Publications by authors named "Guohong Li"

202 Publications

The Clinical Value of Computed Tomography (CT)-Guided I Brachytherapy for Locally Advanced Non-Small Cell Lung Cancer After Progression of Concurrent Radiochemotherapy.

Cancer Manag Res 2021 5;13:5297-5307. Epub 2021 Jul 5.

Interventional Radiology Program, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, People's Republic of China; Guangdong Provincial Key Lab of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, People's Republic of China.

Purpose: To further evaluate the efficacy and safety of computed tomography (CT)-guided iodine 125 (I) brachytherapy to treat locally advanced non-small cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT).

Methods: This study obtained written consent from all patients and was approved by our institution. From January 2006 to June 2018, 210 NSCLC patients (progression of first-line CCRT) were retrospectively recruited and then divided into two groups. A total of 116 patients were given CT-guided I brachytherapy and second-line chemotherapy (group A), and 94 were treated with second-line chemotherapy alone (group B).

Results: In group A, local response rate (LRR) within 3 years was significantly better (P<0.05). Mean survival time [progression-free survival time (PFST) and overall survival (OS)] was 15.1±1.4 months and 21.2±1.6 months in group A compared with 10.0±1.4 months and 16.2±1.7 months in group B (PFST: P<0.01, HR=1.472, 95% CI 1.097-1.975; OS: P = 0.036, HR=1.342, 95% CI 1.005-1.791). Tumor size and No. of first cycle chemotherapy were independent factors that affected survival, ≤3cm largest tumor diameter and more than 4 first cycles of chemotherapy showed longer PFST and OS (P<0.05). Tumor-related clinical symptoms were relieved in group A (P<0.01). No serious complications occurred in the two groups.

Conclusion: I brachytherapy is effective and safe in locally advanced NSCLC after progression of CCRT.
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http://dx.doi.org/10.2147/CMAR.S313438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275038PMC
July 2021

HBO1 is a versatile histone acyltransferase critical for promoter histone acylations.

Nucleic Acids Res 2021 Jul 14. Epub 2021 Jul 14.

Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.

Recent studies demonstrate that histones are subjected to a series of short-chain fatty acid modifications that is known as histone acylations. However, the enzymes responsible for histone acylations in vivo are not well characterized. Here, we report that HBO1 is a versatile histone acyltransferase that catalyzes not only histone acetylation but also propionylation, butyrylation and crotonylation both in vivo and in vitro and does so in a JADE or BRPF family scaffold protein-dependent manner. We show that the minimal HBO1/BRPF2 complex can accommodate acetyl-CoA, propionyl-CoA, butyryl-CoA and crotonyl-CoA. Comparison of CBP and HBO1 reveals that they catalyze histone acylations at overlapping as well as distinct sites, with HBO1 being the key enzyme for H3K14 acylations. Genome-wide chromatin immunoprecipitation assay demonstrates that HBO1 is highly enriched at and contributes to bulk histone acylations on the transcriptional start sites of active transcribed genes. HBO1 promoter intensity highly correlates with the level of promoter histone acylation, but has no significant correlation with level of transcription. We also show that HBO1 is associated with a subset of DNA replication origins. Collectively our study establishes HBO1 as a versatile histone acyltransferase that links histone acylations to promoter acylations and selection of DNA replication origins.
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http://dx.doi.org/10.1093/nar/gkab607DOI Listing
July 2021

Transcription-coupled structural dynamics of topologically associating domains regulate replication origin efficiency.

Genome Biol 2021 Jul 12;22(1):206. Epub 2021 Jul 12.

State Key Laboratory of Membrane Biology, Biomedical Pioneer Innovation Center (BIOPIC), School of Life Sciences, Peking University, Beijing, 100871, China.

Background: Metazoan cells only utilize a small subset of the potential DNA replication origins to duplicate the whole genome in each cell cycle. Origin choice is linked to cell growth, differentiation, and replication stress. Although various genetic and epigenetic signatures have been linked to the replication efficiency of origins, there is no consensus on how the selection of origins is determined.

Results: We apply dual-color stochastic optical reconstruction microscopy (STORM) super-resolution imaging to map the spatial distribution of origins within individual topologically associating domains (TADs). We find that multiple replication origins initiate separately at the spatial boundary of a TAD at the beginning of the S phase. Intriguingly, while both high-efficiency and low-efficiency origins are distributed homogeneously in the TAD during the G1 phase, high-efficiency origins relocate to the TAD periphery before the S phase. Origin relocalization is dependent on both transcription and CTCF-mediated chromatin structure. Further, we observe that the replication machinery protein PCNA forms immobile clusters around TADs at the G1/S transition, explaining why origins at the TAD periphery are preferentially fired.

Conclusion: Our work reveals a new origin selection mechanism that the replication efficiency of origins is determined by their physical distribution in the chromatin domain, which undergoes a transcription-dependent structural re-organization process. Our model explains the complex links between replication origin efficiency and many genetic and epigenetic signatures that mark active transcription. The coordination between DNA replication, transcription, and chromatin organization inside individual TADs also provides new insights into the biological functions of sub-domain chromatin structural dynamics.
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http://dx.doi.org/10.1186/s13059-021-02424-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276456PMC
July 2021

Charge Density Wave Vortex Lattice Observed in Graphene-Passivated 1T-TaS by Ambient Scanning Tunneling Microscopy.

Nano Lett 2021 Jul 7;21(14):6132-6138. Epub 2021 Jul 7.

Department of Physics and Astronomy, Rutgers, the State University of New Jersey, 136 Frelinghuysen Road, Piscataway, New Jersey 08854, United States.

The nearly commensurate charge density wave (CDW) excitations native to the transition-metal dichalcogenide crystal, 1T-TaS, under ambient conditions are revealed by scanning tunneling microscopy (STM) and spectroscopy (STS) measurements of a graphene/TaS heterostructure. Surface potential measurements show that the graphene passivation layer prevents oxidation of the air-sensitive 1T-TaS surface. The graphene protective layer does not however interfere with probing the native electronic properties of 1T-TaS by STM/STS, which revealed that nearly commensurate CDW hosts an array of vortex-like topological defects. We find that these topological defects organize themselves to form a lattice with quasi-long-range order, analogous to the vortex Bragg glass in type-II superconductors but accessible in ambient conditions.
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http://dx.doi.org/10.1021/acs.nanolett.1c01655DOI Listing
July 2021

Structure specific DNA recognition by the SLX1-SLX4 endonuclease complex.

Nucleic Acids Res 2021 07;49(13):7740-7752

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

The SLX1-SLX4 structure-specific endonuclease complex is involved in processing diverse DNA damage intermediates, including resolution of Holliday junctions, collapse of stalled replication forks and removal of DNA flaps. The nuclease subunit SLX1 is inactive on its own, but become activated upon binding to SLX4 via its conserved C-terminal domain (CCD). Yet, how the SLX1-SLX4 complex recognizes specific DNA structure and chooses cleavage sites remains unknown. Here we show, through a combination of structural, biochemical and computational analyses, that the SAP domain of SLX4 is critical for efficient and accurate processing of 5'-flap DNA. It binds the minor groove of DNA about one turn away from the flap junction, and the 5'-flap is implicated in binding the core domain of SLX1. This binding mode accounts for specific recognition of 5'-flap DNA and specification of cleavage site by the SLX1-SLX4 complex.
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http://dx.doi.org/10.1093/nar/gkab542DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287910PMC
July 2021

Correction: Rating Hospital Performance in China: Review of Publicly Available Measures and Development of a Ranking System.

J Med Internet Res 2021 Jun 22;23(6):e31370. Epub 2021 Jun 22.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

[This corrects the article DOI: 10.2196/17095.].
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http://dx.doi.org/10.2196/31370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277383PMC
June 2021

Rating Hospital Performance in China: Review of Publicly Available Measures and Development of a Ranking System.

J Med Internet Res 2021 06 17;23(6):e17095. Epub 2021 Jun 17.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: In China, significant emphasis and investment in health care reform since 2009 has brought with it increasing scrutiny of its public hospitals. Calls for greater accountability in the quality of hospital care have led to increasing attention toward performance measurement and the development of hospital ratings. Despite such interest, there has yet to be a comprehensive analysis of what performance information is publicly available to understand the performance of hospitals in China.

Objective: This study aims to review the publicly available performance information about hospitals in China to assess options for ranking hospital performance.

Methods: A review was undertaken to identify performance measures based on publicly available data. Following several rounds of expert consultation regarding the utility of these measures, we clustered the available options into three key areas: research and development, academic reputation, and quality and safety. Following the identification and clustering of the available performance measures, we set out to translate these into a practical performance ranking system to assess variation in hospital performance.

Results: A new hospital ranking system termed the China Hospital Development Index (CHDI) is thus presented. Furthermore, we used CHDI for ranking well-known tertiary hospitals in China.

Conclusions: Despite notable limitations, our assessment of available measures and the development of a new ranking system break new ground in understanding hospital performance in China. In doing so, CHDI has the potential to contribute to wider discussions and debates about assessing hospital performance across global health care systems.
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http://dx.doi.org/10.2196/17095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277410PMC
June 2021

Genomic insights into molecular adaptation to intertidal environments in the mangrove Aegiceras corniculatum.

New Phytol 2021 Jun 11. Epub 2021 Jun 11.

State Key Laboratory of Biocontrol, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, 510275, China.

Mangroves have colonised extreme intertidal environments characterised by high salinity, hypoxia and other abiotic stresses. Aegiceras corniculatum, a pioneer mangrove species that has evolved two specialised adaptive traits (salt secretion and crypto-vivipary) is an attractive ecological model to investigate molecular mechanisms underlying adaptation to intertidal environments. We assembled de novo a high-quality reference genome of A. corniculatum and performed comparative genomic and transcriptomic analyses to investigate molecular mechanisms underlying adaptation to intertidal environments. We provide evidence that A. corniculatum experienced a whole-genome duplication (WGD) event c. 35 Ma. We infer that maintenance of cellular environmental homeostasis is an important adaptive process in A. corniculatum. The 14-3-3 and H -ATPase protein-coding genes, essential for the salt homeostasis, were preferentially retained after the recent WGD event. Using comparative transcriptomics, we show that genes upregulated under high-salt conditions are involved in salt transport and ROS scavenging. We also found that all homologues of DELAY OF GERMINATION1 (DOG1) had lost their heme-binding ability in A. corniculatum, and that this may contribute to crypto-vivipary. Our study provides insight into the genomic correlates of phenotypic adaptation to intertidal environments. This could contribute not only within the genomics community, but also to the field of plant evolution.
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http://dx.doi.org/10.1111/nph.17551DOI Listing
June 2021

[Analysis of clinical features and genetic variants among 12 children with Gitelman syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2021 Jun;38(6):526-530

Department of Endocrinology, Children's Hospital, Capital Institute of Pediatrics, Beijing 100020, China.

Objective: To summarize clinical manifestations and results of genetic testing in 12 children with Gitelman syndrome (GS).

Methods: Clinical data of the children was collected. Whole exome sequencing(WES) was carried out to screen potential variants of genomic DNA. Candidate variants were verified by Sanger sequencing.

Results: The patients have included 10 boys and 2 girls, whom were diagnosed at between 2.8 to 15.0 year old. Six patients were due to infections, 5 were due to short stature, and 1 was due to lower limb weakness. All patients were found to carry variants of SLC12A3 gene, which included 11 with compound heterozygous variants and 1 with homozygous variant. All of the 19 alleles of the SLC12A3 gene carried by the patients were delineated, which included 15 missense variants, 2 frameshift variants and 2 splice region variants. These variants were unreported previously, which included c.578_582dupCCACC (p.Asn195Profs*109), c.251C>T (p.Pro84Leu) and c.2843G>A (p.Trp948X).

Conclusion: The clinical symptoms of GS in children are atypical and often seen in older children. For children with occasional hypokalemia associated with growth failure, GS should be suspected. The majority of GS children carry two pathogenic variants of the SLC12A3 gene, mainly compound heterozygotes, among which p.Thr60Met is the most common one. The discovery of new variants has enriched the spectrum of SLC12A3 gene variants.
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http://dx.doi.org/10.3760/cma.j.cn511374-20200224-00096DOI Listing
June 2021

Efficacy of computerized cognitive training on improving cognitive functions of stroke patients: A systematic review and meta-analysis of randomized controlled trials.

Int J Nurs Pract 2021 May 25:e12966. Epub 2021 May 25.

Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.

Aim: To evaluate the effects of computerized cognitive training on the cognitive functions of stroke patients.

Background: With increased publications on computerized cognitive training, a meta-analysis is essential to determine the effects of computerized cognitive training among stroke patients.

Design: A systematic review and meta-analysis of randomized controlled studies.

Data Sources: Cochrane Library, Pubmed, EBSCO, Scopus, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were explored to search for research studies from inception to January 2020.

Review Methods: Six outcomes indicators were considered to determine the effects of computerized cognitive training. Two reviewers were selected to search and independently appraise the available articles from various databases. Meta-analysis was performed using the RevMan 5.3 software.

Results: A total of 622 patients with 17 studies were included. Computerized cognitive training significantly improves global cognition, working memory, attention and executive function of stroke patients. However, there was inadequate evidence to demonstrate any effects of computerized cognitive training on activities of daily living and depression.

Conclusion: Computerized cognitive training improves the cognitive functions of stroke patients. However, further research studies are needed to confirm its efficacy in activities of daily living as well as on alleviating depression.
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http://dx.doi.org/10.1111/ijn.12966DOI Listing
May 2021

Structures and Functions of Chromatin Fibers.

Annu Rev Biophys 2021 05;50:95-116

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; email:

In eukaryotes, genomic DNA is packaged into chromatin in the nucleus. The accessibility of DNA is dependent on the chromatin structure and dynamics, which essentially control DNA-related processes, including transcription, DNA replication, and repair. All of the factors that affect the structure and dynamics of nucleosomes, the nucleosome-nucleosome interaction interfaces, and the binding of linker histones or other chromatin-binding proteins need to be considered to understand the organization and function of chromatin fibers. In this review, we provide a summary of recent progress on the structure of chromatin fibers in vitro and in the nucleus, highlight studies on the dynamic regulation of chromatin fibers, and discuss their related biological functions and abnormal organization in diseases.
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http://dx.doi.org/10.1146/annurev-biophys-062920-063639DOI Listing
May 2021

DNA polymerase Gp90 activities and regulations on strand displacement DNA synthesis revealed at single-molecule level.

FASEB J 2021 05;35(5):e21607

Key Laboratory of Environment and Female Reproductive Health, West China School of Public Health & West China Fourth Hospital, Sichuan University, Chengdu, China.

Strand displacement DNA synthesis (SDDS) is an essential step in DNA replication. With magnetic tweezers, we investigated SDDS kinetics of wild-type gp90 and its exonuclease-deficient polymerase gp90 exo at single-molecule level. A novel binding state of gp90 to the fork flap was confirmed prior to SDDS, suggesting an intermediate in the initiation of SDDS. The rate and processivity of SDDS by gp90 exo or wt-gp90 are increased with force and dNTP concentration. The rate and processivity of exonuclease by wt-gp90 are decreased with force. High GC content decreases SDDS and exonuclease processivity but increases exonuclease rate for wt-gp90. The high force and dNTP concentration and low GC content facilitate the successive SDDS but retard the successive exonuclease for wt-gp90. Furthermore, increasing GC content accelerates the transition from SDDS or exonuclease to exonuclease. This work reveals the kinetics of SDDS in detail and offers a broader cognition on the regulation of various factors on SDDS at single-polymerase level.
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http://dx.doi.org/10.1096/fj.202100033RRDOI Listing
May 2021

Person-environment fit and medical professionals' job satisfaction, turnover intention, and professional efficacy: A cross-sectional study in Shanghai.

PLoS One 2021 27;16(4):e0250693. Epub 2021 Apr 27.

School of Public Health, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Objectives: Using the person-environment (PE) fit theory, this study aims to explore factors affecting medical professionals' job satisfaction, turnover intention, and professional efficacy, and to examine individual characters associated with PE fit.

Design And Methods: This study used data from the sixth National Health Service Survey conducted in 2018, with a focus on job outcomes among medical professionals in Shanghai. The reliability and validity of the tools for measuring PE and job outcomes were calculated. A structural equation model was used to examine the relationship among person-job (PJ) fit and person-group (PG) fit, job satisfaction, turnover intention, and professional efficacy. Finally, a hierarchical regression model was used to analyze the association between demographic variables and the PJ and PG fit.

Results: PG fit was directly and positively associated with job satisfaction and professional efficacy. PJ fit had a direct and positive association with job satisfaction but had a direct and negative association with turnover intention. The indirect association of PJ fit with turnover intention was statistically significant. The results from the hierarchical regression analysis showed that younger physicians generally had a lower level of PJ fit and older physicians with higher education tended to have a lower level of PG fit.

Conclusions: Medical professionals with higher PJ or PG fit have higher job satisfaction, and those with higher PG fit have higher professional efficacy. The impact of PJ fit on turnover intention was mediated by job satisfaction. Healthcare managers should take actions to effectively promote medical professionals' PJ and PG fit to improve their retention and efficiency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078800PMC
April 2021

Novel Cyclic Peptides from Lethal Mushrooms through a Genome-Guided Approach.

J Fungi (Basel) 2021 Mar 11;7(3). Epub 2021 Mar 11.

Yunnan Key Laboratory for Fungal Diversity and Green Development, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, China.

Most species in the genus are ectomycorrhizal fungi comprising both edible and poisonous mushrooms. Some species produce potent cyclic peptide toxins, such as α-amanitin, which places them among the deadliest organisms known to mankind. These toxins and related cyclic peptides are encoded by genes of the "MSDIN" family (named after the first five amino acid residues of the precursor peptides), and it is largely unknown to what extent these genes are expressed in the basidiocarps. In the present study, and were sequenced through the PacBio and Illumina techniques. Together with our two previously sequenced genomes, and , in total, 46 previously unknown genes were discovered. The expression of over 80% of the genes was demonstrated in . Through a combination of genomics and mass spectrometry, 12 genes were shown to produce novel cyclic peptides. To further confirm the results, three of the cyclic peptides were chemically synthesized. The tandem mass spectrometry (MS/MS) spectra of the natural and the synthetic peptides shared a majority of the fragment ions, demonstrating an identical structure between each peptide pair. Collectively, the results suggested that the genome-guided approach is reliable for identifying novel cyclic peptides in species and that there is a large peptide reservoir in these mushrooms.
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http://dx.doi.org/10.3390/jof7030204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998459PMC
March 2021

Curaxin-Induced DNA Topology Alterations Trigger the Distinct Binding Response of CTCF and FACT at the Single-Molecule Level.

Biochemistry 2021 02 11;60(7):494-499. Epub 2021 Feb 11.

Department of Immunology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China.

The candidate anticancer drug curaxins can insert into DNA base pairs and efficiently inhibit the growth of various cancers. However, how curaxins alter the genomic DNA structure and affect the DNA binding property of key proteins remains to be clarified. Here, we first showed that curaxin CBL0137 strongly stabilizes the interaction between the double strands of DNA and reduces DNA bending and twist rigidity simultaneously, by single-molecule magnetic tweezers. More importantly, we found that CBL0137 greatly impairs the binding of CTCF but facilitates trapping FACT on DNA. We revealed that CBL0137 clamps the DNA double helix that may induce a huge barrier for DNA unzipping during replication and transcription and causes the distinct binding response of CTCF and FACT on DNA. Our work provides a novel mechanical insight into CBL0137's anticancer mechanisms at the nucleic acid level.
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http://dx.doi.org/10.1021/acs.biochem.1c00014DOI Listing
February 2021

Optimizing preventive medicine to bridge the gap between clinical medicine and public health for disease control in China: A lesson from COVID-19.

Prev Med 2021 02 10;143:106324. Epub 2020 Nov 10.

China Hospital Development Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

The pandemic of Coronavirus Disease 2019 (COVID-19) highlights the importance of early detection of disease outbreaks, taking swift and decisive public health actions, and strengthening public health systems. Preventive medicine, as a specialty of medicine, trains students on both clinical medicine and public health and is of a particular need in battling against this pandemic. In China, preventive medicine plays a unique role in the disease control system where preventive medicine graduates represent a large share of the workforce. However, there is a shortage of qualified staff in the Chinese disease control system. The reasons for such a shortage are multifaceted. From the human resource perspective, the undergraduate preventive medicine curricula and exclusive public health training for preventive medicine postgraduates limit their clinical capacities. A series of disease control and public health education reforms may further incapacitate preventive medicine graduates' clinical skills, unintentionally widening the gap between public health and clinical medicine and thus posing threats to effective disease detection and control. The authors call for reforming and optimizing preventive medicine to bridge the gap between clinical medicine and public health by strengthening curricula on clinical medicine, diversifying curricula on public health, enhancing preventive medicine residency programs, and rectifying regulations that restrict preventive medicine graduates from practicing curative medicine.
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http://dx.doi.org/10.1016/j.ypmed.2020.106324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654361PMC
February 2021

Improving fiscal space for health from the perspective of efficiency in low- and middle-income countries: What is the evidence?

J Glob Health 2020 Dec;10(2):020421

Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Conceptual frameworks of fiscal space for health have traditionally considered health system efficiency improvements as a means to free up resources for the sector. However, there has been no comprehensive review of the evidence to confirm the relationship between efficiency and fiscal space.

Methods: We conducted a systematic review to synthesize evidence on whether efficiency gains increase fiscal space for health. We searched bibliographic databases for specific keywords - namely, fiscal space, efficiency and health - and identified 22 articles that examined links between efficiency gains and fiscal space for health. The articles, which encapsulated 28 case studies, were included in the analysis.

Results: The 28 case studies varied widely with regard to how efficiency was evaluated, the extent to which efficiency was explored, and how efficiency gains could be achieved. Half of the studies assessed both technical and allocative efficiency, and the other half assessed technical efficiency only. The indicators to examine potential inefficiencies varied substantially among studies. The most frequently cited inefficiencies stemmed from public financial management (budget implementation, budget allocation and strategic purchasing) and governance issues, even though these were characterized in various ways. The second most cited set of inefficiencies that caused health systems to function poorly were those related to health service delivery. Procurement and delivery of input factors was also mentioned in some studies as a source of inefficiency. Though most studies conceded that efficiency gains were a potential means to improve fiscal space for health, very few quantified the potential gains or explored practical mechanisms to translate efficiency gains into fiscal space for health.

Conclusions: While the conceptual link between efficiency gains and fiscal space for health may be assumed, there is no direct empirical evidence proving that efficiency gains translate into more resources for the health sector. Mechanisms to translate efficiency gains into fiscal space are barely explored in the fiscal space literature. Public financial management rules and related rules for reallocating funds within the sector need to be further examined to guide countries in the transformation of efficiency gains into more resources for health.
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http://dx.doi.org/10.7189/jogh.10.020421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568933PMC
December 2020

Retrospective analysis of medical malpractice claims in tertiary hospitals of China: the view from patient safety.

BMJ Open 2020 09 24;10(9):e034681. Epub 2020 Sep 24.

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Objectives: The study analysed medical malpractice claims to assess patient safety in hospitals. The information derived from malpractice claims reflects potential risks and could help lead to reducing medical errors and improving patient safety.

Design, Setting: We analysed 4380 medical malpractice claims from 351 grade-A tertiary hospitals in China for 2008-2017. We examined the characteristics of medical errors and patient safety, including the types of medical errors, proportionate liabilities and payments for medical malpractice in different clinical specialties.

Main Outcome Measures: We assessed claim characteristics, payment amounts and liability.

Results: Our data analysis demonstrated that 72.5% of the claims involved medical errors, with average payments of US$31 430. The hospital's errors in medical malpractice resulted in 41.4% average liability in patient injury payments. Most medical malpractice cases occurred in Shanghai (817 claims, 18.7%) and Beijing (468 claims, 10.7%). The highest risks for medical error and malpractice claims were related to orthopaedics (11.3% of all claims, 72.8% with medical errors) and obstetrics and gynaecology (10.0% of all claims, 76.0% with medical errors). The highest rates related to proportionate liabilities were observed in otolaryngology (51.9%) and endocrinology (47.7%). Respiratory medicine had the highest proportion of claims in death rates (77.3%). Medical technology errors accounted for 91.8% of the claims and medical ethics errors for 5.8%. The highest average payment was found in cardiovascular surgery (US$41 733) and the lowest in stomatology (US$8822).

Conclusions: A previous study found that grade-A tertiary hospitals in China have similar medical error rates to general Chinese hospitals. Different specialties had different risk characteristics regarding medical errors, payments and proportionate liabilities. Orthopaedics had the highest number of malpractices claims and higher proportionate liability but lower death rates.
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http://dx.doi.org/10.1136/bmjopen-2019-034681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7517568PMC
September 2020

Inhibition of PI3Kγ by AS605240 plus low-dose tissue plasminogen activator (tPA) combination improves thrombolytic therapy in a rat model of embolic stroke.

Neurosci Lett 2020 11 31;738:135339. Epub 2020 Aug 31.

Department of Neurosurgery, the Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA. Electronic address:

Our previous study showed that PI3Kγ inhibition with AS605240 plus a standard rat-dose tPA (10 mg/kg) combination attenuates delayed tPA-induced brain hemorrhage and ameliorates acute stroke injury 3 days after ischemic stroke in rats. The purpose of this study was to investigate whether combining AS605240 with tPA can enhance thrombolytic efficacy, so that lower doses of tPA can be applied to improve long-term outcome after ischemic stroke. The results showed that AS605240 plus low-dose tPA (5 mg/kg) combination therapy at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 24 h after stroke compared with saline, AS605240 or low-dose tPA alone group. Importantly, the combination therapy significantly reduced the delayed tPA-associated brain hemorrhage. Moreover, the combination therapy significantly decreased the size of the residual embolus within the middle cerebral artery, which was associated with a decrease in plasma plasminogen activator inhibitor-1 (PAI-1) activity compared with saline and tPA alone. Finally, AS605240 plus low-dose tPA combination improved long-term outcome for at least 35 days after stroke compared with the saline-treated group. Taken together, these findings suggest that PI3Kγ inhibition with AS605240 might act as an adjunct approach for enhancing tPA thrombolytic efficacy in acute ischemic stroke.
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http://dx.doi.org/10.1016/j.neulet.2020.135339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171661PMC
November 2020

Analysis of Local Chromatin States Reveals Gene Transcription Potential during Mouse Neural Progenitor Cell Differentiation.

Cell Rep 2020 07;32(4):107953

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of the Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Chromatin dynamics play a critical role in cell fate determination and maintenance by regulating the expression of genes essential for development and differentiation. In mouse embryonic stem cells (mESCs), maintenance of pluripotency coincides with a poised chromatin state containing active and repressive histone modifications. However, the structural features of poised chromatin are largely uncharacterized. By adopting mild time-course MNase-seq with computational analysis, the low-compact chromatin in mESCs is featured in two groups: one in more open regions, corresponding to an active state, and the other enriched with bivalent histone modifications, considered the poised state. A parameter called the chromatin opening potential index (COPI) is also devised to quantify the transcription potential based on the dynamic changes of MNase-seq signals at promoter regions. Use of COPI provides effective prediction of gene activation potential and, more importantly, reveals a few developmental factors essential for mouse neural progenitor cell (NPC) differentiation.
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http://dx.doi.org/10.1016/j.celrep.2020.107953DOI Listing
July 2020

In Depth Natural Product Discovery from the Basidiomycetes Species.

Microorganisms 2020 Jul 15;8(7). Epub 2020 Jul 15.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming 650032, China.

Natural metabolites from microorganisms play significant roles in the discovery of drugs, both for disease treatments in humans, and applications in agriculture. The Basidiomycetes genus has been a source of such bioactive compounds. Here we report on the structures and activities of secondary metabolites from . Their structural types include sesquiterpenoids, polyketides, vibralactones, triterpenoids, sterols, carboxylic acids and saccharides. Most of them showed biological activities including cytotoxic, antibacterial, antifungal, antiviral, radical scavenging activity, autophagy inducing activity, inhibiting pancreatic lipase against malarial parasite, nematocidal and so on. The syntheses of some metabolites have been studied. In this review, 238 secondary metabolites from 10 known species and various unidentified species of were summarized over the last seven decades.
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http://dx.doi.org/10.3390/microorganisms8071049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409058PMC
July 2020

Regulation of plant architecture by a new histone acetyltransferase targeting gene bodies.

Nat Plants 2020 07 13;6(7):809-822. Epub 2020 Jul 13.

Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Axillary meristem development determines both plant architecture and crop yield; this critical process is regulated by the PROLIFERATING CELL FACTORS (TCP) family of transcription factors. Although TCP proteins bind primarily to promoter regions, some also target gene bodies for expression activation. However, the underlying regulatory mechanism remains unknown. Here we show that TEN, a TCP from cucumber (Cucumis sativus L.), controls the identity and mobility of tendrils. Through its C terminus, TEN binds at intragenic enhancers of target genes; its N-terminal domain functions as a non-canonical histone acetyltransferase (HAT) to preferentially act on lysine 56 and 122 of the histone H3 globular domain. This HAT activity is responsible for chromatin loosening and host-gene activation. The N termini of all tested CYCLOIDEA and TEOSINTE BRANCHED 1-like TCP proteins contain an intrinsically disordered region; despite their sequence divergence, they have conserved HAT activity. This study identifies a non-canonical class of HATs and provides a mechanism by which modification at the H3 globular domain is integrated with the transcription process.
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http://dx.doi.org/10.1038/s41477-020-0715-2DOI Listing
July 2020

The 3D organization of genome in the nucleus: from the nucleosome to the 4D nucleome.

Authors:
Guohong Li

Sci China Life Sci 2020 Jun 9;63(6):791-794. Epub 2020 May 9.

National laboratory of Bio-macromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing, 100101, China.

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http://dx.doi.org/10.1007/s11427-020-1723-yDOI Listing
June 2020

Histone variant H2A.Z regulates nucleosome unwrapping and CTCF binding in mouse ES cells.

Nucleic Acids Res 2020 06;48(11):5939-5952

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

Nucleosome is the basic structural unit of chromatin, and its dynamics plays critical roles in the regulation of genome functions. However, how the nucleosome structure is regulated by histone variants in vivo is still largely uncharacterized. Here, by employing Micrococcal nuclease (MNase) digestion of crosslinked chromatin followed by chromatin immunoprecipitation (ChIP) and paired-end sequencing (MNase-X-ChIP-seq), we mapped unwrapping states of nucleosomes containing histone variant H2A.Z in mouse embryonic stem (ES) cells. We found that H2A.Z nucleosomes are more enriched with unwrapping states compared with canonical nucleosomes. Interestingly, +1 H2A.Z nucleosomes with 30-80 bp DNA is correlated with less active genes compared with +1 H2A.Z nucleosomes with 120-140 bp DNA. We confirmed the unwrapping of H2A.Z nucleosomes under native condition by re-ChIP of H2A.Z and H2A after CTCF CUT&RUN in mouse ES cells. Importantly, we found that depletion of H2A.Z results in decreased unwrapping of H3.3 nucleosomes and increased CTCF binding. Taken together, through MNase-X-ChIP-seq, we showed that histone variant H2A.Z regulates nucleosome unwrapping in vivo and that its function in regulating transcription or CTCF binding is correlated with unwrapping states of H2A.Z nucleosomes.
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http://dx.doi.org/10.1093/nar/gkaa360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293034PMC
June 2020

Nanoparticle Delivery of CD147 Antagonistic Peptide-9 Protects against Acute Ischemic Brain Injury and tPA-Induced Intracerebral Hemorrhage in Mice.

ACS Appl Bio Mater 2020 Apr 3;3(4):1976-1985. Epub 2020 Mar 3.

Department of Neurosurgery, The Pennsylvania State, University College of Medicine, Hershey, Pennsylvania 17033, United States.

CD147 has emerged as a potential therapeutic target in many human diseases. We have demonstrated that inhibition of CD147 using its function-blocking antibody ameliorates acute ischemic brain injury and promotes long-term functional recovery in mice. Recently, peptide-nanoparticle conjugates have emerged as powerful tools for biomedical applications. The present study aimed to investigate the therapeutic potential of CD147 antagonist peptide-9 (AP9) in acute ischemic stroke in mice using nanomaterial as the drug delivery vehicles. AP9-conjugated nanoparticles (APN), with an average size of about 40 nm, were fabricated by maleimide linkage and characterized using dynamic light scattering and transmission electron microscopy. We found that APN specifically bound to CD147 in cultured mouse brain endothelial cells (bEnd.3) and to ischemia-induced CD147 in mouse cerebral microvessels. Using a mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated, for the first time, that systemic delivery of APN (2.5 mg/kg, I.V.) initiated at 1 h after tMCAO significantly reduced brain infarct size, improved functional outcome, and attenuated delayed (5 h after tMCAO) tPA-induced intracerebral hemorrhage in acute ischemic stroke. These protective effects were associated with profound inhibition of MMP-9 and MMP-3 in both ischemic brain and plasma. In conclusion, the CD147 antagonist peptide-9 represents a potentially promising therapeutic candidate for the treatment of ischemic stroke.
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http://dx.doi.org/10.1021/acsabm.9b01141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195622PMC
April 2020

RYBP/YAF2-PRC1 complexes and histone H1-dependent chromatin compaction mediate propagation of H2AK119ub1 during cell division.

Nat Cell Biol 2020 04 23;22(4):439-452. Epub 2020 Mar 23.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.

Stable propagation of epigenetic information is important for maintaining cell identity in multicellular organisms. However, it remains largely unknown how mono-ubiquitinated histone H2A on lysine 119 (H2AK119ub1) is established and stably propagated during cell division. In this study, we found that the proteins RYBP and YAF2 each specifically bind H2AK119ub1 to recruit the RYBP-PRC1 or YAF2-PRC1 complex to catalyse the ubiquitination of H2A on neighbouring nucleosomes through a positive-feedback model. Additionally, we demonstrated that histone H1-compacted chromatin enhances the distal propagation of H2AK119ub1, thereby reinforcing the inheritance of H2AK119ub1 during cell division. Moreover, we showed that either disruption of RYBP/YAF2-PRC1 activity or impairment of histone H1-dependent chromatin compaction resulted in a significant defect of the maintenance of H2AK119ub1. Therefore, our results suggest that histone H1-dependent chromatin compaction plays a critical role in the stable propagation of H2AK119ub1 by RYBP/YAF2-PRC1 during cell division.
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http://dx.doi.org/10.1038/s41556-020-0484-1DOI Listing
April 2020

Rett syndrome-causing mutations compromise MeCP2-mediated liquid-liquid phase separation of chromatin.

Cell Res 2020 05 28;30(5):393-407. Epub 2020 Feb 28.

Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.

Rett syndrome (RTT), a severe postnatal neurodevelopmental disorder, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). MeCP2 is a chromatin organizer regulating gene expression. RTT-causing mutations have been shown to affect this function. However, the mechanism by which MeCP2 organizes chromatin is unclear. In this study, we found that MeCP2 can induce compaction and liquid-liquid phase separation of nucleosomal arrays in vitro, and DNA methylation further enhances formation of chromatin condensates by MeCP2. Interestingly, RTT-causing mutations compromise MeCP2-mediated chromatin phase separation, while benign variants have little effect on this process. Moreover, MeCP2 competes with linker histone H1 to form mutually exclusive chromatin condensates in vitro and distinct heterochromatin foci in vivo. RTT-causing mutations reduce or even abolish the ability of MeCP2 to compete with histone H1 and to form chromatin condensates. Together, our results identify a novel mechanism by which phase separation underlies MeCP2-mediated heterochromatin formation and reveal the potential link between this process and the pathology of RTT.
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http://dx.doi.org/10.1038/s41422-020-0288-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196128PMC
May 2020

A Multicenter, Comparative Study of Two Pressure-Redistribution Mattresses with Repositioning Intervals for Critical Care Patients.

Adv Skin Wound Care 2020 Mar;33(3):1-9

In Jinling Hospital, Nanjing University School of Medicine, China, Qixia Jiang, MSN, RN, ET, is Head Nurse, Outpatient Department; and Yuxiu Liu, MM, is Director, Department of Medical Administration. Hui Yu, MSN, RN, is Nurse, Wuxi No. 3 People's Hospital, Jiangnan University. Siping Song, BSN, RN, is a master's degree candidate, Medical School of Nanjing University. Guohong Li, MPH, RN, is Director, Department of Nursing Administration, Zhongda Hospital, Southeast University, Nanjing. Haiying Liu, BSN, RN, is Associate Director, Department of Nursing Administration, Wuxi No. 2 People's Hospital, Nanjing Medical University. Yi Zhou, BSN, RN, is Director, Department of Nursing Administration, Changshu No. 2 People's Hospital, Yangzhou University. Yajun Zhu, BSN, RN, ET, is Associate Director, Department of Nursing Administration, Jingjiang People's Hospital, Yangzhou University. Jing Jia, BSN, RN, ET, is a head nurse of Department of Nursing Administration, Zhenjiang People's Hospital, Jiangsu University. Yunjuan Huang, MSN, RN, is Director, Department of Nursing Administration, Wuxi People's Hospital, Nanjing Medical University. Jiandong Wang, PhD, MD, is Associate Professor, Department of Pathology, Jinling Hospital, Nanjing University of Medicine. Acknowledgments: The authors thank Andrea Baird, MD, and Jennifer Barrett, PhD, from Liwen Bianji, Edanz Editing China, for editing a draft of this manuscript. This study was sponsored by the Jinling Hospital Science Research Fund (no. 2010M012 and no. 2013NYL014; partly supported by 20WQ027, WZGF 20200101) and Taica Shanghai Co, Ltd (Shanghai, China), manufacturer of pressure redistribution mattresses. The authors have disclosed no other financial relationships related to this article. Submitted May 13, 2019; accepted in revised form July 3, 2019.

Objective: To compare the effectiveness of two protocols for preventing pressure injuries (PIs) in Chinese hospitals.

Design And Setting: A multicenter, open-label, comparative study conducted in seven Chinese acute care hospitals.

Patients And Intervention: In total, 1,654 eligible patients were identified, and 1,204 were enrolled in the study. Enrolled patients were randomly assigned into the trial group (4-hour repositioning combined with a viscoelastic foam mattress; n = 602) or the control group (2-hour repositioning combined with a powered air pressure redistribution mattress; n = 602). Participants received their respective protocols until they were discharged, died, or for at least 7 days.

Main Outcome Measures: The incidence of PIs, Braden Scale scores, and the time to development of PIs.

Main Results: Ultimately, 596 trial group patients and 598 control group patients were analyzed. Thirteen patients had single new stage 2 or worse PIs. The total incidence of PIs was 1.1%. The difference between the two groups was significant (0.3% vs 1.8%). However, the difference between the groups' Braden Scale score median during the intervention was not significant (13 vs 13.5).

Conclusions: The 4-hour repositioning interval combined with a viscoelastic foam mattress did not increase PI incidence or risk. These findings could help providers select the right pressure redistribution mattresses and repositioning intervals for critical care patients.
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http://dx.doi.org/10.1097/01.ASW.0000653160.13611.5dDOI Listing
March 2020
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