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Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients.We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo.This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p 0.001). The subgroup without concurrent medication had the same result (p 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo.This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life.PROSPERO CRD42021269451.

The association of prior bariatric surgery (BS) with infection rate and prognosis of coronavirus disease 2019 (COVID-19) remains unclear. We conducted a meta-analysis of observational studies to address this issue.We searched databases including MEDLINE, Embase, and CENTRAL from inception to May, 2022. The primary outcome was risk of mortality, while secondary outcomes included risk of hospital/intensive care unit (ICU) admission, mechanical ventilation, acute kidney injury (AKI), and infection rate.Eleven studies involving 151,475 patients were analyzed. Meta-analysis showed lower risks of mortality [odd ratio (OR)= 0.42, 95% CI: 0.27-0.65, p 0.001, IOur results showed a correlation between prior BS and less severe COVID-19, which warrants further investigations to verify.

This meta-analysis was aimed at investigating the effectiveness and safety of phrenic nerve infiltration (PNI) against ipsilateral shoulder pain (ISP) after thoracic surgery.A systematic review and meta-analysis of randomized controlled trials (RCTs).Operating room.Patients undergoing thoracic surgery.PNI.MEDLINE, Cochrane Library, and EMBASE databases were searched from inception through December 2021. The primary outcome was the overall incidence of ISP, with secondary outcomes including incidence and severity of ISP at postoperative 6, 24, and 48 hours. Six RCTs involving 482 patients undergoing thoracic surgery were included. Pooled results found a significantly lower incidence of overall ISP in patients with PNI (ie, 23.6%) compared to those without (ie, 53.2%; risk ratio: 0.46, 95% confidence interval: 0.34-0.61; IThis meta-analysis showed that PNI not only reduced the incidence but also improved the severity of ipsilateral shoulder pain after thoracic surgery with a prophylactic effect lasting up to 48 hours. The limited number of included studies warrants further research to support these findings.

Background Despite the known positive correlation between exercise and weight loss following bariatric surgery as well as the established association of hemoglobin level with maximal aerobic power and endurance performance, the correlation between preoperative hemoglobin concentration (Pre-Hb) and postoperative weight loss remains unknown. Object This study aimed at assessing the association of Pre-Hb with postoperative percentage weight loss (%WL) at 3, 6, 12 and 24 months after surgery. Setting A single tertiary referral center Methods Outcomes of 282 patients undergoing laparoscopic sleeve gastrectomy at the four timepoints within a 24-month follow-up period were assessed. The primary study endpoint was the relationship between Pre-Hb and postoperative %WL at 12-month follow-up. Results The 282 patients had a mean preoperative body mass index (Pre-BMI) of 39.0 ± 4.5 kg/m 2 with a slight female predominance (57.4%). Follow-up data were available for 221 of 282 (78.4%) patients (mean %WL: 30.9 ± 6.6 %) at one year. Pearson’s correlation showed that Pre-Hb correlated positively with Post-Hb (r=0.778, p p p =0.331). Multiple linear regression analyses including baseline variables of age, sex, Pre-BMI, and diabetes revealed that Pre-Hb, age and Pre-BMI were independent predictors of %WL. There was no evidence of multicollinearity among these variables. Conclusion The present study showed a potential positive relationship between preoperative hemoglobin concentration and postoperative weight loss. Further well-design large-scale studies are warranted to clarify the impact of hemoglobin level on postoperative weight loss in this patient population.

Objective Although inguinal hernia and aortic aneurysm share similar pathogenic mechanisms of collagen and elastin destruction, their clinical association in geriatric patients is inconclusive. We assessed the association between hernia and the subsequent occurrence of aortic aneurysm in geriatric patients. Methods Adult patients with hernias between 2000 and 2012 were identified from a longitudinal claims database of 1 million beneficiaries from Taiwan's National Health Insurance program, and a control group of patients without hernia were matched by propensity score in a ratio of 1:3. Patients previously diagnosed with aortic aneurysms or connective tissue diseases were excluded. Follow-up ended on December 31, 2013. The incidence rate of aortic aneurysm was compared between patients with hernia and those without. Cox proportional hazards models were used to estimate relative hazards. Results After propensity score matching, there were 16,933 patients with hernia (aged 20-64 years: 10,326; ≥65 years: 6607) and 50,799 patients without hernia (aged 20-64: 30,978; ≥65: 19,821). Patients with hernia had a greater incidence rate and hazard ratio of aortic aneurysm than did patients without hernia (6.4 vs 4.8/10,000 person-years; adjusted subdistribution hazard ratio [sdHR], 1.34; 95% confidence interval [CI], 1.02-1.76; P = .03), especially for those aged ≥65 years (15.6 vs 10.4/10,000 person-years; adjusted sdHR, 1.44; 95% CI, 1.07-1.94; P = .01) In addition, geriatric patients with hernia were associated with a marginally greater risk of thoracic (adjusted sdHR, 1.66; 95% CI, 0.96-2.86) and abdominal (adjusted sdHR, 1.36; 95% CI, 0.96-1.94) aortic aneurysm rupture. Conclusions Geriatric patients with hernia were associated with a greater incidence of aortic aneurysm than were those without.

