Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.

Objective To compare the influence of laparoscopic inguinal hernia repair ( TAPP) and open inguinal hernia repair(Lichtenstein) on clinical serum swelling and the prevention and treatment strategy.Methods From September 2015 to September 2016,117 patients with inguinal hernia in the Second People's Hospital of Shantou were selected.The patients were divided into TAPP group and Lichtenstein group according to the operation mode .The incidence of seroma,occurrence,characteristics and diagnosis and treatment of the two groups were compared.Results There were 64 cases in the TAPP group,aged 25-73 years old,the median age was 57 years,58 cases of indirect inguinal hernia,4 cases of direct hernia ,2 cases of femoral hernia ,3 cases of refractory hernia.There were 53 cases in the Lichtenstein group,aged 24-84 years old,the median age was 63 years,41 cases of indirect inguinal hernia , 10 cases of direct hernia,2 cases of femoral hernia ,7 cases of refractory hernia.There was no statistically significant difference in the incidence rate of seroma between the two groups (P＝0.875).There were no statistically significant differences in the incidence rate of different types of seroma (all P＞0.05).There was no need for treatment of 0-II type seroma.The type III -IVa clinical seroma could be given local puncture parallel compression treatment , improved after treatment.After drainage and anti -inflammatory treatment, type IVb seroma was improved. Conclusion There is no difference in the incidence of seroma and the treatment between the two surgical procedures after inguinal hernia repair.

Objective The scale lists applied in the diagnosis and treatment of heat stroke generally draw on other specialty scales, and there is no specific scoring system on heat stroke verified by large-scale clinical trials.The paper compared common acute physiology and chronic health evaluationⅡ( APACHEⅡ) , dissolved inorganic carbon score( DIC score) , multiple organ dysfunction score( MOD score) for the prognostic evaluation of heat stroke patients, the sum of three scores and the sum of the percentages of three scores to the score sum on prognostic evaluation of heat stroke patients in order to find a scoring method with higher clinical value. Methods APACHEⅡ, MOD score, DIC score, the sum of three scores and the sum of three scores were applied on 43 patients with heat stroke admitted in our neurological intensive care unit ( NICU) or in intensive care unit ( ICU) .The analysis of the area under the receiver operating characteristic ( ROC) curve( AUC) analysis was made among five scores. Results The weighted sum of three scores has the largest AUC ( 0.896 ) in predicting the death of HS patients according to AUC.The optimal MOD score was 5.5 in predicting the death of HS with a sensitivity of 72.7%and a specifici-ty of 99.69%.The optimal DIC score was 1.5 in predicting the death of HS with a sensitivity of 100%and a specificity of 56.2%.The op-timal score of the sum of the percentages of three scores to the score sum was 0.727 in predicting the death of HS with a sensitivity of 72.7%and a specificity of 100%. Conclusion All the five scores can predict the prognosis of patients with heat stroke.However, due to the deficiency in the prognosis value, a more specific scoring system needs to be developed.

Objective To investigate the different influencing on the healing of anastomotic stoma between two kinds of alimentary canal reconstruction after laparoscopic radical resection of low rectal cance.Methods The clinical data of July 2013 -January 2016 suffering from stage Ⅱ -Ⅲ low rectal cancer and in our hospital underwent laparoscopic colorectal cancer radical surgery patients was retrospectively analyzed.Through accessing to medical records,the patients of diabetes,hypoproteinemia,malnutrition,preoperative uncorrectable cases and received neoadjuvant therapy were excluded.More than a total of 59 cases were enrolled,34 cases of them received traditional alimentary canal reconstruction(traditional group,including 26 cases of low rectal cancer,8 cases of super low rectal cancer,also 21 cases of them in stageⅡand 13 cases in stage Ⅲ),25 cases of them received anal anastomosis resection (including 18 cases of low rectal cancer,7 cases of super low rectal cancer,also 20 cases of them in stage Ⅱ and 5 cases in stageⅢ).Results In the traditional group,1case of 34 patients with anastomotic leakage,3 cases of anastomotic bleeding, while in the improved group,2cases of 25 patients with anastomotic leakage,2 cases of anastomotic bleeding.There was no significant difference in the incidence of anastomotic leakage and anastomotic bleeding between the two groups (3cases vs.2cases,1case vs.2cases,χ2 =0.13,0.75,all P >0.05).All cases did not occur in patients with anastomotic stenosis,and all patients were cured and discharged.Conclusion Each of the two methods have their advantages and disadvantages.Through preoperative,intraoperative evaluation of tumor status,reasonable choice of tumor treatment and anastomosis,is more conducive to postoperative recovery.

Objective To explore the levels of leptin(LEP) and soluble leptin receptor (sOB‐R) in breast cancer patients′ser‐um ,and to discuss the relationship between LEP ,sOB‐R ,free leptin index(FLI) and the patients′clinical pathologic features .Meth‐ods 70 serum specimens of breast cancer patients who confirmed by pathological diagnosis were collected before the surgery ,the serum of benign breast disease group(n=50) and normal group(n=50) were also collected as control .The levels of LEP and sOB‐Rinserumweredetected,andtheresultafterbodymassindex(BMI)correctionwereanalyzed.Finally,therelationshipbetweenthe expression of LEP ,sOB‐R and clinical pathologic features were analyzed .Results The serum level of LEP in breast cancer group was highly increased than the other two groups (P<0 .05) ,and sOB‐R was reduced(P<0 .05) .After BMI correction ,LEP was still highly increased(P<0 .05) ,but sOB‐R was no significant difference (P>0 .05) .The level of LEP in the postmenopausal breast cancer patients were highly increased than menopause patients (P>0 .05) ,and the expression of LEP in cancer group were signifi‐cant higher than two control groups by both postmenopausal and menopause (P>0 .05) .The result suggested the serum level of LEP and FLI are associated with pTNM stages and lymph node metastases (P<0 .05) ,and elevated level of LEP in postmenopausal patients had differences in pTNM stages and lymph node metastases (P< 0 .05) .Conclusion The serum LEP level and the FLI may be potential indicators to evaluate the prognosis of the patient with breast cancer .The serum LEP may promoted the process of the postmenopausal patients of breast cancer .

Objective To investigate the effect of Ruigan (L-omithine-L-aspartate) on liver function of perio-perative treatment. Methods 58 patients with obstructive jaundice and having been done operation were randomly di-vided into two groups:ruigan group (cured group,32 cases) and routine hugan group (control group,26 cases). The levels of liver function and endotoxin were detected when being in hospital, before operation and after operation re-spectively. Results Treatment with ruigan could improve the liver function in perioperation, which has significant difference when compared to the control group (P < 0.05).. Ruigan could reduce the level of endotoxin before and af-ter operation (P < 0.05) and improve endotoxaemia in obstructive jaundice. Conclusion Ruigan would improve the liver function and the endotoxaemia in the perioperative obstructive jaundice.

Objective To investigate the effect of ultrasound-guided percutaneous tube drainage in early acute pancreatitis of closed abdominal injury. Methods The clinical data about fifteen ca.ses of acute pancreatitis of closed abdominal injury in our hospital were reviewed retrospectively. Results By ultrasound-guided percutaneous tube drainage, 11 cases were cured, 2 cases were drainaged by open operation with the complication of pancreatic pseudocyst, 2 eases were transfered to superior hospital with state of an illness sharpened. Conclusion Ultrasoundguided percutaneous tube drainage was effective treatment in early acute pancreatitis of dosed abdominal injury,and avoided open operation.