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.

Objective:To evaluate the diagnostic efficacy of the multiparametric MRI (mpMRI) deep learning artificial intelligence (AI) analysis system combined with 68Ga-prostate specific membrane antigen (PSMA) PET for prostate cancer. Methods:Data of 103 patients (age: 45-85 years) who underwent 68Ga-PSMA PET/MR at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from May 2018 to October 2023 for suspected or confirmed prostate cancer were retrospectively collected. ROI was delineated to measure SUV max of primary tumor or prostate, and a deep learning AI system was applied to analyze MR images of the prostate. The diagnostic efficacies of T 2 weighted imaging (WI), diffusion WI (DWI), mpMRI, PET SUV max, and PET/MR for prostate cancer were assessed, with using the pathological results as the gold standard. Results:Among 103 patients, 82 cases (79.61%) were with prostate cancer. PET unimodality demonstrated the best specificity (100%, 21/21), positive predictive value (100%, 58/58), and AUC (0.860, 95% CI: 0.777-0.920). The mpMRI AI analysis provided rapid diagnostic results and the sensitivity and accuracy were improved by combining with PET (sensitivities of PET, mpMRI and the combination of the two were 70.73%(58/82), 86.59%(71/82), and 92.68%(76/82), respectively; the accuracies were 76.70%(79/103), 81.55%(84/103) and 86.41%(89/103), respectively). Among 44 patients with negative PET, 30 patients received an accurate diagnosis when the results of mpMRI AI analysis were added. Conclusions:68Ga-PSMA PET demonstrates good specificity for prostate cancer and mpMRI AI analysis is time-saving. The combined application improves the diagnostic sensitivity and accuracy, which provides a valuable tool for 68Ga-PSMA PET/MR image analysis.

Objective:To analyze and summarize the clinical manifestations, pathological characteristics, treatment, and outcomes of primary malignant melanoma of the esophagus(PMME)in elderly Chinese patients.Methods:A case study of an elderly patient with PMME was conducted at the Department of Gastroenterology in the China-Japan Friendship Hospital.Additionally, literature and case data on elderly PMME cases reported in China up to July 2023 were gathered and analyzed to summarize the epidemiological characteristics, endoscopic manifestations, clinical presentations, diagnosis, treatment, and prognosis of the disease.Results:A comprehensive review of the literature up to July 2023 documented a total of 114 cases of elderly patients with PMME in China, which also included cases from our hospital.Among these cases, there were 68 male patients(59.6%)and 46 female patients(40.4%), ranging in age from 60 to 81 years, with a median age of 65 years.The predominant clinical manifestations observed were dysphagia and choking while eating, followed by chest pain and retrosternal burning sensation.The majority of the lesions were found in the middle and lower segments of the esophagus, predominantly protruding into the lumen, with only 2 cases(1.8%)displaying esophageal mucosal pigmentation.Immunohistochemical analysis revealed that HMB45 was positive in 74 cases(64.9%)and negative in 3 cases(2.6%), while S-100 was positive in 66 cases(57.9%)and negative in 2 cases(1.8%), although data for some patients were not available.Lymph node or distant metastases were present in 45 cases(39.5%), while 38 patients(33.3%)had tumors confined to the esophagus without metastases.Of the 114 patients, 61(53.5%)had a follow-up period ranging from 0.3 to 39 months, with a median follow-up time of 6.75 months.Among the patients who survived during the follow-up period, there were 30 cases(26.3%), with a follow-up time of 1 to 39 months and a median follow-up time of 7.5 months.For the deceased patients, the time from consultation to death ranged from 0.3 to 31 months.Conclusions:Elderly individuals with PMME in China typically present with a gradual onset, nonspecific symptoms, frequent metastasis upon diagnosis, aggressive behavior, and unfavorable outcomes.

Objective:To investigate the value of ultrasonography in diagnosis of transposition of great arteries of the fetus at 11-13 + 6 weeks gestation. Methods:A prospective study was conducted on fetuses screened by ultrasound in the first trimester in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region between January 2015 and March 2022. Fetal heart structure was screened by three-section screening method. Fetuses with suspected transposition of the great arteries at 11-13 + 6 weeks gestation underwent followed-up ultrasound examination, chromosome and gene test results. The ultrasound characteristics and prognosis pregnancy outcomes were summarized. Results:Twenty-one cases of transposition of the great arteries were detected by ultrasonography, including complete transposition of great arteries (20 cases) and congenitaly corrected transposition of the great arteries (1 case). Two cases were miss diagnosed. Twenty-one cases showed parallel signs of two major arteries on grayscale outflow section at 11-13 + 6 weeks gestation. There were 6 cases with aneuploid ultrasonographic soft markers abnormality, 2 cases with extracardiac malformation. Chromosome and microarray analysis were performed in 13 cases. 4 cases with chromosomal abnormality. Four cases of chromosomal abnormalities were associated with ultrasonographic soft markers abnormality, and 1 case with extracardiac malformation.In the 23 cases, 20 cases were induced, 1 miscarried, and 2 delivered to term. Among the fetuses delivered at term, 1 case died before neonatal operation and 1 case survived. Conclusions:Standardized ultrasound scan at 11-13 + 6 weeks has high accuracy in diagnosis of transposition of the great arteries. And the incidence of chromosomal abnormality is high with ultrasonographic soft markers abnormality or extracardiac malformation.

Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.

Objective:To explore the diagnostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for the restaging of patients with colorectal cancer and its impact on treatment strategy. Methods:Patients with colorectal cancer who underwent 68Ga-FAPI PET imaging in the PET Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2021 were retrospectively analyzed. PET images were evaluated by 3 experienced imaging physicians. Biopsy or postoperative pathology, clinical and imaging follow-up results were as the gold standard. The diagnostic value of PET was compared with conventional imaging (CT/MR), and the impact of 68Ga-FAPI PET on guiding treatment was evaluated. χ2 test and Fisher exact test were used to compare the differences between groups. Results:A total of 33 patients were included (17 males, 16 females, age (52.8±12.3) years), of which 24 were finally diagnosed as recurrence/metastases/progression. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of 68Ga-FAPI PET in detecting recurrence/metastases/progression of colorectal cancer were 93.9%(31/33), 100%(24/24), 7/9, 92.3%(24/26) and 7/7, respectively. Its accuracy, sensitivity and negative predictive value were significantly higher than those of conventional imaging (64.5%(20/31), 56.5%(13/23) and 7/17; χ2 values: 8.549 and 10.786, all P<0.05). Compared with the clinical or pathological stage before examination, 68Ga-FAPI PET led upstaging to stage Ⅳ in 12 patients (50.0%, 12/24). Of the 31 patients who were correctly diagnosed by 68Ga-FAPI PET, the treatment regimen of 22 patients (71.0%) was changed because of 68Ga-FAPI PET imaging. Conclusion:68Ga-FAPI PET has good diagnostic performance in the restaging of colorectal cancer, which is helpful to further guide clinical treatment strategy.

Objective To explore clinical curative effects of superficial temporal artery-middle cer-ebral artery bypass combining with encephalo-duroarterio-synangiosis( STA-MCA+EDMS) in the treatment of moyamoya disease. Methods Thirteen cases were confirmed to be moyamoya disease by digital subtrac-tion angiography ( DSA) , and treated with STA-MCA+EDMS methods. Four cases were ischemic, and the others were hemorrhagic in this group. Results The follow-up was 6-12 months. The clinical symptoms were improved significantly, without cerebral ischemic attack in 4 ischemic cases. Seven hemorrhagic cases got blood from the external carotid artery by means of vascular bypass or temporal muscle, and established effective collateral circulation half a year after operation. Two hemorrhagic cases bleed again in July after operation. However, the family gave up treatment. Ten cases were good, one case was moderate, while two cases got bad. The total effective rate was 76. 9％. Conclusions STA-MCA+EDMS can improve cerebral hemodynamics of moyamoya disease, improve quality of life, and reduce incidence of stroke.

Objective: To explore the impact of insulin resistance (IR) and adiponectin (APN) lacking on myocardial remodeling in experimental mice. Methods:16 normal C57 mice were divided into 2 groups: Control group and IR group; in addition, 16 APN gene knockout(APNKO) mice were divided into another 2 groups: APNKO group and APNKO+IR group.n=8 in each group. The mice in Control group and APNKO group were fed with normal diet, in IR group and APNKO+IR group were fed with high fat diet to create the IR model. All animals were treated for 12 weeks. Blood levels of total cholesterol(TC), triglycerides(TG),fasting plasma glucose(FPG) and fasting insulin(FINS) were examined; heart weight and left ventricular weight were measured; left ventricular myocardial morphological changes and the degree of ifbrosis were assessed by HE staining and Masson staining; protein expressions of myocardial matrix metalloproteinase-9 (MMP-9) and APN were detected by immunehistochemistry and Western blot analysis. Results: Compared with Control group, IR group, APNKO group and APNKO+IR group showed elevated blood levels of TC, TG, FPG and FINS; increased heart weight and left ventricular weight, allP<0.05; IR group, APNKO group and APNKO+IR group presented more myocardial hypertrophy, decreased protein expression of APN and increased protein expression of MMP-9, allP<0.05.Conclusion: IR and APN lacking could incur myocardial remodeling in experimental mice and they had synergistically facilitated effect.

In order to evaluate the diagnostic accuracy of glucose-6-phosphate isomerase in patients with rheumatoid arthritis, retrieval was performed using the data bases of Medline, Embase, Cochrane library, Cmcc and Cbmdisc (1990 to 2007). We included the articles which reported the studies of GPI measured by enzyme-linked immunosorbent assay in the diagnosis of RA patients. Then we reviewed 15 article and used RevMan Software for analysis; the heterogeneity among the articles was determined to be high (chi2 = 191.65, P < 0.00001). When we analyzed the 5 articles wherein serum was used as the standard, we noticed homogeneity (chi2 = 6.97, P = 0.14). The summary sensitivity was 25%; the summary specificity was 80%; the area under the curve was 0.6279. Our study demonstrated that GPI exhibited high specificity and low sensitivity in diagnosing RA cases. We suggest that GPI be used in conjunction with some assay or other that is characterized by high sensitivity.
Arthritis, Rheumatoid ; blood ; diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Glucose-6-Phosphate Isomerase ; blood ; Humans ; Male ; ROC Curve ; Sensitivity and Specificity

Objective To investigate the level of five auto-antibodies including MCV and GPI in the serum of RA patients and assess the application value of five auto-antibodies in RA diagnosis.Methods The five auto-antibodies were detected by ELISA in serum samples of 150 patients with RA and 40 healthy controls,32 patients of SLE,30 patients of OA,20 patients of AS,20 patients of SS,20 patients of CTD.Results The positive rates of these five auto-antibodies in RA patients were significantly higher than in other group(X2=88.5,76.0,279.2,88.2,94.8,P＜0.05).Except anti-AKA,there was no the differences in the level of other antibodies among groups(X2=21.9,9.4,20.2,43.2,41.6,P＞0.05).Anti-MCV and anti-GPI has the highest sensitivity(78.0% and 83.3%),while anti-CCP has the highest specificity(97.1%)and anti-AKA has good specificity(96.1%)and lowest sensitivity(49.4%).When two antibodies were detected together,the sensitivity and specificity of MCV/CCP were highest(92.7% and 96.9%).When RF/GPI/CCP were detected together,the sensitivity and specificity were 90.7% and 96.9%,respectively.When RF/MCv/CCP were detected together,the sensitivity and specificity were 94.0% and 96.9%.Conclusions Anti-MCV and anti-GPI has the hishest sensitivity in laboratory diagnosis of RA,while anti-CCP has the highest specificity and anti-AKA have good specificity and lowest sensitivity.The combination detection can decrease the amount of missed diagnosis caused by single test. The combination detection of RF/GPI/CCP and RF/MCV/CCP will improve sensitivity and specificity for diagnosis to the RA patients.