Ubiquitin-specific protease 7(USP7)is a deubiquitinating enzyme involved in a wide range of cellular processes,playing a key role in the regulation of cell proliferation and apoptosis,cell division,differentiation,DNA damage repair,epigenetic regulation and other biological processes.This article briefly summarizes the structure and extensive biological functions of USP7,and also describes the research progress of USP7 in colorectal cancer in recent years and potential directions for future research.

Microglia are the primary immune cells in the central nervous system.The activation is of microg-lia crucial in neurological injury and neurodegenerative diseases.In recent years,research on microglia-targeted therapies has gained increasing attention.Microglia replacement therapy has shown promising results in treating various neurological diseases.This therapy involves the forced removal of dysfunctional microglia and their replacement with fully differentiated microglia through drug or gene targeting.This article discusses the potential pathophysiological mechanisms and effective therapeutic strategies of microglia replacement therapy in neurological diseases,including Alzheimer's disease and stroke.Moreover,it serves as a reference for the in-depth study of neurobiological mechanisms and treatment of neurological dis-eases.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To evaluate the efficacy and safety of endoscopic stricturotomy (EST) under balloon-assisted enteroscopy (BAE) in treatment of benign jejuno-ileal stenosis.Methods:From December 2015 to August 2021, at the Air Force Medical Center, 41 patients who were diagnosed with benign jejuno-ileal stenosis underwent BAE deep small bowel EST and/or surgery due to ineffective or ineffective drug treatment were retrospectively analyzed. Twenty-one patients were treated with EST (EST group) and 20 patients were treated with surgery (surgery group). The etiology and follow-up time were analyzed, the general conditions (male proportion and age), the immediate technical success rate (the percentage of the stenosis that the enteroscope could pass through after EST in the total number of treated stenoses), the incidence of complications (including perforation, bleeding, etc.), the symptom remission rates at 3-month, 6-month, and 1-year after treatment (the percentage of patients with complete or partial remission in the total number of patients), cumulative symptom-free survival rate (no obstruction-related symptoms after EST or surgery till the last follow-up) and cumulative surgery-free survival rate of two groups were compared. Chi-square test, independent t-test, Fisher′s exact probability method and Kaplan-Meier analysis were used for statistical analysis. Results:The main etiology of stricture of EST group and surgery group was Crohn′s disease (71.4%, 15/21 and 60.0%, 12/20, respectively), and the median follow-up time was 12 months (6 to 46 months) and 45 months (14 to 73 months), respectively. There were no significant differences in male proportion, age, immediate technical success rate and incidence of complication between EST group and surgery group (57.1%, 12/21 vs. 65.0%, 13/20; (45.2±17.4) years old vs. (43.1±20.3) years old; 95.3%, 41/43 vs. 100.0%, 30/30; 26.9%, 7/26 vs. 10.0%, 2/20, all P>0.05). In the EST group, 9.5% (2/21) of the patients received surgery because of perforation during EST, 76.2% (16/21) of the patients did not need surgery after EST, and the median symptom-free survival time of patients without symptoms in EST group was 13.3 months. There was no significant difference in the symptom remission rate at 3-month after treatment between EST group and the surgery group (17/19 vs. 100.0%, 20/20, P>0.05). The symptom remission rate at 6-month and 1-year of EST group were lower than those of the surgery group (15/19 vs. 100.0%, 20/20; 8/11 vs. 100.0%, 20/20), and the differences were statistically significant (both were Fisher′s exact probability method, P=0.047 and 0.037). The cumulative symptom-free survival rates at 3-month, 6-month and 1-year of EST group and surgery group were 66.0% vs. 90.0%, 61.0% vs. 85.0% and 54.0% vs. 80.0%, respectively.The results of Kaplan-Meier analysis indicated that there was no significant difference in the symptom-free survival curve between two groups ( P>0.05). The 3-month, 6-month and 1-year cumulative surgery-free survival rates after treatment in EST group were 90.0%, 81.0% and 73.0%, respectively. The 3-month, 6-month and 1-year cumulative surgery-free survival rates after treatment in surgery group were all 100.0%. Conclusion:EST under BAE is technically feasible, and safe in the treatment of benign jejuno-ileal stenosis, and can effectively relieve clinical obstruction symptoms and avoid or delay surgery in the short term.

Objective:To evaluate the efficacy and safety of combination of sufficient argon plasma coagulation(APC) cauterization and clipping in the treatment of colonic diverticular bleeding.Methods:From June 2018 to April 2022, the clinical data of patients were retrospectively analyzed, who visited Department of Gastroenterology of Air Force Medical Center due to overt gastrointestinal bleeding, and were confirmed or suspected to have colonic diverticular bleeding and received combination of sufficient APC cauterization and clipping treatment. The deadline for follow-up was September 30, 2022. During the follow-up after endoscopic treatment, the re-bleeding rate, hemoglobin level difference between the last follow-up and before treatment, wound healing under colonoscopy as well as the intraoperative and postoperative complications of patients were statistically analyzed. Descriptive analysis was used for statistical analysis.Results:A total of 15 patients were enrolled, including 13 males and 2 females, aged (60.8±14.8) years old. The course of the disease was 1 day to 13 years. A total of 145 colonic diverticula of 15 patients were treated under endoscopy. The median follow-up time was 14.5 months (5.3 to 49.5 months) months. Among the 15 patients, 12 patients received endoscopic therapy once and no bleeding occurred till the end of follow-up. Three patients suspected with diverticular bleeding received a second endoscopic treatment because of bleeding at the 12 days, 3 months and 8 months after the first treatment, respectively.No rebleeding occurred after the second endoscopic therapy till the end of follow-up. The re-bleeding rate of the first treatment was 3/15 and the re-bleeding rate of re-treatment was 0. At the end of follow-up, the hemoglobin concentration increased (35.9±26.3) g/L compared with that before the treatment. Two patients had perforation during operation and were closed with multiple titanium clips. There was no abdominal pain or other symptoms after operation. And the patients were discharged 3 and 4 days after treatment, respectively. Two patients suffered short-term postoperative wound bleeding and successful hemostasis was achieved after endoscopic treatment. One patient developed postoperative infection and the symptoms disappeared after anti-infection treatment.Conclusions:Combination of sufficient APC cauterization and titanium clipping is safe and effective in the treatment of colonic diverticular bleeding. For patients with dominant diverticular hemorrhage, or patients with recurrent gastrointestinal bleeding, if other etiology are excluded and colonic diverticular bleeding is highly suspected, the combination of sufficient APC cauterization and titanium clipping under endoscopy is feasible.

Objective:To compare the early and mid-term results of hybrid coronary revascularization (HCR) and minimally invasive multivessel coronary artery bypass grafting (MICS-CABG) in coronary artery disease patients with low left ventricular ejection fraction and non diabetes mellitus, and to explore the indication of HCR and MICS-CABG.Methods:A retrospective cohort analysis of HCR and MICS-CABG cases with preoperative left ventricular ejection fraction less than 0.40, and without diabetes mellitus were conducted in Xijing Hospital from January 2015 to December 2019. 36 cases in HCR group and 17 cases in MICS group were included in this study. For HCR procedure, minimally invasive left internal mammary artery(LIMA) to the left anterior descending artery (LAD) bypass surgery were performed, and followed by percutaneous coronary intervention (PCI) to treat non LAD lesion 1 to 4 weeks later. MICS-CABG procedure was performed through left anterior small thoracotomy minimally invasive direct coronary artery bypass grafting for multiple diseased vessels.Results:The preoperative SYNTAX score in MICS group was significantly higher than that in HCR group ( P<0.05). There was no perioperative death in both groups. Troponin I, postoperative drainage volume, blood transfusion volume and ventilator ventilation time in MICS group were significantly higher than those in HCR group ( P<0.05). After 12 months follow-up, no patient died in both groups. Furthermore, all LIMA grafts were patency. The stenosis rate of drug-eluting stents in HCR group was similar to that of great saphenous vein grafts in MICS group. LVEF and left ventricular end diastolic diameter of both groups were significantly improved 12 months after operation ( P<0.05). Conclusion:HCR and MICS-CABG are minimally invasive and safe treatment for multivessel coronary artery disease patients with low ejection fraction and non diabetese mellitus. The early and mid-term therapeutic effects are satisfactory. If coronary artery lesions other than LAD are suitable for PCI, HCR should be the preferred treatment.

Objective:To explore the clinical and imaging features of leucine-rich glioma inactivated 1 antibody associated autoimmune encephalitis (LGI1-AE).Methods:Nine LGI1-AE patients had conformed diagnosis in Department of Neurology, First Affiliated Hospital, School of Medicine, Zhejiang University from January 2016 to December 2021 were enrolled. A retrospective analysis was performed on the clinical manifestations, MRI and PET-CT features, and clinical outcomes of these patients.Results:One patient had acute onset due to sudden disturbance of consciousness; 3 had subacute onset with a duration of 10-15 d, manifested as dizziness, memory loss, unconsciousness and limb convulsions; 5 had chronic onset with a duration of 6 months-2 years, manifested as amnesia, memory loss, dizziness, and headache in the early stage of the disease, including 2 accompanied by emotional stress and personality changes. Eight patients were followed up for an average of 8 months: 1 with acute onset had organic mental disorder (dementia state), 3 had recurrent seizures (1 with subacute onset and 2 with chronic onset), and the remaining 4 had symptom relief or disappearance. In these 9 patients, 8 patients, enjoying good prognosis, showed typical imaging findings: lesions were located at the limbic system, morphological swelling was accompanied by increased T2WI signal, and PET showed reduced or increased metabolism; 1 patient, enjoying poor prognosis, had atypical imaging finding: asymmetric hyperintensity in the basal ganglia, the clinical symptoms were more severe than the 8 patients having lesions at the limbic system, and rapid disease progress was noted.Conclusion:The prognosis of LGI1-AE patients with atypical imaging manifestations might be relatively poor.

Objective    To investigate the therapeutic effect, safety and effectiveness of multiple valvular surgery through right anterolateral intercostal thoracotomy, as well as the mid-term follow-up results and surgeon's learning curve. Methods    The clinical data of 154 patients with multiple valvular disease were performed minimally invasive cardiac surgery in the Department of Cardiovascular Surgery, The First Affiliated Hospital of Air Force Medical University, from 2015 to 2019 were retrospectively analyzed. There were 103 males and 51 females, aged 23-68 years. Closed cardiopulmonary bypass was established through femoral artery and femoral vein, and the thoracic cavity was entered through a 6 cm transverse incision in the fourth intercostal space on the right side of sternum. Baseline and perioperative characteristics and postoperative outcomes were reviewed. Results    There was no perioperative death. The average cardiopulmonary bypass time was 159.3±39.4 min, and the aortic clamping time was 102.3±20.3 min. One patient underwent thoracotomy during the operation, and two patients underwent second thoracotomy for hemostasis. During the follow-up period of 10-55 months, 1 patient died, 2 patients developed mild perivalvular regurgitation, 6 patients developed moderate tricuspid regurgitation, and no serious cardiovascular events occurred in the rest of the patients. Conclusion    Our findings demonstrate that multiple valvular surgery through right anterolateral intercostal thoracotomy is safe, and in an acceptable risk of complication. The early and middle follow-up results are satisfactory. The minimally invasive cardiac surgery can also meet the requirements of cosmetology, and is conducive to the recovery of patients' mental and physical health. This method is worthy of application in medical centers with rich experience in routine cardiac surgery.

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.

Objective To investigate the effects of hyperbaric oxygen (HBO) therapy on interleukin-1 β( IL-1 β) and interleukin-6 ( IL-6 ) levels in patients with moderate or severe traumatic brain injury ( TBI ) and to analyze its therapeutic efficacy.MethodsOne hundred and fifty-six patients with moderate or severe TBI were randomly divided into a control group and an HBO adjunctive therapy group with 78 cases in each.The control group received essential neurosurgical treatment and conventional drug treatment,and the HBO group was given one HBO therapy session in addition.IL-1 β and IL-6 were quantitatively determined using sandwich ELISA,and the patients'scores on the Glasgow coma scale (GCS) were measured before and after treatment.The Glasgow outcome scale (GOS) was used to evaluate in a follow-up 6 months after injury.ResultsThe average IL-1 β and IL-6 levels of the two groups and their average GCS scores were not significantly different before treatment.After treatment,IL-1 βand IL-6 levels decreased significantly and GCS scores increased significantly in both groups,but there were significant inter-group differences in all three measures.Six months after injury the GOS evaluation indicated that significantly more patients had better outcomes in the HBO group than in the control group. Conclusion Conventional treatment combined with HBO therapy can promote neurofunction recovery in TBI patients.The mechanism may be related to down-regulation of serum IL-1 β and IL-6.