Search

The impact of diabetes mellitus (DM) on the survival of patients with hepatocellular carcinoma (HCC) is still unclear. The present study aims to draw a firm conclusion in terms of evaluating the impact of DM on the prognosis of HCC after hepatectomy.The pattern of recurrence for HCC was often stratified into early-stage (2 years) and late-stage (≥2 years) recurrence. Because the early-stage recurrence was mainly attributed to aggressive tumor pathological characteristics, patients who recurrence or die within 2 years were excluded. Cumulative overall survival (OS) and recurrence-free survival (RFS) were determined by the method of Kaplan-Meier, and the independent risk factors of OS/RFS were determined by Cox regression analysis.A total of 426 patients were eventually included. The 3- and 5-year OS in patients with and without DM was 83.7%, 55.1%; and 90.9%, 77.4%, respectively. Multivariate analysis showed that DM was an independent risk factor for OS (HR 1.166, 95% CI 1.056-2.036,DM is an independent risk factor for long-term prognosis in patients with HCC. Patients with DM after hepatectomy for HCC, thus, need to actively control DM and closer follow-up.

With technical development and evolution of endoscopic instruments, endoscopic spinal surgery has become one of the standard treatments for various lumbar spinal diseases ranging from a simple contained disc to complicated cases such as highly migrated disc herniation and other pathology combined with bony degeneration to produce foraminal and canal stenosis. Favorable clinical results of endoscopic decompression for lumbar stenotic disease were reported by several authors. However, studies have also reported limitations, such as steep learning curves and a relatively high complication rate compared with conventional techniques. The endoscopic lumbar decompression technique consists of many essential skills to manage different endoscopic anatomic structures of the spine. From the perspective of surgical completion and safety, this article discusses issues related to technical considerations in endoscopic lumbar decompression.

We investigated the association between transient receptor potential vanilloid (TRPV) expression in human urothelium tissue and lower urinary tract dysfunction (LUTD).We prospectively enrolled men who planned to undergo surgical treatment for benign prostatic obstruction to analyze TRPV1 and TRPV4 expression in the urothelium using enzyme-linked immunosorbent assay and immunofluorescence staining. Patients were divided into two groups based on urodynamics: the detrusor underactivity (DU) group and the non-DU group. Levels of TRPV1 and TRPV4 were compared between the two groups. We also divided patients into two groups according to degree of subjective urinary urgency symptoms using a 5-point urinary sensation scale and compared the differences in TRPV1 and TRPV4 levels between the two groups. The correlations between urodynamic parameters with TRPV1 or TRPV 4 in all patients were also analyzed.The levels of TRPV1 and TRPV 4 were not significantly different between the DU group (n=10) and the non-DU group (n=11). When we divided the patients according to degree of subjective urgency, the level of TRPV1 was not significantly different between the urgency group (n=10) and the non-urgency group (n =11), but the level of TRPV4 was significantly increased in the urgency group (p=0.029). There was no significant correlation between the level of TRPV1 or TRPV4 and urodynamic parameters in any patients.TRPV4 could be a useful diagnostic biomarker for patients with LUTD.

Purpose. The purpose of our study is to compare the results of spinal decompression using the full-endoscopic interlaminar technique, tubular retractor, and a conventional microsurgical laminotomy technique and evaluate the advantages and clinical feasibility of minimally invasive spinal (MIS) lumbar decompression technique in the lumbar canal and lateral recess stenosis. Methods. The authors retrospectively reviewed clinical and radiological data from 270 patients who received microsurgical (group E: 72 patients), tubular (group T: 34 patients), or full-endoscopic decompression surgery (group E: 164 patients) for their lumbar canal and lateral recess stenosis from June 2016 to August 2017. Clinical (VAS, ODI, and Mcnab criteria), radiologic (spinal canal diameter, segmental dynamic angle, and disc height), and surgical outcome parameters (CPK level, Operative time, blood loss, and hospital stay) were evaluated pre- and postoperatively and compared among the three groups by means of statistical analysis. Failed cases and complications were reviewed in all groups. Results. The mean follow-up period was 6.38 months. The Overall clinical success rate was 89.4%. All groups showed favorable clinical outcome. The clinical and radiologic results were similar in all groups. Regarding surgical outcome, group E showed longer operation time than group M and T (group E: 84.17 minutes/level, group M: 52.22 minutes/level, and group T: 66.12 minutes/level) (p Conclusions. MIS decompression technique is clinically feasible and safe to treat the lumbar canal and lateral recess stenosis, and it has many surgical advantages such as less muscle trauma, minimal postoperative back pain, and fast recovery of the patient compared to traditional open microscopic technique.

Acute Cystitis Symptom Score (ACSS) is a simple self-reporting questionnaire initially developed in Uzbek language to help diagnose acute uncomplicated cystitis (AUC). The purpose of this study was to translate the ACSS to Korean and validate the Korean version of ACSS using Korean-speaking women.The original version of ACSS in Uzbek was translated into the target (Korean) version according to internationally accepted guidelines for the translation and cultural adaptation. Cognitive interviews were then conducted for five women with symptoms of AUC and five women without AUC who were native speakers of the Korean language to investigate the clarity, understandability, and acceptability of the translation. The final Korean version of the ACSS was tested in 50 women (31 AUC patients and 19 controls) for clinical validation.Reliability test for 9 questions (6 questions about typical symptoms of AUC, and 3 questions on quality of life) showed high values (Cronbach's alpha=0.853). The sum score of typical symptoms showed the highest balance for diagnostic sensitivity and specificity (area under the ROC curve=0.935). Sensitivity and specificity to predict AUC were 90.3% and 89.5% at cut-off score 6 of the typical domain.The Korean version of the ACSS showed high levels of reliability and validity, similar to other validated versions in different languages. It will play an important role in practice and/or clinical research for diagnosis and treatment efficacy monitoring of Korean-speaking women suffering from AUC.

We performed a nationwide epidemiological study of testicular torsion using the National Health Insurance System database for the entire male population of Korea.Age, sex, socioeconomic status, regional information, and diagnostic codes were retrieved from January 2009 to December 2019. To clearly identify the diagnosis of testicular torsion, patients who had not undergone orchiectomy or orchiopexy were excluded from the study. Multivariable logistic regression models were used to analyze the association between demographic characteristics and testicular loss.The overall incidence of testicular torsion in males was 2.02 cases per 100,000 person-years and 6.99 cases per 100,000 person-years in males under 19 years of age. Testicular torsion most commonly occurred either in infancy or adolescence. The total testicular salvage rate was 75.22% and highest in children at 79.91%. The rate of orchiectomy was high in infancy and in the oldest patients. We determined that age distribution was related to the risk of testicular loss.This study is the first nationwide epidemiological study of testicular torsion, which contains the entire Korean population. Although the testicular salvage rate in Korea was higher compared to other countries, it is necessary to educate males under 19 years of age on the seriousness of acute testicular pain to minimize the possibility of testicular loss.

Objective Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug‐refractory essential tremor (ET). Although stimulation‐induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet. Methods Twelve patients with ET and bilateral VIM‐DBS with self‐reported dysphagia after VIM‐DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim‐ON and in the stim‐OFF condition. Presence, severity, and improvement of dysphagia were recorded. Results During stim‐ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim‐OFF, all patients experienced a statistically significant improvement of swallowing function. Interpretation VIM‐DBS may have an impact on swallowing physiology in ET‐patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.

