Publications by authors named "Jie Zhang"

7,280 Publications

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Polyadenylation-related isoform switching in human evolution revealed by full-length transcript structure.

Brief Bioinform 2021 May 11. Epub 2021 May 11.

Laboratory of Bioinformatics and Genomic Medicine, Institute of Molecular Medicine, Peking University, Beijing, China.

Rhesus macaque is a unique nonhuman primate model for human evolutionary and translational study, but the error-prone gene models critically limit its applications. Here, we de novo defined full-length macaque gene models based on single molecule, long-read transcriptome sequencing in four macaque tissues (frontal cortex, cerebellum, heart and testis). Overall, 8 588 227 poly(A)-bearing complementary DNA reads with a mean length of 14 106 nt were generated to compile the backbone of macaque transcripts, with the fine-scale structures further refined by RNA sequencing and cap analysis gene expression sequencing data. In total, 51 605 macaque gene models were accurately defined, covering 89.7% of macaque or 75.7% of human orthologous genes. Based on the full-length gene models, we performed a human-macaque comparative analysis on polyadenylation (PA) regulation. Using macaque and mouse as outgroup species, we identified 79 distal PA events newly originated in humans and found that the strengthening of the distal PA sites, rather than the weakening of the proximal sites, predominantly contributes to the origination of these human-specific isoforms. Notably, these isoforms are selectively constrained in general and contribute to the temporospatially specific reduction of gene expression, through the tinkering of previously existed mechanisms of nuclear retention and microRNA (miRNA) regulation. Overall, the protocol and resource highlight the application of bioinformatics in integrating multilayer genomics data to provide an intact reference for model animal studies, and the isoform switching detected may constitute a hitherto underestimated regulatory layer in shaping the human-specific transcriptome and phenotypic changes.
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http://dx.doi.org/10.1093/bib/bbab157DOI Listing
May 2021

Disturbance Observer-Based Feedback Linearization Control for a Quadruple-Tank Liquid Level System.

ISA Trans 2021 Apr 27. Epub 2021 Apr 27.

College of Automation, Qingdao University, No. 308, Ningxia Road, Qing dao, China.

A novel input/output feedback linearization control method by utilizing nonlinear disturbance observer (NDOB) is proposed for a quadruple-tank liquid level (QTLL) system in this paper. Firstly, the mathematical model of QTLL system is established by using Bernoulli's law and mass conservation. Secondly, in view of the nonlinear and coupling characteristics of the QTLL system, a input/output feedback linearization controller is designed. Then, a NDOB is proposed to estimate disturbances and applied to compensation control. Finally, simulation and experimental results show that the proposed strategy has better control performances than PID control and the disturbance observer-based sliding mode control (DOBSMC).
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http://dx.doi.org/10.1016/j.isatra.2021.04.021DOI Listing
April 2021

A Novel Use of Coblation in the Treatment of Tracheal Tumors.

Ear Nose Throat J 2021 May 11:1455613211015739. Epub 2021 May 11.

Department of Respiratory and Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Radiofrequency coblation is a new method of electrosurgical intervention. Most recently, its use has been reported in the treatment of laryngotracheal pathology. However, studies on coblation for tracheal tumors have not been reported. In this article, we described a novel use of coblation technology, in which a new type of airway-specific wand was used to ablate tracheal benign or malignant tumors in 3 cases. The results suggest the possibility of usage of coablation in the treatment of tracheal tumors. More studies that are larger and have longer follow-up are needed to further evaluate the use of this technique in the treatment of tracheal tumors.
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http://dx.doi.org/10.1177/01455613211015739DOI Listing
May 2021

First detection and complete genome analysis of the Lyon IARC polyomavirus in China from samples of diarrheic cats.

Virus Genes 2021 May 10. Epub 2021 May 10.

Institute of Military Veterinary Medicine, The Academy of Military Medical Sciences, Changchun, 130122, China.

Lyon IARC polyomavirus (LIPyV), a newly discovered polyomavirus (PyV), was first identified in 2017 in human skin samples in the USA. Later, it was detected in several other countries in samples of human and feline origin. Our aim was to find out if the virus occurs in China. To this end, 100 fecal samples were collected from cats with diarrhea in Guangxi Province during 2016 and 2018 and tested with polymerase chain reaction (PCR). Only 2 samples that originated from two related individuals were found to be positive. Based on the sequence identity of the 240-bp PCR products, the two positive samples supposedly contained identical viruses. Therefore, only one of them, which was designated as LIPyV-GXNN01, was selected for full genome amplification, cloning, sequencing and analysis. LIPyV-GXNN01, which comprises 5,263 nucleotides, has an early region that consists of small T antigen (ST-Ag) and large T antigen (LT-Ag) and a late region coding for the VP1, VP2, and VP3 structural proteins. Moreover, the LIPyV-GXNN01 strain structural proteins share 95.9-99.4%, 97.6-99.2%, and 97.1-99.2% nucleic acid identity with the VP1, VP2, and VP3of other LIPyV reference strains, respectively. A phylogenetic analysis revealed that GXNN01 clustered together with previously reported LIPyV strain. This present study is the first report of LIPyV in China.
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http://dx.doi.org/10.1007/s11262-021-01840-1DOI Listing
May 2021

Ice-Templated Large-Scale Preparation of Two-Dimensional Sheets of Conjugated Polymers: Thickness-Independent Flexible Supercapacitance.

ACS Nano 2021 May 10. Epub 2021 May 10.

State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, 15 North Third Ring Road East, Chaoyang District, Beijing 100029, China.

Two-dimensional (2D) organic materials hold great promise for use in a multitude of contemporary applications due to their outstanding chemical and physical properties. Herein, 2D sheets of poly(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) are prepared from a commercially available PEDOT:PSS suspension using ice as a template. The 2D PEDOT:PSS sheets grow in the boundaries of ice crystals as the polymers are "squeezed" out of the suspension when the water solidifies. The mechanical robustness of the sheets can be enhanced by incorporating WO nanowires, and the PSS component can be conveniently removed with a concentrated solution of HSO to afford stable suspensions of PEDOT or WO@PEDOT sheets, either of which can be converted into flexible films with tunable thicknesses filtration. Swagelok- or pouch-type supercapacitor devices prepared from the WO@PEDOT films exhibit outstanding energy-storage characteristics, including high rate capability, thickness-independent energy storage (.., 701 mF cm is achieved with a 1-mm-thick film), high resistance toward mechanical deformation, and good cycling stability. Additionally, a high energy density of 0.083 mWh cm is measured for a device prepared using a 1-mm-thick film at a high power density of 10 mW cm. The methodology described establishes an efficient and readily scalable approach for accessing 2D organic sheets.
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http://dx.doi.org/10.1021/acsnano.1c01459DOI Listing
May 2021

Effects of climate change and crop management on changes in rice phenology in China from 1981 to 2010.

J Sci Food Agric 2021 May 10. Epub 2021 May 10.

Key Laboratory of Land Surface Pattern and Simulation, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, 100101, China.

Background: Crop phenology change is co-determined by climate change and adaptation strategies, such as crop management, but their combined and isolated impacts on rice phenology are still unclear. Quantifying the impacts and identifying the main contributors are critical to food security under climate change. Thus, we distinguished and quantified the relative contribution of climate change and crop management to rice (Oryza sativa L.) phenological changes in China from 1981 to 2010, using a first-difference multivariate regression method.

Results: Rice phenology has changed over the past 30 years in China. The mean length of the phenological stage from emergence to transplanting was shortened, whereas the mean length of the stage from transplanting to heading, from heading to maturity was prolonged. The relative contribution of crop management was greater than that of climate change for single and late rice, which took up over 90% of the total change in certain phenology stages. Among the climatic factors, temperature was the dominant contributor for which accounted for more than 50% of the change of rice phenology. The stage from transplanting to heading of early rice and late rice had strongly negative sensitivities to the increasing temperature.

Conclusions: Crop management has offset the adverse effects of climate change on single and early rice phenology in China over the past 30 years to some extent, while further adaptation measures such as adjusting sowing date, shifting rice varieties, applying nitrogen fertilizer, and irrigation, should be applied to late rice in southern China, especially in a warmer future. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jsfa.11300DOI Listing
May 2021

Development of a Potential Penside Colorimetric LAMP Assay Using Neutral Red for Detection of African Swine Fever Virus.

Front Microbiol 2021 23;12:609821. Epub 2021 Apr 23.

State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.

African swine fever (ASF) has caused huge economic losses to the swine industry worldwide. Since there is no commercial ASF vaccine available, an early diagnosis is extremely important to prevent and control the disease. In this study, ASF virus (ASFV) capsid protein-encoding gene (p72) was selected and used to design primers for establishing a one-step visual loop-mediated isothermal amplification (LAMP) assay with neutral red, a pH-sensitive dye, as the color shift indicator. Neutral red exhibited a sharp contrast of color change from faint orange (negative) to pink (positive) during LAMP for detection of ASFV. The designed primer set targeting highly conserved region of the p72 gene was highly specific to ASFV and showed no cross-reactivity with other swine viruses. The detection limit for the one-step visual LAMP developed was 10 copies/reaction based on the recombinant plasmid containing the p72 gene of ASFV. More importantly, the developed one-step visual LAMP showed high consistency with the results of the real-time polymerase chain reaction (qPCR) method recommended by World Organization for Animal Health (OIE). Furthermore, the results demonstrate that the colorimetric detection with this LAMP assay could be directly applied for the whole blood and serum samples without requiring genome extraction. Based on our results, the developed one-step visual LAMP assay is a promising penside diagnostic tool for development of early and cost-effective ASF monitoring program that would greatly contribute to the prevention and control of ASF.
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http://dx.doi.org/10.3389/fmicb.2021.609821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102904PMC
April 2021

A case of HIV negative cryptococcal meningitis with antiphospholipid syndrome.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Apr;46(4):438-443

Department of Neurology, Second Xiangya Hospital, Central South University, Changsha 410011, China.

Cryptococcal meningitis has become the largest cause for the death of infectious diseases in the central nervous system infectious disease worldwide. Most patients with cryptococcal meningitis have AIDS, autoimmune diseases, hematologic malignancies, and some other relevant diseases. It is mainly caused by infection with or . Although the relationship between cryptococcal meningitis and autoimmune diseases, such as systemic lupus erythematosus, has been recognized, little has been studied about it. Furthermore, with the use of glucocorticoids and immunosuppressants, the incidence of cryptococcal meningitis is increasing year by year. Cryptococcal meningitis accounts for 15% of HIV-related deaths globally, compared with little research on HIV-negative cryptococcal diseases. A 54-year-old female patient with gingival bleeding was admitted to the Department of Neurology at the Second Xiangya Hospital of Central South University. The patient subsequently developed a series of central nervous system symptoms such as headache, ischemic stroke, and epilepsy. The number of thrombocytes was at 4×10/L, antinuclear antibody was (+), antihuman globulin was (++), globulin IgG anticardiolipin antibody IgG, IgA, and IgM was positive, lupus anticoagulant was strong positive, antibody against β2 glycoprotein 1 IgM >841 AU/mL with elevated cerebrospinal fluid (CSF) pressure. The CSF India ink staining was positive, CSF was cultured cryptococcus neoformans. Antiphospholipid syndrome (APS) and cryptococcal neoformans meningitis were diagnosed. After active antifungal therapy and control of APS, the patient still had a serial of complications including high CSF pressure, persistent positive India ink staining, refractory electrolyte disturbance, hemolytic anemia recurs, heart failure, and finally death. No cases of the combination of the two diseases have been reported, and this case of cryptococcal meningitis with APS may provide a new direction to the diagnosis and treatment for this kind of disease.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.200471DOI Listing
April 2021

Study on the biocompatibility of Ga-based and Al-assisted self-driven liquid metal in cell and animal experiments for drug delivery.

Biomed Mater Eng 2021 May 6. Epub 2021 May 6.

Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, China.

Background: With inherent flexibility, high electroconductivity, excellent thermal conductivity, easy printability and biosafety, Ga-based functional liquid metals (LMs) have been extensively evaluated for biomedical applications. When implanted in the biological environment, the safety of the LMs is a major concern for future application.

Methods: In this study, we conducted several biocompatibility assessments through immersion experiments, in vitro cytotoxicity experiments and in vivo embedding experiments.

Results: The results showed that both the Al-assisted self-driven LM and the LM per se own good biocompatibility and retrievable properties when contacted with living organisms for a relatively long period of time.

Conclusion: This study provides preliminary evidence about the biocompatibility of the functional LM materials, such as LM-based soft machine, which would promote and inspire other research to address other tough biomedical issues.
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http://dx.doi.org/10.3233/BME-201146DOI Listing
May 2021

A narrative review of research progress on the relationship between hypoxia-inducible factor-2α and wound angiogenesis.

Ann Palliat Med 2021 Apr;10(4):4882-4888

Department of Burns and Plastic, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.

Objective: This article aims to pay attention to the latest research on the expression, activation and function of hypoxia-inducible factor-2α (HIF-2α) under hypoxia and non-hypoxia conditions, and summarizes the current knowledge about the interaction between hypoxia-inducible factor-2 and angiogenesis, hoping to understand its actions in physiology and disease, with the goal of providing a new strategy for the diagnosis and treatment of wounds.

Background: Wound healing is a complex and continuous process, involving coagulation, inflammation, angiogenesis, new tissue formation and extracellular matrix remodeling. Of these, angiogenesis is an essential step. One of the main reasons for non-healing or delayed healing of wounds in peripheral vascular diseases and diabetes is the reduced ability to regenerate microvessels through the process of angiogenesis, which has become the focus of new methods for treating chronic wounds. HIF-2α regulates many aspects of angiogenesis, including vascular maturation, cell migration, proliferation and metastasis.

Methods: Throughout extensive search of PubMed, summarize the medical research on HIF-2α to 2020.

Conclusions: HIF-2α is necessary for normal embryonic development by stimulating the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF). It is essential for the formation of new blood vessels in physiological and pathophysiological environments. Targeting HIF-2α in wound healing has much clinical significance for tissue repair.
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http://dx.doi.org/10.21037/apm-21-450DOI Listing
April 2021

Recyclable and Magnetically Functionalized Metal-Organic Framework Catalyst: IL/FeO@HKUST-1 for the Cycloaddition Reaction of CO with Epoxides.

ACS Appl Mater Interfaces 2021 May 9. Epub 2021 May 9.

School of Chemistry, Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116023, P.R. China.

A recyclable and magnetic nanocomposite catalyst (IL/FeO@HKUST-1) was synthesized via grafting ionic liquid (IL) [AEMIm]BF into magnetically functionalized metal-organic framework FeO@HKUST-1 in a water-ethanol media. The properties of IL/FeO@HKUST-1 were fully characterized by powder X-ray diffraction, electron microscopy, Fourier-transform infrared spectroscopy, nitrogen adsorption-desorption, density-functional theory, and a magnetic property measurement system. IL/FeO@HKUST-1 showed high activity in the solvent-free cycloaddition of CO with epoxides under mild conditions. Furthermore, the catalyst can be easily separated from the reaction mixture, and the recycled catalyst maintained high performance for several cycles. The synergistic effect of the Lewis acid and base sites in IL/FeO@HKUST-1 contributes to its greater reactivity than individual IL or HKUST-1.
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http://dx.doi.org/10.1021/acsami.1c03345DOI Listing
May 2021

CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis.

J Orthop Surg Res 2021 May 8;16(1):302. Epub 2021 May 8.

Department of Rheumatism, Dongying City People's Hospital, No. 317, Nanyi Road, Dongying City, Shandong Province, China.

Background: Previous study showed that circular RNA Absent-Small-Homeotic-2--Like protein (circASH2L) was higher in rheumatoid arthritis (RA) patients. However, the roles and mechanisms of circASH2L in RA progression remain unclear.

Methods: Levels analysis was conducted using western blot and qRT-PCR. The proliferation, apoptosis, cell cycle progression, migration, invasiveness, and inflammation of RA fibroblast-like synoviocytes (RA-FLSs) were determined via MTT, flow cytometry, western blot, transwell, and ELISA assays.

Results: CircASH2L knockdown in RA-FLSs suppressed cell proliferative, migratory, and invasive capacities, triggered cell cycle arrest, promoted apoptosis, and inhibited inflammation. Mechanistically, circASH2L targeted miR-129-5p, and repression of miR-129-5p abolished the functions of circASH2L silencing on the growth, motility, and inflammation of RA-FLSs. Besides, miR-129-5p was found to directly target HIPK2, and suppressed the tumor-like biologic behaviors and inflammation of RA-FLSs via regulating HIPK2. Importantly, we proved that circASH2L could modulate HIPK2 expression via miR-129-5p.

Conclusion: CircASH2L promoted RA-FLS growth, motility, and inflammation through miR-129-5p/HIPK2 axis.
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http://dx.doi.org/10.1186/s13018-021-02432-3DOI Listing
May 2021

A somatic mutation in PIK3CD unravels a novel candidate gene for lymphatic malformation.

Orphanet J Rare Dis 2021 May 8;16(1):208. Epub 2021 May 8.

Department of Otolaryngology-Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: Lymphatic malformations (LMs) are benign congenital malformations that stem from the abnormal development of the lymphatic vessels during early embryogenesis. Somatic PIK3CA gene mutations are conventional cause leading to LMs. Both macrocystic and microcystic LMs arise due to lymphatic endothelial cell-autonomous defects, depending on the time in development at which PIK3CA gene mutation occurs. Recent study finds a PIK3CA mutation in 79% of LMs. However, discovering new genetic events in this disease is crucial to identify the molecular mechanism of the pathogenesis and further develop new targeted therapies.

Results: Here, we initially performed whole-exome sequencing in six children with LMs to find a new causal gene. Somatic mutations in PIK3CA (c.1633G > A [p. E545K] and PIK3CD (c.1997T > C [p.L666P]) were discovered in two different individuals. In vitro functional studies were conducted to demonstrate the pathogenicity of the novel mutation c.1997T > C in PIK3CD. We found that L666P promoted the cell proliferation and migration of human umbilical vein endothelial cells (HUVECs) and induced hyperactivation of the mTOR pathway. These findings indicate that the PIK3CD mutation affects downstream signalling in endothelial cells, which may impair normal lymphangiogenesis.

Conclusions: This study reveals a novel candidate gene associated with the development of LMs, which is consistent with previous researches. These findings in our study may offer a novel gene target for developing therapies, which acts in tight interaction with the previously known PIK3CA.
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http://dx.doi.org/10.1186/s13023-021-01782-9DOI Listing
May 2021

Research on rapid cultivation of aerobic granular sludge (AGS) with different feast-famine strategies in continuous flow reactor and achieving high-level denitrification via utilization of soluble microbial product (SMP).

Sci Total Environ 2021 Apr 22;786:147237. Epub 2021 Apr 22.

Key Laboratory of Water Science and Water Environment Recovery Engineering, Beijing University of Technology, Beijing 100123, China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090, China.

The mixture of partial AGS and flocculent sludge in continuous flow reactors were operated with periodic famine (PF) strategy and continuous feast (CF) strategy to reveal the impact of the feast-famine strategies on cultivation of AGS and the dynamics of microbial communities. The experimental results showed that the mature AGS were cultivated with PF and CF strategy on the 31st and the 71st days respectively, which was the result of good extracellular polymeric substance (EPS) secretion with PF strategy. It could accelerate the formation of microbial aggregates due to the conditions of periodic famine. High-level denitrification with PF strategy via utilization of SMP was examined by EEM-PARAFAC on cycle test. The high-throughput pyrosequencing showed that the dominant bacteria with PF strategy involved functional bacteria of nutrient removal and EPS secreting bacteria, while the dominant bacteria were fast-growing heterotrophic organisms with CF strategy.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147237DOI Listing
April 2021

Toll9 from functions as a pattern recognition receptor that shares features with Toll-like receptor 4 from mammals.

Proc Natl Acad Sci U S A 2021 May;118(19)

Guangdong Laboratory for Lingnan Modern Agriculture, Laboratory of Insect Molecular Biology and Biotechnology, Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, 510642 Guangzhou, China;

Toll/Toll-like receptors (TLRs) are key regulators of the innate immune system in both invertebrates and vertebrates. However, while mammalian TLRs directly recognize pathogen-associated molecular patterns, the insect Toll pathway is thought to be primarily activated by binding Spätzle cytokines that are processed from inactive precursors in response to microbial infection. Phylogenetic and structural data generated in this study supported earlier results showing that Toll9 members differ from other insect Tolls by clustering with the mammalian TLR4 group, which recognizes lipopolysaccharide (LPS) through interaction with myeloid differentiation-2 (MD-2)-like proteins. Functional experiments showed that BmToll9 from the silkmoth also recognized LPS through interaction with two MD-2-like proteins, previously named BmEsr16 and BmPP, that we refer to in this study as BmMD-2A and BmMD-2B, respectively. A chimeric BmToll9-TLR4 receptor consisting of the BmToll9 ectodomain and mouse TLR4 transmembrane and Toll/interleukin-1 (TIR) domains also activated LPS-induced release of inflammatory factors in murine cells but only in the presence of BmMD-2A or BmMD-2B. Overall, our results indicate that BmToll9 is a pattern recognition receptor for LPS that shares conserved features with the mammalian TLR4-MD-2-LPS pathway.
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http://dx.doi.org/10.1073/pnas.2103021118DOI Listing
May 2021

Comparison of Needle, Ultrasonic, and Laser Irrigation for the Removal of Calcium Hydroxide from Mandibular Molar Root Canals.

Photobiomodul Photomed Laser Surg 2021 May 9;39(5):349-354. Epub 2020 Dec 9.

State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, P.R. China.

This study aimed to compare the efficacy of conventional needle irrigation (CI), ultrasonically activated irrigation (UAI), photon-induced photoacoustic streaming (PIPS), and shock wave-enhanced emission photoacoustic streaming (SWEEPS) in removing calcium hydroxide [Ca(OH)] from root canals of mandibular molars using microcomputed tomography. Various adjunctive irrigation strategies have been recommended to improve the removal of Ca(OH). No reports have evaluated the SWEEPS laser-activated method for the removal of Ca(OH) from root canals of mandibular molars. Forty mandibular molars were instrumented and filled with Ca(OH). Four irrigation groups (CI, UAI, PIPS, and SWEEPS) were established. The volume of root canals and Ca(OH) and the Ca(OH) volume reduction percentage (%Rd) were calculated. Data were analyzed by one-way analysis of variance and Kruskal-Wallis analysis of variance. The residual Ca(OH) in the apical third was higher than that in the cervical and middle thirds in all groups ( < 0.05). Comparison of the %Rd of Ca(OH) in mesial canals revealed that PIPS and SWEEPS removed more Ca(OH) than CI and UAI in the cervical third ( < 0.05). The middle third of the mesial canals and the cervical and middle thirds of the distal canals did not show significant differences among groups ( > 0.05). Significant differences in the %Rd of Ca(OH) were noted between CI and other groups in the apical third of mesial and distal canals ( < 0.05). No group demonstrated complete removal of Ca(OH). UAI and laser-activated irrigation significantly improved Ca(OH) removal in the apical third of mesial and distal canals. No agitation technique could completely remove Ca(OH).
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http://dx.doi.org/10.1089/photob.2019.4798DOI Listing
May 2021

Digital Microfluidics: Magnetic Transportation and Coalescence of Sessile Droplets on Hydrophobic Surfaces.

Langmuir 2021 May 7. Epub 2021 May 7.

Department of Mechanical and Aerospace Engineering, Missouri University of Science and Technology, 400 W. 13th Street, Rolla, Missouri 65409, United States.

Magnetic digital microfluidics is advantageous over other existing droplet manipulation methods, which exploits magnetic forces for actuation and offers the flexibility of implementation in resource-limited point-of-care applications. This article discusses the dynamic behavior of a pair of sessile droplets on a hydrophobic surface under the presence of a permanent magnetic field. A phase field method-based solver is employed in a two-dimensional computational domain to numerically capture the dynamic evolution of the droplet interfaces, which again simultaneously solves the magnetic and flow fields. On a superhydrophobic surface (i.e., θ = 150°), the nonuniform magnetic field forces the pair of sessile droplets to move toward each other, which eventually leads to a jumping off phenomenon of the merged droplet from the solid surface after coalescence. Also, there exists a critical magnetic Bond number , beyond which no coalescence event between droplets is observed. Moreover, on a less hydrophobic surface (θ ≤ 120°), the droplets still coalesce under a magnetic field, although the merged droplet does not experience any upward flight after coalescence. Also, the merging phenomenon at lower contact angle values (i.e., θ = 90°) appears significantly different than at higher contact angle values (i.e., θ = 120°). Additionally, if the pair of sessile droplets is dispersed to a different surrounding medium, the viscosity ratio plays a significant role in the upward flight of the merged droplet, where the coalesced droplet exhibits increased vertical migration at higher viscosity ratios.
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http://dx.doi.org/10.1021/acs.langmuir.1c00141DOI Listing
May 2021

CDK5 positively regulates Notch1 signaling in pancreatic cancer cells by phosphorylation.

Cancer Med 2021 May 7. Epub 2021 May 7.

Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China.

The marked overexpression of cyclin-dependent kinase 5 (CDK5) or Notch1 receptor, which plays critical roles in pancreatic ductal adenocarcinoma (PDAC) development, has been detected in numerous PDAC cell lines and tissues. Although, a previous study has demonstrated that CDK5 inhibition disrupts Notch1 functions in human umbilical vein endothelial cells, the mechanism underlying Notch1 activation regulated by CDK5 remains unclear. Herein, we identified a physical interaction between CDK5 and Notch1 in PDAC cells, with the Notch1 peptide phosphorylated by CDK5/p25 kinase. CDK5 blockade resulted in the profound inhibition of Notch signaling. Accordingly, CDK5 inhibition sensitized PDAC cell proliferation and migration following Notch inhibition. In conclusion, CDK5 positively regulates Notch1 function via phosphorylation, which in turn promotes cell proliferation and migration. The combinational inhibition of CDK5 and Notch signaling may be an effective strategy in the treatment of PDAC.
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http://dx.doi.org/10.1002/cam4.3916DOI Listing
May 2021

Postpubertal Spermatogonial Stem Cell Transplantation Restores Functional Sperm Production in Rhesus Monkeys Irradiated Before and After Puberty.

Andrology 2021 May 6. Epub 2021 May 6.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, 77030.

Background: Cancer treatment of prepubertal patients impacts future fertility due to the abolition of spermatogonial stem cells (SSCs). In macaques, spermatogenesis could be regenerated by intratesticular transplantation of SSCs, but no studies have involved cytotoxic treatment before puberty and transplantation after puberty, which would be the most likely clinical scenario.

Objectives: To evaluate donor-derived functional sperm production after SSC transplantation to adult monkeys that had received testicular irradiation during the prepubertal period.

Materials And Methods: We obtained prepubertal testis tissue by unilaterally castrating 6 prepubertal monkeys and 2 weeks later irradiated the remaining testes with 6.9 Gy. However, because spermatogenic recovery was observed, we irradiated them again 14 months later with 7 Gy. Three of the monkeys were treated with GnRH-antagonist (GnRH-ant) for 8 weeks. The cryopreserved testis cells from the castrated testes were then allogeneically transplanted into the intact testes of all monkeys. Tissues were harvested 10 months later for analyses.

Results: In three of the six monkeys, 61%, 38% and 11% of the epididymal sperm DNA were of the donor genotype. The ability to recover donor-derived sperm production was not enhanced by the GnRH-ant pretreatment. However, the extent of filling seminiferous tubules during the transplantation procedure was correlated with the eventual production of donor sperm. The donor epididymal sperm from the recipient with 61% donor contribution were capable of fertilizing rhesus eggs and forming embryos. Although the transplantation was done into the rete testis, two GnRH-ant treated monkeys, which did not produce donor-derived epididymal sperm, displayed irregular tubular cords in the interstitium containing testicular sperm derived from the transplanted donor cells.

Discussion And Conclusion: The results further support that sperm production can be restored in non-human primates from tissues cryopreserved prior to prepubertal and postpubertal gonadotoxic treatment by transplantation of these testicular cells after puberty into seminiferous tubules.
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http://dx.doi.org/10.1111/andr.13033DOI Listing
May 2021

Surgical treatment for huge vaginal stone secondary to vaginal mesh exposure with stress urinary incontinence.

Int Urol Nephrol 2021 May 7. Epub 2021 May 7.

Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

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http://dx.doi.org/10.1007/s11255-021-02865-zDOI Listing
May 2021

A nomogram for individualized prediction of overall survival in patients with newly diagnosed glioblastoma: a real-world retrospective cohort study.

BMC Surg 2021 May 6;21(1):238. Epub 2021 May 6.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Background: This study aimed to identify the most valuable predictors of prognosis in glioblastoma (GBM) patients and develop and validate a nomogram to estimate individualized survival probability.

Methods: We conducted a real-world retrospective cohort study of 987 GBM patients diagnosed between September 2010 and December 2018. Computer generated random numbers were used to assign patients into a training cohort (694 patients) and internal validation cohort (293 patients). A least absolute shrinkage and selection operator (LASSO)-Cox model was used to select candidate variables for the prediction model. Cox proportional hazards regression was used to estimate overall survival. Models were internally validated using the bootstrap method and generated individualized predicted survival probabilities at 6, 12, and 24 months, which were compared with actual survival.

Results: The final nomogram was developed using the Cox proportional hazards model, which was the model with best fit and calibration. Gender, age at surgery, extent of tumor resection, radiotherapy, chemotherapy, and IDH1 mutation status were used as variables. The concordance indices for 6-, 12-, 18-, and 24-month survival probabilities were 0.776, 0.677, 0.643, and 0.629 in the training set, and 0.725, 0.695, 0.652, and 0.634 in the validation set, respectively.

Conclusions: Our nomogram that assesses individualized survival probabilities (6-, 12-, and 24-month) in newly diagnosed GBM patients can assist healthcare providers in optimizing treatment and counseling patients.

Trial Registration: retrospectively registered.
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http://dx.doi.org/10.1186/s12893-021-01233-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101102PMC
May 2021

Lycium barbarum mitigates radiation injury via regulation of the immune function, gut microbiota, and related metabolites.

Biomed Pharmacother 2021 May 3;139:111654. Epub 2021 May 3.

Tianjin University of Traditional Chinese Medicine, Tianjin, China; Beijing Institute of Radiation Medicine, Beijing, China. Electronic address:

Previous studies have suggested that Lycium barbarum (L. barbarum) has a radioprotective function, although more in-depth investigation is still required. We investigated the radioprotective efficacy of extract of the fruits of L. barbarum (LBE) and its radioprotective mechanisms. Mice were exposed to 8.5 Gy, 5.5 Gy, or 6.0 Gy total body irradiation (TBI), and the survival rate, lymphocyte percentage, amount of cytokines, and viability of the irradiated cells, as well as the gut microbiome and fecal metabolomics were studied. LBE enhanced the survival of the mice exposed to 8.5 Gy γ-ray TBI or 5.5 Gy X-ray TBI. After 6.0 Gy γ-ray TBI, LBE exhibited good immunomodulatory properties, mainly characterized by the accelerated recovery of lymphocyte percentages, and the enhanced expression of immune-related cytokines. LBE reconstituted the gut microbiota of irradiated mice, increased the relative abundance of potentially beneficial genera (e.g., Turicibacter, Akkermansia), and decreased the relative abundance of potentially harmful bacterial genera (e.g., Rikenellaceae_RC9_gut_group). Beneficial regulatory effects of LBE on the host metabolites were also noted, and the major upregulated metabolites induced by LBE, such as Tetrahydrofolic acid and N-ornithyl-L-taurine, were positively correlated with the immune factor interleukin (IL)-6. In vitro, LBE also increased the vitality of rat small intestinal epithelial cells (IEC-6) after 4.0 Gy γ-ray irradiation and promoted the growth of Akkermansia muciniphila. These results confirmed a radioprotective function of LBE and indicated that the radioprotective mechanism may be due to immunomodulation and the synergistically modulating effect on the gut microbiota and related metabolites.
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http://dx.doi.org/10.1016/j.biopha.2021.111654DOI Listing
May 2021

Faster lipid β-oxidation rate by acetyl-CoA carboxylase 2 inhibition alleviates high-glucose-induced insulin resistance via SIRT1/PGC-1α in human podocytes.

J Biochem Mol Toxicol 2021 May 6:e22797. Epub 2021 May 6.

Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.

Diabetic nephropathy (DN) is becoming a research hotspot in recent years because the prevalence is high and the prognosis is poor. Lipid accumulation in podocytes induced by hyperglycemia has been shown to be a driving mechanism underlying the development of DN. However, the mechanism of lipotoxicity remains unclear. Increasing evidence shows that acetyl-CoA carboxylase 2 (ACC2) plays a crucial role in the metabolism of fatty acid, but its effect in podocyte injury of DN is still unclear. In this study, we investigated whether ACC2 could be a therapeutic target of lipid deposition induced by hyperglycemia in the human podocytes. Our results showed that high glucose (HG) triggered significant lipid deposition with a reduced β-oxidation rate. It also contributed to the downregulation of phosphorylated ACC2 (p-ACC2), which is an inactive form of ACC2. Knockdown of ACC2 by sh-RNA reduced lipid deposition induced by HG. Additionally, ACC2-shRNA restored the expression of glucose transporter 4 (GLUT4) on the cell surface, which was downregulated in HG and normalized in the insulin signaling pathway. We verified that ACC2-shRNA alleviated cell injury, apoptosis, and restored the cytoskeleton disturbed by HG. Mechanistically, SIRT1/PGC-1α is close related to the insulin metabolism pathway. ACC2-shRNA could restore the expression of SIRT1/PGC-1α, which was downregulated in HG. Rescue experiment revealed that inhibition of SIRT1 by EX-527 counteracted the effect of ACC2-shRNA. Taken together, our data suggest that podocyte injury mediated by HG-induced insulin resistance and lipotoxicity could be alleviated by ACC2 inhibition via SIRT1/PGC-1α.
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http://dx.doi.org/10.1002/jbt.22797DOI Listing
May 2021

Architectural Design for Enhanced C Product Selectivity in Electrochemical CO Reduction Using Cu-Based Catalysts: A Review.

ACS Nano 2021 May 6. Epub 2021 May 6.

School of Chemistry, Monash University, Clayton, VIC 3800, Australia.

Electrochemical CO reduction to value-added chemicals and fuels is a promising approach to mitigate the greenhouse effect arising from anthropogenic CO emission and energy shortage caused by the depletion of nonrenewable fossil fuels. The generation of multicarbon (C) products, especially hydrocarbons and oxygenates, is of great interest for industrial applications. To date, Cu is the only metal known to catalyze the C-C coupling in the electrochemical CO reduction reaction (eCORR) with appreciable efficiency and kinetic viability to produce a wide range of C products in aqueous solutions. Nonetheless, poor product selectivity associated with Cu is the main technical problem for the application of the eCORR technology on a global scale. Based on extensive research efforts, a delicate and rational design of electrocatalyst architecture using the principles of nanotechnology is likely to significantly affect the adsorption energetics of some key intermediates and hence the inherent reaction pathways. In this review, we summarize recent progress that has been achieved by tailoring the electrocatalyst architecture for efficient electrochemical CO conversion to the target C products. By considering the experimental and computational results, we further analyze the underlying correlations between the architecture of a catalyst and its selectivity toward C products. Finally, the major challenges are outlined, and directions for future development are suggested.
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http://dx.doi.org/10.1021/acsnano.0c10697DOI Listing
May 2021

Prognostic factor analysis of patients with small cell lung cancer: Real-world data from 988 patients.

Thorac Cancer 2021 May 6. Epub 2021 May 6.

Department of Thoracic Oncology II, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing, China.

Background: Small cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large-scale real-world analysis is lacking.

Methods: Patients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan-Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors.

Results: Among 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS-SCLC) and extensive stage small cell lung cancer (ES-SCLC), separately. Limited-stage, good performance status (PS) (ECOG 0-1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first-line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS-SCLC; while good PS (ECOG 0-1), without liver, bone, or subcutaneous metastases, response to first-line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES-SCLC.

Conclusions: The present study retrieved from large real-world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS-SCLC and ES-SCLC, respectively.
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http://dx.doi.org/10.1111/1759-7714.13846DOI Listing
May 2021

Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer.

Nat Commun 2021 05 5;12(1):2540. Epub 2021 May 5.

Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.

Lung cancer is a highly heterogeneous disease. Cancer cells and cells within the tumor microenvironment together determine disease progression, as well as response to or escape from treatment. To map the cell type-specific transcriptome landscape of cancer cells and their tumor microenvironment in advanced non-small cell lung cancer (NSCLC), we analyze 42 tissue biopsy samples from stage III/IV NSCLC patients by single cell RNA sequencing and present the large scale, single cell resolution profiles of advanced NSCLCs. In addition to cell types described in previous single cell studies of early stage lung cancer, we are able to identify rare cell types in tumors such as follicular dendritic cells and T helper 17 cells. Tumors from different patients display large heterogeneity in cellular composition, chromosomal structure, developmental trajectory, intercellular signaling network and phenotype dominance. Our study also reveals a correlation of tumor heterogeneity with tumor associated neutrophils, which might help to shed light on their function in NSCLC.
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http://dx.doi.org/10.1038/s41467-021-22801-0DOI Listing
May 2021

Neuroactive Type-A γ-Aminobutyric Acid Receptor Allosteric Modulator Steroids from the Hypobranchial Gland of Marine Mollusk, .

J Med Chem 2021 May 5. Epub 2021 May 5.

Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.

In a program to identify pain treatments with low addiction potential, we isolated five steroids, conosteroids A-E (-), from the hypobranchial gland of the mollusk . Compounds - were active in a mouse dorsal root ganglion (DRG) assay that suggested that they might be analgesic. A synthetic analogue was used for a detailed pharmacological study. Compound significantly increased the pain threshold in mice in the hot-plate test at 2 and 50 mg/kg. Compound at 500 nM antagonizes type-A γ-aminobutyric acid receptors (GABARs). In a patch-clamp experiment, out of the six subunit combinations tested, exhibited subtype selectivity, most strongly antagonizing αβγ and αβγ receptors (IC 1.5 and 1.0 μM, respectively). Although the structures of - differ from those of known neuroactive steroids, they are cell-type-selective modulators of GABARs, expanding the known chemical space of neuroactive steroids.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00562DOI Listing
May 2021

Neural cell adhesion molecule (NCAM-1) is required for ventricular conduction system development.

Development 2021 May 4. Epub 2021 May 4.

Department of Medicine, NYU Grossman School of Medicine, NY 10016, USA.

Cardiac Purkinje cells (PCs) comprise the most distal portion of the ventricular conduction system (VCS) and are essential for synchronous activation of the ventricular myocardium. Contactin-2 (CNTN2), a member of the immunoglobulin superfamily cell adhesion molecules (IgSF-CAMs), was previously identified as a marker of the VCS. Through differential transcriptional profiling we discovered two additional highly enriched IgSF-CAMs in the VCS, NCAM-1 and ALCAM. Immunofluorescence staining showed dynamic expression patterns for each IgSF-CAM during embryonic and early post-natal stages, but ultimately all three proteins became highly enriched in mature PCs. Mice deficient in NCAM-1, but not CNTN2 or ALCAM, exhibited defects in Purkinje cell gene expression and VCS patterning, as well as cardiac conduction disease. Moreover, using ST8sia2 and ST8sia4 knockout mice, we show that inhibition of post-translational modification of NCAM-1 by polysialic acid (PSA) disrupts trafficking of sarcolemmal intercalated disc proteins to Purkinje cell junctional membranes and abnormal expansion of the extracellular space between apposing Purkinje cells. Taken together, our data provide novel insights into the complex developmental biology of the ventricular conduction system.
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http://dx.doi.org/10.1242/dev.199431DOI Listing
May 2021

Dominant egg surface bacteria of Holotrichia oblita (Coleoptera: Scarabaeidae) inhibit the multiplication of Bacillus thuringiensis and Beauveria bassiana.

Sci Rep 2021 May 4;11(1):9499. Epub 2021 May 4.

State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Holotrichia oblita (Coleoptera: Scarabaeidae) and some other scarab beetles are the main soil-dwelling pests in China. Bacillus thuringiensis (Bt) and Beauveria bassiana (Bb) are entomopathogens that have been used as biocontrol agents of various pests. However, scarab larvae especially H. oblita exhibited strong adaptability to these pathogens. Compared to other scarabs, H. oblita could form a specific soil egg case (SEC) structure surrounding its eggs, and young larvae complete the initial development process inside this structure. In this study, we investigated the role of SEC structure and microorganisms from SEC and egg surface in pathogen adaptability. 16S rRNA gene analysis revealed low bacterial richness and high community unevenness in egg surface, with Proteobacteria, Firmicutes, Bacteroidetes and Fusobacteria dominating. In terms of OTUs composition analysis, the data show that the egg surface contains a large number of unique bacteria, indicating that the egg bacterial community may be derived from maternal transmission. Furthermore, we found that all culturable bacteria isolated from egg surface possessed antimicrobial activity against both Bt and Bb. The Pseudomonas bacteria with a significantly higher abundance in egg surface showed strong Bt- and Bb antagonistic ability. In conclusion, this study demonstrated a unique and antimicrobial bacterial community of H. oblita egg surface, which may contribute to its adaptability. Furthermore, the specific SEC structure surrounding the H. oblita eggs will provide a stable microenvironment for the eggs and egg surface bacteria, which probably provides more advantages for H. oblita adaptation ability.
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http://dx.doi.org/10.1038/s41598-021-89009-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096819PMC
May 2021

Analysis of Medication Adherence and Its Influencing Factors in Patients with Schizophrenia in the Chinese Institutional Environment.

Int J Environ Res Public Health 2021 Apr 29;18(9). Epub 2021 Apr 29.

Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, 165 Sanlin Road, Shanghai 200124, China.

Background: Factors related to medication adherence in patients with schizophrenia have always been key to the treatment and rehabilitation of these patients. However, the treatment modes in different countries are not the same, and there is no research on the factors influencing medication adherence under different mental health service modes.

Objectives: The purpose of this study was to explore medication adherence and its influencing factors in patients with schizophrenia in the Chinese institutional environment.

Methods: We conducted a cross-sectional study of hospitalized persons living with schizophrenia from November 2018 to January 2019. A systematic sampling method was used to select 217 hospitalized persons living with schizophrenia. The Medication Adherence Rating Scale (MARS), Positive and Negative Syndrome Scale (PANSS), General Self-Efficacy Scale (GSES), Schizophrenia Quality of Life Scale (SQLS), and Scale of Social Skills for Psychiatric Inpatients (SSPI) were used to explore medication compliance and its influencing factors in the Chinese institutional environment.

Results: The descriptive analysis and ANOVA showed that there were no significant differences in medication adherence when assessed by demographic characteristics such as sex, marital status, and education level ( > 0.05). A correlation analysis showed that there was no significant correlation between medication adherence and mental symptoms ( > 0.05) but that there was a positive correlation with self-efficacy, quality of life, and activities of daily living ( < 0.01). The linear regression analysis showed that self-efficacy, psychosocial factors, symptoms/side effects, and activities of daily living had significant effects on medication adherence (F = 30.210, < 0.001).

Conclusions: Our findings show that the self-efficacy, quality of life, and social function of patients with schizophrenia are important self-factors influencing medication adherence in the Chinese institutional environment.
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http://dx.doi.org/10.3390/ijerph18094746DOI Listing
April 2021