This study investigated the molecular mechanism of phenotypic switching of vascular smooth muscle cells (VSMCs), which play a crucial role in vascular remodeling using 9H-Carbazol-3-yl 4-aminobenzoate (CAB). CAB significantly attenuated platelet-derived growth factor (PDGF)-induced VSMC proliferation and migration. CAB suppressed PDGF-induced STAT3 activation by directly binding to the SH2 domain of STAT3. Downregulation of STAT3 phosphorylation by CAB attenuated CIAPIN1/JAK2/STAT3 axis through a decrease in CIAPIN1 transcription. Furthermore, abrogated CIAPIN1 decreased KLF4-mediated VSMC dedifferentiation and increased CDKN1B-induced cell cycle arrest and MMP9 suppression. CAB inhibited intimal hyperplasia in injury-induced neointima animal models by inhibition of the CIAPIN1/JAK2/STAT3 axis. However, CIAPIN1 overexpression attenuated CAB-mediated suppression of VSMC proliferation, migration, phenotypic switching, and intimal hyperplasia. Our study clarified the molecular mechanism underlying STAT3 inhibition of VSMC phenotypic switching and vascular remodeling and identified novel active CAB. These findings demonstrated that STAT3 can be a major regulator to control CIAPIN1/JAK2/STAT3 axis that may be a therapeutic target for treating vascular proliferative diseases.

Background: To evaluate the incidence and related factors of rheumatoid arthritis (RA) flares after switching from intravenous tocilizumab (TCZ-IV) to subcutaneous tocilizumab (TCZSC) injection in stable RA patients. Methods: We retrospectively evaluated the medical records of stable RA patients who used TCZ-IV for more than 6 months and switched to TCZ-SC between January 2013 and April 2020. RA flare was defined as an increase of more than 1.2 in the RA disease activity as assessed by the disease activity score in 28 joints. The factors associated with RA flare were evaluated by logistic regression analysis. Results: Among 106 patients treated with TCZ-IV for > 6 months, 37 patients were switched to TCZ-SC after the acquisition of remission or low disease activity. RA flares occurred in 11 (29.7%) of patients who switched TCZ-SC. Results from the multivariable logistic analysis revealed that the dose of TCZ-IV per weight at switching (odds ratio [OR], 20.70; 95% confidence interval [CI], 2.22–192.84; P = 0.008) and methotrexate (MTX) non-use (OR, 8.53; 95% CI, 1.21–60.40; P = 0.032) were associated with the risk of RA flares after switching to TCZ-SC. Interestingly, most patients who switched back to TCZ-IV had their RA activity controlled again. Conclusion MTX non-use and high dose of TCZ-IV per weight were associated with a risk of RA flare after switching to TCZ-SC. RA patients with these factors need to be carefully observed for flare after switching from TCZ-IV to TCZ-SC.

We describe the occurrence of acute type A aortic dissection in a patient with situs inversus totalis. A 37-year-old man presented to the emergency department with acute chest pain. Initial chest X-ray findings showed a right-sided heart and a left-sided liver. Contrast-enhanced computed tomography revealed a Stanford type A acute aortic dissection, aortic root dilatation, and situs inversus totalis. All of the thoracic structures were mirror-image reversed and an abnormal coronary artery was observed. The Bentall operation was performed. This report demonstrates that computed tomography and echocardiography were useful for understanding the anatomy and the presence or absence of concurrent anomalies in a patient with situs inversus totalis. The patient’s postoperative course was uneventful.

Ultrasound-guided percutaneous radiofrequency (RF) ablation has become one of the most promising local cancer therapies for both resectable and nonresectable hepatic tumors. Although RF ablation is a safe and effective technique for the treatment of liver tumors, the outcome of treatment can be closely related to the location and shape of the tumors. There may be difficulties with RF ablation of tumors that are adjacent to large vessels or extrahepatic heat-vulnerable organs and tumors in the caudate lobe, possibly resulting in major complications or treatment failure. Thus, a number of strategies have been developed to overcome these challenges, which include artificial ascites, needle track ablation, fusion imaging guidance, parallel targeting, bypass targeting, etc. Operators need to use the right strategy in the right situation to avoid the possibility of complications and incomplete thermal tissue destruction; with the right strategy, RF ablation can be performed successfully, even for hepatic tumors in high-risk locations. This article offers technical strategies that can be used to effectively perform RF ablation as well as to minimize possible complications related to the procedure with representative cases and schematic illustrations.
Ascites ; Bile Duct Diseases/etiology ; Carcinoma, Hepatocellular/*surgery/ultrasonography ; Catheter Ablation/adverse effects ; Humans ; Liver Neoplasms/*surgery/ultrasonography ; Neoplasm, Residual/etiology

The purpose of this study was to establish a prediction rule for severe illness in adult patients hospitalized with pandemic influenza A (H1N1) 2009. At the time of initial presentation, the baseline characteristics of those with severe illness (i.e., admission to intensive care unit, mechanical ventilation, or death) were compared to those of patients with non-severe illnesses. A total of 709 adults hospitalized with pandemic influenza A (H1N1) 2009 were included: 75 severe and 634 non-severe cases. The multivariate analysis demonstrated that altered mental status, hypoxia (PaO2/FiO2 < or = 250), bilateral lung infiltration, and old age (> or = 65 yr) were independent risk factors for severe cases (all P < 0.001). The area under the ROC curve (0.834 [95% CI, 0.778-0.890]) of the number of risk factors were not significantly different with that of APACHE II score (0.840 [95% CI, 0.790-0.891]) (P = 0.496). The presence of > or = 2 risk factors had a higher sensitivity, specificity, positive predictive value and negative predictive value than an APACHE II score of > or = 13. As a prediction rule, the presence of > or = 2 these risk factors is a powerful and easy-to-use predictor of the severity in adult patients hospitalized with pandemic influenza A (H1N1) 2009.
APACHE ; Adult ; Aged ; Antiviral Agents/therapeutic use ; Female ; Hospitalization ; Humans ; Influenza A Virus, H1N1 Subtype/*isolation & purification ; Influenza, Human/drug therapy/*epidemiology/mortality ; Intensive Care Units ; Male ; Middle Aged ; Pandemics ; Predictive Value of Tests ; ROC Curve ; Respiration, Artificial ; Risk Factors ; Severity of Illness Index

BACKGROUND: The aim of this study was to investigate the effects of preoperative statin therapy on myocardial protection and morbidity endpoints following off-pump coronary bypass graft surgery (OPCAB) in patients with elevated serum high-sensitivity C-reactive protein (hs-CRP) levels. METHODS: Of the 492 patients who underwent multivessel OPCAB from March 2007 to February 2009, the records of 144 patients whose baseline hs-CRP level > 2 mg/L were reviewed. According to the history of preoperative statin therapy for at least one week, patients were classified as either statin group or control group (72 subjects each). Preoperative and operative characteristics and postoperative data including troponin (Tn)-T level and major morbidity endpoints were obtained and compared. Major morbidity endpoints were defined as permanent stroke, renal dysfunction, hemostatic re-exploration, deep sternal wound infection, and the number of patients requiring prolonged ventilation. RESULTS: Preoperative and operative characteristics were similar between the two groups. There were no significant differences in the incidence of morbidity endpoints between the two groups, except for the number of patients requiring dialysis, which was significantly lower in the statin group (8 vs. 1, P = 0.033). Tn-T level at 24 h after surgery was also significantly lower in the statin group. CONCLUSIONS: In this study, we observed beneficial effects of preoperative statin therapy for at least one week in terms of less myocardial enzyme release and fewer patients requiring dialysis following OPCAB in patients whose preoperative hs-CRP was elevated.
C-Reactive Protein ; Dialysis ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Stroke ; Transplants ; Troponin ; Ventilation ; Wound Infection

