogels that overcome these limitations and excel h-BN and water substrates at strain relaxation enabling superiorly uniform and reproducible centimeter-sized sheets of unstrained monolayers. The ultimate strain relaxation and uniformity are rationalized by the extreme structural adaptability of the hydrogel surface owing to its high liquid content and low Young's modulus, and are universal to all 2D materials irrespective of their crystalline structure. Such platforms can be integrated into field effect transistors and demonstrate enhanced charge carrier mobilities in graphene. These results present a universal strategy for attaining uniform and strain-free sheets of 2D materials and underline the opportunities enabled by interfacing them with soft matter.

Manoalide Induces Intrinsic Apoptosis by Oxidative Stress and Mitochondrial Dysfunction in Human Osteosarcoma Cells.

Osteosarcoma (OS) is the most common primary malignant bone tumor that produces immature osteoid. Metastatic OS has a poor prognosis with a death rate of >70%. Manoalide is a natural sesterterpenoid isolated from marine sponges. It is a phospholipase A2 inhibitor with anti-inflammatory, analgesic, and anti-cancer properties. This study aimed to investigate the mechanism and effect of manoalide on OS cells. Our experiments showed that manoalide induced cytotoxicity in 143B and MG63 cells (human osteosarcoma). Treatment with manoalide at concentrations of 10, 20, and 40 µM for 24 and 48 h reduced MG63 cell viability to 45.13-4.40% (p < 0.01). Meanwhile, manoalide caused reactive oxygen species (ROS) overproduction and disrupted antioxidant proteins, activating the apoptotic proteins caspase-9/-3 and PARP (Poly (ADP-ribose) polymerase). Excessive levels of ROS in the mitochondria affected oxidative phosphorylation, ATP generation, and membrane potential (ΔΨm). Additionally, manoalide down-regulated mitochondrial fusion protein and up-regulated mitochondrial fission protein, resulting in mitochondrial fragmentation and impaired function. On the contrary, a pre-treatment with n-acetyl-l-cysteine ameliorated manoalide-induced apoptosis, ROS, and antioxidant proteins in OS cells. Overall, our findings show that manoalide induces oxidative stress, mitochondrial dysfunction, and apoptosis, causing the cell death of OS cells, showing potential as an innovative alternative treatment in human OS.

Intra-Articular Lactate Dehydrogenase A Inhibitor Oxamate Reduces Experimental Osteoarthritis and Nociception in Rats via Possible Alteration of Glycolysis-Related Protein Expression in Cartilage Tissue.

Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.

Estrogen upregulates DNA2 expression through the PI3K-AKT pathway in endometrial carcinoma. / é›Œæ¿€ç´ é€šè¿‡PI3K-AKTé€šè·¯ä¸Šè°ƒå­å®«å† è†œç™Œä¸­DNA2的表达.

Endometrial cancer is the most common gynecological malignancy, affecting up to 3% of women at some point during their lifetime (Morice et al., 2016; Li and Wang, 2021). Based on the pathogenesis and biological behavioral characteristics, endometrial cancer can be divided into estrogen-dependent (I) and non-estrogen-dependent (II) types (Ulrich, 2011). Type I accounts for approximately 80% of cases, of which the majority are endometrioid carcinomas, and the remaining are mucinous adenocarcinomas (Setiawan et al., 2013). It is generally recognized that long-term stimulation by high estrogen levels with the lack of progesterone antagonism is the most important risk factor; meanwhile, there is no definite conclusion on the specific pathogenesis. The incidence of endometrial cancer has been on the rise during the past two decades (Constantine et al., 2019; Gao et al., 2022; Luo et al., 2022). Moreover, the development of assisted reproductive technology and antiprogestin therapy following breast cancer surgery has elevated the risk of developing type I endometrial cancer to a certain extent (Vassard et al., 2019). Therefore, investigating the influence of estrogen in type I endometrial cancer may provide novel concepts for risk assessment and adjuvant therapy, and at the same time, provide a basis for research on new drugs to treat endometrial cancer.

