Objective To explore the mechanism by which the sanguis draconis flavones(SDF)regulates the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway to mediate cell pyroptosis and improve cerebral ischemia-reperfusion injury(CIRI)in rats.Methods The experimental rats were randomly divided into the control group(Ctrl),the CIRI group,the low-dose SDF group(SDF-L),the high-dose SDF group(SDF-H),and the SDF-H+ROS/TXNIP pathway activator,trimethylamine oxide(TMAO)group(SDF-H+TMAO).Among them,except for the control group,the remaining rats all needed to establish the CIRI rat model by the modified suture method.Zea Longa scoring was performed on rats from each group.ELISA was used to detect the levels of serum inflammatory factors interleukin(IL)-1β,IL-18 and oxidative stress-related factors superoxide dismutase(SOD),malondialdehyde(MDA),glutathione peroxidase(GSH-Px).Flow cytometry was used to measure the ROS levels.Cerebral edema was detected.Cerebral infarction was detected by 2,3,5-triphenyl tetrazolium chloride(TTC)staining.HE staining was used to detect the pathological changes of brain tissue.Immunohistochemistry was used to detect the expression of pyrolytic effector protein dermolin D(GSDMD).Western blotting was used to detect the expression of proteins related to the ROS/TXNIP pathway.Results Compared with the control group,a large area of cerebral infarctions were observed in the brain tissue of the CIRI group,accompanied by mild hemorrhage and obvious infiltration of inflammatory cells.Neuronal cells underwent degeneration and necrosis,with sparse and disordered arrangement.The phenomena of nuclear condensation and nucleolus lysis were obvious.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-related punctate protein(ASC),and Caspase-1 increased,while the activities of SOD and GSH-Px decreased(P＜0.05).Compared with the CIRI group,the pathological damage of brain tissues in the SDF-L group and the SDF-H group was significantly improved.The Zea Longa score,cerebral infarction volume,brain tissue water content,levels of IL-1β,IL-18,ROS,MDA,and the expressions of GSDMD,TXNIP,NLRP3,ASC,and Caspase-1 decreased.The activities of SOD and GSH-Px increased(P＜0.05);TMAO treatment partially reversed the improvement effect of SDF on CIRI in rats.Conclusion SDF ameliorates cerebral CIRI in rats by inhibiting ROS/TXNIP pathway-mediated pyroptosis.

The pathogenesis of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is highly heterogeneous and still unclear. Additional novel variants have been recently detected in the population. The molecular and cellular effects of these previously unreported variants are still poorly understood and require further characterization. To address this problem, we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD deficiency. Marked deficiencies in fatty acid oxidation (FAO) and other mitochondrial defects were observed in cells carrying one of these six variants (c.541C>T, c.863T>G, c.895A>G, c.1238T>C, c.1276G>A, and c.1505T>A), including reductions in mitochondrial respiratory-chain function and adenosine triphosphate (ATP) production, and increased levels of mitochondrial reactive oxygen species (ROS). Intriguingly, higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited stress. Moreover, the stability of the mutant homodimer was disturbed, and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics (MD) simulation. The data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.

Auditory function in vertebrates depends on the transduction of sound vibrations into electrical signals by inner ear hair cells. In general, hearing loss resulting from hair cell damage is irreversible because the human ear has been considered to be incapable of regenerating or repairing these sensory elements following severe injury. Therefore, regeneration and protection of inner ear hair cells have become an exciting, rapidly evolving field of research during the last decade. However, mammalian auditory hair cells are few in number, experimentally inaccessible, and barely proliferate postnatally in vitro. Various in vitro primary culture systems of inner ear hair cells have been established by different groups, although many challenges remain unresolved. Here, we briefly explain the structure of the inner ear, summarize the published methods of in vitro hair cell cultures, and propose a feasible protocol for culturing these cells, which gave satisfactory results in our study. A better understanding of in vitro hair cell cultures will substantially facilitate research involving auditory functions, drug development, and the isolation of critical molecules involved in hair cell biology.
Animals ; Cells, Cultured ; Hair Cells, Auditory/physiology* ; Mice ; Mice, Inbred C57BL

PURPOSEWe once reported blast-induced traumatic brain injury (bTBI) in confined space. Here, bTBI was studied again on goats in the open air using 3.0 kg trinitrotoluene.

METHODSThe goats were placed at 2, 4, 6 and 8 m far from explosion center. Trinitrotoluene (TNT) was used as the source of the blast wave and the pressure at each distance was recorded. The systemic physiology, electroencephalogram, serum level of S-100 beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 h after the exposure.

RESULTSSimple blast waveforms were recorded with parameters of 702.8 kPa-0.442 ms, 148.4 kPa-2.503 ms, 73.9 kPa-3.233 ms, and 41.9 kPa-5.898 ms at 2, 4, 6 and 8 m respectively. Encephalic blast overpressure was on the first time recorded in the literature by us at 104.2 kPa-0.60 ms at 2 m, where mortality and burn rate were 44% and 44%. Gross examination showed that bTBI was mainly manifested as congestive expansion of blood vessels and subarachnoid hemorrhage, which had a total incidence of 25% and 19% in 36 goats. Microscopical observation found that the main pathohistological changes were enlarged perivascular space (21/36, 58%), small hemorrhages (9/36, 25%), vascular dilatation and congestion (8/36, 22%), and less subarachnoid hemorrhage (2/36, 6%). After explosion, serum levels of S-100b and NSE were elevated, and EEG changed into slow frequency with declined amplitude. The results indicated that severity and incidence of bTBI is related to the intensity of blast overpressure.

CONCLUSIONBlast wave can pass through the skull to directly injure brain tissue.

Animals ; Blast Injuries ; complications ; Brain ; pathology ; Brain Injuries, Traumatic ; etiology ; pathology ; Electroencephalography ; Goats ; Male ; Phosphopyruvate Hydratase ; blood ; S100 Calcium Binding Protein beta Subunit ; blood

OBJECTIVETo investigate the correlation between Angle's class III patients' occlusion plane and anterior overbite by controlling the changes in occlusion plane during orthodontic treatment.

METHODSIn total, 90 Angle's class III adult orthodontic patients were selected as the experimental group, and 30 normal adults were selected as the control group. According to the overbite, the class III patients were divided into three groups, and 14 indicators were measured. ANOVA and multiple comparison analysis were used to analyze the difference between class III patients, and linear analysis was used to analyze the correlation between anterior overbite and anterior-posterior occlusion plane.

RESULTSIn class Ill patients, posterior occlusion plane and anterior overbite size were negatively correlated (r = -0.24, P < 0.05), whereas anterior occlusal plane and anterior overbite size were positive correlated (r = 0.23, P < 0.05).

CONCLUSIONThe shape of the occlusion plane varies in different anterior overbite patients. During orthodontic treatment in different overbite class III patients, the vertical height of the posterior teeth and the rotation of the occlusion plane should be controlled.

Adult ; Dental Occlusion ; Humans ; Malocclusion, Angle Class III ; Overbite ; Tooth

Objective To investigate the correlation between Angle’s class Ⅲ patients’ occlusion plane and anterior overbite by controlling the changes in occlusion plane during orthodontic treatment. Methods In total, 90 Angle’s class Ⅲ adult orthodontic patients were selected as the experimental group, and 30 normal adults were selected as the control group. According to the overbite, the class Ⅲ patients were divided into three groups, and 14 indicators were measured. ANOVA and multiple comparison analysis were used to analyze the difference between class Ⅲ patients, and linear analysis was used to analyze the correlation between anterior overbite and anterior-posterior occlusion plane. Results In class Ⅲ patients, posterior occlusion plane and anterior overbite size were negatively correlated (r=-0.24, P<0.05), whereas anterior occlusal plane and anterior overbite size were positive correlated (r=0.23, P<0.05). Conclusion The shape of the occlusion plane varies in different anterior overbite patients. During orthodontic treatment in different overbite class Ⅲ patients, the vertical height of the posterior teeth and the rotation of the occlusion plane should be controlled.

OBJECTIVETo explore the feasibility and safety of conditioning regimen containing fludarabine (Flud) for haploidentical hematopoietic stem cell transplantation (HSCT).

METHODSPreparative regimen containing Flud 40 mgxm(-2)xd(-1) on day -7 to -3 in place of cyclophosphamide (CTX) for haploidentical HSCT was given to 35 patients with hematologic malignancies (4 standard risk, 16 high risk, 15 relapse with no remission). All donors received rhG-CSF followed by HSC harvest. One patient received peripheral blood HSCT (PBSCT), one bone marrow transplantation (BMT), and the others BM combination with PBSCT. The regimen-associated side effect, engraftment, incidence of graft-versus-host disease (GVHD) and disease-free survival (DFS) probabilities were observed.

RESULTSAll patients achieved sustained, full donor-type engraftment. Thirty-four patients obtained primary durable engraftment, and 1 who rejected graft from his mother obtained successful durable engraftment after the second graft from his father. The cumulative incidence of grade III-IV acute GVHD and chronic GVHD was 12.1% and 31.7%, respectively. With a follow-up duration of 8-25 months, 6 patients were dead, in which 3 died of relapse, 2 of acute GVHD, 1 of fungal infection, none died of regimen-associated side effect. The other 29 patients remained alive and DFS probability was 79.7%.

CONCLUSIONFlud based conditioning regimens for haploidentical HSCT is safe and feasible, which reduces regimen-associated side effect, with no increasing the rate of relapse and infection, and decreases the incidence of aGVHD.

Adolescent ; Adult ; Child ; Child, Preschool ; Cyclophosphamide ; Feasibility Studies ; Female ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Transplantation Conditioning ; adverse effects ; methods ; Transplantation, Homologous ; Vidarabine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult

OBJECTIVETo describe the early experiences with rFVIIa in the management of bleeding after cardiovascular surgery.

METHODSFrom May 2006 through December 2007, 16 patients received rFVIIa during or after surgery despite conventional medical therapy and transfusion of blood products. There were 15 male patients and 1 female patients, aged from 36 to 77 years old with a mean of 52 years old. The surgical procedures include aortic procedures for 8 cases, valve replacement for 6 cases, pulmonary thromboendarterectomy for 1 case and atrial septal defect repair for 1 case. The data of these patients were reviewed and the safety and efficacy of rFVIIa after cardiovascular surgery were evaluated.

RESULTSrFVIIa was administered as a first dose of 27.6 to 54.5 microg/kg with a mean of 40.2 microg/kg. Six patients achieved hemostasis after the first dose. Nine patients received a second administration within 30 min, with a cumulative dose of 59.3 to 90.9 microg/kg, a mean of 80.3 microg/kg. Eight patients achieved hemostasis and 1 patient went to exploration. One patient received four doses of rFVIIa with a cumulative dose of 203.4 microg/kg and the bleeding stopped. Mean amount of chest drain loss and the amount of red blood cell, fresh frozen plasma, cryoprecipitate, and platelet transfusions decreased significantly after rFVIIa administration. The total amount of chest drain losses, transfusions of red blood cell and cryoprecipitate within 12 h postoperatively was positively correlated with the time from the end of bypass to administration of rFVIIa. No thromboembolic complications and other adverse reactions were noted.

CONCLUSIONSThe use of rFVIIa is associated with reduced blood loss, rapid improvement of coagulation variables, and decreased need for blood products. rFVIIa is safe and efficacious in the management of refractory postcardiotomy bleeding.

Adult ; Aged ; Cardiovascular Surgical Procedures ; Coagulants ; administration & dosage ; therapeutic use ; Factor VIIa ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Postoperative Hemorrhage ; drug therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies

OBJECTIVETo compare the grafts' blood flow after on-pump and off-pump coronary artery bypass graftings.

METHODSFive hundred and forty-seven cases were studied, including four hundred and three cases undergoing off-pump coronary artery bypass (OPCAB, off-pump group) and one hundred and forty-four cases undergoing on-pump coronary artery bypass (CCABG, on-pump group). In all cases left internal mammary artery (LIMA) was routinely anastomosed to left anterior descending artery (LAD), and saphenous vein (SV) to the other target vessels in sequential mode when there were more than two anastomoses. After all anastomoses were completed and hemodynamic status was stable, transit time flow-meter was utilized to measure and record the grafts' flow wave, pulsatility index (PI), value of mean flow, diastolic and systolic peak flow, vascular resistance, insufficiency ratio and mean blood pressure.

RESULTSPI, insufficiency ratio and diastolic peak flow of LIMA in off-pump group were 2.7 +/- 1.8, (2.2 +/- 4.3)%, (46.8 +/- 2.7) ml/min respectively; those in on-pump group were 2.8 +/- 2.0, (3.4 +/- 3.1)% and (52.8 +/- 3.7) ml/min respectively. And those of SV in off-pump group were 2.8 +/- 0.1, (1.8 +/- 0.3)% and (85.8 +/- 3.2) ml/min respectively and those in on-pump group were 2.6 +/- 0.2, (1.3 +/- 0.2)% and (93.9 +/- 5.6) ml/min respectively. For both LIMA and SV grafts' blood flow there was no significant difference in PI, insufficiency ratio, diastolic peak flow and mean blood pressure in both groups (P > 0.05). The mean flow and systolic peak flow in off-pump group were significantly less than those in on-pump, while the vascular resistance in off-pump group was significantly greater than that in on-pump group (P < 0.01).

CONCLUSIONThere is no significant difference in grafts' patency between OPCAB and CCABG.

Adult ; Aged ; Aged, 80 and over ; Coronary Artery Bypass ; Coronary Artery Bypass, Off-Pump ; Female ; Humans ; Male ; Mammary Arteries ; physiology ; transplantation ; Middle Aged ; Monitoring, Intraoperative ; Regional Blood Flow ; Saphenous Vein ; physiology ; transplantation ; Vascular Patency ; Vascular Resistance

OBJECTIVETo analyze retrospectively 1018 patients who underwent coronary artery bypass grafting surgery (CABG) in order to summarize surgical techniques and clinical outcome.

METHODSFrom 1997 through 2004, data of same surgeon for 508 patients who underwent conventional coronary artery bypass surgery on pump (CCABG) and 510 patients who underwent off-pump CABG (OPCAB) were collected and analyzed retrospectively. Eight hundred and fifty-two patients had unstable angina, 582 patients were over 60 years old (57.2%) and 784 patients had concomitant diseases including valve lesion, hypertension, diabetes, myocardial infarction, left ventricular aneurysm with septal defect, stroke, chronic obstructive pulmonary diseases, renal failure and cancer. A hundred and fifty-six patients had left main stem (LIMS) stenosis and 671 patients, triple-vessel disease.

RESULTSTotal mortality was 0.39% (4-case death) and morbidity, 1.6% (sternal dehiscence, stroke and mediastinitis). The grafts per patient with CCABG and OPCAB were 3.3 +/- 0.6 vs. 2.5 +/- 0.4. Left internal mammary artery use was 93.8% of the patients, 29 patients were implanted intra-aortic balloon pump intraoperatively. Follow-up was 4 months to 7 years.

CONCLUSIONSScientific surgical strategies, excellent surgical techniques and improvement of cardiac anesthesia and cardiopulmonary bypass make the mortality and morbidity decrease significantly, CABG surgery is safe and effective in patients with coronary artery disease.

Aged ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; methods ; mortality ; Coronary Artery Bypass, Off-Pump ; Coronary Disease ; mortality ; surgery ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome