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Background: 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. Methods: 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. Results: 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

Objectives: This study aimed to establish reference values for fetal aortic isthmus blood flow velocity and associated indices during the first trimester, utilizing a novel ultrasonographic technique known as high-definition flow imaging (HDFI). Additionally, the correlation between Doppler profiles of aortic blood flow and key fetal parameters, including nuchal thickness (NT), crown-rump length (CRL), and fetal heartbeat (FHB), was investigated. Methods: A total of 262 fetuses were included in the analysis between December 2022 and December 2023. Utilizing 2D power Doppler ultrasound images, aortic blood flow parameters were assessed, including aortic peak systolic velocity (PS), aortic end-diastolic velocity (ED), aortic time average maximal velocity (TAMV), and various indices such as aortic systolic velocity/diastolic velocity (S/D), aortic pulsatile index (PI), aortic resistance index (RI), aortic isthmus flow velocity index (IFI), and aortic isthmic systolic index (ISI). Concurrently, fetal FHB, NT, and CRL were evaluated during early trimester Down syndrome screening. Results: Significant findings include a positive correlation between gestational age (GA) and PS (PS = 3.75 × (GA) − 15.4, r2 = 0.13, p < 0.01), ED (ED = 0.42 × (GA) − 0.61, r2 = 0.04, p < 0.01), PI (PI = 0.07 × (GA) + 1.03, r2 = 0.04, p < 0.01), and TAMV (TAMV = 1.23 × (GA) − 1.66, r2 = 0.08, p < 0.01). In contrast, aortic ISI demonstrated a significant decrease (ISI = −0.03 × (GA) + 0.57, r2 = 0.05, p < 0.05) with gestational age. No significant correlation was observed for aortic RI (p = 0.33), S/D (p = 0.39), and IFI (p = 0.29) with gestational age. Aortic PS exhibited positive correlations with NT (0.217, p = 0.001) and CRL (0.360, p = 0.000) but a negative correlation with FHB (−0.214, p = 0.001). Aortic PI demonstrated positive correlations with CRL (0.208, p = 0.001) and negative correlations with FHB (−0.176, p = 0.005). Aortic TAMV showed positive correlations with NT (0.233, p = 0.000) and CRL (0.290, p = 0.000) while exhibiting a negative correlation with FHB (−0.141, p = 0.026). Aortic ISI demonstrated negative correlations with NT (−0.128, p = 0.045) and CRL (−0.218, p = 0.001) but a positive correlation with FHB (0.163, p = 0.010). Conclusions: Power Doppler angiography with Doppler ultrasound demonstrates the ability to establish accurate reference values for fetal aortic blood flow during the first trimester of pregnancy. Notably, aortic PS, TAMV, and ISI exhibit significant correlations with NT, CRL, and FHB, with ISI appearing more relevant than IFI, PS, TAMV, and FHB. The utilization of HDFI technology proves advantageous in efficiently detecting the site of the aortic isthmus compared to traditional color Doppler mode in early second trimesters.

BackgroundInfluenza A virus (IAV) infection poses a persistent global health challenge, necessitating a nuanced grasp of host immune responses for optimal interventions. While the interplay between aging, immunosenescence, and IAV is recognized as key in severe lower respiratory tract infections, the role of specific patient attributes in shaping innate immune reactions and inflammasome activity during IAV infection remains under-investigated. In this study, we utilized an ex vivo infection model of human lung tissues with H3N2 IAV to discern relationships among patient demographics, IAV nucleoprotein (NP) expression, toll-like receptor (TLR) profiles, PD-1/PD-L1 markers, and cytokine production.MethodsOur cohort consisted of thirty adult patients who underwent video-assisted thoracoscopic surgery during 2018–2019. Post-surgical lung tissues were exposed to H3N2 IAV for ex vivo infections, and the ensuing immune responses were profiled using flow cytometry.ResultsWe observed pronounced IAV activity within lung cells, as indicated by marked NP upregulation in both epithelial cells (P = 0.022) and macrophages (P = 0.003) in the IAV-exposed group relative to controls. Notably, interleukin-2 levels correlated with variations in TLR1 expression on epithelial cells and PD-L1 markers on macrophages. Age emerged as a modulating factor, dampening innate immune reactions, as evidenced by reduced interleukin-2 and interferon-γ concentrations (both adjusted P < 0.05). Intriguingly, a subset of participants with pronounced tumor necrosis factor-alpha post-mock infection (Cluster 1) showed attenuated cytokine responses in contrast to their counterparts in Cluster 2 and Cluster 3 (all adjusted P < 0.05). Individuals in Cluster 2, characterized by a low post-mock infection NP expression in macrophages, exhibited reduced variations in both NP and TLR1–3 expressions on these cells and a decreased variation in interleukin-2 secretion in comparison to their Cluster 3 counterparts, who were identified by their elevated NP macrophage expression (all adjusted P < 0.05).ConclusionOur work elucidates the multifaceted interplay of patient factors, innate immunity, and inflammasome responses in lung tissues subjected to ex vivo H3N2 IAV exposure, reflecting real-world lower respiratory tract infections. While these findings provide a foundation for tailored therapeutic strategies, supplementary studies are requisite for thorough validation and refinement.