A modified laparoscopic lateral suspension with mesh for apical and anterior pelvic organ prolapse: a retrospective cohort study.

Introduction: Pelvic organ prolapse (POP), a common and benign condition, is characterized by the descent of one or more aspects of the vagina and uterus. A wide variety of mesh-based surgical techniques have been proved to be effective in the treatment of pelvic organ prolapse (POP). Aim: To evaluate the efficacy of a modified laparoscopic lateral suspension with mesh (mLLSM) in patients with apical and anterior pelvic organ prolapse. Material and methods: All patients diagnosed with apical and anterior pelvic organ prolapse underwent a modified laparoscopic lateral suspension with mesh (mLLSM). Perioperative parameters including surgical time, blood loss and complications were recorded. At the minimal 12-month follow-up, primary outcome measures included both anatomical and functional points. The anatomical cure rate was evaluated using the Pelvic Organ Prolapse Questionnaire (POP-Q) assessment. Patient satisfaction was evaluated using questionnaires. Results: Mean surgical time was 91.56 ±15.33 min; mean estimated blood loss was 55.42 ±36.73 ml; no intraoperative complications were noted in the perioperative period. After a minimal 12-month follow-up period, rates of anatomical success and subjective satisfaction were 96.33% and 94.50%, respectively. Symptom severity and quality of life also improved significantly. Conclusions: We found mLLSM to be a safe and effective treatment for patients suffering apical and anterior pelvic organ prolapse. We found mLLSM to result in excellent outcomes and fewer mesh complications, underscoring its potential as an alternative treatment option for the management of apical and anterior pelvic organ prolapse.

Unique interface reflection phenomena tailored by nanoscale electromagnetic boundary conditions.

Local interface response effects are neglected based on the traditional electromagnetic boundary conditions (EMBCs) in an abrupt interface model. In this study, generalized nanoscale EMBCs are derived with interface response functions (IRFs) representing field inhomogeneity across the interface based on integral Maxwell's equations. They are rewritten in two different forms that correspond to the equivalent abrupt interface models with interface-induced dipoles or charges and currents. Interesting behaviors of Brewster angle shifting, non-extinction at Brewster angle, and unique absorption or gain effects are revealed based on the advanced Fresnel formula. IRFs-controlled GH-shift and angular GH-shift of a Gaussian beam near the Brewster angles are generated by the gradient interface. These unique phenomena provide some guidance for measuring the IRFs and expanding interface photonics at the nanoscale.

Tough, Self-Healing, and Conductive Elastomer ─Ionic PEGgel.

Ionically conductive elastomers are necessary for realizing human-machine interfaces, bioelectronic applications, or durable wearable sensors. Current design strategies, however, often suffer from solvent leakage and evaporation, or from poor mechanical properties. Here, we report a strategy to fabricate ionic elastomers (IHPs) demonstrating high conductivity (0.04 S m-1), excellent electrochemical stability (>60,000 cycles), ultra-stretchability (up to 1400%), high toughness (7.16 MJ m-3), and fast self-healing properties, enabling the restoration of ionic conductivity within seconds, as well as no solvent leakage. The ionic elastomer is composed of in situ formed physically cross-linked poly(2-hydroxyethyl methacrylate) networks and poly(ethylene glycol) (PEG). The long molecular chains of PEG serve as a solvent for dissolving electrolytes, improve its long-term stability, reduce solvent leakage, and ensure the outstanding mechanical properties of the IHP. Surprisingly, the incorporation of ions into PEG simultaneously enhances the strength and toughness of the elastomer. The strengthening and toughening mechanisms were further revealed by molecular simulation. We demonstrate an application of the IHPs as (a) flexible sensors for strain or temperature sensing, (b) skin electrodes for recording electrocardiograms, and (c) a tough and sensing material for pneumatic artificial muscles. The proposed strategy is simple and easily scalable and can further inspire the design of novel ionic elastomers for ionotronics applications.

Microtubule-severing protein Fidgetin-like 1 promotes spindle organization during meiosis of mouse oocytes.

Microtubule-severing proteins (MTSPs) play important roles in mitosis and interphase. However, to the best of our knowledge, no previous studies have evaluated the role of MTSPs in female meiosis in mammals. It was found that FIGNL1, a member of MTSPs, was predominantly expressed in mouse oocytes and distributed at the spindle poles during meiosis in the present study. FIGNL1 was co-localized and interacted with γ-tubulin, an important component of the microtubule tissue centre (MTOC). Fignl1 knockdown by specific small interfering RNA caused spindle defects characterized by an abnormal length:width ratio and decreased microtubule density, which consequently led to aberrant chromosome arrangement, oocyte maturation and fertilization obstacles. In conclusion, the present results suggested that FIGNL1 may be an essential factor in oocyte maturation by influencing the meiosis process via the formation of spindles.

Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress-Mitochondrial Apoptotic and Autophagic Signaling Pathway.

Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50-60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.

Tooth extraction within 2 weeks before radiotherapy and osteoradionecrosis: A nationwide cohort study.

OBJECTIVES: The theory of at least 2-week waiting period between tooth extraction and head and neck radiotherapy could reduce osteoradionecrosis remains controversial. Thus, this study examined the theory and associated factors. MATERIALS AND METHODS: Data were retrieved from the National Health Insurance Research Database, Taiwan Cancer Registry Database, and Cause of Death Statistics. We included 24,353 patients with head and neck cancer who received radiotherapy from 2011 to 2017 and were followed up until 2019. The patients were divided into three groups: those undergoing tooth removal 2-8 weeks before radiotherapy, those undergoing tooth removal within 2 weeks before radiotherapy, and others. Confounding factors were clinical information, physical conditions, and risky habits. We used the Cox regression model to assess osteoradionecrosis risk. RESULTS: No significant difference in osteoradionecrosis risk was observed between those undergoing tooth extraction within 2 weeks before radiotherapy and the other groups. An irradiation dose of ≥60 Gy, chemotherapy, tumor excision, post-radiotherapy tooth extraction, mandibulectomy, hyperlipidemia, and oral cavity as the tumor subsite were significantly positively associated with osteoradionecrosis risk. CONCLUSION: A waiting period of ≥2 weeks between tooth extraction and radiotherapy did not significantly reduce osteoradionecrosis risk.

Design and Validation of an Augmented Reality Teaching System for Primary Logic Programming Education.

Programming is a skill that requires high levels of logical thinking and problem-solving abilities. According to the Curriculum Guidelines for the 12-Year Basic Education currently implemented in Taiwan, programming has been included in the mandatory courses of middle and high schools. Nevertheless, the guidelines simply recommend that elementary schools conduct fundamental instructions in related fields during alternative learning periods. This may result in the problem of a rough transition in programming learning for middle school freshmen. To alleviate this problem, this study proposes an augmented reality (AR) logic programming teaching system that combines AR technologies and game-based teaching material designs on the basis of the fundamental concepts for seventh-grade structured programming. This system can serve as an articulation curriculum for logic programming in primary education. Thus, students are able to develop basic programming logic concepts through AR technologies by performing simple command programming. This study conducted an experiment using the factor-based quasi-experimental research design and questionnaire survey method, with 42 fifth and sixth graders enrolled as the experimental subjects. The statistical analysis showed the following results: In terms of learning effectiveness, both AR-based and traditional learning groups displayed a significant performance. However, of the two groups, the former achieved more significant effectiveness in the posttest results. Regarding learning motivation, according to the evaluation results of the Attention, Relevance, Confidence, and Satisfaction (ARCS) motivation model, the AR-based learning group manifested significantly higher levels of learning motivation than the traditional learning group, with particularly significant differences observed in the dimension of Attention. Therefore, the experimental results validate that the proposed AR-based logic programming teaching system has significant positive effects on enhancing students' learning effectiveness and motivation.

