Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery. Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024. Morphological evaluation, immunohistochemical staining, and next generation sequencing (NGS) targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions. Results All three implanted lesions exhibited morphological similarity to their primary counterparts, but displayed enriched mutational profiles. Case 1: a 13-year-old female. The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma, while the implanted lesion was follicular carcinoma. Both lesions harbored MEN1 mutations, with an additional PTPRT mutation detected in the implanted lesion. Case 2: a 45-year-old male. The primary lesion was bilateral nodular goiter, and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus. No mutations were identified in the primary lesion, whereas the implanted lesion exhibited MEN1, GLIS3, EZH1, and KMT2C mutations. Case 3: a 42-year-old female. The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter. A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively. The primary lesion harbored TERT, GLIS3, and SPOP mutations, while the implanted lesion showed TERT, GLIS3, EIF1AX, and KMT2C mutations. Conclusions Endoscopic thyroid surgery is widely applied in clinical practice, however, implantation dissemination of thyroid lesions along surgical pathways may occur, encompassing both benign and malignant entities. Implanted lesions exhibit pathological similarities to their primary counterparts, but demonstrate mutational enrichment.

Objective To investigate the predictive value of β3-adrenergic receptor(β3-AR)expression levels for recurrence after radiofrequency ablation in patients with atrial fibrillation(AF).Methods Patients with AF who underwent their first radiofrequency ablation in the Department of Cardiology from January 2022 to February 2024(AF group,n=166)and healthy individuals undergoing routine medical check-ups during the same period(control group,n=100)were selected as study subjects.Based on whether AF recurred after the procedure during follow-up,AF patients were divided into a non-recurrence group and a recurrence group.General clinical data and relevant laboratory indices of AF patients were collected.The relative expression lev-el of lymphocyte β3-AR mRNA was measured using fluorescence real-time quantitative PCR.Multivariate lo-gistic regression analysis was used to identify risk factors for AF recurrence after surgery,and receiver operat-ing characteristic(ROC)curve analysis was employed to evaluate the predictive value of β3-AR mRNA ex-pression levels for AF recurrence after ablation.Results After 9 months of follow-up post-radiofrequency ab-lation,among 166 AF patients,42 experienced recurrence,with a recurrence rate of 25.3%.Compared with the non-recurrence group,patients in the recurrence group had significantly higher levels of sST2,IL-6 and left at-rial diameter(LAD),with a statistically significant differences(P<0.05).The relative expression level of β3-AR was higher in the recurrence group than in the non-recurrence group,with a statistically significant differ-ence(P<0.05).Multivariate logistic regression analysis showed that LAD,sST2,IL-6,and β3-AR were inde-pendent risk factors for AF recurrence after surgery(P<0.05).ROC curve analysis indicated that the area under the curve for β3-AR mRNA relative expression level in predicting AF recurrence after radiofrequency ablation was 0.884(95%CI:0.794 to 0.975;P<0.05).Conclusion High preoperative expression levels of β3-AR in AF patients are associated with recurrence after radiofrequency ablation,and β3-AR can serve as a potential biological marker for predicting AF recurrence.

Integrated metabolomic and lipidomic profiling,utilizing liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS),has emerged as a pivotal strategy for biomarker discovery.However,the inherent polarity disparity between metabolites and lipids complicates simultaneous analysis.To address this,a dual-stationary phase polarity-extended liquid chromatography(PELC)system was developed,which surpassed conventional one-dimensional LC(1D-LC)by enabling comprehensive coverage of both polar and non-polar compounds within a single injection.This system enhanced chromatographic resolution,peak capacity,and throughput while minimizing analytical variability.Extracellular vesicles(EVs),lipid bilayer-enclosed nanoparticles ubiquitously present in biofluids,had gained prominence as reservoirs of cancer biomarkers due to their cargo stability and pathophysiological relevance.Herein,the application of PELC-HRMS for concurrent metabolome-lipidome profiling in EVs was pioneered.A total of 193 metabolites were identified using this technique coupled with MS-DIAL software and Human Metabolome Database.Subsequently,this technique was employed to explore potential biomarkers for prostate cancer(PCa).Multivariate analysis identified 17 differentially abundant metabolites in PCa,implicating dysregulated pathways including purine metabolism,starch and sucrose metabolism,galactose metabolism,cysteine and methionine metabolism,and biosynthesis of unsaturated fatty acids.Notably,creatine(AUC=0.92)and DG 42:5(AUC=0.80)demonstrated robust diagnostic efficacy,attributable to their broad polarity ranges and EV-specific enrichment.This study established PELC as a high-fidelity platform for multi-omics integration in complex biospecimens,advancing mechanistic insights into metabolic rewiring and disease pathophysiology.

Being a minimally-invasive surgery,the transcatheter arterial embolization treats tumor and vascular diseases mainly through the way of selective endovascular obstruction.Clinically,a variety of embolic agents are available,which include solid embolic agents,liquid embolic agents,and embolic devices.Owing to the consistency of particle size and controllable delivery,the solid embolic agents,especially microspheres-based embolic agents,can effectively achieve the accurate embolization of the tumor blood vessels.Such embolic agents can not only obstruct blood flow but also carry effective anticancer drugs which can be released at the same time of embolization procedure,thus,enhancing the therapeutic effect.Besides,embolic microspheres containing radiopaque components such as iodine,barium,and tantalum,can achieve inherent traceability and monitor the real-time location of embolic agent within body,providing timely information feedback to physicians.As the first part of the topic,this paper makes a comprehensive review about the recent advances in solid embolic agents(focusing on embolic microspheres),aiming to promote the development of this scientific research field.

Being a minimally-invasive procedure,transcatheter arterial embolization can treat tumors and vascular diseases by obstructing the lesion s blood vessels.Embolic agents have been constantly developed so as to meet the requirements in clinical practice.Compared with solid embolic agents,liquid embolic agents and new-type liquid-solid phase conversion type embolic agents have more unique physicochemical properties,which,theoretically,are capable of occluding all the fine vascular branches at the target site.Besides,the microrobot drugs emerging in recent years can be delivered to lesion sites that are difficult to reach in the human body by using multiple external driving sources(such as sound,light,magnetic,etc.),which is of a great advantage in embolization therapy.As the second part of the topic,this paper makes a comprehensive review about the research achievements in embolic equipment,liquid embolic agents and liquid-solid phase conversion type embolic agents,and discusses their characteristics,advantages,clinical application prospects and their shortcomings,aiming to promote the development of this scientific research field.

Objective:To explore the association between acute muscle wasting during hospitalization and poor prognosis in older patients with severe community-acquired pneumonia (SCAP) in emergency department.Methods:This study was a prospective cohort study. From January 1, 2022 to October 31, 2022, consecutive patients aged ≥65 years who met the diagnostic criteria of SCAP and had an interval of 14 days between two CT scans in the emergency department of Beijing Chao-Yang Hospital were enrolled. The general clinical data and cross-sectional area of the erector spinae muscle (ESMcsa) of the thoracic 12 level derived from chest CT on day 1 and day 14 were recorded and the differences between the two measurements were calculated. Patients were divided into survival group and non-survival group based on whether they died within 28 days. Two independent samples t-test and Mann Whitney U test were used to compare the dynamic changes of ESMcsa between two groups, and paired t-test and Wilcoxon signed rank test were used to compare the changes of ESMcsa within two groups. Multivariable Cox regression analysis was used to identify the risk factors for 28-day mortality, and receiver operating characteristic (ROC) curves were used to determine the predictive value of ESMcsa loss for 28-day mortality. The optimal cutoff value was determined on the basis of the Youden index (YI), patients were divided into a high muscle loss group and a low muscle loss group, and Kaplan Meier survival curve was drawn. Results:A total of 106 older patients with SCAP were included, with a median age of 82.0 years and 59 were men (55.7%). The ESMcsa levels of patients in non-survival group were lower than those in survival group both at admission and on the 14th day (both P<0.01). The ESMcsa levels on admission were lower than those on the 14th day in non-survival group ( P<0.001). The loss of ESMcsa in non-survival group [3.01 (-1.51, 7.73) cm 2vs. 0.80 (-2.58, 4.57) cm 2, P=0.020] was higher than that in the survival group. Multivariable Cox regression showed that ESMcsa loss was an independent risk factor for 28-day mortality ( HR=1.116, 95%CI: .029-1.210, P=0.010), the AUC for predicting 28-day mortality was 0.646 (95% CI: 0.528-0.763, P=0.020), and the optimal cut-off value was 6.22 cm 2. Kaplan Meier survival curve showed that the 28-day mortality risk in the high muscle loss group was higher than that in the low muscle loss group ( χ2=11.412, P=0.001). Conclusion:Acute muscle wasting during hospitalization was associated with 28-day mortality among older patients with SCAP, which provides a basis for improving patient prognosis from a muscle perspective.

Objective:To explore the feasibility and effectiveness of full free-breathing cardiac magnetic resonance (CMR) in clinical practice.Methods:The study prospectively included patients who underwent full free-breathing CMR and traditional breath-holding cine imaging between June 1 and June 30, 2024. An analysis and comparison were conducted on the image acquisition time, image quality, and left ventricular function parameters under two scanning methods, including left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO),left ventricular end diastolic volume (LVEDV), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume (LVESV), left ventricular end systolic volume index (LVESVI), left ventricular stroke volume (LVSV), and left ventricular mass (LVM). In addition, the study conducted both quantitative and qualitative analyses of other sequences in full free-breathing CMR, including T 1 mapping, T 2 mapping, flow imaging, and late gadolinium enhancement (LGE). Group comparisons were performed using the Wilcoxon signed-rank test or paired t-test. Consistency assessments included Bland-Altman analysis, intraclass correlation coefficient ( ICC), and linear regression analysis. Results:Totally, 150 patients were recruited into the study. The average acquisition time of full free-breathing CMR was (22.1±3.1) min, with an average short axis cine sequence examination time of (2.7±0.4) min; The average acquisition time of short axis images in a breath-holding state was (4.9±1.4) min, which was significantly longer than the cine scan in the free-breathing state ( P0.001). The cine and LGE images quality scores obtained from full free-breathing CMR were 4 (4, 4) points and 5 (4, 5) points, respectively, while the cine image quality score obtained in a breath-holding state was 5 (4, 5) points. Compared with traditional breath-hold CMR, free-breathing CMR measurements showed slightly higher LVESV, and LVESVI, while LVEDV, LVEDVI, LVSV, LVCO, LVEF, and LVM were slightly lower, except for LVSV and LVCO, which showed no statistically significant difference, the differences in other cardiac function parameters were statistically significant ( P0.05). However, the two methods demonstrated good consistency( ICC0.947) and correlation (0.808 r0.993, P0.001). The Bland-Altman analysis showed that the bias for all cardiac function parameters was within 8.0%. The Native T 1 and T 2 values for free-breathing CMR were (1 277.5±57.0) ms and 40.1 (38.5, 41.4) ms, respectively, and the results of flow imaging and echocardiography were basically consistent. Conclusions:Free-breathing CMR is feasible and effective in clinical practice, showing a high level of consistency with left ventricular functional parameters obtained from traditional breath-hold scanning. It significantly shortens examination time and holds great clinical value for the promotion and widespread use of CMR.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

OBJECTIVE: Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal. METHODS: We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence. RESULTS: Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia. CONCLUSION Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.
Humans ; Mendelian Randomization Analysis ; Inflammatory Bowel Diseases/complications* ; Dementia/etiology* ; Observational Studies as Topic ; Genome-Wide Association Study