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1.
Front Bioeng Biotechnol ; 12: 1337808, 2024.
Article in English | MEDLINE | ID: mdl-38681963

ABSTRACT

Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons. Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC's measurement stability across diverse hospital settings and MR scanning machines. Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics. Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging.

2.
Cancer Control ; 31: 10732748241247170, 2024.
Article in English | MEDLINE | ID: mdl-38662732

ABSTRACT

Among the post-transcriptional modifications, m6A RNA methylation has gained significant research interest due to its critical role in regulating transcriptional expression. This modification affects RNA metabolism in several ways, including processing, nuclear export, translation, and decay, making it one of the most abundant transcriptional modifications and a crucial regulator of gene expression. The dysregulation of m6A RNA methylation-related proteins in many tumors has been shown to lead to the upregulation of oncoprotein expression, tumor initiation, proliferation, cancer cell progression, and metastasis.Although the impact of m6A RNA methylation on cancer cell growth and proliferation has been extensively studied, its role in DNA repair processes, which are crucial to the pathogenesis of various diseases, including cancer, remains unclear. However, recent studies have shown accumulating evidence that m6A RNA methylation significantly affects DNA repair processes and may play a role in cancer drug resistance. Therefore, a comprehensive literature review is necessary to explore the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.In conclusion, m6A RNA methylation is a crucial regulator of gene expression and a potential player in cancer development and drug resistance. Its dysregulation in many tumors leads to the upregulation of oncoprotein expression and tumor progression. Furthermore, the impact of m6A RNA methylation on DNA repair processes, although unclear, may play a crucial role in cancer drug resistance. Therefore, further studies are warranted to better understand the potential biological role of m6A-modified DNA repair processes in human cancer and cancer drug resistance.


Subject(s)
DNA Damage , DNA Repair , Drug Resistance, Neoplasm , Neoplasms , Humans , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/therapy , Neoplasms/drug therapy , Drug Resistance, Neoplasm/genetics , Chemoradiotherapy/methods , Gene Expression Regulation, Neoplastic
3.
Cell Cycle ; 22(5): 506-526, 2023 03.
Article in English | MEDLINE | ID: mdl-36214587

ABSTRACT

Radiation-induced liver disease (RILD), also known as radiation hepatitis, is a serious side effect of radiotherapy (RT) for hepatocellular carcinoma. The therapeutic dose of RT can damage normal liver tissue, and the toxicity that accumulates around the irradiated liver tissue is related to numerous physiological and pathological processes. RILD may restrict treatment use or eventually deteriorate into liver fibrosis. However, the research on the mechanism of radiation-induced liver injury has seen little progress compared with that on radiation injury in other tissues, and no targeted clinical pharmacological treatment for RILD exists. The DNA damage response caused by ionizing radiation plays an important role in the pathogenesis and development of RILD. Therefore, in this review, we systematically summarize the molecular and cellular mechanisms involved in RILD. Such an analysis is essential for preventing the occurrence and development of RILD and further exploring the potential treatment of this disease.


Subject(s)
Carcinoma, Hepatocellular , Liver Diseases , Liver Neoplasms , Radiation Injuries , Humans , Liver Neoplasms/genetics , Liver Neoplasms/radiotherapy , Liver Neoplasms/complications , Liver Diseases/genetics , Liver Diseases/pathology , Liver/pathology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/radiotherapy , Radiation Injuries/genetics , Radiation Injuries/complications , DNA Damage
5.
Cell Cycle ; 21(11): 1121-1139, 2022 06.
Article in English | MEDLINE | ID: mdl-35192423