Studies about social functioning in obsessive-compulsive disorder (OCD) are lacking, even though neuroimaging studies and metacognition evaluation results suggest abnormal neural responses during social interactions. This study examined neural responses of OCD patients during handshakes with a virtual avatar. Because of the nature of the handshaking task, we expected that OCD patients with predominantly contamination/washing symptoms (CON) would show different neural responses compared to healthy controls (HCs) and to disease-controlled (NCON) patients. Thirteen CON, 13 NCON, and 18 HC participants performed handshake tasks with clean or dirty virtual avatars while undergoing functional magnetic resonance imaging. During handshakes with a clean avatar, deactivation in the left anterior cingulate cortex was found in CON patients compared to NCON and HC subjects. This cortical deactivation also occurred with dirty-avatar handshakes, but the difference was significant only between the two OCD groups and HC patients. Deactivation in the left anterior cingulate cortex was correlated with both OCD symptom severity and social anxiety traits. This cortical deactivation in OCD, especially in CON patients, suggests that social dysfunction in OCD may be due to interactions between OCD symptoms and impairment in social cognition, including emotional processing.

We aim to investigate the role of mitochondrial DNA (mtDNA), a novel endogenous pro-inflammatory cytokine, in the development of ventilator-induced lung injury (VILI). Moreover, the protective effect of epigallocatechin gallate (EGCG) on VILI through inhibiting local mtDNA release was examined.From March 2015 to March 2016, bronchoalveolar lavage fluid (BALF) from 36 patients with VILI and well-matched 36 patients without VILI after major surgery were consecutively collected. The expression levels of mtDNA and inflammatory cytokines in BALF were tested. SD rats were divided into five groups: control, low tidal volume (7 ml/kg) group, high tidal volume (HTV, 40 ml/kg) group, HTV+low dose EGCG and HTV+high dose EGCG groups. BALF were collected to examine the expression levels of mtDNA and several inflammatory cytokines and the lung tissue was harvested for pathological examinations. In addition, cyclic stretch cell culture was used and culture media was collected to analyze expressions of inflammatory cytokines. Administration of mtDNA in a rat model and in vitro cell culturing were used to confirm its pro-inflammatory properties in the development of inflammatory lung injury.A Significant elevation of mtDNA was detected in BALF from patients with VILI (581 ± 193 vs. 311 ± 137, p 0.05) and also in rats ventilated with HTV. EGCG could significantly inhibit HTV-induced local mtDNA release and attenuate the level of inflammatory lung injuries (reduced infiltration of local inflammatory cells, lower lung wet/dry ratio and expression levels of inflammatory cytokines). The beneficial effects of EGCG on preventing inflammatory lung injuries were in a concentration-dependent manner. Meanwhile, higher expression levels of mtDNA and inflammatory cytokines were observed in the media of cyclic stretched cell culture compared to those in the control group (p 0.05). Furthermore, intra-tracheal administration of mtDNA in rats could lead to a marked increase of local inflammatory cytokines and subsequent inflammatory lung injuries (p 0.05). And by adding mtDNA into the cell culture, higher level of inflammatory cytokines in the media was detected (p 0.05). EGCG also showed preventive effects on inflammatory responses on a concentration-dependent manner (p 0.05).The increased expression level of mtDNA and subsequent inflammatory cytokines overproduction may play an important role in the development of VILI. EGCG may be a potential novel therapeutic candidate for protection against VILI by inhibiting the local release of mtDNA.

Purpose We evaluated changes in the expression of uroplakin (UP) in the urothelium of patients with ulcerative interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and methods Bladder samples were collected from 19 patients with ulcerative IC/BPS who were treated with augmentation ileocystoplasty and from 5 control patients. Frequency-volume charts, the pain visual analogue scale (VAS), and the O'Leary-Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI) were used to evaluate the patients' symptoms preoperatively. The expression levels of UP-Ib and UP-III in the urothelium were compared between the IC/BPS patients and control patients. Results Sixteen women and three men with IC/BPS were evaluated. Their values for preoperative mean voiding frequency, number of nocturia episodes, and functional bladder capacity as recorded in frequency-volume charts were 21.1±12.8, 5.9±4.2, and 151.1±62.7 mL, respectively. The mean pain VAS, ICSI, and ICPI scores were 8.4±1.3, 17.7±2.2, and 14.7±1.8, respectively. Immunofluorescence staining showed that UP-Ib and UP-III were localized in the urothelium. Upon Western blot analysis, the expression of UP-III was significantly increased in the IC/BPS group compared with the control group. However, expression of UP-Ib did not differ significantly between the IC/BPS and control groups. Conclusions UP-III was significantly upregulated in patients with ulcerative IC/BPS. UP-III is a potential biomarker for the diagnosis of ulcerative IC/BPS.

Objectives To assess Asian data from Global Prevalence Study on Infections in Urology (GPIU study) which has been performed more than 10 years. Methods Seventeen Asian countries participated in the GPIU study between 2004 and 2013. Data for these countries were collected from the web-based GPIU database. The point prevalence of urinary tract infections (UTI) and antimicrobial susceptibility of representative pathogens were analysed for Asian geographic regions. Results A total of 6706 patients (5271 male, 1435 female) were assessed during the study period, and 659 patients were diagnosed with a UTI (9.8%). Of these UTI patients, 436 were male and 223 were female. Mean patient age was 54.9 ± 19.3 years. Pyelonephritis and cystitis were the most common clinical diagnoses, representing 30.7% and 29.9% of patients, respectively. Escherichia coli was the most frequently identified uropathogen (38.7%). For the patients with urinary tract infection, cephalosporins were the most frequently used antibiotics (34.4%), followed by fluoroquinolones (24.1%), aminoglycosides (16.8%). Fluoroquinolone resistance was relatively high (ciprofloxacin 54.9%, levofloxacin 39.0%), and cephalosporin resistance 42% (42.5–49.4%). Of the antibiotics evaluated, uropathogens had maintained the highest level of susceptibility to amikacin and imipenem (24.9% and 11.3% resistance rates, respectively). Conclusion Uropathogens in many Asian countries had high resistance to broad-spectrum antibiotics. Knowledge of regional and local resistance data and prudent use of antibiotics are important for proper management of UTI in Asian countries.

Background Aortoesophageal fistula (AEF) and arch pseudoaneurysm are rare complications induced by a foreign body, and considerable controversy remains regarding the appropriate management strategies. We herein report a successful one-stage hybrid treatment in a patient with AEF and arch pseudoaneurysm. Case presentation The patient, a 40-year-old man, presented to the emergency room because of intense retrosternal discomfort for 3 days and hematemesis for 3 h. The esophagoscopy and thoracic enhanced computed tomography (CT) showed two irregular mural ulcers in the esophagus and a large saccular pseudoaneurysm at the aortic isthmus, respectively. The laboratory examinations confirmed no widespread inflammation and infection. We have successfully performed a successful one-stage hybrid treatment for this patient. Six-month follow-up shows the patient is in good condition and the esophagoscopy reveals the two mural ulcers had completely healed. Conclusion The treatment decision-making process should depend upon the patients’ specific situations. Our case suggest the one-stage hybrid treatment could be an valuable alternative in some selected patients. Electronic supplementary material The online version of this article (10.1186/s12893-018-0335-1) contains supplementary material, which is available to authorized users.