Acne, an inflammatory disease of the pilosebaceous unit, is now recognized and investigated as a chronic disease. Since the physiological and psychosocial impact of acne may be long-lasting, the treatment of acne vulgaris poses a formidable challenge for dermatologists.The present study aims at investigating the validity and reliability of a self-developed instrument "acne self-regulation inventory" (ASRI) based on self-regulation theory in assessing the selfregulation ability of acne patients as part of the therapeutic strategy.All proposed items to be included in ASRI, which consisted of four subscales (i.e., self-monitoring, self-judgment, self-reaction, and self-motivation), were first reviewed by 5 experts in the field. Pilot testing of scale reliability and validity of ASRI were then performed by recruiting 144 acne patients, followed by conduction of formal questionnaire survey by enrolling other 90 acne patients to complete a questionnaire comprising the refined ASRI, Cardiff Acne Disability Index (CADI), and Dermatology Life Quality Index (DLQI) to obtain constructive validity to evaluate the associations of ASRI with clinical acne grading scores, CADI, and DLQI.Expert review resulted in the inclusion of totally 31 items for pilot testing (i.e., self-monitoring 6 items, self-judgment 6 items, self-reaction 12 items, and self-motivation 7 items). The differentiating ability of each item was confirmed by significant difference between the higher third scorers and those of the lower third using t-test for independent means (all p0.001). Moreover, Cronbach's α indicated that deletion of a single item in ASRI did not elevate mean value above 0.958 and removal of each item in the four subscales did not increase the mean value of the set Cronbach's α value for each subscale (i.e., 0.886; 0.860; 0.895; 0.907, respectively), suggesting suitability of the 31 items. A high Cronbach's α coefficient of the whole scale as well as the four subscales (i.e., 0.958; 0.886, 0.860, 0.895, and 0.907) demonstrated a high reliability of the ASRI. Pearson's correlation demonstrated moderate to high discriminant validity of ASRI with coefficients between each pair of the four subscales ranging from 0.637-0.798. Formal questionnaire survey demonstrated significant difference between the higher third ASRI scorers and those of the lower third in comparison with clinical acne grading scores, CADI, and DLQI, using t-test for independent means (both p=0.001).The results of the present study demonstrated the usefulness of a self-developed ASRI as an assessment tool to be included in the treatment strategy for acne patients.

Background: Although various pharmacological interventions and hormone replacement therapies for depressive symptoms in menopausal women have been investigated, their relative efficacies and safety remain unclear. Methods: Based upon literature search on PubMed, Cochrane Library, and ScienceDirect, randomized controlled trials (RCTs) examining all the pharmacological interventions or hormone replacement therapy for depressive symptoms in menopausal women had been included. Data that met inclusion criteria were extracted from RCTs. The current network meta-analysis was conducted under the frequentist model. Findings: Seventy RCTs in total were included with a total of 18,530 women (mean age = 62.5). The network meta-analysis (NMA) demonstrated that fluoxetine plus oral combined therapy [standardized mean difference (SMD) = -1.59, 95% confidence interval (CI) = -2.69 to -0.50], transdermal estradiol (SMD = -0.67, 95% CIs= -1.15 to -0.19), tibolone only (SMD = -0.64, 95% CIs= -1.18 to -0.09), and oral estrogen therapy (SMD = -0.55, 95% CIs= -0.92 to -0.18) were associated with significantly better overall improvement in depressive symptoms than that for placebos in menopausal women. Fluoxetine plus oral combined therapy was ranked the best among all the interventions. Similar findings were also noted in the subgroup of participants with definite diagnosis of depression; while for patients without diagnosis of depression, no pharmacological or hormone replacement therapy was better than placebo. Finally, most medications showed good tolerability with drop-out rate and rate of discontinuation due to adverse events comparable to those in placebo groups. Interpretation: This NMA demonstrated that fluoxetine plus oral combined therapy was associated with the best improvement in menopausal depressive symptoms among the investigated interventions. Future large-scale RCTs on pharmacologic relief of depressive symptoms in menopausal women, especially in aspect of antidepressant regimens, are warranted to support or refute the results of the current study. Funding Statement: The authors of this work were supported by the following grants: Brendon Stubbs is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs was partly funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs is also supported by the Maudsley Charity, King’s College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. Declaration of Interests: The authors report no financial interests or potential conflicts of interest.

In this study, we tested the hypothesis that a combined adipose-derived mesenchymal stem cell (ADMSC) and ADMSC-derived exosome therapy protected rat kidney from acute ischemia-reperfusion (IR) injury (i.e., ligation of both renal arteries for 1h and reperfusion for 72h prior to euthanization).Adult-male SD rats (n=40) were equally categorized into group 1 (sham control), group 2 (IR), group 3 [IR+exosome (100μg)], group 4 [IR+ADMSC (1.2×10(6) cells)], and group 5 (IR-exosome-ADMSC). All therapies were performed at 3h after IR procedure from venous administration. By 72h, the creatinine level and kidney injury score were the lowest in group 1 and the highest in group 2, significantly higher in group 3 than in groups 4 and 5, and significantly higher in group 4 than in group 5 (all P0.0001). The protein expression of inflammatory (TNF-α/NF-κB/IL-1β/MIF/PAI-1/Cox-2), oxidative-stress (NOX-1/NOX-2/oxidized protein), apoptotic (Bax/caspase-3/PARP), and fibrotic (Smad3/TGF-β) biomarkers showed an identical pattern, whereas the anti-apoptotic (Smad1/5, BMP-2) and angiogenesis (CD31/vWF/angiopoietin) biomarkers and mitochondrial cytochrome-C showed an opposite pattern of creatinine level among the five groups (all P0.001). The microscopic findings of glomerular-damage (WT-1), renal tubular-damage (KIM-1), DNA-damage (γ-H2AX), inflammation (MPO/MIF/CD68) exhibited an identical pattern, whereas the podocyte components (podocin/p-cadherin/synaptopodin) displayed a reversed pattern of creatinine level (all P0.0001).Combined exosome-ADMSC therapy was superior to either one for protecting kidney from acute IR injury.

We tested the hypothesis that tissue plasminogen activator (tPA) deficiency protected against acute ischemic stroke (AIS)-induced brain injury.Wild-type mice (n=54) were categorized into group 1 (sham control, n=18) and group 3 [AIS by permanent ligation of left common carotid artery (CCA) and cramping right CCA for 1h and then reperfusion followed by hypoxia (11% of oxygen supply for 2h), n=36]. Similarly, tPA knockout (tPA(-/-)) mice (n=54) were randomized into group 2 (sham control, n=18) and group 4 (AIS, n=36). By day 28 after AIS procedure, mortality rate was higher in group 3 (77.8%) than in group 4 (38.9%) and lowest in groups 1 (0%) and 2 (0%) (p0.001). By days 3 and 28, MRI demonstrated a pattern of changes in brain-infarct volume identical to that of mortality among four groups (p0.001). By day 28, protein expressions of inflammatory (MMP-9, TNF-α, NF-κB, iNOS, PAI-1, RANTES), oxidative (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase-3PARP, Bax), and fibrotic (Smad3, TGF-β) biomarkers and cellular expressions of inflammation (CD11, F4/80, GFAP), DNA-damage (γ-H2AX) and brain-edema (AQP4) markers exhibited an identical pattern compared to that of mortality (all p0.001), whereas protein expressions of endothelial (eNOS, CD31), anti-fibrotic (Smad1/5, BMP-2) biomarkers, and number of small vessels displayed an opposite pattern (all p0.001) among four groups. Expressions of protein and cellular angiogenesis markers (VEGF, SDF-1α, CXCR4) were progressively increased from groups 1 and 2 to group 4 (all p0.0001).tPA deficiency protected the brain from AIS injury.

We tested the hypothesis that transfusion of autologous peripheral blood-derived endothelial progenitor cells (PBDEPC) via the internal carotid artery could reduce brain-infarct zone (BIZ) and neurological deficit in rats following acute ischemic stroke (IS) induced by 50-min left middle cerebral artery occlusion.Adult male Sprague-Dawley rats (n=60) were equally divided into group 1 [sham control (SC)], group 2 [SC-PBDEPC (5.7 × 10(6)/kg)], group 3 (IS), group 4 [IS-low-dose PBDEPC (1.7 × 10(6)/kg)], group 5 [IS-high-dose PBDEPC (5.7×10(6)/kg)]. Groups 2 to 5 received G-CSF (35 μg/kg subcutaneously) for 4 days before drawing blood for PBDEPC culture.By day 90, BIZ determined by histopathology (area) and brain MRI (volume) were highest in group 3, lowest in groups 1 and 2, higher in group 4 than in group 5 (all p0.0001), and not significantly different between groups 1 and 2. Sensorimotor functional results exhibited an opposite pattern of BIZ among groups 3 to 5 (p0.005). Angiogenesis biomarkers (SDF-1α, CXCR4, VEGF, angiopoietin-1) significantly increased progressively from groups 1 and 2 to group 5 (all p0.0001). Oxidative-stress (NOX-1, NOX-2, oxidized protein), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), inflammatory (MMP-9, TNF-α, AQP-4, GFAP, iNOS), and brain-damaged (cytosolic cytochrome-C) biomarkers showed an identical pattern, whereas anti-inflammatory (Bcl-2), mitochondrial preservation (mitochondrial cytochrome-C, PGC-1α), and endothelial function (CD31+, vWF+, eNOS) biomarkers, and vessel density showed an opposite pattern of BIZ among these five groups (all p0.001).Higher-dose was superior to lower-dose EPC treatment for reducing BIZ and improving neurological functional outcome.

We hypothesized that combined therapy with shock wave (SW) and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) is superior to either therapy alone for alleviating left ventricular (LV) dysfunction.Male mini-pigs (n=30) equally divided into group 1 (sham control), group 2 [acute myocardial infarction (AMI) by left coronary artery ligation], group 3 (AMI-SW), group 4 (AMI-BMDMSC), and group 5 (AMI-SW-BMDMSC) were sacrificed by day 60 and the hearts were collected for studies. Baseline LV injection fraction [LVEF (%)] and LV chamber size did not differ among the five groups (p0.5). By day 60, LVEF was highest in group 1 and lowest in group 2, significantly higher in group 5 than that in groups 3 and 4, and significantly higher in group 4 than that in group 3 (p0.001). Cellular and protein levels of VEGF, CXCR4, and SDF-1α were significantly increased progressively from groups 1 to 5 (all p0.05). Small vessel number and protein expressions of CD31 and eNOS were highest in groups 1 and 5, lowest in group 2, and significantly higher in group 4 than those in group 3 (p0.001). Protein (MMP-9, TNF-1α and NF-κB) and cellular (CD14+, CD40+) levels of inflammatory biomarkers, protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), apoptosis (Bax, caspase-3, PARP), infarct size, and LV dimensions showed a pattern opposite to that of LVEF among all groups (all p0.001).Combined SW-BMDMSC therapy is superior to either therapy alone for improving LVEF, reducing infarct size, and inhibiting LV remodeling.

