Alzheimer's disease (AD) is the most common cause of dementia in elderly population. There are two hallmark pathological lesions: the intracellular neurofibrillary tangles (NFTs) and the extracellular amyloid deposits in the senile plaques (SP). The NFTs are aggregates of hyperphosphorylated microtubule Tau protein. The amyloid deposits in the SP are the beta-amyloid (Abeta) peptides-Abeta40 and Abeta42. The Abeta peptides are derived from the amyloid precursor protein (APP) which is considered very important for the AD pathogenesis. In recent years, studies have focused on understanding the generation of Abeta peptides by the alpha-, beta- and gamma- secretase activity on APP, as cause and progression of both familial and sporadic AD (FAD and SAD). This review covers the trafficking and processing of APP, the amyloid cascade hypothesis in AD pathogenesis, the mutations in the genes encoding APP, PS1 and PS2 of early-onset and late-onset AD. The risk factor apolipoprotein E (ApoE) for AD and therapeutic anti-beta-amyloid vaccination strategies for prevention of AD are also discussed.
Alzheimer Disease ; genetics ; metabolism ; pathology ; therapy ; Alzheimer Vaccines ; immunology ; Amyloid beta-Peptides ; antagonists & inhibitors ; genetics ; immunology ; metabolism ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Apolipoproteins E ; genetics ; Humans ; Immunotherapy, Active ; Membrane Proteins ; genetics ; Peptide Fragments ; genetics ; Plaque, Amyloid ; pathology ; Presenilin-1 ; Presenilin-2

Adolescent ; Adult ; Automobile Driving ; China ; Electrocardiography ; Female ; Heart ; physiopathology ; Humans ; Male ; Middle Aged ; Noise, Occupational ; adverse effects ; Occupational Exposure ; adverse effects ; Stress, Psychological ; etiology ; physiopathology ; Vibration ; adverse effects

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.

Aim The effects of midazolam on the whole-cell sodium currents in rat sympathetic neurons were studied to explore the mechanisms where by midazolam mediates hypotension. Methods Whole-cell patch-clamp recordings were performed on enzymatically isolated rat superior cervical sympathetic neurons. Results Midazolam dose-dependently blocked the whole-cell sodium currents evoked by a voltage step to 0 mV from a holding potential of -80 mV with a mean drug concentration required to produce 50% current inhibition (IC50) values of 18.35 ?mol?L-1; Clinically relevant concentration of midazolam(0.3 ?mol?L-1) reduced sodium peak currents by 19.98%(P

Objective To investigate the curative effect of granulated cancellous bone autograft in treatment of refractory bone nonunion after limited contouring of bone ends. Methods Between 2003 and 2006, 13 patients with refractory bone nonunion were treated with external fixation and granulated cancellous bone autograft after limited contouring of bone ends. Results The mean follow-up period was 22.6 months (19-30 months), which showed that all patients gained bone union and resumed com-plete weight loading or previous job at final follow-up. The mean fixation time of external fixators was 10.6 months (7-18 months). The intermittent or persistent pin-track infection occurred in eight patients and relieved by pin-track care and oral or parenteral antibiotics, with no infection after removing external fixator. Conclusion The granulated cancellous bone autograft after limited contouring of bone ends is an effective method for treatment of refractory bone nonunion.

OBJECTIVETo investigate the feasibility and therapeutic effect of free posterior interrosseous artery flap in a bridge fashion for combined skin and bilateral artery defects at palmar side of fingers.

METHODS6 cases with combined skin and bilateral artery defects at palmar side of fingers were treated with long-pedicled free posterior interrosseous artery flap in a bridge fashion. The flap size ranged from 3.5 cm x 2.0 cm to 6.5 em x 3.0 cm. The wounds at donor sites were closed directly.

RESULTSAll the 6 flaps survived completely without any complication, and the wounds healed primarily. The blood supply and vein drainage in all the 6 fingers were normal. 4 cases were followed up for 1-12 months (average, 7 months). Satisfactory cosmetic and functional results were achieved. The flaps looked a little bit thicker than the surrounding tissue.

CONCLUSIONSThe long-pedicled free posterior interrosseous artery flap in a bridge fashion is a good option for reconstruction of the combined skin and bilateral artery defects at palmar side of fingers in one stage.

Arteries ; Feasibility Studies ; Fingers ; blood supply ; surgery ; Free Tissue Flaps ; blood supply ; transplantation ; Humans ; Reconstructive Surgical Procedures ; Surgical Flaps ; blood supply ; transplantation ; Transplant Donor Site ; surgery ; Veins

OBJECTIVETo investigate the feasibility and effect of different types of axial pattern flaps in repairing soft tissue defects of the fingers.

METHODSFive types of axial pattern flaps were used to repair soft tissue defects of the fingers of 30 patients admitted to the Second Hospital of Shaoxing Municipality from 2005 to 2010, including distally-based dorsal thumb neurocutaneous vascular flaps in 4 cases, free flaps from the fibular side of the great toe in 6 cases, modified retrograde dorsal metacarpal artery flaps in 8 cases, free flaps based on the radial dorsal septum muscular perforator of the posterior interosseous artery in 6 cases, and free posterior interosseous artery flaps carrying a long segment of the posterior interosseous artery in 6 cases. The flap size ranged from 2.5 cm × 2.0 cm to 8.0 cm × 3.0 cm. The donor sites were sutured directly or covered with skin graft. The condition of flaps was observed. The local feeling, function, and appearance of affected hands were followed up.

RESULTSTwenty-seven flaps grew well without infection. Partial necrosis at the distal portion in two flaps and venous congestion in 1 flap were observed after surgery, and they were healed with suitable treatment. Eighteen patients were followed up for 1 to 12 months. The flaps were found to have good color, texture, and thickness. Satisfactory appearance and function both in the donor sites and in the recipient areas were found in most patients. The sense of two-point discrimination of repaired fingers ranged from 5 to 9 mm.

CONCLUSIONSOptimizing the repair method for soft tissue defects in the fingers by taking both the characteristics of various axial pattern flaps and the specific conditions of soft tissue defects into account can achieve expected effect.

Adolescent ; Adult ; Female ; Finger Injuries ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; methods ; Soft Tissue Injuries ; surgery ; Surgical Flaps ; Young Adult

AIMTo determine the involvement of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in the expression of endothelin receptor type B (ETB) during culture.

METHODSSB386023, a specific inhibitor for ERK1/2 pathway, was used to define the intracellular signaling pathway for the upregulation of ETB receptors and sarafotoxin 6c (S6c), a selective agonist for ETB receptors, induced contraction in isolated rat superior mesenteric arteries. The contraction was recorded by a sensitive in vitro myograph and the receptor mRNA was quantified by a real-time PCR. The phosphorylated ERK1/2 proteins were analyzed by phosphoELISA assay.

RESULTSS6c induced strong contractile responses of the artery after culture for 24 h, while there was no response to S6c in fresh vessel segments. The enhanced contractile response to S6c paralleled with an increase of mRNA for ETB receptors. The phosphorylated ERK1/2 proteins significantly increased after culture for 3 h. After co-culture with SB386023 for 24 h, S6c-induced contractions significantly decreased with reduction of Emax from (217 +/- 14) % to (127 +/- 23) % (P <0.01). This response paralleled with a decreased level of ETB receptor mRNA.

CONCLUSIONERK1/2 pathway was involved in the up-regulation of ETB receptors on smooth muscle cells isolated from rat mesenteric arteries during culture.

Animals ; Cells, Cultured ; Male ; Mesenteric Arteries ; cytology ; Mitogen-Activated Protein Kinase 1 ; antagonists & inhibitors ; metabolism ; Mitogen-Activated Protein Kinase 3 ; antagonists & inhibitors ; metabolism ; Muscle Contraction ; drug effects ; Muscle, Smooth, Vascular ; cytology ; metabolism ; Organ Culture Techniques ; Phosphorylation ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptor, Endothelin B ; biosynthesis ; genetics ; Signal Transduction ; Up-Regulation ; Vasoconstrictor Agents ; pharmacology ; Viper Venoms ; pharmacology

Objective To study the effects of erythrecyte on brain edema after traumatic intrace- rebral hemorrhage(TICH)and explore the mechanisms of erythrocyte in brain edema development follow- ing TICH.Methods Firstly,the brain injury model of SD rat was established by applying a free-fall- ing device,then whole blood(WB),lysed RBC(LRBC)or parked RBC(PRBC)were infused with ste- reotactic guidance into injured cortex to produce the model of TICH.All rats were killed at 1,3,and 5 days after injury.The brain water content was measured,immunohistochomistry(SABC)was applied to test HO-1 and TNF-?expressions.Results 1.In WB group,PRBC group and TBI group,the brain water content was the highest on the third day.The brain water content of LRBC group was markedly higher on the first day than on the third and fifth days.Comparison among the four groups showed the wa- ter content was the highest on the 1st day in LRBC group,and on the 3rd day in WB and PRBC groups; there was no significant difference among the four groups on 5th day.2.The positive expression of HO-1 and TNF-?coincided with the change of the water content in groups of WB,PRBC and LRBC.Conclu- sions In rat model of TICH,RBC plays an important role in delayed brain edema formation(3 days after injury),but has no influence at early stage(1 day after injury).The mechanisms of delayed brain edema involves RBC breakdown and inflammation reaction.

OBJECTIVETo summarize and analyze the clinical features of bladder tumor patients who received transurethral partial cystectomy by 2 microm continuous wave laser, in 1 year post operation follow-up visits.

METHODSFrom December 2007 to May 2008, 47 bladder carcinoma patients were treated with 2 microm laser transurethrally under sacral block. Operation characteristics, operation time, intraoperative hemorrhages and postoperative complications, and pathology staging of the tumor were observed and postoperative follow-up visits were performed.

RESULTSAll of the operation procedures were successful. The surgery time was 5 to 15 minutes. Blood loss in the operation was minimal. There was no obturator nerve reflection, and no hemorrhaging was detected after the operation. The pathological stages can be judged correctly with the obtained specimens. There was one case with peritoneum perforation. The patients received 12 to 17 months of postoperative follow-up visits, and there was no recurrence at the resection site. The survival rate was 100%.

CONCLUSIONSTransurethral partial cystectomy in the treatment of bladder tumor by 2 microm continuous wave laser is a safe, efficient and effective method. The tumor and all the basal part of bladder wall could be excised completely and the pathological stages can be judged correctly using these specimens to fulfill partial cystectomy for the treatment of bladder carcinoma.

Adult ; Aged ; Aged, 80 and over ; Cystectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Laser Therapy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Urinary Bladder Neoplasms ; surgery