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.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Parkinson's disease(PD)is a common neurodegenerative disease with a complex pathogenesis,and a large number of studies have shown that mitochondrial dysfunction is an important causative factor for PD,whereas dysregulation of mitochondrial quality control is a key factor leading to mitochondrial dysfunction,and that aberrant mitochondrial biogenesis,fusion/fission imbalance,and mitochondrial hyperautophagy are closely associated with the onset of PD,but the role of the mitochondrial quality control system in the progression of PD is unclear.Therefore,this paper reviews the mechanism of mitochondrial quality control system in PD,with the aim of providing new ideas and theoretical basis for the clinical prevention and treatment of PD.

Objective To discuss the detection rate of the arc of Bühler(AOB)in CTA and DSA examinations and its clinical significance.Methods A computerized retrieval of academic papers concerning AOB from the databases of PubMed,Web of Science,Scopus,Embase,Google Scholar,CBM,CNKI,WanFang,VIP and Baidu Scholar was conducted.Stata 17.0 software was used to make meta-analysis.Results A total of 11 articles including 3 837 subjects and 65 AOB cases were included in this analysis.The pooled prevalence of AOB was 1.9％(0.8％-3.2％).CTA showed a pooled prevalence of AOB of 2.0％(0.5％-4.3％)and DSA showed a pooled prevalence of AOB of 1.8％(0.5％-3.9％).Conclusion Clinically,AOB is a rarely-seen anatomical variation.The possibility of the presence of an AOB should be considered when performing the relevant abdominal surgery so as to avoid causing operation difficulties and complications such as abdominal visceral organ ischemia or bleeding.(J Intervent Radiol,2024,33:604-609)

PD is a neurodegenerative disease characterized by degenerative death of dopaminergic neurons in the substantia nigra,exhibiting a range of motor and non-motor symptoms with serious effects on quality of life.circRNA is a covalently closed-loop non-coding RNA that plays a major role in PD progression.This article reviews the involvement of circRNA in oxidative stress,regulation of transcription,neuroinflammation,autophagy,and α-synuclein.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.

Objective:To investigate the efficacy of the plan-do-check-action (PDCA) quality circle in improving the ability for teaching rounds among clinical mentors, and to enhance the construction of teaching staff and the quality of teaching rounds.Methods:The hospital-level assessment scores of the ability for teaching rounds were collected from 34 clinical mentors in different clinical departments of Zhongnan Hospital of Wuhan University in 2021, and such data were used to investigate the influencing factors for the quality of teaching rounds. Then a PDCA plan was developed and executed to improve the quality of teaching rounds. After the implementation of this plan, hospital-level assessment of the ability for teaching rounds was performed for 34 clinical mentors who were randomly selected from different clinical departments in 2022. The 34 clinical mentors who received the hospital-level assessment of the ability for teaching rounds in 2021 were enrolled as control group, and the 34 clinical mentors who received such assessment in 2022 were enrolled as experimental group. The assessment scores were compared between the two groups to evaluate the implementation effect of PDCA, and SPSS 20.0 was used for data analysis. Categorical data were expressed as number of cases or percentage and were analyzed using the chi-square test, and continuous data were expressed as mean±standard deviation and were analyzed using the t-test. Results:Assessment indices included the preparation, execution, skills, and overall impression of teaching rounds. After the implementation of PDCA, there was a significant increase in the excellence rate of assessment scores (76.47% vs. 50.00%) and a significant reduction in the unqualified rate of assessment scores (2.94% vs. 20.59%), with a significant difference ( P=0.031). There was a tendency of increase in the scoring rates of ward round execution (83.44% vs. 88.26%), ward round skills (82.60% vs. 91.09%), and overall impression (90.20% vs. 93.63%), and there were also significant increases in the scores of ward round skills [(14.87±3.02) vs. (16.40±1.53), P=0.020], improvement of the clinical thinking abilities of trainees through diagnosis and differential diagnosis [(7.96±1.66) vs. (8.93±0.93), P=0.006], guidance for trainees to formulate reasonable diagnosis and treatment regimens [(4.18±1.11) vs. (4.82±0.47), P=0.005], and emphasis on key and challenging points in the teaching process [(3.01±0.76) vs. (3.97±0.17), P<0.001]. Conclusions:The application of PDCA can improve the performance of clinical mentors in the process of teaching rounds, enhance their ability for teaching rounds, fortify the team construction of clinical mentors, and help to improve the quality of teaching rounds.

