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Introduction: The association between age-related macular degeneration and asthma is controversial. Transforming growth factor beta (TGF-β), which plays a critical role in asthma, has been extensively studied with regard to its function in choroidal neovascularization (CNV). In the present study, we aimed to investigate the role of TGF-β and the possible mechanism of CNV formation complicated with asthma and to explore the effect of a TGF-β inhibitor on CNV development in asthma mouse models. Methods: Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into 5 groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group, and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography and histology of CNV lesions stained with haematoxylin-eosin were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-β1, TGF-β2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissues from each group. Results: In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-β1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissues were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-β inhibitor, a distinct decline in VEGF, TGF-β1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased. Conclusion: We provide new evidence that asthma could be a risk factor for CNV development via the TGF-β1/Smad signalling pathway. A TGF-β inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients. [ABSTRACT FROM AUTHOR]

Objectives: In the present study, inflammatory factors, including interleukin (IL) and tumor necrosis factor-α (TNF-α) in the peripheral blood of patients with sporadic amyotrophic lateral sclerosis (sALS), were evaluated, and the issue of whether these variables were associated with the progression and severity of the disease examined. Methods: Data on inflammatory factors, including IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α, were retrospectively collected from 248 sALS patients admitted to the Chinese PLA General Hospital between March 2018 and March 2021. The relationships between the variables and clinical features, including gender, age at onset, site of onset, time from onset to hospital admission, ALS functional rating scale score, and diagnostic category were analyzed. Results: IL-1, IL-2, IL-6, IL-8, IL-10, and TNF-α levels were elevated in 43.75%, 7.04%, 16.42%, 25.35%, 1.41%, and 50.72% of ALS patients, respectively, compared with the normal value range. IL-2 and IL-6 levels were inversely associated with the ALS functional rating scale score (r = −0.280, p = 0.004 and r = −0.198, p = 0.048). Conclusion: Elevated levels of inflammatory cytokines support the hypothesis of an inflammatory response in ALS, and IL-2 and IL-6 may be used as an inflammation-related biomarker for disease severity. [ABSTRACT FROM AUTHOR]

Objective: This retrospective study analyzed the clinical characteristics and prognosis of the elderly amyotrophic lateral sclerosis (ALS) population in a large sample. Methods: The study included 1,005 patients with sporadic ALS admitted to Chinese PLA General Hospital between March 2011 and March 2021. We stratified the ALS patients into young and old groups using 2 cutoffs for the age at disease onset (≥65 or ≥70 years old) and compared their demographic, clinical, and survival data. Results: The mean onset age of all patients was 52.79 ± 10.55 years, with 123 (12.24%) having a disease onset ≥65 years and 44 (4.38%) having an onset ≥70 years. There were 624 (62.1%) male patients. More bulbar-onset cases were in the late-onset group (p = 0.001). The sex distribution, time from onset to diagnosis, and the time of symptom spread from spinal or bulbar localization to a generalized localization did not differ between groups. Late-onset patients progressed more rapidly and had a significantly shorter survival. Conclusions: Chinese ALS patients have an earlier age at onset and a relatively smaller proportion of old onset than European and Japanese patients. Elderly patients are more likely to have bulbar onset, which is related to rapid progression and a shorter survival. [ABSTRACT FROM AUTHOR]

Background: Cellulose powder (CP) has been reported as a safe and effective complementary treatment for allergic rhinitis (AR). Currently, CP has gained increasing application for clinical management worldwide, particularly in China. However, studies focusing on the effect of CP on normal human nasal epithelial cells (hNECs) and ciliary function are lacking. Here, we aimed to explore the adverse effects of CP on the activity and ciliary function of hNECs. Methods: We biopsied ethmoid sinus or middle turbinate tissues during surgical resection from control subjects who underwent endoscopic sinus surgery for diseases other than AR. Cells were isolated and passaged, followed by differentiation in an air-liquid interface (ALI). Flow cytometry and cell viability test (cell counting kit-8) were performed to detect the cytotoxicity of CP (effects on cell proliferation) on normal hNECs. By using the ALI culture model, we investigated the effects of CP on ciliary beat frequency (CBF). Results: There was a significant reduction in hNEC count at high concentrations of CP (2.5 mg/mL) at days 3 and 7 (both p < 0.05). As the concentration increased, cell death increased progressively from day 3 to day 7. However, these effects were not evident at low concentrations (0.25 mg/mL, p > 0.05). High-dose CP (2.5 mg) significantly reduced the CBF (p < 0.05). At lower concentrations (0.25–2.5 mg/mL), CP initially increased but subsequently reduced the CBF of hNECs compared with control group. Conclusions: Cytotoxicity and the suppression of ciliary beat at high concentrations justify more prudent use of CP for the management of AR. [ABSTRACT FROM AUTHOR]

>bold<>italic/italic<>/bold< There are sparse and limited studies on small sample size reporting the application of next-generation sequencing (NGS) in the detection of central nervous system (CNS) viral infections. We assessed the diagnostic performance of NGS of cerebrospinal fluid (CSF) for predicting viral infections of the CNS caused by the neurotropic herpes viruses in a pilot population. >bold<>italic/italic<>/bold< We prospectively collected CSF samples from 24 patients with CNS viral infection from April 2017 to October 2018. Of the 24 patients, 19 patients were infected with herpes simplex virus 1 (HSV-1), 1 patient with HSV-2, and 4 patients with varicella-zoster virus (VZV). All CSF samples were screened for viral DNA using NGS technologies to detect viral CNS infections. >bold<>italic/italic<>/bold< Of the 24 patients with confirmed viral CNS infection caused by the neurotropic herpes viruses, 10 (10/24, 41.67%) patients exhibited positive NGS results. With the help of NGS, HSV-1 DNA was detected in the CSF of 6 patients (6/19; 31.58%). HSV-2 DNA was detected in 1 patient (1/1; 100%) and VZV DNA was detected in 3 patients (3/4; 75%). The positive rate of virus detected by NGS decreased with time. The positive rates of NGS of CSF in the first, second, and third weeks were 54.5% (6/11), 44.4% (4/9), and 0% (0/4), respectively. >bold<>italic/italic<>/bold< NGS method is a promising pathogen detection tool for identifying viral CNS infections. It should be recommended to sequence viral DNA of CSF in the early stage of CNS viral infections. [ABSTRACT FROM AUTHOR]

Background/Aims: Androgen and its receptor (AR) play an important role in maintaining spermatogenesis and male fertility. Our previous studies showed that testosterone at a physiological concentration induces cytoplasmic AR translocation to the Sertoli cell plasma membrane of within 5 minutes. Methods: In this study, mass spectrometry (MS) and bioinformatic analyses were applied to identify candidate proteins mediating AR trafficking. The candidate proteins were knocked down by shRNA transfection. Results: Nine candidate proteins were identified by MS. The data was verified by co-immunoprecipitation and Western blot. Of the candidates, CSN6 regulated AR transport through the phosphorylation signaling pathway and Rab34 affected AR trafficking by regulating Ras activity. Conclusions: CSN6 and Rab34 are involved in AR trafficking by regulating the phosphorylation signaling pathway. These findings provide new insights into the testosterone signaling pathway in Sertoli cells that mediates spermatogenesis. [ABSTRACT FROM AUTHOR]

Background/Aims: Adult cardiomyocytes can re-enter cell cycle as stimulated by prohypertrophic factors although they withdraw from cell cycle soon after birth. p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution to this process remains largely unclear. Methods: The gene expression profile in left ventricle (LV) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined using quantitative PCR array and verified by real-time PCR and Western blotting. Hypertrophic response of H9c2 cells and neonatal rat ventricular myocytes (NRVM) were induced by angiotensin II (1 μmol/L). Cardiac hypertrophy of mice was elicited by isoproterenol (ISO) infusion (40 mg/kg per day for 14 days). p21-adenovirus and p21-siRNA were employed to transfect NRVM, and sterigmatocystin (STE, 3 mg/kg, ip, qd) was used to inhibit p21 activity. mRNA and protein expression levels of α- and β-myosin heavy chain (MHC), p21WAF1/CIP1, calcineurin (CaN) and atrial natriuretic peptide (ANP) were assayed by realtime PCR and WB, respectively. Results: Sixteen genes showed two-fold or greater changes between SHR and WKY rats, in which the expression of p21WAF1/CIP1 was upregulated by 4.15- fold (P=0.002) and reversed by losartan. Surface area, protein content, mRNA and protein expressions of β-MHC, ANP and p21WAF1/CIP1 in H9c2 cells treated with AngII elevated significantly compared with control group. p21-Ad transfection markedly increased the surface area and β-MHC mRNA expression of normal NRVMs, and p21-siRNA transfection decreased them in AngII-treated NRVMs. STE treatment decreased HW/BW and cross-sectional area, expression levels of β-MHC, ANP and p21 significantly in ISO-treated mice. Conclusion: Our findings suggest that p21 facilitates the development of cardiac hypertrophy, and regulating the expression of p21 may be an approach to attenuate hypertrophic growth of cardiomyocytes. [ABSTRACT FROM AUTHOR]

Background: The fusing of the epicardium and sternum due to adhesion is a common problem during repeated cardiac surgery and carries with it an increased risk of bleeding. The use of barriers and patches has been tested to prevent the formation of adhesions, but the very presence of a patch can provoke adhesion formation. The objective of this study was, therefore, to investigate both biodegradable and bioresorbable polylactone patches [(polycaprolactone-poly(ethylene oxide)-polycaprolactone tri-block copolymer (PCE)]. The patches were also tested with a controlled release of rapamycin, which prevents cell migration and extracellular matrix deposition. The clinical effectiveness of rapamycin in pericardial patches has not previously been examined. Materials and Methods: Three groups of 6 female Danish Landrace pigs underwent sternotomy and abrasion of the epicardium, before being randomized to either group 1 - the control group (with no patch), group 2 - PCE patch implanted between the sternum and epicardium, or group 3 - PCE patch and slow-release 1.6-mg rapamycin. After a median time period of 26 days, the pigs were euthanized and their hearts removed en bloc with the sternum, for macroscopic, histological and pathological examination. Results: Upon macroscopic examination, a significantly lower degree of adhesion in group 2, as compared to group 1 (p < 0.05), was found. Histological analysis of the tissues showed significantly more fibrosis, inflammation and foreign body granulomas (p < 0.05) in both group 2 and group 3, when compared to group 1. Conclusion: A PCE patch following sternotomy in animal subjects reduces postoperative macroscopic adhesions without reducing microscopic fibrosis or inflammation. Loading the patch with rapamycin was found not to increase the antifibrotic effect. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: We investigated the correlation between disease severity and electrophysiological characteristics in 77 Chinese myasthenia gravis (MG) patients. Materials and Methods: Disease severity was assessed and compared with repetitive nerve stimulation (RNS) and needle electrode electromyography (NEMG) evaluations. Results: The quantified myasthenia gravis (QMG) and MG-activities of daily living (MG-ADL) scores correlated well with the proximal muscle decremental response rate. NEMG revealed that 22 patients (28.6%) had myopathic changes, but none demonstrated spontaneous potentials. Only motor unit potentials showed short durations and low amplitude changes. Patients with myopathic changes had higher QMG and MG-ADL scores, and their classifications were different from patients with normal NEMG results. Conclusions: Decreased RNS compound muscle action potential amplitudes correlated with MG severity, and were more pronounced in the proximal than in the distal muscles. Patients with myopathic changes showed more severe disease characteristics. Thus, electrophysiological tests are useful for MG diagnosis and can indicate disease severity. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To identify the associations of the two complement factor I (CFI) polymorphisms rs10033900 and rs2285714 with risk of neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a Chinese case-control study. Methods: A total of 900 subjects - 300 controls, 300 cases with nAMD and 300 cases with PCV - were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs10033900 and rs2285714 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between the cases and controls were tested by a χ2 test with age and gender adjusted for by logistic regression analysis. We also performed a meta-analysis of the case-control studies of rs10033900 and rs2285714 based on the currently available evidence from the literature. The meta-analysis was conducted via an inverse-variance, fixed-effects model, as previously described. Results: No statistically significant association was observed between the two polymorphisms of CFI and AMD risk, including nAMD, PCV and combined AMD (p > 0.05 for all comparisons). By meta-analysis, we detected significant associations between both of the SNPs and late AMD, which is consistent with previous results (odds ratio, OR, rs10033900 = 0.814, p rs10033900 < 0.001; OR rs2285714 = 1.221, p rs2285714 < 0.001). For rs2285714, the results of the meta-analysis were less reliable due to its heterogeneity. Conclusions: In our case-control study, neither of the two SNPs most studied (rs10033900 or rs2285714) in the CFI gene was a risk factor for developing nAMD or PCV in a Chinese population. Additional large, comprehensive and well-designed association studies are needed to better understand the role of ethnicity and other gene interactions in the association between the CFI gene and AMD. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To analyze the association between ABCA1 rs1883025 variants with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a northern Chinese population. Methods: The study enrolled 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV. Genomic DNA was extracted from venous blood leukocytes. Single-nucleotide polymorphisms in the ABCA1 (rs1883025) gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results: The ABCA1 rs1883025 polymorphism was not significantly associated with nAMD (22.5%; p > 0.05) or PCV (20.8%; p > 0.05) in a northern Chinese population. The association remained insignificant after adjustment for age and gender differences (p > 0.05). Conclusions: This study suggests that ABCA1 rs1883025 variants are not associated with nAMD or PCV in a Chinese population, which is likely due to an ethnic difference. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Although evidence supports a role for inflammation in interstitial cystitis/bladder pain syndrome (IC/BPS), the mechanism remains unknown. We determined whether inflammation causes an elevated expression of nerve growth factor (NGF) and transient receptor potential vanilloid receptor subtype 1 (TRPV1) and correlated them with the symptoms. Methods: Bladder biopsies were obtained from 53 IC/BPS patients and 27 controls, and hematoxylin and eosin staining, immunostaining and Western blotting were performed to detect inflammation, TRPV1-immunoreactive and PGP9.5-immunoreactive nerve fibers, and NGF, respectively. Symptoms were assessed using the Pelvic Pain/Urgency/Frequency (PUF) questionnaire and pain visual analogue scale scores. Suburothelial nerve fiber density was quantified and correlated with PUF scores. Results: Increased severity of inflammation was correlated with a higher TRPV1-immunoreactive nerve fiber density (r = 0.4113, p = 0.0024) and higher NGF levels (r = 0.3775, p = 0.0052). Suburothelial TRPV1-immunoreactive nerve fiber density was significantly correlated with pain scores and urgency scores (r = 0.3320, p = 0.0145 and r = 0.3823, p = 0.0039, respectively). PGP9.5-immunoreactive nerve fibers were significantly increased in IC/BPS (p = 0.0193) and had a positive relationship with inflammation severity (r = 0.6138, p < 0.0001). Conclusions: Our study revealed increased severity of inflammation correlated with a higher expression of TRPV1-immunoreactive nerve fibers and NGF in IC/BPS and correlated with clinical symptoms. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Familial aggregation has been shown for Alzheimer's disease (AD) and Parkinson's disease (PD) separately, and it has been hypothesized that these diseases also coaggregate in families. Methods: The authors investigated familial coaggregation of AD and PD by conducting a systematic review and meta-analysis. PubMed was searched for relevant studies published through the end of October 2012. Three independent investigators screened publications and extracted data. Relative risk estimates of AD risk associated with family history of PD or parkinsonism, or PD risk associated with family history of AD or dementia, were summarized into metaestimates using random effects models. Heterogeneity and publication bias were tested using Higgins' and Egger's tests, respectively. Results: We included 16 studies in the review, with 14 included in any meta-analysis. AD risk associated with family history of PD yielded a summary hazard ratio of 1.18 (95% CI: 1.00-1.39) based on 5 reconstructed cohort studies and a summary odds ratio (OR) of 1.40 (95% CI: 0.92-2.12) based on 7 case-control studies. PD risk associated with family history of AD yielded a summary OR of 0.75 (95% CI: 0.49-1.16) based on 3 studies. There was no significant heterogeneity among studies, nor significant publication bias. Conclusions: There may be familial coaggregation of AD and PD, although the association was modest and only apparent when studying AD risk associated with family history of PD. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To compare operative time, safety and effectiveness of minimally invasive percutaneous nephrolithotomy (MPCNL) in the supine lithotomy versus prone position. Methods: Between January 2008 and December 2010, a total of 109 consecutive patients with upper urinary tract calculi were enrolled and randomly divided into group A (53 patients, supine lithotomy position) and group B (56 patients, prone position). The MPCNL procedures were performed under the guidance of real-time grayscale ultrasound system. The preoperative characteristics, intraoperative and postoperative parameters were analyzed and compared. Results: All patients were successfully operated. There was no significant difference between the two groups in stone-free rate (group A 90.1 vs. group B 87.5%, p = 0.45), mean blood loss, number of access tracts, calyx puncture, mean hospital stay (group A 6 ± 1.1 vs. group B 6 ± 1.5 days, p = 0.38) and complications. But the operative time was significantly shortened in supine lithotomy position (group A 56 ± 15 vs. group B 86 ± 23 min, p < 0.001). Conclusions: The effectiveness and safety of the supine lithotomy position for MPCNL were similar to the prone position. However, the supine lithotomy position has an important advantage of reducing the operative time. The supine lithotomy position could be a good choice to perform MPCNL. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between surgeon's experience, tumor characteristics, absent detrusor muscle (DM) tissue in resected specimens, and residual tumor after an initial transurethral resection. Patients and Methods: We conducted an analysis of 216 patients from two centers over a 3-year period. Patients with primary bladder tumors that were judged to have been completely resected were recruited. The data included tumor characteristics, surgeon category, and DM status. Logistic regression multivariate analyses were conducted. Results: Large tumors, lateral/dome/anterior wall tumors, and surgery performed by junior surgeons were independently associated with absent DM. Large tumors, dome/anterior wall tumors, T1 and absent DM were independently associated with residual disease. The absence and presence of the DM were associated with residual tumor rates of 51.8 and 20.9%, respectively (OR 15.537). Resection by senior surgeons was associated with the presence of DM and clean resection (OR 0.274 and 0.141, respectively). Conclusions: Absent DM and residual tumor were more likely to occur in cases involving large tumors that were located in the lateral/dome/anterior wall, especially when the surgery was performed by a junior surgeon. Absent DM appears to be a surrogate marker for residual disease. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]