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Qingqing Meng,1,* Aiping Wang,1,2,* Hongchen Hua,1 Ying Jiang,1 Yiyun Wang,1 Hongjie Mu,1 Zimei Wu,1 Kaoxiang Sun1 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, People’s Republic of China; 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, People’s Republic of China *These authors contributed equally to this work Background: Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD).Purpose: To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment.Methods: HupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry.Results: Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively.Conclusion: Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier. Keywords: Huperzine A, lactoferrin, N-trimethyl chitosan, nose-to-brain, nanoparticles, Alzheimer’s disease

The incompletely eliminated Treponema pallidum ( T. pallidum ) during primary syphilis chancre infection can result in the progression of secondary, tertiary, or latent syphilis in individuals, suggesting that T. pallidum has successfully evaded the immune response and spread to distant sites. The mechanism underlying the dissemination of T. pallidum is unclear. Here, a syphilitic rabbit model dorsal-injected with recombinant Tp0136 protein or Tp0136 antibody subcutaneously was used to demonstrate the role of Tp0136 protein in promoting the dissemination of T. pallidum to the testis and angiogenesis in vivo ; vascular endothelial cell line HMEC-1 was employed to display that Tp0136 protein enhances the angiogenesis. Furthermore, the three-dimensional microfluidic angiogenesis system showed that the angiogenesis would heighten vascular permeability. Then transcriptome sequencing analysis, in conjunction with cell-level validation, elucidated the critical role of the PI3K-AKT signaling pathway in the promotion of angiogenesis by Tp0136 protein, resulting in heightened permeability. These findings elucidate the strategy employed by T. pallidum in evading immune clearance.

The evasive tactics of Treponema pallidum pose a major challenge in combating and eradicating syphilis. Natural killer (NK) cells mediate important effector functions in the control of pathogenic infection, preferentially eliminating targets with low or no expression of major histocompatibility complex (MHC) class I. To clarify T. pallidum's mechanisms in evading NK-mediated immunosurveillance, experiments were performed to explore the cross-talk relations among T. pallidum , NK cells, and platelets. T. pallidum adhered to, activated, and promoted particle secretion of platelets. After preincubation with T. pallidum , platelets expressed and secreted high levels of MHC class I, subsequently transferring them to the surface of T. pallidum , potentially inducing an immune phenotype characterized by the "pseudo-expression" of MHC class I on the surface of T. pallidum (hereafter referred to a "pseudo-expression" of MHC class I). The polA mRNA assay showed that platelet-preincubated T. pallidum group exhibited a significantly higher copy number of polA transcript than the T. pallidum group. The survival rate of T. pallidum mirrored that of polA mRNA, indicating that preincubation of T. pallidum with platelets attenuated NK cell lethality. Platelets pseudo-expressed the MHC class I ligand on the T. pallidum surface, facilitating binding to killer cell immunoglobulin-like receptors with two immunoglobulin domains and long cytoplasmic tail 3 (KIR2DL3) on NK cells and initiating dephosphorylation of Vav1 and phosphorylation of Crk, ultimately attenuating NK cell lethality. Our findings elucidate the mechanism by which platelets transfer MHC class I to the T. pallidum surface to evade NK cell immune clearance.

Objectives: To evaluate the diagnostic performance of different brands of immunochromatographic test (ICT) reagents for Chlamydia trachomatis using homogenized samples to provide a reference for reagent quality control., Methods: Eight commercially available ICT reagents were evaluated, of which three used the latex method and five used the colloidal gold method. Analytical performance evaluation using a pure culture broth of C. trachomatis , as well as clinical application validation using cervical epithelial cell samples acquired from the research subjects, were conducted. The concentration of C. trachomatis was quantified using a nucleic acid amplification test., Results: The limit of detection (LOD) of different ICT reagents in the analytical performance evaluation varied from 9.5 × 10 3 to 1 × 10 5 IFU/mL, and only one reagent met the LOD specified in the manufacturer's instructions. Likewise, only one reagent in the clinical application validation achieved the analytical LOD, four reagents were 2.1-4.2-fold of the analytical LODs, and three reagents failed to detect positive results in clinical samples., Conclusions: The diagnostic performance of different methods and different brands of ICT reagents in clinical practice was different from the manufacturer's instructions and the results of laboratory evaluation. The diagnostic performance of reagents should be evaluated before they are actually used in clinical practice., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier B.V.)

The aim of this study was to assess the effects of local wound infiltration anaesthesia on postoperative wound pain in patients undergoing open liver resection. The Cochrane Library, PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM) and Wanfang databases were searched. The search period spanned from database creation to December 2022. All relevant studies on local wound infiltration anaesthesia for analgesia after hepatectomy were included. Two investigators independently screened the literature, extracted data and evaluated the quality of each study. Review Manager (RevMan) 5.4 software (Cochrane Collaboration) was used for the meta-analysis, in which 12 studies with 986 patients were included. The results show that local wound infiltration anaesthesia effectively reduced surgical site wound pain at 4 h (mean difference [MD]: -1.26, 95% confidence intervals [CIs]: -2.15 to -0.37, P = .005), 12 h (MD: -0.84, 95% CIs: -1.26 to -0.42, P < .001), 24 h (MD: -0.57, 95% CIs: -1.01 to -0.14, P = .009) and 48 h (MD: -0.54, 95% CIs: -0.81 to -0.26, P < .001) postoperatively; however, there was no significant difference in analgesia at 72 h postoperatively (MD: -0.10, 95% CIs: -0.80 to 0.59, P = .77). These findings suggest that local wound infiltration anaesthesia administered to patients undergoing open liver resection provides good postoperative wound analgesia at the surgical site., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The ethnobotanical plant Marsdenia tenacissima has been used for hundreds of years for Dai people in Yunnan Province, China. Previously, chemical investigations on this plant have revealed that pregnane glycosides were the main biological constituents. Nine new pregnane glycosides, marsdeosides A-I ( 1 - 9 ), were isolated from cultivated dried stems of the medicinal plant Marsdenia tenacissima in this study. The structures were analyzed by extensive spectroscopic analysis, including 1D, 2D NMR, HRESIMS, and IR spectroscopic analysis. The absolute configurations of the sugar moieties were identified by comparing the R f values and specific optical rotations with those of the commercially available standard samples and the data reported in the literature. Marsdeosides A ( 1 ) featured an unusual 8,14- seco -pregnane skeleton. Compounds 1 , 8 , and 9 showed activity against nitric oxide production in lipopolysaccharide-activated macrophage RAW264.7, with IC 50 values of 37.5, 38.8, and 42.8 μM (L-NMMA was used as a positive control, IC 50 39.3 μM), respectively. This study puts the knowledge of the chemical profile of the botanical plant M. tenacissima one step forward and, thereby, promotes the sustainable utilization of the resources of traditional folk medicinal plants.

Background and Objectives: EUS has recently gained attraction in mainland China. This study aimed to evaluate the development of EUS from results of two national surveys., Methods: EUS-related information, including infrastructure, personnel, volume, and quality indicator, was extracted from the Chinese Digestive Endoscopy Census. Data from 2012 and 2019 were compared, and differences among various hospitals and regions were analyzed. The EUS rates (EUS annual volume per 100,000 inhabitants) between China and developed countries were also compared., Results: The number of hospitals performing EUS in mainland China increased from 531 to 1236 (2.33-fold), and 4025 endoscopists performed EUS in 2019. The volumes of all EUS and interventional EUS increased from 207,166 to 464,182 (2.24-fold) and 10,737 to 15,334 (1.43-fold), respectively. The EUS rate in China was lower than that in developed countries but showed a higher growth rate. EUS rate varied substantially among different provincial regions (in 2019: 4.9-152.0 per 100,000 inhabitants) and showed significant positive association with gross domestic product per capita (in 2019: r = 0.559, P = 0.001). The EUS-FNA-positive rate in 2019 was comparable between hospitals in terms of annual volume (≥50 or < 50: 79.9% vs. 71.6%, P = 0.704) and practice duration (starting EUS-FNA before or after 2012: 78.7% vs. 72.6%, P = 0.565)., Conclusion: EUS has developed considerably in China in recent years but still needs substantial improvement. More resources are in demand for hospitals in less-developed regions and with low EUS volume., Competing Interests: None

