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Fang Li - Top 30 Publications

Subclinical left ventricular systolic dysfunction detected by two-dimensional speckle tracking echocardiography in patients with pheochromocytoma and paraganglioma and preserved ejection fraction.

Excessive catecholamine leads to pressure overload and left ventricular (LV) remodeling. The goal of this study was to explore subclinical LV systolic dysfunction and the mechanism of preserved left ventricular ejection fraction (LVEF) in patients with pheochromocytoma and paraganglioma using two-dimensional speckle tracking echocardiography.

Luminol, horseradish peroxidase, and glucose oxidase ternary functionalized graphene oxide for ultrasensitive glucose sensing.

Luminol, horseradish peroxidase (HRP), and glucose oxidase (GOx) ternary functionalized graphene oxide (HRP/GOx-luminol-GO) with excellent chemiluminescence (CL) activity and specific enzymatic property was prepared via a simple and general strategy for the first time. In this approach, luminol functionalized GO (luminol-GO) was prepared by gently stirring GO with luminol. Then HRP and GOx were further co-immobilized onto the surface of luminol-GO by storing HRP and GOx with luminol-GO at 4 °C overnight, to form HRP/GOx-luminol-GO bionanocomposites. The synthesized HRP/GOx-luminol-GO could react with H2O2 generated from GOx catalyzed glucose oxidization reaction, to produce strong CL emission in the presence of co-immobilized HRP. Thus, we developed an ultrasensitive, homogeneous, reagentless, selective, and simple CL sensing system for glucose detection. The resulting biosensors exhibited ultra-wide linear range from 5.0 nM to 5.0 mM, and an ultra-low detection limit of 1.2 nM, which was more than 3 orders of magnitude lower than previously reported methods. Furthermore, the sensing system was successfully applied for the detection of glucose in human blood samples.

Highly active graphene oxide-supported cobalt single-ion catalyst for chemiluminescence reaction.

Graphene or graphene oxide (GO)-supported metallic nanoparticles and single metal atom as potentially effective cata-lysts for chemical reactions have recently received extensive research interests. However, metal utilization in nanopar-ticle catalysts is limited and metal atoms are readily to drift on graphene surface and consequently form aggregated large particles, making practical applications limited. Here, we report metal ions directly immobilized on GO as a novel GO-supported single-ion catalyst for chemiluminecence (CL) reactions. It is found that GO-supported cobalt ions with good stability could catalyze strongly luminol-H2O2 and lucigenin-H2O2 CL reactions, accompanied by dramatically enhanced CL emission. Theoretical studies reveal that the coupling between Co2+ and GO induces effective polarization charges, improving chemical activity of reaction site, which promotes the generation of intermediate radicals and ac-celerates the CL reactions. This work may be generalized to other GO-supported metal ions as catalysts for a wide range of chemical reactions. The developed GO-supported cobalt single-ion nanocomposites as nanointerfaces may find future applications in CL bioassays.

Voxel-based comparison of brain glucose metabolism between patients with Cushing's disease and healthy subjects.

Cognitive impairment and psychiatric symptoms are common in patients with Cushing's disease (CD) owing to elevated levels of glucocorticoids. Molecular neuroimaging methods may help to detect changes in the brain of patients with CD. The aim of this study was to investigate the characteristics of brain metabolism and its association with serum cortisol level in CD. We compared brain metabolism, as measured using [(18)F]-fluorodeoxyglucose positron emission tomography (FDG PET), between 92 patients with CD and 118 normal subjects on a voxel-wise basis. Pearson correlation was performed to evaluate the association between cerebral FDG uptake and serum cortisol level in patients with CD. We demonstrated that certain brain regions in patients with CD showed significantly increased FDG uptake, including the basal ganglia, anteromedial temporal lobe, thalamus, precentral cortex, and cerebellum. The clusters that demonstrated significantly decreased uptake were mainly located in the medial and lateral frontal cortex, superior and inferior parietal lobule, medial occipital cortex, and insular cortex. The metabolic rate of the majority of these regions was found to be significantly correlated with the serum cortisol level. Our findings may help to explain the underlying mechanisms of cognitive impairment and psychiatric symptoms in patients exposed to excessive glucocorticoids and evaluate the efficacy of treatments during follow-up.

