Publications by authors named "Jianping Ding"

195 Publications

New exon and accelerated evolution of placental gene Nrk occurred in the ancestral lineage of placental mammals.

Placenta 2021 Aug 14;114:14-21. Epub 2021 Aug 14.

CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China; Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China. Electronic address:

Introduction: The chorioallantoic placenta is a specific organ for placental mammals. However, the adaptive events during its emergence are still poorly investigated.

Methods: We scanned the chromosome X to detect the accelerated evolution in the ancestral lineage of placental mammals, and constructed 3D protein structure models of a candidate by homology modeling.

Results: Eight branch-specific accelerated regions were identified. Five of these regions (P=5.61×10 ~ 9.03×10) are located in the five exons of Nik-related kinase (Nrk), which is essential in placenta development and fetoplacental induction of labor. Nrk belongs to the germinal center kinase-IV subfamily with the overall similar protein structure; however, a new exon emerged in ancestors of placental mammals and its sequence has been conserved since then. Structure modelling of NRK suggests that the accelerated exons and the placental-mammal-specific exon (as a new loop) could change the enzymatic activity and the structure of placental mammal NRK.

Discussion: Since the new loop is surrounded by the accelerated protein regions, it is likely that the new loop occurred and shifted the function of NRK, and then the accelerated evolution of Nrk occurred to adapt the structure change caused by the new loop in the ancestral lineage of placental mammals. Overall, this work suggests that the fundamental process of placental development and fetoplacental induction of labor has been targeted by positive Darwinian selection.
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http://dx.doi.org/10.1016/j.placenta.2021.08.048DOI Listing
August 2021

MRI study of changes in knee bone marrow edema-like signal in asymptomatic amateur marathon runners before and after half-marathon running.

Clin Imaging 2021 May 18;80:150-157. Epub 2021 May 18.

Department of Radiology, The Affiliated Hospital of Hangzhou Normal University, No. 126, Wenzhou Road, Gongshu District, Hangzhou 310000, Zhejiang, China.

Objective: To evaluate the incidence of knee bone marrow edema-like signal and its changes before and after running a half marathon running in asymptomatic amateur marathon runners to explore the impact of the half marathon on knee bone marrow edema-like signal.

Methods: 50 asymptomatic amateur marathon runners (30 males, 20 females) were recruited. T1-weighted imaging (T1WI), fat-suppressed protein density weighted imaging (fs-PDWI) and three-dimensional double-echo steady-state (3D-DESS) sequence on the right knee were performed before and within 3 h after a half-marathon running. 20 healthy volunteers were recruited as control. According to the whole-organ magnetic resonance imaging score (WORMS) system, the involvement of bone marrow edema-like signal in 15 regions of knee was graded from 0 to 3. The results were classified and Mann Whitney U test was used for comparison between groups.

Results: The total incidence of bone marrow edema-like signal in amateur marathon group was 62%. Among them, the incidence of grade 1-3 was 48% (24/50), 12% (6/50), 2% (1/50), respectively, which was statistically significant compared with the controls (P = 0.007). There was no significant difference between gender before running (P = 0.172) and after running (P = 0.162). There was no significant difference before and after running (P > 0.05). However, 3 subjects showed new lesions, 8 subjects showed progression and 4 subjects showed decreased signal.

Conclusion: The occurrence of knee bone marrow edema-like signal in amateur marathon runners is more common. The lesions of bone marrow edema-like signal will show aggravation or improvement in a certain extent after the half marathon.
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http://dx.doi.org/10.1016/j.clinimag.2021.05.005DOI Listing
May 2021

Metamaterial perfect absorber with morphology-engineered meta-atoms using deep learning.

Opt Express 2021 Jun;29(13):19955-19963

Metamaterial perfect absorbers (MPAs) typically have regularly-shaped unit structures owing to constraints on conventional analysis methods, limiting their absorption properties. We propose an MPA structure with a general polygon-shaped meta-atom. Its irregular unit structure provides multiple degrees-of-freedom, enabling flexible properties, such as dual-band absorption. We constructed a deep neural network to predict the parameters of the corresponding MPA structure with a given absorptivity as input, and vice versa. The mean-square error was as low as 0.0017 on the validation set. This study provides a basis for the design of complicated artificial electromagnetic structures for application in metamaterials and metasurfaces.
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http://dx.doi.org/10.1364/OE.427593DOI Listing
June 2021

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

Nucleic Acids Res 2021 Aug;49(14):8037-8059

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
August 2021

Efficacy and safety of normobaric hyperoxia combined with intravenous thrombolysis on acute ischemic stroke patients.

Neurol Res 2021 Jun 15:1-6. Epub 2021 Jun 15.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Intravenous thrombolysis elevates the prognostic level of acute ischemic stroke (AIS) patients. Normobaric hyperoxia (NBO) delays the progression of the infarct core and promotes neurological recovery. However, it is uncertain whether NBO can further raise the prognostic level of AIS patients based on intravenous thrombolysis. To explore the efficacy and safety of NBO combined with intravenous thrombolysis on AIS patients. This observational study included anterior circulation stroke patients who received intravenous thrombolysis within 4.5 h after stroke onset. These patients were divided into two groups based on whether or not they received NBO therapy. The baseline data and the prognosis of the two groups were compared. The primary outcome was the proportion of functional independence (modified Rankin Scale 0-2) at 90 days post discharge. A total of 227 patients were included in this study. 125 patients received NBO therapy combined with intravenous thrombolysis, while 102 patients received intravenous thrombolysis only. Overall, the rate of recanalization was 83.3%. Consequently, 101 patients (80.8%) who received NBO combined with intravenous thrombolysis and 63 patients (61.8%) in the control group achieved functional independence (P = 0.002). Multivariable logistic regression analysis showed that NBO combined with intravenous thrombolysis over intravenous thrombolysis alone was associated with 90-day functional independence (OR: 2.318; 95% CI: 1.226-4.381; P = 0.01). This study verified the efficacy and safety of NBO combined with intravenous thrombolysis in AIS patients. Prospective study is needed to further substantiate these findings.
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http://dx.doi.org/10.1080/01616412.2021.1939234DOI Listing
June 2021

Nonvolatile Optically Reconfigurable Radiative Metasurface with Visible Tunability for Anticounterfeiting.

Nano Lett 2021 Jun 2;21(12):5269-5276. Epub 2021 Jun 2.

State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou 310027, China.

Control of thermal emission underpins fundamental science, as it is related to both heat and infrared electromagnetic wave transport. However, realizing nonvolatile reconfigurable thermal emission is challenging due to the inherent complexity or limitation in conventional radiative materials or structures. Here, we experimentally demonstrate a nonvolatile optically reconfigurable mid-infrared coding radiative metasurface. By applying laser pulses, infrared emissive patterns are directly encoded into an ultrathin (∼25 nm) GeSbTe layer integrated into a planar optical cavity with the optically crystallized GeSbTe spots, and the peak spectral emissivity is repeatedly switched between low (∼0.1) and high (∼0.7) values. In addition, the visible scattering patterns are independently modulated with submicron-sized bumps generated by high-power laser pulses. An anticounterfeiting label is demonstrated with spatially different infrared emission and visible light scattering information encoded. This approach constitutes a new route toward thermal emission control and has broad applications in encryption, camouflage, and so on.
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http://dx.doi.org/10.1021/acs.nanolett.1c01396DOI Listing
June 2021

Optical frequency conversion of light with maintaining polarization and orbital angular momentum.

Opt Lett 2021 May;46(10):2300-2303

Optical frequency conversion provides a fundamental and important approach to manipulate light in frequency domain. In such a process, manipulating the frequency of light without changing information in other degrees of freedom of light will enable us to establish an interface between various optical systems operating in different frequency regions and have many classical and quantum applications. Here we experimentally demonstrate a frequency conversion with maintaining polarization and orbital angular momentum (OAM) by successfully upconverting various polarization-OAM composite states in a nonlinear Sagnac interferometer. Our scheme offers a new possibility for building different wave band interfaces in more degrees of freedom.
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http://dx.doi.org/10.1364/OL.419753DOI Listing
May 2021

Twin curvilinear vortex beams.

Opt Express 2021 Apr;29(9):14112-14125

We report on a novel curvilinear optical vortex beam named twin curvilinear vortex beams (TCVBs) with intensity and phase distribution along a pair of two- or three-dimensional curves, both of which share the same shape and the same topological charge. The TCVBs also possess the character of perfect optical vortex, namely having a size independent of topological charge. We theoretically demonstrate that a TCVB rather than a single-curve vortex beam can be created by the Fourier transform of a cylindrically polarized beam. The behavior of TCVBs generated through our method is investigated by simulation and experiment, including interference experiments for identifying the vortex property of the TCVBs. The TCVBs may find applications in optical tweezers, such as trapping low refractive index particles in the dark region between two curves and driving them moving along the curvilinear trajectory.
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http://dx.doi.org/10.1364/OE.423803DOI Listing
April 2021

A Resting-state Functional Magnetic Resonance Imaging Study of Whole-brain Functional Connectivity of Voxel Levels in Patients With Irritable Bowel Syndrome With Depressive Symptoms.

J Neurogastroenterol Motil 2021 Apr;27(2):248-256

Department of Radiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China.

Background/aims: Depressive symptom is one of the most common symptoms in patients with irritable bowel syndrome (IBS), but its pathogenetic mechanisms remain unclear. As a voxel-level graph theory analysis method, degree centrality (DC) can provide a new perspective for exploring the abnormalities of whole-brain functional network of IBS with depressive symptoms (DEP-IBS).

Methods: DC, voxel-wise image and clinical symptoms correlation and seed-based functional connectivity (FC) analyses were performed in 28 DEP-IBS patients, 21 IBS without depressive symptoms (nDEP-IBS) patients and 36 matched healthy controls (HC) to reveal the abnormalities of whole brain FC in DEP-IBS.

Results: Compared to nDEP-IBS patients and HC, DEP-IBS patients showed significant decrease of DC in the left insula and increase of DC in the left precentral gyrus. The DC's z-scores of the left insula negatively correlated with depression severity in DEP-IBS patients. Compared to nDEP-IBS patients, DEP-IBS patients showed increased left insula-related FC in the left inferior parietal lobule and right inferior occipital gyrus, and decreased left insula-related FC in the left precentral gyrus, right supplementary motor area (SMA), and postcentral gyrus. In DEP-IBS patients, abstracted clusters' mean FC in the right SMA negatively correlated with depressive symptoms.

Conclusions: DEP-IBS patients have abnormal FC in brain regions associated with the fronto-limbic and sensorimotor networks, especially insula and SMA, which explains the vicious circle between negative emotion and gastrointestinal symptoms in IBS. Identification of such alterations may facilitate earlier and more accurate diagnosis of depression in IBS, and development of effective treatment strategies.
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http://dx.doi.org/10.5056/jnm20209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026363PMC
April 2021

Non-diffracting and self-accelerating Bessel beams with on-demand tailored intensity profiles along arbitrary trajectories.

Opt Lett 2021 Apr;46(7):1494-1497

Owing to their robustness against diffraction, Bessel beams (BBs) offer special advantages in various applications. To enhance their applicability, we present a method to generate self-accelerating zeroth-order BBs along predefined trajectories with tunable direction intensity profiles. The character of tunable direction intensity profiles in non-diffracting self-accelerating BBs potentially can attract interest in the regimes of particle manipulation, microfabrication, and free-space optical interconnects.
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http://dx.doi.org/10.1364/OL.418928DOI Listing
April 2021

Molecular mechanism for vitamin C-derived C-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1.

Nat Commun 2021 02 2;12(1):744. Epub 2021 Feb 2.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

C-glyceryl-methylcytosine (5gmC) is a novel DNA modification catalyzed by algal TET homologue CMD1 using vitamin C (VC) as co-substrate. Here, we report the structures of CMD1 in apo form and in complexes with VC or/and dsDNA. CMD1 exhibits comparable binding affinities for DNAs of different lengths, structures, and 5mC levels, and displays a moderate substrate preference for 5mCpG-containing DNA. CMD1 adopts the typical DSBH fold of Fe/2-OG-dependent dioxygenases. The lactone form of VC binds to the active site and mono-coordinates the Fe in a manner different from 2-OG. The dsDNA binds to a positively charged cleft of CMD1 and the 5mC/C is inserted into the active site and recognized by CMD1 in a similar manner as the TET proteins. The functions of key residues are validated by mutagenesis and activity assay. Our structural and biochemical data together reveal the molecular mechanism for the VC-derived 5gmC DNA modification by CMD1.
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http://dx.doi.org/10.1038/s41467-021-21061-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854593PMC
February 2021

Structural basis for self-cleavage prevention by tag:anti-tag pairing complementarity in type VI Cas13 CRISPR systems.

Mol Cell 2021 03 19;81(5):1100-1115.e5. Epub 2021 Jan 19.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China. Electronic address:

Bacteria and archaea apply CRISPR-Cas surveillance complexes to defend against foreign invaders. These invading genetic elements are captured and integrated into the CRISPR array as spacer elements, guiding sequence-specific DNA/RNA targeting and cleavage. Recently, in vivo studies have shown that target RNAs with extended complementarity with repeat sequences flanking the target element (tag:anti-tag pairing) can dramatically reduce RNA cleavage by the type VI-A Cas13a system. Here, we report the cryo-EM structure of Leptotrichia shahii LshCas13a in complex with target RNA harboring tag:anti-tag pairing complementarity, with the observed conformational changes providing a molecular explanation for inactivation of the composite HEPN domain cleavage activity. These structural insights, together with in vitro biochemical and in vivo cell-based assays on key mutants, define the molecular principles underlying Cas13a's capacity to target and discriminate between self and non-self RNA targets. Our studies illuminate approaches to regulate Cas13a's cleavage activity, thereby influencing Cas13a-mediated biotechnological applications.
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http://dx.doi.org/10.1016/j.molcel.2020.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274241PMC
March 2021

Structure, substrate specificity, and catalytic mechanism of human D-2-HGDH and insights into pathogenicity of disease-associated mutations.

Cell Discov 2021 Jan 12;7(1). Epub 2021 Jan 12.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China.

D-2-hydroxyglutarate dehydrogenase (D-2-HGDH) catalyzes the oxidation of D-2-hydroxyglutarate (D-2-HG) into 2-oxoglutarate, and genetic D-2-HGDH deficiency leads to abnormal accumulation of D-2-HG which causes type I D-2-hydroxyglutaric aciduria and is associated with diffuse large B-cell lymphoma. This work reports the crystal structures of human D-2-HGDH in apo form and in complexes with D-2-HG, D-malate, D-lactate, L-2-HG, and 2-oxoglutarate, respectively. D-2-HGDH comprises a FAD-binding domain, a substrate-binding domain, and a small C-terminal domain. The active site is located at the interface of the FAD-binding domain and the substrate-binding domain. The functional roles of the key residues involved in the substrate binding and catalytic reaction and the mutations identified in D-2-HGDH-deficient diseases are analyzed by biochemical studies. The structural and biochemical data together reveal the molecular mechanism of the substrate specificity and catalytic reaction of D-2-HGDH and provide insights into the pathogenicity of the disease-associated mutations.
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http://dx.doi.org/10.1038/s41421-020-00227-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801405PMC
January 2021

Structure and allosteric regulation of human NAD-dependent isocitrate dehydrogenase.

Cell Discov 2020 Dec 22;6(1):94. Epub 2020 Dec 22.

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

Human NAD-dependent isocitrate dehydrogenase or HsIDH3 catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the TCA cycle. HsIDH3 exists and functions as a heterooctamer composed of the αβ and αγ heterodimers, and is regulated allosterically and/or competitively by numerous metabolites including CIT, ADP, ATP, and NADH. In this work, we report the crystal structure of HsIDH3 containing a β mutant in apo form. In the HsIDH3 structure, the αβ and αγ heterodimers form the αβγ heterotetramer via their clasp domains, and two αβγ heterotetramers form the (αβγ) heterooctamer through insertion of the N-terminus of the γ subunit of one heterotetramer into the back cleft of the β subunit of the other heterotetramer. The functional roles of the key residues at the allosteric site, the pseudo allosteric site, the heterodimer and heterodimer-heterodimer interfaces, and the N-terminal of the γ subunit are validated by mutagenesis and kinetic studies. Our structural and biochemical data together demonstrate that the allosteric site plays an important role but the pseudo allosteric site plays no role in the allosteric activation of the enzyme; the activation signal from the allosteric site is transmitted to the active sites of both αβ and αγ heterodimers via the clasp domains; and the N-terminal of the γ subunit plays a critical role in the formation of the heterooctamer to ensure the optimal activity of the enzyme. These findings reveal the molecular mechanism of the assembly and allosteric regulation of HsIDH3.
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http://dx.doi.org/10.1038/s41421-020-00220-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752914PMC
December 2020

Imaging manifestations and pathological analysis of intramuscular myxoma: A case report and literature review.

Radiol Case Rep 2021 Feb 30;16(2):300-304. Epub 2020 Nov 30.

Departments of Radiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China.

Intramuscular Myxoma(IM) is a rare benign soft tissue tumor, and its etiology and histology source is still unclear. It is important to understand the pathological components of IM and its corresponding imaging features, as well as performing accurate and careful imaging assessments of IM before surgery. We present a case of a 43-year-old male who presented a lump in his left thigh and gradually enlarged during the past 8 years. The patient underwent CT, MRI, and CTA examined and was later pathologically confirmed as IM. This article will combine the literature,to explore the imaging manifestations and its pathological basis of intramuscular myxoma.
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http://dx.doi.org/10.1016/j.radcr.2020.10.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711187PMC
February 2021

Effects of seasonal ambient heat stress on expression of microRNAs in the mammary gland of Holstein cows.

Int J Biometeorol 2021 Feb 29;65(2):235-246. Epub 2020 Oct 29.

College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, People's Republic of China.

This study was conducted to assess the link of miRNA expressions in cow's mammary gland undergoing heat stress. Twelve Holstein cows were allocated either to undergo heat stress (HS) or remain in a thermoneutral environment (non-heat stress, NS), respectively. The experiment with HS cows was carried out in August, and the experiment with NS cows was done in November. After a month, three cows from each group were slaughtered, and mammary gland samples were obtained, and then miRNA were extracted from the samples for later sequencing. From the miRNA-seq, we obtained a total of 124 differentially expressed miRNAs in HS and NS cows' mammary gland. The differentially expressed miRNA could be predicted to influence multiple target genes. The target interleukin-1 (IL-1), which play a role in regulating the function of mammary gland in dairy cows, could be affected by bta-let-7c, bta-let-7e, bta-miR-181d, bta-miR-452, and bta-miR-31. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that mitogen-activated protein kinase (MAPK) pathway plays an important role in the mammary glands of dairy cows and bta-miR-25 and bta-miR-382 may influence MAPK pathway through c-Jun N-terminal kinase (JNK) gene to affect the function of mammary gland in HS cows. In conclusion, this study characterized expression profile of miRNAs in the Holstein cows' mammary gland under summer heat stress or not. We observed miRNA expression during heat stress, which was significantly different from non-heat stress states. A comprehensive analysis of the miRNA's expression will be helpful to further study the link of miRNAs with mechanisms regulating heat stress in the cow mammary gland.
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http://dx.doi.org/10.1007/s00484-020-02025-5DOI Listing
February 2021

Molecular Epidemiology of HIV-1 in Jiangsu Province, Southeast China: Genotypes and HIV-1 Transmission Networks Among Newly Diagnosed Men Having Sex with Men in 2017.

AIDS Res Hum Retroviruses 2021 01 21;37(1):62-69. Epub 2020 Oct 21.

Department of HIV/STD Prevention and Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

Investigation of disease and intervention in populations of men having sex with men (MSM) has garnered attention globally, a primary reason being the rapid increase in the prevalence of human immunodeficiency virus (HIV)-1 among MSM. The purpose of this study was to understand the current HIV-1 molecular characteristics and characterize HIV-1 transmission networks in the MSM population. Nine hundred and fourteen newly diagnosed HIV-positive MSM were included in this study. The HIV-1 gene region was amplified and sequenced. A maximum likelihood phylogenetic tree was constructed, and transmission clusters were identified using 1.5% distance and 0.9 bootstrap values. In total, 767 sequences were successfully obtained, with CRF01_AE being the major genotype (43.3%, 332/767), followed by CRF07_BC (31.3%, 240/767), CRF67_01B (7.2%, 55/767), and URF (6.4%, 49/767). The transmitted HIV drug resistance rate was 4.0% (31/767), and the most common mutations were E138G ( = 4) and G190A ( = 4). A total of 182 (23.7%) sequences were included in the HIV-1 transmission networks, forming 79 clusters. Four clusters were identified as fast-growing, and the proportion of young MSM was higher than that of non-MSM (51.6% vs. 31.8%). The genetic diversity of HIV-1 in Jiangsu was complex, and cross-region transmission might exist for CRF67_01B. Transmission among young MSM within networks was greater than the other age groups; thus, they could be essential in the control of the HIV epidemic in Jiangsu. This study was approved by the ethical review board of the National Center for AIDS/STD Control and Prevention (Project No. X140617334).
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http://dx.doi.org/10.1089/AID.2020.0165DOI Listing
January 2021

Altered gray matter structural covariance networks at both acute and chronic stages of mild traumatic brain injury.

Brain Imaging Behav 2021 Aug;15(4):1840-1854

Center for Studies of Psychological Application, South China Normal University, Guangzhou, 510631, China.

Cognitive and emotional impairments observed in mild traumatic brain injury (mTBI) patients may reflect variances of brain connectivity within specific networks. Although previous studies found altered functional connectivity (FC) in mTBI patients, the alterations of brain structural properties remain unclear. In the present study, we analyzed structural covariance (SC) for the acute stages of mTBI (amTBI) patients, the chronic stages of mTBI (cmTBI) patients, and healthy controls. We first extracted the mean gray matter volume (GMV) of seed regions that are located in the default-mode network (DMN), executive control network (ECN), salience network (SN), sensorimotor network (SMN), and the visual network (VN). Then we determined and compared the SC for each seed region among the amTBI, the cmTBI and the healthy controls. Compared with healthy controls, the amTBI patients showed lower SC for the ECN, and the cmTBI patients showed higher SC for the both DMN and SN but lower SC for the SMN. The results revealed disrupted ECN in the amTBI patients and disrupted DMN, SN and SMN in the cmTBI patients. These alterations suggest that early disruptions in SC between bilateral insula and the bilateral prefrontal cortices may appear in amTBI and persist into cmTBI, which might be potentially related to the cognitive and emotional impairments.
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http://dx.doi.org/10.1007/s11682-020-00378-4DOI Listing
August 2021

Comparison of Common Methods for Precision Volume Measurement of Hematoma.

Comput Math Methods Med 2020 17;2020:6930836. Epub 2020 Jul 17.

College of Science, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China 310018.

Purpose: Our aim is to conduct analysis and comparison of some methods commonly used to measure the volume of hematoma, for example, slice method, voxelization method, and 3D-Slicer software method (projection method).

Method: In order to validate the accuracy of the slice method, voxelization method, and 3D-Slicer method, these three methods were first applied to measure two known volumetric models, respectively. Then, a total of 198 patients diagnosed with spontaneous intracerebral hemorrhage (ICH) were recruited. The patients were split into 3 different groups based on the hematoma size: group 1: volume < 10 ml ( = 89), group 2: volume between 10 and 20 ml ( = 59), and group 3: volume > 20 ml ( = 50). And the shape of the hematoma was classed into regular (round to ellipsoid) with smooth margins ( = 76), irregular with frayed margins ( = 85), and multilobular ( = 37). The slice method, voxelization method, and 3D-Slicer method were adopted to measure the volume of hematoma, respectively, considering the nonclosed models and the models which may contain inaccurate normal information during CT scan. Moreover, the results were compared with the 3D-Slicer method for closed models.

Results: There was a significant estimation error ( < 0.05) using these three methods to calculate the volume of the closed hematoma model. The estimated hematoma volume was calculated to be 14.2086743 ± 0.900559087 ml, 14.2119130 ± 0.900851812 ml, and 14.2123825 ± 0.900835916 ml using slice method 1, slice method 2, and the voxelization method, respectively, compared to 14.212656 ± 0.900992371 ml using the 3D-Slicer method. The mean estimation error was 0.00398172 ml, 0.00074303 ml, and 0.00027354 ml caused by slice method 1, slice method 2, and voxelization method, respectively. There was a significant estimation error ( < 0.05), applying these three methods to calculate the volume of the nonclosed hematoma model. The estimated hematoma volume was calculated to be 14.1928246 ± 0.902210314 ml using the 3D-Slicer method. The mean estimation error was calculated to be 0.00402121 ml, 0.00078237 ml, -0.00031288 ml, and 0.01983136 ml using slice method 1, slice method 2, voxelization method, and 3D-Slicer method, respectively.

Conclusions: The 3D-Slicer software method is considered as a stable and capable method of high precision for the calculation of a closed hematoma model with correct normal direction, while it would be inappropriate for the nonclosed model nor the model with incorrect normal direction. The slice method and voxelization method can be the supplement and improvement of the 3D-Slicer software method, for the purpose of achieving precision medicine.
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http://dx.doi.org/10.1155/2020/6930836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382736PMC
May 2021

Efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke: a multicenter, randomized, double-blind, placebo-controlled trial.

BMC Neurol 2020 Jul 14;20(1):282. Epub 2020 Jul 14.

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, China.

Background: Ischemic stroke is a leading cause of morbidity and mortality. Thrombolytic therapy improves disability and survival rates; however, to be effective, it must be given within 4.5 h of onset. Moreover, thrombolytic therapy is frequently contraindicated. Therefore, alternative therapeutic options are required. In China, cinepazide maleate injection has been shown to improve the cerebral collateral circulation and further reduce disability in stroke patients; however, very few studies investigating this therapy have been conducted to date. Therefore, this study aimed to further confirm the efficacy and safety of cinepazide maleate injection in patients with acute ischemic stroke.

Methods: Patients with acute ischemic stroke were administered an intravenous infusion of 320 mg cinepazide maleate or placebo once daily for 14 days. All patients were also administered basic therapy (citicoline sodium). The primary efficacy endpoint was the proportion of patients with a modified Rankin scale (mRS) ≤2 on day 90. Secondary efficacy endpoints included Barthel Index ≥95. Safety was evaluated by recording all adverse events (AEs), monitoring laboratory parameters and vital signs, and electrocardiogram.

Results: In total, 937 patients with an acute ischemic stroke were included, with a mean (standard deviation, SD) National Institutes of Health Stroke Scale score of 8.8 (2.4) and a mean (SD) stroke onset of 30.9 (11.4) hours prior. Following treatment for 90 days, the proportion of patients with an mRS score ≤ 2 was significantly higher in the cinepazide maleate group than in the control group (60.9% vs. 50.1%; p = 0.0004). Moreover, the proportion of patients with a Barthel Index of ≥95 on day 90 was also significantly higher in the cinepazide maleate group than in the control group (53.4% vs. 46.7%; p = 0.0230). There were no statistically significant differences in safety parameters between the cinepazide maleate and control groups.

Conclusions: The results of this study show that cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery in patients with acute ischemic stroke. Cinepazide maleate injection was safe and well tolerated with no unexpected AEs reported.

Trial Registration: Chinese Clinical Trial Registry CTR20160292 and ChiCTR1900023827 . Retrospectively registered June 13, 2019.
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http://dx.doi.org/10.1186/s12883-020-01844-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359492PMC
July 2020

Structure basis of the FERM domain of kindlin-3 in supporting integrin αIIbβ3 activation in platelets.

Blood Adv 2020 07;4(13):3128-3135

Collaborative Research Program for Cell Adhesion Molecules, Shanghai University School of Life Sciences, Shanghai, China.

Kindlin-3, a protein 4.1, ezrin, radixin, and moesin (FERM) domain-containing adaptor in hematopoietic cells, is essentially required for supporting the bidirectional integrin αIIbβ3 signaling in platelets by binding to the integrin β3 cytoplasmic tail. However, the structural details of kindlin-3's FERM domain remain unknown. In this study, we crystalized the kindlin-3's FERM domain protein and successfully solved its 3-dimensional structure. The structure shows that the 3 kindlin-3's FERM subdomains (F1, F2, and F3) compact together and form a cloverleaf-shaped conformation, which is stabilized by the binding interface between the F1 and F3 subdomains. Interestingly, the FERM domain of kindlin-3 exists as a monomer in both crystal and solution, which is different from its counterpart in kindlin-2 that is able to form a F2 subdomain-swapped dimer; nonetheless, dimerization is required for kindlin-3 to support integrin αIIbβ3 activation, indicating that kindlin-3 may use alternative mechanisms for formation of a functional dimer in cells. To evaluate the functional importance of the cloverleaf-like FERM structure in kindlin-3, structure-based mutations were introduced into kindlin-3 to disrupt the F1/F3 interface. The results show that integrin αIIbβ3 activation is significantly suppressed in platelets expressing the kindlin-3 mutant compared with those expressing wild-type kindlin-3. In addition, introduction of equivalent mutations into kindlin-1 and kindlin-2 also significantly compromises their ability to support integrin αIIbβ3 activation in CHO cells. Together, our findings suggest that the cloverleaf-like FERM domain in kindlins is structurally important for supporting integrin αIIbβ3 activation.
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http://dx.doi.org/10.1182/bloodadvances.2020001575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362375PMC
July 2020

MRI features of and factors related to ankle injuries in asymptomatic amateur marathon runners.

Skeletal Radiol 2021 Jan 6;50(1):87-95. Epub 2020 Jul 6.

Department of Radiology, The Affiliated Hospital of Hangzhou Normal University, No. 126, Wenzhou Road, Gongshu District, Hangzhou, 310000, Zhejiang, China.

Objective: To analyze the MRI manifestations of and factors related to ankle injuries in asymptomatic amateur marathon runners.

Materials And Methods: A total of 113 amateur marathon runners without any ankle joint symptoms were recruited. Each participant was asked to complete a questionnaire at the beginning of the study and underwent MRI of the ankle. The MRI manifestations of ankle injuries were summarized, and binary logistic regression analysis was applied to analyze the factors related to ankle injuries.

Results: The main MRI features were bone marrow edema-like signal intensity, peritendinous effusion, and partial lateral collateral ligament injury. Others included Achilles tendinopathy, cyst-like lesions, osteochondral lesions, and subcutaneous soft tissue edema. The risk factor for bone marrow edema-like signal intensity in amateur marathon runners was a rearfoot strike pattern (p = 0.028, OR = 1.172); the risk factors for peritendinous effusion were a higher weekly running distance (p = 0.013, OR = 1.685) and increased running years (p = 0.039, OR = 1.113), whereas a rearfoot strike pattern (p = 0.005, OR = 0.831) was a protective factor for peritendinous effusion; the risk factor for Achilles tendinopathy was increased age (p = 0.008, OR = 1.412); the risk factors for anterior talofibular ligament injury were a rearfoot strike pattern (p = 0.017, OR = 1.346) and higher weekly running distance (p = 0.022, OR = 1.171); and the factors for calcaneofibular ligament injury were a higher weekly running distance (p = 0.029, OR = 1.570) and rearfoot strike pattern (p = 0.035, OR = 1.463).

Conclusion: The main MRI features of asymptomatic amateur marathon runners are bone marrow edema-like signal intensity, peritendinous effusion, and partial lateral collateral ligament injury. In addition, increased age, increased running years, higher weekly running distance, and different foot strike patterns are risk factors for ankle injuries.
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http://dx.doi.org/10.1007/s00256-020-03530-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677287PMC
January 2021

Coronavirus Disease 2019: Initial High Resolution Computed Tomography Imaging Feature Analysis: Report of 7 Cases.

Jpn J Infect Dis 2020 Nov 29;73(6):459-461. Epub 2020 May 29.

Affiliated Hospital of Hangzhou Normal University, Zhejiang Province, China.

The number of reported cases of the new coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has increased since December 2019. The initial high-resolution computed tomography (HRCT) images of 7 patients diagnosed with COVID-19 in the Affiliated Hospital of Hangzhou Normal University, China, were collected and analyzed. The study showed that all patients had had close contact with other COVID-19 patients and presented with fever. The initial white blood cell counts of all patients were normal. Subsequently, the percentage of lymphocytes decreased in 3 patients. In all 7 patients with COVID-19, ground-glass opacity (GGO) was found in the HRCT images, mainly distributed in the subpleural region of the lungs. The HRCT scans of 6 patients showed bilateral lobar lesions, with mainly peripheral subpleural distribution; 1 patient, instead, showed unilateral lobar involvement. The right lung was more extensively involved than the left lung in 6 patients, and the lower lobe was more extensively involved than the upper lobe in 5 patients. The initial chest HRCT images of the lungs of the analyzed COVID-19 patients had specific characteristics. The typical manifestation at both lungs was an extensive GGO-type infiltrate, with thickened vascular bundles and focal center consolidation. Pleural effusion, bilateral hilar, and mediastinal lymphadenopathy were rare.
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http://dx.doi.org/10.7883/yoken.JJID.2020.098DOI Listing
November 2020

Molecular basis for the functions of dominantly active Y35N and inactive D60K Rheb mutants in mTORC1 signaling.

J Mol Cell Biol 2020 09;12(9):741-744

State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

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http://dx.doi.org/10.1093/jmcb/mjaa025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749741PMC
September 2020

Transcription profiles of oocytes during maturation and embryos during preimplantation development in vivo in the goat.

Reprod Fertil Dev 2020 Apr;32(7):714-725

Anhui Province Key Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; and Corresponding authors. Emails:

RNA sequencing performed on goat matured oocytes and preimplantation embryos generated invivo enabled us to define the transcriptome for goat preimplantation embryo development. The largest proportion of changes in gene expression in goat was found at the 16-cell stage, not as previously defined at the 8-cell stage, and is later than in other mammalian species. In all, 6482 genes were identified to be significantly differentially expressed across all consecutive developmental stage comparisons, and the important signalling pathways involved in each development transition were determined. In addition, we identified genes that appear to be transcribed only at a specific stage of development. Using weighted gene coexpression network analysis, we found nine stage-specific modules of coexpressed genes that represent the corresponding stage of development. Furthermore, we identified conserved key members (or hub genes) of the goat transcriptional networks. Their association with other embryo genes suggests that they may have important regulatory roles in embryo development. Our cross-mammalian species transcriptomic comparisons demonstrate both conserved and goat-specific features of preimplantation development.
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http://dx.doi.org/10.1071/RD19391DOI Listing
April 2020

The efficacy of transcranial alternating current stimulation for treating post-stroke depression: Study Protocol Clinical Trial (SPIRIT Compliant).

Medicine (Baltimore) 2020 Apr;99(16):e19671

Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX.

Background: The treatment of post-stroke depression (PSD) with anti-depressant drugs is partly practical. Transcranial alternating current stimulation (tACS) offers the potential for a novel treatment modality for adult patients with PSD. In this study, we will assess the efficacy and safety of tACS for treating PSD and explore its effect on gamma and beta-oscillations involving in emotional regulation.

Methods: The prospective study is an 8-week, double-blind, randomized, placebo-controlled trial. Seventy eligible participants with mild to moderate PSD aged between 18 years and 70 years will be recruited and randomly assigned to either active tACS intervention group or sham group. Daily 40-minute, 77.5-Hz, 15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4), and an additional 4-week observational period (week 8) will be followed up. The primary outcome is the proportion of participants having an improvement at week 8 according to the Hamilton Depression Rating Scale 17-Item (HAMD-17) score, including the proportion of participants having a decrease of ≥ 50% in HAMD-17 score or clinical recovery (HAMD-17 score ≤ 7). Secondary outcomes include neurological function, independence level, activities of daily living, disease severity, anxiety, and cognitive function. The exploratory outcomes are gamma and beta-oscillations assessed at baseline, week 4, and week 8. Data will be analyzed by logistical regression analyses and mixed-effects models.

Discussion: The study will be the first randomized controlled trial to evaluate the efficacy and safety of tACS at a 77.5-Hz frequency and 15-mA current in reducing depressive severity in patients with PSD. The results of the study will present a base for future studies on the tACS in PSD and its possible mechanism.

Trial Registration Number: NCT03903068, pre-results.
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http://dx.doi.org/10.1097/MD.0000000000019671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220515PMC
April 2020

Molecular mechanism of the dual regulatory roles of ATP on the αγ heterodimer of human NAD-dependent isocitrate dehydrogenase.

Sci Rep 2020 04 10;10(1):6225. Epub 2020 Apr 10.

State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai, 200031, China.

Human NAD-dependent isocitrate dehydrogenase (NAD-IDH) is responsible for the catalytic conversion of isocitrate into α-ketoglutarate in the Krebs cycle. This enzyme exists as the αβγ heterotetramer composed of the αβ and αγ heterodimers. Our previous biochemical data showed that the αγ heterodimer and the holoenzyme can be activated by low concentrations of ATP but inhibited by high concentrations of ATP; however, the molecular mechanism was unknown. Here, we report the crystal structures of the αγ heterodimer with ATP binding only to the allosteric site (αγ) and to both the allosteric site and the active site (αγ). Structural data show that ATP at low concentrations can mimic ADP to bind to the allosteric site, which stabilizes CIT binding and leads the enzyme to adopt an active conformation, revealing why the enzyme can be activated by low concentrations of ATP. On the other hand, at high concentrations ATP is competitive with NAD for binding to the catalytic site. In addition, our biochemical data show that high concentrations of ATP promote the formation of metal ion-ATP chelates. This reduces the concentration of free metal ion available for the catalytic reaction, and thus further inhibits the enzymatic activity. The combination of these two effects accounts for the inhibition of the enzyme at high concentrations of ATP. Taken together, our structural and biochemical data reveal the molecular mechanism for the dual regulatory roles of ATP on the αγ heterodimer of human NAD-IDH.
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http://dx.doi.org/10.1038/s41598-020-63425-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148312PMC
April 2020

Convergent syndromic atrophy of pain and emotional systems in patients with irritable bowel syndrome and depressive symptoms.

Neurosci Lett 2020 04 25;723:134865. Epub 2020 Feb 25.

Department of Radiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China; Department of Radiology, Third Affiliated Hospital of Southern Medical University (Academy of Orthopedics Guangdong Province), Guangzhou, Guangdong, China. Electronic address:

Irritable bowel syndrome (IBS) is a brain-gut disorder that is often accompanied by psychiatric comorbidities, particularly depression. However, the neuroanatomical substrates of IBS with depressive symptoms (DEP-IBS) and how depressive symptoms and brain morphology modulate IBS symptoms remain unknown. In this study, structural MRI data were processed using a voxel-based morphometry technique and one-way analysis of covariance (ANCOVA) and post-hoc t-tests were performed to compare gray matter volume (GMV) among 28 patients with DEP-IBS, 21 patients with IBS who lacked depressive symptoms (nDEP-IBS), and 36 healthy controls (HC). Correlation and mediation analyses were performed to evaluate the relationship between differing GMV in DEP-IBS and clinical variables. We found that GMV in the bilateral prefrontal, insular, and dorsal striatal areas, as well as the left temporal pole, were significantly lower in the DEP-IBS group than in the HC group. Moreover, compared with the nDEP-IBS group, the DEP-IBS group exhibited decreased GMV in the bilateral medial, dorsolateral prefrontal, and orbitofrontal cortices, bilateral dorsal striatum, and left insular cortices. Correlation analysis revealed that GMV in these atrophic brain areas of the DEP-IBS group was negatively correlated with depression, gastrointestinal symptoms, and disease duration. Our results further revealed that depressive symptoms served as a mediator between gastrointestinal symptoms and GMV in the left insula, right medial prefrontal cortex, and right middle frontal gyrus, while gastrointestinal symptoms served as a mediator between depression and GMV in these regions. Our results suggest convergent syndromic atrophy in the pain and emotional systems of patients with DEP-IBS.
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http://dx.doi.org/10.1016/j.neulet.2020.134865DOI Listing
April 2020

Probable risk factors of internal jugular vein stenosis in Chinese patients-A real-world cohort study.

Clin Neurol Neurosurg 2020 04 13;191:105678. Epub 2020 Jan 13.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China; Advanced Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Department of China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Objectives: Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age.

Results: A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ± 15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others.

Conclusion: This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.
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http://dx.doi.org/10.1016/j.clineuro.2020.105678DOI Listing
April 2020

Comparing hepatic steatosis distribution patterns between non-alcoholic fatty liver disease and fatty liver disease with chronic hepatitis B by second-harmonic generation/two-photon excited fluorescence method.

Ann Hepatol 2020 May - Jun;19(3):313-319. Epub 2019 Dec 3.

Center for Translational Medicine, The Affiliated Hospital of Hangzhou Normal University, 126 Wenzhou Road, Building 18, Floor 5, Hangzhou 310015, Zhejiang Province, China; Department of Hepatology, The Affiliated Hospital of Hangzhou Normal University, 126 Wenzhou Road, Building 6, Floor 6, Hangzhou 310015, Zhejiang Province, China. Electronic address:

Introduction And Objectives: Hepatitis B virus (HBV) might be an etiological factor modulating fat distribution in steatotic livers. We aim to compare hepatic steatosis distribution patterns between NAFLD and FL&CHB patients with second-harmonic generation (SHG)/two-photon excited fluorescence (TPEF) method.

Patients And Methods: 42 patients with NAFLD, 46 with FL&CHB and 55 without steatosis were enrolled in the study. Overall and regional steatosis in liver sections were quantified by SHG/TPEF method. The accuracy of which was validated by pathologist evaluation and magnetic resonance spectroscopy (MRS). Difference in degree of overall and regional steatosis between NAFLD and FL&CHB groups was analyzed by Mann-Whitney U test. Multivariable linear regression analysis was used to model factors contributing to steatosis distribution.

Results: The hepatic steatosis measured by SHG/TPEF method was highly correlated with pathologist grading (r=0.83, p<0.001) and MRS measurement (r=0.82, p<0.001). The level of overall steatosis in FL&CHB group is significantly lower than that in NAFLD group (p<0.001). In NAFLD group, periportal region has significantly lower steatosis percentage than lobule region and overall region (p<0.001); while in FL&CHB group there is no difference among regions. The ratio of steatosis at periportal region to lobule region is significantly higher in FL&CHB group than that in NAFLD group (p<0.05). Multivariable linear regression analysis shows that HBV infection is the major contributing factor (β=0.322, p<0.01).

Conclusions: SHG/TPEF method is an accurate and objective method in hepatic steatosis quantification. By quantifying steatosis in different histological regions, we found steatosis distribution patterns are different between FL&CHB and NAFLD patients.
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http://dx.doi.org/10.1016/j.aohep.2019.11.003DOI Listing
June 2021
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