Objective:To compare the effects of different reference brain regions on the semi-quantitative SUV ratio (SUVR) of 18F-Florzolotau PET images of Alzheimer′s disease (AD). Methods:The 18F-Florzolotau PET images of 28 (13 males, 15 females, age (57.3±9.5) years) normal controls (NC), 19 patients (4 males, 15 females, age (73.3±7.3) years) with β-amyloid (Aβ)-positive mild cognitive impairment (MCI) and 40 patients (19 males, 21 females, age (61.9±9.1) years) with AD were collected from Huashan Hospital, Fudan University between November 2018 and July 2020. Six semi-quantitative reference brain regions were defined, including whole cerebellum (WC), cerebellar gray matter (GM), cerebellar white matter (WM), parametric estimation of reference signal intensity (PERSI), WC after partial volume correction (WC_pvc), cerebellar GM after partial volume correction (GM_pvc). SUVR was calculated for 14 ROIs, which included the whole brain defined by the automated anatomical labeling (AAL) template, fusiform, inferior temporal, lingual, middle temporal, occipital, parahippocampal, parietal, posterior cingulate, precuneus defined by the AAL template, and Meta ROI composed of the above brain regions, and braak_Ⅰ-Ⅱ, braak_Ⅲ-Ⅳ, braak_Ⅴ-Ⅵ defined by the Desikan Killiany template. AUC was used to evaluate the classification ability of SUVR, and the correlation between SUVR and clinical scale scores were assessed by Spearman rank correlation analysis. Results:The SUVRs of most brain regions showed a steady upward trend in the AD disease spectrum. In the classification task of NC and MCI, the overall performance of SUVR based on WC_pvc was relatively optimal (AUCs: 0.975-1.000). In the classification task of NC and AD, SUVRs of 10 ROIs based on the WC_pvc method showed the relatively best performance (AUCs: 0.976-1.000). The correlation between SUVR of fusiform based on cerebellar WM and mini-mental state examination (MMSE) score was the strongest ( rs=-0.72, P<0.001), and the SUVR of precuneus based on WC_pvc showed the strongest correlation with clinical dementia rating (CDR) score ( rs=0.78, P<0.001). Conclusion:The SUVR based on WC_pvc method performs well in classification and correlation tasks, and is recommended to be used in semi-quantification of 18F-Florzolotau PET images of AD.

Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

Objective To investigate the differences in efficacy and safety in the treatment of patients with cerebral palsy at different grades of the Gross Motor Function Classification System (GMFCS) by selective posterior rhizotomy (SPR). Methods Relevant literatures on SPR treatment for cerebral palsy were retrieved from Pubmed, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure (CNKI), Wanfang Database, and VIP Database. Clinical trials on SPR treatment for cerebral palsy were included for Meta-analysis. At least two researchers independently screened the literatures, extracted data, and assessed the quality of the literatures. Data analysis was performed by Review Manager 5.4 software. Results A total of 2, 726 literatures were retrieved, and 8 literatures were finally included after screening. The results of the Meta-analysis showed that the gross motor function and self-care ability of patients with cerebral palsy at all GMFCS grades improved significantly after surgery, and muscle tone decreased significantly after surgery (P < 0.05). In comparison of the improvement in gross motor function before and after SPR, patients with grades Ⅱ and Ⅲ of GMFCS benefited the most, followed by those with grade Ⅰ, and those with grades Ⅳ and V benefited less. In terms of improving self-care ability, patients with grade Ⅰ benefited the most, followed by those with grade Ⅲ, and those with grades Ⅱ and IV benefited less. No significant adverse reactions were reported in previous literatures. Conclusion SPR is a relatively safe and effective treatment option for patients with cerebral palsy. Patients at grades Ⅱ and Ⅲ of GMFCS benefit the most from SPR, and patients at grades Ⅳ and V with poor preoperative physical status can also benefit from SPR.