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Objective:A case of advanced nasopharyngeal carcinoma with autonomic dysfunction was reported and its pathophysiological mechanism was discussed.Methods:The diagnosis and treatment of a nasopharyngeal carcinoma patient with autonomic nervous dysfunction such as paroxysmal syncope was summarized, and the pathophysiological mechanism of this case was analyzed by searching related literature.Results:Nasopharyngeal carcinoma characterized by autonomic dysfunction was rare and had a poor prognosis. Autonomic dysfunction caused by nasopharyngeal carcinoma was associated with carotid sinus syndrome, parapharyngeal space syncope syndrome, glossopharyngeal nerve reflex and paraneoplastic neuropathy.Conclusions:Early detection and treatment is a key factor affecting the prognosis of nasopharyngeal carcinoma. Clinicians should consider nasopharyngeal carcinoma as one of the differential diagnoses in the diagnosis and treatment of patients with autonomic nervous dysfunction combined with cranial nerve damage.
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SHP2 is a protein tyrosine phosphatase (PTP) that can regulate the tyrosine phosphorylation level. Overexpression of SHP2 will promote the development of cancer diseases, so SHP2 has become one of the popular targets for the treatment of cancer. Studies have reported that both SHP099 and SHP844 are inhibitors of SHP2 and bind to different allosteric sites 1 and 2, respectively. Studies have shown that combining SHP099 with SHP844 will enhance pharmacological pathway inhibition in cells. This study uses molecular dynamic simulations to explore the dual allosteric targeted inhibition mechanism. The result shows that the residues THR108-TRP112 (allosteric site 1) move to LEU236-GLN245 (αB-αC link loop in PTP domain) , the residues of GLN79-GLN87 (allosteric site 2) get close to LEU262-GLN269 (αA-αB link loop in PTP domain) and HIS458-ARG465 (P-loop) come near to ARG501-THR507 (Q-loop) in SHP2-SHP099-SHP844 system, which makes the "inactive conformation" more stable and prevents the substrate from entering the catalytic site. Meanwhile, residue GLU110 (allosteric site 1), ARG265 (allosteric site 2), and ARG501 (Q-loop) are speculated to be the key residues that causing the SHP2 protein in auto-inhibition conformation. It is hoped that this study will provide clues for the development of the dual allosteric targeted inhibition of SHP2.
Subject(s)
Neoplasms , Protein Tyrosine Phosphatase, Non-Receptor Type 11 , Allosteric Regulation , Allosteric Site , Humans , Molecular Dynamics Simulation , Neoplasms/drug therapy , Protein Tyrosine Phosphatase, Non-Receptor Type 11/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolismABSTRACT
Objective:To explore the clinical predictive effect of the preoperative ratio of C reactive protein to albumin (CAR) on perioperative delirium (POD) in geriatric patients with femoral intertrochanteric fracture.Methods:The clinical data were analyzed retrospectively of the 398 patients who had undergone surgery for femoral intertrochanteric fractures at Department of Orthopedics, Xuanwu Hospital from January 2013 to March 2016. According to the presence or absence of POD, all the patients were divided into 2 groups: a delirium group and a normal group. The 2 groups were compared in terms of general clinical data like gender, age, body mass index, blood routine, CAR, biochemical indicators, blood coagulation indicators and concomitant internal diseases. After a single factor logistic regression analysis of the general clinical data of the patients, factors with P<0.10 were introduced into the multivariate logistic binary regression model to screen out the risk factors for POD in geriatric patients with femoral intertrochanteric fracture. The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value and optimal cut-off point of CAR for POD in geriatric patients with femoral intertrochanteric fracture. Results:The incidence of POD in this cohort was 14.32%(57/398). The age, C-reactive protein, CAR, platelet and probability of pulmonary infection in the delirium group were significantly higher than those in the normal group, but the hemoglobin, albumin and prealbumin in the former were significantly lower than those in the latter ( P< 0.05). The multivariate logistic binary regression analysis showed that hemoglobin ( OR=0.975, 95% CI: 0.957 to 0.993, P=0.006) and CAR( OR=53.713, 95% CI: 17.713 to 162.876, P<0.001) were risk factors for POD in geriatric patients with femoral intertrochanteric fracture. The area under ROC of CAR in predicting POD in geriatric patients with femoral intertrochanteric fracture was 0.906 (95% CI: 0.873 to 0.933, P<0.001), and the cut-off point was 2.06. When CAR>2.06, its predicted incidence of POD was 50.50%, with a sensitivity of 89.47% and a specificity of 85.34%. Conclusion:As CAR is a risk factor for POD in geriatric patients with femoral intertrochanteric fracture, it can be used as an effective indicator to predict POD.
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Objective:To analyze the reasons of early failure of the PHILOS in proximal humerus frac-tures.Methods:From Nov.2010 to Nov.2014,there were 117 patients with humerus fractures treated with PHILOS locking plate in Department of Orthopaedics,Xuanwu Hospital.All of the patients were treated with the plate by open reduction internal fixation,and we analyzed these cases retrospectively. After the operation,we removed the drainage tube within 48 h,and the patients were allowed to do the passive motion 3 days after the surgery if the X-Ray showed the plate and screws were reliable.Eight ca-ses failed within 4 weeks after the operation.We analyzed the reasons of the failure.Results:The rate of the failed cases was 6.83%(8 /117).The average age was 72.4(66 -82)years.In the 8 failed cases, 3 were on the right side,and the other 5 on the left side.As for the reason of the fractures,2 cases were because of car accidents,and the other 6 because of daily life injury.According to the Neer classifica-tion,3 cases were 2-part fractures,and the other 5 3-part fractures.Three cases were total failure,and the other 5 partial failure.All the 8 failed cases failed within 4 weeks after the operation,of which 1 was on the sixth day after surgery,the other 7 2 to 4 weeks after the surgery.The 3 totally failed cases were treated by removing the screws and plates,the other 5 by conservative methods.All of the cases were malunion at the end.Conclusion:The early failure of the PHILOS locking plate in proximal humerus fractures is related to the bad reduction during the operation,the loss of medial cortex support,the limi-tation of screw length,the osteoporosis and the improper rehabilitation after operation.It is very important to do good preoperative plan for a surgeon.During the operation,we should try our best in the fracture reduction,use the appropriate plate and screws,and then pay attention to the rehabilitation after the operation.After all of this,the rate of failure may be decreased.
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Objective To investigate the effect of cobalt chromium alloy onlay on the direct repair of cracked vital pulp teeth with the resin compostie filling and porcelain-fused-to-metal (PFM ) crown repair as the control .Methods 201 cracked vital pulp teeth from 201 cases were randomly divided into 3 groups according to the clinical symptoms :mild discomfort at occlusion (group A) ,pain at occlusion accompanied with transient pain to cold or hot stimulation (group B) and pain at occlusion accompanied with continuous pain to cold or hot stimulation(group C) .The cracked teeth directly were restored by the resin composite filling ,cobalt chromium alloy onlay and PFM crown repair and the effective rate in each group was observed after 2-year follow up .Results The effective rate of the group A ,B and C were statistically significant different from each other (P<0 .05) .The effective rate of the co-balt chromium alloy onlay and the PFM crown was statistically significant higher than that of resin composite (P<0 .05) .Conclusion The direct repair with cobalt chromium alloy onlay is an effective repair method for the cracked vital pulp teeth with mild discomfort at occlusion and mild pain accompanied with transient pain to cold or hot stimulation .
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Objective To investigate the relationship between Post stroke depression (PSD) and Post stroke cognitive impairment (PSCI) using proton magnetic resonance spectroscopy.Methods 82 patients of acute stroke,which were met with the third edition of the Chinese Classification of Mental Disorders (CCMD-Ⅲ) and expert consensus of cognitive impairment since January 2012 to December 2012,Select continuously 82 patients who are hospitalized in our hospital due to acute stroke from January 2012 to December 2012 from Zhongnan Hospital of Wuhan University,were examined by 1H-MRS in one month.They were divided into PSD and PSCI simultaneously (n =19),PSD (n =21),PSCI (n =22) and control group (n =20).Results The differences between PSD and PSCI was not significant.On hippocampus japonicas,the Cho/Cr ratio in patients of A group (left (1.05 ± 0.10),right(1.18 ± 0.15)),showed higher than those in B group (left (0.84 ± 0.10),right (0.88 ± 0.08)),C group (left(0.88 ±0.08),right (0.87 ±0.07)),D group(left(0.87 ±0.06),right(0.89 ±0.06)).The difference was statistically significant.PSD and PSCI promoted each other in influencing Cho/Cr ratio.Conclusion There is no significant relationship between PSD and PSCI in the produce of disease,and they can promote each other in hippocampus japonicas Cho/Cr ratio.
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OBJECTIVE: To analyze the possible mechanism of Fas mediated apoptosis, investigate the correlation of exercise with apoptosis of cardiomyocytes,skeletal muscle and lymphocytes, and explain the changes of histocyte injury under exercise training from a new level of recognition, so as to provide scientific theoretical evidences for the prevention and treatment of overtraining.DATA SOURCES: A computer-based online search of Springlinker and Pubmed databases was undertaken to identify articles related to Fas mediated apoptosis of cardiomyocytes, skeletal muscle and lymphocytes published in English from January 1994 to December 2004 by using the keywords of "Fas, apoptosis, exercise, skeletal muscle, cardiomyocyte, lymphocyte". Meanwhile, Chinese relevant articles published from January 1994 to December 2004 were searched in the Chinese journal full-text database with the keywords of "apoptosis, exercise, skeletal muscle, cardiomyocyte, lymphocyte" in Chinese.STUDY SELECTION: The data were checked firstly. Inclusive criteria:studies related to Fas mediated apoptosis of cardiomyocytes, skeletal muscle and lymphocytes. The repetitive ones were excluded.DATA EXTRACTION: Totally 58 literatures were collected, 29 repetitive studies were excluded, and the other 29 were accorded with the inclusive criteria.DATA SYNTHESIS: Apoptosis is a gene-controlled process of spontaneous death for cells, and it is the physiological cell death. As a death factor inducing apoptosis, Fas is of important biological significance in regulating apoptosis. The study on exercise and the mechanism of apoptosis signal conduction will explain the changes of histocyte injury under exercise training from a new level of recognition, and provide scientific theoretical evidences for the prevention and treatment of overtraining, Besides,Fas plays an important role in various tumors, diseases of immune system and spinal cord injury.CONCLUSION: The deeper investigation on exercise and Fas mediated apoptosis may disclose the mechanism for the treatment of disease, and introduce new methods of exercise treatment, which undoubtably has important practical significance in accelerating healthy of human being.
