A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1.

The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer

An Investigation of the Differential Expression of Her2/neu Gene Expression in Normal Oral Mucosa, Epithelial Dysplasia, and Oral Squamous Cell Carcinoma in Taiwan

BackgroundHer2/neu was thought to be a proto-oncogene with sequence homology to epidermal growth factor receptor (EGFR). Its overexpression was seen in many cancers and referred to regimens of anticancer therapy. The aim of this study was to investigate whether the abnormal expression existed in oral carcinogenesis.MethodsImmunohistochemistry (IHC) was used to detect Her2/neu expression in normal oral mucosa (NOM) (n = 20), oral precancerous lesions of epithelial dysplasia (ED) (n = 20), and oral squamous cell carcinoma (OSCC) (n = 30). The association of clinicopathologic covariates of areca use, tumor size, neck lymph node metastasis, differentiation and stages of cancer with the expression of Her2/neu was examined. The significance of Neu immunoreactivity in different groups or with different covariates was investigated using Fisher's exact test.ResultsHer2/neu immunoreactivity was very low with Her2/neu(+) in 10% (2/20) of NOM cases and in 25% (5/20) of ED cases, respectively. The Her2/neu expression was high in OSCC cases, with 40% (12/30) of Her2/neu(+) and 10% (3/30) of Her2/neu(++). Significant difference was observed between NOM/ED and OSCC cases (p < 0.05). All clinicopathologic covariates showed no significant relation to the expression of Her2/neu in OSCC cases.ConclusionThese findings suggested a dynamic change in Her2/neu expression during the development of OSCC. The overexpression of Her2/neu can be used as a marker in distinguishing NOM/ED from OSCC

Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line

Cisplatin (CDDP) is one of the most active drugs to treat nasopharyngeal carcinoma (NPC) patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu) derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP

Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of comparative genomic hybridization results

Nasopharyngeal carcinoma (NPC) is a highly prevalent disease in Southeast Asia and its prevalence is clearly affected by genetic background. Various theories have been suggested for its high incidence in this geographical region but to these days no conclusive explanation has been identified. Chromosomal imbalances identifiable through comparative genomic hybridization may shed some light on common genetic alterations that may be of relevance to the onset and progression of NPC. Review of the literature, however, reveals contradictory results among reported findings possibly related to factors associated with patient selection, stage of disease, differences in methodological details etc. To increase the power of the analysis and attempt to identify commonalities among the reported findings, we performed a meta-analysis of results described in NPC tissues based on chromosomal comparative genomic hybridization (CGH). This meta-analysis revealed consistent patters in chromosomal abnormalities that appeared to cluster in specific "hot spots" along the genome following a stage-dependent progression

The LEGUE Input Catalogue for Dark Night Observing in the LAMOST Pilot Survey

We outline the design of the dark nights portion of the LAMOST Pilot Survey, which began observations in October 2011. In particular, we focus on Milky Way stellar candidates that are targeted for the LEGUE (LAMOST Experiment for Galactic Understanding and Exploration) survey. We discuss the regions of sky in which spectroscopic candidates were selected, and the motivations for selecting each of these sky areas. Some limitations due to the unique design of the telescope are discussed, including the requirement that a bright (V < 8) star be placed at the center of each plate for wavefront sensing and active optics corrections. The target selection categories and scientific goals motivating them are briefly discussed, followed by a detailed overview of how these selection functions were realized. We illustrate the difference between the overall input catalog - Sloan Digital Sky Survey (SDSS) photometry - and the final targets selected for LAMOST observation.Comment: 11 pages, 7 figures, accepted for publication in RA

A mixed-methods study on toilet hygiene practices among Chinese in Hong Kong.

BACKGROUND: Public toilets are a common transmission vector of infectious diseases due to environmental contamination. Research on Chinese people's hygiene practices in public lavatories are lacking. This study examined Chinese people's hygiene practices in public lavatories in Hong Kong. METHODS: We conducted qualitative interviews and a self-administered questionnaire survey with local residents from June 2016 to April 2018. Four focus group discussions and three individual interviews informed the design of the questionnaire. We recruited interviewees and survey respondents via social service centers. The interviews and questionnaire focused on the public's daily practices and hygiene behaviors in public toilets. Content analysis of qualitative data was conducted. Multivariable logistic regressions were used to examine the association between age and toilet hygiene behaviors. RESULTS: Our qualitative component revealed a range of handwashing practices, from not washing at all, washing without soap, to washing for a longer time than instructions. Other toilet use practices were identified, such as not covering toilet lid before flushing and stepping on toilet seats due to dirtiness, and spitting into toilet bowls or hand basin. Totally, 300 respondents completed the questionnaire. Among them, 212 (70.9%) were female and 246 (86.1%) were aged 65 or below. More than two thirds always washed hands with soap (68.7%) and dried hands with paper towels (68.4%). Up to 16.2% reported stepping on toilet seats and 43.9% never covered the toilet lid before flushing. Over one fourth (26.4%) spit into squat toilets/ toilet bowl. Regression analyses showed that the elderly group were less likely to report stepping on toilet seats (adjusted odds ratio, AOR = 0.17, 95%CI 0.03-0.88), flushing with the toilet lid closed (AOR = 0.40, 0.16-0.96), but more likely to spit into squat toilets/ toilet bowl (AOR = 4.20, 1.50-11.74). CONCLUSIONS: Hong Kong Chinese's compliance to hygiene practices in public toilets is suboptimal. Stepping on toilet seat is a unique Chinese practice due to the dirtiness of toilet seats. Spitting practices may increase the risk of airborne infectious diseases and need improvement. Measures are needed to improve toilet hygiene behaviors, including public education campaigns and keeping toilet environment clean

Anesthetic management of patients undergoing cardiac myxoma resection: a single-center retrospective analysis

BackgroundMyxomas are the most common primary cardiac tumors. Intracardiac myxomas, although benign, could cause serious consequences such as tricuspid or mitral valve obstruction, hemodynamic collapse, and acute heart failure, which pose challenges during anesthetic management. The current study was designed to summarize the anesthetic management of patients undergoing cardiac myxoma resection.MethodsThis study was performed retrospectively from the perioperative period of patients who underwent myxoma resection. Patients were divided into two groups according to whether the myxoma prolapsed into the ventricle (group O) or not (group N) to evaluate the impact of tricuspid or mitral valve with obstruction.Results110 patients, aged 17–78 years, undergoing cardiac myxoma resection between January 2019 and December 2021 were collected, and their perioperative characteristics were recorded. In the preoperative evaluation, common clinical symptoms included dyspnea and palpitation, whereas embolic events occurred in 8 patients, including 5 (4.5%) cerebral thromboembolic events, 2 (1.8%) femoral artery, and 1 (0.9%) obstructive coronary artery. According to the echocardiography, left atrial myxoma was detected in 104 (94.5%) patients, the average dimension of myxoma was 4.03 cm ± 1.52 cm in the largest diameter, and 48 patients were divided into group O. During intraoperative anesthetic management, hemodynamic instability occurred in 38 (34.5%) patients after anesthesia induction. More patients in group O had hemodynamic instability (47.9% vs. 24.2%, p = 0.009) than in group N. The mean postoperative length of stay in the hospital was 10.64 ± 3.01 days, and most of the patients made an uneventful postoperative recovery.ConclusionsAnesthetic management for myxoma resection can be composed by assessing the myxoma, particularly the echocardiography evaluation and preventing cardiovascular instability. Typically, tricuspid or mitral valve with obstruction is a premier ingredient in anesthetic management

Effect of patient decision aids on choice between sugammadex and neostigmine in surgeries under general anesthesia: a multicenter randomized controlled trial

Background Shared decision making using patient decision aids (PtDAs) was established over a decade ago, but few studies have evaluated its efficacy in Asian countries. We therefore evaluated the application of PtDAs in a decision conflict between two muscle relaxant reversal agents, neostigmine and sugammadex, and sequentially analyzed the regional differences and operating room turnover rates. Methods This multicenter, outcome-assessor-blind, randomized controlled trial included 3,132 surgical patients from two medical centers admitted between March 2020 and August 2020. The patients were randomly divided into the classical and PtDA groups for pre-anesthesia consultations. Their clinicodemographic characteristics were analyzed to identify variables influencing the choice of reversal agent. On the day of the pre-anesthesia consultation, the patients completed the four SURE scale (sure of myself, understand information, risk-benefit ratio, encouragement) screening items. The operating turnover rates were also evaluated using anesthesia records. Results Compared with the classical group, the PtDA group felt more confident about receiving sufficient medical information (P < 0.001), felt better informed about the advantages and disadvantages of the medications (P < 0.001), exhibited a superior understanding of the benefits and risks of their options (P < 0.001), and felt surer about their choice (P < 0.001). Moreover, the PtDA group had a significantly greater tendency to choose sugammadex over neostigmine (P < 0.001). Conclusions PtDA interventions in pre-anesthesia consultations provided surgical patients with clear knowledge and better support. PtDAs should be made available in other medical fields to enhance shared clinical decision-making

Healthcare costs associated with progressive diabetic retinopathy among National Health Insurance enrollees in Taiwan, 2000-2004

<p>Abstract</p> <p>Background</p> <p>Diabetic retinopathy is one of the most common microvascular complications of diabetes and one of the major causes of adult visual impairment in national surveys in Taiwan. This study aimed to identify the healthcare costs of Taiwan's National Health Insurance program on behalf of diabetic patients with stable or progressive retinopathy.</p> <p>Methods</p> <p>A retrospective cohort study was conducted with 4,988 medication-using diabetic retinopathy subjects ≥ 40 years of age under National Health Insurance Program coverage between 2000 and 2004. Study cohort subjects were recorded as having diabetic retinopathy according to ICD-9-CM codes. States of diabetic retinopathy were strategically divided into stable and progressive categories according to subjects' conditions at follow-up in 2004. Expenditures were calculated and compared for the years 2000 and 2004.</p> <p>Results</p> <p>During the 4-year follow-up (2000 through 2004), 4,116 subjects (82.5%) of 4,988 diabetic subjects were in the stable category, and 872 (17.5%) were in the progressive category. Average costs of those in the normal category increased by US $48 from US$1921 in 2000 to US $1969 in 2004 (p = 0.594), whereas costs for those progressing from normal to non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) increased by US$1760, from US $1566 in 2000 to US$3326 in 2004 (p < 0.001). The PDR category had the highest average costs at US $3632 in 2000. The NPDR-to-PDR category experienced the greatest increase in costs at US$3482, from US $2723 in 2000 to US$6204 in 2004 (p = 0.042), and the greatest percentage of increase at 2.3% (2.2% when adjusted by comparing to normal category).</p> <p>Conclusions</p> <p>This large-scale longitudinal study provides evidence that increased healthcare costs are associated with progressive diabetic retinopathy among diabetic NHI enrollees in Taiwan.</p

Association Between Acid-Sensing Ion Channel 3 Gene Variants and Balance Impairment in People With Mild Traumatic Brain Injury

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown.Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test.Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01).Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance