Publications by authors named "Li Ming Liu"

63 Publications

Evaluation of the "safe multidisciplinary app-assisted remote patient-self-testing (SMART) model" for warfarin home management during the COVID-19 pandemic: study protocol of a multi-center randomized controlled trial.

BMC Health Serv Res 2021 Aug 26;21(1):875. Epub 2021 Aug 26.

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

Background: Warfarin treatment requires frequent monitoring of INR (international normalized ratio) to adjust dosage in a therapeutic range. In China, patients living in small towns usually go to tertiary hospitals to get warfarin monitoring and dosing, resulting in low frequencies of follow-ups and high incidence of complications. Influenced by the COVID-19 pandemic, patients on warfarin have further reduced their visits to healthcare institutions. While patient self-testing (PST) via using a point-of-care testing device for INR measuring at home has been widely used in developed countries and demonstrated improved clinical outcomes compared to usual care in clinics, it is rarely applied in developing countries, including China. This proposed study will develop and assess the "Safe Multidisciplinary App-assisted Remote patient-self-Testing (SMART) model" for warfarin home management in China during the COVID-19 pandemic.

Methods: This is a multi-center randomized controlled trial. We will carry out the study in three county hospitals, three small tertiary hospitals and three large tertiary hospitals with anticoagulation clinics in Hunan province of China. Eligible patients will be randomly assigned to the SMART model group (n = 360) or the control group (usual care clinic group, n = 360; anticoagulation clinic group, n = 120). Patients in the SMART model group do PST at home once every two to 4 weeks. Controls receive usual care in the clinics. All the patients will be followed up through outpatient clinics, phone call or online interviews at the 3rd, 6th, 9th and 12th month. The percentage of time in therapeutic range (TTR), incidence of warfarin associated major bleeding and thromboembolic events and costs will be compared between the SMART model group and control groups.

Discussion: Patients in the SMART model group would show improved TTR, lower incidence of complications and better quality of life compared to the control groups. Our design, implementation and usage of the SMART model will provide experience and evidence in developing a novel model for chronic disease management to solve the problem of healthcare service maldistribution, an issue particularly obvious in developing countries during the COVID-19 pandemic.

Trial Registration: ChiCTR, ChiCTR 2000038984 . Registered 11 October, 2020.
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http://dx.doi.org/10.1186/s12913-021-06882-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390025PMC
August 2021

Arginine Methyltransferase PRMT1 Regulates p53 Activity in Breast Cancer.

Life (Basel) 2021 Aug 5;11(8). Epub 2021 Aug 5.

Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.
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http://dx.doi.org/10.3390/life11080789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400051PMC
August 2021

Multiple drug-resistant HBV mutation may contribute to poor response of adefovir + entecavir in entecavir-resistant patients.

J Infect Dev Ctries 2021 01 31;15(1):131-140. Epub 2021 Jan 31.

The Institute of Infectious Diseases, Fifth Medical Center of PLA General Hospital (Beijing 302 Hospital), Beijing, China.

Introduction: Adefovir plus entecavir (ADV+ETV) rescue therapy in ETV-resistant patients with chronic hepatitis B virus (HBV) infection is suboptimal in some patients. This study aims to elucidate the evolutionary characteristics of drug-resistant HBV mutants and their association with clinical responses in such patients.

Methodology: Thirty-seven ETV-resistant patients were enrolled, among whom twelve had an inadequate virological response to ADV+ETV rescue therapy. The clonal sequence (³ 20 clones/sample) of HBV reverse transcriptase gene was performed to identify the resistance mutations. Phenotypic analysis was performed to evaluate the replication capacity and drug susceptibility of the mutants.

Results: ETV-resistant mutants were continuously detected in 10 of the 12 patients, and multidrug-resistant (MDR) mutants, including a novel strain (rtL180M+A181V+T184A+S202G+M204V), were detected in two patients. Seven of the 12 patients who subsequently received tenofovir (TDF)-based therapy for 38 (23-60) months all achieved undetectable HBV DNA after treatment, and ETV-resistant mutants converted to wild-type in the four patients' samples. In contrast, the other five patients who did not achieve an adequate virological response had remaining of ETV-resistant mutants. The novel MDR strain exhibited multiple resistances to LAM, ADV, and ETV, and 11.2-fold lower susceptibility to TDF.

Conclusions: This study is the first to demonstrate that MDR HBV mutations may contribute to the poor efficacy of ADV+ETV combination therapy in ETV-resistant patients. Moreover, a novel MDR HBV strain was identified. Our results indicate that a TDF-based rescue therapy would be effective for the treatment of the refractory cases.
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http://dx.doi.org/10.3855/jidc.12643DOI Listing
January 2021

Traditional Chinese medicine for gouty arthritis: A protocol for meta-analysis.

Medicine (Baltimore) 2021 Jan;100(3):e23699

Department of Geriatrics of the Affiliated Hospital, North Sichuan Medical College, Nanchong.

Background: Gouty arthritis (GA) is a chronic disease caused by monosodium urate crystal deposition. Repeated attacks of arthritis may lead to the deposition of urate to form gout stone, resulting in joint deformity and joint damage. Although GA is not fatal, it causes low work productivity and low quality of life. Western drug, such as febuxostat, colchicine, allopurinol, often cannot get satisfying curative effect, and may even lead to serious side effects, such as exfoliative dermatitis or uremia. However, the therapeutic effect of Traditional Chinese medicine is very satisfactory. The treatment effect of simiao powder, a Chinese patent medicine, combined with acupuncture was widely used on treatment of GA. Although it has been widely used in clinical practice, its relative effectiveness and safety have not been confirmed. Therefore, this study will use meta-analysis to verify the efficacy and safety of simiao powder combined with acupuncture in the treatment of GA.