BACKGROUND: The aim of this study was to investigate the effects of preoperative statin therapy on myocardial protection and morbidity endpoints following off-pump coronary bypass graft surgery (OPCAB) in patients with elevated serum high-sensitivity C-reactive protein (hs-CRP) levels. METHODS: Of the 492 patients who underwent multivessel OPCAB from March 2007 to February 2009, the records of 144 patients whose baseline hs-CRP level > 2 mg/L were reviewed. According to the history of preoperative statin therapy for at least one week, patients were classified as either statin group or control group (72 subjects each). Preoperative and operative characteristics and postoperative data including troponin (Tn)-T level and major morbidity endpoints were obtained and compared. Major morbidity endpoints were defined as permanent stroke, renal dysfunction, hemostatic re-exploration, deep sternal wound infection, and the number of patients requiring prolonged ventilation. RESULTS: Preoperative and operative characteristics were similar between the two groups. There were no significant differences in the incidence of morbidity endpoints between the two groups, except for the number of patients requiring dialysis, which was significantly lower in the statin group (8 vs. 1, P = 0.033). Tn-T level at 24 h after surgery was also significantly lower in the statin group. CONCLUSIONS: In this study, we observed beneficial effects of preoperative statin therapy for at least one week in terms of less myocardial enzyme release and fewer patients requiring dialysis following OPCAB in patients whose preoperative hs-CRP was elevated.
C-Reactive Protein ; Dialysis ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Stroke ; Transplants ; Troponin ; Ventilation ; Wound Infection

(S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-HT2A, Ki=0.61 nM, 5-HT2C, Ki=20.7 nM) and dopamine (D2, Ki=45.9 nM, D3, Ki=42.1 nM) receptors with over 10~100-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing (ED50=0.93 mg/kg) and DOI-induced head twitch (ED50=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine (ED50=0.54 mg/kg) and the avoidance response (ED50=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose (ED50=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.
Amphetamine ; Animals ; Antipsychotic Agents ; Brain ; Catalepsy ; Dopamine ; Head ; Mice ; Rats ; Schizophrenia ; Serotonin

PURPOSE: Authors evaluated results of palatoplasty by speech analysis in bilateral, unilateral complete, and unilateral incomplete and submucous cleft palate patients. METHODS: The speech outcomes were studied in 15 bilateral, 28 unilateral complete, and 46 unilateral incomplete and submucous cleft palate patients who underwent push-back palatoplasties from January 1998 to July 2004. The patients were divided into 2 groups as 3 to 6, 7 to 10-year-old and compared with 20 normal children(control groups were divided into 10 children on each side). Nasal emission test, hypernasality test, and articulation test were done by speech evaluation table which was composed of 39 different words. RESULTS: In all speech evaluation tests, the group of bilateral cleft palate patients got the worst score. And 7 to 10-year-old groups got better score when compared to the same type cleft palate. CONCLUSION: Bilateral cleft palate patients have many more speech problems than other patients. In cleft palate patients, the speech problem was improved with ages, postoperatively. And the speech therapy can improve the operative outcomes.
Child ; Cleft Palate ; Humans ; Speech Therapy

OBJECTIVE: Schizophrenia, a devastating mental disorder, displays a wide range of cognitive impairments including attentional impairment. Prepulse inhibition (PPI), in which a startle response to a loud acoustic noise is reduced by a preceding auditory stimulus of a lower intensity, is impaired in schizophrenic patients and rats injected with apomorphine (APO) or phencyclidine (PCP) mimicking attentional deficits in schizophrenics. Here we examined therapeutic efficacy of a newly developed atypical antipsychotic compound (YKP1447;YKP) on PPI impairment induced by various doses of APO and PCP. METHODS: This study was composed of 3 experiments. YKP (0.5-15 mg/kg) or vehicle (VEH) was administered 15 min before the injection of APO (0.5 mg/kg, Exp1) or PCP (2.0 mg/kg, Exp2:1.5 mg/kg, Exp3). They were then tested for PPI in which a mix of startle stimulus and prepulse was presented. RESULTS: APO or PCP treatment effectively impaired PPI in tested animals (VEH/APO or VEH/PCP). Impaired PPI in APO group was reversed in animals that were pretreated with YKP (5-10 mg/kg) (Exp1). However YKP treatment was not effective in PCP group (Exp2-3). CONCLUSION: High concentration of YKP pretreatment had antipsychotic effect on APO-induced impairment in attentional function suggesting that the compound could potentially be used to treat cognitive impairment due to increased dopaminergic receptorbinding.
Acoustics ; Animals ; Antipsychotic Agents ; Apomorphine ; Humans ; Mental Disorders ; Noise ; Phencyclidine ; Rats ; Schizophrenia