Inorganic arsenic speciation analysis in food using HPLC/ICP-MS: Method development and validation.

Arsenic (As) compounds can be classified as organic or inorganic, with inorganic arsenic (iAs) having significantly higher toxicity than organic As. As may accumulate in food materials that have been exposed to As-contaminated environments. Thus, the "Sanitation Standard for Contaminants and Toxins in Foods" published by the Ministry of Health and Welfare set the standard limits for iAs content in rice, seaweed, seafood, and marine oils to safeguard public health. Therefore, a robust analytical method must be developed to selectively and quantitatively determine iAs content in rice, seaweed, seafood, and marine oils. Herein, we reported and verified the method of combined high-performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) to determine iAs content in a wide variety of food. The fish oil samples were spiked with different concentrations of the As(III) standard solution, and their iAs analyzes were obtained via extraction procedures using the 1% (w/w) nitric acid (HNO3) solution containing 0.2 M hydrogen peroxide (H2O2) under sonication. The extracts were subsequently analyzed for their As(V) contents using HPLC/ICP-MS with aqueous ammonium carbonate as the mobile phase. The As(III) species had completely oxidized into the As(V) species, which prevented interferences between organic and iAs during chromatography. The method showed good extraction efficiencies (generally >90%) for the iAs samples, and their limits of quantification in fish oil were 0.02 mg/kg. The method was verified via the iAs speciation analytes of rice, seaweed, seafood, and marine oil matrices. The average recoveries for the fortified samples of each matrix ranged from 87.5 to 112.4%, with their coefficients of variation being less than 10%. Surveillance studies were conducted on the iAs contents of food samples purchased from local Taiwanese markets. The results showed that the only Hijiki (Sargassum fusiforme) higher than the maximum limit of the sanitation standard for iAs in seaweed, whereas the remaining samples met their corresponding requirements. This method is quick and straightforward, and it can be applied for the routine analysis of iAs content in a wide variety of food products to ensure public health safety.

Chondroprotective Effects of a Histone Deacetylase Inhibitor, Panobinostat, on Pain Behavior and Cartilage Degradation in Anterior Cruciate Ligament Transection-Induced Experimental Osteoarthritic Rats.

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

Up-regulation of DNA2 results in cell proliferation and migration in endometriosis.

Accumulating evidence has suggests that women with advanced endometriosis exhibit alterations in the expression of genes in the endometrium compared to healthy controls. Furthermore, replication stress is a characteristic feature of cancer cells, which results from sustained proliferative signaling induced by either the activation of oncogenes or the loss of tumor suppressors. In the present study, we propose that DNA replication ATP-dependent helicase/nuclease 2 (DNA2) might be upregulated in endometriosis. Immunohistochemical staining results confirmed the hypothesis that DNA2 is overexpressed in the eutopic/ectopic endometrium compared to that in a control endometrium from a healthy donor. Subsequently, ectopic endometrium-derived endometrial mesenchymal stem cells (EMSCs) showed the highest level of DNA2 and checkpoint kinase 1 (CHK1), as well as the strongest proliferation and migration capabilities, followed by eutopic endometrium-derived EMSCs, and then control EMSCs. To further analyze the function of DNA2, we knocked-down DNA2 expression in KLE cells. As expected, proliferation and migration declined when cells were transfected with DNA2 small interfering RNA. Taken together, our study demonstrated the overexpression of DNA2 in human endometriosis, which might be responsible for the upregulated cell proliferation and migration. This study provides insights into the mechanisms underlying human endometriosis.

Health literacy and cancer screening behaviors among community-dwelling female adults in Taiwan.