Methods: All randomized controlled trial of simiao powder combined with acupuncture for the treatment of RA from their inception 29 October, 2020 will be searched form the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library. Two authors will independently select studies, extract data based on pre-designed inclusion and exclusion criteria. Methodological quality assessment and risk of bias will be assessed using Cochrane bias risk tool. All data analysis will be conducted using Revman5.3, WinBUGS 1.4.3, and Stata14.2 software.

Results: We will compare the different outcome indicators of various studies to provide a synthesis of the efficacy and safety of Simiao powder combined with acupuncture for GA patients. The main outcome measures included efficacy, remission rate (no drug symptoms), recurrence rate, clinical absolute score and relative score. Secondary outcome measures included related adverse reactions and uric acid concentration.

Conclusion: The findings of the study will provide helpful evidence for the efficacy and safety of simiao powder combined with acupuncture in the treatment of GA.

Registration Number: This study protocol have been funded through a protocol registry. The registry number is INPLASY2020110028.
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http://dx.doi.org/10.1097/MD.0000000000023699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837833PMC
January 2021

Clinical value of CT-based patient-specific 3D preoperative design combined with conventional instruments in primary total knee arthroplasty: a propensity score-matched analysis.

J Orthop Surg Res 2020 Dec 9;15(1):591. Epub 2020 Dec 9.

Center for Joint Surgery, Southwest Hospital, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400036, China.

Purpose: To evaluate the operation and early clinical effect in primary total knee arthroplasty (TKA) about the novel combination of CT-based patient-specific three-dimensional (3D) preoperative design and conventional osteotomy instruments, compared with the conventional method.

Methods: After a 1:1 propensity score-matching (PSM), patients were matched to the novel technique group and the conventional group, 109 cases in each group. The conventional group adopted a preoperative design based on a full-length radiograph (FLX) and received TKA with conventional osteotomy instruments. The novel technique group used a CT-based patient-specific 3D preoperative design combined with conventional osteotomy instruments; during the surgery, the femoral entry point, femoral valgus osteotomy angle, the fix point of tibial plateau extramedullary guide pin, and the position of tibial extramedullary positioning rod were accurately selected according to the preoperative 3D design to ensure accurate intraoperative implementation. The lower limb alignment, component position, operation time, tourniquet time, hospital stay, blood loss volume, incidence of postoperative complications, visual analog scale (Vas) score, and New Knee Society Score System (NEW-KSS) at 1 day before operation and 1, 6, and 12 months after operation were recorded and compared.

Results: The novel technique group was significantly better than the conventional group in controlling lateral tibial component angle (LTC) (P < 0.001), and the novel technique group had lower percentages of hip-knee-ankle angle (HKA) outliers (P < 0.001) and overcorrection (P = 0.003). The operation time, tourniquet time, and hospital stay of the novel technique group was shorter (P < 0.05). In 1 month after the operation, the novel technique group achieved a significantly better VAS score (P < 0.05), but a similar NEW-KSS score (P > 0.05) when compared with the conventional group. But in 6 and 12 months after surgery, no statistical differences were seen in the above two scores (P > 0.05).

Conclusion: The novel technique of CT-based patient-specific 3D preoperative design combined with conventional instruments can improve the accuracy of osteotomy in primary total knee arthroplasty, with benefits of significantly reducing pain and rapid recovery during the early postoperative period, but having no obvious effect on outcome after a 1-year follow-up.
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http://dx.doi.org/10.1186/s13018-020-02123-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724895PMC
December 2020

Evaluating the cost-effectiveness of catheter ablation of atrial fibrillation.

Cardiovasc Diagn Ther 2020 Oct;10(5):1200-1215

Department of Cardiovascular Surgery, Second Xiangya Hospital, Central South University, Changsha, China.

Background: The pursuit of a clearer understanding of the pathogenesis of atrial fibrillation (AFib) and the development of new technology has resulted in a surge of interest in the surgical ablation for AFib. Here, we report our 8-year experience in the surgical treatment and management of AFib alongside, evaluating the cost-effectiveness in southern Mainland China over a 1-year follow-up.

Methods: Data of 3,068 patients from March 2011 through June 2019 was retrospectively extracted from The Provincial National Cardiac Database of Xiangya Second Hospital. The activities considered (and costs calculated) were outpatient consultations, hospital admissions, and drug treatment. Quality of life (QoL) questionnaires were also carried out to assess whether concomitant AFib correction procedures increase risk in patients, or improve patient's QoL.

Results: A total of 3,068 patients completed the questionnaires at a minimum of one time-point during the follow-up. The total cost was combined to obtain incremental costs per quality-adjusted life-years (QALYs). The total costs of the AFib catheter ablation group were remarkably higher compared to surgery as usual group. The incremental cost-effectiveness ratio was $76,513,227 (¥542,287,667) per QALY, with an acceptability line graph for cost at 43%.

Conclusions: AFib is an extraordinarily costly and worrisome public health problem. Precision medicine is vital as it provides a platform for the clinical translation of targeted interventions that are designed to help treat and prevent AFib. Thus, to improve the QoL expectancy outcome(s), both therapeutic and surgical interventions should be aimed at addressing the underlying heart disease rather than restoring sinus rhythm.
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http://dx.doi.org/10.21037/cdt-20-574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666964PMC
October 2020

General Plane-Based Clustering With Distribution Loss.

IEEE Trans Neural Netw Learn Syst 2021 Sep 31;32(9):3880-3893. Epub 2021 Aug 31.

