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Shan-Mei Wang,1,* Xian He,2,* Nan Li,1,* Feng Yu,3 Yang Hu,1 Liu-Sheng Wang,1 Peng Zhang,4 Yu-Kui Du,1 Shan-Shan Du,1 Zhao-Fang Yin,1 Ya-Ru Wei,1 Xavier Mulet,5 Greg Coia,6 Dong Weng,1 Jian-Hua He,3 Min Wu,7 Hui-Ping Li1 1Department of Respiratory Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 2School of Medicine, Suzhou University, SuZhou, 3Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 4Department of Chest Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 5CSIRO (Commonwealth Scientific and Industrial Research) Materials Science and Engineering, Clayton, 6CSIRO Materials Science and Engineering, Parkville, Melbourne, VIC, Australia; 7Department of Basic Sciences, University of North Dakota, Grand Forks, ND, USA *These authors contributed equally to this work Abstract: Lung-targeting drugs are thought to be potential therapies of refractory lung diseases by maximizing local drug concentrations in the lung to avoid systemic circulation. However, a major limitation in developing lung-targeted drugs is the acquirement of lung-specific ligands. Pulmonary surfactant protein A (SPA) is predominantly synthesized by type II alveolar epithelial cells, and may serve as a potential lung-targeting ligand. Here, we generated recombinant rat pulmonary SPA (rSPA) as an antigen and immunized an alpaca to produce two nanobodies (the smallest naturally occurring antibodies) specific for rSPA, designated Nb6 and Nb17. To assess these nanobodies’ potential for lung targeting, we evaluated their specificity to lung tissue and toxicity in mice. Using immunohistochemistry, we demonstrated that these anti-rSPA nanobodies selectively bound to rat lungs with high affinity. Furthermore, we intravenously injected fluorescein isothiocyanate-Nb17 in nude mice and observed its preferential accumulation in the lung to other tissues, suggesting high affinity of the nanobody for the lung. Studying acute and chronic toxicity of Nb17 revealed its safety in rats without causing apparent histological alterations. Collectively, we have generated and characterized lung-specific nanobodies, which may be applicable for lung drug delivery. Keywords: nanobodies, rSPA, phage-nanobody library, VHH, lung-targeting drugs

ZnO nanoparticles (NPs) are used in skin treatments and cosmetics, the toxicity of long-term and continuous exposure to ZnO NPs is unknown. Mice with epidermal barrier dysfunction revealed melanoma-like lesions after continuous exposure to ZnO NPs. However, the effects of metallic NPs on the skin microenvironment and immune system remain poorly understood. Mice with epidermal barrier failure were given continuous exposure to ZnO NPs for 7 weeks. The malignant transformation of melanocytes was induced with ZnO NPs 2.5 μg/ml for 72 h exposure. The supernatant of the culture medium from dendritic cells after being exposed to 10 μg/ml ZnO NPs for 24 h was applied to melanocytes to explore the effect of recruitment of DCs. The expressure of ZnO NPs resulted in a tendency of malignant transformation of melanocytes, the recruitment of DCs induces this process by produce inflammatory factors such as TNF-α. These DC-produced inflammatory factors, which were induced by ZnO NP exposure, increased the production of matrix metalloproteinases in melanocytes and expedited the malignant transformation process. Our findings revealed that the disrupted cutaneous microenvironment by ZnO NPs penetrated directly promoted the malignant transformation of melanocytes, which process also indirectly enhanced by the TNF-αsecreted from the recruited DCs., 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 Ltd. All rights reserved.)

The drive to enhance enzyme performance in industrial applications frequently clashes with the practical limitations of exhaustive experimental screening, underscoring the urgency for more refined and strategic methodologies in enzyme engineering. In this study, xylanase Xyl-1 was used as the model, coupling evolutionary insights with energy functions to obtain theoretical potential mutants, which were subsequently validated experimentally. We observed that mutations in the nonloop region primarily aimed at enhancing stability and also encountered selective pressure for activity. Notably, mutations in this region simultaneously boosted the Xyl-1 stability and activity, achieving a 65% success rate. Using a greedy strategy, mutant M4 was developed, achieving a 12 °C higher melting temperature and doubled activity. By integration of spectroscopy, crystallography, and quantum mechanics/molecular mechanics molecular dynamics, the mechanism behind the enhanced thermal stability of M4 was elucidated. It was determined that the activity differences between M4 and the wild type were primarily driven by dynamic factors influenced by distal mutations. In conclusion, the study emphasizes the pivotal role of evolution-based approaches in augmenting the stability and activity of the enzymes. It sheds light on the unique adaptive mechanisms employed by various structural regions of proteins and expands our understanding of the intricate relationship between distant mutations and enzyme dynamics.

Background: Bivalirudin, a direct thrombin inhibitor, is used in anticoagulation therapies as a substitute for heparin, especially during cardiovascular procedures such as percutaneous coronary intervention., Aim: To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome (ACS)., Methods: In total, 165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study. From June 2020 to June 2022, elderly patients with ACS with complete data were selected and treated with interventional therapy. The study cohort was randomly divided into a study group ( n = 80, administered bivalirudin) and a control group ( n = 85, administered unfractionated heparin). Over a 6-mo follow-up period, differences in emergency processing times, including coronary intervention, cardiac function indicators, occurrence of cardiovascular events, and recurrence rates, were analyzed., Results: Significant differences were observed between the study cohorts, with the observation group showing shorter emergency process times across all stages: Emergency classification; diagnostic testing; implementation of coronary intervention; and conclusion of emergency treatment ( P < 0.05). Furthermore, the left ventricular ejection fraction in the observation group was significantly higher ( P < 0.05), and the creatine kinase-MB and New York Heart Association scores were notably lower than those in the control group ( P < 0.05)., Conclusion: In elderly patients receiving interventional therapy for ACS, bivalirudin administration led to increased activated clotting time achievement rates, enhanced myocardial reperfusion, and reduced incidence of bleeding complications and adverse cardiac events., Competing Interests: Conflict-of-interest statement: The authors declare they have nothing to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV., Results: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined., Conclusion: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology., (© 2024. The Author(s).)

Purpose: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery., Methods: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally., Results: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1., Conclusion: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE., (© 2023. The Author(s).)

Previous research has demonstrated that humans combine multiple sources of spatial information such as self-motion and landmark cues while navigating through an environment. However, it is unclear whether this involves comparing multiple representations obtained from different sources during navigation (parallel hypothesis) or building a representation first based on self-motion cues and then combining with landmarks later (serial hypothesis). We tested these two hypotheses (parallel vs serial) in an active navigation task using wireless mobile scalp EEG recordings. Participants walked through an immersive virtual hallway with or without conflicts between self-motion and landmarks (i.e., intersections) and pointed toward the starting position of the hallway. We employed the oscillatory signals recorded during mobile wireless scalp EEG as a means of identifying when participant representations based on self-motion versus landmark cues might have first emerged. We found that path segments, including intersections present early during navigation, were more strongly associated with later pointing error, regardless of when they appeared during encoding. We also found that there was sufficient information contained within the frontal-midline theta and posterior alpha oscillatory signals in the earliest segments of navigation involving intersections to decode condition (i.e., conflicting vs not conflicting). Together, these findings suggest that intersections play a pivotal role in the early development of spatial representations, suggesting that memory representations for the geometry of walked paths likely develop early during navigation, in support of the parallel hypothesis., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome with up to 90% lifetime cancer risk. Cancer screening, including annual whole-body MRI (WB-MRI), is recommended due to known survival advantage, with cancer detection rate of 7% on initial screening. Intervention and cancer detection rates on subsequent screenings are unknown. Clinical data for pediatric and adult patients with LFS (n = 182) were reviewed, including instances of WB-MRI screening and interventions based on screening results. For each WB-MRI screening, interventions including biopsy and secondary imaging, as well as rate of cancer diagnosis, were analyzed comparing initial versus subsequent WB-MRI. Of the total cohort (n = 182), we identified 68 adult patients and 50 pediatric patients who had undergone at least two WB-MRI screenings, with a mean of 3.8 ± 1.9 (adults) and 4.0 ± 2.1 (pediatric) screenings. Findings on initial screening led to an imaging or invasive intervention in 38% of adults and 20% of children. On follow up, overall intervention rates were lower for adults (19%, P = 0.0026) and stable for children (19%, P = NS). Thirteen cancers were detected overall (7% of adult and 14% of pediatric scans), on both initial (pediatric: 4%, adult: 3%) and subsequent (pediatric: 10%, adult: 6%) screenings. Rates of intervention after WB-MRI screening decreased significantly in adults between first and subsequent exams and remained stable in pediatric patients. Cancer detection rates were similar on screening (3%-4% initial, 6%-10% subsequent) for both children and adults. These findings provide important data for counseling patients with LFS about screening outcomes., Prevention Relevance: The cancer detection rate, burden of recommended interventions, and rate of false-positive findings found on subsequent WB-MRI screenings in patients with LFS are not well understood. Our findings suggest that annual WB-MRI screening has clinical utility and likely does not result in an unnecessary invasive intervention burden for patients., (©2023 American Association for Cancer Research.)

The postmortem interval (PMI) estimation is a key and difficult point in the practice of forensic medicine, and forensic scientists at home and abroad have been searching for objective, quantifiable and accurate methods of PMI estimation. With the development and combination of high-throughput sequencing technology and artificial intelligence technology, the establishment of PMI model based on the succession of the microbial community on corpses has become a research focus in the field of forensic medicine. This paper reviews the technical methods, research applications and influencing factors of microbial community in PMI estimation explored by using high-throughput sequencing technology, to provide a reference for the related research on the use of microbial community to estimate PMI.

An important question regards the nature of our spatial memories for the paths that we have walked and, in particular, whether such distortions might violate the topological properties of the shape of the paths (i.e., creating an intersection when two paths did not intersect or vice versa). To investigate whether and how this might occur, we tested humans in situations in which they walked simple paths and idiothetic and visual cues either matched or mismatched, with the mismatching cues creating the greatest potential for topological distortions. Participants walked four-segment paths with 90° turns in immersive virtual reality and pointed to their start location when they arrived at the end of the path. In paths with a crossing, when the intersection was not presented, participants pointed to a novel start location suggesting a topological distortion involving non-crossed paths. In paths without a crossing, when a false intersection was presented, participants pointed to a novel start location suggesting a topological distortion involving crossed paths. In paths without crossings and without false intersections, participants showed reduced pointing errors that typically did not involve topological distortions. Distortions more generally, as indicated by pointing errors to the start location, were significantly reduced for walked paths involving primarily idiothetic cues with limited visual cues; conversely, distortions were significantly increased when idiothetic cues were diminished and navigation relied primarily on visual cues. Our findings suggest that our spatial memories for walked paths sometimes involve topological distortions, particularly when resolving the competition between idiothetic and visual cues., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Chinese Jiang-flavor Baijiu is the most widely consumed liquor. Jiang-flavor Daqu, a fermentation starter, is important sources of key flavors of Jiang-flavor Baijiu. Some microbes play significant roles in flavor formation of Daqu. In order to clarify the microbial population that promotes the formation of Daqu flavor, we use high throughput sequencing technology combined with headspace solid-phase microextraction gas chromatography-mass spectrometry to investigate microbial population and volatile compounds in Jiang-flavor Daqu. In addition, the dynamic changes of physicochemical factors and enzyme activities in Jiang-flavor Daqu were investigated. Correlations between microbial population, volatile compounds, physicochemical factors, and enzyme activities of Jiang-flavor Daqu were disclosed by redundancy analysis and Spearman correlation analysis. A total of 66 volatile compounds were identified and 14 primary microorganisms were selected. Results showed that high temperature environment could promote the formation of acids, aldehydes and ketones, phenols, furans by affecting the growth of Monascus, Trichomonascus, Cutaneotrichosporon, Wallemia, Millerozyma, Nigrospora, Cladosporium, Bacillus, and Pediococcus in the early fermentation stage. While high nitrogen environment was more suitable for the growth of Virgibacillus and Kroppenstedtia, who could promote the formation of pyrazines in the late fermentation stage. PRACTICAL APPLICATIONS: This study has provided a scientific basis for the directed regulation of Daqu fermentation through physicochemical factors, developed scientific basis for artificially constructing Daqu microbial population and obtaining an easy-to-operate, reproducible fermentation system for Daqu production., (© 2022 Wiley Periodicals LLC.)

Previous research indicates that while animals who locomote on surfaces have a more variable and less precise spatial coding vertically than horizontally, animals who fly do not demonstrate a horizontal advantage (Hayman et al., 2011; Yartsev and Ulanovsky, 2013). The current study investigated whether humans' localization is more variable vertically than horizontally in different locomotion modes. In an immersive virtual room, participants learned the locations of objects presented on one wall. By locomoting from a location on the floor to each object, they replaced objects using memories. One group of participants (the flying group) flew three-dimensionally along their viewing direction by pushing a joystick. The second group (floor-wall group) locomoted only on the floor and the wall along the projection of the viewing direction onto the current travelling surface. The third group pressed a button to be teleported from the floor to the wall and then locomoted on the wall (wall-only group). The results showed that the variance of localization error was larger vertically than horizontally in the flying and floor-wall groups but that the pattern reversed in the wall-only group. In addition, while both the flying and wall-only groups locomoted straight towards the target location, the floor-wall group locomoted straight towards the projection of the target location onto the ground rather than straight towards the wall, indicating that the floor-wall group tried to avoid horizontal movement on the wall. These results suggest that for humans a horizontal advantage occurs in encoding the objects' locations presented on the wall whereas a vertical advantage occurs in locomotion on the wall., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: To evaluate the placement feasibility and safety of the newly designed retropharyngeal reduction plate by cadaveric test and to perform morphometric trajectory analysis., Methods: The five cadaveric specimens with intact atlantoaxial joint were enrolled in this study. They were used for simulating the placement process and evaluating the placement feasibility of the retropharyngeal reduction plate. The atlantoaxial dislocation (AAD) of five cadaveric specimens were obtained by proper external force after dissecting ligaments. The retropharyngeal reduction plate was placed on atlantoaxial joint of cadaveric specimens. The X-ray and three-dimensional (3D) spiral CT were used for evaluating the placement safety of retropharyngeal reduction plate. The DICOM data was obtained after 3D spiral CT scanning for the morphometric trajectory analysis., Results: The reduction plates were successfully placed on the atlantoaxial joint of five cadaveric specimens through the retropharyngeal approach, respectively. The X-ray and 3D spiral CT showed the accurate screw implantation and satisfying plate placement. The length of the left/right atlas screw trajectory (L/RAT) was, respectively, 1.73 ± 0.01 cm (LAT) and 1.71 ± 0.02 cm (RAT). The length of odontoid screw trajectory (OST) was 1.38 ± 0.02 cm. The length of the left/right axis screw trajectory (L/RAXT) was, respectively, 1.67 ± 0.02 cm (LAXT) and 1.67 ± 0.01 cm (RAXT). There was no statistical significance between left side and right side in terms of AT and AXT (P > 0.05). The angles of atlas screw trajectory angle (ASTA), axis screw trajectory angle (AXSTA), and odontoid screw trajectory angle (OSTA) were 38.04° ± 2.03°, 56.92° ± 2.66°, and 34.78° ± 2.87°, respectively., Conclusion: The cadaveric test showed that the retropharyngeal reduction plate is feasible to place on the atlantoaxial joint, which is also a safe treatment choice for atlantoaxial dislocation. The meticulous preoperative planning of screw trajectory based on individual differences was also vital to using this technique., (© 2022 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objectives: To study the effects of temperature and time for diatoms digestion and find out suitable digestive temperature and time., Methods: Eighty pieces of liver tissues were collected, each piece of tissue was 2 g, and 2 mL Pearl River water was added to each piece of tissue. The digestion temperature was set at 100 ℃, 120 ℃, 140 ℃, 160 ℃, 180 ℃ and the digestion time was set at 40, 50, 60, 70, 80 min. The liver tissue and water mixture were divided into 8 portions in each group. All the samples were tested by microwave digestive - vacuum filtration - automated scanning electron microscopy method. The quantity of diatom recovered and the quality of residue on the membrane were recorded., Results: When the digestion time was set to 60 min, there were statistically significant differences in the number of diatoms recovered at different temperatures ( P <0.05). The maximum number of diatoms recovered was (28 797.50±6 009.67) at 140 ℃, and the minimum residue was (0.60±0.28) mg at 180 ℃. When the digestion temperature was set at 140 ℃, there were statistically significant differences in the number of diatoms recovered at different digestion times ( P <0.05). The number of diatoms recovered was the highest at 40 min, it was up to (20 650.88±1 950.29), and the residue quality of each group had no statistical significance among different digestion time groups( P >0.05)., Conclusions: The effect of diatom digestion is related to temperature and time. When the digestion temperature was 140 ℃ and the digestion time was 40, 50 and 60 min, it is favorable for diatom test.

Objectives: To explore the application values of diatom artificial intelligence (AI) search system in the diagnosis of drowning., Methods: The liver and kidney tissues of 12 drowned corpses were taken and were performed with the diatom test, the view images were obtained by scanning electron microscopy (SEM). Diatom detection and forensic expert manual identification were carried out under the thresholds of 0.5, 0.7 and 0.9 of the diatom AI search system, respectively. Diatom recall rate, precision rate and image exclusion rate were used to detect and compare the efficiency of diatom AI search system., Results: There was no statistical difference between the number of diatoms detected in the target marked by the diatom AI search system and the number of diatoms identified manually ( P >0.05); the recall rates of the diatom AI search system were statistically different under different thresholds ( P <0.05); the precision rates of the diatom AI system were statistically different under different thresholds( P <0.05), and the highest precision rate was 53.15%; the image exclusion rates of the diatom AI search system were statistically different under different thresholds ( P <0.05), and the highest image exclusion rate was 99.72%. For the same sample, the time taken by the diatom AI search system to identify diatoms was only 1/7 of that of manual identification., Conclusions: Diatom AI search system has a good application prospect in drowning cases. Its automatic diatom search ability is equal to that of experienced forensic experts, and it can greatly reduce the workload of manual observation of images.

Objectives: To study whether diatoms can enter the body through the lymphatic system of the digestive tract., Methods: Twenty experimental rabbits were divided into the test group and the control group randomly, and intragastric administration was performed with 20 mL water sample from the Pearl River and 20 mL ultrapure water, respectively. After 30 min, lymph, lungs, livers and kidneys were extracted for the diatom test. The concentration, size and type of diatoms were recorded., Results: The concentration of diatoms of the test group was higher than that of the control group ( P <0.05). In the test group, Stephanodiscus , Coscinodiscus , Cyclotella, Melosira , Nitzschia , Synedra , Cymbella , and Navicula were detected; in the control group, Stephanodiscus , Coscinodiscus and Cyclotella were detected. The long diameter and the short diameter of diatoms of the test group were higher than those of the control group ( P <0.05). In the test group, 1-2 diatoms were detected in 3 lung samples and 2 liver samples, which were Stephanodiscus or Cyclotella , and no diatoms were detected in the kidney samples; in the control group, 1-2 diatoms were detected in 2 lung samples and 3 liver samples, which were Stephanodiscus or Coscinodiscus , and no diatoms were detected in the kidney samples., Conclusions: Diatoms can enter the body through the lymphatic fluid, which is one of the reasons for the presence of diatoms in tissues and organs of non-drowning cadavers.

Objectives: To retrospectively analyze diatom test cases of corpses in water and discuss the value of quantitative analysis of diatoms in the diagnosis of drowning., Methods: A total of 490 cases of water-related death were collected. They were divided into drowning group and postmortem immersion group according to the cause of death. Diatoms in lung, liver, kidney tissue and water sample were analyzed quantitatively by microwave digestion-vacuum filtration-automated scanning electron microscopy (MD-VF-Auto SEM) method. The ratios of content of diatoms in lung tissue and water sample ( C L / C D ) were calculated., Results: The results of diatom test for three organs (lung, liver and kidney) were all positive in 400 cases (85.5%); the content of diatom in lung, liver, kidney tissues, and water samples of drowning group were (113 235.9±317 868.1), (26.7±75.6), (23.3±52.2) and (12 113.3±21 760.0) cells/10 g, respectively; the species of diatom were (7.5±2.8), (2.6±1.9), (2.9±2.1) and (8.9±3.0) types, respectively; the C L / C D of drowning group and postmortem immersion group were (100.6±830.7) and (0.3±0.4), respectively., Conclusions: Quantitative analysis of diatoms can provide supportive evidence for the diagnosis of drowning, and the parameter C L / C D can be introduced into the analysis to make a more accurate diagnosis of drowning.

Objectives: To compare the application effect of microwave digestion - vacuum filtration - automated scanning electron microscopy (MD-VF-Auto SEM) method and plankton gene multiplex PCR system in the diagnosis of drowning., Methods: Lung, liver and kidney tissue of 10 non-drowning cases and 50 drowning cases were prepared for further MD-VF-Auto SEM method analysis and plankton gene multiplex PCR system analysis. The positive detection rate of the two methods in each tissue was calculated., Results: The positive rate of the MD-VF-Auto SEM method detecting diatoms in drowning cases was 100%, and few diatoms were detected in the liver and kidney tissues of 6 non-drowning cases. By using the plankton gene multiplex PCR system, the diatom positive rate of drowning cases was 84%, and all the non-drowning cases were negative. There were significant differences in the positive rate of the liver, kidney tissues between MD-VF-Auto SEM method and plankton gene multiplex PCR system ( P <0.05), as well as the total positive rate of cases. However, no significant differences were found in the positive rates of lung tissues ( P >0.05)., Conclusions: MD-VF-Auto SEM method is more sensitive than plankton gene multiplex PCR system in diatom test. But the plankton gene multiplex PCR system can also detect plankton other than diatoms. Combination of the two methods can provide a more reliable basis for the diagnosis of drowning.

Alzheimer's disease is a common neurodegenerative disease in the elderly. This study explored the curative effect and possible mechanism of Acori graminei rhizoma on Alzheimer's disease. In this paper, 8 active components of Acori graminei rhizoma were collected by consulting literature and using the TCMSP database, and 272 targets were screened using the PubChem and Swiss Target Prediction databases. Introduce it into the software of Cytoscape 3.7.2 and establish the graph of "drug-active ingredient-ingredient target." A total of 276 AD targets were obtained from OMIM, Gene Cards, and DisGeNET databases. Import the intersection targets of drugs and diseases into STRING database for enrichment analysis, and build PPI network in the Cytoscape 3.7.2 software, whose core targets involve APP, AMPK, NOS3, etc. GO analysis and KEGG analysis showed that there were 195 GO items and 30 AD-related pathways, including Alzheimer's disease pathway, serotonin synapse, estrogen signaling pathway, dopaminergic synapse, and PI3K-Akt signaling pathway. Finally, molecular docking was carried out to verify the binding ability between Acori graminei rhizoma and core genes. Our results predict that Acori graminei rhizoma can treat AD mainly by mediating Alzheimer's signal pathway, thus reducing the production of A β , inhibiting the hyperphosphorylation of tau protein, regulating neurotrophic factors, and regulating the activity of kinase to change the function of the receptor., Competing Interests: The authors have no conflicts of interest., (Copyright © 2021 Yi Kuan Du et al.)

This study investigated to what extent humans can encode spatial relations between different surfaces (i.e., floor, walls, and ceiling) in a three-dimensional (3D) space and extend their headings on the floor to other surfaces when locomoting to walls (pitch 90°) and the ceiling (pitch 180°). In immersive virtual reality environments, participants first learned a layout of objects on the ground. They then navigated to testing planes: south (or north) walls facing Up, or the ceiling via walls facing North (or South). Participants locomoted to the walls with pitch rotations indicated by visual and idiothetic cues (Experiment 1) and only by visual cues (Experiment 2) and to the ceiling with visual pitch rotations only (Experiment 3). Using the memory of objects' locations, they either reproduced the object layout on the testing plane or did a Judgements of Relative Direction (JRD) task ("imagine standing at object A, facing B, point to C") with imagined headings of south and north on the ground. The results showed that participants who locomoted onto the wall with idiothetic cues showed a better performance in JRD for an imagined heading from which their physical heading was extended (e.g., imagined heading of North at the north wall). In addition, the participants who reproduced the layout of objects on the ceiling from a perspective extended from the ground also showed a sensorimotor alignment effect predicted by an extended heading. These results indicate that humans encode spatial relations between different surfaces and extend headings via pitch rotations three-dimensionally, especially with idiothetic cues.

Older adults typically perform worse on spatial navigation tasks, although whether this is due to degradation of memory or an impairment in using specific strategies has yet to be determined. An issue with some past studies is that older adults are tested on desktop-based virtual reality: a technology many report lacking familiarity with. Even when controlling for familiarity, these paradigms reduce the information-rich, three-dimensional experience of navigating to a simple two-dimensional task that utilizes a mouse and keyboard (or joystick) as means for ambulation. Here, we utilize a wireless head-mounted display and free ambulation to create a fully immersive virtual Morris water maze in which we compare the navigation of older and younger adults. Older and younger adults learned the locations of hidden targets from same and different start points. Across different conditions tested, older adults remembered target locations less precisely compared to younger adults. Importantly, however, they performed comparably from the same viewpoint as a switched viewpoint, suggesting that they could generalize their memory for the location of a hidden target given a new point of view. When we implicitly moved one of the distal cues to determine whether older adults used an allocentric (multiple landmarks) or beaconing (single landmark) strategy to remember the hidden target, both older and younger adults showed comparable degrees of reliance on allocentric and beacon cues. These findings support the hypothesis that while older adults have less precise spatial memories, they maintain the ability to utilize various strategies when navigating., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McAvan, Du, Oyao, Doner, Grilli and Ekstrom.)

This research investigated the association between prolonged disposable diaper (DD) wearing in infancy and primary enuresis (PNE). As a case-control study, we collected data from 376 children with enuresis and 379 healthy children who were sex- and age-matched at three tertiary care institutions in mainland China from August 2017 to July 2018. The results of adjusted logistic regression showed the odds ratios (95% confidence intervals) for PNE across the categories of age of daytime DD use cessation were as follows: ≥ 25 months: 1.00, 18-24 months: 0.25 (0.17-0.37), and ≤ 17 months: 0.11 (0.06-0.20), independent of age, mother education, residence, toilet training approach, breastfeeding duration, UTI, constipation, anaphylactic disease and family history. After a similar multivariable adjustment, increased age of daytime DD use (per-month) had a positive correlation with PNE, OR = 1.17, 95% CI 1.13-1.20 and non-linear relationship was detected, whose point was 21 months (the effect sizes and the 95%CI on the left and right sides of inflection point were 1.04 (0.99-1.10), P = 0.131 and 1.25 (1.18-1.31), P < 0.001). Subgroup analysis found that the effect of duration of disposable diaper exposure for each additional month, those children had accepted assisted infant toilet training/elimination communication (AITT/EC) practice had a lower risk of PNE (OR = 1.08, 95% CI 1.04-1.12), compared with those without AITT/EC practice (OR = 1.20, 95% CI 1.14-1.27), P for interaction < 0.001. In conclusion, the children diagnosed with primary enuresis after age 5 stopped using disposable diapers at daytime later than the control group. Association between duration of DD exposure and the risk of childhood enuresis is modified by AITT/EC practice. Timely cessation use of disposable diaper and practice AITT/EC may shorten the time to nocturnal continence, and the prospective cohort studies are needed to verify the discoveries.

Objectives: Occipitocervical fusion (OCF) is an effective treatment for instability of occipitocervical junction (OCJ). The occipital condyle screw serves as a novel surgical technique for occipitocervical fixation. However, the intraoperative procedures for the occipital condyle screw technique have relied on surgeons' experience, so the pool of surgeons who are able to perform this surgery safely is limited. The present study aims to evaluate the feasibility and safety of the occipital condyle screw technique using human cadavers and to provide image anatomy for clinical application basis., Methods: The scientific study comprised 10 fresh-frozen cadaveric specimens from the anatomy department of Qingdao University. Placement of the occipital condyle screws (3.5 mm diameter and 20.0 mm length) was performed in the 10 fresh-frozen cadaveric specimens with intact occipitocervical junctions, respectively. Occipitocervical CT was performed for all specimens and the DICOM data was obtained. Occipitocervical CT three-dimensional (3D) reconstruction was performed for the cadavers. Morphometric analysis was performed on the bilateral occipitocervical junction of 10 cadaveric specimens based on the 3D reconstruction CT images. Detailed morphometric measurements of the 20 occipital condyles screws were conducted including the average length of the screw trajectory, inside and upper tilting angles of screws, distance to the hypoglossal canal, and to the medial wall of occipital condyle., Results: Placement of the occipital condyle screws into the 20 occipital condyles of the 10 cadaveric specimens was performed successfully and the trajectory of implantation was satisfactory according to 3D CT reconstruction images, respectively. There was no obvious injury to the spinal cord, nerve root, and vertebral artery. The length of the bilateral screw trajectory was, respectively, 20.96 ± 0.91 mm (left) and 20.59 ± 0.77 mm (right) (t = 1.306, P > 0.05). The upper tilting angle of bilateral screws was, respectively, 11.24° ± 0.74° (left) and 11.11° ± 0.64° (right) (t = 0.681, P > 0.05). The inside tilting angle of bilateral screws was, respectively, 31.00° ± 1.32° (left) and 30.85° ± 1.27° (right) (t = 0.307, P > 0.05). The screw's distance to the bilateral hypoglossal canal was, respectively, 4.84 ± 0.54 mm (left) and 4.70 ± 0.54 mm (right) (t = 0.685, P > 0.05). The screw's distance to the medial wall of the bilateral occipital condyle was, respectively, 5.13 ± 0.77 mm (left) and 5.04 ± 0.71 mm (right) (t = 0.384, P > 0.05)., Conclusion: The occipital condyle screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction with meticulous preoperative planning of the screw entry point and direction based on individual differences. Morphometric trajectory analysis is also an effective way to evaluate the surgical procedure., (© 2020 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Background: Globally, attitudes and practices towards toilet training have changed several decades ago and children are completing toilet training at a later age compared to previous generations. Concurrently, there has been an increase in the incidence of pediatric bladder bowel dysfunction (BBD), including lower urinary tract dysfunction (LUTD). Whether the fact of delayed toilet training may negatively impact the ability of children to obtain bladder and bowel control and cause LUT dysfunction remains controversial., Objectives: To investigate the association between age at initiation of toilet training or approach to toilet training and the risks of lower urinary tract (LUT) dysfunction., Methods: A comprehensive search of the CENTRAL, EMBASE and MEDLINE via Ovid SP, and CINAHL via EBSCO databases was conducted to identify RCTs, cohort or case-control studies investigating the association between age at initiation of toilet training, approach used for toilet training, and pediatric LUT dysfunction., Results: A total of 10 studies with 24,121 participants (aged 5-17) were included for pooled analysis. Overall, the odds ratio (OR) with 95% confidence interval (95%CI) of LUT dysfunction in children who initiated toilet training at a younger age when compared to those who initiated toilet training at an older age, was 0.71 (0.63-0.81), P < 0.001), irrespective of the approach used for toilet training (Table). Subgroup analysis for day-time incontinence (persistent daytime wetting) was 0.77 (0.62-0.95), P = 0.014; although the outcomes for enuresis fluctuated, favorable results were still observed in the earlier training group (OR:0.63, 95%CI:0.43-0.94, P = 0.023). Subgroup analysis for age at initiating toilet training vs LUT dysfunction also showed favorable results in children who were trained earlier, i.e., before 24 months (OR:0.77, 95% CI 0.63-0.94, P = 0.009). Sensitivity analysis confirmed that the results were robust., Discussion: Although the definition about the age of initial toilet training varied greatly in studies, findings from the current study suggested that the optimal time for initiating toilet training may be prior to the age of 24 months; if toilet training was initiated after 24 months or later, it may result in increased prevalence of LUT dysfunction. Since no RCTs studies were included in the current meta-analysis, well-designed longitudinal studies with larger sample size and from different cultural background are needed to confirm these results., Conclusion: This meta-analysis presents preliminary findings that show the incidence of LUTD may be decreased by initiating toilet training in children at a younger age., Competing Interests: Declaration of competing interest All authors declare that they have no competing interests., (Copyright © 2020 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Chromatin dynamics regulated by epigenetic modification is crucial in genome stability and gene expression. Various epigenetic mechanisms have been identified in the pathogenesis of human diseases. Here, we examined the effects of ten epigenetic agents on pseudorabies virus (PRV) infection by using GFP-reporter assays. Inhibitors of bromodomain protein 4 (BRD4), which receives much more attention in cancer than viral infection, was found to exhibit substantial anti-viral activity against PRV as well as a range of DNA and RNA viruses. We further demonstrated that BRD4 inhibition boosted a robust innate immune response. BRD4 inhibition also de-compacted chromatin structure and induced the DNA damage response, thereby triggering the activation of cGAS-mediated innate immunity and increasing host resistance to viral infection both in vitro and in vivo. Mechanistically, the inhibitory effect of BRD4 inhibition on viral infection was mainly attributed to the attenuation of viral attachment. Our findings reveal a unique mechanism through which BRD4 inhibition restrains viral infection and points to its potent therapeutic value for viral infectious diseases., Competing Interests: The authors have declared that no competing interests exist.

Autophagy maintains cellular homeostasis by degrading organelles, proteins, and lipids in lysosomes. Autophagy is involved in the innate and adaptive immune responses to a variety of pathogens. Some viruses can hijack host autophagy to enhance their replication. However, the role of autophagy in porcine reproductive and respiratory syndrome virus (PRRSV) infection is unclear. Here, we show that N-Myc downstream-regulated gene 1 ( NDRG1 ) deficiency induced autophagy, which facilitated PRRSV replication by regulating lipid metabolism. NDRG1 mRNA is expressed ubiquitously in most porcine tissues and most strongly in white adipose tissue. PRRSV infection downregulated the expression of NDRG1 mRNA and protein, while NDRG1 deficiency contributed to PRRSV RNA replication and progeny virus assembly. NDRG1 deficiency reduced the number of intracellular lipid droplets (LDs), but the expression levels of key genes in lipogenesis and lipolysis were not altered. Our results also show that NDRG1 deficiency promoted autophagy and increased the subsequent yields of hydrolyzed free fatty acids (FFAs). The reduced LD numbers, increased FFA levels, and enhanced PRRSV replication were abrogated in the presence of an autophagy inhibitor. Overall, our findings suggest that NDRG1 plays a negative role in PRRSV replication by suppressing autophagy and LD degradation. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped single-positive-stranded RNA virus, causes acute respiratory distress in piglets and reproductive failure in sows. It has led to tremendous economic losses in the swine industry worldwide since it was first documented in the late 1980s. Vaccination is currently the major strategy used to control the disease. However, conventional vaccines and other strategies do not provide satisfactory or sustainable prevention. Therefore, safe and effective strategies to control PRRSV are urgently required. The significance of our research is that we demonstrate a previously unreported relationship between PRRSV, NDRG1, and lipophagy in the context of viral infection. Furthermore, our data point to a new role for NDRG1 in autophagy and lipid metabolism. Thus, NDRG1 and lipophagy will have significant implications for understanding PRRSV pathogenesis for developing new therapeutics., (Copyright © 2019 Wang et al.)

Information on anatomy of the Cun position at wrist is lacking; whether the blood vessel taking pulse in Cun is the radial artery or the superficial palmar branch is also clinically controversial. The objective was to investigate the boundaries and contents, and the vascular distribution and their pulse points in Cun. Thirty-two upper extremities of 16 human cadavers were investigated for dissection and observation. The boundaries, contents, and blood vessel distribution in Cun were observed; the location of pulse points in Cun was identified; the length of the superficial palmar branch in wrist pulse (L1), the pulp width of the index finger (L2), and the angle between the radial artery and the superficial palmar branch were measured. The results showed that the Cun was located in the region formed by the bulge of the prominent bone proximal to the palm, the radial flexor tendon, the tubercle of scaphoid, and the abductor longus muscle tendon. In this area, the radial artery could be pulsed part in the medial side of the abductor longus muscle tendon, while the superficial palmar branch lied near the surface and was easy to pulse in the lateral side of the radial flexor tendon and the medial side of the tubercle of scaphoid. The ratio of L1 to L2 was 1.2±0.8, and the angle was 23.3±9.9°. The results suggested that it could not be generalized that the blood vessel taking pulse in Cun was the radial artery or the superficial palmar branch; it might depend on the vascular distribution in Cun, the region of finger positioning, and the patient's pulse condition.

Azithromycin (AZM), that is a macrolide antibiotic, has been found to treat diffuse panbronchiolitis (DPB) effectively. However, the mechanism of action underlying the therapeutic effects remains unclear. We selected 64 patients with DPB from 305 patients who were diagnosed with DPB at the outpatient clinic in Shanghai Pulmonary Hospital from Jan 2010 to Oct 2014. The primary PBLs, CD4 + T cells, and Jurkat T cells were treated with AZM or erythromycin (EM), and the effects of AZM and EM on IL-17A and CXCL-2 production, proliferation, apoptosis and autophagy were evaluated. AZM and EM significantly inhibited IL-17A and CXCL-2 production in patients' PBLs (all P < 0.05). AZM significantly inhibited proliferation and promoted apoptosis of T cells from DPB patients. AZM can enhance autophagosome formation of T cells by suppressing S6RP phosphorylation, which is a downstream target of mTOR pathway (all P < 0.05). AZM and EM significantly decreased secreted IL-17A levels (P < 0.05) in the primary CD4 + T cells of patients with DPB. AZM may treat DPB patients by targeting cytokine production, proliferation, apoptosis and autophagy of T cell. The mechanism of therapeutic effects of AZM on DPB may be associated with a specific inhibition of mTOR pathway in the T lymphocytes., (Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF., Objectives: Our purpose is to investigate the role of infection in AE-IPF., Methods: Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed., Results: Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN- γ , MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%) .Conclusions . IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.

Researches on associations between phthalates exposure and child attention deficit hyperactivity disorder (ADHD) are inconsistent. This study aimed to evaluate the associations of urinary phthalates with ADHD, co-occurring oppositional defiant disorder (ODD), related symptoms and behavior problems among Chinese children. We enrolled 225 ADHD cases and 225 healthy controls aged 6-13 years old in Liuzhou, China. Each child provided repeated urine samples at 4 visits. Eight phthalate metabolites were measured by high-performance liquid chromatography and tandem mass spectrometry. Child ADHD symptoms and related behaviors were assessed using Swanson, Nolan, and Pelham Version IV scale and child behavior checklist. Higher urinary concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono-(2-ethyl)-hexyl phthalate (MEHP) were dose-dependently associated with ADHD [odds ratios (ORs) ranged from 2.35 to 3.04 for the highest vs. the lowest tertile] and co-occurring ODD (ORs ranged from 3.27 to 4.44 for the highest vs. the lowest tertile) in the multivariable logistic regression models (all p for trend ≤ 0.01), which were consistent with positive trends of increased scores of inattention domain, hyperactive domain and ODD symptoms (all p for trend ≤ 0.01). Besides, the monomethyl phthalate (MMP) concentration was associated with higher scores of inattention domain and ODD symptoms (both p < 0.05). Additionally, the MEHHP, MEOHP and MEHP concentrations were related to child attention problems, aggressive behaviors and externalizing behaviors (all p < 0.05). We also observed positive associations of the MEHP concentration with depressed behaviors and internalizing behaviors (all p < 0.05). Our results indicate that child exposure to phthalates may contribute to ADHD, ODD and externalizing and internalizing behavior problems., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

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Nanobody (Nb) is a promising vector for targeted drug delivery. This study aims to identify an Nb that can specifically target the lung by binding human pulmonary surfactant protein A (SP-A). Human lung frozen tissue sections were used for 3 rounds of biospanning of our previously constructed Nb library for rat SP-A to establish a sub-library of Nb, which specifically bound human lung tissues. Phage-ELISA was performed to screen the sub-library to identify Nb4, which specifically bound human SP-A. The binding affinity Kd of Nb4 to recombinant human SP-A was 7.48 × 10 -7 M. Nb4 (19 kDa) was stable at 30 °C-37 °C and pH 7.0-7.6 and specifically bound the SP-A in human lung tissue homogenates, human lung A549 cells, and human lung tissues, whereas didn't react with human liver L-02 cells, kidney 293T cells, and human tissues from organs other than the lung. Nb4 accumulated in the lung of nude mice 5 minutes after a tail vein injection of Nb4 and was excreted 3 hours. Short-term exposure (one month) to Nb4 didn't cause apparent liver and kidney toxicity in rats, whereas 3-month exposure resulted in mild liver and kidney injuries. Nb4 may be a promising vector to specifically deliver drugs to the lung.

A dose-response experiment with 5 analyzed dietary crude protein (CP) levels (17.61, 19.73, 21.58, 23.24, and 25.32%) was conducted to investigate the effects of low-protein diets on growth performance and carcass yields of French meat quails from 15 to 42 d of age. All diets were formulated to contain a similar dietary energy level and amino acid profile. A total of 400 fifteen-day-old French quails were divided into 5 experimental treatments and each treatment contained 4 replicate pens of 20 birds (10♂+10♀). At 42 d of age, weight gain, feed intake, CP intake, feed/gain, and the yields of breast part with bone, leg part with bone, and liver of quails from each pen were measured. The results showed significant effects of the low-CP diets on CP intake, weight gain, feed intake, and feed/gain at different experiment periods except for the sixth wk of age (P < 0.05). In addition, as dietary CP decreased from 25.32 to 17.61%, feed intake and feed/gain were increased linearly (P < 0.05), whereas CP intake showed the opposite trend and decreased gradually. On the other hand, the carcass yields of quail were not influenced by reducing dietary CP at 42 day of age (P > 0.05). Based on broken-line regression, 23.0%, 22.5%, and 20.4% were the minimum dietary CP to keep weight gain similar to the quails fed with 25.32% CP diets during the third, fourth, and fifth wk of age, respectively. In summary, with crystalline amino acid supplementation based on a similar amino acid profile, it was possible to formulate the low-protein diets containing about 22.0% CP for growing meat quails without adverse effects on growth and carcass yields of meat quails., (© 2016 Poultry Science Association Inc.)

Objectives: The purpose of this study was to determine the diagnostic and prognostic values of serum KL-6 levels in Chinese patients with interstitial lung disease (ILDs)., Methods: A total of 1084 subjects including 373 cases of ILDs, 584 cases of non-ILD pulmonary diseases, and 127 healthy individuals were recruited from three clinical centers in China between January 2011 and December 2013. A total of 106 patients undergoing treatments for ILDs in Shanghai Pulmonary Hospital between January 2011 and December 2013 were enrolled. Baseline and posttreatment serum KL-6 levels were determined., Results: Serum KL-6 levels in patients with ILDs were significantly higher than those in patients with non-ILD pulmonary diseases or in healthy individuals (1492.09 ± 2230.08 U/mL vs 258.67 ± 268.73 U/mL or 178.73 ± 71.17 U/mL, all P < 0.05). At the cut-off value of 500 U/mL, the sensitivity and specificity of serum KL-6 as a diagnostic marker for ILDs was 77.75% and 94.51%, respectively. The Kappa value was 0.743 (P < 0.001). The area below the receiver operating characteristic curve was 0.922 with a 95% Confidence interval of 0.904-0.941 (P < 0.001). The posttreatment serum KL-6 levels significantly reduced in patients with improved ILDs, whereas markedly increased in patients with exacerbated ILDs (All P < 0.05)., Conclusions: Serum KL-6 levels might be a promising diagnostic biomarker for ILDs in Chinese patients. The prognostic value of serum KL-6 levels for ILDs remains to be verified by large-scaled studies., (© 2015 John Wiley & Sons Ltd.)

Objective: To assess the test-retest reliability and criterion validity of the Simplified Chinese-character version of the International Physical Activity Questionnaire Long form (IPAQ-L) in urban community-dwelling adults in Hanghzou, China., Methods: A total of 158 eligible participants aged 25-59 years from 6 neighbourhoods in two central districts of Hangzhou completed the IPAQ-L questionnaire twice within a 7-day interval. Half of the subjects wore pedometers during the first 7 days. Test-retest reliability was examined by comparing the first (Day 1) and the second (Day 9) survey of IPAQ-L. Criterion validity was assessed by comparing IPAQ-L with pedometer data., Results: Modest to good test-retest reliability was found with intraclass correlation coefficients of 0.67 for total PA, 0.37 to 0.73 for specific dimensions, and 0.56 to 0.71 for different intensities of PA. Total PA measured by IPAQ-L was moderately correlated with exercise levels (partial r = 0.27, P = 0.020) and walking distance (partial r = 0.31, P = 0.007), which were measured by a pedometer, after adjusting for gender, age, educational attainment and employment status., Conclusion: Our results indicate that the IPAQ-L is a reliable and validated measure for assessing physical activity levels in this population and possibly the adult population in other mainland Chinese cities., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Cervical radiculopathic pain is a very common symptom that may occur with cervical spondylosis. Mechanical allodynia is often associated with cervical radiculopathic pain and is inadequately treated with current therapies. However, the precise mechanisms underlying cervical radiculopathic pain-associated mechanical allodynia have remained elusive. Compelling evidence from animal models suggests a role of large-diameter dorsal root ganglion neurons and plasticity of spinal circuitry attached with Aβ fibers in mediating neuropathic pain. Whether cervical radiculopathic pain condition induces plastic changes of large-diameter dorsal root ganglion neurons and what mechanisms underlie these changes are yet to be known. With combination of patch-clamp recording, immunohistochemical staining, as well as behavioral surveys, we demonstrated that upon chronic compression of C7/8 dorsal root ganglions, large-diameter cervical dorsal root ganglion neurons exhibited frequent spontaneous firing together with hyperexcitability. Quantitative analysis of hyperpolarization-activated cation current ( I h ) revealed that I h was greatly upregulated in large dorsal root ganglion neurons from cervical radiculopathic pain rats. This increased I h was supported by the enhanced expression of hyperpolarization-activated, cyclic nucleotide-modulated channels subunit 3 in large dorsal root ganglion neurons. Blockade of I h with selective antagonist, ZD7288 was able to eliminate the mechanical allodynia associated with cervical radiculopathic pain. This study sheds new light on the functional plasticity of a specific subset of large-diameter dorsal root ganglion neurons and reveals a novel mechanism that could underlie the mechanical allodynia associated with cervical radiculopathy.

Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.

Objective: To understand the prevalence of domestic violence and the correlation between domestic violence and posttraumatic stress disorder (PTSD) so as to improve the mental health status of women in Wuhan city of China. Methods: A cross-sectional study was conducted in the community health service center in Wuhan. Participants were women who came to the center for gynecological examination. Data on general condition, social support, injury, epidemiological characteristics of domestic violence and PTSD were gathered. Chi -square, student- t and Cochran-Armitage trend tests were employed to compare the distribution of each characteristic variable between PTSD and non-PTSD group. Binary logistic regression was used to analyze the correlation between domestic violence and PTSD. Results: A total of 1 015 women were effectively surveyed. The life-time incidence rates of events related to domestic, psychological, physical and sexual violence were 29.36%, 28.28%, 6.60% and 3.55%, respectively. The overall prevalence rate of PTSD was 4.73%. Women who suffered from domestic violence had higher risk of PTSD ( OR =2.11, 95 %CI : 1.04-4.29) than those who never experiencing domestic violence. Women who suffered from psychological or physical violence were 5.06 times more likely to suffer from PTSD ( OR =5.06, 95 % CI : 1.91-13.42). Conclusion: A strong correlation between domestic violence and PTSD was seen. Victims who suffered from domestic violence should be provided with psychological counseling to reduce the risk of PTSD.

Stressful life events have been implicated in the etiology of kinds of psychopathology related to nonsuicidal self-injury (NSSI); however, few studies have examined the association between NSSI and stressful life events directly in Chinese school adolescents. In this study, we aim to estimate the prevalence rate of NSSI and examine its association with stressful life events in Southern Chinese adolescents. A total sample of 4405 students with age ranged from 10 to 22 years was randomly selected from 12 schools in 3 cities of Guangdong Province, China. NSSI, stressful life events, self-esteem, emotional management, and coping methods were measured by structured questionnaires. Multinomial logistic regression was used to examine the association of NSSI with stressful life events. Results showed the 1 year self-reported NSSI was 29.2%, with 22.6% engaged in "minor" NSSI (including hitting self, pulling hair, biting self, inserting objects under nails or skin, picking at a wound) and 6.6% in "moderate/sever" NSSI (including cutting/carving, burning, self-tattooing, scraping, and erasing skin). Self-hitting (15.9%), pulling hair out (10.9%), and self-inserting objects under nails or skin picking areas to dram blood (18.3%) were the most frequent types of NSSI among adolescents. Results also showed that "Minor NSSI" was associated with stressful life events on interpersonal, loss and health adaption, and "moderate/severe NSSI" was associated with life events on interpersonal, health adaption in Southern Chinese adolescents, even after adjusted for sex, age, residence, self-esteem, coping style, and emotional management. Results further suggested stressful life events were significantly associated with less risk of NSSI in those who had good emotional management ability.

Purpose: To explore and establish an animal model of AE-IPF., Methods: An animal model of idiopathic pulmonary fibrosis (IPF) was established using bleomycin (BLM). Then, BLM was administered a second time on day 21 to induce AE-IPF (which mimics human AE-IPF). Evaluation of the success of animal model was based on the survival of mice, as well as assessment of pathological changes in lung tissue. Preliminary investigation into the immunological mechanism of AE-IPF was also explored via the detection and identification of the inflammatory cells in mouse bronchoalveolar lavage fluid (BALF) and the concentrations of six cytokines (IL-4, IL-6, IL-10, IL-17A, MIG, and TGF-β1) in BALF supernatants, which were closely associated with IPF and AE-IPF. The intervention role of IL-17A antibody to AE was explored., Results: By week 4 after the second BLM administration, the mortality in the AE-IPF group was significantly greater (45%, 9/20) than that in stable-IPF group (0/18) (P = .0017). The average body weight in AE-IPF group was significantly lower than that in stable group (P < .0001). In AE-IPF group, inflammation and fibrosis were severer by histopathology analysis. In BALF, IL-17A, MIG (CXCL-9), IL-6, and TGF-β1 levels in AE group were significantly higher. The percentages of neutrophils and Th17 cells in BALF were significantly higher in AE group (P < .01; P = .0281). IL-17A antibody could attenuated the lung inflammation induced by twice BLM challenges., Conclusion: A mouse model of AE-IPF can be established using two administrations of BLM; Th17 cells may play a key role during the pathological process of AE-IPF.

Background: Because the prevalence of connective tissue disease (CTD)-associated interstitial lung disease (ILD; CTD-ILD) in China is unknown, we wanted to analyze the clinical characteristics of this disease in Chinese patients., Methods: The medical records of patients who received a diagnosis of ILD and treated in Shanghai Pulmonary Hospital from January 1999 to January 2013 were reviewed. Based on the records, patients who also received a diagnosis of CTD were identified, and their records of follow-up examinations for a minimum of 12 months until the end of December 2013 were reviewed., Results: Of the 2,678 patients who received a diagnosis of ILD, 1,798 (67%) were identified as having CTD-ILD; 299 (11.2%) had idiopathic pulmonary fibrosis (IPF). Complete clinical data were available for 1,044 patients with CTD-ILD and 178 with IPF. We found that 332 of the 1,044 patients with CTD-ILD (32%) did not receive an accurate diagnosis at the initial hospital admission, 195 (18.7%) of the 1,044 patients showed persistent negative test results for autoantibodies, and 262 (25.1%) of the 1,044 patients had negative autoantibodies at the initial hospital admission and then became positive at follow-up examinations. Of the 288 patients who had confirmed CTD-ILD, 41 (14%) showed pulmonary symptoms as the initial clinical manifestation (PSIM) and 247 (86%) showed extrapulmonary symptoms as the initial clinical manifestation (EPSIM). For the 756 patients who had undifferentiated CTD-ILD, the proportion of PSIM and EPSIM was 44% and 56%, respectively. For patients who presented with PSIM, 23 who had confirmed CTD-ILD (56%) and 216 who had unconfirmed CTD-ILD (65%) did not receive an accurate diagnosis at the initial visit but were ultimately diagnosed at subsequent follow-up examinations., Conclusions: Patients with CTD-ILD do not receive an accurate diagnosis at the initial hospital admission possibly because of negative serologic test results for autoantibodies and the absence of obvious extrapulmonary symptoms. Thus, patients with ILD should be examined for extrapulmonary symptoms and tested for autoantibodies at follow-up examinations., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Glycation product accumulation during aging of slowly renewing tissues may be an important mechanism underlying aging of the testis. Adipose-derived stem cells (ADSCs) have shown promise in a novel tissue regenerative technique and may have utility in treating sexual dysfunction. ADSCs have also been found to be effective in antiaging therapy, although the mechanism underlying their effects remains unknown. This study was designed to investigate the anti-aging effect of ADSCs in a D-galactose (D-gal)-induced aging animal model and to clarify the underlying mechanism. Randomly selected 6-week-old male Sprague-Dawley rats were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, D-gal-induced aging rats were randomized to receive caudal vein injections of 3 × 10(6) 5-bromo 2'deoxy-uridine-labeled ADSCs or an equal volume of phosphate-buffered saline. Serum testosterone level, steroidogenic enzymes (3-β-hydroxysteroid dehydrogenase), and superoxide dismutase (SOD) activity decreased significantly in aging rats compared with the control group; serum lipid peroxidation, spermatogenic cell apoptosis, and methane dicarboxylic aldehyde (MDA) expression increased significantly. ADSCs increased the SOD level and reduced the MDA level in the aging animal model and restored levels of serum testosterone, steroidogenic enzymes, and spermatogenic cell apoptosis. These results demonstrate that ADSCs can contribute to testicular regeneration during aging. ADSCs also provide functional benefits through glycation suppression and antioxidant effects in a rat model of aging. Although some ADSCs differentiated into Leydig cells, the paracrine pathway seems to play a main role in this process, resulting in the reduction of apoptosis., (© 2015 Wiley Periodicals, Inc.)

Background: In this study, we sought to identify differentially expressed proteins in the serum of patients with sarcoidosis or tuberculosis and to evaluate these proteins as markers for the differential diagnosis of sarcoidosis and sputum-negative tuberculosis., Methods: Using protein microarrays, we identified 3 proteins exhibiting differential expression between patients with sarcoidosis and tuberculosis. Elevated expression of these proteins was verified using the enzyme-linked immunosorbent assay (ELISA) and was further confirmed by immunohistochemistry. Receiver operating characteristic (ROC) curve, logistic regression analysis, parallel, and serial tests were used to evaluate the diagnostic efficacy of the proteins., Results: Intercellular Adhesion Molecule 1(ICAM-1) and leptin were screened for differentially expressed proteins relevant to sarcoidosis and tuberculosis. Using ROC curves, we found that ICAM-1 (cutoff value: 57740 pg/mL) had an area under the curve (AUC), sensitivity, and specificity of 0.718, 62.3%, and 79.5% respectively, while leptin (cutoff value: 1193.186 pg/mL) had an AUC, sensitivity, and specificity of 0.763, 88.3%, and 65.8%, respectively. Logistic regression analysis revealed that the AUC, sensitivity, and specificity of combined leptin and ICAM-1 were 0.787, 89.6%, and 65.8%, respectively, while those of combined leptin, ICAM-1, and body mass index (BMI) were 0.837, 90.9%, and 64.4%, respectively, which had the greatest diagnostic value. Parallel and serial tests indicated that the BMI-leptin parallel with the ICAM-1 serial was the best diagnostic method, achieving a sensitivity and specificity of 86.5% and 73.1%, respectively. Thus, our results identified elevated expression of ICAM-1 and leptin in serum and granulomas of sarcoidosis patients., Conclusions: ICAM-1 and leptin were found to be potential markers for the diagnosis of sarcoidosis and differential diagnosis of sarcoidosis and sputum-negative tuberculosis.

Objective: To investigate the role of Pediatric Critical Illness Score (PCIS) in evaluating the prognosis and severity of severe hand-foot-mouth disease (HFMD)., Methods: This study included 424 children with severe HFMD, consisting of 390 survivors and 34 deceased patients. Related physiological parameters and clinical data were collected for calculating PCIS scores. The area under receiver operating characteristic curve (AUC) was employed to assess the performance of PCIS in evaluating the complications and outcomes., Results: The median of PCIS scores for survivors was higher than that for deceased patients (P<0.01). Of the 424 children with severe HFMD, only 26 (6.1%) had critical illness according to the severity assessment using PCIS. The AUC (95%CI) of PCIS was 0.74 (0.66, 0.82) in predicting pulmonary edema, 0.82 (0.74, 0.90) in predicting pulmonary hemorrhage, and 0.83 (0.75, 0.92) in predicting death., Conclusions: PCIS can predict the complications and prognosis in children with severe HFMD. However, the existing scoring system of PCIS cannot fully assess the severity of HFMD.

The anatomical basis for the concept of acupuncture points/meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the fascia research progress and the relationship among acupuncture points/meridians, primo vascular system (PVS), and fascia. Fascia is as a covering, with common origins of layers of the fascial system despite diverse names for individual parts. Fascia assists gliding and fluid flow and holds memory and is highly innervated. Fascia is intimately involved with nourishment of all cells of the body, including those of disease and cancer. The human body's fascia network may be the physical substrate represented by the meridians of TCM. The PVS is a newly found circulatory system; recent increased interest has led to new research and new discoveries in the anatomical and functional aspects of the PVS. The fasciology theory provides new insights into the physiological effects of acupuncture needling on basic cellular mechanisms including connective tissue mechanotransduction and regeneration. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

Objective: The purpose of this study was to investigate the effects of cigaret smoke (CS) on a mouse model of emphysema and examine the protective role of N-acetylcysteine (NAC) in the CS-induced exacerbation of pulmonary damage in the mice., Method: Particulate matter (PM) in sidestream cigaret smoke aerosol was analyzed by a scanning mobility particle sizer spectrometer. A mouse model of emphysema was established by an injection of porcine pancreatic elastase (PPE) into the trachea. Mice with emphysema were then exposed to filtered air, or sidestream CS with intragastric administration of NAC or normal saline. Mouse body weight, survival, pulmonary tissue histology, total antioxidant capacity (T-AOC) and malonaldehyde (MDA) contents in lung tissue, and inflammatory responses were examined., Results: Particles with a size of ≤346 nm constituted 99.06% of CS PM. Mice exhibited ruptured alveolar septal, alveolar fusion, significantly increased mean lining interval, and reduced mean alveolar number (all p < 0.05), 21 d after PPE injection. Exposure of mice with emphysema to CS exacerbated the pulmonary tissue damage, caused weight loss, significantly increased mortality, decreased T-AOC, elevated MDA contents in lung tissue, and increased interleukin (IL)-1β levels in bronchoalveolar lavage (BAL) fluids (all p < 0.05). Administration of NAC attenuated those CS-induced adverse effects in the mice and increased anti-inflammatory factor IL-10 levels in BAL fluids significantly (all p < 0.05)., Conclusions: Exposure of mice with emphysema to CS exacerbated the pulmonary damage, and NAC reduced the CS-mediated pulmonary damage by preventing oxidative damage and reducing inflammatory responses.