Inhibition of IL-8-mediated endothelial adhesion, VSMCs proliferation and migration by siRNA-TMEM98 suggests TMEM98's emerging role in atherosclerosis.

Transmembrane protein 98 (TMEM98), known as a novel gene related to lung cancer, hepatocellular carcinoma, differentiation of T helper 1 cells and normal eye development, has no defined role reported in terms of atherosclerosis (AS). To investigate the potential involvement of TMEM98 during AS processes, its obvious secretion and expression has been initially characterized in hyperlipidemia patients' serum and AS mice's serum respectively. We then explored the possible role of TMEM98 in the pathogenesis of AS in vitro. IL-8, a pro-atherogenesis cytokine, was used to induce the expression of TMEM98 in both endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). Collectively, TMEM98 expression significantly increased in ECs and VSMCs, both induced by IL-8. Additionally, the adhesion ability of monocytes to ECs as well as the proliferation and migration of VSMCs were all decreased after siRNA-TMEM98 treatment. Furthermore, siRNA-TMEM98 dramatically inhibited the expression of ICAM-1 in ECs and the expression of p-AKT, p-GSK3β and Cyclin D1 from VSMCs, and AKT agonist partially restored the proliferation and migration of VSMC after siRNA-TMEM98 treatment. Taken together, siRNA-TMEM98 inhibits IL-8 mediated EC adhesion by down-regulating the expression of ICAM-1. Additionally, it also hinders the proliferation and migration of VSMCs through suppressing the AKT/GSK3β/Cyclin D1 signaling pathway. Our study provides sufficient evidence to support that TMEM98 could be a novel gene associated with AS for the first time.

Posterior Mediastinal, Intraspinal, Intradural, Intramedullary Lipoma through a Kovalevsky Canal in the Thoracic Spine.

Endothelin-1 promotes human germinal vesicle-stage oocyte maturation by downregulating connexin-26 expression in cumulus cells.

Does endothelin-1 (ET-1) promote human oocyte maturation and by what mechanism?

Is it necessary to perform prehabilitation exercise for patients undergoing total knee arthroplasty: meta-analysis of randomized controlled trials.

This study was designed to test whether it is necessary to perform prehabilitation exercise for patients undergoing total knee arthroplasty (TKA).

Clinical Values of Combined Diffused Optical Tomography and PET-CT in the Diagnosis of Breast Cancer.

Objective To investigate the clinical values of combined diffused optical tomography (DOT) combined positron emission tomography-computed tomography (PET-CT) in the diagnosis of breast cancer. Methods We performed DOT and PET-CT examinations in 38 patients with 40 lesions and compared these images with the pathological results to analyze the sensitivity,specificity,accuracy,positive predictive value,and negative predictive value of these two techniques and their combination.Results The sensitivity,specificity,accuracy,positive predictive value,and negative predictive value in diagnosing breast cancer were 78.26%,76.47%,77.50%,72.22%,and 81.81% for DOT,86.96%,82.35%,85.00%,86.96%,and 82.35% for PET-CT,and 86.96%,94.12%,90.00%,95.23%,and 84.21% for the combination of PET-CT and DOT.Conclusions DOT and PET-CT are both effective diagnostic methods for breast cancer.Combined DOT and PET-CT can improve the diagnostic efficacy in terms of specificity,positive predictive value,and accuracy.

Positron Emission Tomography Using a GRPR Antagonist (68)Ga-RM26 in Healthy Volunteers and Prostate Cancer Patients.

This study was designed to study the safety, biodistribution, radiation dosimetry of a gastrin-releasing peptide receptor (GRPR) antagonist positron emission tomography (PET) tracer (68)Ga-RM26, to assess its clinical diagnostic value in prostate cancer patients, and to perform a direct comparison between GRPR antagonist (68)Ga-RM26 and agonist (68)Ga-BBN. Methods: Five healthy volunteers were enrolled to validate the safety of (68)Ga-RM26 and calculate dosimetry. A total of 28 patients with prostate cancer (17 newly diagnosed and 11 post therapy) were recruited with written informed consent. All the cancer patients underwent PET/CT scans at 15-30 min after intravenous injection of 1.85 MBq (0.05 mCi) per kilogram body weight of (68)Ga-RM26. Among them, 22 patients (11 newly diagnosed and 11 post therapy) accepted (68)Ga-BBN PET/CT for comparison within 1 week. (99m)Tc-MDP bone scans were performed within 2 weeks for comparison. GRPR immunohistochemical staining of tumor samples was performed. Results: The administration of (68)Ga-M26 was well tolerated by all subjects with no adverse symptoms being noticed or reported during the whole procedure and 2 weeks follow up. The total effective dose equivalent (EDE) and effective dose (ED) were 0.0912 ± 0.0140 and 0.0657 ± 0.0124 mSv/MBq, respectively. In the 17 patients with newly diagnosed prostate cancer, (68)Ga-RM26 PET/CT showed positive prostate-confined findings in 15 tumors with SUVmax of 6.49 ± 2.37. In the 11 patients underwent prostatectomy or brachytherapy with/without androgen deprivation therapy (ADT), (68)Ga-RM26 PET/CT detected 8 metastatic lymph nodes in three patients with SUVmax of 4.28 ± 1.25, and 21 bone lesions in 8 patients with SUVmax of 3.90 ± 3.07. Compared with (68)Ga-RM26 PET/CT, GRPR agonist (68)Ga-BBN PET/CT detected less primary lesions and lymph node metastases as well as lower tracer accumulation. There was a significant positive correlation between SUV derived from (68)Ga-RM26 PET and the expression level of GRPR (P < 0.001). Conclusion: This study indicates the safety and significant efficiency of GRPR antagonist (68)Ga-RM26. (68)Ga-RM26 PET/CT would have remarkable value in detecting both primary prostate cancer and metastasis. (68)Ga-RM26 is also expected to be better than GRPR agonist as an imaging marker to evaluate GRPR expression in prostate cancer.

Endocrinal description of two Chinese Kennedy's disease pedigrees.

Kennedy's disease (KD), also known as X-linked spinal and bulbar muscular atrophy (SBMA), is caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the first exon of the androgen receptor (AR) gene. KD is a late-onset neural-endocrinal disease that is characterized by the degeneration of motor neurons in the brainstem and spinal cord. In addition, partial androgen insensitivity is an important manifestation of KD. Here, we report two Chinese KD pedigrees that reveal the clinical and genetic manifestations and fully elaborate the endocrinal characteristics of KD patients. The proband in pedigree 1 was referred to an endocrinologist for gynaecomastia and sexual dysfunction. A gene analysis of this patient revealed that there were 53 CAG repeats in the AR gene. A family survey identified an additional two KD patients in pedigree 1. The proband in pedigree 2 was diagnosed by a neurologist and did not have gynaecomastia or sexual dysfunction. A family survey identified an additional subclinical patient, and both patients exhibited partial androgen insensitivity at a hormonal level. We therefore suggest that a family survey and hormone tests should be routinely performed in KD patients and that physicians should increase their understanding of the different symptoms of KD to achieve correct diagnoses in affected patients.

Migration Stress, Poor Mental Health, and Engagement in Sex with High-Risk Partners: A Mediation Modeling Analysis of Data from Rural-to-Urban Migrants in China.

There is a growing need for better understanding of mechanisms underpinning the relationship between migration stress and HIV risk behaviors for the development of HIV prevention and control policy.

Preclinical PET imaging of HIP/PAP using 1'-(18)F-fluoroethyl-β-D-lactose.

This study aims at preclinical evaluation of a recently reported lactose analogue, 1'-(18)F-fluoroethyl-β-D-lactose ((18)F-FEL), in binding to hepatocarcinoma-intestine-pancreas and pancreatitis-associated protein (HIP/PAP) in vitro and in vivo.

Pertussis Outbreak in a Primary School in China: Infection and Transmission of the Macrolide-Resistant Bordetella pertussis.

