OBJECTIVE: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). RESULTS: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. CONCLUSION: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Amygdala ; Animals ; Depression* ; Hippocampus ; Phenotype ; Prefrontal Cortex ; Rats* ; Receptor, Serotonin, 5-HT1A ; Serotonin 5-HT1 Receptor Agonists ; Serotonin* ; Social Control, Formal ; Social Isolation

OBJECTIVE: The objective of this study was to explore the association of longitudinal CA-125 measurements with overall survival (OS) time by developing a flexible model for patient-specific CA-125 profiles, and to provide a simple and reliable prediction of OS. METHODS: A retrospective study was performed on 275 patients with ovarian cancer who underwent at least one cycle of primary chemotherapy in our institute. Serial measurements of patients' CA-125 levels were performed at different frequencies according to their clinical plans. A statistical model coupling the Cox proportional hazards and the mixed-effects models was applied to determine the association of OS with patient-specific longitudinal CA-125 values. Stage and residual tumor size were additional variables included in the analysis. RESULTS: A total of 1,601 values of CA-125 were included. Longitudinal CA-125 levels, stage, and the residual tumor size were all significantly associated with OS. A patient-specific survival probability could be calculated. Validation showed that, in average, 85.4% patients were correctly predicted to have a high or low risk of death at a given time point. Comparison with a traditional model using CA-125 half-life and time to reach CA-125 nadir showed that the longitudinal CA-125 model had an improved predicative value. CONCLUSION: Longitudinal CA-125 values, measured from the diagnosis of ovarian cancer to the completion of primary chemotherapy, could be used to reliably predict OS after adjusting for the stage and residual tumor disease. This model could be potentially useful in clinical counseling of patients with ovarian cancer.
Counseling ; Diagnosis ; Drug Therapy ; Half-Life ; Humans ; Models, Statistical ; Neoplasm, Residual ; Ovarian Neoplasms* ; Retrospective Studies

PURPOSE: The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. METHODS: An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. RESULTS: Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. CONCLUSION: Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.
Blotting, Western ; Breast Neoplasms ; Cell Death ; Cell Line ; DNA Nucleotidylexotransferase ; Drosophila ; Fluorescent Antibody Technique ; Glycoproteins ; Humans ; Immunoprecipitation ; In Vitro Techniques ; Interleukin-6 ; Interleukins ; Janus Kinase 2 ; Phosphorylation ; Phosphotransferases ; Polymerase Chain Reaction ; Receptors, Interleukin-6 ; Reverse Transcription ; STAT3 Transcription Factor ; Transducers ; Tyrosine

Compounds from Lingzhi has been demonstrated the ability for inhibiting tyrosinase (a key enzyme in melanogenesis) activity. In this study, we investigated the anti-melanogenic activity from the submerged mycelial culture of Ganoderma weberianum and elucidated the skin lightening mechanism by B16-F10 murine melanoma cells. From the cellular context, several fractionated mycelium samples exhibited anti-melanogenic activity by reducing more than 40% extracellular melanin content of B16-F10 melanoma cells. In particular, the fractionated chloroform extract (CF-F3) inhibited both secreted and intracellular melanin with the lowest dosage (25 ppm). Further analysis demonstrated that CF-F3 inhibited cellular tyrosinase activity without altering its protein expression. Taken together, our study has demonstrated that the chemical extracts from submerged mycelial culture of G. weberianum have the potential to serve as an alternative anti-melanogenic agent.
Chloroform ; Ganoderma ; Melanins ; Melanoma ; Monophenol Monooxygenase ; Mycelium ; Reishi ; Skin

Objective: This study aimed to determine the effect of radiotherapy (RT) on the risk of herpes zoster (HZ) in patients with gynecological cancers via a nationwide population-based study. Methods: Based on patient data obtained from the National Health Insurance Research Database, 1928 gynecological cancer patients were identified with 1:1 matching for RT and non-RT cohorts by age, index date, and cancer type. Another cohort consisting of 964 noncancer individuals matched was used as normal control. The incidence of HZ was compared between cancer patients with and without RT. Age, comorbidities, cancer-related surgery and chemotherapy (CT), and cancer type were adjusted as confounders. Results: The risk of HZ in cancer patients was higher than that of non-cancer individuals (14.23 versus 8.34 per 1,000 person-years [PY], the adjusted hazard ratio [aHR]=1.38, p=0.044). In the cancer population, the incidence of HZ for the RT and non-RT cohorts was 20.55 versus 10.23 per 1,000 PY, respectively (aHR=1.68, p=0.009). Age >50 years was an independent factor for developing HZ. The 5-year actuarial incidence for patients receiving neither RT nor CT, RT alone, CT alone, and combined modalities was 5.4%, 6.9%, 3.7%, and 9.9%, respectively (p<0.001). In the RT cohort, the risk rose rapidly in the first year, becoming steady thereafter. Conclusion This population-based study showed that gynecological cancer patients receiving RT combined with CT had the highest cumulative risk of HZ. Health care professionals should be aware of the potential toxicities.

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.

OBJECTIVES: This cohort study investigated the correlation between Parkinson’s disease (PD) risk and chronic obstructive pulmonary disease (COPD) risk under particulate matter with an aerodynamic diameter ≤2.5 μm (PM2.5) exposure. METHODS: Data from the National Health Research Institutes of Taiwan were used in this study. The Environmental Protection Administration of Taiwan established an air quality monitoring network for monitoring Taiwan’s general air quality. COPD was indicated by at least 3 outpatient records and 1 hospitalization for COPD. After the implementation of age, sex, and endpoint matching at a 1:4 ratio, 137 patients and 548 patients were included in the case group and control group, respectively. Based on the 2005 World Health Organization (WHO) standards, monthly air particle concentration data were classified into the following 4 groups in analyses of exposure–response relationships: normal level, and 1.0, 1.5, and 2.0 times the WHO level ([concentration ≥2]×25 μg/m3×number of exposure months). RESULTS: A multivariate logistic regression revealed that the 1.0 and 1.5 WHO level groups did not significantly differ from the normal level group, but the 2.0 WHO level did (odds ratio, 4.091; 95% confidence interval, 1.180 to 14.188; p=0.038). CONCLUSIONS Elevated PM2.5 concentrations were significantly correlated with an increased risk of PD among patients with COPD. Furthermore, exposure to high PM2.5 levels can further increase the risk of PD.

The prevalence of obstructive sleep apnea (OSA) is estimated to be 1–5% of the adult population world-wide, and in Korea, it is reported at 4.5% of men and 3.2% of women (Age 40 to 69 years old). Active treatment of OSA is associated with decrease in insulin resistance, cardiovascular disease, psychosocial problems, and mortality. Surgical treatment of OSA has evolved in the era of neuromodulation with the advent of hypoglossal nerve stimulation (HGNS). We share this review of HGNS with our maxillofacial surgical colleagues to expand the scope of surgical care for OSA.
Adult ; Cardiovascular Diseases ; Female ; Humans ; Hypoglossal Nerve* ; Insulin Resistance ; Korea ; Male ; Mortality ; Oral and Maxillofacial Surgeons* ; Prevalence ; Sleep Apnea, Obstructive* ; Snoring

Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence in-situ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.
Abortion, Habitual ; Abortion, Spontaneous ; Alleles ; Aneuploidy ; Biopsy ; Blastocyst ; Chimera ; Chromosome Aberrations ; Comparative Genomic Hybridization ; Cryopreservation ; Embryonic Structures ; Endometrium ; Female ; Fluorescence ; Genetic Testing ; Genome ; Humans ; Live Birth ; Mass Screening ; Maternal Age ; Mitochondrial Diseases ; Mosaicism ; Ovarian Hyperstimulation Syndrome ; Patient Dropouts ; Polar Bodies ; Polymorphism, Single Nucleotide ; Pregnancy ; Preimplantation Diagnosis ; Prostaglandins D ; Translocation, Genetic ; Transportation ; Vitrification

OBJECTIVE: To compare the clinical utility of the different imaging techniques used for the evaluation of tracheobronchial diseases. MATERIALS AND METHODS: Forty-one patients with tracheobronchial diseases [tuberculosis (n = 18), bronchogenic carcinoma (n = 10), congenital abnormality (n = 3), post-operative stenosis (n = 2), and others (n = 8)] underwent chest radi-ography and spiral CT. Two sets of scan data were obtained: one from routine thick-section axial images and the other from thin-section axial images. Multiplanar reconstruction (MPR) and shaded surface display (SSD) images were obtained from thin-section data. Applying a 5-point scale, two observers compared chest radiography, routine CT, thin-section spiral CT, MPR and SSD imaging with regard to the detection, localization, extent, and characterization of a lesion, information on its relationship with adjacent structures, and overall information. RESULTS: SSD images were the most informative with regard to the detection (3.95 +/-0.31), localization (3.95 +/-0.22) and extent of a lesion (3.85 +/-0.42), and overall information (3.83 +/-0.44), while thin-section spiral CT scans provided most information regarding its relationship with adjacent structures (3.56 +/-0.50) and characterization of the lesion (3.51 +/-0.61). CONCLUSION: SSD images and thin-section spiral CT scans can provide valuable information for the evaluation of tracheobronchial disease.
Bronchial Diseases/*radiography ; Comparative Study ; Female ; Human ; *Imaging, Three-Dimensional ; Male ; Middle Age ; *Tomography, X-Ray Computed/methods ; Tracheal Diseases/*radiography