Publications by authors named "Fen Xie"

20 Publications

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Serum exosomes from young rats improve the reduced osteogenic differentiation of BMSCs in aged rats with osteoporosis after fatigue loading in vivo.

Stem Cell Res Ther 2021 07 27;12(1):424. Epub 2021 Jul 27.

National Clinical Research Center for Metabolic Diseases, Institute of Metabolism and Endocrinology, Central South University, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Background: Osteoporosis is a major public health concern for the elderly population and is characterized by fatigue load resulting in bone microdamage. The ability of bone mesenchymal stem cells (BMSCs) to repair bone microdamage diminishes with age, and the accumulation of bone microdamage increases the risk of osteoporotic fracture. There is a lack of effective means to promote the repair of bone microdamage in aged patients with osteoporosis. Exosomes have been shown to be related to the osteogenic differentiation of BMSCs. Here, we aimed to evaluate the changes in the osteogenic differentiation capacity of BMSCs in aged osteoporotic rats after fatigue loading and the treatment potential of serum exosomes from young rats.

Methods: The tibias of six aged osteoporotic rats were subjected to fatigue loading in vivo for 2 weeks, and the bone microdamage, microstructures, and mechanical properties were assessed. Subsequently, BMSCs were extracted to evaluate their proliferation and osteogenic differentiation abilities. In addition, the BMSCs of aged osteoporotic rats after fatigue loading were treated with serum exosomes from young rats under osteogenic induction conditions, and the expression of osteogenic-related miRNAs was quantified. The osteogenetic effects of miRNA-19b-3p in exosomes and the possible target protein PTEN was detected.

Results: Obvious bone microdamage at the fatigue load stress point, the bone microstructure and biomechanical properties were not obviously changed. A decreased osteogenic differentiation ability of BMSCs was observed after fatigue loading, while serum exosomes from young rats highly expressing miRNA-19b-3p improved the decreased osteogenic differentiation ability of BMSCs. Transfection with miRNA-19b-3p mimic could promote osteoblastic differentiation of BMSCs and decreased the expression of PTEN. After transfection of miRNA-19b-3p inhibitor, the promotional effect of exosomes on bone differentiation was weakened. Treatment with transfected exosomes increased the expression of PTEN.

Conclusion: Serum exosomes derived from young rats can improve the decreased osteogenic differentiation ability of BMSCs in aged rats with osteoporosis after fatigue loading and can provide a new treatment strategy for the repair of bone microdamage and prevention of fractures.
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http://dx.doi.org/10.1186/s13287-021-02449-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314589PMC
July 2021

The influence of white matter hyperintensity on cognitive impairment in Parkinson's disease.

Ann Clin Transl Neurol 2021 Sep 26;8(9):1917-1934. Epub 2021 Jul 26.

Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, 510282, P.R. China.

The aim of this meta-analysis was to review systematically and to identify the relationship between the severity and location of white matter hyperintensities (WMHs) and the degree of cognitive decline in patients with Parkinson's disease (PD). We searched the PubMed, EMBASE, Web of Science, Ovid, and Cochrane Library databases for clinical trials of the severity and location of WMHs on the degree of cognitive impairment in PD through October 2020. We conducted the survey to compare the association of WMH burden in patients with PD with mild cognitive impairment (PD-MCI) versus those with normal cognition (PD-NC) and in patients with PD with dementia (PDD) versus those with PD without dementia (PD-ND). Nine studies with PD-MCI versus PD-NC and 10 studies with PDD versus PD-ND comparisons were included. The WMH burden in PD-MCI patients was significantly different compared to that in PD-NC patients (standard mean difference, SMD = 0.39, 95% CI: 0.12 to 0.66, p = 0.005), while there was no correlation shown in the age-matched subgroup of the comparison. In addition, PDD patients had a significantly higher burden of WMHs (SMD = 0.8, 95% CI: 0.44 to 1.71, p < 0.0001), especially deep white matter hyperintensities (SMD = 0.54, 95% CI: 0.36 to 0.73, p < 0.00001) and periventricular hyperintensities (SMD = 0.70, 95% CI: 0.36 to 1.04, p < 0.0001), than PD-NC patients, regardless of the adjustment of age. WMHs might be imaging markers for cognitive impairment in PDD but not in PD-MCI, regardless of age, vascular risk factors, or race. Further prospective studies are needed to validate the conclusions.
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http://dx.doi.org/10.1002/acn3.51429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419402PMC
September 2021

Novel homozygous protein-truncating mutation of BBS9 identified in a Chinese consanguineous family with Bardet-Biedl syndrome.

Mol Genet Genomic Med 2021 Aug 2;9(8):e1731. Epub 2021 Jul 2.

Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Bardet-Biedl syndrome (BBS) is a rare and genetically heterogeneous disease with a broad spectrum of clinical features, including but not limited to rod-cone dystrophy, postaxial polydactyly, central obesity, intellectual disability, hypogonadism, and renal dysfunction. Twenty-one BBS (Bardet-Biedl syndrome) genes have been identified to date. There is minimal mutation information on BBS in Chinese populations and the exact pathogenic mechanism of the null mutation of BBS9 remains unknown.

Methods: A patient from a Chinese consanguineous family presented with polydactyly, truncal obesity, intellectual disability, genital anomaly, and retinitis pigmentosa was analyzed in this study. Blood DNA and RNA were extracted from the blood of the proband and the parents. The proband was screened for mutations by whole-exome sequencing. The likely pathogenic mutation detected in the proband was further confirmed by the Sanger sequence in the family. Real-time RT-PCR was used to measure the expression of BBS9 in the proband and the control.

Results: Targeted exome sequencing identified a novel homozygous null mutation (NM_198428.3: c.445C>T) in the 6th exon of the BBS9 gene in the proband and Sanger sequencing was used to validate the heterozygosity in the parents. The mutation was validated to induce the nonsense-mediated decay of BBS9 messenger RNAs by real-time RT-PCR.

Conclusions: The molecular findings helped to explain the clinical manifestations. The novel homozygous pathogenic variation expanded the mutational spectrum of the BBS9 gene in the Chinese population and will help to understand the pathogenic mechanism of BBS9 null mutation.
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http://dx.doi.org/10.1002/mgg3.1731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404240PMC
August 2021

Fibrinogen is an Independent Risk Factor for White Matter Hyperintensities in CADASIL but not in Sporadic Cerebral Small Vessel Disease Patients.

Aging Dis 2021 Jun 1;12(3):801-811. Epub 2021 Jun 1.

1Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangdong 510282, China.

The relationship between fibrinogen and white matter hyperintensities (WMHs) are inconsistent. Whether there are different relationships between WMHs and fibrinogen in disparate subtypes of cerebral small vessel disease (CSVD) remains unknown. Here, we investigated the roles of plasma fibrinogen in sporadic CSVD (sCSVD) and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients. We performed a cross-sectional study that included 74 CSVD patients (19 CADASIL and 55 sporadic) and 74 age- and gender-matched healthy controls (HCs). Plasma fibrinogen was determined, and the severity of WMHs in CSVD patients was rated according to Fazekas scales. Univariate analysis and ordinal logistic regression were performed to evaluate the relationship between fibrinogen and the severity of WMHs in CSVD. Both CADASIL and sCSVD patients showed significantly higher plasma fibrinogen levels than HCs. No significant difference in the plasma fibrinogen level was observed between CADASIL and sCSVD. Univariate analysis and ordinal logistic regression indicated that fibrinogen is an independent risk factor for the severity of WMHs in CADASIL patients (odds ratio [OR] =1.064; 95% Confidence interval (CI, 1.004-1.127); p =0.037). However, age (odds ratio [OR] =1.093; 95% CI (1.033-1.156); P = 0.002), but not fibrinogen (odds ratio [OR] =1.004; 95% CI (0.997-1.011); P=0.262), is an independent risk factor for the severity of WMHs in sCSVD patients. Our results suggest that high levels of plasma fibrinogen are associated with the severity of WMHs in CADASIL but not in sCSVD patients, indicating that the role of fibrinogen may be different in disparate subtypes of CSVD. A better understanding of fibrinogen may yield insights into the pathogenesis of CSVD.
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http://dx.doi.org/10.14336/AD.2020.1110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139197PMC
June 2021

Comparison of Chemical Constituents in Pseudostellariae Radix with Different Dosage Forms Based on HPLC-Q-Exactive Orbitrap/MS Combined with Multivariate Statistical Analysis.

Evid Based Complement Alternat Med 2021 8;2021:6644127. Epub 2021 May 8.

Department of Clinical Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi 214000, China.

Background: Pseudostellariae Radix (PR) is an important traditional Chinese herbal medicine with vast clinical consumptions, which has two different dosage forms, PR decoction pieces and PR formula granules. However, these two forms are bound to have an impact on the accumulation of the effective components in PR, so the effectiveness of clinical use cannot be guaranteed.

Objective: To determine the effective composition of PR.

Methods: In this research, PR decoction pieces and formula granules were collected, and their composition was detected by HPLC-Q-Exactive Orbitrap/MS; multivariate statistical analysis was used to distinguish differential metabolites between PR decoction pieces and formula granules.

Results: A clear cut difference in the composition of the two groups was observed. 98 differential chemical constituents could be identified in the positive mode, while 52 differential chemical compositions could be identified in the negative mode. The differential chemical compositions were mainly concentrated in flavonoids, organic acids, fatty acids, and amino acids and present different change rules, mainly involved in the isoquinoline alkaloid biosynthesis metabolic pathways.

Conclusions: This study provides basic information to reveal the influence law of different dosage forms on the metabolite synthesis and quality formation mechanism of PR.
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http://dx.doi.org/10.1155/2021/6644127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128553PMC
May 2021

HS attenuates oxidative stress via Nrf2/NF-κB signaling to regulate restenosis after percutaneous transluminal angioplasty.

Exp Biol Med (Maywood) 2021 01 30;246(2):226-239. Epub 2020 Sep 30.

Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Restenosis after angioplasty of peripheral arteries is a clinical problem involving oxidative stress. Hydrogen sulfide (HS) participates in oxidative stress regulation and activates nuclear factor erythroid 2-related factor 2 (Nrf2). This study investigated the effect of HS and Nrf2 on restenosis-induced arterial injury. Using an rat model of restenosis, we investigated whether HS inhibits restenosis after percutaneous transluminal angioplasty (PTA) and the oxidative stress-related mechanisms implicated therein. The involvement of Nrf2 was explored using Nrf2-shRNA. Neointimal formation and the deposition of elastic fibers were assessed histologically. Inflammatory cytokine secretion and the expression of proteins associated with oxidative stress and inflammation were evaluated. The artery of rats subjected to restenosis showed increased arterial intimal thickness, with prominent elastic fiber deposition. Sodium hydrosulfide (NaHS), an HS donor, counteracted these changes . Restenosis caused a decrease in anti-oxidative stress signaling. This phenomenon was inhibited by NaHS, but Nrf2-shRNA counteracted the effects of NaHS. In terms of inflammation, inflammatory cytokines were upregulated, whereas NaHS suppressed the induced inflammatory reaction. Similarly, Nrf2 downregulation blocked the effect of NaHS. studies using aortic endothelial and vascular smooth muscle cells isolated from experimental animals showed consistent results as those of studies, and the participation of the nuclear factor-kappa B signaling pathway was demonstrated. Collectively, HS played a role in regulating post-PTA restenosis by alleviating oxidative stress, modulating anti-oxidant defense, and targeting Nrf2-related pathways via nuclear factor-kappa B signaling.
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http://dx.doi.org/10.1177/1535370220961038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871122PMC
January 2021

Fetal bovine serum-derived exosomes regulate the adipogenic differentiation of human bone marrow mesenchymal stromal cells in a cross-species manner.

Differentiation 2020 Sep - Oct;115:11-21. Epub 2020 Jul 25.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China; National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, 410011, China; Hunan Provincial Key Laboratory of Metabolic Bone Diseases, Changsha, Hunan, 410011, China. Electronic address:

Fetal bovine serum (FBS) contains a large number of exosomes which may disturb the analysis of exosomes derived from cultured cells. We investigated the effect of FBS-derived exosomes (FBS-Exos) on the adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBM-MSCs) and the underlying molecular mechanism. The uptake of FBS-Exos by hBM-MSCs could be detected by the laser confocal microscopy, and the treatment of exosomes resulted in the decreased lipid droplet formation and reduced expression of genes associated with adipogenic differentiation of hBM-MSCs. miR-1246 was identified as an abundant microRNA in FBS-Exos by public sequencing data identification and RT-qPCR validation. Moreover, miR-1246 overexpression in hBM-MSCs led to decreased adipogenic differentiation level, while miR-1246 knockdown in FBS-Exos attenuated the inhibitory effect on the adipogenic differentiation. Our results indicate that FBS-Exos inhibit the adipogenic differentiation of hBM-MSCs in a cross-species manner and miR-1246 transferred by FBS-Exos partly contributes to this effect.
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http://dx.doi.org/10.1016/j.diff.2020.06.004DOI Listing
August 2021

Contra-Directional Expression of Plasma Superoxide Dismutase with Lipoprotein Cholesterol and High-Sensitivity C-reactive Protein as Important Markers of Parkinson's Disease Severity.

Front Aging Neurosci 2020 6;12:53. Epub 2020 Mar 6.

Department of Neurology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.

: Oxidative stress and inflammation play critical roles in the neuropathogenesis of PD. We aimed to evaluate oxidative stress and inflammation status by measuring serum superoxide dismutase (SOD) with lipoprotein cholesterol and high-sensitivity C-reactive protein (hsCRP) respectively in PD patients, and explore their correlation with the disease severity. : We performed a cross-sectional study that included 204 PD patients and 204 age-matched healthy controls (HCs). Plasma levels of SOD, hsCRP, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. A series of neuropsychological assessments were performed to rate the severity of PD. : The plasma levels of SOD (135.7 ± 20.14 vs. 147.2 ± 24.34, < 0.0001), total cholesterol, HDL-C and LDL-C in PD were significantly lower than those in HCs; the hsCRP level was remarkably increased in PD compared to HC (2.766 ± 3.242 vs. 1.637 ± 1.597, < 0.0001). The plasma SOD was negatively correlated with the hsCRP, while positively correlated with total cholesterol, HDL-C, and LDL-C in PD patients. The plasma SOD were negatively correlated with H&Y, total UPDRS, UPDRS (I), UPDRS (II), and UPDRS (III) scores, but positively correlated with MoCA and MMSE scores. Besides, hsCRP was negatively correlated with MoCA; while total cholesterol, HDL-C and LDL-C were positively correlated with the MoCA, respectively. : Our findings suggest that lower SOD along with cholesterol, HDL-C and LDL-C, and higher hsCRP levels might be important markers to assess the PD severity. A better understanding of SOD and hsCRP may yield insights into the pathogenesis of PD.
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http://dx.doi.org/10.3389/fnagi.2020.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068795PMC
March 2020

Structural basis for electron transport mechanism of complex I-like photosynthetic NAD(P)H dehydrogenase.

Nat Commun 2020 01 30;11(1):610. Epub 2020 Jan 30.

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

NAD(P)H dehydrogenase-like (NDH) complex NDH-1L of cyanobacteria plays a crucial role in cyclic electron flow (CEF) around photosystem I and respiration processes. NDH-1L couples the electron transport from ferredoxin (Fd) to plastoquinone (PQ) and proton pumping from cytoplasm to the lumen that drives the ATP production. NDH-1L-dependent CEF increases the ATP/NADPH ratio, and is therefore pivotal for oxygenic phototrophs to function under stress. Here we report two structures of NDH-1L from Thermosynechococcus elongatus BP-1, in complex with one Fd and an endogenous PQ, respectively. Our structures represent the complete model of cyanobacterial NDH-1L, revealing the binding manner of NDH-1L with Fd and PQ, as well as the structural elements crucial for proper functioning of the NDH-1L complex. Together, our data provides deep insights into the electron transport from Fd to PQ, and its coupling with proton translocation in NDH-1L.
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http://dx.doi.org/10.1038/s41467-020-14456-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992706PMC
January 2020

GDF-15 is associated with thrombus burden in patients with deep venous thrombosis.

Thromb Res 2020 03 21;187:148-153. Epub 2020 Jan 21.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Introduction: Growth differentiation factor-15 (GDF-15) has been identified as a predictor in cardiovascular diseases and acute pulmonary embolism. However, the association of GDF-15 and deep venous thrombosis (DVT) remains unclear. This study aimed to investigate levels of GDF-15 in patients with DVT, and determine its association with the thrombus burden.

Materials And Methods: 72 newly diagnosed DVT patients and 30 healthy volunteers were enrolled, and the levels of plasma GDF-15 were detected. To explore the relationship between GDF-15 and thrombus severity, we analyzed the thrombus burden and the association with pulmonary embolism of DVT patients. In vitro, the effect of GDF-15 on platelet aggregation and thrombin/antithrombin activity were investigated.

Results: We found that the mean levels of plasma GDF-15 in DVT patients were significantly higher than those in healthy controls (1448.78 ± 61.98 pg/ml VS 805.70 ± 112.95 pg/ml, P < 0.001). Furthermore, GDF-15 showed an increase with more venous segments with thrombus (P < 0.001), and the patients with higher levels of GDF-15 and more thrombus segments showed higher scores of Wells-PE and Geneva and increased incidence of pulmonary embolism (P < 0.05). In vitro, we confirmed that GDF-15 significantly reduced platelet aggregation induced by ADP and the effect was concentration-dependent (P < 0.001). However, GDF-15 showed no direct effect on thrombin and anti-thrombin activity.

Conclusions: Increased GDF-15 level was associated with more thrombus severity of DVT patients and GDF-15 could inhibit platelet aggregation induced by ADP in vitro. These findings suggest that GDF-15 might not only be an indicator for thrombus severity but also be a potential treatment target in DVT.
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http://dx.doi.org/10.1016/j.thromres.2020.01.022DOI Listing
March 2020

Plasma Lipoprotein-associated Phospholipase A2 and Superoxide Dismutase are Independent Predicators of Cognitive Impairment in Cerebral Small Vessel Disease Patients: Diagnosis and Assessment.

Aging Dis 2019 Aug 1;10(4):834-846. Epub 2019 Aug 1.

1Department of Neurology and.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and superoxide dismutase (SOD) are linked to regulating vascular/neuro-inflammation and stroke. Using a retrospective design, we investigated whether circulating Lp-PLA2 and SOD in cerebral small vessel disease (CSVD) patients were associated with cognitive impairment. Eighty-seven CSVD patients were recruited. Plasma Lp-PLA2 and SOD were determined, and cognitive status was measured by the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The severity of white matter hypoerintensities (WMHs) in CSVD patients was rated according to Fazekas scales, and Lp-PLA2/SOD levels and MMSE/MoCA were compared. Multiple linear regressions were used to evaluate the relationship between Lp-PLA2 and SOD and the cognitive impairment. Ordinal logistic regression and generalized linear models (OLRGLMs) were applied to confirm whether Lp-PLA2 and SOD are independent risk factors for cognitive impairment in CVSD. Lp-PLA2 and SOD with mild or severe cognitive impairment were lower than those with normal congnition. Lp-PLA2 and SOD in CSVD patients with severe WMHs were significantly lower than those with mild or moderate WMH lesions. We noted positive linear associations of Lp-PLA and SOD with cognitive impairment in CSVD, independent of LDL-C. OLRGLMs confirmed that Lp-PLA2 and SOD were independent risk factors of cognitive impairment in CSVD. Lp-PLA2 and SOD are independently associated with cognitive impairment and WMH lesion, and may be useful for the rapid evaluation of cognitive impairment in CSVD. Lp-PLA2/SOD are modifiable factors that may be considered as therapeutic targets for preventing cognitive impairment in CSVD.
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http://dx.doi.org/10.14336/AD.2019.0304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675532PMC
August 2019

[Risk factors for female pelvic organ prolapse and urinary incontinence].

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2018 Dec;43(12):1345-1350

Department of Rehabilitation Medicine, Third Xiangya Hospital, Central South University, Changsha 410013, China.

Objective: To explore the risk factors for and the pathogenic mechanisms of pelvic organ prolapse and urinary incontinence.
 Methods: A total of 2 668 females who completed pelvic floor functional detection from July 2014 to October 2015 in the Physical Examination Center of the Third Xiangya Hospital of Central South University. The patients were divide into 4 groups: an urinary incontinence group, an organ prolapse group, an organ prolapse with urinary incontinence group, and a normal group. We compared the age, BMI, menopause, gravidity and parity, delivery pattern, the coordination of pelvic floor and abdominal muscles among the 4 groups.
 Results: There were statistical differences in age and BMI values among the 4 groups (P<0.05).There were statistical differences in menopause rate, gravidity and parity history among the normal group and the other 3 groups (P<0.05), and between the organ prolapse group and the organ prolapse with urinary incontinence group (P<0.05). However, the urinary incontinence group was not statistically different from the organ prolapse group and the normal group (P>0.05). In the mode of delivery, there were statistical difference among the normal group and the other 3 groups (P<0.05), and between the organ prolapse group with urinary incontinence group and the organ prolapse or the urinary incontinence group (P<0.05). There was no significant difference between the urinary incontinence group and the organ prolapse group (P>0.05). Among the 4 groups, the normal group was the best one in coordination between pelvic floor and abdominal muscles, following by the organ prolapse group, the pelvic organ prolapse group and the urinary incontinence group.
 Conclusion: Aging, menopause, number of pregnancies and delivery, BMI, and mode of delivery all affect the occurrence of pelvic organ prolapse and urinary incontinence. Females with urinary incontinence or organ prolapse are not good in coordination between the pelvic floor and abdominal muscles.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2018.12.010DOI Listing
December 2018

Advances in the Research of Risk Factors and Prodromal Biomarkers of Parkinson's Disease.

ACS Chem Neurosci 2019 02 11;10(2):973-990. Epub 2019 Jan 11.

Department of Neurology , Zhujiang Hospital of Southern Medical University , Gongye Road 253 , Guangzhou , Guangdong 510280 , P. R. China.

Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. With the advent of an aging population and improving life expectancy worldwide, the number of PD patients is expected to increase, which may lead to an urgent need for effective preventive and diagnostic strategies for PD. Although there is increasing research regarding the pathogenesis of PD, there is limited knowledge regarding the prevention of PD. Moreover, the diagnosis of PD depends on clinical criteria, which require the occurrence of bradykinesia and at least one symptom of rest tremor or rigidity. However, converging evidence from clinical, genetic, neuropathological, and imaging studies suggests the initiation of PD-specific pathology prior to the initial presentation of these classical motor clinical features by years or decades. This latent stage of neurodegeneration in PD is a particularly important stage for effective neuroprotective therapies, which might retard the progression or prevent the onset of PD. Therefore, the exploration of risk factors and premotor biomarkers is not only crucial to the early diagnosis of PD but is also helpful in the development of effective neuroprotection and health care strategies for appropriate populations at risk for PD. In this review, we searched and summarized ∼249 researches and 31 reviews focusing on the risk factors and prodromal biomarkers of PD and published in MEDLINE.
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http://dx.doi.org/10.1021/acschemneuro.8b00520DOI Listing
February 2019

Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

Parkinsonism Relat Disord 2018 07 19;52:37-42. Epub 2018 Mar 19.

Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address:

Introduction: Progressive supranuclear palsy (PSP) was previously thought as a cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density cholesterol lipoprotein-C (LDL-C) are known to play critical roles in Parkinsonism, it is unknown whether they can be used as markers to distinguish PSP patients from healthy subjects and to determine disease severity.

Methods: We conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of 40 patients with PSP and 40 healthy age-matched controls. An extended battery of motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE), was used to evaluate the disease severity. Receiver operating characteristic (ROC) curves were adopted to assess the prognostic accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects.

Results: Patients with PSP exhibited significantly higher plasma levels of Cys C and lower LDL-C. The levels of plasma Cys C were positively and inversely correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for the combination of Cys C and LDL-C yielded a better accuracy for distinguishing PSP from healthy subjects than the separate curves for each parameter.

Conclusions: Plasma Cys C and LDL-C may be valuable screening tools for differentiating PSP from healthy subjects; while they could be useful for the PSP intensifies and severity evaluation. A better understanding of Cys C and LDL-C may yield insights into the pathogenesis of PSP.
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http://dx.doi.org/10.1016/j.parkreldis.2018.03.014DOI Listing
July 2018

Microstructural properties of trabecular bone autografts: comparison of men and women with and without osteoporosis.

Arch Osteoporos 2018 03 5;13(1):18. Epub 2018 Mar 5.

Department of Endocrinology and Metabolism, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Disease, The Second XiangYa Hospital, Central South University, 139 Renmin Middle Road, Changsha, 410011, China.

The microstructure of autologous bone grafts from men over 50 years old and postmenopausal women undergoing spinal fusion were evaluated using micro-CT. We demonstrated postmenopausal women, especially those with osteoporosis (OP) presented more serious microarchitectural deterioration of bone grafts.

Purpose: This study was undertaken to determine microstructural properties of cancellous bone used as autologous bone grafts from osteoporosis patients undergoing lumbar fusion by comparing microstructural indices to controls.

Methods: Cancellous bone specimens from spinous processes were obtained from 41 postmenopausal women (osteoporosis women, n = 19; controls, n = 22) and 26 men over 50 years old (osteoporosis men, n = 8; controls, n = 18) during lumbar fusion surgery. The microstructural parameters were measured using micro-CT.

Results: Significant difference in bone volume fraction (BV/TV), specific bone surface (BS/BV), trabecular thickness (Tb.Th), and structure model index (SMI) value existed between postmenopausal women with OP and controls. Significant difference in trabecular number (Tb.N) existed between men over 50 years old with OP and controls. Postmenopausal women exhibited lower BV/TV, Tb.Th, and higher SMI value than men over 50 years old. Postmenopausal women with OP exhibited lower BV/TV, Tb.Th, and higher BS/BV than men over 50 years old with OP.

Conclusions: Post-menopausal women and older men with OP have worse bone quality in autografts than non-osteoporotic men and women. Postmenopausal women with OP presented serious microarchitectural deterioration in older population.
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http://dx.doi.org/10.1007/s11657-018-0422-zDOI Listing
March 2018

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Liraglutide Alters Bone Marrow Exosome-Mediated miRNA Signal Pathways in Ovariectomized Rats with Type 2 Diabetes.

Med Sci Monit 2017 Nov 14;23:5410-5419. Epub 2017 Nov 14.

Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland).

BACKGROUND Compared with normal postmenopausal women, estrogen deficiency and hyperglycemia in postmenopausal women with type 2 diabetes (T2DM) lead to more severe bone property degradation. Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been reported to improve bone condition among people with T2DM but the precise mechanisms remain unclear. Exosomes work as mediators in cell-to-cell communication, delivering functional miRNAs between cells. We aimed to explore the role of exosomes in T2DM-related bone metabolic disorders and the bone protective mechanisms of liraglutide. MATERIAL AND METHODS We made comparative analyses of bone marrow-derived exosomal miRNAs from ovariectomized (OVX) control rats, OVX + T2DM rats, and OVX + T2DM + liraglutide-treated rats. miRNA profiles were generated using high-throughput sequencing. Target gene prediction and pathway analysis were performed to investigate the signal pathway alterations. Three miRNAs were randomly chosen to validate their absolute expression levels by real-time quantitative PCR. RESULTS Bone marrow-derived exosomal miRNAs were different with respect to miRNA numbers, species, and expression levels. miRNA spectra varied under T2DM condition and after liraglutide treatment. By bioinformatics analysis, we found T2DM and liraglutide administration lead to significant changes in exosomal miRNAs which targeted to insulin secretion and insulin-signaling pathway. Wnt signaling pathway alteration was the critical point regarding bone metabolism. CONCLUSIONS Our findings show the selective packaging of functional miRNA cargoes into exosomes due to T2DM and liraglutide treatment. Bone marrow exosome-mediated Wnt signaling pathway alteration may play a part in the bone protective effect of liraglutide.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699170PMC
http://dx.doi.org/10.12659/msm.906603DOI Listing
November 2017

Two-level time-domain decomposition based distributed method for numerical solutions of pharmacokinetic models.

Comput Biol Med 2011 Apr;41(4):221-7

School of IoT Engineering, Jiangnan University, Wuxi 214122, Jiangsu Province, China.

In order to predict variations of drug concentration during a given period of time, numerical solutions of pharmacokinetic models need to be obtained efficiently. Analytical solutions of linear pharmacokinetic models are usually obtained using the Laplace transform and inverse Laplace tables. The derivations of solutions to complex nonlinear models are tedious, and such solution process may be difficult to implement as a robust software code. For nonlinear models, the fourth-order Runge-Kutta (RK4) is the most classical numerical method in obtaining approximate numerical solutions, which is impossible to be implemented in distributed computing environments without much modification. The reason is that numerical solutions obtained by using RK4 can only be computed in sequential time steps. In this paper, time-domain decomposition methods are adapted for nonlinear pharmacokinetic models. The numerical Inverse Laplace method for PharmacoKinetic models (ILPK) is implemented to solve pharmacokinetic models with iterative inverse Laplace transform in each time interval. The distributed ILPK algorithm, which is based on a two-level time-domain decomposition concept, is proposed to improve its efficiency. Solutions on the coarser temporal mesh at the top level are obtained one by one, and then those on the finer temporal mesh at the bottom level are calculated concurrently by using those initial solutions that have been obtained at the top level decomposition. Accuracy and efficiency of the proposed algorithm and its distributed equivalent are investigated by using several test models. Results indicate that the ILPK algorithm and its distributed equivalent are good candidates for both linear and nonlinear pharmacokinetic models.
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http://dx.doi.org/10.1016/j.compbiomed.2011.02.003DOI Listing
April 2011

Direct electrochemistry and electrocatalysis of heme proteins on SWCNTs-CTAB modified electrodes.

Talanta 2009 Feb 19;77(4):1343-50. Epub 2008 Sep 19.

College of Chemistry and Chemical Engineering, Hubei University, Wuhan, PR China.

Direct electrochemistry and electrocatalysis of heme proteins including hemoglobin (Hb), myoglobin (Mb) and horseradish peroxidase (HRP) were studied with the protein incorporated single walled carbon nanotubes (SWCNTs)-cetylramethylammonium bromide (CTAB) nanocomposite film modified glassy carbon electrodes (GCEs). The incorporated heme proteins were characterized with Fourier transform infrared spectroscopy (FTIR), ultraviolet visible (UV) spectroscopy, atomic force microscopy (AFM) and electrochemistry, indicating the heme proteins in SWCNTs-CTAB nanocomposite films keep their secondary structure similar to their native states. The direct electron transfer between the heme proteins in SWCNTs-CTAB films and GCE was investigated. The electrochemical parameters such as formal potentials and apparent heterogeneous electrontransfer rate constants (k(s)) were estimated by square wave voltammetry with nonlinear regression analysis. The heme protein-SWCNT-CTAB electrodes show excellent electrocatalytic activities for the reduction of H(2)O(2) and NO(2)(-), which have been utilized to determine the concentrations of H(2)O(2) and NO(2)(-).
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http://dx.doi.org/10.1016/j.talanta.2008.09.019DOI Listing
February 2009

Electrochemical study of brucine on an electrode modified with magnetic carbon-coated nickel nanoparticles.

Anal Bioanal Chem 2007 Feb 16;387(3):933-9. Epub 2006 Dec 16.

Ministry-of-Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, School of Chemistry and Chemical Engineering, Hubei University, Wuhan, 430062, People's Republic of China.

A novel type of glassy carbon electrode modified with magnetic carbon-coated nickel nanoparticles (C-Ni/GCE) was fabricated and the electrochemical properties of brucine were studied using it. The carbon-coated nickel nanoparticles showed excellent electrocatalytic activity for the redox of brucine and an enhanced electron transfer rate. The electrochemical behavior of brucine on the C-Ni/GCE was explored by cyclic voltammetry (CV), and a redox mechanism for brucine was proposed. A series of electrochemical parameters were calculated for brucine by CV and controlled-potential electrolysis. The C-Ni/GCE showed good sensitivity, selectivity and stability, and was applied to determine the concentration of brucine. The differential pulse voltammetry (DPV) response of the C-Ni/GCE showed that the catalytic current was linear with the concentration of brucine in the range of 4.7 x 10(-8) to 2.4 x 10(-4) mol l(-1), with a correlation coefficient of 0.998. The detection limit was 1.4 x 10(-8) mol l(-1).
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http://dx.doi.org/10.1007/s00216-006-0984-2DOI Listing
February 2007

[Studies on second metabolites of an endophytic fungus (II)].

Zhongguo Zhong Yao Za Zhi 2002 Mar;27(3):204-6

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.

Objective: To study the chemical constituents from the cultured mycelia of a fungus Cephalosporium which accelerate the growth of plant.

Method: The constituents were isolated by column chromatography and identified by advanced physical and spectral analysis.

Result: Eleven compounds including 3-isopropyl-6-(1-methylpropyl) piperazine-2,5-dione(I), choline sulfate(II), 2-[(2-hydroxy tetracosanoyl) amino]-1,3,4-octadecatriol(III) were isolated and identified.

Conclusion: Compound I, II were isolated from Cephalosporium genus for the first time.
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March 2002
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