Objective The purpose of this study was to compare radiologic and clinical outcomes in patients with L4-5 lumbar spondylolisthesis who have undergone either instrumented anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), or posterior lumbar interbody fusion (PLIF), especially with regard to the development of adjacent segment disease (ASD). Methods Eighty-two patients with preoperative L4-5 spondylolisthesis and minimal ASD who underwent instrumented L4–5 fusion were divided into 3 groups according to the surgical approach used for treatment (ALIF: 27 patients, LLIF: 24 patients, PLIF: 31 patients). Radiographic measurements including preoperative and postoperative foraminal and disk height, segmental and lumbar lordosis, percentage of vertebral slippage, and reduction rate were reviewed. The incidence of ASD and clinical outcomes were evaluated and compared between the 3 groups. Results ASD was found in 37.0% (10/27), 41.7% (10/24), and 64.5% (20/31) of the patients in the ALIF, LLIF, and PLIF groups, respectively (mean follow-up duration: 35.42 ± 9.35 months). The ALIF and LLIF groups had significantly increased disk and foraminal height compared with the PLIF group. The ALIF group had significantly improved lordosis compared with the PLIF and LLIF groups. There were no statistically significant intergroup differences in clinical outcomes assessed by visual analog scale and Oswestry Disability Index. Conclusion The 3 different fusion techniques investigated can all produce good outcomes in treating lumbar spondylolisthesis in L4-5, but ALIF and LLIF are more advantageous in preventing the development of ASD.

We investigated the efficacy and safety of desmopressin add-on therapy for men with persistent nocturia on α-blocker for lower urinary tract symptoms in this placebo controlled study.The study included men 40 to 65 years old with lower urinary tract symptoms and persistent nocturia despite α-blocker therapy for at least 8 weeks. Patients were randomized to once daily placebo or desmopressin 0.2 mg for 8 weeks. The primary end point was to assess changes in the mean number of nocturia episodes from baseline to the final assessment. Other secondary end points and adverse events were evaluated.A total of 86 patients were randomized to treatment, including placebo in 39 and desmopressin 0.2 mg in 47. Baseline characteristics were similar in the 2 groups. The desmopressin add-on group was significantly superior to placebo in terms of the change from baseline in the mean number of nocturia episodes (-1.13 ± 0.92 vs -0.68 ± 0.79, p = 0.034), the changes in nocturnal urine volume (p0.001), total I-PSS (International Prostate Symptom Score) (p = 0.041), the nocturnal polyuria index (p = 0.001) and ICIQ-N (International Consultation on Incontinence Questionnaire-Nocturia) (p = 0.001), and the willingness to continue (p = 0.025). The incidence of adverse events in the desmopressin add-on group was similar to that in the placebo group. Most adverse events were mild.Desmopressin add-on therapy in men 40 to 65 years old with persistent nocturia on α-blocker monotherapy for lower urinary tract symptoms is effective and well tolerated.

Neuroinflammation has been raised as a candidate of unifying pathogenesis and a target of a disease-modifying strategy for Alzheimer's disease (AD). Aminoacyl-tRNA synthetase complex (ARS)-interacting multifunctional protein 1 (AIMP1) is a cytokine that is known to amplify the actions of tumor necrosis factor-α and to be involved in microglial activation and neuronal death. In this respect, AIMP1 could be a plausible target for the treatment of AD. Therefore, we aimed to examine whether anti-AIMP1 antibody could exert therapeutic effects against cognitive impairment using 3xTg-AD mice. Through the passive avoidance test, we found that an intraperitoneal injection of anti-AIMP1 antibody over 4 weeks was effective in protecting memory function in 3xTg-AD mice (16 weeks old). In addition, to address the translational implications of AIMP1, we measured blood AIMP1 levels in patients with AD (n=22), mild cognitive impairment (n=25), and normal cognition (n=23). Blood AIMP1 levels were associated negatively with global cognitive function and were significantly higher in individuals with a higher degree of medial temporal lobe atrophy, which is one of the representative clinical markers of AD. Our results suggested a possible association of AIMP1 with AD pathogenesis, as well as the potential of the anti-AIMP1 antibody as a novel therapeutic option for AD.

Purpose To investigate the change in urinary urgency and predictors of urgency improvement after holmium laser enucleation of the prostate (HoLEP) in men with benign prostatic hyperplasia (BPH). Materials and methods We retrospectively analyzed the medical records of patients who were treated with HoLEP for BPH and had preoperative urgency measuring ≥3 on a 5-point urinary sensation scale. Those with prostate cancer diagnosed prior to or after HoLEP, a history of other prostatic and/or urethral surgery, moderate to severe postoperative complications, and neurogenic causes were excluded. Patients who had improved urgency with antimuscarinic medication after HoLEP were excluded. We divided the patients into 2 groups based on urgency symptoms 3 months after HoLEP: improved and unimproved urgency. Improved urgency was defined as a reduction of 2 or more points on the 5-point urinary sensation scale. Preoperative clinical and urodynamic factors as well as perioperative factors were compared between groups. Results In total, 139 patients were included in this study. Voiding parameters in all patients improved significantly after HoLEP. Seventy-one patients (51.1%) had improved urgency, while 68 (48.9%) did not show any improvement. A history of acute urinary retention (AUR) and postvoid residual were associated with postoperative urgency improvement in univariate analysis. In multivariate analysis, a history of AUR was an independent factor affecting urgency improvement. Conclusions A preoperative history of AUR could influence the change in urgency after HoLEP surgery in patients with BPH.

We investigated treatment satisfaction with flexible-dose fesoterodine in patients with overactive bladder (OAB) who were dissatisfied with previous anticholinergic therapy.The subjects were prescribed fesoterodine 4 mg for 4 weeks and fesoterodine 4 mg or 8 mg for another 8 weeks. The primary end point of this study was patients' satisfaction after 12 weeks of fesoterodine treatment on a five-point Likert scale. Secondary end points included a change in the number of daytime micturition, urgency incontinence episodes, urgency episodes, and nocturnal micturition in a 24-hour period from baseline to final assessment.Overall, 84 patients were assigned to the treatment group in this study and 63 patients completed the 12-week treatment course. A final fesoterodine dose of 4 mg and 8 mg was used by 45 (71.4%) and 18 (28.6%) patients, respectively. The satisfaction and dissatisfaction rates at 12 weeks were 69.9% and 14.2%, respectively. Mean changes in the daytime micturitions (9.73 ± 4.72 vs. 7.76 ± 2.86), urgency episodes (7.73 ± 5.68 vs. 3.71 ± 4.09), and nocturnal micturitions (2.13 ± 1.36 vs. 1.68 ± 1.12) in 24 hours improved significantly with flexible-dose fesoterodine treatment (P.05). Most adverse events were mild and none were severe.The flexible dose fesoterodine represents an alternative treatment modality in patients with OAB who are dissatisfied with previous anticholinergic therapy in Korea.

