AIMTo review the accumulated 30 patients with different area of Y chromosome microdeletions, focusing on their correlation with the clinical and pathological findings.

METHODSA total of 334 consecutive infertile men with azoospermia (218 patients) and severe oligoasthenospermia (116 patients) were screened. Complete physical and endocrinological examinations, general chromosome study and multiplex polymerase chain reaction assay to evaluate the Y chromosome microdeletion were performed. Ten patients received testicular biopsy. Then the clinical and pathological findings were analyzed with reference to the areas of Y chromosome microdeletion.

RESULTSThere is a decline of the percentage of sperm appearing in semen in the group that the gene deletion region from AZFc to AZFb. The clinical evidence of the impairment (decreased testicular size and elevated serum FSH) is also relevantly aggravated in this group. However, the pathology of testicular biopsy specimen was poorly correlated with the different deletion areas of the Y chromosome, which may be due to the limited number of specimens.

CONCLUSIONThe clinical correlation of spermatogenic impairment to the different AZF deletion regions may provide the information for the infertile couples in pre-treatment counseling.

Adult ; Aged ; Chromosome Deletion ; Chromosomes ; Chromosomes, Human, Y ; Counseling ; Gene Deletion ; Humans ; Male ; Middle Aged ; Oligospermia ; pathology ; Sperm Injections, Intracytoplasmic ; Testis ; pathology ; Tissue Embedding

Before progress was recently made in the application of temporary anchorage devices (TADs) in bio-mechanical design, orthodontists were rarely able to intrude molars to reduce upper posterior dental height (UPDH). However, TADs are now widely used to intrude molars to flatten the occlusal plane or induce counterclockwise rotation of the mandible. Previous studies involving clinical or animal histological evaluation on changes in periodontal conditions after molar intrusion have been reported, however, studies involving human histology are scarce. This case was a Class I malocclusion with a high mandibular plane angle. Upper molar intrusion with TADs was performed to reduce UPDH, which led to counterclockwise rotation of the mandible. After 5 months of upper molar intrusion, shortened clinical crowns were noticed, which caused difficulties in oral hygiene and hindered orthodontic tooth movement. The mid-treatment cone-beam computed tomography revealed redundant bone physically interfering with buccal attachment and osseous resective surgeries were followed. During the surgeries, bilateral mini screws were removed and bulging alveolar bone and gingiva were harvested for biopsy. Histological examination revealed bacterial colonies at the bottom of the sulcus. Infiltration of chronic inflammatory cells underneath the non-keratinized sulcular epithelium was noted, with abundant capillaries being filled with red blood cells. Proximal alveolar bone facing the bottom of the gingival sulcus exhibited active bone remodeling and woven bone formation with plump osteocytes in the lacunae.On the other hand, buccal alveolar bone exhibited lamination, indicating slow bone turnover in the lateral region.

Purpose: Stroke survivors and their informal family caregivers may share the impact of the disease, which may affect family functioning and quality of life (QoL) for both. This study compared the perceptions of stroke survivors and informal family caregivers regarding family functioning and QoL and examined the QoL of those reporting effective versus ineffective family functioning. Methods: A cross-sectional study design and convenience sampling were used. Stroke survivoreinformal family caregiver dyads were recruited from a medical university hospital. We assessed participants’ demographic and clinical variables, including disease severity, family functioning, and QoL. Independent t-test, paired t-test, Wilcoxon signed-rank test, and ManneWhitney U test were used to analyze the data. Results: Seventy-one stroke survivoreinformal family caregiver dyads participated in the current study. Most stroke survivors and informal family caregivers reported effective family functioning, with no significant differences. However, significant differences existed in the seven domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, and role-emotional) of QoL, except emotional health. Stroke survivors reporting ineffective family functioning had a significantly lower mental component summary score, unlike informal family caregivers. Conclusions Our findings suggest that family functioning is crucial to ensure stroke survivors’ QoL, particularly regarding their mental health. Health professionals should prioritize mental health assessments and provide appropriate care interventions for stroke survivors in the first 1e6 months after stroke onset.

BACKGROUNDEstrogen deficiency results in loss of bone mass. Phytoestrogens are plant-derived non-steroidal compounds with estrogen-like activity that bind to estrogen receptors. The main aim of this study was to investigate the effect of the phytoestrogen puerarin on adult mouse osteoblasts.

METHODSOsteoblast cells were harvested from 8-month old female imprinting control region (ICR) mice. The effects of puerarin stimulation on the proliferation, differentiation and maturation of osteoblasts were examined. The production of nitric oxide (NO) and the expression of bone morphogenetic protein-2 (BMP-2), SMAD4, mitogen-activated protein kinases (MAPK), core binding factor α1/ runt-related transcription factor 2 (Cbfa1/Runx2), osteoprotegerin (OPG), and receptor activator of NF-κB ligand (RANKL) genes were analyzed. The activation of signal pathways was further confirmed by specific pathway inhibitors.

RESULTSThe osteoblast viability reached its maximum at 10(-8) mol/L puerarin. At this concentration, puerarin increases the proliferation and matrix mineralization of osteoblasts and promotes NO synthesis. With 10(-8) mol/L puerarin treatment, BMP-2, SMAD4, Cbfa1/Runx2, and OPG gene expression were up-regulated, while the RANKL gene expression is down-regulated. Concurrent treatment involving the (bone morphogenetic protein) BMP antagonist Noggin or the NOS inhibitor L-NAME diminishes puerarin induced cell proliferation, Alkaline phosphatase (ALP) activity, NO production, as well as the BMP-2, SMAD4, Cbfa1/Runx2, OPG, and RANKL gene expression.

CONCLUSIONSIn this in vitro study, we demonstrate that puerarin is a bone anabolic agent that exerts its osteogenic effects through the induction of BMP-2 and NO synthesis, subsequently regulating Cbfa1/Runx2, OPG, and RANKL gene expression. This effect may contribute to its induction of osteoblast proliferation and differentiation, resulting in bone formation.

Animals ; Bone Morphogenetic Protein 2 ; genetics ; physiology ; Cell Differentiation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Female ; Isoflavones ; pharmacology ; MAP Kinase Signaling System ; physiology ; Mice ; Mice, Inbred ICR ; Nitric Oxide ; physiology ; Osteoblasts ; drug effects ; metabolism ; Osteogenesis ; drug effects ; Phytoestrogens ; pharmacology ; RANK Ligand ; genetics

Objective: Problematic use of social media (PUSM) may affect sleep quality and self-stigma in people with schizophrenia and consequently reduce their quality of life (QoL). This longitudinal study investigated if sleep quality and self-stigma mediated relationships between PUSM and QoL. Methods: One-hundred-and-ninety-three outpatients with schizophrenia were recruited from a psychiatric center in Taiwan from April 2019 to August 2021 and participated in a longitudinal study at intervals of three months between measurements. QoL was assessed using the World Health Organization Quality of Life Questionnaire Brief Version; sleep quality using the Pittsburgh Sleep Quality Index; self-stigma using the Self-Stigma Scale-Short; and PUSM using the Bergen Social Media Addiction Scale. Via SPSS 20.0, general estimating equation models assessed temporal associations between variables. Via R software, mediating effects of self-stigma and sleep quality were examined through Monte Carlo simulations with 20,000 repetitions. Results: Mean scores of physical, psychological, social and environmental QoL ranged from 11.86 to 13.02. Mean scores of sleep quality and self-stigma were 9.1±4.5 and 2.2±0.8, respectively. Sleep quality and self-stigma were directly related to QoL (p<0.001) and mediated indirect relationships between PUSM and all components of QoL with a range of 95% confidence intervals spanning from -0.0591 to -0.0107 for physical QoL; -0.0564 to -0.0095 for psychological QoL; -0.0292 to -0.0035 for social QoL; and -0.0357 to -0.0052 for environmental QoL. Conclusion Sleep quality and self-stigma mediated relationships between PUSM and QoL in people with schizophrenia. Developing interventions targeting PUSM, sleep, and self-stigma may help improve QoL in people with schizophrenia.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II–IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC.

Triple-negative breast cancer (TNBC) remains difficult to treat and urgently needs new therapeutic options. Nintedanib, a multikinase inhibitor, has exhibited efficacy in early clinical trials for HER2-negative breast cancer. In this study, we examined a new molecular mechanism of nintedanib in TNBC. The results demonstrated that nintedanib enhanced TNBC cell apoptosis, which was accompanied by a reduction of p-STAT3 and its downstream proteins. STAT3 overexpression suppressed nintedanib-mediated apoptosis and further increased the activity of purified SHP-1 protein. Moreover, treatment with either a specific inhibitor of SHP-1 or SHP-1-targeted siRNA reduced the apoptotic effects of nintedanib, which validates the role of SHP-1 in nintedanib-mediated apoptosis. Furthermore, nintedanib-induced apoptosis was attenuated in TNBC cells expressing SHP-1 mutants with constantly open conformations, suggesting that the autoinhibitory mechanism of SHP-1 attenuated the effects of nintedanib. Importantly, nintedanib significantly inhibited tumor growth via the SHP-1/p-STAT3 pathway. Clinically, SHP-1 levels were downregulated, whereas p-STAT3 was upregulated in tumor tissues, and SHP-1 transcripts were associated with improved disease-free survival in TNBC patients. Our findings revealed that nintedanib induces TNBC apoptosis by acting as a SHP-1 agonist, suggesting that targeting STAT3 by enhancing SHP-1 expression could be a viable therapeutic strategy against TNBC.
Apoptosis* ; Breast Neoplasms ; Disease-Free Survival ; Humans ; Protein-Tyrosine Kinases* ; RNA, Small Interfering ; Triple Negative Breast Neoplasms* ; Tyrosine*

Bipolar disorder (BD) is a major psychiatric disorder that is easily misdiagnosed. Patient adherence to a treatment regimen is of utmost importance for successful outcomes in BD. Several trials of antipsychotics suggested that depot antipsychotics, including long-acting first- and second-generation agents, are effective in preventing non-adherence, partial adherence, and in reducing relapse in BD. Various long-acting injectable (LAI) antipsychotics are available, including fluphenazine decanoate, haloperidol decanoate, olanzapine pamoate, risperidone microspheres, paliperidone palmitate, and aripiprazole monohydrate. Due to the increasing number of BD patients receiving LAI antipsychotics, treatment guidelines have been developed. However, the clinical applicability of LAI antipsychotics remains a global cause for concern, particularly in Asian countries. Expert physicians from Taiwan participated in a consensus meeting, which was held to review key areas based on both current literature and clinical practice. The purpose of this meeting was to generate a practical and implementable set of recommendations for LAI antipsychotic use to treat BD; target patient groups, dosage, administration, and adverse effects were considered. Experts recommended using LAI antipsychotics in patients with schizophrenia, rapid cycling BD, BD I, and bipolar-type schizoaffective disorder. LAI antipsychotic use was recommended in BD patients with the following characteristics: multiple episodes and low adherence; seldom yet serious episodes; low adherence potential per a physician's clinical judgment; preference for injectable agents over oral agents; and multiple oral agent users still experiencing residual symptoms.
Antipsychotic Agents* ; Asian Continental Ancestry Group ; Bipolar Disorder* ; Consensus* ; Fluphenazine ; Haloperidol ; Humans ; Judgment ; Microspheres ; Patient Compliance ; Psychotic Disorders ; Recurrence ; Risperidone ; Schizophrenia ; Taiwan ; Aripiprazole ; Paliperidone Palmitate

Background/Aims: Real-world studies assessing the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) plus ribavirin (RBV) for Child-Pugh B/C hepatitis C virus (HCV)-related cirrhosis are limited. Methods: We included 107 patients with Child-Pugh B/C HCV-related cirrhosis receiving SOF/VEL plus RBV for 12 weeks in Taiwan. The sustained virologic response rates at off-treatment week 12 (SVR12) for the evaluable population (EP), modified EP, and per-protocol population (PP) were assessed. Thesafety profiles were reported. Results: The SVR12 rates in the EP, modified EP and PP were 89.7% (95% confidence interval [CI], 82.5–94.2%), 94.1% (95% CI, 87.8–97.3%), and 100% (95% CI, 96.2–100%). Number of patients who failed to achieve SVR12 were attributed to virologic failures. The SVR12 rates were comparable regardless of patient characteristics. One patient discontinued treatment because of adverse events (AEs). Twenty-four patients had serious AEs and six died, but none were related to SOF/VEL or RBV. Among the 96 patients achieving SVR12, 84.4% and 64.6% had improved Child-Pugh and model for endstage liver disease (MELD) scores. Multivariate analysis revealed that a baseline MELD score ≥15 was associated with an improved MELD score of ≥3 (odds ratio, 4.13; 95% CI, 1.16–14.71; P=0.02). Patients with chronic kidney disease (CKD) stage 1 had more significant estimated glomerular filtration rate declines than patients with CKD stage 2 (-0.42 mL/min/1.73 m2/month; P=0.01) or stage 3 (-0.56 mL/min/1.73 m2/month; P<0.001). Conclusions SOF/VEL plus RBV for 12 weeks is efficacious and well-tolerated for Child-Pugh B/C HCV-related cirrhosis.