Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm²), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.
Humans ; Male ; Esophagogastric Junction/pathology* ; Aged ; Carcinoma, Neuroendocrine/pathology* ; Vacuoles/pathology* ; Esophageal Neoplasms/pathology* ; Cell Nucleus/pathology* ; Adenocarcinoma, Papillary/pathology* ; Stomach Neoplasms/pathology*

Objective To investigate whether ginsenoside Rg3 can ameliorate glomerular endothelial injury in diabetic nephropathy(DN)mice through Ras homologous gene family member A(Rho A)/Rho-associated coiled-coil forming protein kinase,(ROCK1)/NLR family pyrin domain protein 3(NLRP3)pathway.Methods Forty mice were randomly divided into 4 groups:control group,DN group,ginsenoside(ginsenoside Rg3)group and RhoA/ROCK pathway inhibition(FD)group,with 10 mice in each group.Fasting blood glucose(FBG)was measured by glucose meter.The levels of urinary protein,urea nitrogen(BUN)and serum creatinine(SCr)were detected by ELISA.PAS staining was used to detect glomerular morphology and structure and to evaluate glomerular injury index(GDI).The expression of platelet-endothelial cell adhesion molecule(PECAM-1 or CD31),von Willefibrilia factor(vWF),RhoA,ROCK and NLRP3 protein related to pyrodeath were detected by immunofluorescence staining.Western blotting detected the expression of intercellular adhesion molecule-1(ICAM-1),vascular cell adhesion molecule-1(VCAM-1),the inflammatory factor interleukin-1β(IL-1β)and IL-18 protein in the glomerulus.Results Compared with the control group,the levels of FPG,urinary protein,BUN and SCr in DN group were increased,and the differences were statistically significant(t=17.59～43.81,all P<0.05).The glomerular structure was significantly damaged and GDI was increased(t=20.73,P<0.05).The expressions of CD31,RhoA,ROCK and NLRP3 in glomeruli were increased,while the expression of vWF was decreased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues were increased,and the differences were statistically significant(t=27.95～40.10,all P<0.05).Compared with the DN group,the levels of FPG,urinary protein,BUN and SCr in ginsenoside group were decreased,and the differences were statistically significant(t=14.87～20.33,all P<0.05).The damage of glomerular structure was improved and GDI was decreased(t=19.80,P<0.05),the expression of CD31,RhoA,ROCK and NLRP3 in glomerular was decreased,and the expression of vWF was increased.The expressions of ICAM-1,VCAM-1,IL-1β and IL-18 in renal tissues of FD group were decreased,and the differences were statistically significant(t=12.62～39.68,all P<0.05).Conclusion Ginsenosides Rg3 can improve the level of glomerular endothelial injury and pyroptosis in DN mice by down-regulating RhoA/ROCK/NLRP3 pathway.

Kinesin superfamily proteins(KIFs)are motor proteins that travel along microtubules and facilitate the transport of small biological molecules within cells.Various kinesin proteins are present in the dorsal root ganglion and spinal dorsal horn,where they modulate the excitability and sensitivity of sensory neurons,contributing to the occurrence and maintenance of pathological pain.Therefore,they represent potential therapeutic targets for the treatment of pathologi-cal pain.This review provides a comprehensive overview of the recent advancements in understanding the peripheral and central mechanisms of kinesins in the context of pathological pain,offering valuable insights for the potential development of analgesic medications targeting kinesin.

Ischemic stroke and hemorrhagic stroke have different pathogenic mechanisms,but share similarities in metabolic dysregulation,inflammatory responses and oxidative stress.This paper summarized 28 metabolic markers shared between ischemic stroke and hemorrhagic stroke with consistent trends through literature review.It also provided an overview of their involvement in abnormal energy metabolism,inflammatory responses,blood-brain barrier disruption,and neural damage in relation to stroke.The aim is to provide a scientific basis for future prognosis,curative efficacy evaluation and future homotherapy of ischemic stroke and hemorrhagic stroke,and provide insights for the development of new therapies and new drugs.