Introduction. The multifocal lumbar pathology including disc herniation and stenosis in the spinal canal or foramen has been considered the most difficult to approach surgically. It often requires mandatory dual approaches and/or fusion techniques. Traditional percutaneous endoscopic lumbar transforaminal and interlaminar approach has been focused on unifocal disc herniation. However, the development of endoscopic spinal instruments and surgical technique has broadened surgical indication and therapeutic boundary in endoscopic spine surgery. Cases Presentation. The authors present outcomes of four patients with multilumbar pathology including highly inferior migrated disc combined with lateral recess stenosis, multifocal disc herniation, bilateral disc herniations in spinal canal and foraminal disc herniation combined with central canal stenosis. They were successfully treated by percutaneous uniportal full endoscopic approach with single incision. Conclusion. Percutaneous endoscopic spine surgery is a safe and effective tool to figure out multilumbar pathology in a minimal invasive way.

Background: Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. Objective: To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. Methods: Four hundred sixty-two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. Results: Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18–1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12–1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19–1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11–1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: “severe” (n = 13; 12%), “intermediate” (n = 31; 29%), and “moderate” (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. Conclusion: Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxia. © 2019 International Parkinson and Movement Disorder Society., SCOPUS: ar.j, info:eu-repo/semantics/published

Tauroursodeoxycholic acid (TUDCA) is known to prevent apoptosis through the Bax pathway and to promote neovascularization by enhancing the mobilization of stem cells, their differentiation. This study was performed to investigate the effect of TUDCA on erythropoiesis in hematopoietic stem cells (HSCs). Since erythropoiesis of CD34+ HSCs is divided into four phases, the total cell number, viable cell number, cell viability, cell morphology, and expressed erythroid markers in each phase were examined. The number of viable control cells and their viability did not differ from those of the TUDCA-treated cells in phase I and II. However, TUDCA increased cell viability compared to the control in phases III and IV. Cell distribution differed that the immature erythroid cell number was higher for the TUDCA-treated cells than for the control cells until phase III, but all developed into RBCs in the last. The final RBC number and viability was significantly higher in TUDCA-treated cells compared to the control cells. Taken together, we suggest that TUDCA addition to cell cultures for artificial RBC production could be used as a new protocol for improving the viability of RBCs.

Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-[Formula: see text]B transcriptional activation and the nuclear translocation of NF-[Formula: see text]B transcription factors. Moreover, Lb-EE inhibited IKK[Formula: see text]/[Formula: see text]-induced activation of the NF-[Formula: see text]B signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKK[Formula: see text]/[Formula: see text]-mediated activation of the NF-[Formula: see text]B signaling pathway during macrophage-mediated inflammatory responses.

To evaluate the outcomes of valve replacement of endocarditis using bioprothetic and mechanical valves.This study comprised 52 patients [mean age (47±18) yr.,mean follow-up time (6.2±3.8) years] underwent valve endocarditis with bioprotheses,The control group were matched (3∶1) with 156 patients of endocarditis underwent mechanical valves replacement using the following variables: age±5 yr.,body mass index (BMI)±20%,time of operation±1 year,replacement position and sex ratio. And evaluate the effects of using bioprothetic and mechanical valves on perioperative and long-term outcomes of valve replacement of endocarditis.The perioperative mortality of the patients receiving bioprothetic and mechanical valves were 17.3%±2.2% and 19.9%±1.8%,respectively,which was independent of valve type (Perioperative mortality and long-term survival are independent to valve types in patients with endocarditis. Mechanical valve shows potential advantage compared with bioprothetic valve in the patients younger than 60-year-old.

To evaluate the efficacy and safety of silodosin on nocturia in patients with benign prostatic hyperplasia (BPH).This was a 12-week, single-arm, open-label, prospective, multicenter study. The study included men aged 50 years or older with nocturia (≥2 events/night) based on a voiding diary, an International Prostate Symptom Score (IPSS) ≥8, and a quality of life score ≥3. Enrolled patients received 8 mg of silodosin once daily for 12 weeks. We evaluated changes in the mean number of nocturia episodes (using a voiding diary) from baseline to the final assessment. Safety assessments included the rate of adverse events and adverse drug reactions.There were 118 patients included in the safety evaluation analysis, and 112 patients in the full analysis set group. The number of nocturia episodes decreased significantly after 12 weeks of treatment with silodosin (-1.12 ± 1.05, P.0001). The secondary efficacy variables, including IPSS, overactive bladder symptom score and International Consultation on Incontinence Questionnaire-Nocturia score, also improved with treatment (P.0001). There were abnormal drug reactions in 11.8% of patients. The most common adverse drug reaction was an ejaculatory disorder (7.6%). There were no significant adverse drug reactions reported.Silodosin was found to be safe and effective in the treatment of nocturia in patients with BPH.

To observe the efficacy and safety of biological heart valves (BHV) and mechanical heart valves (MHV) in childbearing age women (CAW) during the perinatal and short-moderate term postoperative (SMTP) periods.There were 33 patients [(25.2±7.1) yr.] undergoing BHV replacement from September 2009 to December 2014 had completely followed-up,whose data were retrospectively collected. A 1∶4 matching study was conducted,therefore there were 132 patients undergoing MHV were included. The collected date included the clinical outcomes in the perioperative, perinatal,and SMTP period event-free survival (EFS) was determined using the Kaplan-Meier method and compared using the log-rank test.The average follow-up time was (5.8±3.6) years,and the two groups had similar baseline . The clinical outcomes difference of perinatal and SMTP between the two groups were not significant. There were 17 patients in BHV group and 60 in MHV group with pregnancy and birth experiences (PBE),which also showed no significant difference for adverse events both in the maternity and in the fetus. The rates of valve-related adverse events of BHV replacement patients with and without PBE were 5.9% and 0% at 3 years after the operation, and 11.8% and 5.9% after 5 years. PBE was not identified as an adverse prognostic factor for EFS (Either artificial BHV or MHV replacement can achieve ideal SMTP effect in CAW. BHV seems not superior to MHV. Pregnancy and birth experience will not increase the risk of BHV relevant adverse events.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-associated mortality worldwide. Right open reading frame kinase 2 (RIOK2) and nin one binding protein (NOB1) are important accessory factors in ribosome assembly. In our previous study, RIOK2 and NOB1 were revealed to be highly expressed in NSCLC, and were associated with the clinicopathological characteristics of patients with NSCLC, i.e. TNM clinical stage, lymph node metastasis and differentiation. In addition, RIOK2 expression was correlated with NOB1. To further explore the mechanism and the RIOK2 and NOB1 signaling pathway, microRNA (miR) regulation was analyzed. The tumor suppressor miR‑145 has been reported to be lowly expressed in numerous types of human cancer; in the present study, the expression levels of miR‑145 were decreased in patients with NSCLC. Furthermore, RIOK2 and NOB1 were predicted to be the direct targets of miR‑145 using bioinformatics software; this was further validated using a dual luciferase reporter assay. In addition, the protein expression levels of RIOK2 and NOB1 were inhibited in response to miR‑145 overexpression, thus resulting in the suppression of cell viability, migration and invasion. These results suggested that RIOK2 and NOB1 may be potential targets in the treatment of NSCLC, and miR‑145 may be considered a therapeutic inhibitor of both genes.

