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Yixue Hu,1 Dongna Wang,2 Tianyu Zhang,2 Meng Lei,3 Yingnan Luo,2 Zhimeng Chen,3 Yuting Li,2 Dandan Duan,2 Liefeng Zhang,1 Yongqiang Zhu1,2 1College of Life Science, Nanjing Normal University, Nanjing, People’s Republic of China; 2School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, People’s Republic of China; 3College of Science, Nanjing Forestry University, Nanjing, People’s Republic of ChinaCorrespondence: Liefeng Zhang; Yongqiang Zhu, College of Life Science, Nanjing Normal University, No. 1 Wenyuan Road, Qixia District, Nanjing, 210023, People’s Republic of China, Tel/Fax +86-25-85898184; +86-25-85891591, Email lfzhang@njnu.edu.cn; zhyqscu@hotmail.comIntroduction: Tumor hypoxia and invasion present significant challenges for the efficacy of photodynamic therapy (PDT) in triple-negative breast cancer (TNBC). This study developed a mitochondrial targeting strategy that combined PDT and gene therapy to promote each other and address the challenges.Methods: The positively charged amphiphilic material triphenylphosphine-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and the photosensitizer chloride e6 (Ce6) formed TPS@Ce6 nanoparticles (NPs) by hydrophobic interaction. They electrostatically condensed microRNA-34a (miR-34a) to form stable TPS@Ce6/miRNA NPs.Results: Firstly, Ce6 disrupted the lysosomal membrane, followed by successful delivery of miR-34a by TPS@Ce6/miRNA NPs. Meanwhile, miR-34a reduced ROS depletion and further enhanced the effectiveness of PDT. Consequently, the mutual promotion between PDT and gene therapy led to enhanced anti-tumor effects. Furthermore, the TPS@Ce6/miRNA NPs promoted apoptosis by down-regulating Caspase-3 and inhibited tumor cell migration and invasion by down-regulating N-Cadherin. In addition, in vitro and in vivo experiments demonstrated that the TPS@Ce6/miRNA NPs achieved excellent anti-tumor effects. These findings highlighted the enhanced anticancer effects and reduced migration of tumor cells through the synergistic effects of PDT and gene therapy.Conclusion: Taken together, the targeted co-delivery of Ce6 and miR-34a will facilitate the application of photodynamic and genic nanomedicine in the treatment of aggressive tumors, particularly TNBC. Keywords: photodynamic therapy, gene therapy, hypoxia, invasion, mitochondrial target, triple-negative breast cancer

Rongxin Sun,1 Desheng Duan,2 Renzeng Li2 1Department of Orthopaedics, The Sixth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Province, People’s Republic of China; 2Second Department of Orthopaedics, Third People’s Hospital of Anyang City, Anyang City, Henan Province, People’s Republic of ChinaCorrespondence: Renzeng Li, Second Department of Orthopaedics, Third People’s Hospital of Anyang City, 363 Dongfeng Road, Beiguan District, Anyang City, Henan Province, People’s Republic of China, Tel +86-13837247813, Email LRZ_doctor@163.comBackground: Recent studies have put forward the viewpoint of “bone immunology”, which holds that the immune system and immune factors play an important regulatory role in the occurrence and development of osteoporosis. This study was intended to identify genetic characteristics of differentially expressed immune-related mRNA and lncRNA in patients combined with osteoporosis and vertebral fracture.Methods: The peripheral blood samples were obtained from 3 groups of subjects: healthy control (HC), osteoporosis patients without vertebral fracture (OWF), and osteoporosis patients combined with vertebral fracture (OVF). The data were integrated to obtain differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs). Subsequently, the protein-protein interaction (PPI) networks were constructed. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were performed. Cytoscape-cytoHubba plug-in was used to identify key DEmRNAs. Furthermore, lncRNA-miRNA-mRNA, mRNA-lncRNA co-expression and transcription factors (TFs) networks were constructed. In addition, real-time PCR verification was performed.Results: Totally of 3378 lncRNA-mRNA pairs were obtained, and the lncRNA co-expressed mRNA was mainly enriched in immune-related pathways, especially in GO-biological process (GO-BP) analysis. A total of 8 hub immune-related DEmRNAs were obtained, including IL18R1, IL18RAP, SLC11A1, CSF2RA, CCR3, IL1R2, PGLYRP1, and IL1R1. The TFs network showed that 8 hub immune-related DEmRNAs had interacting TFs. The co-expression network showed that 7 hub immune-related DEmRNAs (IL18R1, IL18RAP, SLC11A1, CSF2RA, IL-1R2, PGLYRP1, and IL1R1) had lncRNA-mRNA co-expression relationship. In addition, the lncRNA-miRNA-mRNA network includes 32 miRNAs, 7 hub immune-related mRNAs (IL18R1, IL18RAP, CSF2RA, CCR3, IL1R2, PGLYRP1, and IL1R1), and 11 lncRNAs.Conclusion: Our study provides a novel and in-depth identification of co-expressed mRNAs and lncRNAs in patients combined with osteoporosis and vertebral fracture at a molecular level. This may provide new candidate biomarkers for the diagnosis of patients with high-risk fractures in the future.Keywords: osteoporosis, vertebral fracture, immune, mRNA, lncRNA, transcriptome

Daisy Duan,1 Chenjuan Gu,2 Vsevolod Y Polotsky,2 Jonathan C Jun,2 Luu V Pham2 1Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Division of Pulmonary and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USACorrespondence: Luu V PhamPulmonary and Critical Care Medicine, 5501 Hopkins Bayview Circle, Asthma and Allergy Center, Johns Hopkins Sleep Disorders Center, Baltimore, MD, 21224, USATel +1 410-550-0741Fax +1 410-550-3374Email luu.pham@jhmi.eduPurpose: Eating time and sleep habits are important modifiable behaviors that affect metabolic health, but the relationship between food intake and sleep remains incompletely understood. Observational data suggest that late food intake is associated with impaired sleep quality. We examined the effect of routine dinner (RD, 5 hours before bedtime) vs late dinner (LD, 1 hour before bedtime) on sleep architecture in healthy volunteers.Participants and Methods: This was a post hoc analysis of a randomized crossover study of RD vs LD with a fixed sleep opportunity in a laboratory setting. On each of the two visits, 20 healthy adult volunteers (10 women) received an isocaloric meal followed by overnight polysomnography. Sleep architecture over the course of the night was assessed using visual sleep staging and EEG spectral power analysis and was compared between RD and LD. We modeled the proportions of spectral power in alpha, beta, delta, and theta bands as functions of dinner timing, time of night, and their interaction with mixed-effect spline regression.Results: Conventional sleep stages were similar between the 2 visits. LD caused a 2.5% initial increase in delta power and a reciprocal 2.7% decrease in combined alpha and beta power (p< 0.0001). These effects diminished as sleep continued with a reversal of these patterns in the latter part of the night.Conclusion: Contrary to the existing literature, shifting dinner timing from 5 hours before sleep to 1 hour before sleep in healthy volunteers did not result in significant adverse changes in overnight sleep architecture. In fact, LD was associated with deeper sleep in the beginning of the night and lighter sleep in the latter part of the night in healthy volunteers. This novel manifestation of postprandial hypersomnia may have therapeutic potential in patients with sleep disorders.Keywords: late eating, dinner timing, sleep architecture, EEG spectral power

Liu Ouyang, Yang Dan, Zengwu Shao, Shuhua Yang, Cao Yang, Guohui Liu, Wu Zhou, Deyu Duan Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China Purpose: Umbelliferone (Umb), a member of coumarin family, is found in many plants and is a promising molecule with potential anti-inflammatory, anti-oxidative, and anti-tumor activities. However, the effect of Umb on arthritis remains unclear.Methods: A rat model with Freund’s complete adjuvant (FCA)-induced arthritis was developed and used to test the efficacy of Umb on arthritis rats. Rats were given an intragastric injection of Umb (20 and 40 mg/kg) once daily from days 21 to 28 after the administration of FCA. Hind paw volume was assessed using a volume meter. The pro-inflammatory cytokine levels and prostaglandin E2 (PEG2) level in serum and synovial fluid were detected by ELISA. HE staining was used to determine representative histological changes in joint tissues, and Western blot analysis was employed to study the effects of Umb on MAPK/NF-κB signaling pathway.Results: Our results showed that Umb suppressed the release of IL-6, IL-1β, tumor necrosis factor-alpha, and PEG2. In addition, Umb could also dramatically ameliorate the pathological changes observed in rat joints. Based on the results of Western blot, we also observed that Umb could strikingly suppress the expression of MAPK/NF-κB pathway molecules.Conclusion: These results proved that treatment with Umb is very effective for arthritis and inhibiting the MAPK/NF-κB signaling pathway may be a potential therapeutic target for treatment of arthritis. Keywords: umbelliferone, arthritis, inflammation, MAPK/NF-κB pathway

Dongyu Duan,1,* Aiping Wang,1,* Ling Ni,2 Liping Zhang,1 Xiuju Yan,1 Ying Jiang,1 Hongjie Mu,1 Zimei Wu,1 Kaoxiang Sun,1 Youxin Li1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, 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 Introduction: Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab’ (antigen-binding fragments cut from TMAB)-modified NPs (Fab'-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells. Material and methods: The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab'-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS).Results: The release kinetics showed that both Fab'-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab'-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab'-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2-) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab'-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab'-Cur-NPs was higher than that of TMAB-Cur-NPs. Conclusion: Fab' fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery. Keywords: trastuzumab-modified curcumin nanoparticles, Fab'-modified curcumin nanoparticles, pharmacokinetics, biodistribution, tumour targeting, breast cancer

Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, Shandong Province, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD.Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs.Results: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum) than R-NPs. The pharmacodynamic study revealed a significant difference (P

Li Gao,1,2 Lunyang Xia,3 Ruhui Zhang,1 Dandan Duan,3 Xiuxiu Liu,2 Jianjian Xu,2 Lan Luo1 1State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 2School of Biological and Medical Engineering, Hefei University of Technology, Hefei, 3Laboratory of Pharmaceutical Research, Anhui Zhongren Science and Technology Co., Ltd., Hefei, People’s Republic of China Purpose: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. Materials and methods: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. Results: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor suppression rate without additional systemic toxicity. Conclusion: These results demonstrate that methotrexate-loaded implants had significant antitumor efficacy in a sarcoma 180 mouse model without dose-limiting side effects, and suggest that the implants could be potentially applied as an intratumoral delivery system to treat cancer. Keywords: methotrexate, implant, sustained release, poly(D,L-lactide-co-glycolide), intratumoral chemotherapy

Yujia Deng,1 Lei Wang,1,2 Lite Ge,1,3 Da Duan,1 Yi Zhuo,1 Ting Yuan,1 Weiping Yan,1 Peiqi Huang,1 Xiaohua Teng,1 Ming Lu1,3 1Department of Neurosurgery, The Second Affiliated Hospital of Hunan Normal University (163 Hospital of the People’s Liberation Army), Changsha, 2Department of Neurosurgery, Affiliated Haikou Hospital, Xiangya School of Central South University, Haikou, 3Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, People’s Republic of China Objective: Insulin-like growth factor binding protein-2 (IGFBP-2), a member of a highly conserved family of six insulin-like growth factor binding proteins (IGFBPs), can regulate several cellular processes through IGF-dependent or IGF-independent pathway. Recent studies have provided solid evidence for the importance to delineate that olfactory ensheathing cells (OEC)-conditioned medium (OCM) can not only facilitate the differentiation of neural stem cell line (C17.2) into neurons, but also promote the survival and proliferation. We have previously reported that IGFBP-2 was detected in OCM. This study is designed to investigate the roles of IGFBP-2 for the regulation of C17.2 differentiation and proliferation.Methods and results: IGFBP-2 was identified and upregulated in OCM to compare with astrocytes-conditioned medium by shotgun proteomics and semiquantitative proteomic analysis. In order to investigate whether exogenous IGFBP-2 could stimulate proliferation in C17.2 cells and differentiate it into glia or neuron, we used various concentrations of IGFBP-2 to induce C17.2 cells which were cultured in DMEM/F12. The results showed that exogenous IGFBP-2 can promote proliferation in C17.2 cells, but had little effect on differentiation. Interestingly, we also found that IGFBP-2 could induce C17.2 cells to differentiate into astrocytes, while inhibiting their differentiation into neurons in a dose-dependent manner when cultured C17.2 cells in OCM. Changes in cell morphology were imaged under a light microscope, and proliferating cells were counted. Cell viability was determined by MTT. In addition, Western blot, immunofluorescence, and flow cytometry analysis were performed to detect protein expression patterns of proliferation-related antigen, proliferating cell nuclear antigen, neuroectodermal stem cell marker, neuron specific class III beta tubulin, and glial fibrillary acidic protein.Conclusion: Exogenous IGFBP-2 could stimulate proliferation in C17.2 cells, and promote the differentiation of C17.2 cells into astrocytes induced by OCM. Its mechanism is related to activation of the extracellular signal-regulated kinase 1/2 pathway. Keywords: IGFBP-2, C17.2 cells, proliferation, differentiation

Ting Yuan,1* Yi Zhuo,1* Chaying Su,2 Xuan Li,1 Da Duan,1 Lite Ge,1 Pei Wu,1 Hao Wang,1 Yujia Deng,1 Ming Lu1 1Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University (163 Hospital of the People’s Liberation Army), Changsha, 2Department of Pediatrics, 169 Hospital of the People’s Liberation Army, Hengyang, Peoples’ Republic of China * These authors contributed equally to this work Abstract: Human olfactory mucosa mesenchymal-like stem cells (hOM-MSCs) secrete paracrine factors that may exert a protective effect on the cerebral ischemia. This study was done to determine the hypoxic and ischemic effects on the mRNA and protein expression level of paracrine factors by hOM-MSCs. The hOM-MSCs were cultured with 5% or 20% serum and under either normoxic (21% O2) or hypoxic (3% O2) conditions. Expression levels of mRNA and protein for vascular endothelial growth factor (VEGF), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and matrix metalloproteinase-2 (MMP-2) were determined by quantitative reverse transcription polymerase chain reaction and Western blot, respectively. Hypoxia reduced gene expression for VEGF (5% serum), GDNF, BDNF (5% serum) and NGF (5% serum) and increased it for BDNF (20% serum), MMP-2 (5% serum) and NGF (20% serum). Ischemia lowered gene expression for VEGF (hypoxia), GDNF, BDNF (hypoxia), MMP-2 (normoxia) and NGF (hypoxia) and increased it for VEGF (normoxia), BDNF (normoxia), MMP-2 (hypoxia) and NGF (normoxia).The protein level of these factors was almost in line with the gene level. These data demonstrate that serum and oxygen levels have a significant effect on the gene and protein expression levels of paracrine factors by hOM-MSCs, which will affect how hOM-MSCs interact in vivo during cerebral ischemia. Keywords: human olfactory mucosa mesenchymal-like stem cells, paracrine factors, hypoxia, ischemia, cerebral ischemia

Min Wei,1 Dongmei Duan21Department of Orthopedics, 2Department of Traditional Chinese Medicine, People’s Liberation Army General Hospital, Beijing, People’s Republic of China Abstract: T-helper 17 (Th17) pathway plays an important and distinct role in autoimmunity and inflammation. A growing body of evidence demonstrates that interleukin-17 (IL-17) is also synthesized in inflammatory arthritis tissues and exerts potent proinflammatory and joint-destructive activities. Clinical studies have been performed to evaluate the therapeutic efficacy of antibodies blocking the IL-17 signaling pathway in patients with rheumatoid arthritis (RA). In this study, we performed a meta-analysis to systematically evaluate the clinical effects of IL-17 antibodies in RA patients. By searching PubMed, five randomized, placebo-controlled randomized controlled clinical trials that tested three antibodies against IL-17A (LY2439821 and secukinumab/AIN457) and the IL-17A receptor (brodalumab) were identified. The primary outcomes that were analyzed include American College of Rheumatology (ACR) Improvement Criteria and Disease Activity Score in 28 joints (DAS28). Meanwhile, the safety and adverse effects were also systematically analyzed. The results of the meta-analysis demonstrated that IL-17 antibody is effective in ameliorating the RA symptoms. Specifically, IL-17-blocking antibody significantly reduced ACR20 and ACR50. It also dramatically reduced DAS28, an index that measures tenderness and swelling severity of joints. The side effects of and intolerance to the antibody treatment were higher than those in the placebo control. The analysis result provides evidence-based information for clinical use of these agents in the treatment of inflammatory arthritis. Keywords: interleukin-17A, arthritis, meta-analysis, rheumatoid arthritis, clinical trials

Xiaomei Pan, Dong Duan, Yuquan Zhu, Hua Pang, Lili Guan, Zhixiang Lv Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Objective: The aim of this study is to investigate the use of 99mTc-methoxyisobutylisonitrile (MIBI) imaging for evaluating the treatment response of differentiated thyroid cancer (DTC) after the first administration of a high dose of 131I.Methods: Patients with DTC who received 131I therapy underwent 99mTc-MIBI imaging after successive increases in the therapeutic dose of 131I, and the serum levels of thyroglobulin (Tg) were measured.Results: A total of 191 patients were enrolled in the final analysis, including 65 metastases and/or thyroid remnant-positive patients (22 patients with metastases and 43 patients with thyroid remnants). The sensitivity of 99mTc-MIBI imaging for detecting positive cases and thyroid remnants was 56.9% and 39.5%, respectively, which was significantly lower than that of 131I imaging (92.3% and 100%, respectively, P0.05). The Tg levels in the positive group were significantly higher than that in the negative group (P

Drought is a major natural disaster that creates a negative impact on socio-economic development and environment. Drought indices are typically applied to characterize drought events in a meaningful way. This study aims at examining variations in agricultural drought severity based on the relationship between standardized ratio of actual and potential evapotranspiration (ET and PET), enhanced vegetation index (EVI), and land surface temperature (LST) derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) platform. A new drought index, called the enhanced drought severity index (EDSI), was developed by applying spatiotemporal regression methods and time-series biophysical data derived from remote sensing. In addition, time-series trend analysis in the 2001−2018 period, along with the Mann−Kendal (MK) significance test and the Theil Sen (TS) slope, were used to examine the spatiotemporal dynamics of environmental parameters (i.e., LST, EVI, ET, and PET), and geographically weighted regression (GWR) was subsequently applied in order to analyze the local correlations among them. Results showed that a significant correlation was discovered among LST, EVI, ET, and PET, as well as their standardized ratios (|r| > 0.8, p < 0.01). Additionally, a high performance of the new developed drought index, showing a strong correlation between EDSI and meteorological drought indices (i.e., standardized precipitation index (SPI) or the reconnaissance drought index (RDI)), measured at meteorological stations, giving r > 0.7 and a statistical significance p < 0.01. Besides, it was found that the temporal tendency of this phenomenon was the increase in intensity of drought, and that coastal areas in the study area were more vulnerable to this phenomenon. This study demonstrates the effectiveness of EDSI and the potential application of integrating spatial regression and time-series data for assessing regional drought conditions.

The hydrodynamic coefficient of an underwater manipulator varies with changes in posture and flow field, presenting significant challenges for precise control and localization. This study, conducted numerical simulations to investigate the patterns of variation in flow field and hydrodynamic coefficients. Results showed that hydrodynamic performance remained consistent when the posture of the manipulator was either axisymmetric or origin-symmetric. Upon rotation, axial flow extended across the entire downstream surface, and the Karman vortex street entirely eliminated. Pressure coefficients on the back pressure surface of the manipulator increased with the Reynolds number within the range of 6x10³ ≤ Re ≤ 3x104, while the pressure coefficient on the upstream surface remained unchanged. Within this range, drag coefficients for the upper and lower arms decreased by 27.4% and 23.9%, respectively. The hydrodynamic performance of the lower arm was independent of the upper arm's posture, with a maximum drag coefficient of 1.48 achieved at α = -90°. As the posture angle of the manipulator varied from 30° to 60°, the pressure coefficient on the upstream surface decreased from 0.75 to 0.25. [ABSTRACT FROM AUTHOR]

The rapid development of industry has led to the generation of a large amount of electroplating wastewater. The direct discharge of untreated electroplating wastewater may lead to the formation of toxic metal-organic complexes, which is a challenging problem for human health and the living environment of organisms. Due to the high solubility of heavy metals in aquatic environments and their easy absorption by organisms, effective treatment of electroplating wastewater is of great significance. The ultimate goal of electroplating wastewater treatment should be to recover metals and water from electroplating wastewater. In indoor experiments, pilot tests, and industrial applications of electroplating wastewater treatment, membrane treatment technology commonly used in wastewater terminal treatment has attracted great attention. Membrane treatment technology seems to be the most promising method for removing heavy metals and organic pollutants from electroplating wastewater. This article reviews the membrane treatment technologies for electroplating wastewater, introduces the advantages and disadvantages of various membranes in the treatment of electroplating wastewater, the removal efficiency of pollutant types, and their comparison. The focus is on the treatment effects of nano-filtration membrane, ultra-filtration membrane, micro-filtration membrane, reverse osmosis membrane, ceramic membrane, biofilm, etc., on electroplating wastewater. Compared with a single treatment method, the combination of different processes shows higher efficiency in removing various pollutants. [ABSTRACT FROM AUTHOR]

The hydrodynamic coefficients of underwater manipulators constantly change during their operation. In this study, the hydrodynamic coefficients of an underwater manipulator were calculated using the finite volume method to better explain its hydrodynamic performance. The drag, lift, and moment coefficients and the Strouhal number of an underwater manipulator for different postures were investigated. The results indicated that in each motion range, the coefficients first increase and then decrease. Meanwhile, when the attitude of the underwater manipulator is axis-symmetric or origin-symmetric, the hydrodynamic coefficients and the Strouhal number obtained are approximately the identical. The drag coefficient, lift coefficient and moment coefficient reach their maximum values of 3.59, 3.29, and 1.78 at angles of 30°, 150°, and 150°, respectively, with minimum values at 90°, 50° and -30°. Furthermore, the leading-edge shape of the underwater manipulator had a significant effect on the hydrodynamic coefficient. Maximum reductions of 44%, 25%, and 50.5% were obtained in the drag, lift, and moment coefficients, respectively, by comparing the semicircular leading edge with the right-angle leading edge. A maximum Strouhal number of 0.219 was obtained when the semicircular leading edge of the underwater manipulator was the upstream surface. This study will provide theoretical guidance to reveal the hydrodynamic performance of the underwater manipulators. It also serves as a reference for the structural design of the underwater manipulators. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that periodontitis promotes metabolic dysregulation and insulin resistance by affecting the function of white adipose tissue (WAT). However, the mechanisms linking periodontitis to adipose tissue dysfunction still need to be explored. Extracellular vesicles (EVs) deliver messages to distal sites and regulate their function. Also, recent studies have shown that periodontitis changes the composition of EVs in body fluids and that EVs might be one of the mechanisms underlying the relationship between periodontitis and insulin resistance. Herein, we explored the impact of polymicrobial oral infection with periodontal pathogens on the function of WAT and the role of gingival EVs (gEVs) in the process. Mice were subjected to oral inoculation with 109 Porphyromonas gingivalis and 108 Fusobacterium nucleatum every other day for 14 wk. This prolonged bacterial infection induced WAT dysfunction, characterized by reduced levels of AKT phosphorylation, adiponectin, leptin, and genes associated with adipogenesis and lipogenesis. We successfully isolated gEVs with satisfactory yield and purity. The RNA sequencing results showed that the differentially expressed microRNAs in the gEVs of mice with polymicrobial oral infection were involved in insulin signaling and adipose tissue function. Notably, our in vitro experiments and RNA sequencing results revealed the functional similarities between gEVs and plasma-derived EVs. Furthermore, intraperitoneal injection with gEVs derived from mice with oral infection induced the dysfunction of WAT in healthy mice. Overall, our findings provide evidence for the influence of polymicrobial oral infection on WAT function and propose gEVs as a novel pathway through which periodontal infection may exert its effects on WAT. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Giant cell tumor of bone (GCTB) is a common primary bone tumor with latent malignant tendency. GCTB is prone to occur around the knee joint, and surgery is the major treatment method. There are relatively few reports on denosumab in the treatment of recurrent GCTB around the knee joint and postoperative function evaluation of patients. This research aimed to explore the appropriate surgical options for the treatment of recurrent GCTB around the knee joint. PATIENTS AND METHODS: 19 patients with recurrent GCTB around the knee joint, who were admitted to Hospital for 3 months following denosumab treatment from January 2016 to December 2019, were included as the research subjects. The prognosis was compared between patients treated with curettage combined with polymethylmethacrylate (PMMA) and those with extensive-resection replacement of tumor prosthesis (RTP). A deep learning model of Inception-v3 combined with a Faster region-based convolutional neural network (Faster-RCNN) was constructed to classify and identify X-ray images of patients. The Musculoskeletal Tumor Society (MSTS) score, short form-36 (SF-36) score, recurrence, and the rate of complications were also analyzed during the follow-up period. RESULTS: The results showed that the Inception-v3 model trained on the low-rank sparse loss function was obviously the best for X-ray image classification, and the classification and identification effect of the Faster-RCNN model was significantly better than that of the convolutional neural network (CNN), U-Net, and Fast region-based convolutional neural network (FastRCNN) models. During the follow-up period, the MSTS score in the PMMA group was significantly higher than that in the RTP group (p<0.05), while there was no significant difference in the SF-36 score, recurrence, and the rate of complications (p>0.05). CONCLUSIONS: The deep learning model could improve the classification and identification of the lesion location in the X-ray images of GCTB patients. Denosumab was an effective adjuvant for recurrent GCTB, and widely extensive-resection RTP could reduce the risk of local recurrence after denosumab treatment for recurrent GCTB. [ABSTRACT FROM AUTHOR]

Wen-Bo Wei,1– 3,&ast; Sha-Jie Dang,4,&ast; Hao-Zhe Liu,5 Da-Peng Duan,1,2 Ling Wei6 1Department of Orthopedics, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 2Shaanxi Province Key Laboratory of Basic and Clinical Translation for Bone and Joint Diseases, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi, People’s Republic of China; 3State Key Laboratory for Manufacturing Systems Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 4Department of Anesthesia, Shaanxi Provincial Cancer Hospital, Xi’an, Shaanxi, People’s Republic of China; 5Department of Surgery, Hancheng Maternal and Child Health Hospital, Hancheng, Shaanxi, People’s Republic of China; 6Department of Pain, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Wei, Department of Pain, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China, 710005, Email sxweiling@126.comBackground: As the latest endoscopic spine surgery, percutaneous endoscopic interlaminar discectomy (PEID) and unilateral biportal endoscopic (UBE) discectomy have distinct technical characteristics. This study aimed to evaluate the clinical outcomes of PEID and UBE discectomy in the treatment of single-level lumbar disc herniation (LDH).Methods: Between February 2019 and April 2022, 115 patients with single-level LDH at L4-5 or L5-S1 received PEID or UBE discectomy. The patients were separated into two groups based on the surgical method used: Group 1 (the PEID group) (n = 60) and Group 2 (the UBE group) (n = 55). Various parameters, including operative time, hospitalization time, fluoroscopy frequency, total costs, complications, visual analogue scale (VAS), and Oswestry Disability Index (ODI), were evaluated and compared between the two groups.Results: There were no significant differences in the VAS and ODI scores in 12 months after the operation between two groups (P > 0.05). However, the VAS of lower back pain on the first day after the operation in Group 2 (2.53± 0.89) was higher than that in Group 1 (2.19± 0.74) (P < 0.05). There were no significant differences in the operation time and incidence of complications between two groups (P > 0.05). But total costs in Group 2 (43,121± 4280) were significantly higher than those in Group 1 (30,069± 3551) (P < 0.05).Conclusion: Both UBE and PEID procedures have similar efficacy in alleviating pain and improving functional ability in patients with LDH. However, UBE surgery results in higher costs than PEID surgery.Keywords: unilateral biportal endoscopic discectomy, percutaneous endoscopic interlaminar discectomy, lumbar disc herniation

Di-fei Duan,1,&ast; Yue Wen,1,&ast; Yu Yan,1 Ling Li,2 Xiang Xiao,3 Xing Li,1 Lin-Jia Yan,4 Deng-Yan Ma1 1Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University /West China School of Nursing, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3West China School of Medicine, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4The Nethersole School of Nursing Faculty of Medicine, The Chinese University of Hong Kong, Hongkong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deng-Yan Ma, Department of Nephrology, West China Hospital of Sichuan University, No. 37 Guoxuexiang, Wuhou District, Chengdu, Sichuan, People’s Republic of China, Email mdy5104@wchscu.cnBackground: Given the importance of diabetic kidney disease (DKD) management, this study aims to explore the knowledge, attitudes, and practices in disease management demonstrated by healthcare workers from the nephrology department.Materials and Methods: This study is a multi-centered cross-sectional study, and adopts snowball sampling, with 530 healthcare workers being recruited to complete a questionnaire covering areas such as demographic characteristics, knowledge, attitude, and practices (KAP) of DKD management. This data was analyzed using descriptive statistics and binary logistics analysis.Results: In this study, 530 healthcare workers were studied, including 94 doctors and 436 nurses. The participants were mainly from general tertiary hospitals in 14 provinces. For Chinese nurse, the results indicate that both poor knowledge level (Odds Ratio (OR) =0.63, 95% Confidence Interval (CI): 0.42– 0.94) and having experience in further medical training in nephrology (OR=1.92, 95% CI: 1.20– 3.08) are associated with the practice levels. For Chinese doctors, having not experience in further medical training in nephrology (OR=0.36, 95% CI: 0.15– 0.83) are associated with their practice levels.Conclusion: In summary, Chinese doctors and nurses in this study showed positive attitudes towards DKD management, but their knowledge and practical skills were lacking. This underscores a notable gap in achieving optimal DKD care. Notably, nurses’ knowledge influenced their management practices, and additional nephrology training correlated with better engagement. To improve patient care, enhancing nephrology healthcare professional training and addressing knowledge-practice disparities are recommended.Keywords: knowledge, attitude, practice, diabetic kidney disease

This paper concentrates on the trajectory tracking problem for a stratospheric airship subject to underactuated dynamics, unmeasured velocities, modeling inaccuracies and environmental disturbances. First, a coordinate transformation is performed to solve the underactuated issue, which simultaneously permits a priori assignment of the tracking accuracy. Second, a finite-time observer is integrated into the control structure to offer the exact information of unmeasured velocities and uncertainties in an integral manner. Then, by combining the backstepping technique with the method of adding a power integrator, a new output-feedback control strategy is derived with several salient contributions: (1) the airship's position errors fall into a predetermined residual region near zero within a finite settling time and stay there, while all the closed-loop signals maintain bounded during operation; and (2) no artificial neural networks and filters are adopted, resulting in a low-complexity control property. Furthermore, the presented method can be extended readily to a broad range of second-order mechanical systems as its design builds upon a transformed system model. Rigorous mathematical analysis and simulations demonstrate the above theoretical findings. [ABSTRACT FROM AUTHOR]

Di-Fei Duan,1,2,&ast; Min Liu,1,2,&ast; Deng-Yan Ma,1,2 Lin-Jia Yan,3 Yue-Yang Huang,1,2 Yi Chen,1,2 Wei Jiang,1,2 Xi Tang,2 An-Qi Xiong,4,5 Yun-Ying Shi2 1West China School of Nursing, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3The Nethersole School of Nursing Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Department of Nursing, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 5Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Deng-Yan Ma, Email mdy5104@163.comPurpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients.Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters.Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction.Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.Keywords: diabetic kidney disease, network analysis, symptom cluster, symptom management

Abstract Background Peutz-Jeghers syndrome (PJS), an autosomal dominant multiple cancerous disorder, is clinically characterized by mucocutaneous macules and multiple gastrointestinal hamartomatous polyps. Gastric-type endocervical adenocarcinoma (G-EAC), a special subtype of cervical adenocarcinoma with non-specific symptoms and signs, is known to occur in approximately 11% of female patients with PJS. Case presentation Here, we report a case of PJS in a 24-year-old female with multiple mucocutaneous black macules who complained of vaginal discharge and menorrhagia. Moreover, we first described the multimodal ultrasonographical manifestations of PJS-correlated G-EAC. The three-dimensional reconstructed view of G-EAC on 3D realisticVue exhibited a distinctive “cosmos pattern” resembling features on magnetic resonance imaging, and the contrast-enhanced ultrasound displayed a “quick-up and slow-down” pattern of the solid components inside the mixed cervical echoes. We reported the multimodal ultrasonographical characteristics of a case of PJS-related G-EAC, as well as reviewed PJS-related literature and medical imaging features and clinical characteristics of G-EAC to provide insight into the feasibility and potential of utilizing multimodal ultrasonography for the diagnosis of G-EAC. Conclusions Multimodal ultrasound can visualize morphological features, solid components inside, and blood supplies of the G-EAC lesion and distinguish the G-EAC lesion from normal adjacent tissues. This facilitates preoperative diagnosis and staging of PJS-related G-EAC, thereby aiding subsequent health and reproductive management for patients with PJS.

The regulation mechanism of wetland plants in response to consecutive drought (D) and re-flooding (RT) events can be identified via nutrient responses. Nutrient responses of Carex schmidtii were tested using a simulation experiment with five treatments: D, wetting (W) and RT resulted in C. schmidtii being re-flooded after 30, 40 and 60 days of drought. D and RT treatments partly affected nutrient stoichiometry of C. schmidtii. Plant nutrient stoichiometry experienced a shift of adaption from drought to flooding and making part or full recoveries after RT with reference to D and W treatments. Plant P concentration had a negative relationship with N:K ratio. D and RT effects on plant trade-offs and scaling exponents of C. schmidtii were profound; the scaling exponent of P~N increased with initial re-flooding time, while that of K~N decreased. Although nutrient trade-offs in D gradually differed from W and RT over time, the nutrient trade-offs of RT recovered with reference to W. The D and RT were recorded to contribute to nutrient flexibility of C. schmidtii; however, strong internal stability of stoichiometric relationships effectively relieved changes in plant nutrient stoichiometry. The findings aid our understanding of nutrient responses of C. schmidtii to D and RT. [ABSTRACT FROM AUTHOR]