The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To explore the value of applying stone burden in evaluating the treatment efficacy of patients with upper ureteral stones undergoing extracorporeal shock wave lithotripsy.Methods:A retrospective selection was conducted on 328 patients with upper ureteral stones admitted to Beijing Friendship Hospital, Capital Medical University from October 2018 to August 2024. The maximum diameter of the stones was 1.0-2.0 cm, and the patients were divided into successful lithotripsy group ( n=306) and failed lithotripsy group ( n=22) based on the success or failure of lithotripsy. Using multi-slice spiral CT scanning to collect the longest diameter, maximum CT value, volume, and average CT value of the stones in the enrolled patients, evaluate the predictive value of stone burden on the effectiveness of extracorporeal shock wave lithotripsy in patients with upper ureteral stones. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used for comparison between groups; count data were expressed as the cases and percentage, and Chi-square test was used for comparison between groups. Univariate and multivariate Logistic regression analysis were used to evaluate the factors affecting the efficacy of extracorporeal shock wave lithotripsy in patients with upper ureteral stones. The area under the curve (AUC) of receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each influencing factor for the therapeutic effect. Results:The results of univariate analysis showed that there were no statistically significant differences in age, gender, disease duration, and stone side between the successful and failed lithotripsy groups ( P>0.05). However, there were statistically significant differences in the longest diameter, maximum CT value, volume, average CT value of the stones and stone burden ( P<0.05). The results of multivariate Logistic regression analysis showed that the longest diameter, maximum CT value, volume, average CT value of the stones and the stone burden were all risk factors affecting the therapeutic effect of extracorporeal shock wave lithotripsy for upper ureteral stones ( P<0.05). The results of ROC curve analysis showed that the AUC of the longest diameter, maximum CT value, volume, average CT value of the stones and the stone burden, burden 1, burden 2, and burden 3 were 0.844, 0.827, 0.948, 0.873, 0.889, 0.835, 0.911 and 0.865, respectively. Conclusion:The stone burden has good predictive value for the therapeutic effect of extracorporeal shock wave lithotripsy in the treatment of upper ureteral stones, and is worthy of promotion and application.

Objective : To identify autophagy-related genes involved in pulmonary infection caused by the highly drug-resistant and virulent methicillin-resistant Staphylococcus aureus strain USA300 ( USA300) ，and to explore the underlying molecular mechanisms ， thereby providing potential targets for immunotherapy． Methods: The GSE220943 dataset of a USA300-induced pulmonary infection mouse model was obtained from the GEO database． Differentially expressed genes ( DEGs ) were identified using the DESeq2 package． Autophagy-related genes ( ARGs) were retrieved from the MSigDB and Autophagy databases．Weighted gene co-expression network analysis ( WGCNA) was performed to construct gene co-expression modules．Genes overlapping among DEGs，ARGs，and WGCNA modules were identified as autophagy-related DEGs．Gene Ontology ( GO) enrichment analysis was con- ducted using the clusterProfiler R package，while Kyoto Encyclopedia of Genes and Genomes ( KEGG) pathway en- richment analysis was performed via the Metascape platform．Immune cell infiltration was analyzed using the Immu- CellAI-mouse website．A protein - protein interaction ( PPI) network was constructed using the STRING database， and hub genes were identified through topological analysis in Cytoscape． Receiver operating characteristic curve ( ROC) curves were plotted via the website https: / /www．bioinformatics．com．cn． Finally，key gene expression was validated in mouse lung tissues by real-time quantitative reverse transcription PCR ( RT-qPCR) ． Results: A total of 6 135，4 075，3 680，and 2 342 differentially expressed genes ( DEGs) were identified at 12，24，48，and 96 hours post-infection，respectively．By integrating DEGs，autophagy-related genes ( ARGs) ，and WGCNA mod- ules，19 autophagy-related DEGs were identified． GO and KEGG enrichment analyses indicated that these genes were mainly involved in CD4 + T cell activation and regulation，innate immune responses，and autophagosome mem- brane formation．Immune infiltration analysis revealed that innate immune cells such as neutrophils and dendritic cells predominated during the early phase of infection，while γδ T cells and M2 macrophages became more promi- nent in the later stages．PPI network analysis identified 12 hub autophagy-related genes，among which three upreg- ulated key genes ( Eif2ak2，Ikbke，and Nfkbiz) were further confirmed．The area under the ROC curve for all three genes was 1. 000．RT-qPCR validation demonstrated significantly elevated expression of these three genes in lung tissues at 24 hours post-infection ( all P＜0. 05) ． Conclusion Eif2ak2，Ikbke，and Nfkbiz may be involved in the pulmonary infection caused by USA300 by promoting autophagy and hold promise as potential targets for immuno- therapy．

OBJECTIVE To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astraga-lus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma(Qi-Zhu-Zao)pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.METHODS Twenty-four BALB/c male mice were randomly divided into sham-operated group,model group,5-FU(5-fluorouracil)group(25 mg·kg-1),and Qi-Zhu-Zao high dose group(5.85 g·kg-1),Qi-Zhu-Zao low dose group(2.925 g·kg-1)(n=6)to construct a mouse model of colorectal cancer in situ transplantation tumor,and the inter-vention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administra-tion;the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E.Pathological staining was used to eval-uate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice.The changes of MDA,SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay(ELISA);the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting(Western blot).RESULTS Compared with the model group,the tumor volume was significantly reduced(P＜0.000 1),liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group,and his-topathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD,MDA,and GSH-Px,up-regulation of ER stress-related proteins p-PERK,p-IF2α,and ATF4,etc.,upregulated the protein expression levels of E-Cadherin,downregulated N-Cadherin,Vimentin,and Snail,and inhibited the EMT process(P＜0.01 or P＜0.05).CONCLUSION In this paper,we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine,and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.

Bone remodeling and bone regeneration are essential for preserving skeletal integrity and maintaining mineral homeostasis.T cells,as key members of adaptive immunity,play a pivotal role in bone remodeling and bone regeneration by producing a range of cytokines and growth factors.In the physiological state,T cells are involved in the maintenance of bone homeostasis through interactions with mesenchymal stem cells,osteoblasts,and osteoclasts.In pathological states,T cells participate in the pathological process of different types of osteoporosis through interaction with estrogen,glucocorticoids,and parathyroid hormone.During fracture healing for post-injury repair,T cells play different roles during the inflammatory hematoma phase,the bone callus formation phase and the bone remodeling phase.Targeting T cells thus emerges as a potential strategy for regulating bone homeostasis.This article reviews the research progress on related mechanisms of T cells immunity involved in bone remodeling and bone regeneration,with a view to providing a scientific basis for targeting T cells to regulate bone remodeling and bone regeneration.

The 16p11.2 microdeletion syndrome is a copy number variant disease associated with multi-system abnormalities.Its clinical manifestations are complex and diverse，including neurodevelopmental disorders（intellectual development disorders，language delay，autism spectrum disorders，etc.），neurological paroxysmal disorders（epilepsy，paroxysmal kinesigenic dyskinesia，etc.），obesity，congenital malformations，etc.The prevalence is approximately 2.8 to 4.3 per 100 000 births.The pathogenesis is that there is a low copy repeat sequence on both sides of the proximal region of 16p11.2，and that the low copy repeat sequence at different positions in the germ cell during meiosis is rearranged through the non-allelic homologous recombination.At present，there is a lack of precise treatment.This article reviews the pathogenesis，classification，and clinical manifestations of 16p11.2 microdeletion syndrome，aiming to provide assistance for the mechanism research，early diagnosis，comprehensive evaluation，rehabilitation intervention，and fertility guidance of this syndrome.

Objective To retrospectively analyze the clinical features and prognosis of patients with massive pulmonary hemoptysis.Methods Patients with massive hemoptysis,who received bronchial artery embolization at authors'hospital between 2016 and 2018,were collected for this study.According to the gender,the patients were divided into female group(n=68)and male group(n=195).The primary disease,age at onset,length of hospital stay,bleeding site,embolization agent used,recurrence rate of hemoptysis,and mortality were calculated.SPSS.27.0 software was used to analyze the correlation between the age of onset,length of hospital stay,gender,recurrence of hemoptysis and death.RStudio4.2.2 software was used to make a normogram of patient's recurrent hemoptysis and death.Results The primary diseases in the top three were bacterial infection,bronchiectasis and old pulmonary tuberculosis,the incidences of them in the female group were 50％,22％and 15％respectively and in the male group were 43％,21％and 21％respectively.The mean age at onset in the female group was(54.6±16.8)years and in the male group was(60.1±14.0)years.The proportions of the bleeding site in the left lung,right lung,or both lungs in the female group were 6％,21％and 73％respectively and in the male group were 17％,21％and 62％respectively.The proportions of the used embolization agent of 350-560 μm PVA particles and 300-500 μm microspheres in the female group were 31％and 24％respectively and in the male group were 50％and 17％respectively.In the patients who had recurrent hemoptysis,the primary diseases in the top three were old pulmonary tuberculosis,pulmonary bacterial infection and bronchiectasis,the incidences of them in the female group were 33％,33％and 33％respectively and in the male group were 44％,34％and 10％respectively.The causes of death were much complex,in which pulmonary infection played an important role.Conclusion In patients with massive pulmonary hemoptysis,there are differences in the primary disease,bleeding site,applicable embolization agent,recurrence rate of hemoptysis,and mortality between females and males,in addition,the age is an independent influencing factor for recurrent hemoptysis and death.(J Intervent Radiol,2024,33:636-641)

Objective·To evaluate the relationship between anxiety level,alexithymia degree and quality of life in patients with anxiety disorders.Methods·Anxiety disorder patients admitted to the outpatient department of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine from October 1,2020 to March 31,2023 were selected as the research subjects,and 438 patients were ultimately included after exclusion.Among them,there were 271 patients with generalized anxiety disorder,101 patients with panic disorder,48 patients with social anxiety disorder,12 patients with agoraphobia,and 6 patients with specific phobia.Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale-17(HAMD-17),the twenty-item Toronto Alexithymia Scale(TAS-20)and World Health Organization Quality of Life Scale-Brief Form Questionnaire(WHOQOL-BREF)were used to assess the patients'anxiety level,depression level,alexithymia degree and quality of life,respectively,and the scale scores of patients with different subtypes of anxiety disorders were evaluated.Spearman correlation coefficient was used to analyze the correlation between anxiety level,depression level,alexithymia degree and quality of life in patients with anxiety disorders.Stepwise regression model was used to analyze the key variables affecting the quality of life in patients with anxiety disorders.Results·There were no significant differences in HAMA score,HAMD-17 score and TAS-20 score among patients with different subtypes of anxiety disorders,but the differences in WHOQOL-BRIEF score were statistically significant(H=10.076,P=0.039).The results of Spearman correlation analysis showed that the WHOQOL-BRIEF score of anxiety disorder patients was negatively correlated with HAMA score,HAMD-17 score and TAS-20 score(r=-0.256,P=0.000;r=-0.311,P=0.000;r=-0.342,P=0.000).The results of stepwise regression analysis showed that age,HAMA score,HAMD-17 score and TAS-20 score had significant impact on the quality of life of patients(all P<0.05).Conclusion·The quality of life in patients with different subtypes of anxiety disorders is different.The anxiety level,depression level and alexithymia degree are the key variables affecting their quality of life.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.