To investigate the usefulness of the ellipsoid formula for assessing compensatory hypertrophy of the contralateral kidney on pre-operative and post-operative CT in renal cell carcinoma (RCC) patients.We retrospectively identified 389 patients who had radical nephrectomy for RCC between 2011 and 2015. Contrast-enhanced CT was performed within 3 months pre-operative and at 1 year post-operative. The kidney volumes were calculated from CT using the ellipsoid formula. We subdivided patients into three groups based on tumour size (I: ≤4 cm, II: 4-7 cm, III: 7 cm). Volumetric renal parameters were compared and multivariate analyses were performed to determine predictors associated with pre-operative and post-operative compensatory hypertrophy.Kidney volume calculation using the ellipsoid method took a median of 51 s. Group III had a significantly larger median pre-operative contralateral renal volume than Groups I and II (I: 140.4, II: 141.6, III: 166.7 ml, p0.05). However, the median ratio of post-operative contralateral renal volume change was significantly higher in Groups I and II than Group III (I: 0.36, II: 0.23, III: 0.12, p0.001). On multivariate analysis, tumour size revealed the strongest positive association with pre-operative contralateral kidney volume (partial regression coefficient: β = 30.8, 7 cm) and ratio of post-operative contralateral kidney volume change (β = 0.214, I vs III; β = 0.168, II vs III).Kidney volume calculation for assessing pre- and post-operative compensatory hypertrophy of the contralateral kidney in RCC patients can be easily and rapidly performed from CT images using the ellipsoid formula. Advances in knowledge: The ellipsoid formula allows reliable method for assessing pre-operative and post-operative compensatory hypertrophy of the contralateral kidney in RCC.

Aortic valve calcification (AVC), which used to be recognized as a passive and irreversible process, is now widely accepted as an active and regulated process characterized by osteoblastic differentiation of aortic valve interstitial cells (AVICs). Apelin, the endogenous ligand for G-protein-coupled receptor APJ, was found to have protective cardiovascular effects in several studies. However, the effects and mechanisms of apelin on osteoblastic differentiation of AVICs have not been elucidated. Using a pro-calcific medium, we devised a method to produce calcific human AVICs. These cells were used to study the relationship between apelin and the osteoblastic calcification of AVICs and the involved signaling pathways. Alkaline phosphatase (ALP) activity/expression and runt-related transcription factor 2 (Runx2) expression were examined as hallmark proteins in this research. The involved signaling pathways were studied using the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, and the phosphatidylinositol 3-kinase (PI3-K) inhibitor, LY294002. The results indicate that apelin attenuates the expression and activity of ALP, the expression of Runx2, and the formation of mineralized nodules. This protective effect was dependent on the dose of apelin, reaching the maximum at 100 pM, and was connected to activity of ERK and Akt (a downstream effector of PI3-K). The activation of ERK and PI3-K initiated the effects of apelin on ALP activity/expression and Runx2, but PD98059 and LY294002 abolished the effect. These results demonstrate that apelin attenuates the osteoblastic differentiation of AVICs via the ERK and PI3-K/Akt pathway.

Although serum bile acid concentrations are approximately 10 µM in healthy subjects, the crosstalk between the biliary system and vascular repair has never been investigated. In this study, tauroursodeoxycholic acid (TUDCA) induced dissociation of CD34+ hematopoietic stem cells (HSCs) from stromal cells by reducing adhesion molecule expression. TUDCA increased CD34+/Sca1+ progenitors in mice peripheral blood (PB), and CD34+, CD31+, and c-kit+ progenitors in human PB. In addition, TUDCA increased differentiation of CD34+ HSCs into EPC lineage cells via Akt activation. EPC invasion was increased by TUDCA, which was mediated by fibroblast activating protein via Akt activation. Interestingly, TUDCA induced integration of EPCs into human aortic endothelial cells (HAECs) by increasing adhesion molecule expression. In the mouse hind limb ischemia model, TUDCA promoted blood perfusion by enhancing angiogenesis through recruitment of Flk-1+/CD34+ and Sca-1+/c-kit+ progenitors into damaged tissue. In GFP+ bone marrow-transplanted hind limb ischemia, TUDCA induced recruitment of GFP+/c-kit+ progenitors to the ischemic area, resulting in an increased blood perfusion ratio. Histological analysis suggested that GFP+ progenitors mobilized from bone marrow, integrated into blood vessels, and differentiated into VEGFR+ cells. In addition, TUDCA decreased cellular senescence by reducing levels of p53, p21, and reactive oxygen species and increased nitric oxide. Transplantation of TUDCA-primed senescent EPCs in hind limb ischemia significantly improved blood vessel regeneration, as compared with senescent EPCs. Our results suggested that TUDCA promoted neovascularization by enhancing the mobilization of stem/progenitor cells from bone marrow, their differentiation into EPCs, and their integration with preexisting endothelial cells. Stem Cells 2015;33:792–805

We investigated changes in the levels of adenosine triphosphate and nitric oxide in the urothelium of men with detrusor underactivity and benign prostatic hyperplasia.We prospectively enrolled in study 30 men who planned to undergo surgical treatment for benign prostatic hyperplasia. The 15 patients with a bladder contractility index less than 100 were assigned to the detrusor underactivity group while the 15 with a bladder contractility index more than 100 were assigned to the no detrusor underactivity group. Bladder mucosal specimens were collected at surgical prostate resection, and adenosine triphosphate and endothelial nitric oxide synthase were analyzed in these specimens. The levels of adenosine triphosphate and endothelial nitric oxide synthase were compared between the 2 groups. The correlation of urodynamic parameters with adenosine triphosphate and endothelial nitric oxide synthase was assessed in all patients.Mean ± SEM endothelial nitric oxide synthase did not significantly differ between the detrusor underactivity and no underactivity groups (3.393 ± 0.969 vs 1.941 ± 0.377 IU/ml, p = 0.247). However, the mean level of adenosine triphosphate in the detrusor underactivity group was significantly lower than in the no detrusor underactivity group (1.289 ± 0.320 vs 9.262 ± 3.285 pmol, p = 0.011). In addition, in all patients adenosine triphosphate positively correlated with the bladder contractility index (r = 0.478, p = 0.018) and with detrusor pressure on maximal flow (r = 0.411, p = 0.046).Adenosine triphosphate was significantly decreased in the urothelium in men with detrusor underactivity and benign prostatic hyperplasia, reflecting the change in detrusor function.

This study was designed to assess the expression levels of bone morphogenic protein-4 (BMP4) in saphenous veins harvested from diabetic patients undergoing coronary artery bypass grafting (CABG), and to investigate its association withFrom January 2013 to December 2014, forty patients with type 2 diabetes mellitus (DM) and risk factors matched non-DM controls (The intimal and medial thickness of the saphenous veins harvested from DM patients were higher than those from non-DM controls. Compared with non-DM patients, the expression level of BMP4 was significantly elevated in diabetic veins (The pre-existing intimal and medial hyperplasia were significantly correlated with the high expression levels of BMP4 in saphenous veins harvested from diabetic patients, implying a potential role of BMP4 in the progression of vein graft stenotic diseases in this cohort of post-CABG patients. Future studies were warranted in investigating novel therapeutic strategy targeting at BMP4 for improving long-term vein graft patency.

Neurobiological models of obsessive-compulsive disorder (OCD) emphasize disturbances of the corticostriatal circuit, but it remains unclear as to how these complex network dysfunctions correspond to heterogeneous OCD phenotypes. We aimed to investigate corticostriatal functional connectivity alterations distinct to OCD characterized predominantly by contamination/washing symptoms. Functional connectivity strengths of the striatal seed regions with remaining brain regions during the resting condition and the contamination symptom provocation condition were compared among 13 OCD patients with predominant contamination/washing symptoms (CON), 13 OCD patients without these symptoms (NCON), and 18 healthy controls. The CON group showed distinctively altered functional connectivity between the ventral striatum and the insula during both the resting and symptom-provoking conditions. Also, the connectivity strength between the ventral striatum and the insula significantly correlated with contamination/washing symptom severity. As common connectivity alterations of the whole OCD subjects, corticostriatal circuits involving the orbitofrontal and temporal cortices were again confirmed. To our knowledge, this is the first study that examined specific abnormalities in functional connectivity of contamination/washing symptom dimension OCD. The findings suggest limbic network dysfunctions to play a pivotal role in contamination/washing symptoms, possibly associated with emotionally salient error awareness. Our study sample allowed us to evaluate the corticostriatal network dysfunction underlying the contamination/washing symptom dimension, which leaves other major symptom dimensions to be explored in the future.

Ascending aortic pseudoaneurysms are rare entities that usually occur secondary to trauma, infection, or as a complication of cardiovascular surgery. We identified a spontaneous large pseudoaneurysm for which no predisposing factor was identified. Such a finding is very rare.

ARS-Interacting Multi-functional Protein 1 (AIMP1) is a cytokine that is involved in the regulation of angiogenesis, immune activation, and fibroblast proliferation. In this study, fibroblast growth factor receptor 2 (FGFR2) was isolated as a binding partner of AIMP peptide (amino acids 6-46) in affinity purification using human bone marrow-derived mesenchymal stem cells (BMMSCs). AIMP1 peptide induced the proliferation of adult BMMSCs by activating Akt, inhibiting glycogen synthase kinase-3β, and thereby increasing the level of β-catenin. In addition, AIMP1 peptide induced the translocation of β-catenin to the nucleus and increased the transcription of c-myc and cyclin D1 by activating the β-catenin/T-cell factor (TCF) complex. By contrast, transfection of dominant negative TCF abolished the effect of AIMP1. The inhibition of Akt, using LY294002, abolished the accumulation and nuclear translocation of β-catenin induced by AIMP1, leading to a decrease in c-myc and cyclin D1 expression, which decreased the proliferation of BMMSCs. An intraperitoneal injection of AIMP1 peptide into C57/BL6 mice increased the colony formation of fibroblast-like cells. Fluorescence activated cell sorting analysis showed that the colony-forming cells were CD29(+)/CD44(+)/CD90(+)/CD105(+)/CD34(-)/CD45(-), which is characteristic of MSCs. In addition, the fibroblast-like cells differentiated into adipocytes, chondrocytes, and osteocytes. Taken together, these data suggest that AIMP1 peptide promotes the proliferation of BMMSCs by activating the β-catenin/TCF complex via FGFR2-mediated activation of Akt, which leads to an increase in MSCs in peripheral blood.

Aims : Reducing craving is a key to success in the treatment of alcohol dependence. The emotion circuit may be involved in pathological craving for alcohol. In this study, we investigated neural correlates of emotional involvement in craving in alcohol dependence. Methods : The study included 17 detoxified alcoholic patients and 25 social drinkers. We used functional magnetic resonance imaging to examine brain activation (blood oxygen level-dependent signals) while participants reported craving and emotion in response to visually presented, alcohol-related stimuli and emotional stimuli. Results : In the craving-rating paradigm, negative emotional stimuli as well as alcohol cues activated craving-related brain regions in alcoholic patients. Activations of the inferior parietal lobule and dorsolateral prefrontal cortex by negative emotional stimuli were negatively correlated with craving; meanwhile limbic activation was positively correlated with craving. For the emotion paradigm, greater limbic activation was evident by alcohol-related stimuli in the alcohol-dependent group. Conclusions : Our findings constitute neural evidence for emotional involvement in pathological craving for alcohol, underscoring the importance of emotion management in abstinent alcoholic patients for relapse prevention.

To assess the anti-adhesive effect of treatment with hyaluronic acid-carboxymethylcellulose following laparoscopic radical prostatectomy. This was a randomized, controlled, single-blind, parallel-group study using hyaluronic acid-carboxymethylcellulose in patients who underwent laparoscopic radical prostatectomy. Sixty patients were enrolled in the study. All patients were randomly assigned to either the hyaluronic acid-carboxymethylcellulose treatment group (n = 30) or the control group (n = 30). Viscera slide ultrasounds and plain X-rays were obtained at enrollment (V0), postoperative week 12 (V1), and 24 (V2). The primary end point was the difference in the excursion distance in the viscera slide ultrasound between V0 and V2. A total of 50 patients completed this study. The average excursion distance at V2 in the experimental group (n = 25) was significantly longer than in the control group (n = 25, 2.7 ± 1.2 vs. 1.3 ± 1.0 cm, respectively; p

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. However, there is a shortage of suitable diagnostic markers for early stages of NSCLC, and therapeutic targets are limited. Right open reading frame (Rio) kinase 2 (RIOK2) and Nin one binding (NOB1) protein are important accessory factors in ribosome assembly and are highly expressed in malignant tumours; moreover, they interact with each other. However, the RIOK2 expression profile and its clinical significance as well as NOB1's mechanism in NSCLC remain unknown. In this study, NSCLC cell lines and 15 NSCLC tumour tissues (paired with adjacent normal lung tissues) were collected for a real-time quantitative PCR (RT-qPCR) analysis. In addition, 153 NSCLC cases and 27 normal lung tissues were used in an immunohistochemical analysis to evaluate the RIOK2 and NOB1 expression profiles, their clinicopathological factors in NSCLC and their correlations with prognoses. RIOK2 and NOB1 were highly expressed in NSCLC cells and tissues, and their expression profiles were significantly associated with the Tumour Node Metastasis (TNM) clinical stage, lymph node metastasis, and differentiation. RIOK2 expression was correlated with NOB1. The results suggested that simultaneously determining the expression of RIOK2 and NOB1 will improve the diagnostic rate in early stages of NSCLC. Moreover, RIOK2 and NOB1 might be potential targets for NSCLC therapy.

The objective was to investigate the expression of endothelial nitric oxide synthase (eNOS) and phosphodiesterase (PDE) 5 in vaginal tissue of premenopausal women experiencing stress urinary incontinence (SUI) with and without sexual dysfunction. Women presenting for treatment of SUI were screened using the Female Sexual Function Index (FSFI) and 10 were selected who met the criteria for female sexual dysfunction (FSD) and 10 asymptomatic controls. Vaginal tissue specimens were obtained from those premenopausal women aged ≥40 years who had had sexual activity ≥2 times every month for the last 6 months and who were scheduled to undergo surgery for SUI. FSD criteria was FSFI scores

The aim of this study is to investigate changes in urinary nerve growth factor (NGF) and prostaglandin E(2) (PGE(2)) in women with overactive bladder (OAB) following anticholinergic treatment.A total of 30 female patients with OAB were enrolled and the control group included 15 healthy women who did not present any bladder symptoms. All subjects with OAB recorded voiding diaries, underwent urodynamic study, and were evaluated for urgency grade. They received anticholinergic treatment for 4 weeks, after which they were again evaluated for urinary urgency grade and voiding diaries. OAB patients were classified into three groups according to the change on the 5-point Urinary Sensation Scale after the treatment: group 1 (no change in urgency grade), group 2 (1 point of improvement), and, group 3 (more than 2 points of improvement). Urinary NGF and PGE(2) levels between controls and OAB patients (before and after treatment in groups 1, 2, and 3) were compared.Urinary NGF and PGE(2) levels were significantly higher in OAB patients than in the controls. NGF levels were not significantly different between pre- and post-treatment in groups 1 and 2. However, in group 3, NGF levels were significantly decreased after treatment. PGE(2) levels were not significantly different between pre- and post-treatment in either group.NGF and PGE(2) have important roles in the development of OAB symptoms in women. Initial reduction of urgency severity after anticholinergic treatment in women with OAB could be associated with decreasing urinary NGF levels.

Bone marrow is a reservoir for hematopoietic stem cells, endothelial precursor cells, and bone marrow stromal cells (also generally called mesenchymal stem cells), whose positive role in tissue repair is highly anticipated. In this report, we introduce a novel function of substance-P (SP), an 11-amino-acid peptide, as an injury-inducible messenger to mobilize bone marrow stem cells to the blood and finally to engage in tissue repair. This new drug may substitute for ex vivo cell culture of therapeutic cells by stimulating cell proliferation in the bone marrow in vivo and mobilizing those therapeutic cells to the patient's own blood stream. Again, the additional role of SP in mitigating inflammation-mediated tissue damage can further rationalize the clinical development of SP-peptide as a stem cell stimulant.

Attributional style means how people typically infer the causes of emotional behaviors. No study has shown neural basis of attributional style in schizophrenia, although it was suggested as a major area of social cognition research of schizophrenia. Fifteen patients with schizophrenia and 16 healthy controls underwent functional magnetic resonance imaging while performing three (happy, angry, and neutral) conditions of attribution task. Each condition included inferring situational causes of an avatar' (virtual character) emotional or neutral behavior. In the between-groups contrast maps of the happy conditions, the patient group compared to the control group showed decreased activations in the inferior frontal (BA 44) and the ventral premotor cortex (BA 6), in which the % signal changes were associated with negative symptoms. In the angry conditions, the patient group compared to the control group exhibited increased activations in the precuneus/posterior cingulate cortex (Pcu/PCC) (BA 7/31), in which the % signal changes were related to positive symptoms. In conclusion, patients with schizophrenia may have functional deficits in mirror neuron system when attributing positive behaviors, which may be related to a lack of inner simulation and empathy and negative symptoms. In contrast, patients may have increased activation in the Pcu/PCC related to self-representations while attributing negative behaviors, which may be related to failures in self- and source-monitoring and positive symptoms.

Individuals sometimes experience an illusory or hallucinatory perception. This unreal perception is usually resolved after the individual recognizes that the perception was not real. In this study, we investigated the brain mechanisms involved in the process to an illusory or hallucinatory perception through ‘obtaining insight into unreality’. We used a novel and intuitive paradigm designed by combining functional magnetic resonance imaging and augmented reality technology to simulate visual illusory stimuli that mimic hallucinations during brain scanning. The results showed various brain activations, predominantly in the amygdala in the early phase, the medial frontal cortex and the occipitotemporal junction in the middle phase, and the thalamus in the late phase, which correlated with a subject's proneness to hallucinating. These activations may correspond to a ‘responding stage’ for a perception-based immediate emotional reaction, a ‘monitoring stage’ for integration and recalibration to ascertain that the perception was not real, and a ‘resolving stage’ for controlling the information and finally settling it, respectively. Our paradigm and findings may be useful in understanding the mechanisms for discriminating and coping with hallucinatory perceptions.

Using proton magnetic resonance spectroscopy and magnetic resonance imaging, we investigated concentrations of various brain metabolites, including glutamate, and measured brain volumes and neuropsychological performances in 13 recently abstinent young alcoholic men compared with 18 controls. No differences were found in volumetric variables between groups (intracranial volume, white matter, grey matter, anterior cingulate, insula, hippocampus, and amygdala). For the anterior cingulate, choline and creatine levels in the patient group were significantly lower than controls, and the glutamate to creatine ratio was significantly increased. These were correlated with altered short-term memory functions. Thus, neurochemical changes can occur even in the brains of young alcoholic men lacking brain atrophy.

OBJECTIVE The aim of this randomized, sham-controlled study was to investigate the therapeutic effects of underlying neurobiological changes after 2-week repetitive transcranial magnetic stimulation (rTMS) treatment using functional connectivity magnetic resonance imaging in patients with major depression. METHODS Twenty-four patients with major depressive disorder diagnosed with DSM-IV-TR criteria were randomly assigned to the active rTMS (n = 13) or sham (n = 11) groups from January 2009 to June 2011. rTMS was given for 2 weeks at 110% of the motor threshold for 10 minutes at 10 Hz over the left dorsolateral prefrontal cortex (DLPFC). Resting state functional connectivity was evaluated before and after rTMS. The 17-item Hamilton Depression Rating Scale (HDRS) was administered, and neurocognitive tasks were performed. We examined between-group differences in functional connectivity changes from the bilateral DLPFC. RESULTS Participants in the active rTMS group showed significant clinical improvement in HDRS scores compared to those in the sham group (P < .001). After 2-week rTMS, there were significant differences in changes in DLPFC-left caudate connectivity (corrected P < .05): the active group showed a greater reduction of connectivity strength between the DLPFC and left caudate compared to the sham group. Reduced levels of DLPFC-left caudate connectivity predicted improvement in depressive symptoms (r = 0.58, P = .001). Additionally, a positive correlation between residual depressive symptoms and connectivity strength after 2-week rTMS was found (r = 0.46, P = .023). CONCLUSIONS High-frequency rTMS over the left DLPFC showed therapeutic effects in patients with major depression. The therapeutic effect of rTMS is related to the modulation of functional connectivity in the frontostriatal network. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01325831​.

Objective: To explore the critical value and possible influencing factors of fractional exhaled nitric oxide (FeNO) in suspected asthma patients. Methods: 923 suspected asthmatics consecutively referred to our hospital during December 2012 to July 2014 were selected. All cases were carried out FeNO measurement at first; next, spirometry, bronchoprovocation tests or bronchodilation tests were used to confirm or exclude asthma. Receiver operating characteristic curve (ROC) was used to determine the best cut-off value of FeNO for asthma diagnosis. Results: In bronchoprovocation test, 125 cases were diagnosed as asthma, other 283 were non-asthmatics. FeNO levels of asthmatics were significantly higher than non-asthmatics (median, 64.8 ppb vs. 27.9 ppb, P < 0.01). In this group of patients, 64 ppb was the best cut-off value of FeNO to identify asthma with sensitivity of 52.0% and specificity of 94.35%. In bronchodilation test, 185 patients were diagnosed as asthma, other 330 were non-asthmatics. FeNO levels of asthmatics were significantly higher than non-asthmatics (median, 60.6 ppb vs. 29.05 ppb, P < 0.01). In bronchodilation test patients, 41 ppb was the best cut-off value of FeNO to identify asthma with sensitivity of 72.43% and specificity of 74.85%. Influencing factors analysis showed that sex was an independent factor affecting patients’ FeNO level. Conclusion: FeNO was an effective auxiliary diagnosis method for bronchial asthma. 64 ppb and 41 ppb was the best cut-off value of FeNO to identify asthma in bronchoprovocation test or bronchodilation test, respectively. Sex was an independent factor affecting patients’ FeNO level.