A pertussis outbreak was studied in a primary school in Xi'an, China in March, 2016. The school consisted of 536 pupils aged 6 to 12 years who were divided into 12 classes of 6 grades (2 classes for each grade). The identified index case was an 11-year-old girl at Class 2 of grade 5.

Esophageal cancer in Kenya.

Kenya belongs to a high incidence region known as Africa's esophageal cancer (EC) corridor. It has one of the highest incidence rates of EC worldwide, but research on EC in Kenya has gone highly unnoticed. EC in Kenya is unique in its high percentage of young cases (< 30 years of age). In this review, we show the current status of EC in the country. We mainly focus on significant risk factors such as alcohol drinking, genetic factors, malnutrition and hot food/drink. Future directions in the study and prevention of EC in Kenya are also discussed.

Primary Pericardial Angiosarcoma Shown on FDG PET/CT.

A 63-year-old woman had persistent bloody pericardial effusion. Tuberculous pericarditis was initially suspected, but empirical antituberculosis therapy was futile. FDG PET/CT study revealed abnormal FDG activity in multiple parts of the pericardium, especially along with aorta and main pulmonary artery, and in the left atrium. However, there was no abnormal activity in other parts of the body. Histopathologic examination revealed primary pericardial angiosarcoma.

Anterior cingulate cortex involved in social food-foraging decision-making strategies of rats.

Decision making as a complex cognitive process involves assessing risk, reward, and costs. Typically, it has been studied in nonsocial contexts. We have developed a novel laboratory model used with rodents to detect food-foraging decision-making strategies in different social settings. However, the brain regions that mediate these behaviors are not well identified. Substantial evidence shows that the anterior cingulate cortex (ACC) participates in evaluation of social information and in decision making.

Evaluate the Efficacy of Electroacupuncture Therapy on Abdominal Fat in Obese Women by Using Magnetic Resonance Imaging.

To evaluate the efficacy of electroacupuncture (EA) therapy on abdominal fat in obese women by using magnetic resonance imaging(MRI).

Cryo-EM structure of porcine delta coronavirus spike protein in the pre-fusion state.

Coronavirus spike proteins from different genera are divergent, although they all mediate coronavirus entry into cells by binding to host receptors and fusing viral and cell membranes. Here we determined the cryo-EM structure of porcine delta coronavirus (PdCoV) spike protein at 3.3-angstrom resolution. The trimeric protein contains three receptor-binding S1 subunits that tightly pack into a crown-like structure and three membrane-fusion S2 subunits that form a stalk. Each S1 subunit contains two domains, N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD). PdCoV S1-NTD has the same structural fold as alpha- and beta-coronavirus S1-NTDs as well as host galectins, and it recognizes sugar as its potential receptor. PdCoV S1-CTD has the same structural fold as alpha-coronavirus S1-CTDs, but its structure differs from that of beta-coronavirus S1-CTDs. PdCoV S1-CTD binds to an unidentified receptor on host cell surfaces. PdCoV S2 is locked in the pre-fusion conformation by structural restraint of S1 from a different monomeric subunit. PdCoV spike possesses several structural features that may facilitate immune evasion by the virus, such as its compact structure, concealed receptor-binding sites, and shielded critical epitopes. Overall, this study reveals that delta-coronavirus spikes are structurally and evolutionally more closely related to alpha-coronavirus spikes than to beta-coronavirus spikes; it also has implications for the receptor recognition, membrane fusion, and immune evasion by delta-coronaviruses as well as coronaviruses in general.SIGNIFICANCE In this study we determined the cryo-EM structure of porcine delta coronavirus (PdCoV) spike protein at 3.3 angstrom. This is the first atomic structure of a spike protein from the delta coronavirus genus, which is divergent in amino acid sequences from the well-studied alpha- and beta-coronavirus spike proteins. In the current study, we described the overall structure of the PdCoV spike and the detailed structure of each of its structural elements. Moreover, we analyzed the functions of each of the structural elements. Based on the structures and functions of these structural elements, we discussed the evolution of PdCoV spike protein in relation to the spike proteins from other coronavirus genera. This study combines the structure, function, and evolution of coronavirus spike proteins, and provides many insights into the receptor recognition, membrane fusion, immune evasion, and evolution of PdCoV spike protein.

Membranous nephropathy in a patient with ankylosing spondylitis: A case report.

Renal complications in ankylosing spondylitis (AS) were rarely observed, and proteinuria associated with AS can be seen often due to amyloidosis in this kind of complications, while membranous nephropathy (MN) is seldom considered. This article reports a case of coexistence of AS and MN, to provide the exact relationship of these 2 entities and recognized some causes of renal involvement in AS.

A metabolite of nobiletin, 4'-demethylnobiletin and atorvastatin synergistically inhibits human colon cancer cell growth by inducing G0/G1 cell cycle arrest and apoptosis.

Combining different chemopreventive agents is a promising strategy to reduce cancer incidence and mortality due to potential synergistic interactions between these agents. Previously, we demonstrated that oral administration of nobiletin (NBT, a citrus flavonoid) at 0.05% (w/w, in diet) together with atorvastatin (ATST, a lipid-lowering drug) at 0.02% (w/w, in diet) produced much stronger inhibition against colon carcinogenesis in rats in comparison with that produced by NBT (at 0.1% w/w in diet) or ATST (at 0.04% w/w in diet) alone at higher doses. To further elucidate the mechanism of this promising synergy between NBT and ATST, herein, we measured the levels of NBT, its major metabolites and ATST in the colonic tissue of rats fed NBT (0.05% w/w, in diet) + ATST (0.02% w/w, in diet), and determined the mode of interaction between the major NBT metabolite and ATST in inhibiting colon cancer cell growth. HPLC-MS analysis showed that 4'-demethylnobiletin (4DN) is the most abundant metabolite of NBT with a level about 5-fold as high as that of NBT in the colonic tissue, which indicated the potential significance of 4DN in mediating the biological effects of NBT in the colon. We found that co-treatments of 4DN/ATST at 2 : 1 concentration ratio produced much stronger growth inhibitory effects on human colon cancer HT-29 cells than 4DN or ATST alone, and isobologram analysis confirmed that this enhanced inhibitory effect by the 4DN/ATST combination was highly synergistic. The co-treatment of 4DN/ATST led to G0/G1 cell cycle arrest and induced extensive apoptosis in HT-29 cells. Furthermore, the 4DN/ATST co-treatment profoundly modulated key signaling proteins related to the regulation of the cell cycle and apoptosis. Our results demonstrated a strong synergy produced by the 4DN/ATST co-treatment in inhibiting colon cancer cell growth, which provided a novel mechanism by which NBT/ATST in combination synergistically inhibit colon carcinogenesis.

Comparative transcriptome analysis reveals host-associated differentiation in Chilo suppressalis (Lepidoptera: Crambidae).

The striped stem borer, Chilo suppressalis Walker (Lepidoptera: Crambidae), is one of the most serious rice pests. Besides attacking rice, it also feeds on an economically important vegetable crop, water-oat Zizania latifolia. The species feeding on water-oat has higher growth and survival rate than those on rice, suggesting their success in adaptation to the new host plant. However, little is known about the molecular mechanisms of host plant adaptation. Here we investigated the midgut transcriptome responses of C. suppressalis larvae reared on rice and water-oat. A total of 1,633 differentially expressed genes were identified, with a greater number up-regulated on the more delicious new host. The up-regulation of most digestive and detoxification-related genes may be the result of adaptation to the changes in nutritional requirements and toxic chemicals during host shift. In contrast, down-regulation of ribosomal genes may be related to their better development performance when feeding on the new host. In conclusion, our results suggest that transcriptional regulation of genes related to digestion, detoxification and ribosome may play an important role in adaptation of C. suppressalis to a new host plant.

Alkaline Ceramidase 1 Protects Mice from Premature Hair Loss by Maintaining the Homeostasis of Hair Follicle Stem Cells.

Ceramides and their metabolites are important for the homeostasis of the epidermis, but much remains unknown about the roles of specific pathways of ceramide metabolism in skin biology. With a mouse model deficient in the alkaline ceramidase (Acer1) gene, we demonstrate that ACER1 plays a key role in the homeostasis of the epidermis and its appendages by controlling the metabolism of ceramides. Loss of Acer1 elevated the levels of various ceramides and sphingoid bases in the skin and caused progressive hair loss in mice. Mechanistic studies revealed that loss of Acer1 widened follicular infundibulum and caused progressive loss of hair follicle stem cells (HFSCs) due to reduced survival and stemness. These results suggest that ACER1 plays a key role in maintaining the homeostasis of HFSCs, and thereby the hair follicle structure and function, by regulating the metabolism of ceramides in the epidermis.

Application of a mobile laser-induced breakdown spectroscopy system to detect heavy metal elements in soil.

In this work, a mobile laser-induced breakdown spectroscopy (LIBS) system has been successfully applied to in situ analysis of heavy metals in soil samples. The LIBS system had two working methods, which were a fixed measuring method and a handheld method. For the fixed measuring method, a simple sample pretreatment was needed to reduce the soil matrix effect generated by moisture and porosity. Experiments proved that this method could be used to semi-quantitatively detect heavy metals when combined with the traditional calibration curve method. The limits of detection for copper, lead, and zinc were all below 10  mg/kg, which satisfied the need of heavy metal detection in soil. Principal component analysis was used for soil classification, which helped to build appropriate calibration curves. On the basis of soil classification, accurate and rapid detection of heavy metals in soil is feasible. For the handheld method, spectrum intensity and stability decreased significantly compared with the fixed measuring method. However, by using the internal standard method, the stability of LIBS data was improved significantly to 6%. For soil samples with serious heavy-metal pollution, the measurement errors were less than 12%, which indicated that handheld LIBS was effective to monitor heavy-metal pollution in soil. The research results provide application support for rapid and on-site monitoring of heavy metals in soil.

Effect of oxygen concentration on outcome of in-vitro fertilization-embryo transfer.

To investigate the effect of low and high oxygen concentration on embryo development, pregnancy outcome and birth defects of in vitro fertilization-embryo transfer (IVF-ET).

Enhanced dispersion stability and heavy metal ion adsorption capability of oxidized starch nanoparticles.

Starch nanoparticles (SNPs) have attracted much research interest recently due to their biodegradability and biocompatibility. However, practical utilization of SNPs is generally restricted due to their weak colloid stability and reduced functionality. In this work, SNPs were functionally modified by sodium hypochlorite (1-5% active chlorine based on dry SNPs weight). The degree of modification, particle size, stability, and adsorption characteristics of the SNPs were systematically investigated. The results showed that as the active chlorine concentration increased, the carbonyl and carboxyl contents increased to 0.150% and 0.855%, respectively. Compared with SNPs, the zeta potential value of SNPs modified with 5% active chlorine increased significantly (p<0.05) from -13 to -31mV and the dispersion stability of modified SNPs was remarkably improved. Moreover, modified SNPs exhibited high adsorption capacities for Pb(2+) and Cu(2+), suggesting that they could be employed as a novel absorbent for removal of heavy metal ions.

Addendum to "Cartilage-Specific Autophagy Deficiency Promotes ER Stress and Impairs Chondrogenesis in PERK-ATF4-CHOP-Dependent Manner".

Chemical and bioactive comparison of flowers of Panax ginseng Meyer, Panax quinquefolius L., and Panax notoginseng Burk.

Although flowers of Panax ginseng Meyer (FPG), Panax quinquefolius L. (FPQ), and Panax notoginseng Burk. (FPN) have been historically used as both medicine and food, each is used differently in practice.

HLA Class I and Class II-Induced Intracellular Signaling and Molecular Associations in Primary Human Endothelial Cells.

The signaling capacity of HLA molecules in vascular cells has been well established. Intracellular signaling and association with the coreceptor integrin β4 has been well-studied for HLA class I. However, little is known regarding HLA class II intracellular signaling in human endothelial cells. Investigation of HLA class II has been challenging due to the loss of HLA class II expression in cultured primary cells. Herein, we describe methods for inducing expression of endogenous alleles and loci of HLA class II molecules, as well as for studying intracellular signaling. This includes siRNA knockdown of proteins and coimmunoprecipitation of putative coreceptors for HLA in primary human aortic endothelial cells.

The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.

Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface.