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Background: Genetic variations in endoplasmic reticulum aminopeptidase (ERAP1, ERAP2) genes are associated with the pathogenesis of multiple diseases, including infectious diseases. The objective of our study was to assess whether ERAP1, ERAP2 genes polymorphisms and methylation levels affect the risk of pulmonary tuberculosis (PTB)., Methods: We genotyped ten single nucleotide polymorphisms (SNPs) in ERAP1, ERAP2 genes among 497 PTB patients and 502 controls by SNPscan technique. Additionally, we detected the ERAP1, ERAP2 genes methylation levels in 98 PTB patients and 97 controls through Illumina Hiseq platform., Results: Our results showed that the GG genotype, G allele frequencies of ERAP2 gene rs2549782 were significantly increased in PTB patients compared to controls, and rs2549782 polymorphism was related to the increased risk of PTB under recessive model. In addition, no significant relationship was found between ERAP1 gene rs13167972, rs17086651, rs469783, rs26618, rs3734016, ERAP2 gene rs17524572, rs1230358, rs2549794, rs117041256 and PTB susceptibility. Among PTB patients, the frequencies of rs17524572 TT genotype, T allele were significantly associated with drug-induced liver injury, and rs1230358, rs2549782, rs2549794 polymorphisms were linked to the occurrence of fever. Haplotype analysis of ERAP2 gene suggested that the frequency of CTGGT haplotype was higher, while the frequency of CTGTT haplotype was lower in PTB patients. When compared with controls, the ERAP1 methylation level was lower in PTB patients, while the ERAP2 methylation level was significantly increased. Moreover, rs1230358 polymorphism was found to affect the ERAP2 methylation level., Conclusion: The ERAP2 rs2549782 variant and altered methylation levels of ERAP1, ERAP2 genes were related to susceptibility to PTB., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethical Committee of Anhui Chest Hospital (K2023-011). All the study subjects provided informed consent to participate in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable., (© 2025. The Author(s).)

Background: The impact of polycyclic aromatic hydrocarbons (PAHs) on lung function has garnered attention, but studies mostly focus on individual effect. This study investigates urinary PAH metabolites as biomarkers of exposure and assesses the relationships between single and combined exposures to nine urinary PAH metabolites and lung function in adults., Methods: Data from 4040 adults in the 2007-2012 National Health and Nutrition Examination Survey (NHANES) were analyzed. Weighted generalized linear models estimated the effects of individual PAH metabolites on lung function. Additionally, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) were employed to evaluate the combined impacts of multiple PAH metabolites., Results: Analyses of individual PAH metabolites revealed negative associations with lung function, excluding forced vital capacity (FVC). The WQS, qgcomp, and BKMR models consistently showed that exposure to multiple PAH metabolites was associated with lung function decrease. WQS indicated that 2-hydroxynaphthalene (2-NAP) was the largest contributor to the reductions in forced expiratory volume in 1 s (FEV1), FVC, peak expiratory flow (PEF), and forced expiratory flow from 25 to 75% of FVC (PEF25-75%). Additionally, 1-hydroxypyrene (1-PYR) was the primary PAH metabolite contributing to the decreases in FEV1/FVC and fractional exhaled nitric oxide (FeNO). The combined effect of urinary PAH metabolites did not affect FVC in the current smokers or FeNO in nonsmokers, but decreased FEV1/FVC in current smokers., Conclusion: This study strengthens the negative relationships between multiple PAH metabolites exposure and lung function in adults. Given the limitations of this study, including the lack of knowledge of other exposure pathways and the uncertainty of urinary metabolites, further research is necessary to explore the mechanisms underlying these associations and to address the limitations in exposure assessment., (© 2024. The Author(s).)

Dietary pollution of Aflatoxin B1 (AFB1) poses a great threat to global food safety, which can result in serious hepatic injuries. Following the widespread use of plastic tableware, co-exposure to microplastics and AFB1 has dramatically increased. However, whether microplastics could exert synergistic effects with AFB1 and amplify its hepatotoxicity, and the underlying mechanisms are still unelucidated. Here, mice were orally exposed to 100 nm polystyrene nanoplastics (NPs) and AFB1 to investigate the influences of NPs on AFB1-induced hepatic injuries. We found that exposure to only NPs or AFB1 resulted in colonic inflammation and the impairment of the intestinal barrier, which was exacerbated by combined exposure to NPs and AFB1. Meanwhile, co-exposure to NPs exacerbated AFB1-induced dysbiosis of gut microbiota and remodeling of the fecal metabolome. Moreover, NPs and AFB1 co-exposure exhibited higher levels of systemic inflammatory factors compared to AFB1 exposure. Additionally, NPs co-exposure further exacerbated AFB1-induced hepatic fibrosis and inflammation, which could be associated with the overactivation of the TLR4/MyD88/NF-κB pathway. Notably, Spearman's correlation analysis revealed that the exacerbation of NPs co-exposure was closely associated with microbial dysbiosis. Furthermore, microbiota from NPs-exposed mice (NPs FMT ) partly reproduced the exacerbation of NPs on AFB1-induced systemic and hepatic inflammation, but not fibrosis. In summary, our findings indicate that gut microbiota could be involved in the exacerbation of NPs on AFB1-induced hepatic injuries, highlighting the health risks of NPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Methamphetamine (Meth) is a potent psychostimulant with well-established hepatotoxicity. Gut microbiota-derived short-chain fatty acids (SCFAs) have been reported to yield beneficial effects on the liver. In this study, we aim to further reveal the mechanisms of Meth-induced hepatic injuries and investigate the potential protective effects of SCFAs. Herein, mice were intraperitoneally injected with 15 mg/kg Meth to induce hepatic injuries. The composition of fecal microbiota and SCFAs was profiled using 16 S rRNA sequencing and Gas Chromatography/Mass Spectrometry (GC/MS) analysis, respectively. Subsequently, SCFAs supplementation was performed to evaluate the protective effects against hepatic injuries. Additionally, Sigma-1 receptor knockout (S1R -/- ) mice and fluvoxamine (Flu), an agonist of S1R, were introduced to investigate the mechanisms underlying the protective effects of SCFAs. Our results showed that Meth activated S1R and induced hepatic autophagy, inflammation, and oxidative stress by stimulating the MAPK/ERK pathway. Meanwhile, Meth disrupted SCFAs product-related microbiota, leading to a reduction in fecal SCFAs (especially Acetic acid and Propanoic acid). Accompanied by the optimization of gut microbiota, SCFAs supplementation normalized S1R expression and ameliorated Meth-induced hepatic injuries by repressing the MAPK/ERK pathway. Effectively, S1R knockout repressed Meth-induced activation of the MAPK/ERK pathway and further ameliorated hepatic injuries. Finally, the overexpression of S1R stimulated the MAPK/ERK pathway and yielded comparable adverse phenotypes to Meth administration. These findings suggest that Meth-induced hepatic injuries relied on the activation of S1R, which could be alleviated by SCFAs supplementation. Our study confirms the crucial role of S1R in Meth-induced hepatic injuries for the first time and provides a potential preemptive therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Previously, convolutional neural networks mostly used deep semantic feature information obtained from several convolutions for image classification. Such deep semantic features have a larger receptive field, and the features extracted are more effective as the number of convolutions increases, which helps in the classification of targets. However, this method tends to lose the shallow local features, such as the spatial connectivity and correlation of tumor region texture and edge contours in breast histopathology images, which leads to its recognition accuracy not being high enough. To address this problem, we propose a multi-level feature fusion method for breast histopathology image classification. First, we fuse shallow features and deep semantic features by attention mechanism and convolutions. Then, a new weighted cross entropy loss function is used to deal with the misjudgment of false negative and false positive. And finally, the correlation of spatial information is used to correct the misjudgment of some patches. We have conducted experiments on our own datasets and compared with the base network Inception-ResNet-v2, which has a high accuracy. The proposed method achieves an accuracy of 99.0% and an AUC of 99.9%., (© 2022 IOP Publishing Ltd.)

Objective: To explore the role of nonalcoholic fatty liver disease (NAFLD) in the development of hepatocellular carcinoma (HCC) in patients with prior hepatitis B virus infection (HBsAg-negative and anti-HBC-positive). Methods: 1605 hospitalized patients who were first diagnosed with HCC at Nanfang Hospital between 2015 to 2017 were retrospectively studied. Patients who developed HCC on the basis of active HBV infection (HBsAg-positive, anti-HBc positive) were used as control. Multivariate logistic regression model was used to analyze the relationship between NAFLD and HCC in patients with prior hepatitis B virus infection. Results: Among HCC patients with both HBsAg and anti-HCV negative, the proportion of prior HBV infection accounted for 86.7%. NAFLD prevalence was higher in patients with HCC based on prior HBV infection than active HBV infection (19.7% vs. 8.5%, P < 0.001). After adjusting for gender, age, hypertension, alanine aminotransferase, and liver cirrhosis, patients with HCC based on prior HBV infection were more likely to develop NAFLD ( OR : 2.29, 95% CI : 1.40-3.74), and this phenomenon was observed only in patients with non-cirrhosis ( OR : 5.26, 95% CI : 2.53-10.96) and aged≥50 years (OR: 2.36, 95% CI : 1.33-4.20). Conclusion: NAFLD may be a risk factor for HCC in a previously infected patients with HBV, especially in non-cirrhotic and population aged≥50 years.

Objective: To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators. Methods: A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets. Results: The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%. Conclusions: To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.

