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Biomedical subjects

Feng Ling

Publications and source records attributed to Feng Ling.

At least 19 recordsLinked to original sources

Mild hypothermia diminishes oxidative DNA damage and pro-death signaling events after cerebral ischemia: a mechanism for neuroprotection.

Mild hypothermia, applied either during or soon after cerebral ischemia, has been shown to confer robust neuroprotection against brain injury in experimental stroke and in patients recovering from cardiac arrest. However, the mechanism underlying hypothermic neuroprotection is not completely understood. In this study, the effect of mild hypothermia on the induction of oxidative DNA damage, an early harmful event during post-ischemic reperfusion that triggers both necrotic and apoptotic cell death in the brain, was studied using the rat model of middle cerebral artery occlusion (MCAO) and reperfusion. Rats were subjected to 2-hr MCAO and reperfusion of various durations up to 3 days. Selective brain hypothermia (33 degrees C) was induced at the onset of ischemia and terminated at the beginning of reperfusion, and this significantly decreased infarct volume 72 hr later. Correlated with this protective effect, intraischemic mild hypothermia markedly attenuated the nuclear accumulations of several oxidative DNA lesions, including 8-oxodG, AP sites, and DNA single-strand breaks, after 2-hr MCAO. Consequently, harmful DNA damage-dependent signaling events, including NAD depletion, p53 activation, and mitochondrial translocation of PUMA and NOXA, were reduced during post-ischemic reperfusion in hypothermia-treated brains. These results suggest that the attenuation of oxidative DNA damage and DNA damage-triggered pro-death signaling events may be an important mechanism underlying the neuroprotective effect of mild hypothermia against ischemic brain injury.

Animals↗

Impaired DNA repair via the base-excision repair pathway after focal ischemic brain injury: a protein phosphorylation-dependent mechanism reversed by hypothermic neuroprotection.

Cerebral ischemia and reperfusion induces rapid accumulation of oxidative DNA lesions in the brain, which, if not repaired promptly, may trigger cell death. The base-excision repair (BER) pathway is the main mechanism employed by neurons to repair various types of oxidative DNA damage. Recent studies have suggested that the cellular activity of BER is highly regulated (up- or down-regulated) after ischemic brain injury, and this regulation may contribute to the outcome of cell injury. The mechanism through which cellular BER is regulated in response to neuronal injury is currently poorly understood. In the present study, we have examined BER regulation in the rat model of focal ischemic brain injury induced by 2 hr of middle cerebral artery occlusion and 0-72 hr of reperfusion. As determined using cerebral nuclear extracts, focal ischemia resulted in a marked reduction in BER activities, including the overall BER activity, AP endonuclease activity and DNA polymerase-beta activity, indicating functional impairment of the BER pathway. BER reduction occurred as early as 0.5 hr after the onset of reperfusion. Thereafter, BER activity failed to recover, and there were persistent accumulations of apurinic/apyrimidinic abasic sites and DNA single-strand breaks in ischemic tissues. The reduction in BER during the early reperfusion phase (less than 6 hr) was not accompanied by any alterations in the levels of essential BER enzymes in brain extracts. However, increased serine- and threonine-specific phosphorylation was detected for both AP endonuclease and DNA polymerase-beta after ischemia, with the time course of serine phosphorylation closely correlated to that of changes in BER activity. Furthermore, dephosphorylation of nuclear extracts with alkaline phosphatase largely restored AP endonuclease and DNA polymerase-beta activities. Taking advantage of the neuroprotective effect of mild hypothermia (33 degrees C), which was induced in the brain during the first 2 hr of reperfusion, we found that the post-ischemic suppression of BER activity is a reversible event. Hypothermic treatment diminished the serine-specific phosphorylation of AP endonuclease and DNA polymerase-beta, promoted BER activities, and attenuated the levels of oxidative DNA lesions after ischemia. These results suggest that the functional impairment of the BER pathway after severe focal cerebral ischemia is due to the loss-of-function post-translational modifications of repair enzymes. Further investigations elucidating the precise mechanism underlying the post-translational regulation of BER enzymes may lead to novel therapeutic strategies for cerebral ischemia.

Animals↗

DNA recombination-initiation plays a role in the extremely biased inheritance of yeast [rho-] mitochondrial DNA that contains the replication origin ori5.

Hypersuppressiveness, as observed in Saccharomyces cerevisiae, is an extremely biased inheritance of a small mitochondrial DNA (mtDNA) fragment that contains a replication origin (HS [rho(-)] mtDNA). Our previous studies showed that concatemers (linear head-to-tail multimers) are obligatory intermediates for mtDNA partitioning and are primarily formed by rolling-circle replication mediated by Mhr1, a protein required for homologous mtDNA recombination. In this study, we found that Mhr1 is required for the hypersuppressiveness of HS [ori5] [rho(-)] mtDNA harboring ori5, one of the replication origins of normal ([rho(+)]) mtDNA. In addition, we detected an Ntg1-stimulated double-strand break at the ori5 locus. Purified Ntg1, a base excision repair enzyme, introduced a double-stranded break by itself into HS [ori5] [rho(-)] mtDNA at ori5 isolated from yeast cells. Both hypersuppressiveness and concatemer formation of HS [ori5] [rho(-)] mtDNA are simultaneously suppressed by the ntg1 null mutation. These results support a model in which, like homologous recombination, rolling-circle HS [ori5] [rho(-)] mtDNA replication is initiated by double-stranded breakage in ori5, followed by Mhr1-mediated homologous pairing of the processed nascent DNA ends with circular mtDNA. The hypersuppressiveness of HS [ori5] [rho(-)] mtDNA depends on a replication advantage furnished by the higher density of ori5 sequences and on a segregation advantage furnished by the higher genome copy number on transmitted concatemers.

Alloxan↗

[Analysis of the causes of surgical complications of medial sphenoidal ridge meningioma].

OBJECTIVE: To find out the causes of severe surgical complications of sphenoidal ridge meningioma of and the methods to avoid them. METHODS: The clinical data of 56 cases of sphenoidal ridge meningioma, 37 being medial (clinoidal) type, 5 being middle (alar) type, and 14 being lateral (pterional) type, with the diameters of 3.5 - 7 cm, 3.8 - 5.2 cm, and 3.8 - 7.5 cm respectively, who underwent operation. RESULTS: The tumors of 19 cases of lateral and middle types were resected completely without surgical complication. Facial nerve injury occurred in 2 cases of medial type because of failure to know well the course of facial nerve and over-stretching of skin flap. Oculomotor nerve injury occurred in 7 cases, 5 of which were transient, and trochlear nerve injury occurred in 1 case, all caused by inappropriate manipulations. Too early resection of tumor-related vessel caused middle cerebral artery injury in one case. Resection of the tumor infiltrating the carotid artery inadequately caused injury of the carotid artery. Lenticulostriate artery injury was caused in 2 cases by over-separation of the lateral fissure. CONCLUSION: Severe surgical complications can be avoided if the surgeons, with great skills, are able to predict different topographic changes and difficulties encountered during operation in the light of the specific conditions in operation.

Adolescent↗

[Effects of puerarin on proliferation of vascular smooth muscle cells induced by thrombin].

OBJECTIVE: To investigate the effects of puerarin on the proliferation of vascular smooth muscle cells (VSMC) induced by thrombin and the mechanism thereof. METHODS: VSMCs were isolated from the thoracic aorta of a SD rat and cultured, then co-cultured with thrombin of the concentration 0.1, 0.3, 1.0, 3.0, and 10 U/L for 24 h, thrombin of the concentration of 1 U/L for 0, 6, 12, 24, 36, and 48 h respectively, or thrombin of the concentration of 1 U/L combined with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), or 1.5 x 10(-3) mol/L for 24 h. Flow cytometry was used to detect the cell number and cell cycle. Western blotting was used to indicate the protein expression of the oncogenes c-fos and bcl-2 RT-PCR was used to evaluate the thrombin receptor (TR) mRNA expression. RESULTS: he numbers of the groups of VSMCs stimulated by 0.1, 0.3, 1.0, 3.0, and 10 U/L thrombin for 24 hours were 4.82 x 10(4)/ml +/- 0.11 x 10(4)/ml, 6.37 x 10(4)/ml +/- 0.09 x 10(4)/ml, 8.78 x 10(4)/ml +/- 0.08 x 10(4)/ml, 7.37 x 10(4)/ml +/- 0.07 x 10(4)/ml, and 5.28 x 10(4)/ml +/- 0.12 x 10(4)/ml respectively, all significantly higher than that of the control group (4.08 +/- 0.054 x 10(4)/ml, all P < 0.05). The effect of thrombin was in a dose-dependent manner within a concentration range of 0.1 - 1.0 U/L. The suppression rates of VSMC proliferation in the combination groups with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), and 1.5 x 10(-3) mol/L were 10.9% +/- 1.6%, 32.1% +/- 3.3%, and 42.6% +/- 5.2% respectively in comparison with the thrombin group (all P < 0.05). The c-fos protein expression of the VSMCs after thrombin stimulation for 24 h increased by 156.0% +/- 11.3% (P < 0.05), and the bcl-2 protein expression of the VSMCs pretreated with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), and 1.5 x 10(-3) mol/L, and then stimulated by thrombin was significantly lower than that of the VSMCs only stimulated by thrombin with the suppression rates of 20.7% +/- 2.1%, 31.6% +/- 5.2%, and 44.5% +/- 7.5% respectively (all P < 0.05). The bcl-2 protein expression of the VSMCs after thrombin stimulation for 24 h increased by 96.7% +/- 8.3% (P < 0.05), and the bcl-2 protein expression of the VSMCs pretreated with puerarin of the concentrations of 1.5 x 10(-5), 1.5 x 10(-4), and 1.5 x 10(-3) mol/L, and then stimulated by thrombin was significantly lower than that of the VSMCs only stimulated by thrombin with the suppression rates of 7.1% +/- 0.8%, 18.8% +/- 1.2%, and 39.6% +/- 6.4% respectively (all P < 0.05). The stimulation of thrombin increased the TR mRNA expression by 183.9% +/- 9.4%. The puerarin of the concentrations of 1.5 x 10(-5) mol/L and 1.5 x 10(-4) mol/L decreased the increase of TR mRNA expression induced by thrombin, however, without significant differences (both P > 0.05), and puerarin of the concentration of 1.5 x 10(-3) mol/L significantly suppressed the increase of TR mRNA expression induced by thrombin by 17.6% +/- 1.7% (P < 0.05). CONCLUSION: Puerarin suppresses the proliferation and DNA synthesis of VSMC induced by thrombin. The inhibitory effect of puerarin is closely related with the suppression of the protein expression of c-fos and bcl-2n, and partly related with the suppression of the TR mRNA expression.

