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 explore the effects of essential tremor(ET)on the mitochondrial morphology of GABAer-gic and glutamatergic neurons in the inferior olive(IO).Methods:The ET mouse model was established via intraper-itoneal injection of harmaline.Twelve 8-week-old male C57BL/6J mice were randomly divided into saline control group and harmaline treatment group(HA).Behavioral tests,including open field test,rotarod test,balance beam test,and tremor scoring,were conducted to assess the behavior of mice.Using genetic engineering technology and the CRISPR/Cas9 system,we designed and generated 6 male GAD2-Mito-GFP mice and 6 male VGLUT2-Mito-GFP mice,all being 8-week-old.The mice of each transgenic line were randomly divided into Control and HA group.Immunofluorescence staining was used to analyze the expression of c-FOS positive cells in the IO of both the Control and HA groups,and to classify different types of neurons.Mitochondrial network analysis(MiNA)was performed to quantitatively analyze the area,mean aspect ratio,branch length,and other of mitochondria in different types of neurons in the IO under ET con-ditions.Results:Compared to the Control group,the HA group exhibited motor abnormalities and significant tremors.Immunofluorescence results showed a significant increase in the number of c-FOS positive cells in the IO,primarily in GABAergic neurons.MiNA results revealed that the mitochondria of GABAergic neurons showed increased area,branch length diameter,demonstrating irregular morphology.Conclusion:ET induces activation of GABAergic neurons in the IO and leads to more prominent mitochondrial morphological changes.This provides a new perspective for further inves-tigation of the pathogenesis of essential tremor and its relationship with mitochondrial.

Objective:To explore the effects of essential tremor(ET)on the mitochondrial morphology of GABAer-gic and glutamatergic neurons in the inferior olive(IO).Methods:The ET mouse model was established via intraper-itoneal injection of harmaline.Twelve 8-week-old male C57BL/6J mice were randomly divided into saline control group and harmaline treatment group(HA).Behavioral tests,including open field test,rotarod test,balance beam test,and tremor scoring,were conducted to assess the behavior of mice.Using genetic engineering technology and the CRISPR/Cas9 system,we designed and generated 6 male GAD2-Mito-GFP mice and 6 male VGLUT2-Mito-GFP mice,all being 8-week-old.The mice of each transgenic line were randomly divided into Control and HA group.Immunofluorescence staining was used to analyze the expression of c-FOS positive cells in the IO of both the Control and HA groups,and to classify different types of neurons.Mitochondrial network analysis(MiNA)was performed to quantitatively analyze the area,mean aspect ratio,branch length,and other of mitochondria in different types of neurons in the IO under ET con-ditions.Results:Compared to the Control group,the HA group exhibited motor abnormalities and significant tremors.Immunofluorescence results showed a significant increase in the number of c-FOS positive cells in the IO,primarily in GABAergic neurons.MiNA results revealed that the mitochondria of GABAergic neurons showed increased area,branch length diameter,demonstrating irregular morphology.Conclusion:ET induces activation of GABAergic neurons in the IO and leads to more prominent mitochondrial morphological changes.This provides a new perspective for further inves-tigation of the pathogenesis of essential tremor and its relationship with mitochondrial.

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 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 Comprehensive standards of active implantable medical devices with high risks are required by China's current industrial development, and standard problems and ideas are discussed in this paper.Methods Analysis of the status of China's active implantable medical device standards and international standards. For the booming field for active implantable medical devices with high risks, international standard’s problems, ideas and trends are analyzed. Results Bottleneck of the development of China's active implantable medical device standards is the lack of Chinese medical devices industry actual independent research and development capability. China's independent standard research on the basis of independent core technology of active implantable medical devices is the opportunity to promote the internationalization of China standard.Conclusion Improving the standards of active implantable medical devices based on independent core technology, combined with problems of existing international standards, to further improve and develop international standards and lead high level international technical standards.

Objective To explore the effect of surgical management of left colon cancer with acute obstruction.Methods A retrospective analysis was made on the clinical data of 85 cases with acute obstructive colorectal carcinoma treated by one-stage resection.Among the 85 cases,there were 48 cases of left colon obstruction (treatment group),and the control group included 37 cases of right colon cancer.To compare the occurrence of postoperative complications.Results 20 cases had postoperative complication in the treatment group,among which,2 cases had anastomosis fistula,4 cases of pulmonary infection,5 cases of abdominal abscess,6 cases of incision infection and 3 cases of intestinal adhesion.In control group,there were 15 cases had complication,among which,1 case had anastomosis fistula,3 cases of pulmonary infection,3 cases of abdominal abscess,5 cases of incision infection and 3 cases of intestinal adhesion.There was no significant difference in incidence rate of complication between two groups (P ＞ 0.05).Conclusion One stage resection in the treatment of left colon cancer with acute obstruction is safe and feasible.

Objective To explore the efficacy of surgery in the treatment of hepatolithiasis .Methods The clinical data of 98 patients with hepatolithiasis treated with different surgical procedures were retrospectively anan -lyzed,there were 91 cases transhepatic cholangiolithotomy treatment and 7 cases hepatolobectomy .Results 25 cases were found residual stone after operation .Recurrence calculus(10 cases),liver abscess(2 cases),and complicated by bile duct carcinoma(4cases) were found in following -up.2 cases were dead.The total effective rate was 97.96%. Conclusion Correct operation methods of calculus of intrahepatic duct was the key of reduction residual stone after operation.Resection extra-lateral lobe and choledchoscope are main means of reduction residual stone after opera -tion.

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 .