In this article, we propose a general model for plane-based clustering. The general model reveals the relationship between cluster assignment and cluster updating during clustering implementation, and it contains many existing plane-based clustering methods, e.g., k-plane clustering, proximal plane clustering, twin support vector clustering, and their extensions. Under this general model, one may obtain an appropriate clustering method for a specific purpose. The general model is a procedure corresponding to an optimization problem, which minimizes the total loss of the samples. Thereinto, the loss of a sample derives from both within-cluster and between-cluster information. We discuss the theoretical termination conditions and prove that the general model terminates in a finite number of steps at a local or weak local solution. Furthermore, we propose a distribution loss function that fluctuates with the input data and introduce it into the general model to obtain a plane-based clustering method (DPC). DPC can capture the data distribution precisely because of its statistical characteristics, and its termination that finitely terminates at a weak local solution is given immediately based on the general model. The experimental results show that our DPC outperforms the state-of-the-art plane-based clustering methods on many synthetic and benchmark data sets.
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http://dx.doi.org/10.1109/TNNLS.2020.3016078DOI Listing
September 2021

Metabolic engineering of carbohydrate metabolism systems in Corynebacterium glutamicum for improving the efficiency of L-lysine production from mixed sugar.

Microb Cell Fact 2020 Feb 18;19(1):39. Epub 2020 Feb 18.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800# Lihu Road, Wuxi, 214122, China.

The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of L-lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from Clostridium acetobutylicum. L-lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTS and PTS) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and L-lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered C. glutamicum strain K-8 capable of producing 221.3 ± 17.6 g/L L-lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of L-lysine production from mixed sugar. This is also the first report for improving the efficiency of L-lysine production by systematic modification of carbohydrate metabolism systems.
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http://dx.doi.org/10.1186/s12934-020-1294-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029506PMC
February 2020

Structure, bioactivity and applications of natural hyperbranched polysaccharides.

Carbohydr Polym 2019 Nov 10;223:115076. Epub 2019 Jul 10.

State Key Laboratory of Food Science and Technology, Jiangnan University, WuXi 214122, China. Electronic address:

In recent years, hyperbranched polymers, especially the natural hyperbranched polysaccharides (HBPSs), are receiving much attention due to their diverse biological activities and applications. With high degree of branching (DB), HBPSs mainly exist in the form of either a comb-brush shape, dendrimer-like particulate, or globular particle. HBPSs also possess some unique properties, such as high density, large spatial cavities, and numerous terminal functional groups, which distinguish them from other polymers. As a natural biopolymer, HBPS has excellent bioavailability, biocompatibility, and biodegradability, which have versatile applications in the fields of food, medicine, cosmetic, and nanomaterials. In this review, the source and structure of HBPSs from plant, animal, microbial and fungal origins as well as their biological functions and applications are covered, with the aim of further advancing the research of their structure and bioactivity.
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http://dx.doi.org/10.1016/j.carbpol.2019.115076DOI Listing
November 2019

p38α MAP kinase promotes asthmatic inflammation through modulation of alternatively activated macrophages.

J Mol Cell Biol 2019 12;11(12):1095-1097

Department of Respiration and Critical Care Medicine, First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu 233004, China.

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http://dx.doi.org/10.1093/jmcb/mjz054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934154PMC
December 2019

Interdependent nitric oxide and hydrogen peroxide independently regulate the coix seed oil-induced triterpene acid accumulation in .

Mycologia 2019 Jul-Aug;111(4):529-540. Epub 2019 Jun 3.

a International Cooperation Base of Science and Technology Innovation on Forest Resource Biotechnology of Hunan Province, Central South University of Forestry & Technology , 498 Southern Shaoshan Road, Changsha 410004 , China.

Recent progress has been made in adding exogenous vegetable oils in culture media to promote bioactive metabolite production in several medicinal mushrooms, but the mechanism is still unclear. In this study, we found that the vegetable oil coix seed oil (CSO) could induce the biosynthesis of triterpene acids (TAs) and also significantly increase cytoplasmic nitric oxide (NO) and hydrogen peroxide (HO) concentrations in the mycelium of . The change in TA biosynthesis caused by CSO could be reversed by adding NO scavenger or HO scavenger, and adding NO scavenger or HO scavenger resulted in the reduction of the cytoplasmic HO or NO concentration under CSO treatment, respectively. Moreover, adding NO scavenger or HO scavenger reversed TA biosynthesis, which could be rescued by HO or NO donor, respectively. Taken together, our study indicated that both NO and HO were involved in the regulation of TA biosynthesis, and CSO-activated NO and HO were interdependent but independently regulated the TA biosynthesis under CSO treatment in .
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http://dx.doi.org/10.1080/00275514.2019.1615816DOI Listing
April 2020

Improvement of l-Leucine Production in by Altering the Redox Flux.

Int J Mol Sci 2019 Apr 24;20(8). Epub 2019 Apr 24.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.

The production of l-leucine was improved by the disruption of encoding transcriptional regulator and overexpression of the key genes () of the l-leucine biosynthesis pathway in XQ-9. In order to improve l-leucine production, we rationally engineered to enhance l-leucine production, by improving the redox flux. On the basis of this, we manipulated the redox state of the cells by mutating the coenzyme-binding domains of acetohydroxyacid isomeroreductase encoded by , inserting NAD-specific leucine dehydrogenase, encoded by from , and glutamate dehydrogenase encoded by from , instead of endogenous branched-chain amino acid transaminase and glutamate dehydrogenase, respectively. The yield of l-leucine reached 22.62 ± 0.17 g·L by strain ΔLtbR-acetohydroxyacid isomeroreductase (AHAIR)/ABNCE, and the concentrations of the by-products (l-valine and l-alanine) increased, compared to the strain ΔLtbR/ABNCE. Strain ΔLtbR-AHAIRLeuDH/ABNCLDH accumulated 22.87±0.31 g·L l-leucine, but showed a drastically low l-valine accumulation (from 8.06 ± 0.35 g·L to 2.72 ± 0.11 g·L), in comparison to strain ΔLtbR-AHAIR/ABNCE, which indicated that LeuDH has much specificity for l-leucine synthesis but not for l-valine synthesis. Subsequently, the resultant strain ΔLtbR-AHAIRLeuDHRocG/ABNCLDH accumulated 23.31 ± 0.24 g·L l-leucine with a glucose conversion efficiency of 0.191 g·g.
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http://dx.doi.org/10.3390/ijms20082020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515235PMC
April 2019

Methylation of C/EBPα by PRMT1 Inhibits Its Tumor-Suppressive Function in Breast Cancer.

Cancer Res 2019 06 23;79(11):2865-2877. Epub 2019 Apr 23.

State Key Laboratory of Medical Molecular Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

C/EBPα is an essential transcription factor involved in regulating the expression or function of certain cell-cycle regulators, including in breast cancer cells. Although protein arginine methyltransferases have been shown to play oncogenic roles in a variety of cancers, little is known about the role of arginine methylation in regulating the antiproliferation activity of C/EBPα. Here, we report that the protein arginine methyltransferase 1 (PRMT1) is overexpressed in human breast cancer and that elevated PRMT1 correlates with cancer malignancy. RNA-sequencing analysis revealed that knockdown of PRMT1 in breast cancer cells is accompanied by a decrease in the expression of pro-proliferative genes, including cyclin D1. Furthermore, tandem affinity purification followed by mass spectrometry identified PRMT1 as a component of the C/EBPα complex. C/EBPα associated with and was methylated by PRMT1 at three arginine residues (R35, R156, and R165). PRMT1-dependent methylation of C/EBPα promoted the expression of cyclin D1 by blocking the interaction between C/EBPα and its corepressor HDAC3, which resulted in rapid growth of tumor cells during the pathogenesis of breast cancer. Inhibition of PRMT1 significantly impeded the growth of cancer cells from patients with triple-negative breast cancer. This evidence that PRMT1 mediates C/EBPα methylation sheds light on a novel pathway and potential therapeutic target in breast cancer. SIGNIFICANCE: This study provides novel mechanistic insight of the role of the arginine methyltransferase PRMT1 in breast cancer pathogenesis.
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http://dx.doi.org/10.1158/0008-5472.CAN-18-3211DOI Listing
June 2019

Metabolic engineering of glucose uptake systems in Corynebacterium glutamicum for improving the efficiency of L-lysine production.

J Ind Microbiol Biotechnol 2019 Jul 1;46(7):937-949. Epub 2019 Apr 1.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, People's Republic of China.

Traditional amino acid producers typically exhibit the low glucose uptake rate and growth deficiency, resulting in a long fermentation time because of the accumulation of side mutations in breeding of strains. In this study, we demonstrate that the efficiency of L-lysine production in traditional L-lysine producer Corynebacterium glutamicum ZL-9 can be improved by rationally engineering glucose uptake systems. To do this, different bypasses for glucose uptake were investigated to reveal the best glucose uptake system for L-lysine production in traditional L-lysine producer. This study showed that overexpression of the key genes in PTS or non-PTS increased the glucose consumption, growth rate, and L-lysine production. However, increasing the function of PTS in glucose uptake led to the increase of by-products, especially for plasmid-mediated expression system. Increasing the participation of non-PTS in glucose utilization showed the best glucose uptake system for L-lysine production. The final strain ZL-92 with increasing the expression level of iolT1, iolT2 and ppgK could produce 201.6 ± 13.8 g/L of L-lysine with a productivity of 5.04 g/L/h and carbon yield of 0.65 g/(g glucose) in fed-batch culture. This is the first report of a rational modification of glucose uptake systems that improve the efficiency of L-lysine production through increasing the participation of non-PTS in glucose utilization in traditional L-lysine producer. Similar strategies can be also used for producing other amino acids or their derivatives.
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http://dx.doi.org/10.1007/s10295-019-02170-wDOI Listing
July 2019

Overexpression of thermostable meso-diaminopimelate dehydrogenase to redirect diaminopimelate pathway for increasing L-lysine production in Escherichia coli.

Sci Rep 2019 02 20;9(1):2423. Epub 2019 Feb 20.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800# Lihu Road, WuXi, 214122, People's Republic of China.

Dehydrogenase pathway, one of diaminopimelate pathway, is important to the biosynthesis of L-lysine and peptidoglycan via one single reaction catalyzed by meso-diaminopimelate dehydrogenase (DapDH). In this study, the thermostable DapDH was introduced into diaminopimelate pathway that increased the final titer (from 71.8 to 119.5 g/L), carbon yield (from 35.3% to 49.1%) and productivity (from 1.80 to 2.99 g/(L∙h)) of L-lysine by LATR12-2∆rpiB::ddh in fed-batch fermentation. To do this, the kinetic properties and the effects of different DapDHs on L-lysine production were investigated, and the results indicated that overexpression of StDapDH in LATR12-2 was beneficial to construct an L-lysine producer with good productive performance because it exhibited the best of kinetic characteristics and optimal temperature as well as thermostability in reductive amination. Furthermore, ammonium availability was optimized, and found that 20 g/L of (NH)SO was the optimal ammonium concentration for improving the efficiency of L-lysine production by LATR12-2∆rpiB::ddh. Metabolomics analysis showed that introducing the StDapDH significantly enhanced carbon flux into pentose phosphate pathway and L-lysine biosynthetic pathway, thus increasing the levels of NADPH and precursors for L-lysine biosynthesis. This is the first report of a rational modification of diaminopimelate pathway that improves the efficiency of L-lysine production through overexpression of thermostable DapDH in E. coli.
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http://dx.doi.org/10.1038/s41598-018-37974-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382763PMC
February 2019

Spin-Polarized Transport and Spin Seebeck Effect in Triple Quantum Dots with Spin-Dependent Interdot Couplings.

Nanoscale Res Lett 2018 Nov 8;13(1):358. Epub 2018 Nov 8.

State Key Laboratory of Electronic Thin Films and Integrated Device, University of Electronic Science and Technology of China, Chengdu, 610054, China.

We study the spin-dependent electronic and thermoelectric transport through a structure composed of triple quantum dots (TQDs) coupled to two metallic leads in the presence of spin-dependent interdot couplings, which is reliable by applying a static magnetic field on the tunnel junctions between different dots. When the TQDs are serially connected, a 100 % spin-polarized conductance and thermopower emerge even for very small spin-polarization of the interdot coupling as the dots are weakly coupled to each other. Whereas if the TQDs are connected in a ring shape, the Fano antiresonance will result in sharp peaks in the conductance and thermopower. In the presence of spin-dependent interdot couplings, the peaks of the spin-up and spin-down thermopowers will shift to opposite directions in the dot level regime, resulting large either 100 % spin-polarized or pure spin thermopowers. The latter generally arises at low temperatures and is robust against the level detuning, the dot-lead coupling, and the system equilibrium temperature.
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http://dx.doi.org/10.1186/s11671-018-2773-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223394PMC
November 2018

Asymmetric assembly of high-value α-functionalized organic acids using a biocatalytic chiral-group-resetting process.

Nat Commun 2018 09 19;9(1):3818. Epub 2018 Sep 19.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.

The preparation of α-functionalized organic acids can be greatly simplified by adopting a protocol involving the catalytic assembly of achiral building blocks. However, the enzymatic assembly of small amino acids and aldehydes to form numerous α-functionalized organic acids is highly desired and remains a significant challenge. Herein, we report an artificially designed chiral-group-resetting biocatalytic process, which uses simple achiral glycine and aldehydes to synthesize stereodefined α-functionalized organic acids. This cascade biocatalysis comprises a basic module and three different extender modules and operates in a modular assembly manner. The engineered Escherichia coli catalysts, which contained different module(s), provide access to α-keto acids, α-hydroxy acids, and α-amino acids with excellent conversion and enantioselectivities. Therefore, this biocatalytic process provides an attractive strategy for the conversion of low-cost achiral starting materials to high-value α-functionalized organic acids.
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http://dx.doi.org/10.1038/s41467-018-06241-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145935PMC
September 2018

Rational modification of Corynebacterium glutamicum dihydrodipicolinate reductase to switch the nucleotide-cofactor specificity for increasing l-lysine production.

Biotechnol Bioeng 2018 07 16;115(7):1764-1777. Epub 2018 Apr 16.

The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, WuXi, People's Republic of China.

l-lysine is an important amino acid in animals and humans and NADPH is a vital cofactor for maximizing the efficiency of l-lysine fermentation. Dihydrodipicolinate reductase (DHDPR), an NAD(P)H-dependent enzyme, shows a variance in nucleotide-cofactor affinity in bacteria. In this study, we rationally engineered Corynebacterium glutamicum DHDPR (CgDHDPR) to switch its nucleotide-cofactor specificity resulting in an increase in final titer (from 82.6 to 117.3 g L ), carbon yield (from 0.35 to 0.44 g [g glucose] ) and productivity (from 2.07 to 2.93 g L  hr ) of l-lysine in JL-6 ΔdapB::Ec-dapB in fed-batch fermentation. To do this, we comparatively analyzed the characteristics of CgDHDPR and Escherichia coli DHDPR (EcDHDPR), indicating that hetero-expression of NADH-dependent EcDHDPR increased l-lysine production. Subsequently, we rationally modified the conserved structure of cofactor-binding motif, and results indicated that introducing the mutation K11A or R13A in CgDHDPR and introducing the mutation R16A or R39A in EcDHDPR modifies the nucleotide-cofactor affinity of DHDPR. Lastly, the effects of these mutated DHDPRs on l-lysine production were investigated. The highest increase (26.2%) in l-lysine production was observed for JL-6 ΔdapB::Ec-dapB , followed by JL-6 Cg-dapB (21.4%) and JL-6 ΔdapB::Ec-dapB (15.2%). This is the first report of a rational modification of DHDPR that enhances the l-lysine production and yield through the modulation of nucleotide-cofactor specificity.
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http://dx.doi.org/10.1002/bit.26591DOI Listing
July 2018

Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B.

Glob Health Action 2018 ;11(1):1433987

b Department of Hepatology , Hubei Third People's Hospital , Wuhan , Hubei , China.

Background: Globally, of the 248 million people chronically infected with the hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB) in China.

Objectives: The aims of this study were to determine rates of adherence to NUC therapy in patients with CHB, to identify the self-perceived barriers to adherence, and to examine the factors associated with adherence.

Methods: Questionnaire-based interviews were administered among Chinese patients with CHB at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults aged 18 years or older prescribed with NUCs were recruited and interviewed to complete a 27-item questionnaire in a private setting, and adherence was measured using the Morisky Medication Adherence Scale (MMAS-8).