ABSTRACT

The maintenance of cellular cholesterol homeostasis is essential for normal cell function and viability. Excessive cholesterol accumulation is detrimental to cells and serves as the molecular basis of many diseases, such as atherosclerosis, Alzheimer's disease, and diabetes mellitus. The peripheral cells do not have the ability to degrade cholesterol. Cholesterol efflux is therefore the only pathway to eliminate excessive cholesterol from these cells. This process is predominantly mediated by ATP-binding cassette transporter A1 (ABCA1), an integral membrane protein. ABCA1 is known to transfer intracellular free cholesterol and phospholipids to apolipoprotein A-I (apoA-I) for generating nascent high-density lipoprotein (nHDL) particles. nHDL can accept more free cholesterol from peripheral cells. Free cholesterol is then converted to cholesteryl ester by lecithin:cholesterol acyltransferase to form mature HDL. HDL-bound cholesterol enters the liver for biliary secretion and fecal excretion. Although how cholesterol is transported by ABCA1 to apoA-I remains incompletely understood, nine models have been proposed to explain this effect. In this review, we focus on the current view of the mechanisms underlying ABCA1-mediated cholesterol efflux to provide an important framework for future investigation and lipid-lowering therapy.


Subject(s)
Apolipoprotein A-I , Lipoproteins, HDL , ATP Binding Cassette Transporter 1 , Apolipoprotein A-I/chemistry , Apolipoprotein A-I/metabolism , Biological Transport , Cholesterol/metabolism , Cholesterol, HDL , Lipoproteins, HDL/metabolism , Phosphatidylcholine-Sterol O-Acyltransferase
6.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-976109

ABSTRACT

@#A diving decompression procedure is a specific rule that divers should follow when they ascend and get out of water. It comes from the decompression theory and algorithm and is designed for the prevention of decompression sickness. With the , , development of diving technology and diving medicine the decompression procedures are constantly innovated and the new , decompression procedure can be used in diving practice after safety verification. In principle the safety verification of , decompression procedures should be conducted on animal experiments before human experiments and the risks of , decompression sickness and oxygen toxicity should be systematically assessed. However the assessment methods used in , , , different studies differ greatly thus it is urgent to establish a standard and universal verification system. Traditionally the risk , , assessment of decompression sickness and oxygen toxicity is mainly carried out by observing the incidence detecting bubbles , theoretical calculation and lung functional test. Furthermore biochemical indicators are increasingly becoming important , , supplements. Due to the special underwater environment the diving operation is prone to accidents. Therefore in addition to , verifying the safety of the new decompression procedure exploring its safety decompression limit is of great significance for the formulation of emergency decompression procedures in emergency situations. The specific approach is to shorten the decompression time and assess the safety until the critical time for detecting bubbles without the occurrence of decompression , , sickness is found. Future studies should continue to optimize safety assessment methods explore sensitive biochemical markers , clarify species associations and improve verification efficiency and reliability of results.

8.
Front Bioeng Biotechnol ; 9: 662432, 2021.
Article in English | MEDLINE | ID: mdl-33928073

ABSTRACT

In this study, acenaphthylene was used as the raw material, and a series of novel 1,8-naphthalimide-1,2,3-triazole derivatives was obtained through oxidation, acylation, alkylation, and click reactions, and subsequently, their anti-tumor activities were tested. After screening, we found that Compound 5e showed good activity against H1975 lung cancer cells, with the half maximal inhibitory concentration (IC50) reaching 16.56 µM.

9.
Ann Transl Med ; 9(2): 183, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33569485

ABSTRACT

Autosomal recessive congenital ichthyosis is a genetically and phenotypically heterogeneous group of skin disorders, including harlequin ichthyosis (HI), lamellar ichthyosis, and bullous congenital ichthyosiform erythroderma. HI is the most phenotypically severe autosomal recessive congenital ichthyosis associated with the mutation of the adenosine triphosphate-binding cassette subfamily A member 12 (ABCA12) gene. The clinical manifestations include generalized hyperkeratotic plaques and deep fissures, ectropion, eclabium, and contractures. However, the severe HI may easily be misdiagnosed as epidermolysis bullosa or syndromic ichthyosis. Meanwhile, no consensus exists about the best used in clinical trials or clinical practice when more elaborate scoring systems have been proposed to evaluate skin xerosis, palmoplantar keratoderma, and disease extension an accurate prenatal diagnosis is necessary. Until the ABCA12 gene was identified as the pathogenic gene, prenatal diagnosis of HI had been performed by the invasive techniques of fetal skin biopsy. Now, advances in ultrasound technology and fetal DNA-based analysis have replaced it. The mortality rate is markedly high and prompt; prenatal diagnosis of neonate HI is critical for appropriate perinatal and postnatal management. It is also essential to prepare parents for future pregnancies and reduce the family's physical and mental distress and financial burden. This report presents a rare case of harlequin ichthyosis diagnosed by the ultrasound and discusses the significance of prenatal ultrasound diagnosis and molecular diagnosis in the prenatal diagnosis of HI.

10.
Ann Palliat Med ; 9(6): 3742-3749, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33302646

ABSTRACT

BACKGROUND: Cystic adenomyosis is a particular type of adenomyosis, High intensity focused ultrasound (HIFU), as a non-invasive method, has also been used to treat adenomyosis. The purpose of this study was to investigate the efficacy, safety, and feasibility of HIFU for the treatment of cystic adenomyosis. METHODS: Diagnosis of cystic adenomyosis was obtained through trans-vaginal ultrasound and magnetic resonance imaging (MRI). Ultrasound-guided HIFU ablation was performed under conscious sedation. The patients were evaluated by the comparison of pre-HIFU and post-HIFU imaging, as well as the Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire subscales, consisting of Symptom Severity Score (SSS) and Heath Related Quality of Life (HRQL). RESULTS: HIFU was effective in treating cystic adenomyosis. No complications were observed in the four patients who were successfully treated with HIFU. Compared to preoperative symptoms and patient satisfaction, symptoms at the first follow-up observed significant improvements, with no dysmenorrhea and high health-related quality of life. During the outpatient follow-up of one month, three months, and six months postoperation, the four patients were still without dysmenorrhea and were highly satisfied with the HIFU ablation. CONCLUSIONS: HIFU, as a non-invasive treatment, supplies a safe and effective possibility for the treatment of cystic adenomyosis.


Subject(s)
Adenomyosis , High-Intensity Focused Ultrasound Ablation , Leiomyoma , Adenomyosis/therapy , Female , Humans , Leiomyoma/therapy , Quality of Life , Treatment Outcome
11.
BMJ Open ; 9(11): e028084, 2019 11 24.
Article in English | MEDLINE | ID: mdl-31767578

ABSTRACT

INTRODUCTION: Osteoporotic fracture is one of the most common causes of disability and a major contributor to medical care costs in many regions of the world. The polymorphisms of genes related to vitamin D metabolism and transportation are associated with variation in bone mineral density and the risk of osteoporosis. METHODS AND ANALYSIS: The China Community-based Cohort of Osteoporosis study is an observational, longitudinal, multicentre, prospective cohort study for middle-aged and older permanent residents of China, which has been ongoing in six cities since 2016. Female residents aged 45-80 years old and male residents aged 50-80 years old are identified through permanent resident lists. All the enrolled participants will complete questionnaires on their personal characteristics and histories. The bone mineral density of their lumbar vertebrae and left hip will be measured and serum bone metabolism parameters assessed. Polymorphisms of genes related to vitamin D metabolism and transportation will be detected, and their relationship with the risk of osteoporosis, and osteoporotic fracture, will be analysed. About 18 000 residents will be involved in the study. ETHICS AND DISSEMINATION: The study was approved by Institutional Ethics Board of Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine (2016LCSY065). Results will be published in peer-reviewed journals. The results of this study are expected to improve the understanding of the association between polymorphisms of genes related to vitamin D metabolism and transportation and the risk of osteoporosis and osteoporotic fracture among middle-aged and older residents of China. TRIAL REGISTRATION NUMBER: NCT02958020.


Subject(s)
Osteoporosis/genetics , Osteoporotic Fractures/etiology , Polymorphism, Single Nucleotide , Vitamin D/metabolism , Absorptiometry, Photon , Aged , Aged, 80 and over , Bone Density , China/epidemiology , Female , Hip/diagnostic imaging , Humans , Longitudinal Studies , Lumbar Vertebrae/diagnostic imaging , Male , Middle Aged , Multicenter Studies as Topic , Observational Studies as Topic , Osteoporosis/diagnosis , Osteoporosis/epidemiology , Osteoporotic Fractures/epidemiology , Prospective Studies , Research Design , Risk Factors
12.
Neural Regen Res ; 14(2): 306-312, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30531014

ABSTRACT

Exogenous electrical nerve stimulation has been reported to promote nerve regeneration. Our previous study has suggested that endogenous automatic nerve discharge of the phrenic nerve and intercostal nerve has a positive effect on nerve regeneration at 1 month postoperatively, but a negative effect at 2 months postoperatively, which may be caused by scar compression. In this study, we designed four different rat models to avoid the negative effect from scar compression. The control group received musculocutaneous nerve cut and repair. The other three groups were subjected to side-to-side transfer of either the phrenic (phrenic nerve group), intercostal (intercostal nerve group) or thoracodorsal nerves (thoracic dorsal nerve group), with sural nerve autograft distal to the anastomosis site. Musculocutaneous nerve regeneration was assessed by electrophysiology of the musculocutaneous nerve, muscle tension, muscle wet weight, maximum cross-sectional area of biceps, and myelinated fiber numbers of the proximal and distal ends of the anastomosis site of the musculocutaneous nerve and the middle of the nerve graft. At 1 month postoperatively, compound muscle action potential amplitude of the biceps in the phrenic nerve group and the intercostal nerve group was statistically higher than that in the control group. The myelinated nerve fiber numbers in the distal end of the musculocutaneous nerve and nerve graft anastomosis in the phrenic nerve and the intercostal nerve groups were statistically higher than those in the control and thoracic dorsal nerve groups. The neural degeneration rate in the middle of the nerve graft in the thoracic dorsal nerve group was statistically higher than that in the phrenic nerve and the intercostal nerve groups. At 2 and 3 months postoperatively, no significant difference was detected between the groups in all the assessments. These findings confirm that the phrenic nerve and intercostal nerve have a positive effect on nerve regeneration at the early stage of recovery. This study established an optimized animal model in which suturing the nerve graft to the distal site of the musculocutaneous nerve anastomosis prevented the inhibition of recovery from scar compression.

13.
Zhongguo Gu Shang ; 29(6): 561-5, 2016 Jun.
Article in Chinese | MEDLINE | ID: mdl-27534090

ABSTRACT

There should be confusion about diagnosis and treatment for multiple segments cervical myelopathy in some respects. The author reviewed the literature and combined with clinical experience, proposed a new classification for cervical myelopathy according to responsibility segment areas, which dividing into single segment,double segments (continues or jumping type), multi-segment (≥ three segments). The responsible segments determination is the premise of diagnosis and also a key to determine surgical decompression segment. Decompression only according to imaging was not desirable, surgical segment should mainly relies on clinical, imaging, electrophysiological and comprehensive analysis to avoid surgery range expansion. Surgical approach and procedures are still the focus and hotspot of cervical myelopathy treatment, and no treatment standards and corresponding guidelines to consult. The author proposes that surgical approach should advocate the individual, and surgical procedure should follow simple instead of complicate, anterior and posterior combined decompression is not necessary in most cases, and anterior and posterior fixation are not need.


Subject(s)
Cervical Vertebrae/surgery , Spondylosis/diagnosis , Spondylosis/surgery , Decompression, Surgical , Humans , Treatment Outcome
14.
Mol Med Rep ; 12(5): 7699-704, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26459830

ABSTRACT

Increasing evidence has indicated that the generation of reactive oxygen species (ROS) contributes to H2O2­induced nerve injury. This may result in oxidative stress that leads to cell damage or death. Dietary or pharmaceutical augmentation of the endogenous antioxidant defense capacity is a potential means by which to prevent ROS­induced damage. The aim of the current study was to investigate the effect of luteolin on H2O2­induced cell apoptosis in cultured rat pheochromocytoma cells (PC12 cells) and to investigate the role of the phosphatidylinositol­3­kinase (PI3K)/protein kinase B (Akt) pathway on H2O2­induced apoptosis. The results demonstrated that luteolin was able to inhibit the reduction in cell viability induced by H2O2. In addition, luteolin reduced ROS generation and lactate dehydrogenase release in H2O2­treated PC12 cells. The levels of superoxide dismutase and glutathione peroxidase activity were increased following treatment with luteolin, however malondialdehyde levels were observed to be reduced. Additionally, luteolin increased the Bcl­2/Bax ratio and enhanced Akt phosphorylation. However, these alterations were attenuated by pretreatment with an inhibitor of the PI3K/Akt pathway. In conclusion, luteolin inhibited H2O2­induced apoptosis via reducing ROS levels and activating the PI3K/Akt pathway.


Subject(s)
Apoptosis/drug effects , Hydrogen Peroxide/metabolism , Luteolin/pharmacology , Neurons/drug effects , Neuroprotective Agents/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Animals , Antioxidants/pharmacology , Neurons/cytology , Neurons/metabolism , Oxidative Stress/drug effects , PC12 Cells , Rats , Signal Transduction/drug effects
15.
Zhonghua Yi Xue Za Zhi ; 93(25): 1989-92, 2013 Jul 02.
Article in Chinese | MEDLINE | ID: mdl-24169251

ABSTRACT

OBJECTIVE: To explore the expression of renin-angiotensin system component (ACE-AngII-AT1/AT2 & ACE2-Ang-(1-7)-Mas) in endometrium of polycystic ovary syndrome (PCOS) patients and normal controls. METHODS: Thirty cases of normal endometrium in proliferative and secretory phases respectively were selected for the protein levels of AngII, AT1, AT2, ACE2, Ang-(1-7) and Mas through immunohistochemistry. And the specimens of proliferative endometrium from 15 PCOS patients and 15 normal controls respectively were prepared for the expressions of AT1, AT2, ACE2 and Mas mRNA through relative quantitative -polymerase chain reaction (RQ-PCR). The histological phases of endometria were confirmed by hematoxylin & eosin staining under microscope. RESULTS: The expressions of AngII, AT1R, AT2R, ACE2, Ang-(1-7) and Mas showed periodical changes in endometrium throughout normal menstrual cycles and shared a similar trend. The expression was more pronounced in epithelial cells than that in stromal cells while it was also more dramatic in secretory phase than proliferative phase; The mRNA expressions of AT1, AT2, ACE2 and MAS were higher in PCOS endometrium than those in normal controls. Statistically significant differences existed between two groups (P < 0.01). CONCLUSIONS: There is local existence of RAS in endometrium; Increased expressions of AT1 mRNA, AT2 mRNA, ACE2 mRNA and Mas mRNA in endometrium of PCOS may influence endometrial development and play a role in the pathological process of PCOS.


Subject(s)
Angiotensin I/metabolism , Endometrium/metabolism , Peptide Fragments/metabolism , Peptidyl-Dipeptidase A/metabolism , Polycystic Ovary Syndrome/metabolism , Proto-Oncogene Proteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Renin-Angiotensin System , Adult , Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2 , Case-Control Studies , Female , Humans , Proto-Oncogene Mas , Receptors, Angiotensin/metabolism , Young Adult
17.
Zhonghua Yi Xue Za Zhi ; 92(17): 1187-9, 2012 May 08.
Article in Chinese | MEDLINE | ID: mdl-22883007

ABSTRACT

OBJECTIVE: To assess the significance of intraluminal ultrasound in the diagnosis of developmental status and treatment effect in normal and idiopathic precocious puberty (ICPP) girls. METHODS: Endorectal ultrasonography was used to measure the parameters of uterine length, width, thickness, cervix length, ovarian volume and maximum follicular length in normal girls and compare their differences between pre- and post-treatment by gonadotropin-releasing hormone analogues (GnRHa) in idiopathic precocious puberty girls. RESULTS: The ultrasonic parameters of uterus and ovary in normal girls significantly increased in average 9-year-old girls (1.87 ± 0.58) ml of uterine volume in 9-year-old group vs (1.03 ± 0.24) ml in 7-year-old group; ovarian volume (3.01 ± 2.73) ml of uterine volume in 9-year-old group vs 0.98 ± 0.36 ml in 7-year-old group. They were much greater in ICPP girls and decreased significantly at post-treatment, (1.16 ± 0.19) ml of uterus volume pre-treatment vs (1.02 ± 0.15) ml post-treatment; (2.11 ± 0.48) ml of ovarian volume pre-treatment, (1.72 ± 0.55) ml post-treatment; (1.36 ± 0.25) cm of the biggest follicular diameter pre-treatment, (1.16 ± 0.36) cm post-treatment. CONCLUSION: Endosonography is an important tool of evaluating the development status and treatment effect in normal and ICPP girls.


Subject(s)
Child Development , Endosonography , Puberty, Precocious/diagnostic imaging , Adolescent , Child , Female , Humans , Ovary/diagnostic imaging , Puberty , Uterus/diagnostic imaging
18.
Zhongguo Gu Shang ; 21(1): 4-6, 2008 Jan.
Article in Chinese | MEDLINE | ID: mdl-19102257

ABSTRACT

OBJECTIVE: To evaluate the therapeutic effect of percutaneous vertebroplasty (PVP) guided by X-ray fluoroscopy in treating osteoporotic spinal compression fractures, hemangioma of vertebra and metastatic carcinoma of vertebra. METHODS: One hundred and ninety patients with 275 diseased vertebra underwent PVP under the guidance of C-arm fluoroscopy (male 80, female 110, ranging in age from 53 to 91 years, with an average of 66 years). Bone marrow biopsy needle was inserted percutaneously via transpedicular way into the diseased vertebra. Polymethylmethacrylate (PMMA) was then injected into the diseased vertebra. Visual analogue scale (VAS), mobility and analgesic usage were evaluated pre-operation and 3 months after PVP. RESULTS: PVP was successful in 190 cases (275 vertebrae). VAS was tested by t test at 3 months after PVP (P < 0.05). Simultaneously, scale of patient's mobility and scale of analgesic usage was tested by rank sum test at 3 months after PVP (P < 0.05). CONCLUSION: As the mimimally invasive operation, PVP can alleviate pain in early time, avoid kinds of complications by shortening the patient's time in bed and have the characteristic of simply operative procedure and low expenses. It is an effective mini-invasive technique for osteoporotic spinal compression fractures, hemangioma of vertebra and metastatic carcinoma of vertebra.


Subject(s)
Fractures, Compression/surgery , Osteoporosis/complications , Spinal Fractures/surgery , Spinal Neoplasms/surgery , Vertebroplasty/methods , Aged , Aged, 80 and over , Female , Fluoroscopy , Humans , Male , Middle Aged , Polymethyl Methacrylate , Postoperative Complications/prevention & control , Vertebroplasty/adverse effects
19.
Chin Med J (Engl) ; 119(20): 1721-6, 2006 Oct 20.
Article in English | MEDLINE | ID: mdl-17097020

ABSTRACT

BACKGROUND: The myocardial ATP sensitive potassium channel (K(ATP) channel) has been known for more than two decades, the properties of this channel have been intensively investigated, especially the myocardial protection effect by opening this channel. Numerous studies, including hypothermic, using K(ATP) agonists to achieve a hyperpolarizing cardioplegic arrest, have shown a better myocardial protection than potassium arrest. However, there is no evidence showing that K(ATP) channel could be opened by its agonists under profound hypothermia. We investigated the effect of temperature on activation of myocardial K(ATP) channel by nicorandil. METHODS: Isolated ventricular myocytes were obtained by collagenase digestion of the hearts of guinea pigs and stored in KB solution at 4 degrees C. With a steady ground current, the myocytes were perfused with 1 mmol/L nicorandil until a steady IK(ATP) occurred. Then the cells were perfused with 1 mmol/L nicorandil plus 1 micromol/L glybenclamide. Currents signals were recorded on whole cells using patch clamp technique at several temperatures. The temperature of the bath solution around myocytes was monitored and was controlled at 4 degrees C, 10 degrees C, 20 degrees C, 25 degrees C and 35 degrees C respectively. About 10 cells were tested at each temperature, the cells were considered useful only when the outward current could be induced by nicorandil and blocked by glybenclamide. All data were analyzed using Graphpad PRISM 3.0 (Graphpad, San Diego, CA, USA). Nonlinear curve fitting was done in Clampfit (Axon) or Sigmaplot (SPSS). RESULTS: At 4 degrees C, 10 degrees C, 20 degrees C, 25 degrees C and 35 degrees C, the time needed to open the myocardial K(ATP) channel was (81.0 +/- 0) minutes, (50.5 +/- 11.7) minutes, (28.8 +/- 2.3) minutes, (9.4 +/- 10.2) minutes and (2.3 +/- 1.0) minutes respectively (P = 0.003). The linear relationship between temperature and time needed to open the channel was y (min) = (4348.790 - 124.277x)/60, where y (min) is time needed to open K(ATP) channel, x is temperature, correlation coefficient r = -0.942 (P = 0.00), regression coefficient b = -124.277 (P = 0.00). The current densities among different temperatures were statistically different (P = 0.022), the current density was greater after the activation of K(ATP) channel at higher temperatures. The lower the temperature, the fewer cells in which K(ATP) channels could be opened. At 4 degrees C, only one cell in which the K(ATP) channel could be opened, took a quite long time (81 minutes) and the I-V curve was quite untypical. CONCLUSIONS: K(ATP) channel activated by nicorandil is temperature dependent and the temperature linearly related to time needed to open K(ATP) channel; the lower the temperature, the longer the time needed to open channel and the smaller the current density. At profound hypothermia, it is difficult to activate K(ATP) channels.


Subject(s)
Adenosine Triphosphate/pharmacology , Myocytes, Cardiac/metabolism , Nicorandil/pharmacology , Potassium Channels/drug effects , Animals , Female , Glyburide/pharmacology , Guinea Pigs , Heart Ventricles , Male , Patch-Clamp Techniques , Potassium Channels/physiology , Temperature
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 27(9): 769-72, 2006 Sep.
Article in Chinese | MEDLINE | ID: mdl-17299961

ABSTRACT

OBJECTIVE: To investigate the carrier ratio and the genotype of thalassemia in the rural people of reproductive age in Nanning, and to analyze the characteristics of hematologic parameter in thalassemia carriers. METHODS: 2044 cases of productive age youths were detected with hemoglobin autoanalyse-Variant (HPLC) and Cell Dyn 1700 automatic hemocyte analysator. Among them,430 cases (75 couples randomly selected in thalassemia screening, 140 couples who were told that one or both of them were positive for thalassemia phenotype through hemocyte analysis) carried out thalassemia gene detection in synchronism. RESULTS: 163 cases were detected beta-thalassemia and the thus beta-thalassemia carrier ratio was 7.97%. 13 cases were detected HbH disease, and 2 cases Hb Manitoba, 2 cases HbJ, and 1 case HbQ. As for genotypes,-alpha (3.7)/alpha,-alpha(CS)/alphaalpha and -alpha(WS)/alphaalpha were common ones with in alpha-thalassemia-2, --(SEA)/alphaalpha the most common one in alpha-thalassemia-1, and 41-42 were the most common ones in beta-thalassemia heterozygotes. The detection ratio of alpha,beta combination thalassemia was also relatively high. Mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were low in all cases of HbH disease and beta-thalassemia, also low in 86 cases of alpha-thalassemia-1 with the exception of normal MCH in 1 case, yet normal in 17 cases out of 66 cases of alpha-thalassemia-2. HbF raised in 32 cases out of 69 cases of beta-thalassemia heterozygote, no case showed raised HbF without the raise of HbA2. Hematologic characteristic of alpha, beta combination thalassemia was mainly caused by beta-thalassemia. CONCLUSION: Carrier ratio of thalassemia in rural productive age youths in Nanning was high while alpha-thalassemia-2 with the genotype -alpha(WS)/alphaalpha and -alpha(CS)/ alphaalpha were common. To those with low MCV and MCH in high-risk region, thalassemia should be suspected.


Subject(s)
alpha-Thalassemia/genetics , beta-Thalassemia/genetics , Adult , Carrier State , China/epidemiology , Genotype , Humans , Mass Screening , Rural Population , alpha-Thalassemia/diagnosis , alpha-Thalassemia/epidemiology , beta-Thalassemia/diagnosis , beta-Thalassemia/epidemiology
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