Background: Upper gastrointestinal endoscopy is critical for esophageal squamous cell carcinoma (ESCC) detection; however, endoscopists require long-term training to avoid missing superficial lesions., Aim: To develop a deep learning computer-assisted diagnosis (CAD) system for endoscopic detection of superficial ESCC and investigate its application value., Methods: We configured the CAD system for white-light and narrow-band imaging modes based on the YOLO v5 algorithm. A total of 4447 images from 837 patients and 1695 images from 323 patients were included in the training and testing datasets, respectively. Two experts and two non-expert endoscopists reviewed the testing dataset independently and with computer assistance. The diagnostic performance was evaluated in terms of the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity., Results: The area under the receiver operating characteristics curve, accuracy, sensitivity, and specificity of the CAD system were 0.982 [95% confidence interval (CI): 0.969-0.994], 92.9% (95%CI: 89.5%-95.2%), 91.9% (95%CI: 87.4%-94.9%), and 94.7% (95%CI: 89.0%-97.6%), respectively. The accuracy of CAD was significantly higher than that of non-expert endoscopists (78.3%, P < 0.001 compared with CAD) and comparable to that of expert endoscopists (91.0%, P = 0.129 compared with CAD). After referring to the CAD results, the accuracy of the non-expert endoscopists significantly improved (88.2% vs 78.3%, P < 0.001). Lesions with Paris classification type 0-IIb were more likely to be inaccurately identified by the CAD system., Conclusion: The diagnostic performance of the CAD system is promising and may assist in improving detectability, particularly for inexperienced endoscopists., Competing Interests: Conflict-of-interest statement: Dr. Wang reports grants from The Science and Technology Commission of Shanghai Municipality during the conduct of the study. Other authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Colorectal cancer remains a considerable challenge in healthcare nowadays. Approximately 60%-80% of colorectal cancer is caused by intestinal polyps, and resection of intestinal polyps has been proved to reduce the incidence of colorectal cancer. The vast majority of intestinal polyps can be found during colonoscopy and removed endoscopically. Therefore, more attention has been paid to the development of endoscopic resection of intestinal polyps. In this study, we compared the efficacy and safety of cold snare polypectomy (CSP) and hot snare polypectomy (HSP)., Aim: To investigate the efficacy and safety of CSP and HSP for colorectal polyps., Methods: Between January and December 2020, 301 patients with colorectal polyps 4-9 mm in diameter were treated with endoscopic therapy in our hospital, and were divided into the CSP group ( n = 154) and HSP group ( n = 147). The operating time, incidence of bleeding and perforation, use of titanium clips, and complete resection rate were compared between the two groups., Results: We included 249 patients (301 polyps). No differences in gender, age, and polyp size, location, shape and type were observed between the CSP and HSP groups, and the resection rates in these two groups were 93.4% and 94.5%, respectively, with no significant difference. The use of titanium clips was 15.6% and 95.9%, the operating time was 3.2 ± 0.5 min and 5.6 ± 0.8 min, the delayed bleeding rate was 0% and 2.0%, and delayed perforation was 0% and 0.7%, in the CSP and HSP groups, respectively., Conclusion: For sessile colorectal polyps < 10 mm, CSP had the same resection rate of impaired tissue integrity as traditional HSP had. The rate of complications was lower in the CSP group. CSP is a safe and effective method for polypectomy., Competing Interests: Conflict-of-interest statement: Meng QQ, Rao M, Gao PJ are employees of the First Hospital of Jilin University., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice., Aim: To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies., Methods: With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital., Results: The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time ( P = 0.32; P = 0.16, respectively)., Conclusion: CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted., Competing Interests: Conflict-of-interest statement: Wu JR, Chen LZ, Chang J and Song P were staff of Tencent Healthcare (Shenzhen) Co. LTD, which supported the work with provision of research grants, prototype software, prototype PC and GPU units. The other authors have no conflicts of interest to declare. The sponsor had no involvement in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, and approval of the manuscript; or the decision to submit the manuscript for publication., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The differentiation of human pluripotent stem cells (hPSCs) to neural stem cells (NSCs) is the key initial event in neurogenesis and is thought to be dependent on the family of Wnt growth factors, their receptors and signaling proteins. The delineation of the transcriptional pathways that mediate Wnt-induced hPSCs to NSCs differentiation is vital for understanding the global genomic mechanisms of the development of NSCs and, potentially, the creation of new protocols in regenerative medicine. To understand the genomic mechanism of Wnt signaling during NSCs development, we treated hPSCs with Wnt activator (CHIR-99021) and leukemia inhibitory factor (LIF) in a chemically defined medium (N2B27) to induce NSCs, referred to as CLNSCs. The CLNSCs were subcultured for more than 40 passages in vitro; were positive for AP staining; expressed neural progenitor markers such as NESTIN , PAX6 , SOX2 , and SOX1 ; and were able to differentiate into three neural lineage cells: neurons, astrocytes, and oligodendrocytes in vitro. Our transcriptome analyses revealed that the Wnt and Hedgehog signaling pathways regulate hPSCs cell fate decisions for neural lineages and maintain the self-renewal of CLNSCs. One interesting network could be the deregulation of the Wnt/β-catenin signaling pathway in CLNSCs via the downregulation of c-MYC, which may promote exit from pluripotency and neural differentiation. The Wnt-induced spinal markers HOXA1-4 , HOXA7 , HOXB1-4, and HOXC4 were increased, however, the brain markers FOXG1 and OTX2 , were absent in the CLNSCs, indicating that CLNSCs have partial spinal cord properties. Finally, a CLNSC simple culture condition, when applied to hPSCs, supports the generation of NSCs, and provides a new and efficient cell model with which to untangle the mechanisms during neurogenesis.

Background: We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated., Methods: Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed., Findings: In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides., Interpretation: CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ketogenic diet (KD) is popular in diabetic patients but its cardiac safety and efficiency on the heart are unknown. The aim of the present study is to determine the effects and the underlined mechanisms of KD on cardiac function in diabetic cardiomyopathy (DCM). We used db/db mice to model DCM, and different diets (regular or KD) were used. Cardiac function and interstitial fibrosis were determined. T-regulatory cell (Treg) number and functions were evaluated. The effects of ketone body (KB) on fatty acid (FA) and glucose metabolism, mitochondria-associated endoplasmic reticulum membranes (MAMs), and mitochondrial respiration were assessed. The mechanisms via which KB regulated MAMs and Tregs were addressed. KD improved metabolic indices in db/db mice. However, KD impaired cardiac diastolic function and exacerbated ventricular fibrosis. Proportions of circulatory CD4 + CD25 + Foxp3 + cells in whole blood cells and serum levels of IL-4 and IL-10 were reduced in mice fed with KD. KB suppressed the differentiation to Tregs from naive CD4 + T cells. Cultured medium from KB-treated Tregs synergically activated cardiac fibroblasts. Meanwhile, KB inhibited Treg proliferation and productions of IL-4 and IL-10. Treg MAMs, mitochondrial respiration and respiratory complexes, and FA synthesis and oxidation were all suppressed by KB while glycolytic levels were increased. L-carnitine reversed Treg proliferation and function inhibited by KB. Proportions of ST2L + cells in Tregs were reduced by KB, as well as the production of ST2L ligand, IL-33. Reinforcement expressions of ST2L in Tregs counteracted the reductions in MAMs, mitochondrial respiration, and Treg proliferations and productions of Treg cytokines IL-4 and IL-10. Therefore, despite the improvement of metabolic indices, KD impaired Treg expansion and function and promoted cardiac fibroblast activation and interstitial fibrosis. This could be mainly mediated by the suppression of MAMs and fatty acid metabolism inhibition via blunting IL-33/ST2L signaling., Competing Interests: All authors declare no potential conflict of interest., (Copyright © 2021 Jun Tao et al.)

Background/aims: Single-balloon enteroscopy (SBE) has been widely used in diagnosing small bowel disease. We conducted this study to systematically appraise its technical and clinical performance., Methods: Studies on SBE published by September 2018 were systematically searched. Technical and clinical performance data were collected and analyzed with descriptive or meta-analysis methods., Results: In total, 54 articles incorporating 4,592 patients (6,036 procedures) were included. Regarding technical parameters, the pooled insertion depths (IDs) for anterograde and retrograde SBE were 209.2 cm and 98.1 cm, respectively. The pooled retrograde ID in Asian countries was significantly greater than that in Western countries (129.0 cm vs 81.1 cm, p<0.001). The pooled anterograde and retrograde procedure times were 57.6 minutes and 65.1 minutes, respectively. The total enteroscopy rate was 21.9%, with no significant difference between Asian and Western countries. Clinically, the pooled diagnostic yield of SBE was 62.3%. Obscure gastrointestinal bleeding (OGIB) was the most common indication (50.0%), with a diagnostic yield of 59.5%. Vascular lesions were the most common findings in Western OGIB patients (76.9%) but not in Asian ones (31.0%). The rates of severe and mild adverse events were 0.5% and 2.5%, respectively., Conclusions: SBE is technically efficient and is clinically effective and safe, but total enteroscopy is relatively difficult to achieve with this technique. Etiologies of OGIB in Asian countries differ from those in Western countries.

BACKGROUND Adenocarcinoma of the lung is a type of non-small cell lung cancer (NSCLC). Clinical outcome is associated with tumor grade, stage, and subtype. This study aimed to identify RNA expression profiles, including long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA, associated with clinical outcome in adenocarcinoma of the lung using bioinformatics data. MATERIAL AND METHODS The miRNA and mRNA expression profiles were downloaded from The Cancer Genome Atlas (TCGA) database, and lncRNA expression profiles were downloaded from The Atlas of Noncoding RNAs in Cancer (TANRIC) database. The independent dataset, the Gene Expression Omnibus (GEO) accession dataset, GSE81089, was used. RNA expression profiles were used to identify comprehensive prognostic RNA signatures based on patient survival time. RESULTS From 7,704 lncRNAs, 787 miRNAs, and 28,937 mRNAs of 449 patients, four joint RNA molecular signatures were identified, including RP11-909N17.2, RP11-14N7.2 (lncRNAs), MIR139 (miRNA), KLHDC8B (mRNA). The random forest (RF) classifier was used to test the prediction ability of patient survival risk and showed a good predictive accuracy of 71% and also showed a significant difference in overall survival (log-rank P=0.0002; HR, 3.54; 95% CI, 1.74-7.19). The combined RNA signature also showed good performance in the identification of patient survival in the validation and independent datasets. CONCLUSIONS This study identified four RNA sequences as a prognostic molecular signature in adenocarcinoma of the lung, which may also provide an increased understanding of the molecular mechanisms underlying the pathogenesis of this malignancy.

Persistent inflammation disrupts functional recovery after spinal cord injury (SCI). Peroxisome proliferator-activated receptor gamma (PPAR- γ ) activation promotes functional recovery in SCI rats by inhibiting inflammatory cascades and increasing neuronal survival. We sought to clarify the relationship between PPAR- γ activation and NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome suppression, and the role of NF- κ B in activating the NLRP3 inflammasome in neurons. In SCI rats, we found that rosiglitazone (PPAR- γ agonist) inhibited the expression of caspase-1. In in vitro neurons, G3335 (PPAR- γ antagonist) reversed the rosiglitazone-induced inhibition of caspase-1, interleukin 1 (IL-1 β ), and interleukin 6 (IL-6). Rosiglitazone inhibited the expression of NLRP3, caspase-1, IL-1 β , and IL-6. However, the activator of NLRP3 could counteract this inhibition induced by PPAR- γ activation. NF- κ B did not participate in the process of rosiglitazone-induced inhibition of NLRP3. Consistent with our in vitro results, we verified that locomotor recovery of SCI rats in vivo was regulated via PPAR- γ , NLRP3, and NF- κ B. These results suggest that PPAR- γ activation exerts an anti-inflammatory effect by suppressing the NLRP3 inflammasome-but not NF- κ B-in neurons and that PPAR- γ activation is a promising therapeutic target for SCI.

Background: Tens of millions of gastrointestinal endoscopic procedures are performed every year in China, but the quality varies significantly and related factors are complex. Individual endoscopist- and endoscopy division-related factors may be useful to establish a model to measure and predict the quality of endoscopy., Aim: To establish a model to measure and predict the quality of gastrointestinal endoscopic procedures in mainland China., Methods: Selected data on endoscopy experience, equipment, facility, qualification of endoscopists, and other relevant variables were collected from the National Database of Digestive Endoscopy of China. The multivariable logistic regression analysis was used to identify the potential predictive variables for occurrence of medical malpractice and patient disturbance. Linear and nonlinear regressions were used to establish models to predict incidence of endoscopic complications., Results: In 2012, gastroscopy/colonoscopy-related complications in mainland China included bleeding in 4,359 cases (0.02%) and perforation in 914 (0.003%). Endoscopic-retrograde-cholangiopancreatography-related complications included severe acute pancreatitis in 593 cases (0.3%), bleeding in 2,151 (1.10%), perforation in 257 (0.13%) and biliary infection in 4,125 (2.11%). Moreover, 1,313 (5.0%) endoscopists encountered with medical malpractice, and 5,243 (20.0%) encountered with the disturbance from patients. The length of endoscopy experience, weekly working hours, weekly night shifts, annual vacation days and job satisfaction were predictors for the occurrence of medical malpractice and patient disturbance. However, the length of endoscopy experience and the ratio of endoscopists to nurses were not adequate to establish an effective predictive model for endoscopy complications., Conclusion: The workload and job satisfaction of endoscopists are valuable predictors for medical malpractice or patient disturbance. More comprehensive data are needed to establish quality-predictive models for endoscopic complications., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest arising from this work.

The aim of this randomized controlled trial was to evaluate the effect of tranexamic acid (TXA) on postoperative blood loss during transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). A total of 60 patients with BPH and undergoing TURP were randomized into TXA and control groups. Patients were intravenously administered 1 g TXA or placebo (0.9% sodium chloride solution), respectively, after the induction of anesthesia for TURP. Intraoperative and postoperative bladder irrigation volumes and blood loss volumes were compared between the two groups. Coagulation function (measured by prothrombin, activated partial thromboplastin and thrombin time and fibrinogen levels) was measured before the operation and at 4 h post-operation. Complications from thromboembolic events, such as lower-limb and pulmonary embolisms, were also noted. The TXA group had significantly decreased blood loss intraoperatively and at 4 h postoperatively compared with the control group (P<0.05). The 24 h postoperative blood loss and coagulation function of the two groups were not significantly different. No thromboembolic events or other complications occurred in either group. In conclusion, a preoperative single dose of TXA was indicated to reduce perioperative blood loss in TURP without a notable increase in thrombosis risk.

The peroxisome proliferator-activated receptor gamma (PPAR- γ ) agonist rosiglitazone inhibits NF- κ B expression and endogenous neural stem cell differentiation into neurons and reduces the inflammatory cascade after spinal cord injury (SCI). The aim of this study was to explore the mechanisms underlying rosiglitazone-mediated neuroprotective effects and regulation of the balance between the inflammatory cascade and generation of endogenous spinal cord neurons by using a spinal cord-derived neural stem cell culture system as well as SD rat SCI model. Activation of PPAR- γ could promote neural stem cell proliferation and inhibit PKA expression and neuronal formation in vitro. In the SD rat SCI model, the rosiglitazone + forskolin group showed better locomotor recovery compared to the rosiglitazone and forskolin groups. MAP2 expression was higher in the rosiglitazone + forskolin group than in the rosiglitazone group, NF- κ B expression was lower in the rosiglitazone + forskolin group than in the forskolin group, and NeuN expression was higher in the rosiglitazone + forskolin group than in the forskolin group. PPAR- γ activation likely inhibits NF- κ B, thereby reducing the inflammatory cascade, and PKA activation likely promotes neuronal cell regeneration.

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the -2000 to -1752 bp segment of the 5'-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→︀CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the -1997 to -1700 and -1091 to -811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.

In this paper; the surface plasmon resonance (SPR) sensor with a porous silica film was studied. The effect of the thickness and porosity of the porous silica film on the performance of the sensor was analyzed. The results indicated that the figure of merit (FOM) of an SPR sensor can be enhanced by using a porous silica film with a low-refractive-index. Particularly; the FOM of an SPR sensor with 40 nm thick 90% porosity porous silica film; whose refractive index is 1.04 was improved by 311% when compared with that of a traditional SPR sensor. Furthermore; it was found that the decrease in the refractive index or the increase in the thickness of the low-refractive-index porous silica film can enlarge the FOM enhancement. It is believed that the proposed SPR sensor with a low-refractive-index porous silica film will be helpful for high-performance SPR sensors development., Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the expression levels of S100A6, Notch1 in multiple myeloma (MM) patients and its clinical significance. Mathods: The expression levels of S100A6, Notch1 in 28 MM cases and 20 healthy controls were determined by real time quantitative PCR (RQ-PCR) , and their relationships with clinical features and outcomes were analyzed. Immunohistochemical was used to analysis the levels of S100A6 and Notch1 in bone marrow biopsy samples and intramedullary metastases soft tissues. RQ-PCR and Western blot were used to test the changes of Notch1 mRNA and Notch1 protein in U266 MM cells after S100A6 silenced by siRNA. Results: ①The expression levels of S100A6, Notch1 in primary MM patients was 2.19±1.25, 2.98±0.64, significantly higher than those in controls (0.71±0.20, 0.58±0.39, P <0.05) and patients in platform status (0.85±0.26, 0.72±0.40, P <0.05) . 8 cases with intramedullary metastasis had significantly higher levels of S100A6 (3.36±1.23) and Notch1 (5.71±3.96) , as compared to those without extra medullary metastases. ②S100A6 expression was positive correlation with Notch1 ( r =0.505, P =0.007) . ③S100A6 and Notch1 proteins were positive in plasma cells of bone marrow biopsy samples and intramedullary metastases soft tissues. ④The Notch1 mRNA and Notch1 expression decreased significantly after 48 hours treatment by S100A6 siRNA in U266 cells. Conclusion: S100A6 and Notch1 were closely associated with MM progress and intramedullary metastasis. They have significant correlation and might be as two prognostic molecular markers in MM.

Aim: To evaluate the numbers of different subsets of monocytes and their associations with the values of clinical measures in mild acute pancreatitis (MAP) patients., Methods: The study included one group of 13 healthy controls and another group of 24 patients with new-onset MAP. The numbers of different subsets of monocytes were examined in these two groups of subjects by flow cytometry. The concentrations of plasma interleukin (IL)-10 and IL-12 were determined by cytometric bead array. The acute physiology and chronic health evaluation (APACHE) II scores of individual patients were evaluated, and the levels of plasma C-reactive protein (CRP) as well as the activities of amylase and lipase were measured., Results: In comparison with that in the controls, significantly increased numbers of CD14+CD163-, CD14+CD163-MAC387+ M1 monocytes, but significantly reduced numbers of CD14+CD163+IL-10+ M2 monocytes were detected in the MAP patients ( P < 0.01 or P < 0.05). Furthermore, significantly higher levels of plasma IL-10 and IL-12 were observed in the MAP patients ( P < 0.01 for all). More importantly, the levels of plasma CRP were positively correlated with the numbers of CD14+CD163- ( R = 0.5009, P = 0.0127) and CD14+CD163-MAC387+ ( R = 0.5079, P = 0.0113) M1 monocytes and CD14+CD163+CD115+ M2 monocytes ( R = 0.4565, P = 0.0249) in the patients. The APACHE II scores correlated with the numbers of CD14+CD163+CD115+ ( R = 0.4581, P = 0.0244) monocytes and the levels of plasma IL-10 ( R = 0.4178, P = 0.0422) in the MAP patients. However, there was no significant association among other measures tested in this population., Conclusion: Increased numbers of CD14+CD163- and CD14+ CD163-MAC387+ monocytes may contribute to the pathogenesis of MAP, and increased numbers of CD14+CD163+CD115+ monocytes may be a biomarker for evaluating the severity of MAP., Competing Interests: Conflict-of-interest statement: The authors declare no financial or commercial conflicts of interest.

Three new limonoid-type triterpenoids, namely toonasins A-C (1-3) with a rare lactam E ring, along with six known compounds (4-9) were isolated from the barks of Toona sinensis. The structures of new compounds were elucidated by interpretation of spectroscopic data, and the relative configuration of compound 1 was further characterized by X-ray crystallographic analyses. The isolated compounds were evaluated for their cytotoxic activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480), and compounds 3 and 5 showed weak cytotoxicities., Competing Interests: The authors declare no conflict of interest.

The antitumor activity of shikonin derivatives is largely dependent on the generation of superoxide radicals and the alkylation activity of their naphthoquinone moiety. However, our recent study showed that 1,4-dioxime-5,8-dimethoxynaphthalene (DMAKO-05), a novel shikonin derivative, displayed more potential antitumor activity and less toxicity compared to fluorouracil (5-FU) both in vitro and in vivo, even though the hydroxyl and carbonyl groups of its naphthoquinone structure were shielded. To understand the underlying mechanisms, we investigated the metabolism of DMAKO-05 in rat liver microsomes. The kinetic analysis indicated that DMAKO-05 underwent a biphasic metabolism in rat liver microsomes. The inhibition experiments showed that CYP1A and CYP3A were the major enzymes in the metabolism of DMAKO-05, along with partial contribution from CYP2A. In addition, the structures of eight DMAKO-05 metabolites, which were characterized by accurate mass and MS/MS fragmentograms, implied that DMAKO-05 was mainly metabolized through the oxygenation of its naphthoquinone nucleus and the hydrolysis of its side chain, instead of the oxidation of hydroxyimine to ketone. Therefore, DMAKO-05 should not be considered as a traditional naphthoquinone prodrug.

We revealed an interesting facet-dependent electrochemical behavior toward heavy metal ions (HMIs) based on their adsorption behaviors. The (111) facet of Co3O4 nanoplates has better electrochemical sensing performance than that of the (001) facet of Co3O4 nanocubes. Adsorption measurements and density-functional theory (DFT) calculations reveals that adsorption of HMIs is responsible for the difference of electrochemical properties. Our combined experimental and theoretical studies provide a solid hint to explain the mechanism of electrochemical detection of HMIs using nanoscale metal oxides. Furthermore, this study not only suggests a promising new strategy for designing high performance electrochemical sensing interface through the selective synthesis of nanoscale materials exposed with different well-defined facets, but also provides a deep understanding for a more sensitive and selective electroanalysis at nanomaterials modified electrodes.