Results: Among 369 participants, only 16.5% had high adherence (score of 8), 32.2% had medium adherence (score of 6 to <8), and 51.2% were measured with low adherence (score of <6). A logistic regression model was used to determine the factors associated with medication adherence. Significant predictors of high adherence consisted of urban residency, non-cirrhotic status, not using prescribed pills other than HBV medications, and reminders from family members. The five most common reasons for skipping NUCs were that medication(s) are expensive (48.7%), forgetfulness (45.1%), have experienced or worry about potential side effects (19.8%), do not want others to know about my medication(s) usage (18.5%), and ran out of pills and do not have time to refill (15.9%).

Conclusions: This study revealed that adherence rates to oral antiviral therapy were far from optimal. This finding should generate public attention, and it would be beneficial for interventional programs to target Chinese patients from rural regions, as well as patients with low socioeconomic status, cirrhosis, and taking multiple medications.
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http://dx.doi.org/10.1080/16549716.2018.1433987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5827725PMC
October 2018

Performance verification and comparison of TianLong automatic hypersensitive hepatitis B virus DNA quantification system with Roche CAP/CTM system.

World J Gastroenterol 2017 Oct;23(37):6845-6853

Center of Clinical Laboratory Medicine, 302 Military Hospital of China, Beijing 100039, China.

Aim: To investigate and compare the analytical and clinical performance of TianLong automatic hypersensitive hepatitis B virus (HBV) DNA quantification system and Roche CAP/CTM system.

Methods: Two hundred blood samples for HBV DNA testing, HBV-DNA negative samples and high-titer HBV-DNA mixture samples were collected and prepared. National standard materials for serum HBV and a worldwide HBV DNA panel were employed for performance verification. The analytical performance, such as limit of detection, limit of quantification, accuracy, precision, reproducibility, linearity, genotype coverage and cross-contamination, was determined using the TianLong automatic hypersensitive HBV DNA quantification system (TL system). Correlation and Bland-Altman plot analyses were carried out to compare the clinical performance of the TL system assay and the CAP/CTM system.

Results: The detection limit of the TL system was 10 IU/mL, and its limit of quantification was 30 IU/mL. The differences between the expected and tested concentrations of the national standards were less than ± 0.4 Log IU/mL, which showed high accuracy of the system. Results of the precision, reproducibility and linearity tests showed that the multiple test coefficient of variation (CV) of the same sample was less than 5% for 10-10 IU/mL; and for 30-10 IU/mL, the linear correlation coefficient = 0.99. The TL system detected HBV DNA (A-H) genotypes and there was no cross-contamination during the "checkerboard" test. When compared with the CAP/CTM assay, the two assays showed 100% consistency in both negative and positive sample results (15 negative samples and 185 positive samples). No statistical differences between the two assays in the HBV DNA quantification values were observed ( > 0.05). Correlation analysis indicated a significant correlation between the two assays, = 0.9774. The Bland-Altman plot analysis showed that 98.9% of the positive data were within the 95% acceptable range, and the maximum difference was -0.49.

Conclusion: The TL system has good analytical performance, and exhibits good agreement with the CAP/CTM system in clinical performance.
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http://dx.doi.org/10.3748/wjg.v23.i37.6845DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645617PMC
October 2017

iPGK-PseAAC: Identify Lysine Phosphoglycerylation Sites in Proteins by Incorporating Four Different Tiers of Amino Acid Pairwise Coupling Information into the General PseAAC.

Med Chem 2017 ;13(6):552-559

Gordon Life Science Institute, Boston, MA 02478. United States.

Background: Occurring at Lys residues, the PGK (lysine phosphoglycerylation) is a special kind of post-translational modification (PTM). It may invert the charge potential of the modified residue and change the protein structures and functions, causing various diseases in liver, brain, and kidney.

Objective: From the angles of both basic research and drug development, we are facing a critical challenging problem: for an uncharacterized protein sequence containing many Lys residues, which ones can be of phosphoglycerylation, and which ones cannot?

Method: To address this problem, we have developed a predictor called iPGK-PseAAC by incorporating into the general PseAAC (pseudo amino acid composition) with four different tiers of amino acid pairwise coupling information, where tiers 1, 2, 3, and 4 refer to the amino acid pairwise couplings between all the 1st, 2nd, 3rd, and 4th most contiguous residues along a protein segment, respectively.

Results: Rigorous cross-validations indicated that the proposed predictor remarkably outperformed its existing counterparts.

Conclusion: The proposed predictor iPGK-PseAAC will become a very useful bioinformatics tool for medicinal chemistry. For the convenience of most experimental scientists, a user-friendly webserver for iGPK-PseAAC has been established at http://app.aporc.org/iPGK-PseAAC/, by which users can easily obtain their desired results without the need to go through the complicated mathematical equations involved.
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http://dx.doi.org/10.2174/1573406413666170515120507DOI Listing
September 2017

Rapamycin modulated brain-derived neurotrophic factor and B-cell lymphoma 2 to mitigate autism spectrum disorder in rats.

Neuropsychiatr Dis Treat 2017 20;13:835-842. Epub 2017 Mar 20.

Department of Pediatrics, Maternal and Children Hospital of Tangshan City, Tangshan, Hebei, People's Republic of China.

The number of children suffered from autism spectrum disorder (ASD) is increasing dramatically. However, the etiology of ASD is not well known. This study employed mammalian target of rapamycin inhibitor rapamycin to explore its effect on ASD and provided new therapeutic strategies for ASD. ASD rat model was constructed and valproic acid (VPA) was injected intraperitoneally into rats on pregnancy day 12.5. Offspring from VPA group were divided into ASD group and ASD + rapamycin (ASD + RAPA) group. Compared with normal group, the frequency and duration of social behavior and straight times of ASD group were shortened, but the grooming times were extended. Meanwhile, in ASD group, the average escape latency and the frequency of crossing plates were decreased, the apoptotic index (AI) detected by TUNEL assay was increased, and the expression of brain-derived neurotrophic factor (BDNF) and B-cell lymphoma 2 (Bcl-2) analyzed was decreased with great difference compared with normal group (<0.01). However, rapamycin treatment in ASD rats mitigated the ASD-like social behavior, such as the frequencies of straight and grooming. Furthermore, rapamycin shortened the average escape latency, but increased the frequency of crossing plates of ASD rats. In hippocampus, rapamycin decreased the AI, but increased the levels of BDNF and Bcl-2 (<0.01) of ASD rats. These findings revealed that rapamycin significantly mitigated the social behavior by enhancing the expression of BDNF and Bcl-2 to suppress the hippocampus apoptosis in VPA-induced ASD rats.
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http://dx.doi.org/10.2147/NDT.S125088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5365326PMC
March 2017

Angiopoietin-like protein 4 improves glucose tolerance and insulin resistance but induces liver steatosis in high-fat-diet mice.

Mol Med Rep 2016 Oct 18;14(4):3293-300. Epub 2016 Aug 18.

Department of Endocrinology, Dahua Hospital of Xuhui District, Shanghai 200237, P.R. China.

Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator‑activated receptors, which are widely used as lipid‑lowering and anti‑diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high‑fat‑diet (HFD) C57 mice. In the present study, mice were divided into three groups, with standard chow mice as a normal control, adenovirus (adv)‑injected HFD mice as a model control and adv‑Angptl4‑injected HFD mice as the Angptl4+ group. Firstly, compared with the normal control group, mice in the model control group gained more body weight with severe liver steatosis and increased serum levels of triglyceride, total cholesterol, free fatty acids, alanine aminotransferase and aspartate aminotransferase. In the Angptl4+ group, Angptl4 reduced the weight growth rate, aggravated hepatic steatosis and further increased all the aforementioned serum indexes. Secondly, compared with the normal control, the model control group had a reduced glucose tolerance and developed insulin resistance. Angptl4 expression and the phosphorylation levels of several insulin signaling pathway‑associated genes, insulin receptor substrate 1, protein kinase B, janus kinase 2, signal transducer and activator of transcription 3 were downregulated in the liver samples. Adv‑Angptl4 injection was observed to improve glucose tolerance and insulin resistance. The genes measured were identified to be upregulated close to normal levels. All the results suggested that Angptl4 served an important role in lipid and glucose metabolism in HFD‑induced obese mice, and this may have a great significance for treatment of hyperlipidemia, diabetes, metabolic syndrome and other diseases.
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http://dx.doi.org/10.3892/mmr.2016.5637DOI Listing
October 2016

[Highly Efficient Bilayer-Structure Yellow-Green OLED with MADN Hole-Transport Layer and the Impedance Spectroscopy Analysis].

Guang Pu Xue Yu Guang Pu Fen Xi 2015 Dec;35(12):3296-9

Abstract Highly efficient bilayer-structure yellow-green organic light-emitting device (OLED) has been demonstrated based on MADN as hole-transport layer (HTL) and host-guest coped system of [Alq₃: 0.7 Wt% rubrene] as emitting and electron-trans- port layer. The device gives yellow-green emission through incomplete energy transfer from the host of Alq₃ to the guest of ru- brene. An electroluminescent peak of 560 nm, 1931 CIE color coordinates of (0.46, 0.52) and a maximum current efficiency of 7.63 cd · A⁻¹ (which has been enhanced by 30% in comparison with the counterpart having conventional NPB HTL) are ob- served. The hole-transporting characteristics of MADN and NPB have been systematically investigated by constructing hole-only devices and employing impedance spectroscopy analysis. Our results indicate that MADN can be served as an effective hole-trans- port material and its hole-transporting ability is slightly inferior to NPB. This overcomes the shortcoming of hole transporting more quickly than electron in OLED and improves carrier balance in the emitting layer. Consequently, the device current efficien- cy is promoted. In addition, the current efficiency of bilayer-structure OLED with MADN as HTL is comparable to that of conv- entinol trilayer-structure device with MADN as HTL and Alq₃ as electron-transport layer. This indicates that the simplified bi- layer-structure device can be achieved without sacrificing current efficiency. The emitting layer of [Alq: 0.7 Wt% rubrene possesses superior elecron-transporting ability.
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December 2015

Age and Ebola viral load correlate with mortality and survival time in 288 Ebola virus disease patients.

Int J Infect Dis 2016 Jan 30;42:34-39. Epub 2015 Oct 30.

Beijing 302 Hospital, Beijing, 100039, China.

Background: A Chinese medical team managed Ebola virus disease (EVD) patients in Sierra Leone from October 2014 to March 2015 and attended to 693 suspected patients, of whom 288 had confirmed disease.

Methods: A retrospective study was conducted of the 288 patients with confirmed disease. Clinical symptoms, manifestations, and serum viral load were analyzed and compared among the different groups for mortality and survival time.

Results: Among the 288 confirmed EVD patients (149 male and 139 female, median age 28 years, and median log viral load 6.68), 98 died, 36 recovered, and 154 were lost to follow-up. Common symptoms were fever (77.78%), fatigue (64.93%), abdominal pain (64.58%), headache (62.85%), and diarrhea (61.81%). Compared to patients aged<18 years, those who were older than 40 years had a higher probability of death (odds ratio 2.855, p=0.044). Patients with a viral load of >10(6) copies/ml had a higher case fatality rate than those with <10(6) copies/ml (odds ratio 3.095, p=0.004). Cox regression showed that age, viral load, and the presence of diarrhea correlated with mortality.

Conclusion: Patients with a high viral load, of older age, and with diarrhea had a higher mortality and shorter survival time.
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http://dx.doi.org/10.1016/j.ijid.2015.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110900PMC
January 2016

Prediction of sumoylation sites in proteins using linear discriminant analysis.

Gene 2016 Jan 9;576(1 Pt 1):99-104. Epub 2015 Nov 9.

School of Statistics, Capital University of Economics and Business, Beijing, 100070, China. Electronic address:

Sumoylation is a multifunctional post-translation modification (PTM) in proteins by the small ubiquitin-related modifiers (SUMOs), which have relations to ubiquitin in molecular structure. Sumoylation has been found to be involved in some cellular processes. It is very significant to identify the exact sumoylation sites in proteins for not only basic researches but also drug developments. Comparing with time exhausting experiment methods, it is highly desired to develop computational methods for prediction of sumoylation sites as a complement to experiment in the post-genomic age. In this work, three feature constructions (AAIndex, position-specific amino acid propensity and modification of composition of k-space amino acid pairs) and five different combinations of them were used to construct features. At last, 178 features were selected as the optimal features according to the Mathew's correlation coefficient values in 10-fold cross validation based on linear discriminant analysis. In 10-fold cross-validation on the benchmark dataset, the accuracy and Mathew's correlation coefficient were 86.92% and 0.6845. Comparing with those existing predictors, SUMO_LDA showed its better performance.
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http://dx.doi.org/10.1016/j.gene.2015.09.072DOI Listing
January 2016

[Prediction method of rural landscape pattern evolution based on life cycle: a case study of Jinjing Town, Hunan Province, China].

Ying Yong Sheng Tai Xue Bao 2014 Nov;25(11):3270-8

Taking Jinjing Town in Dongting Lake area as a case, this paper analyzed the evolution of rural landscape patterns by means of life cycle theory, simulated the evolution cycle curve, and calculated its evolution period, then combining CA-Markov model, a complete prediction model was built based on the rule of rural landscape change. The results showed that rural settlement and paddy landscapes of Jinjing Town would change most in 2020, with the rural settlement landscape increased to 1194.01 hm2 and paddy landscape greatly reduced to 3090.24 hm2. The quantitative and spatial prediction accuracies of the model were up to 99.3% and 96.4%, respectively, being more explicit than single CA-Markov model. The prediction model of rural landscape patterns change proposed in this paper would be helpful for rural landscape planning in future.
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November 2014

Solitary bone cyst of the odontoid process and body of the axis: a case report.

Orthop Surg 2014 Nov;6(4):317-21

Department of Orthopaedics, West China Hospital, Chengdu, China.

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http://dx.doi.org/10.1111/os.12138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583157PMC
November 2014

Clinical and radiographic outcomes of dynamic cervical implant replacement for treatment of single-level degenerative cervical disc disease: a 24-month follow-up.

Eur Spine J 2014 Aug 29;23(8):1680-7. Epub 2014 Jan 29.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.

Purpose: To determine the role of dynamic cervical implant (DCI) replacement for single-level degenerative cervical disc disease in Chinese patients.

Methods: Thirty patients with single-level degenerative cervical disc disease were prospectively enrolled between April 2010 and August 2010 (12 women, 18 men; mean age 56.5 years). All patients underwent anterior cervical decompression, DCI replacement, clinical and radiological assessments preoperatively and at 1, 6, 12, and 24 months postoperatively, and Japanese Orthopaedic Association (JOA), Visual Analogue Scale (VAS), Neck Disability Index (NDI), and Short Form 36 (SF-36) scores. Lateral neutral radiographs provided the intervertebral space height. Lateral dynamic radiographs were taken to measure the range of motion (ROM) of the cervical spine and functional spinal unit (FSU) of the treated segment. We compared the amount of motion of the adjacent vertebral endplate and the intrinsic motion of the implant and calculated a correlation analysis.

Results: DCI showed good clinical and radiographic outcomes. At the final follow-up, JOA, VAS, NDI, and SF-36 average scores improved significantly. The intervertebral space height increased slightly after operation and was maintained during follow up. The ROM of the cervical spine and FSU decreased at early follow-up, but recovered to the preoperative level within 1-2 years. There was a high index of linear correlation between the motion of the adjacent vertebral endplate and the intrinsic motion of the implant.

Conclusions: DCI provided elastic dynamic stability for the targeted segment, and restored and sustained intervertebral space height and ROM of the cervical spine.
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http://dx.doi.org/10.1007/s00586-014-3180-7DOI Listing
August 2014

Primary leiomyoma: a rare space occupying lesion in the right ventricle.

Ann Thorac Surg 2014 Jan;97(1):324-6

Department of Cardiothoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China. Electronic address:

A case of primary cardiac leiomyoma arising from the infundibulum of the right ventricle of a 24-year-old woman is presented. The mass protruded into the cavity of the right ventricle and caused severe right ventricular outflow tract obstruction. We resected the tumor under cardiopulmonary bypass successfully, and confirmed it histologically to be a benign leiomyoma. To the authors' knowledge, this is the first case report of a primary cardiac leiomyoma in an adult woman.
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http://dx.doi.org/10.1016/j.athoracsur.2013.05.097DOI Listing
January 2014
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