Objective: To investigate the proportion of hepatitis B-related hepatocellular carcinoma (HCC) patients who have received antiviral therapy and compare the clinical characteristics of HCC patients who have received antiviral therapy with those who have not received antiviral therapy. Methods: Data of 2590 newly diagnosed hepatitis B-related HCC cases who were hospitalized in Nanfang Hospital from 2015 to 2017 were collected. Two independent sample t-tests, Mann-Whitney U test, and χ (2) test were used to compare the clinical characteristics of hepatitis B-related HCC patients who had received antiviral therapy and those who had not received antiviral therapy. Propensity score was used to match some clinical characteristics of the two groups of patients, and the differences in clinical characteristics of the two groups of patients after matching were further compared. Patients with HCC who had not received antiviral therapy were used as reference, and then the clinical characteristics of HCC patients who had received antiviral treatment were analyzed using multivariate logistic regression. Results: Among the 2 590 patients with hepatitis B-related HCC, only 18.10% of patients had received antiviral therapy, while 82.20% of patients who did not receive antiviral therapy met the treatment criteria. HCC patients who had received antiviral therapy were older ( P < 0.05), had a higher proportion of liver cirrhosis ( P < 0.001), and lower levels of platelets and alanine aminotransferases and smaller maximum tumor diameter ( P < 0.001). In terms of metabolic disease, patients who had received antiviral treatment had higher prevalence of diabetes (14.50% vs. 7.70%, P < 0.001), hypertension (16.60% vs. 11.20%, P < 0.05), obesity (28.50% vs. 22.30%, P < 0.05), overweight (53.80% vs. 43.50%, P < 0.001) and non-alcoholic fatty liver disease (18.30% vs.8.00%, P < 0.001). After matching other different clinical characteristics, the prevalence of diabetes, hypertension, and non-alcoholic fatty liver disease in patients who received antiviral therapy was still higher than that of patients who did not receive antiviral therapy (14.50% vs. 9.80%, P < 0.05; 16.60% vs. 10.20%, P < 0.05; 18.30% vs. 7.00%, P < 0.001). Multivariate logistic regression analysis showed that HCC patients who had received antiviral therapy had a higher risk of developing non-alcoholic fatty liver disease ( OR : 2.054, 95% CI : 1.404~3.004) than those who had not received antiviral therapy. Conclusion: Among patients with hepatitis B-related HCC, the proportion of patients who have received antiviral therapy is significantly low (under 20%), which suggests that the popularization and promotion of antiviral therapy has a long way to go. Compared with HCC patients who have not received antiviral therapy, the proportion of HCC patients who have received antiviral therapy combined with metabolic diseases is higher; therefore, it is necessary to pay more attention to the role of metabolic factors in the pathogenesis of hepatitis B-related HCC.

Background: Isolated vaginal metastases from intestinal signet ring cell carcinoma are extremely rare. There are no reported cases in the domestic or foreign literature. The characteristics of such cases of metastasis remain relatively unknown. As a life-threatening malignant tumor, it is very important to carry out a systemic tumor examination and transvaginal biopsy, even though clinical symptoms are not typical and there is no systemic tumor history., Case Presentation: We present a case of an isolated vaginal metastasis from intestinal cancer in a 45-year-old female patient. The patient experienced a small amount of irregular vaginal bleeding and difficulty urinating. She had no history of systemic cancer. An early physical examination and transvaginal ultrasound (TVS) showed marked thickening of the entire vaginal wall. Pelvic nuclear magnetic resonance imaging (MRI) and a colposcopic biopsy were used to diagnose her with chronic vaginitis. An analysis of the vaginal wall biopsy showed signet ring cell carcinoma. Colorectal colonoscopy revealed advanced interstitial signet ring cell carcinoma as the primary source of vaginal wall infiltration. We review previous case reports of vaginal metastases from colorectal cancer and discuss the symptoms, pathological type, and outcomes., Conclusions: We hypothesize that vaginal wall thickening and stiffness accompanied by chronic inflammatory-like changes may be clinical features of a vaginal metastasis of signet ring cell carcinoma of the intestine. We also emphasize that it is very important to perform a systemic tumor examination in a timely manner when a patient has the abovementioned symptoms.

Water is a crucial environmental element that affects various ecological processes in wetlands. Poyang Lake is the largest freshwater lake in China, where seasonal variation in water level generates a unique landscape of wetland in the dry season-a critical habitat for Siberian migratory birds. Nevertheless, the water quality of the Poyang Lake wetland has not been systematically and rigorously studied. In this study, we analyzed the spatial pattern of water quality in the Poyang Lake wetland based on four key physicochemical parameters[i.e. chlorophyll-a (Chl-a), chemical oxygen demand using permanganate index, total nitrogen (TN), total phosphorus (TP)] at 30 randomly selected sample sites. We also investigated the relationships between water quality parameters and land use types at different spatial scales. We found that water quality at the sample sites varied from level III (fair) to level V (very poor), with an average of level IV (poor). TN and TP were the main pollutants in the water of Poyang Lake wetland, while Chl-a content and permanganate index were comparatively low. There were significant correlations between water quality parameters and land use types at different spatial scales. Land use types within a 500 m buffer zone had the strongest explanatory power on the spatial variation of permanganate index, while those within a 1 km buffer zone had the strongest relationships with Chl-a, TN, TP, and the overall water quality. Land use types in buffer zones exhibited stronger explanatory power than those at watershed scales. Built-up land was positively correlated with all water quality parameters, while farmland had positive relationships with TN and TP. Rivers within a 200 m buffer zone were positively correlated with TN and TP, indicating that the river input might be an important source of nitrogen and phosphorus in Poyang Lake. The percentage of lake area had negative relationships with Chl-a, TN, and TP, suggesting that wetland was a source of pollutants compared with the main region of Poyang Lake. Our study shows that controlling the land use patterns within small spatial scales (≤ 1 km), especially minimizing the area of built-up land and farmland, is important for the protection of water resources in the Poyang Lake wetland.