Animals↗

[Different methods of intracranial-extracranial bypass surgery for the treatment of intracranial aneurysms].

OBJECTIVE: To investigate the effects and methods of intracranial-extracranial (IC-EC) bypass surgery in the treatment of intracranial aneurysms. METHODS: The clinical material of 9 cases, who performed IC-EC bypass surgery before occlusion of the parental arteries of intracranial aneurysms, was studied retrospectively, especially how to evaluate the co-lateral circulation of the parental arteries and how to select the different methods of IC-EC bypass surgery. RESULTS: The co-lateral circulation in 9 cases was not enough to meet the need of the cerebral blood flow after occlusion of the parental arteries of the aneurysms. Revascularization by different methods of IC-EC bypass surgery and then occlusion of the parental arteries, ischemia in the brain area feeding by occluded parental arteries of the aneurysms did not occurred. CONCLUSION: When the co-lateral circulation of the parental arteries of intracranial aneurysm is not enough, the revascularization by different methods of IC-EC bypass surgery is needed before occlusion of these arteries.

Adolescent↗

Dynamic change of coagulation and anticoagulation markers of patients with acute cerebral infarction during intravenous urokinase thrombolysis.

BACKGROUND AND OBJECTIVE: The variations of blood coagulation and anticoagulation are of clinical importance in patients with acute cerebral infarction during intravenous urokinase (UK) thrombolysis. Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes, specifically the effect of thrombolytic agents on hemostasis. In this study, we dynamically monitored the activated partial thromboplastin time (APTT), the prothrombin time (PT), the thrombin time (TT) and the activated partial thromboplasmin time (APTT) in 56 patients with acute cerebral infarction during intravenous urokinase thrombolysis and analysed the relationship among the blood coagulation biomarkers (APTT, PT, TT, AT-III), as well as baseline patient characteristics and clinical outcomes. This allowed us to explore the valuable biomarkers for securing the thrombolysis regimen in clinical practice. METHODS: The levels of PT, APTT, TT and AT-III in peripheral blood of 56 patients with acute cerebral infarction and 50 normal controls were assayed by ELISA. Dynamic transformation of these markers at the baseline and the time points of the first, second, fourth, eighth, 12th, 24th, 48th, 72nd and 96th hour after intravenous UK thrombolysis was monitored serially. The relationship between the levels of these biomarkers and the clinical effectiveness and safety of urokinase thrombolysis was evaluated. RESULTS: The levels of PT, APTT, TT and AT-III in patients before intravenous UK thrombolysis were significantly lower than those in age- and sex-matched normal controls (all p<0.05). After treatment with UK, the levels of PT and APTT rose quickly during the first 4 hours (all p< 0.05), and then gradually recovered, reaching baseline at about the 48th hour. The activity of AT-III was slightly increased and showed fluctuations after UK infusion (p< 0.05), however the fluctuated range was not remarkable and lacked specificity. CONCLUSIONS: Dynamic monitoring of PT, APTT and TT can indicate coagulative and anticoagulative functions of patients with acute cerebral infarction during intravenous urokinase thrombolysis. Monitoring of these markers can be helpful both in regulating the infusion speed and the dosage of UK, as well as increasing the efficacy and safety of UK therapy. However, assay for AT-III might be unnecessary.

Aged↗

Late angiographic stent thrombosis in a drug-eluting stent that occurred 20 months after premature discontinuation of clopidogrel administration.

Late angiographic stent thrombosis (LAST) in a drug-eluting stent has been reported in several studies. Most LAST occur just after discontinuation of antiplatelet therapy. We report the first case of LAST that occurred 21 months after implantation of a Cypher stent and 20 months after discontinuation of clopidogrel, results that suggest a mechanism other than the discontinuation of antiplatelet therapy might be responsible for LAST.

Adult↗

[Evaluation by perfusion-weighted magnetic resonance to hemodynamic character and surgical effect of carotid system stenoses or occlusion].

OBJECTIVE: To evaluate hemodynamic character and surgical effect of stenoses or occlusion of carotid artery system by perfusion-weighted MRI. METHODS: Twenty-one patients with stenoses or occlusion of carotid artery system underwent surgical treatment. Two patients underwent endarterectomy, extracranial-intracranial arterial bypass to 10 patients, and percutaneous stent angioplasty to 9 patients. RESULTS: Preoperative perfusion-weighted magnetic resonance (MR) revealed normal regional cerebral blood flow in all patients, with delayed time to peak in both middle cerebral artery distribution and border zone. Postoperative perfusion-weighted MR revealed normal time to peak in border zone, but abnormal in middle cerebral artery distribution. Evaluated by perfusion-weighted MR, it showed that surgical method can improve the hemodynamic disorder of this kind of disease. The early curative effect of endarterectomy and percutaneous stent angioplasty is better than extracranial-intracranial arterial bypass. CONCLUSIONS: Perfusion-weighted MR is a good method to evaluate hemodynamic character of stenoses or occlusion of carotid artery system. Surgical method is helpful to this kind of disease, and its curative effect can be evaluated impersonally and accurately by this new technique.

Adult↗

[Percutaneous transluminal stenting for stenosis of internal carotid artery: a report of 355 cases].

OBJECTIVE: To discuss the benefits and complications of percutaneous transluminal stenting for stenosis of internal carotid artery (ICA). METHODS: 355 patients with ICA stenosis were included from 1997 to 2003. All of them took periprocedual anticoagulation treatment, cerebral vascular angiography and cervical Doppler sonography. 72 patients used cerebral protection of filter devices. Among the 283 patients without cerebral protection 202 patients (71.38%) underwent predilation, 66 patients (23.32%) underwent postdilation; and 3 patients underwent neither. RESULTS: The heart rates of 25.0% of all the patients decreased. Dislocation of microemboli happened in 5 patients. 2 of them improved after treatment. 3 of them got dyskinesia of one side. 2 patients (0.56%) died of intracerebral hemorrhage (ICH). 256 patients (84.77%) turned for the better. 260 patients (73.34%) were followed up. Restenosis occurred in 11 patients (4.23%). CONCLUSION: Percutaneous transluminal stenting for stenosis of internal carotid artery is safe if proper periprocedual treatment and operative procedure are taken. However, enough attention should be paid to the occurrence of ICH resulting from over-flow after operation.

Adult↗

Complication analysis of intracranial aneurysm embolization with controllable coils.

OBJECTIVE: To explore the causes, prevention, and management of the complications during intracranial aneurysm embolization with controllable coils (mechanical detachable spiral, MDS; and Guglielmi detachable coil, GDC). METHODS: Retrospective review of 120 cases with 125 intracranial aneurysms embolized with controllable coils from March 1995 to July 1999 was conducted. The 20 accidents (in 18 cases) including aneurysm rupture, over-embolization, protrusion of coil end into the parent artery, and thrombosis of the parent artery were analyzed. RESULTS: Among the 20 accidents, there were 6 aneurysm ruptures, 6 over-embolizations (in 5 cases), 6 coil protrusions, and 2 thromboses (one was secondary to coil protrusion). The embolization-related mortality was 3.33% (4/120), the permanent neurological deficit was 1.67% (2/120), and the transitory neurological deficit was 3.33% (4/120). The occurrence and outcome of the complications were related to the embolizing technique, the pattern of aneurysm and its parent artery, the imperfection of embolic materials, and the observation and management during embolization. CONCLUSION: Skilled embolizing technique, better understanding of the angio-anatomy of an aneurysm and its parent artery, correct judgement and management during embolization, and improvement of embolic materials are beneficial to the reduction of complications and to the melioration of the outcome of complications.

Aneurysm, Ruptured↗