Abstract Background Dementia [i.e., Alzheimer disease (AD)], the most common neurodegenerative disease, causes profound negative impacts on executive function and quality of life. Available pharmacological treatments often fail to achieve satisfactory outcomes. Noninvasive brain stimulation (NIBS) techniques, which focally modify cortical function and enhance synaptic long-term potentiation, are potentially beneficial for the cognition in patients with AD. The aim of the current network meta-analysis (NMA) was to evaluate the efficacy and safety of different NIBS interventions in patients with AD through NMA. Methods Only randomized controlled trials (RCTs) examining NIBS interventions in patients with AD had been included. All NMA procedures were performed under the frequentist model. The primary and secondary outcomes were changes in cognitive function and quality of life, respectively. Results Nineteen RCTs (639 participants) were included. The mean treatment and follow-up durations were 5.7 and 10.5 weeks, respectively. The combination of cathodal tDCS of the left dorsolateral prefrontal cortex and anodal tDCS over the right supraorbital region (c-tDCS-F3 + a-tDCS-Fp2) was associated with a significant beneficial effect on cognition compared with sham controls (standardized mean difference=2.43, 95% confidence interval=0.61–4.26, n=12 and 11). It was also associated with the greatest beneficial effect on cognition among all the investigated NIBS approaches. All the methods were well tolerated with regard to the safety profile, as reflected in the rates of adverse events or local discomfort, as well as acceptability, as indicated by dropout rate. Conclusions The present findings provide evidence of the benefits of NIBS, especially tDCS, for beneficial effect on cognition in patients with AD. However, because of few studies included, this effect was not replicated yet in the other studies. Therefore, future larger-scale and longer follow-up duration RCTs should be warranted. Trial registration PROSPERO CRD42020209516. The current study had been approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).

Abstract Background Current pharmacologic prophylactic strategies for migraine have exhibited limited efficacy, with response rates as low as 40%–50%. In addition to the limited efficacy, the acceptability of those pharmacologic prophylactic strategies were unacceptable. Although noninvasive brain/nerve stimulation strategies may be effective, the evidence has been inconsistent. The aim of this network meta-analysis (NMA) was to compare strategies of noninvasive brain/nerve stimulation for migraine prophylaxis with respect to their effectiveness and acceptability. Methods The PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov , ClinicalKey, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of June 4th, 2021 for randomized controlled trials (RCTs). Patients with diagnosis of migraine, either episodic migraine or chronic migraine, were included. All NMA procedures were conducted under the frequentist model. Results Nineteen RCTs were included (N = 1493; mean age = 38.2 years; 82.0% women). We determined that the high frequency repetitive transcranial magnetic stimulation (rTMS) over C3 yielded the most decreased monthly migraine days among all the interventions [mean difference = − 8.70 days, 95% confidence intervals (95%CIs): − 14.45 to − 2.95 compared to sham/control groups]. Only alternating frequency (2/100 Hz) transcutaneous occipital nerve stimulation (tONS) over the Oz (RR = 0.36, 95%CIs: 0.16 to 0.82) yielded a significantly lower drop-out rate than the sham/control groups did. Conclusions The current study provided a new direction for the design of more methodologically robust and larger RCTs based on the findings of the potentially beneficial effect on migraine prophylaxis in participants with migraine by different noninvasive brain/nerve stimulation, especially the application of rTMS and tONS. Trial registration CRD42021252638. The current study had been approval by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB No. B-109-29).

BackgroundBehçet’s disease (BD) is a unique autoimmune chronic systemic vasculitis that affects veins and arteries of all sizes. BD can lead to recurrent vascular events, especially venous thrombosis, with an incidence rate of 40%, or pseudoaneurysms formed under long-term inflammatory reaction or iatrogenic stimulation. BD-related risk factors promote endothelial dysfunction, platelet activation and overactivation of tissue factors leading to mural inflammatory thrombi. Thrombosis may be the first clinical manifestation of BD.Case presentationA 32-year-old man complaining of progressive swelling and pain in the right lower extremity for 30 days was initially diagnosed with “venous thrombosis of the right lower extremity,” using color Doppler ultrasonography. Patient underwent inferior vena cava filter placement combined with deep vein angioplasty of the right lower extremity and catheter-directed urokinase thrombolysis. Postoperative oral anticoagulant therapy was administered. However, the patient was readmitted 20 days later for pulsatile pain in the right groin. Prior medical history included 4 years of repeated oral and perineal ulcers, and 2 months of blurred vision. Abdominal computed tomography angiography (CTA) revealed rupture of the right common iliac artery (CIA) and left internal iliac artery (IIA), complicated by a pseudoaneurysm. Based on the clinical manifestations and other auxiliary examination results, the patient was re-diagnosed with “BD combined with deep venous thrombosis of the right lower extremity and an iliac artery pseudoaneurysm.” Stent implantation was performed for iliac artery pseudoaneurysm after symptoms were controlled with timely immunosuppressive therapy. After endovascular treatment, the patient underwent continued immunosuppressive therapy and dynamic reexaminations of abdominal CTA, which revealed that a small amount of contrast agent at the stent in the right CIA continued to flow into the cavity of the pseudoaneurysm; in addition, the size of the pseudoaneurysm was gradually increasing. Therefore, the patient underwent a second stent implantation for iliac artery pseudoaneurysm, and the condition improved further.ConclusionThe importance of early diagnosis of BD should be recognized, and the choice of interventional and surgical procedures should be carefully evaluated, as this may trigger further damage to vascular access in BD patients with aneurysm.

Abstract Beta-adrenergic blocking agents (abbreviated as beta-blockers) have been used for treating various cardiovascular diseases. However, the potential for asthma exacerbation is one of the major adverse effects of beta-blockers. This study aimed to compare the level of risk for an asthma attack in patients receiving various beta-blockers. We searched for randomized controlled trials (RCTs) of either placebo-controlled or active-controlled design. The current network meta-analysis (NMA) was conducted under a frequentist model. The primary outcome was the incidence of asthmatic attack. A total of 24 RCTs were included. Overall NMA revealed that only oral timolol [risk ratio (RR) = 3.35 (95% confidence interval (CI) 1.04–10.85)] and infusion of propranolol [RR = 10.19 (95% CI 1.29–80.41)] were associated with significantly higher incidences of asthma attack than the placebo, whereas oral celiprolol [RR = 0.39 (95% CI 0.04–4.11)], oral celiprolol and propranolol [RR = 0.46 (95% CI 0.02–11.65)], oral bisoprolol [RR = 0.46 (95% CI 0.02–11.65)], oral atenolol [RR = 0.51 (95% CI 0.20–1.28)], infusion of practolol [RR = 0.80 (95% CI 0.03–25.14)], and infusion of sotalol [RR = 0.91 (95% CI 0.08–10.65)] were associated with relatively lower incidences of asthma attack than the placebo. In participants with a baseline asthma history, in addition to oral timolol and infusion of propranolol, oral labetalol, oxprenolol, propranolol, and metoprolol exhibited significantly higher incidences of asthma attack than did the placebo. In conclusion, oral timolol and infusion of propranolol were associated with a significantly higher risk of developing an asthma attack in patients, especially in those with a baseline asthma history, and should be avoided in patients who present a risk of asthma. Trial registration: PROSPERO CRD42020190540.