Objective: In order to explore the effects of human umbilical cord mesenchymal stem cells (UCMSC) transplantation on the treatment of two noncontinuous segments spinal cord compression injury and to investigate whether repeated intravenous injection UCMSC was more beneficial for the recovery of spinal cord function. Methods: A total of 30 adult rabbits were randomly divided into three groups: control group (received PBS), single injection group, repeated injection group with 3 days intervals. A noncontinuous two segments SCI model was established by using the 2F Fogarty balloon catheter. Rabbits were infused with either a single total dose or three divided doses of 2×10(6) UCMSC (3 intervals) at first day post-decompreesion. Behavioral scores, somatosensory evoked potentials (SSEP) and histopathological were used to evaluate therapeutic effects. The rates of stem cell homing were studied by immunofluorescence test and the apoptosis of the spinal cord was evaluated by TUNEL test. Results: Behavior alanalyses showed that the rabbits in the UCMSC injection groups showed better motor performance than those in the control group ( P <0.01), and the motor performance in the repeated transplantation group was better than that in the single transplantation group ( P <0.01). The SSEP latencies were (22.53±0.75) ms, (24.52±0.45) ms and (26.31±0.69) ms in the repeated injection group, single injection group and control group (all P <0.01), respectively. Treatment with UCMSC increased ventral horn motor neurons preservation and decreased the number of TUNEL-positive cells compared with control group ( P <0.01). The rates of stem cell homing in the repeated injection group was significantly higher than that in single injection group ( P <0.01). Conclusion: Transplantation of UCMSC after spinal cord compression injury of two noncontinuous segments can promote functional recovery through enhancement anti-apoptotic and neuroprotective effects, and the recovery was more pronounced in the rabbits repeatedly injected at 3-day intervals.

Introduction: Bronchial papilloma and pulmonary sclerosing hemangioma (PSH) are rare tumors. The development of PSH combined with bronchial papilloma in lung is extremely rare. We herein presented a case of the co-occurrence of bronchial papilloma and PSH in a male., Case Description: A 48-year-old man was referred to our department for further treatment of the productive purulent cough and fever. After bronchoscopy, the biopsy of the specimen showed a bronchial papilloma in the lumen of posterior segment of the right upper lobar bronchus. For computed tomography demonstrated a focal lesion with an air bubble in the posterior segment of the right upper lobe, a lobectomy was performed and PSH was diagnosed., Discussion: The report emphasizes the fact that even though some of bronchial papilloma and PSH may have a low prevalence, nonetheless, the low prevalence of both diseases in a male has meant that it has not been possible to explore the depth of association between them., Conclusions: The paper reports a case of PSH in a male suffering from bronchial papilloma which is the exceptional concurrence of these two extremely infrequent events.

Vacuole membrane protein 1 (VMP1) was recently found to be involved in the process of tumor metastasis and is also considered to play a vital role in balancing apoptosis and autophagy. In the present study, the expression of VMP1 in colorectal cancer and matched adjacent non‑cancerous tissues was evaluated by immunohistochemistry (IHC) for studying the role of VMP1 in the process of colorectal cancer. Kaplan‑Meier analysis and the log-rank test were used to calculate the correlation of classic clinicopathological characteristics related to survival and the expression of VMP1. In vitro, a VMP1 stable gene silencing cell model was constructed using a lentiviral vector. The invasive ability and proliferation of colorectal cancer cells were evaluated by Transwell and MTT assays, respectively, and the underlying signaling pathway was explored by western blotting. Additionally, drug susceptibility to cisplatin, oxaliplatin and 5-FU was tested before and after VMP1 knockout. Finally, an animal model was constructed to explore the role of VMP1 in the physiopathologic process of colorectal cancer. Our results indicated that VMP1 showed increased expression in the adjacent non-cancer tissues compared with that in the colorectal cancer tissues. For different stages of colorectal cancer, expression of VMP1 had a negative correlation with the malignancy of the cancer. In clinical research, we also found that the median survival of patients with low VMP1 expression was much shorter than the survival of patients with high expression. In vitro, after infection with the lentivirus, cells with VMP1 knockout gained significant aggressive properties in regards to invasion and proliferation, and the mechanisms may be related to the activation of the PI3K/Akt/ZO-1/E-cadherin pathway. We also found that shVMP1 cells were more sensitive to 5-FU, but not cisplatin and oxaliplatin. Finally, we found a higher number of formed nodules in nude mice after intraperitoneal injection with shVMP1 cells in the in vivo study.

Background: Deregulation of centromere protein (CENP)-A, a centromere-specific histone variant, has in the past been linked to cancer initiation and progression. Additionally, our previous work has shown that CENP-A upregulation predicts a poor overall survival in patients with lung adenocarcinoma. The aim of this study was to uncover the biological role of CENP-A in lung adenocarcinoma growth and invasion, including its underlying molecular mechanisms., Methods: CENP-A expression was knocked down in human lung adenocarcinoma A549 and PC-9 cells using a short hairpin RNA (shRNA) technology. Subsequently, the effects of this knock down on the proliferation, apoptosis, cell cycle progression, colony formation, migration, invasion and tumorigenicity were assessed. Additionally, Western blot analyses were performed to examine concomitant expression changes in key proteins involved in cell cycle regulation and apoptosis., Results: We found that shRNA-mediated knock down of CENP-A significantly inhibited the in vitro proliferation and colony formation of A549 and PC-9 cells as compared to control shRNA-transfected cells. In addition, CENP-A down-regulation was found to induce G0/G1 cell cycle arrest and apoptosis, and to inhibit the in vitro migration and invasion of A549 and PC-9 cells. Down-regulation of CENP-A was also found to significantly suppress the in vivo growth of xenografted A549 cells. At the protein level, we found that the expression of p21, p27, CHK2 and Bax was markedly increased and that the expression of CCNG1, Skp2, Cks1 and Bcl-2 was markedly decreased in CENP-A down-regulated cells., Conclusion: Based on our results we conclude that down-regulation of CENP-A may attenuate the aggressive phenotype of lung adenocarcinoma cells. As such, CENP-A may serve as a promising therapeutic target for lung adenocarcinoma.

Background: Small-cell neuroendocrine carcinoma (SCNEC) of the head and neck is rare. The prognosis of SCNEC in the nasal cavity and larynx is poor. The aim of this study was to investigate the clinicopathological features of nasal and laryngeal SCNEC and to determine the expression of HIF-1α, GLUT-1, PI3K, and p-Akt in SCNEC., Methods: Between 2003 and 2012, 10 consecutive patients with histologically demonstrated nasal and laryngeal SCNEC were enrolled. Clinicopathological materials and follow-up data were analyzed retrospectively. Immunohistochemistry was used to detect GLUT-1, HIF-1α, PI3K, and p-Akt expression in paraffin wax-embedded tumor specimens., Results: The subjects were eight males and two females with a mean age of 60.8 (range: 53 to 71) years. Tumors were located in the maxillary sinus (n = 3) and larynx (n = 7). At last follow-up, four patients (40.0%) had local recurrence and five patients (50.0%) had developed distant metastases. Six patients died. The mean overall survival was 19.3 ± 2.1 months. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was seen in sinonasal and laryngeal SCNEC in 80 (8 out of 10), 50 (5 out of 10), 40 (4 out of 10), and 40% (4 out of 10) of cases, respectively. Expression of GLUT-1, HIF-1α, PI3K, and p-Akt was higher in sinonasal and laryngeal SCNEC than in precancerous lesions., Conclusions: Primary sinonasal and laryngeal SCNEC is rare. This paper presents 10 cases of sinonasal and laryngeal SCNEC with more common local recurrence and distant metastasis. HIF-1α, GLUT-1, PI3K, and p-Akt expression was higher in sinonasal and laryngeal SCNEC than in precancerous lesions.

A coumarin-based fluorescent chemosensor CAQA has been synthesized. It can selectively and sensitively recognize Cu(2+) in aqueous acetonitrile solutions. Using the Cu-containing complex CAQA-Cu(2+) as a sensing ensemble, the device demonstrates highly selective recognition of His/biothiols and was applied in fluorescence imaging of histidine in hard-to-transfect living cells.

Th17 cytokines IL-17A and IL-17F as pro-inflammatory cytokines played an important role in triggering inflammatory responses. However, little was known about the expression of IL-17A and IL-17F in acute lung injury (ALI). Therefore, the present study investigated the expression of IL-17A and IL-17F in lipopolysaccharide (LPS)-induced ALI in rats and rat pulmonary microvascular endothelial cells (PMVEC) by enzyme-linked immunosorbant assay or reverse transcription-polymerase chains reaction. Anisodamine and methylprednisolone were also investigated as anti-inflammatory strategy in the process of LPS-induced ALI. Lung injury was evaluated by histological changes, right lung wet weight:body weight (LW/BW) ratios, and protein education and total leukocyte count of bronchoalveolar lavage fluid (BALF). Our findings showed that LPS exposure elevated the levels of leukocyte number, protein education in BALF and the ratios of LW/BW, increased the expression of IL-17A and IL-17F in the lung tissues homogenate, BALF and serum of ALI rats. Up-regulation of IL-17F expression was also observed after LPS challenge in rat PMVEC. Treatment with anisodamine or methylprednisolone significantly inhibited the increases of parameters of ALI induced by LPS, and markedly reduced the expression of IL-17A and IL-17F in rats and the IL-17F expression in PMVEC. These data suggested that IL-17A and IL-17F maybe play an important role in LPS-induced ALI via autocrine and paracrine mechanisms, and anisodamine is similar in extent to methylprednisolone that contributes to relieve LPS-induced ALI., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To investigate the role of caveolin-1 (Cav-1) in the modulation of rat pulmonary microvascular endothelial cells (RPMVEC) injury induced by lipopolysaccharide (LPS)., Methods: Cultured RPMVEC were randomly divided into time-dependent injury group induced by LPS and intervention group in which cells were pretreated by protein kinase A inhibitor (PKI). In the time-dependent injury group, monolayers of cells were constructed to determine permeability changes after 10 μg/mL LPS challenge for 0, 1, 3, 6, 12 and 24 hours with the method of Evans blue-labeled albumin flux across the monolayer (Pd). Western blotting was used to determine the Cav-1 expression after LPS stimulation and the phosphorylation-Cav-1 (p-Cav-1) expression after LPS challenge for 0, 10, 30, 60, 90, 120 minutes. In the intervention group, after pre-treatment with 10 μmol/L PKI for 30 minutes, RPMVECs were challenged with 10 μg/mL LPS, and the expression of p-Cav-1 was determined 30 minutes after LPS challenge, the permeability and the Cav-1 protein expression were assessed by Pd and Western blotting, respectively. Non-stimulation group and single PKI simulation group served as controls., Results: Western blotting revealed that the expression of Cav-1 protein was elevated at 1 hour (2.97 ± 0.07), peaking at 3 hours (3.77 ± 0.37), then it lowered gradually, but it was still higher at 24 hours (1.45 ± 0.18) when compared with 0 hour group (1.12±0.08) with significant differences (F=178.047, P=0.000). After RPMVEC monolayers were challenged by LPS for different periods (0, 1, 3, 6, 12 and 24 hours), there were significant increases in a time-dependent manner in Cav-1 expression in the permeability as measured by Pd [(99.67 ± 4.32)%, (118.17 ± 2.32)%, (159.00 ± 2.61)%, (141.17 ± 2.64)%, (120.17 ± 2.79)% and (108.83 ± 2.04)%, F=345.869, P=0.000] which was similar to the changes in Cav-1 expression. LPS also increased Cav-1 phosphorylation in a time-dependent manner occurring at 10 minutes (2.41 ± 0.11), peaking at 30 minutes (2.83 ± 0.10), and then it decreased gradually, finally returned to basal levels (1.03±0.04) at 120 minutes (1.04 ± 0.04) after LPS treatment with significant difference (F=519.417, P=0.000). When PKI was pre-treated with RPMVEC the expression of Cav-1 was significantly increased (5.07 ± 0.22 vs. 3.81 ± 0.23, P<0.01), and p-Cav-1 (3.93 ± 0.23 vs. 2.77±0.10, P<0.01), and RPMVEC monolayers permeability was enhanced [(184.17 ± 5.49)% vs. (151.50 ± 3.08)%, P<0.01] after being challenged., Conclusions: Up-regulated expression of Cav-1 and phosphorylation-Cav-1 that may be modulated by protein kinase A signal pathway plays an important role in RPMVEC permeability injury as induced by LPS.

Objective: To explore the effects of tumor necrosis factor-alpha (TNF-α) or methylprednisolone on the expression of interleukin-17 receptor C (IL-17RC) in rat pulmonary microvascular endothelial cells (RPMVEC)., Methods: Culture RPMVEC were randomly divided into dose-dependent and time-dependent groups. In dose-dependent group, cells were cultured with TNF-α (0, 0.1, 1, 10 µg/L TNF-α) for 3 h. In time-dependent group, cells were cultured with TNF-α (10 µg/L) for 0, 1, 3, 6, 12 h. In the drug intervention group, cells were cultured with TNF-α (10 µg/L) or methylprednisolone (200 µg/L) +TNF-α (10 µg/L) for 3 h respectively. The expression of IL-17RC in isolated and cultured RPMVEC was identified by reverse transcription-polymerase chain reaction (RT-PCR), Western blot and immunocytochemistry. The changes of IL-17RC mRNA were detected by RT-PCR after the stimulation of RPMVEC by TNF-α or methylprednisolone., Results: RT-PCR and Western blot revealed that IL-17RC mRNA and protein were present in RPMVEC. The product of IL-17RC immunocytochemical reaction was predominantly located in cytoplasm and cytomembrane. In RPMVEC TNF-α significantly up-regulated IL-17RC mRNA in a dose-dependent manner (0 µg/L TNF-α group: 0.241 ± 0.010, 0.1 µg/L TNF-α group: 0.372 ± 0.017, 1 µg/L TNF-α group: 0.452 ± 0.017, 10 µg/L TNF-α group: 0.643 ± 0.042, F = 33.774, P < 0.05). In time-dependent group, the expression of IL-17RC mRNA rose at 1 h (0.417 ± 0.038), peaked at 3 h (0.674 ± 0.018), then decreased gradually at 6 h (0.378 ± 0.035), but stayed higher at 12 h (0.318 ± 0.032). When compared with 0 h group (0.197 ± 0.008), there were significant differences (F = 37.903, P < 0.05). Methylprednisolone caused a marked attenuation of TNF-α-induced IL-17RC expression (0.333 ± 0.031 vs 0.660 ± 0.026, F = 89.637, P < 0.05)., Conclusions: IL-17RC is predominantly present in cytomembrane and cytoplasm of RPMVEC. TNF-α up-regulates the expression of IL-17RC mRNA. Methylprednisolone inhibits the elevated expression of IL-17RC mRNA induced by TNF-α so as to relieve the inflammatory response of PMVEC.

We present here a woman with an intracardiac leiomyoma originating from uterine leiomyomatosis. The tumor was completely removed in a one-stage procedure using cardiopulmonary bypass without cardiac arrest. Most one-stage operations were performed with total circulation arrest; however, using of on-pump beating-heart technique when removing the intracardiac mass has seldom been reported in detail. The patient was asymptomatic with no evidence of recurrence on 13-month follow-up., (Georg Thieme Verlag KG Stuttgart · New York.)

A multiplicity of vital cellular and tissue level functions are controlled by caveolin-1 and it is considered to be an important candidate for targeted therapeutics. Rac1-cortactin signaling plays an important role in maintaining the functions of the endothelial barrier in microvascular endothelial cells. The activity of Rac1 has been shown to be regulated by caveolin-1. Therefore, the present study investigated the consequences of down-regulating caveolin-1 and the subsequent changes in activity of Rac1 and the endothelial barrier functions in primary rat pulmonary microvascular endothelial cells (RPMVECs). RPMVECs were transfected with a small hairpin RNA duplex to down-regulate caveolin-1 expression. This procedure significantly increased the activity of Rac1. Moreover, down-regulation of caveolin-1 attenuated TNF-α-induced decrease in TER, increase in the flux of FITC-BSA and the disappearance of cortactin from the cell periphery in RPMVEC. Rac1 inhibitors significantly abolished this barrier-protective effect induced by down-regulation of caveolin-1 in response to TNF-α in RPMVECs. In conclusion, our data suggest a mechanism for the regulation of Rac1 activity by caveolin-1, with consequences for activation of endothelial cells in response to TNF-α.

Aim: To investigate the utility of prostate-specific antigen velocity (PSAV) and PSAV per initial volume (PSAVD) for early detection of prostate cancer (PCa) in Chinese men., Methods: Between January 2009 and June 2012, a total of 193 men (aged 49-84 years, median 67 years) with at least 2 transrectal ultrasonography (TRUS) procedures and concurrent serum PSA measurements underwent prostate biopsy because of suspicion of PCa. The total group were classified into PCa and non-PCa groups, and the variables of the two groups were compared. Univariate and multivariate analyses were used to investigate which variables were predictove. The diagnostic values of PSAV, PSAVD and prostate-specific antigen density (PSAD) were compared using receiver operating characteristic (ROC) analysis., Results: Prostate cancer was diagnosed in 44 (22.8%) of the 193 men. There were significant differences between the groups in last and initial prostate volumes determined by TRUS, initial age, last serum PSA levels, PSAV, PSAD and PSAVD. After adjusting for confounding factors, the odds ratios of PCa across the quartile of PSAVD were 1, 4.06, 10.6, and 18.9 (P for trend <0.001).The area under the ROC curves (AUCs) of PSAD (0.779) and PSAVD (0.776) were similar and both significantly greater than that of PSA (AUC 0.667). PSAVD was a significantly better indicator of PCa than PSAV (AUC 0.736). There was no statistical significant difference between the AUC of PSAV and that of last serum PSA level. The sensitivity and specificity of PSAVD at a cutoff of 0.023ng in participants with last serum PSA levels of 4.0 ng/mL-10.0 ng was 73.7% and 70.7%, respectively., Conclusions: The results of this study demonstrated PSAVD may be a useful tool in PCa detection, especially in those undergoing previous TRUS examination.

Objective: To explore an optimal method for the measurement of pulmonary microvascular endothelial cell (PMVEC) permeability coefficient., Methods: A monolayer of rat PMVEC model was constructed by culturing a cell suspension on transwell filter or polycarbonate filter membrane. After the state of confluence of cells was affirmed with epithelial volt-ohm meter or inverted microscope, the permeability coefficient was determined by means of transendothelial electrical resistance (TER), fluoresceinisothiocyanate-dextran (Pd), and permeation of Hanks solution (Lp) across monolayers. Meanwhile,changes in PMVEC permeability expressed by the ratio of the observed value and the original value were observed after lipopolysaccharide (LPS) challenge for 0. 5 hour or 2 hours., Results: The cells reached the state of confluence as observed under inverted microscope on the third day post-seeding, and the TER and Pdat this time-point were C(39. 45 ± 3. 96) ( 2 cm2] and [(8. 52 + 0. 50) X 10-6cm/s], respectively. After PMVEC were seeded on transwell filters, the TER increased steadily in a time-dependent manner after seeding of PMVEC, reaching the summit at the fourth day post-seeding C(49. 84 ± 3. 93)f " cm2].Under the natural state, the TER, Pd and Lp of confluent PMVEC monolayers were (49.84 ±3.93) ·.* cm2, (6.15±0.63) X 106 cm/s and (6.80 + 0.62) X10< cm * s-' * cm HZO-', respectively.After PMVEC monolayers were challenged with 10 mg/L LPS for both 0. 5 hour and 2 hours, there was significant decrease in the permeability coefficient as measured by TER (0. 87+ 0. 03, 0.45 0. 04 vs. 1.00+0.08, respectively, both P< 0.05), and an increase in the permeability coefficient measured by Pd (1.33±0. 11, 2.43±0. 14 vs. 1.00+0.10, respectively, both P<0. 05) and the permeability coefficient measured by Lp (1.30± 0.07, 2.38 0.15 vs. 1.00 + 0.11, respectively, both P< 0.05) when compared with the normal group., Conclusion: Three methods, namely TER, Pd and Lp are available to use to assess PMVEC permeability coefficient. The combination of an inverted microscope, TER and Pd enhances the accuracy in determining PMVEC permeability coefficient, and it provides an experimental technique for studying the pathogenesis of acute lung injury in vitro.

Objective: The aim of the study was to investigate the role of src-suppressed C kinase substrate (SSeCKS) in the modulation of rat pulmonary microvascular endothelial cells (RPMVEC) permeability elicited by interleukin (IL)-1β and tumor necrosis factor (TNF)-α., Methods: The gene expression of SSeCKS was analyzed by reverse transcription-polymerase chain reaction. Immunoblotting was used to determine the SSeCKS protein expression and the activation of the protein kinase C (PKC) signaling pathway. A RPMVEC monolayer was constructed to determine changes of transendothelial electrical resistance (TER) and FITC-dextran flux (P (d)) across the monolayer. SSeCKS-specific small interfering RNA was transfected into RPMVEC., Results: IL-1β and TNF-α activated the PKC signaling pathway in RPMVEC, and up-regulated the gene and protein expression of SSeCKS. Depletion of endogenous SSeCKS in RPMVEC significantly attenuated cytokine-induced decrease in TER and increase in P (d), but not to the basal levels. PKC inhibitors also significantly decreased cytokine-induced hyperpermeability and SSeCKS expression., Conclusions: SSeCKS is involved in the endothelial hyperpermeability induced by IL-1β and TNF-α in inflammatory process.

Background: Interleukin (IL)-17F is involved in lung inflammation, but the effect of IL-17F on endothelial permeability and its signaling pathway remain ill-defined. The current study sought to investigate the effect of IL-17F on endothelium and assess the role of protein kinase C (PKC) and src-suppressed C kinase substrate (SSeCKS) in this process., Methods: Rat pulmonary microvascular endothelial monolayers were constructed to determine changes of permeability as measured by means of FITC-dextran and Hank's solution flux across monolayers and transendothelial electrical resistance with or without IL-17F and PKC inhibitors. Additional monolayers were stained using FITC-phalloidin for filamentous actin (F-actin). The gene expression of SSeCKS was analyzed by the reverse transcription-polymerase chains. Alterations of SSeCKS protein were investigated by immunoblotting and immunoprecipitation., Results: IL-17F increased endothelial monolayer permeability in a dose- and time-dependent manner. F-actin staining revealed that permeability changes were accompanied by reorganization of cytoskeleton. In the presence of PKC inhibitors, the IL-17F-induced hyperpermeability and reorganization of F-actin were attenuated. The gene and protein expression of SSeCKS were conspicuously elevated after IL-17F challenge. The process of SSeCKS phosphorylation followed a time course that mirrored the time course of hyperpermeability induced by IL-17F. IL-17F-induced SSeCKS phosphorylation was abrogated after PKC inhibitors pretreatment. The translocation of SSeCKS from the cytosol to the membrane and a significant increase in the SSeCKS association with the cytoskeleton were found after IL-17F treatment., Conclusions: IL-17F is an important mediator of increased endothelial permeability. PKC and SSeCKS are integral signaling components essential for IL-17F-induced hyperpermeability., ((c) 2010. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the effect of platelet-activating factor (PAF) on the production of Src-suppressed C kinase substrate (SSeCKS) mRNA in rat pulmonary microvascular endothelial cell (RPMVEC) and its signal transduction pathways., Methods: Cellular in situ hybridization was performed to reveal changes in SSeCKS mRNA expression in the cultured RPMVECs after giving PAF stimulation., Results: Normal RPMVECs expressed SSeCKS mRNA at a low level, which appeared throughout the cytoplasm with specific hybridization signals. 1.5 hours of 10(-10), 10(-9), 10(-8), 10(-7) mol/L PAF incubation induced a progressive increase in SSeCKS mRNA expression. When compared to the normal control group each difference had statistical significance (0.054 9 + or - 0.000 7, 0.059 9 + or - 0.001 8, 0.069 0 + or - 0.001 8, 0.075 4 + or - 0.001 9 vs. 0.036 8 + or - 0.003 7, respectively, all P<0.05). Within 0.5, 1.5, 3, 6, 12, 24 hours of 10(-7) mol/L PAF challenge, the level of SSeCKS mRNA expression raised at 0.5 hour markedly (0.071 0 + or - 0.001 5), peaked at 1.5 hours (0.075 6 + or - 0.001 7), then began to decline gradually, and still persisted at a higher level than the normal control group until 24 hours (0.043 9 + or - 0.001 0 vs. 0.038 2 + or - 0.004 1, all P<0.05). Pre-incubation of 10 micromol/L pyrrolidine dithiocarbamate (PDTC) that inhibits activity of nuclear factor-KappaB (NF-KappaB) in RPMVECs caused a conspicuous attenuation of PAF-induced SSeCKS mRNA expression (0.049 7 + or - 0.003 2 vs. 0.071 9 + or - 0.001 9, P<0.05), whereas no change of PAF-induced effect was found by pretreatment of protein kinase C (PKC) inhibitor bis-indolylmaleimide (BIM, 0.069 7 + or - 0.002 1 vs. 0.071 9 + or - 0.001 9, P>0.05)., Conclusion: PAF can up regulate the expression of SSeCKS mRNA in a dose- and time-dependent manner in RPMVECs. It is NF-KappaB rather than PKC signal pathway that is involved in modulation of the intracellular signaling process.

In this paper, we present a technique for the preparation of polymer nanowires with the protein molecule imprinted and binding sites at surface. These surface imprinting nanowires exhibit highly selective recognition for a variety of template proteins, including albumin, hemoglobin, and cytochrome c. This recognition may be through a multistep adsorption, with the specificity conferred by hydrogen bonding and shape selectivity. Due to the protein imprinted sites are located at, or close to, the surface; these imprinted nanowires have a good site accessibility toward the target protein molecules. Furthermore, the large surface area of the nanowires results in large protein molecule binding capacity of the imprinted nanowires.