Objective To evaluate the efficacy of parecoxib sodium for prevention of post-thoracotomy pain syndrome.Methods Ninety ASA physical status Ⅰ or Ⅱ patients,aged 40-64 yr,weighing 50-80 kg,scheduled for elective thoracotomy,were equally and randomly divided into 3 groups using a random number table:control group (group C) and two different treatments with parecoxib sodium groups (P1 and P2 groups).At 20 min before skin incison,parecoxib sodium 40 mg was injected intravenously in P1 and P2 groups,while the equal volume of normal saline was given in group C.An increment of parecoxib sodium 40 mg was given every 12 h for 6 times after surgery in group P2.General anesthesia combined with epidural anesthesia was used during surgery and patient-controlled epidural analgesia was used for postoperative analgesia in the three groups.Morphine was used as rescue analgesic to maintain VAS score ≤ 3.The consumption of morphine within 72 h after operation,development of adverse effects and development and duration of pain (VAS score ＞ 3) within 6 months after operation were recorded.The blood coagulation was measured at 72 h after operation.Results Morphine was not used within 72 h after operation in P2 group.The abnormality of blood coagulation at 72 h after operation was not observed in the three groups.Compared with group C,no significant changes were found in the incidence and duration of pain within 6 months after operation in P1 group (P ＞ 0.05),the incidence of pain was significantly decreased and duration of pain was shortened within 6 months after operation in P2 group,and the incidence of nausea,vomiting and pruritus was decreased in P1 and P2 groups (P ＜ 0.05 or 0.01).The incidence of nausea,vomiting and pruritus was significantly lower in P2 group than in P1 group (P ＜ 0.01).Conclusion Continuous application of parecoxib sodium for 72 h can decrease the development of post-thoracotomy pain syndrome without increasing the incidence of adverse effects.

The major defining pathological hallmarks of Alzheimer's disease (AD) are the accumulations of Abeta in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble Abeta oligomers and hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological protein species are accompanied by cytoskeletal changes, mitochondrial dysfunction, Ca2+ dysregulation, and oxidative stress. In this review, we discuss how the binding of Abeta to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by Abeta oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of Abeta generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and beta-integrins are physically associated with each other.
Alzheimer Disease ; Amyloid ; Cytoskeleton ; Endocytosis ; Focal Adhesions ; Integrins ; Mitochondria ; Neurofibrillary Tangles ; Neuropil Threads ; Oxidative Stress ; Plaque, Amyloid

OBJECTIVEThe sex therapy is not yet popularized at present. This study aimed to evaluate the effect of the combination of the improved sex therapy and oral sildenafil on erectile dysfunction (ED).

METHODSA total of 3130 Uigur cases of ED received in Xinjiang Bogda Hospital were divided into a control group (n=625) and a trial group (n=2505), the former treated with oral sildenafil alone, and the latter by the combination of the improved genital therapy and sildenafil, both for 3 months and followed up at 6 and 12 months after the treatment. The therapeutic effects were evaluated and compared using IIEF-5.

RESULTSThe IIEF-5 scores of the control group were 12.80 +/- 3.76 and 18.10 +/- 2.61 before and after the treatment, and 17.35 +/- 2.73 and 16.64 +/- 2.63 at 6 and 12 months, respectively, while those of the trial group were 12.73 +/- 3.52 and 19.06 +/- 4.07 before and af- ter the treatment, and 19.86 +/- 2.42 and 20.47 +/- 2.38 at 6 and 12 months, respectively, with statistically significant differences either between pre- and post-treatment (P < 0.05) or between the control and trial groups at 6 and 12 months (P < 0.05).

CONCLUSIONThe combination of the improved sex therapy and oral sildenafil is superior to sildenafil alone in the treatment of ED, and its efficacy is relatively stable at 12 months.

Adult ; Aged ; Asian Continental Ancestry Group ; Erectile Dysfunction ; drug therapy ; ethnology ; Humans ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Retrospective Studies ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Treatment Outcome ; Young Adult

Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.