Introduction to Computer Science (ICS), which is a compulsory theoretical course for freshmen of the electrical engineering (EE) department, lays the foundation for more advanced courses. Nevertheless, since ICS covers a wide variety of concepts that are difficult to completely comprehend, incomplete understanding and a loss of learning incentive are possible problems. The aim of implementing hands-on practice (HOP) activities was to prepare the students for the actual hardware manipulation in the field of EE and also to enhance their performance in the future advanced practice courses. Through organizing optional evening hands-on practice (HOP) activities, this study investigated whether the first-year college students who participated in HOP would exhibit a better understanding in ICS compared to those who did not. The enrollment in HOP was optional in which the performance did not affect the score in the ICS course. The results showed that HOP participants not only had significantly higher academic scores (p < 0.05), but were also less stressed toward the ICS course (p < 0.05) than the non-participants. The former also showed increased interest in accepting challenges (e.g. Two HOP participants later entered the National Microcomputer Design Competition and were awarded the third prize). In conclusion, the introduction of optional HOP for freshmen of electrical engineering not only alleviated the stress that they face in response to the ICS course, but also improved the students' academic performance and class attendance rate as well as raising their interest and boosting their confidence in further challenges in the field of electrical engineering.

This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left femoral artery.Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0 mg/kg)] and group 4A [CLI-tPA (intravenously at 3 h after CLI)]. Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group 1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], and group 4B (CLI-tPA).The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p0.05) at 6 h and 18 h post-CLI. Levels of these biomarkers decreased again 14 days after CLI in tPA(-/-) mice compared to those in wild-type between the respective groups (all p0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α+, and CD31+ cells) levels was highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA(-/-) mice (p0.01).tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.

Dural metastasis with subdural hemorrhage is very rare. We report a 69-year-old woman who visited our emergency department with a history of nausea and vomiting for 6 days. Computed tomography of the brain with enhancement showed a space-occupying lesion over temporal skull with subdural hematoma. Abdominal sonography revealed a liver tumor. Emergent craniotomy and resection of intracranial tumor were performed because of impaired consciousness on the 4 th day after admission. A pathological analysis of the cranial lesion later confirmed the diagnosis of metastatic hepatocellular carcinoma with skull involvement. After a complete survey of her hepatoma, she received tumor embolization and was discharged. However, 6 months later, she died because of multiple brain metastases, leading to subdural hemorrhage and intracranial hemorrhage. Although intracranial metastatic lesions are rare, they are life-threatening because of the lack of obvious history that usually leads to delayed diagnosis. A literature review was performed to shed light on the frequency and importance of this rare but important clinical entity.

This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p

We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis.Adipose tissue from adult-male Fischer 344 rats (n = 6) were cultured in endothelial progenitor cell culture medium for 14 d with (25 μmol/L) or without sitagliptin. CLI was induced by ligation of the left femoral artery. Rats (n = 32) were equally separated into four groups: untreated controls (group 1), sitagliptin (4 mg/kg per day; group 2), CLI (group 3) and CLI with sitagliptin (group 4).In vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-1/CD31+, CXCR4+, c-kit+ and CD34+ cells) and Western blot (vascular endothelial growth factor, CXCR4 and stromal-derived factor [SDF]-1α) were remarkably higher in group 4 than in the other groups (all P 0.01). In vivo, 2 and 14 d after the CLI procedure, circulating angiogenic cell (Sca-1/CD31+, Sca-1+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P 0.001). Additionally, the messenger RNA and protein expression of angiogenic biomarkers (CXCR4, SDF-1α and vascular endothelial growth factor), immunofluorescent staining of angiogenic cells (CXCR4+, SDF-1α+, CD31+, von Willebrand factor + cells) and immunohistochemical staining of small vessel numbers in the ischemic area were significantly higher in group 4 than in the other groups (all P 0.01). Furthermore, laser Doppler showed that the ratio of ischemic/normal blood flow was remarkably higher group 4 than in group 3 by days 14 and 28 after the CLI procedure (all P 0.01).Sitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area.

It has been reported that plasmin induces migration of endothelial cells. We hypothesized that tissue plasminogen activator (tPA) enhanced endothelial progenitor cell (EPC) mobilization from bone marrow (BM) into the circulation and angiogenesis in murine critical limb ischemia (CLI).Forty male B6 mice were randomly divided into group 1 (control), group 2 [control+recombinant tPA (intra-venous 4 mg/kg)], group 3 (CLI) and group 4 (CLI+tPA).The results demonstrated higher MMP-9 activity in BM and circulatory SDF-1α level in groups 2 and 3 than in group 1, and highest in group 4 (all p0.01) at 18 h after CLI. Compared with circulation, SDF-1α level in BM showed an opposite trend (all p0.03). The circulating EPC (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) levels at 18 h after CLI were higher in group 2 than in groups 1 and 3, and highest in group 4 (all p0.03). EPC (C-kit/CD31, Sca-1/KDR) levels in BM were lower in group 1 than in groups 2 to 4 (all p0.03), whereas number of CXCR4/CD34-positive EPCs in BM did not differ among the four groups at 18 h after CLI. Protein expressions of SDF-1α, CXCR4, eNOS, and VEGF, numbers of CD31+, CXCR4+, SDF-1α+, and vWF+ cells through immunofluorescent staining, numbers of small vessels (15 μm) and blood flow measured by Laser Doppler in an ischemic area were significantly higher in group 4 than in group 3 (all p0.005) at day 14 after CLI.tPA treatment enhanced number of circulating EPCs, angiogenesis, and blood flow to ischemic tissue in a murine model of limb ischemia.

Using frequency and rank order statistics (FROS), this study analyzed the fluctuations in arterial waveform amplitudes recorded from an air pressure sensing system before and after reactive hyperemia (RH) induction by temporary blood flow occlusion to evaluate the vascular endothelial function of aged and diabetic subjects. The modified probability-weighted distance (PWD) calculated from the FROS was compared with the dilatation index (DI) to evaluate its validity and sensitivity in the assessment of vascular endothelial function. The results showed that the PWD can provide a quantitative determination of the structural changes in the arterial pressure signals associated with regulation of vascular tone and blood pressure by intact vascular endothelium after the application of occlusion stress. Our study suggests that the use of FROS is a reliable noninvasive approach to the assessment of vascular endothelial degeneration in aging and diabetes.

Arteriovenous (AV) graft is frequently used as vascular access in hemodialysis patients. However, clotting or thrombosis of AV grafts often occurs and requires surgical removal. At present, the molecular pathogenesis underlying thrombosis of AV graft is not clear. The PTEN/Akt signaling has been implicated in the pathogenesis of vascular diseases. In this study, elevated PTEN expression and concomitant Akt inactivation was observed in endothelium of atherosclerotic brachial arteries from hemodialysis patients. To investigate whether PTEN upregulation affects endothelial function, adenovirus-mediated PTEN (Ad-PTEN) overexpression was performed in aorta rings and cultured endothelial cells. It was found that PTEN overexpression potently inhibited the microvessel sprouting in aorta rings and the angiogenic activities of endothelial cells including migration and tube formation. On the contrary, PTEN knockdown by RNA interference promoted the endothelial migration and reversed the Ad-PTEN-induced inhibition of endothelial migration. Expression analysis showed that PTEN overexpression attenuated the expression of endothelin-1 (ET-1) and endothelin B receptor (ETBR) in endothelial cells at transcriptional levels. However, exogenous ET-1 supply only partially reversed the PTEN-induced inhibition of migration and tube formation. This was delineated due to that PTEN overexpression also perturbed endothelial nitric oxide synthase (eNOS) activation and vascular endothelial growth factor (VEGF) release. In summary, PTEN upregulation induces endothelial dysfunction by attenuating the availability and signaling of multiple angiogenic pathways in endothelial cells, thereby may contribute to thrombosis of AV graft.

The aim of this study was to investigate the incidence of composite short-term and long-term major adverse upper gastrointestinal (UGI) events (MAUGIEs; defined as gastric ulcer, duodenal ulcer, gastroduodenal ulcer, or UGI bleeding) in patients with acute ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention and routinely received dual-antiplatelet therapy. From May 2002 to September 2010, a total of 1,368 consecutive patients who experienced ST-segment elevation myocardial infarction and underwent primary percutaneous coronary intervention were prospectively enrolled in the study. The incidence of in-hospital UGI bleeding complications and composite MAUGIEs was 8.9% and 9.9%, respectively. The in-hospital mortality rate was significantly higher in patients with in-hospital MAUGIEs than in those without (p0.001). Multivariate analysis showed that age, advanced Killip score (≥3), and respiratory failure were the strongest independent predictors of in-hospital composite MAUGIEs (all p0.003). The cumulative composite of MAUGIEs after uneventful discharge in patients without adverse UGI events who continuously received dual-antiplatelet therapy for 3 to 12 months, followed by aspirin therapy, was 10.4% during long-term (mean 4.0 years) follow-up. In conclusion, the results of this study show a remarkably high incidence of composite short-term and long-term MAUGIEs in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention and received routine dual-antiplatelet therapy. Age, advanced Killip score, and respiratory failure were significantly and independently predictive of in-hospital composite MAUGIEs.

We investigated the potential benefits and the underlying mechanisms of autologous bone marrow-derived mononuclear cell (BMDMNC) implantation in a porcine model of acute anterior wall myocardial infarction (AAWMI) by studying 6-month left ventricular (LV) function and LV remodeling.After being aspirated from the iliac crest and cultured for 1 week, BMDMNCs were implanted immediately after AAWMI induction through the left anterior descending artery ligation. Thirty male mini-pigs (16-18 kg) were equally divided into group 1 [AAWMI plus saline injection into infarct-ischemia area (IA)], group 2 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into non-IA), group 3 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into IA), group 4 (sham control plus 3.0 × 10⁷ BMDMNC transplantation into LV myocardium), and group 5 (normal control).By day 90, echocardiography demonstrated an increased LV end-diastolic and end-systolic dimensions but reduced LV ejection fraction (LVEF) in groups 1 and 2 than in other groups (all p0.01). Six-month angiographic study showed a lower LVEF and wall motion score but a higher mitral regurgitation in groups 1 and 2 than in other groups (all p0.01). In IA and peri-infarct area, the number of small vessels and mRNA expressions of endothelial nitric oxide synthase, Bcl-2, interleukin (IL)-10, and peroxisome proliferator-activated receptor-γ coactivator-1α were lower, whereas the number of apoptotic nuclei, caspase-3, Bax, endothelin-1, IL-8, and matrix metalloproteinase was higher in groups 1 and 2 than in other groups (all p0.01).Autologous BMDMNC transplantation into IA rather non-IA improves LV function and reduces LV remodeling via eliciting a broad-spectrum of molecular-cellular defensive mechanisms.

Objectifs Nous avons examine si une onde de choc (OC) offre un benefice additionnel pour ameliorer la fonction ventriculaire gauche (VG) apres un infarctus du myocarde aigu (AMI) chez des lapins recevant une transplantation de cellules mononucleees de moelle osseuse autologue traitees par OC (BMDMNCs). Methodes et resultats Du serum physiologique (750 μL ; groupe 2), des BMDMNCs (1,0 × 107 ; groupe 3), ou des BMDMNCs traitees par OC avant implant (groupe 4) ont ete implantes dans la zone d’infarctus de lapins males 15 min apres ligature de l’artere coronaire gauche, tandis que huit lapins sans IMA servaient de controles (groupe 1 ; n = 8 par groupe). Les resultats ont montre que dans la region infarcie du VG, l’expression de la proteine Cx43 et du cytochrome C dans les mitochondries et l’expression endotheliale de l’ARNm de la synthetase de l’oxyde nitrique etaient moindres dans le groupe 2 que dans les autres groupes, et diminuees dans le groupe 3 par rapport aux groupes 1 et 4 (toutes valeurs de p Conclusions L’application de BMDMNCs autologues traitees par OC est superieure aux BMDMNCs seules pour preserver la fonction VG apres IMA.

We tested whether shock wave (SW) offers additional benefits in improving left ventricular (LV) function after acute myocardial infarction (AMI) in rabbits receiving SW-treated autologous bone marrow-derived mononuclear cells (BMDMNCs) transplantation.Saline (750 microL; group 2), BMDMNCs (1.0 x 10(7); group 3), or preimplant SW-treated BMDMNCs (group 4) were implanted into the infarct area of male rabbits 15 minutes after left coronary artery ligation, whereas eight rabbits without AMI served as controls (group 1; n = 8 per group). The results showed that in infarct area of LV, protein expressions of Cx43 and cytochrome C in mitochondria and endothelial nitric oxide synthase mRNA expression were lower in group 2 than in other groups, and decreased in group 3 as compared with groups 1 and 4 (all p values0.01). Conversely, mRNA expressions of endothelin-1 and matrix metalloproteinase-9, mitochondrial oxidative stress, and total fibrotic area were higher in group 2 than in other groups (all p values0.05). Furthermore, 6-month LV function by 2-D echo/angiogram showed significant impairment in group 2 than in other groups and in group 3 than in groups 1 and 4 (all p values0.005).Application of SW-treated autologous BMDMNCs is superior to BMDMNCs alone for preserving LV function after AMI.

Objectifs Le but de cette etude etait de presenter une technique originale et sure avec un succes procedural eleve pour le stenting de l’artere carotide (CAS). Methodes D’avril 2004 a mai 2009, 161 patients ont eu un CAS avec un abord arteriel transradial haut (TRA, defini comme 10 cm au-dessus de la styloide) ou un abord arteriel transbrachial (TBA) avec un introducteur 7F. Une angiographie carotidienne selective etait faite avec un catheter guide 6F de Kimny et un guide en teflon (260 cm de long) par la Catheter Looping And Retrograde Engagement Technique (CLARET) avec le catheter de guidage cale sur la valve coronaire droite et son extremite engagee dans l’artere carotide commune (CCA). Le guide en teflon etait introduit dans l’ACC apres la procedure diagnostique, puis le catheter de guidage de 6F Kimny remplace par un catheter Kimny de 7F pour CAS en utilisant une des techniques suivantes : (1) methode d’engagement direct, c.-a-d., de l’artere innominee droite dans la CCA droite ; (2) methode de bouclage avec la technique de double guide (utilisant deux guides de teflon pour avoir un support adapte) pour les CCA droite et gauche ; et (3) technique de bouclage avec un ballon PercuSurge engage dans l’artere carotide externe. Resultats Cette technique a offert un succes diagnostic de 100% et un succes de CAS dans 99,4% des cas. Deux patients (1,2%) ont eu un AVC ischemique majeur apres CAS et deux (1,2%) sont morts pendant l’hospitalisation. Conclusion Les resultats de cette etude ont prouve que les voies TRA haute/TBA utilisant CLARET pour CAS chez les patients ayant une stenose serree de l’artere carotide sont sures et techniquement faisables avec un taux de reussite tres eleve.

Although magnolol is cytoprotective against warm ischemia/reperfusion injury, its effect on cold preservation has not been fully investigated. This study aimed at examining whether magnolol maintains the liver graft integrity after cold preservation and elucidating the underlying mechanisms in terms of apoptotic signaling under both normothermic and hypothermic conditions. After being preserved in Ringer's lactate (RL) at 4 degrees C for 6h ex vivo, the magnolol-treated grafts demonstrated significantly higher AST, ALT, and LDH levels in perfusates than those from negative controls. TUNEL staining showed no difference in the number of apoptotic nuclei in both groups, whereas a more intense apoptotic signal in magnolol-treated grafts was shown as compared with the controls. In vitro data showed no significant difference in viability of RL-preserved clone-9 hepatocytes between the magnolol-treated and control groups, while magnolol pretreatment at 30min before cold preservation prominently induced hepatocyte cell death. RT-PCR and Western blotting analyses revealed a suppression in Bcl-2, but an up-regulation in Bax expression in clone-9 cells after magnolol treatment. Magnolol suppressed the ratios of NF-kappaB to I-kappaBalpha protein contents and I-kappaBalpha phosphorylation induced by TNF-alpha, and potentiated mitochondrial cytochrome c release and subsequent caspase-3 cleavage. Conversely, caspase-3 inhibitor attenuated magnolol-induced hepatotoxicity. We concluded that magnolol could not protect liver grafts from cold ischemia/reperfusion injury. High concentration of magnolol under serum-reduced conditions attenuates NF-kappaB-mediated signaling and induces intrinsic apoptotic pathway, thereby inducing in vitro hepatotoxicity.

Liver retransplantation carries a significantly higher morbidity and mortality compared with patients after single transplantations. The aim of this study was to review our outcomes in liver retransplantations. From February 1984 to February 2007, 409 liver transplantations were performed on 396 patients, including 13 retransplantations (3.2%) in 12 patients. The mean follow-up was 1.6 +/- 0.4 years (range, 0.1-5.2). The mean duration between the first and the second transplantation was 2.8 +/- 1.0 years (range, 15 days-11.6 years). The indications for the first liver transplantation included biliary atresia (n = 3), hepatitis B virus (HBV)-related cirrhosis with hepatoma (n = 3), fulminant hepatic failure (n = 2), HBV-related end-stage liver disease (n = 1), hepatitis C virus (HCV)-related end-stage liver disease (n = 1), neonatal hepatitis (n = 1), and glycogen storage disease (n = 1). The indications for retransplantations were secondary biliary cirrhosis (n = 3), veno-occlusive disease-related liver failure (n = 2), hepatic arterial occlusion and graft failure (n = 2), chronic rejection with hepatic graft failure (n = 2), recurrent HBV (n = 1) and de novo HBV-related decompensated cirrhosis (n = 1), and idiopathic graft failure (n = 1). There were 4 living donor and 9 deceased donor liver retransplantations. The cumulative survival rate was 71.4 +/- 14.4%, with an estimated mean survival time of 3.9 +/- 0.7 years. Our results showed that minimizing the rate of retransplantation was critical to enhance overall patient survival. Moreover, living donor liver retransplantation is another option within the short, yet critical, waiting period, after failure of the first graft. Provided that a suitable living donor is available, we recommend early retransplantation to minimize the risk of morbidity and mortality.

Propofol (PPF), a widely used intravenous anesthetic for induction and maintenance of anesthesia during surgeries, was found to possess suppressive effect on host immunity. This study aimed at investigating whether PPF plays a modulatory role in the lipopolysaccharide (LPS)-induced inflammatory cytokine expression in a cell line of rat hepatocytes. Morphological observation and viability assay showed that PPF exhibits no cytotoxicity at concentrations up to 300 microM after 48 h incubation. Pretreatment with 100 microM PPF for 24 h prior to LPS stimulation was performed to investigate the modulatory effect on LPS-induced inflammatory gene production. The results of semi-quantitative RT-PCR demonstrated that PPF pretreatment significantly suppressed the LPS-induced toll-like receptor (TLR)-4, CD14, tumor necrosis factor (TNF)-alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression. Western blotting analysis showed that PPF pretreatment potentiated the LPS-induced TLR-4 downregulation. Flow cytometrical analysis revealed that PPF pretreatment showed no modulatory effect on the LPS-upregulated CD14 expression on hepatocytes. In addition, PPF pretreatment attenuated the phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and IkappaBalpha, as well as the nuclear translocation of NF-kappaB primed by LPS. Moreover, addition of PD98059, a MAPK kinase inhibitor, significantly suppressed the LPS-induced NF-kappaB nuclear translocation and GM-CSF production, suggesting that the PPF-attenuated GM-CSF production in hepatocytes may be attributed to its suppressive effect on MAPK/ERK signaling pathway. In conclusion, PPF as an anesthetic may clinically benefit those patients who are vulnerable to sepsis by alleviating sepsis-related inflammatory response in livers.

The steatotic liver is characterized by deranged intrahepatic microvasculature that is believed to predispose it to ischemia-reperfusion injury. The aim of this study was to investigate the distorted hepatic hemodynamics and its impact on the redox status of the steatotic liver. Hepatic hemodynamic parameters, hepatic microcirculatory perfusion (HMP), and in vivo reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] autofluorescence, which reflects the mitochondrial redox status and tissue oxygen levels, were measured in obese (n = 7) and lean Zucker rats (n = 7). Portal venous and total hepatic blood flow per unit of liver weight were found to exhibit a 37.9% and 35.9% reduction, respectively, in the steatotic liver compared to the nonsteatotic liver of the lean group (P0.0001) as was HMP (obese, 96.1 +/- 18.1 PU; lean, 143.8 +/- 12.0 PU, P0.05) that showed a 33.2% decrease in the former. Hepatic arterial resistance, however, was 38.7% lower in the obese rat (83.1 +/- 9.1 mmHg. ml(-1). min) than in the lean rat (135.5 +/- 15.8 mmHg. ml(-1). min) (P0.05). NAD(P)H fluorescence intensity was significantly elevated in the steatotic liver (0.16 +/- 0.001 aU) compared with the lean one (0.14 +/- 0.007 aU) (P = 0.014). Our results suggest that, in response to a reduced portal venous blood flow, there is a significant decrease in hepatic arterial resistance that, nevertheless, cannot completely compensate for the drop in overall hepatic perfusion and oxygenation of the microvascular bed in the steatotic liver of the obese Zucker rat.