This study aimed to investigate the effects of preoperative Valsalva leak point pressure (VLPP) on the outcomes of the single-incision midurethral sling procedure (Needleless® System) in female stress urinary incon­tinence (SUI).We evaluated 112 patients who underwent midurethral sling placement for SUI using the Needleless® System. Patients were divided into two groups according to their preoperative VLPP values: VLPP90 cmH2O (group 1) and VLPP 60-90 cmH2O (group 2). After the postoperative period, SUI status and satisfac­tion were compared between the two groups. Subjective cure was defined as the absence of any episodes of urinary incontinence associated with conditions that increase intra-abdominal pressure in daily life. Treatment satisfaction was analyzed according to patient responses as 'satisfied', 'neutral', and 'dissatisfied'. Postoperative other lower urinary tract symptoms except SUI were compared between the two groups too.There were no significant differences in age, body weight, and urodynamic parameters (except VLPP) between the two groups. The mean VLPPs were 105.9 ± 12.3 cmH2O (range, 93.6-118.2 cmH2O) in group 1 and 75.4 ± 10.5 cmH2O (range, 65-85.9 cmH2O) in group 2. The overall subjective cure rates were 65.0% in group 1 and 62.5% in group 2 (P = .744). The overall satisfaction rates were 58.8% in group 1 and 68.8% in group 2 (P = .600). Complication rates did not differ between the two groups.When stratified as90 cmH2O or ≤ 90 cmH2O, preoperative VLPP did not affect Needleless® Sys­tem outcomes in female SUI patients.

STUDY DESIGN A rare case of retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis is presented. OBJECTIVE To discuss the pathomechanism of retro-odontoid pseudotumor in diffuse idiopathic skeletal hyperostosis. SUMMARY OF BACKGROUND DATA Reports describing craniovertebral manifestations of diffuse idiopathic skeletal hyperostosis are quite rare. Only two cases of an atlantoaxial subluxation and one case of an odontoid fracture have been reported. Myelopathy resulting from retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis has not been reported previously. METHODS A 74-year-old man presented with spastic tetraparesis caused by a retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis. Transoral removal of the extradural mass combined with a dorsal atlantoaxial fusion was performed using a titanium frame with sublaminar cable wiring. RESULTS Yellowish amorphous material extruded from between the odontoid process and the arch of C1 when the anterior capsule had been incised. The retro-odontoid mass was very firmly attached to the hypertrophied ligaments. The mass therefore had to be sharply dissected away to expose the dura. The histologic appearance of the mass consisted of poorly cell-degenerated ligament, fibrocartilage, and fibrin. There was a focal proliferation of small vessels, but no significant inflammatory component and no evidence of neoplasia. The ligaments appeared fibrillated, disintegrated, and fragmented. After surgery, the patient's neurologic function improved. CONCLUSIONS This is the first reported case of a retro-odontoid pseudotumor combined with diffuse idiopathic skeletal hyperostosis. The secondary transfer of mechanical stress to the atlantoaxial segment was presented as a pathomechanism underlying the formation of this retro-odontoid pseudotumor.

ARS-interacting multifunctional protein 1 (AIMP1) induces production of inflammatory cytokines from immune cells. Since osteoclastogenesis is promoted by positive regulation of inflammatory cytokines, whether AIMP1 could promote osteoclastogenesis was investigated. AIMP1 induced osteoclastogenesis and acted synergistically with RANKL to promote osteoclastogenesis. Down-regulation of CD23, an AIMP1 receptor, abolished AIMP1-mediated osteoclastogenesis. Enzyme-linked immunosorbent assays showed that the AIMP1 level was significantly higher in the peripheral blood (PB) and synovial fluid of rheumatoid arthritis patients than in normal PB. A monoclonal antibody (clone 15B3AF) that blocked the cytokine activity of AIMP1 inhibited the AIMP1-mediated production of inflammatory cytokines. Clone 15B3AF inhibited the AIMP1-mediated osteoclastogenesis in vitro. We then cloned the complementary determining regions of clone 15B3AF and generated a chimeric antibody (atliximab). In a collagen-induced arthritis mouse model (CIA), atliximab administration significantly attenuated disease severity and improved various histopathological parameters. Three-dimensional micro-computed tomography scanning confirmed that atliximab enhanced the joint structures in CIA mice. Furthermore, atliximab decreased the expression of inflammatory cytokines in the serum and inflamed joints of CIA mice. Taken together, our findings suggest that AIMP1 exacerbates RA by promoting inflammation and osteoclastogenesis and that atliximab could be developed as a therapeutic antibody to target inflammatory diseases, including RA.

Cannabinoid type 1 receptor (CB1R), which is traditionally located on axon terminals, plays an important role in the pathology of epilepsy and neurodegenerative diseases by modulating synaptic transmission. Using the pilocarpine model of chronic spontaneous recurrent seizures, which mimics the main features of mesial temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) in humans, we examined the expression of CB1R in hippocampal astrocytes of epileptic rats. Furthermore, we also examined the expression of astrocytic CB1R in the resected hippocampi from patients with medically refractory mesial TLE. Using immunofluorescent double labeling, we found increased expression of astrocytic CB1R in hippocampi of epileptic rats, whereas expression of astrocytic CB1R was not detectable in hippocampi of saline treated animals. Furthermore, CB1R was also found in some astrocytes in sclerotic hippocampi in a subset of patients with intractable mesial TLE. Detection with immune electron microscopy showed that the expression of CB1R was increased in astrocytes of epileptic rats and modest levels of CB1R were also found on the astrocytic membrane of sclerotic hippocampi. These results suggest that increased expression of astrocytic CB1R in sclerotic hippocampi might be involved in the cellular basis of the effects of cannabinoids on epilepsy.

Summary Aim The aim of this study was to evaluate the impact of depression and somatic symptoms on treatment outcomes in Korean male patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) attending a routine clinical practice. Methods This was a 12-week prospective observational study (n = 80). The Korean version of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) to measure the severity of CP/CPPS, the Korean version of the Patient Health Questionnaire-9 (PHQ-9) to assess depression, the Korean version of the Patient Health Questionnaire-15 (PHQ-15) to evaluate somatisation and the Korean version of the EuroQol Questionnaire-5 Dimensions (EQ-5D), specifically the EQ-5D utility index and the EQ-5D visual analogue scale (EQ-5D VAS), to assess quality of life, were utilised and given at baseline and week 12. The primary and secondary end-points in this study were changes in the NIH-CPSI total score from baseline to week 12 according to depression and somatisation. Results The change in NIH-CPSI total score was significantly higher in those without depression than in those with depression (p = 0.003), with a magnitude of difference of 2.8. The responder rate (a ≥ 4 point decrease in NIH-CPSI total score from baseline) was significantly higher in those without depression (42.9%) than in those with depression (17.2%, p = 0.023). However, significant differences were not observed between the two groups in the other outcome measures or in all study outcomes between subjects with or without somatisation. A logistic regression analysis revealed that the presence or absence of depression may be a principal predictor of response to treatment. Conclusion These preliminary results indicate that depression may have a negative impact on treatment outcome and is a likely predictor of response to treatment in patients with CP/CPPS. However, additional studies with adequate power and improved design are necessary to further support the present findings.