This study was designed to explore the association among health literacy and cancer screening behaviors in Taiwanese females. A total of 353 community-dwelling females were recruited in this cross-sectional study from February to October 2015. Demographic, socioeconomic and personal behavior variables including physical activity, community activity, smoking, alcohol consumption, and betel nut chewing were recorded. Health literacy was evaluated using the Mandarin version of the European Health Literacy Survey Questionnaire. Data on screening behaviors for cervical, breast and colorectal cancers were confirmed by the Taiwanese National eHealth Database. Most respondents with inadequate or problematic general health literacy had no or irregular screening behaviors for cervical, breast and colorectal cancers. In multivariable regression analysis, women with inadequate health literacy were at a greater risk (Odds ratio = 5.71; 95% CI: 1.40-23.26) of having no previous Pap smear screening or >3 years screening interval regardless of education level. However, this association was not detected for breast or colorectal cancer. Women with inadequate health literacy were more likely to have irregular cervical cancer screening, however no associations among health literacy and breast or colorectal cancer were detected. The impact of health literacy on cancer screening behavior warrants further attention and research.

Effects of Streptococcus thermophilus on anterior cruciate ligament transection-induced early osteoarthritis in rats.

Osteoarthritis (OA) is the most common joint disorder and is classically defined as a progressively degenerative disease of articular cartilage. It manifests as joint pain and disability and currently has no comprehensive treatments. The primary purpose of the present study was to test the effects of probiotics, Streptococcus thermophilus (TCI633), on anterior cruciate ligament transection (ACLT)-induced experimental osteoarthritis (OA) in rats. In the current study, the experimental groups were given TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) and glucosamine sulfate (250 mg/kg) between week 8 and 20 following ACLT. The results showed that oral administration of TCI633 and glucosamine had significant therapeutic effects on pain behaviors and knee swelling. Dose-dependent effects of TCI633 were also observed in ACLT-treated rats. Histopathological analysis demonstrated that ACLT+TCI633 (5x109, 5x1010 and 5x1011 CFU/kg/day) improved the synovial inflammation and cartilage damage of ACLT rats. Histology evaluation using the Osteoarthritis Research Society International system and synovial inflammatory score analysis showed the dose-dependent inhibition of TCI633 on synovial inflammation and cartilage damage. Immunohistochemical staining and TUNEL apoptosis staining showed that TCI633 could effectively increase the expression of type II collagen and reduce the amount of chondrocyte apoptosis in cartilage. Therefore, the present study demonstrated that oral intake of TCI633 could significantly suppressing pain behavior, reduce joint swelling and synovial tissue inflammation and increase type II collagen expression in cartilage. There was also a reduction in chondrocyte apoptosis and decreased progression of OA in ACLT-treated rats.

Serum amyloid A protein in cancer prognosis: a meta-analysis and systematic review.

BACKGROUND: Published studies showed divergent results of the prognostic value of serum amyloid A protein (SAA) in patients with different cancers. Therefore, we conducted this meta-analysis so as to assess the association between SAA and cancer prognosis. METHODS: A comprehensive search was conducted to identify the literatures working over SAA and survival in patients with cancers published until January 2020. Sufficient data for assessing overall survival in cancers were extracted descriptively and quantitatively from the studies and a pooled odds ratio was calculated using the Mantel-Haenszel fixed-effect or random-effect model. RESULTS: Ten eligible papers were identified by two reviewers independently, including 4 studies that evaluated renal cell carcinoma (RCC), 2 studies evaluated lung cancer and the other 3 studies evaluated melanoma, gastric cancer and different cancers. Elevated SAA expression and shorter overall survival (OS) had a statistically significant relation [pooled 1-year OR was 5.07, 95% confidence interval (CI), 3.71-6.94, Q=9.15, I2=0%; pooled 3-year OR was 4.21, 95% CI, 3.18-5.56, Q=14.94, I2=46%; pooled 5-year OR was 5.69, 95% CI, 2.66-12.18, Q=24.83, I2=80%]. Subgroup analysis of RCC patients showed remarkable association between SAA and shorter OS (pooled 1-year OR =4.76, 95% CI, 3.00-7.56, Q=4.18, I2=4%; pooled 3-year OR =4.89, 95% CI, 3.06-7.81, Q=2.88, I2=0%). CONCLUSIONS: High SAA status is correlated with an unfavorable OS in different cancers, especially in RCC, and digestive cancer.