Summary: Background: Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD. Methods: An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100–400 mg), medium (1 g), and high (at least 2 g). Findings: A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=−1.76 days (95% confidence intervals (95% CIs): −3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18–1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00–0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00–1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07–0.62) in refractory-stage KD. Interpretation: The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results. Funding: None.

Background: Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. Methods: The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. Findings: Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. Interpretation: The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin. Funding: none.

To assess hotspot micro-vessel flow velocity waveforms in human papillomavirus (HPV) cervical infections using transvaginal power Doppler ultrasound (TV-PDU) and to explore the associations of these sonographic parameters with HPV condyloma and low-grade squamous intraepithelial lesions (LSIL) of the cervix. A total of 39 patients with cervical HPV infections with abnormal cytology and colposcopy results (26 cases of LSIL; 13 cases of HPV condyloma) were enrolled to assess the vascular classification of the cervix and micro-vessel flow velocity using TV-PDU before treatment; 40 individuals with a pathologically normal cervix were used as the control group; seven parameters were measured, including vascular grading classification (Class I, Class II, and Class III), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), time average maximum velocity (TAMV), and the vascular index (VI = PS/ED). According to vascular classification, most LSILs were class I (69.2%, 18/26), followed by class II (26.9%, 7/26) and class III (3.8%, 1/26). Most HPV condylomas were class I (92.3%, 12/13), and one was class II (7.7%, 1/13). PI, RI, VI (p < 0.0001), and the PSs (p < 0.05) were significantly lower in these cases than in the controls. The ED and TAMV were not significantly different between the patients and controls (p = 0.4985 and p = 0.1564). No sonographic parameter was significantly different between LSIL and HPV condyloma. The mean PI, RI, and VI were significantly lower in LSIL than in the controls. For HPV condyloma, a PI of 1.07 had an 84.6% sensitivity, 85.0% specificity, and an AUC of 88.8%; for LSIL, a PI of 1.08 had a 100% sensitivity, 85% specificity, and an AUC of 94.2%; for HPV infection (HPV condyloma + LSIL), a PI of 1.08 had a 94.9% sensitivity, 85% specificity, and an AUC of 92.4%. Hotspot vascular classification and micro-vessel flow velocity waveforms may provide a potential practical method for the auxiliary diagnosis of cervical HPV infection. The PI may represent a valuable index for distinguishing the micro-vessel flow velocity waveforms in LSIL and HPV condyloma. Since the case numbers were limited in the current study, further validation is needed.

Summary: Background: Transumbilical approach has been shown to be feasible to perform lung wedge resection and anatomic lobectomy. This study uses a canine model to assess the feasibility of transumbilical segmentectomy. Methods: Transumbilical segmentectomy was performed in 10 beagle dogs using a 3-cm umbilical incision combined with a 2.5-cm diaphragmatic incision. We evaluated the surgical outcomes, operative complications, physiologic changes, hemodynamic changes, and inflammatory changes of the procedures. Results: Transumbilical segmentectomy was successfully completed in eight of ten animals. There was one mortality complication related to lung injury causing hemodynamic collapse. Another animal required conventional thoracotomy to complete the surgery due to limited working space. There were no notable events in the postoperative period for all eight dogs that completed the segmentectomy via the transumbilical approach. Conclusion: This animal study demonstrates that the pulmonary segmentectomy can be performed with current standard endoscopic instruments via a single transumbilical incision.We believe that advancing surgical innovation and good collaboration between multi-disciplinary research teams will further establish clearer roles for transumbilical segmentectomy in thoracic surgery. Keywords: Animal study, Transumbilical lung segmentectomy, Video assisted thoracic surgery

We have conducted cervical imaging of uterine and micro-vessel flow velocity waveforms in acute pelvic inflammatory disease (PID) by transvaginal power Doppler ultrasound (TVPDU) in order to explore the associations of sonographic parameters with simple and complex cervicitis. Thirty-eight patients with acute PID (26 with acute simple cervicitis and 12 with complex cervicitis) were enrolled for an assessment of vascular grading of cervix and micro-vessel flow velocity using TVPDU before treatment. Seven parameters, including vascular grading (VG), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end diastolic velocity (ED), time average maximum velocity (TAMV), and vascular index (VI = PS/ED), were measured and recorded. Forty-one healthy patients were assessed as the control group. Vascular grading (VG) was significantly higher in the study group than the control group (p < 0.0001). The PI, RI, and VI were significantly lower in the study group than control group (p < 0.0001). No significant associations were observed between seven sonographic parameters and acute simple or/and complex cervicitis. For acute simple cervicitis, a PI cutoff of 1.1 had a sensitivity of 85.4% and a specificity of 92.1% (area under ROC curve [AUC], 93.2%). A RI of 0.6 had a sensitivity of 85.4% and a specificity of 78.9% (AUC, 86.1%). A VI of 2.6 had a sensitivity of 85.4% and a specificity of 78.9% (AUC, 84.9%). Power Doppler angiography of micro-vessel flow velocity waveforms in the cervix could represent a practical method to assist the diagnosis of pelvic inflammatory disease presented as acute cervicitis detected on transvaginal ultrasound before medical or surgical treatment. Cervical PI may be a useful index to detect micro-vessel flow velocity waveforms in acute cervicitis and differentiate acute simple cervicitis from complex cervicitis.

The application of transcranial direct current stimulation (tDCS) to targeted cortices has been found to improve in skill acquisition; however, these beneficial effects remained unclear in fine and complicated skill. The aim of the current meta-analysis was to investigate the association between tDCS application and the efficacy of surgical performance during surgical skill training. We included randomized controlled trials (RCTs) investigating the efficacy of tDCS in enhancing surgical skill acquisition. This meta-analysis was conducted under a random-effect model. Six RCTs with 198 participants were included. The main result revealed that tDCS was associated with significantly better improvement in surgical performance than the sham control (Hedges’ g = 0.659, 95% confidence intervals (95%CIs) = 0.383 to 0.935, p < 0.001). The subgroups of tDCS over the bilateral prefrontal cortex (Hedges’ g = 0.900, 95%CIs = 0.419 to 1.382, p < 0.001) and the primary motor cortex (Hedges’ g = 0.599, 95%CIs = 0.245 to 0.953, p = 0.001) were both associated with significantly better improvements in surgical performance. The tDCS application was not associated with significant differences in error scores or rates of local discomfort compared with a sham control. This meta-analysis supported the rationale for the tDCS application in surgical training programs to improve surgical skill acquisition.

Platelet rich plasma (PRP) contains various cytokines and growth factors which may be beneficial to the healing process of injured muscle. The purpose of this study is to investigate the effect and molecular mechanism of PRP releasate on proliferation of skeletal muscle cells. Skeletal muscle cells intrinsic to Sprague–Dawley rats were treated with PRP releasate. Cell proliferation was evaluated by 3-[4,5-Dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and immunocytochemistry with Ki-67 stain. Flow cytometric analysis was used to evaluate the cell cycle progression. Western blot analysis was used to evaluate the protein expressions of PCNA, cyclin E1, cyclin A2, cyclin B1, cyclin dependent kinase (cdk)1 and cdk2. The results revealed that PRP releasate enhanced proliferation of skeletal muscle cells by shifting cells from G1 phase to S phase and G2/M phases. Ki-67 stain revealed the increase of proliferative capability after PRP releasate treatment. Protein expressions including cyclin A2, cyclin B1, cdk1, cdk2 and PCNA were up-regulated by PRP releasate in a dose-dependent manner. It was concluded that PRP releasate promoted proliferation of skeletal muscle cells in association with the up-regulated protein expressions of PCNA, cyclin A2, cyclin B1, cdk1 and cdk2.

Background: Pathologic N2 non-small-cell lung cancer (NSCLC) was demonstrated with poor survival among literature. In this study, we retrospectively reviewed patients with pathologic N2 NSCLC and received anatomic resection (i.e. lobectomy) for further relapse risk factor analysis. The aim of this study is to identify the clinicopathologic factors related to relapse among resectable N2 NSCLC patients and to help clinicians in developing individualized follow up program and treatment plan. Method: From January 2005 to July 2012, 90 diagnosed pathologic N2 NSCLC patients were enrolled into this study. We retrospectively reviewed medical records, image studies, and pathology reports to collect the patient clinico-pathologic factors. Result: We identified that patients with visceral pleural invasion (p = 0.001) and skip metastases along mediastinal lymph node (p = 0.01) had a significant relationship to distant and disseminated metastases. Patients who had 2 or more risk factors for relapse demonstrated poor disease free survival than those who had less than 2 risk factors (p = 0.02). The number of involved metastatic area were significantly influential to the period of time-to-progression. The duration of time-to-progression was correlated with square of number of involved metastatic areas. (Pearson correlation coefficient = −0.29; p = 0.036). Conclusion: Relapse risk factors of resectable pathologic N2 NSCLC patient after anatomic resection were visceral pleural invasion, skip mediastinal lymph node involvement, and the receipt of neoadjuvant therapy. The duration of time-to-progression was correlated with square of number of involved metastatic areas.

[This corrects the article DOI: 10.1371/journal.pone.0206386.].

INTRODUCTION:Tumor characteristics in computed tomography (CT) are correlated to pathologic presentation and survival. However, most studies have been based on thin slice thickness CT while lymph node metastatic pattern has remained unclear. The aim of this study was to analyze the correlation between image characteristics under 5 mm slice thickness and pathology findings in non small lung cancer patients who have received curative resection. MATERIALS AND METHODS:From January 2010 to May 2014, 440 patients who underwent curative resection were included and medical records were reviewed retrospectively. The tumor size and consolidation tumor ratio were simultaneously evaluated and measured by a physician, a thoracic surgeon, and a radiologist. The correlation between image and pathology characteristics and its survival impact was analyzed. RESULTS:Tumor sizes, as measured by CT and by pathologic measurement were highly coincident. (p < 0.001) GGO predominant lesions were correlated to well-differentiated adenocarcinoma, (p< 0.001), and less tumor necrosis (p

BACKGROUND:Scrub typhus is endemic in the Asia-Pacific region including China, and the number of reported cases has increased dramatically in the past decade. However, the spatial-temporal dynamics and the potential risk factors in transmission of scrub typhus in mainland China have yet to be characterized. OBJECTIVE:This study aims to explore the spatiotemporal dynamics of reported scrub typhus cases in mainland China between January 2006 and December 2014, to detect the location of high risk spatiotemporal clusters of scrub typhus cases, and identify the potential risk factors affecting the re-emergence of the disease. METHOD:Monthly cases of scrub typhus reported at the county level between 2006 and 2014 were obtained from the Chinese Center for Diseases Control and Prevention. Time-series analyses, spatiotemporal cluster analyses, and spatial scan statistics were used to explore the characteristics of the scrub typhus incidence. To explore the association between scrub typhus incidence and environmental variables panel Poisson regression analysis was conducted. RESULTS:During the time period between 2006 and 2014 a total of 54,558 scrub typhus cases were reported in mainland China, which grew exponentially. The majority of cases were reported each year between July and November, with peak incidence during October every year. The spatiotemporal dynamics of scrub typhus varied over the study period with high-risk clusters identified in southwest, southern, and middle-eastern part of China. Scrub typhus incidence was positively correlated with the percentage of shrub and meteorological variables including temperature and precipitation. CONCLUSIONS:The results of this study demonstrate areas in China that could be targeted with public health interventions to mitigate the growing threat of scrub typhus in the country.

Recently Echinoderm microtubule-associated protein-like 4- anaplastic lymphoma kinase (EML4-ALK) fusion gene has become an important biomarker for ALK tyrosine kinase inhibitor (crizotinib) treatment in NSCLC. However, the best detection method and the significance of EML4-ALK variant types remain uncertain.Reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescence in Situ hybridization (FISH) and Immunohistochemical (IHC) stain were performed on tumor tissues of 312 NSCLC patients for detection of ALK rearrangements. Mutation analyses for EGFR and KRAS genes were also performed.Thirteen of the 312 patients (4.17%) had ALK rearrangements detected by RT-PCR. If RT-PCR data was used as the gold standard, FISH tests had a low sensitivity (58.33%), but very good specificity (99.32%). IHC stain had better sensitivity (91.67%) than FISH, but lower specificity (79.52%), when the cut off was IHC2+. All of the 8 patients with high abundance of EML4-ALK positive cells in tumor tissues (assessed by the signal intensities of the RT-PCR product), were also have high expression of ALK protein (IHC3+), and positive for FISH, except one failed in FISH. Variants 3a+3b (4/5, 80%) of EML4-ALK fusion gene were more common to have high abundance of EML4-ALK positive cells in tumor tissues than variant 1 (1/3, 33.3%). Meta-analysis of the published data of 2273 NSCLC patients revealed that variant 3 (23/44, 52.3%) was the most common type in Chinese population, while variant 1 (28/37, 75.7%) was most common in Caucasian.Among the three detection methods, RT-PCR could detect not only the presence of EML4-ALK fusion gene and their variant types, but also the abundance of EML4-ALK positive cells in NSCLC tumor tissues. The latter two factors might affect the treatment response to anti-ALK inhibitor. Including RT-PCR as a diagnostic test for ALK inhibitor treatment in the prospective clinical trials is recommended.

BACKGROUND: Natural orifice transluminal endoscopy has been developed for abdominal surgical procedures. The aim of this study was to compare the surgical outcome between a novel transoral approach and a standard transthoracic approach for the thoracic cavity in a canine model. METHODS: Twenty-eight dogs were assigned to transoral (n = 14) or standard thoracoscopy (n = 14). Each group underwent thoracic exploration, pre-determined surgical lung biopsy, and pericardial window creation. Blood draws were obtained before surgery and at postoperative days 1, 3, 7, and 14. Operative time, complications, laboratory parameters, hemodynamic parameters, and inflammatory parameters were compared between the two procedures. The animals were monitored for two weeks and necropsy were performed for surgical outcome evaluation. RESULTS: The thoracic procedures were successfully performed in all of the dogs, with the exception of one animal in the transoral group. There were no serious acute or delayed complications related to surgery. There was no difference between the two surgical groups for each of the hemodynamic parameters that were evaluated. Regarding the immunological impact of the surgeries, transoral thoracoscopy was associated with significant elevations in interleukin 6 and c-reactive protein levels on postoperative days 1 and 3, respectively, when compared with the standard thoracoscopy. All dogs recovered well, without signs of mediastinitis or thoracic infection. Necropsy revealed absence of infection, no injury to vital organs, and confirmed the success of the novel procedure. CONCLUSIONS: This study suggests that both techniques were comparable with respect to procedure success rate, hemodynamic impact, and inflammatory changes. Furthermore, there was no difference in the incidence of postoperative discomfort between groups.

In the crystal structure of the title organic salt, C16H19N2+·C9H11O3S−·H2O, the cations pack head-to-tail within a sheet and are aligned in opposite directions in neighboring sheets. The benzene ring of the anion makes an angle of 76.99 (6)° with the plane of the cationic chromophore. The cations are situated in the ab plane, whereas the benzene rings of the anions lie in the ac plane.

The title compound, KZnB3O6 contains a remarkable [B6O12]6− group (overline{1} symmetry) formed by two rings linked by edge-sharing BO4 tetrahedra, a feature that has only been observed previously under high pressure conditions. These borate groups are connected through distorted ZnO4 tetrahedra in edge-shared pairs (overline{1} symmetry), forming a three-dimensional network whose cavities are filled by K+ cations.

"Genres of Listening: An Ethnography of Psychoanalysis in Buenos Aires" is a book that explores the cultural practices of psychoanalysis in Buenos Aires, Argentina. The author examines how psychoanalysis has permeated Argentine society and become part of everyday life. The book focuses on the linguistic aspects of psychoanalysis and highlights the importance of listening as a core cultural practice in Argentine social interactions. It also discusses the influence of psychoanalysis in popular culture and its role in addressing social suffering in a postcolonial context. While the book lacks an explanation for why psychoanalysis has become popular, it offers valuable insights into healthcare phenomena in postcolonial contexts and is recommended for readers interested in this topic. [Extracted from the article]