Hepatic stellate cells (HSC) are nonparenchymal liver cells which reside in the space of Disse within the hepatic microcirculatory unit. HSC can be distinguished using intravital fluorescent microscopy (IVFM) due to the autofluorescence from their intracellular vitamin A. Herein we report on a novel approach for the quantification of video-recorded rat HSC images acquired by IVFM (excitation 360 nm/emission 420 nm) by the combined use of the "Cell counting macro" and the "Measurement macros" in the NIH image software. The approach involved two major steps using (i) the "Cell counting macro" for automatic detection, threshold-setting, and generation of a binary image of the vitamin A autofluorescence in the HSC images and (ii) the "Compute percent black and white" command in the "Measurement macros" to automatically determine the HSC density (%), which was then expressed as percentage of the total area of vitamin A autofluorescence-associated sites per observation area. Comparing the vitamin A autofluorescence areas in the original and the binary fashion HSC images revealed that the "Cell counting macro" was an optimal option for the analysis of the low-magnification (x10 objective) HSC images, whereas this macro was not suitable for the analysis of the higher magnification (40x objective) HSC images unless modifications were made. Our analysis revealed that HSC represent approximately 4-5% of the total area of the liver surface. In analyzing the higher magnification HSC microfluorographs, the use of the original "Cell counting macro" resulted in a significant underestimation of HSC density (60% reduction, P0.01) when compared with those analyzed using our modified macro. This study represents the first report of an automatic and reliable approach to the intravital fluorescent microscopic quantification of HSC using a computer-NIH image analysis system.

Purpose This study tested the hypothesis that combined therapy with and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Methods and Materials Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil; (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5; (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were hemodynamically assessed on day 90 after MCT administration and then were euthanized with the hearts and lungs harvested for morphometric studies, and for protein and mRNA analyses. Results Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p Conclusions Combined therapy with nicorandil and colchicine is superior to either alone in attenuating MCT-induced PAH in rats.

Background: This study reported the incidence and prognostic outcome of chronic obstructive lung disease (COPD) patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Between January 2002 and May 2011, totally 1554 consecutive patients who experienced STEMI undergoing primary PCI were enrolled into the study. Results: Of the 1554 patients, 124 (9.7%) with diagnosis of COPD and 1430 (90.3%) without COPD were categorized into group 1 and group 2. Although no difference in in-hospital mortality was noted between the two groups (p = 0.726). However, the hospitalization duration was notably longer (p = 0.003), the incidences of recurrent MI and re-hospitalization for congestive heart failure were significantly higher in group 1 than in group 2 (all p < 0.02). Although Kaplan-Meier analysis demonstrated that the incidence of freedom from one-year major adverse clinical outcome (MACO) (defined as recurrent MI, re-admission for congestive heart failure was significantly lower in group 1 than group 2 (p = 0.012), multivariate Cox regression analysis showed COPD was not an independent predictor of MACO-free time after adjusting traditional risk factors. Conclusion: COPD was not an independent predictor of short-term and medium-term MACO in patients with STEMI undergoing primary PCI.

Background: Conventional therapy against acute pediatric cardiopulmonary failure (APCPF) caused by a variety of disease entities remains unsatisfactory with extremely high morbidity and mortality. For refractory APCPF, extracorporeal membrane oxygenation (ECMO) is one of the last resorts. Methods: In this study, the in-hospital outcomes of pediatric patients with refractory APCPF receiving ECMO support were reviewed. Results: Between August 2006 and May 2011, a single-center cohort study was performed in pediatric patients who required ECMO support due to cardiogenic shock or severe hypoxemia. A total of 22 patients with mean age of 7.0 ± 6.3 years received ECMO (male = 11; female = 11). The indications included acute fulminant myocarditis (AFM) ( n = 6), congenital diaphragmatic hernia (CDH) ( n = 3), acute respiratory distress syndrome (ARDS) ( n = 6), enterovirus 71 ( n = 3), viral sepsis ( n = 2), refractory ventricular fibrillation due to long QT syndrome ( n = 1), and pulmonary edema with brain herniation ( n = 1). Eighteen patients received veno-arterial (VA) mode ECMO, while another four patients undertook the veno-venous (VV) mode. The duration of ECMO use and hospitalization were 6.1 ± 3.1 and 24.4 ± 19.4 days, respectively. The survival rate in patients with AFM was 100% ( n = 6). Successful ECMO weaning with uneventful discharge from hospital was noted in 14 (63.6%) patients, whereas in-hospital mortality despite successful ECMO weaning occurred in 5 patients (22.7%). Failure in ECMO weaning and in-hospital death was noted in 3 patients (13.6%). Conclusions: ECMO resuscitation is an effective strategy in the clinical setting of APCPF.

Although trauma-induced simple pubic ramus fracture is common in the emergency department (ED), it can result in life-threatening hemorrhagic shock. We describe a 58-year-old woman with closed minimally displaced simple pubic ramus fracture. Hemodynamic instability became apparent 2 hours later. She was successfully treated with transarterial embolization and discharged uneventfully 10 days later. Literature review showed involvement of the superior pubic ramus in all reported cases probably because of hemorrhage from “corona mortis” with delay in shock presentation mostly within 6 hours, suggesting at least an equivalent observation period for these patients, particularly those at high risk for hemorrhage.

Introduction Fragmented central venous access device (CVAD) catheters can be retrieved percutaneously but a pertinent approach for catheters in various locations has not been addressed. Report Comparing 14 fragmented CVAD catheters managed with direct snaring with 35 catheters treated by a modified protocol with repositioning of intrapulmonary or intracardiac catheters (21/35 cases) to the inferior vena cava before snaring, the latter group had a shorter fluoroscopic time (23.0 ± 10.6 vs. 11.0 ± 4.0 min, P = 0.005) and less chest symptoms (42.8% vs. 8.7%, P = 0.011). Conclusion Fragmented CVAD catheters managed with a modified protocol with repositioning before snaring are feasible with reductions in fluoroscopic time and chest symptoms.