Objective:To explore the clinicopathologic features of early-onset pancreatic cancer (EOPC) and its correlation with dyslipidemia and prognostic analysis.Methods:This is a retrospective cohort study. Clinical and pathological data of 455 patients with pancreatic cancer who underwent radical surgery from January 2013 to September 2020 in the Department of Pancreatic Surgery, Qilu Hospital, Shandong University were retrospectively collected. According to the onset age≤50 years, the patients were divided into EOPC group(67 cases) and later-onset pancreatic cancer (LOPC) group(388 cases). There were 48 males and 19 females in the EOPC group, aged (44.4±5.7) years(range: 28.0 to 50.0 years); and 230 males and 158 females in the LOPC group, aged (63.0±7.2)years (range: 51.0 to 86.0 years). EOPC was divided into two groups according to the blood lipid status: dyslipidemia (50 cases) and normal (17 cases). General information, blood lipid data, clinicopathological parameters and follow-up information were collected. χ2 test, Mann-Whitney U test and Logistic regression analysis were used to evaluate the difference or correlation between groups, and Cox regression analysis and Kaplan-Meier survival curve were used to analyze the impact of EOPC and dyslipidemia on the prognosis. Propensity score matching was used to match two groups of patients in a 1∶1 ratio using nearest neighbor matching, with a caliper set at 0.05. Results:Compared with LOPC group, EOPC group with a higher proportion of patients with body mass index ≥24 kg/m 2 (55.8%(24/43) vs. 38.7%(113/292), χ2=4.542 ,P=0.033), dyslipidemia(74.6%(50/67) vs. 57.7%(224/388), χ2=6.808, P=0.009), pancreatic head cancer (73.1% (49/67) vs. 60.0%(231/385), χ2=4.176, P=0.041) and a lower proportion of patients with type 2 diabetes (9.0%(6/67) vs. 24.2%(94/388), χ2=7.771, P=0.005) and hypertension (9.0%(6/67) vs. 33.0%(128/388), χ2=15.885, P<0.01). Compared the proportion of dyslipidemia in the two groups,there was a higher proportion of high density lipoprotein cholesterol(HDL-C) abnormality in the EOPC group (65.7%(44/67) vs. 42.8%(166/388), χ2=12.044, P<0.01), whereas there was no significant difference in other lipid indices. Kaplan-Meier survival curve analysis of dyslipidemia did not have a significant effect on the prognosis of EOPC patients ( P=0.430). The results of further Logistic regression analysis showed that gender( OR=6.445 (95% CI: 1.692 to 24.548), P=0.006) and tumor location ( OR=5.352 (95% CI: 1.374 to 20.846), P=0.016) were independent related factors with serum lipid level in patients with EOPC. Conclusions:Compared with LOPC, EOPC is more likely to be combined with obesity and HDL-C abnormalities, and the proportion of pancreatic head cancer is also higher, but there is no significant difference in prognosis between the two groups. In the EOPC patients, serum lipid level is associated with gender and tumor site, but has no effect on survival.

Objective To evaluate the value of an optimized three-dimensional inversion-recovery with real reconstruction (3D-real IR) sequence with a longer repetition time (TR, 16 000 ms) based on modulated flip angle technique in refocused imaging with extended echo train (MATRIX) in the endolymphatic hydrops (EH) imaging after intratympanic gadolinium (Gd) administration, and to compare it with a conventional 3D-real IR based on the turbo spin echo (TSE) sequence. Methods From July 2021 to November 2022, twenty-seven patients received both the conventional and optimized 3D-real IR sequences after bilateral intratympanic Gd administration. Images of the two sequences were qualitativly evaluated and compared. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and area ratio of endolymph against the total lymphatic space from the two sequences were measured and compared. Results 14(25.9%) ears with insufficient contrast for the EH diagnosis on the conventional sequence were clearly displayed on the optimized sequence. Image score, CNR and SNR of the optimized sequence were significantly higher than those of the conventional sequence (P ＜ 0.001). The scanning time of two sequences was similar. The area ratio of endolymph against the total lymphatic space in the cochlear was significantly higher on the conventional 3D-real IR than that on the optimized 3D-real IR (P ＜ 0.001); there was no statistical difference in the vestibule between the two sequences. Conclusions Compared with conventional sequence, optimized 3D-real IR sequence with a longer TR may be better for evaluation of EH after intratympanic Gd administration.

Objective To investigate the value of artificial intelligence-assisted compressed sensing (ACS) technology for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear using three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequence. Methods The patients received gadolinium contrast-enhanced magnetic resonance imaging using ACS and united compressed sensing (uCS) 3D-FLAIR at Zhongshan Hospital, Fudan University from January to November 2024 were prospectively enrolled. The repetition time was 16 000 ms, and acquisition time was 6 min 40 s and 10 min 24 s in ACS 3D-FLAIR and uCS 3D-FLAIR, respectively. The images on the two sequences were evaluated independently by two radiologists. The image quality of the two sequences was subjectively evaluated and compared. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared between the two sequences. The grading consistencies using two sequences and between the two doctors were analyzed. Results There was no statistically difference in subjective score of image quality between the two sequences. SNR and CNR of the ACS 3D-FLAIR sequence were significantly higher than those of the uCS 3D-FLAIR sequence (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops were 0.942 and 0.888 using two sequences (P＜0.001). The kappa values of grades of cochlear and vestibular endolymphatic hydrops using the ACS 3D-FLAIR sequence between the two doctors were 0.784 and 0.831, respectively (P＜0.001); the kappa values of grades of cochlear and vestibular endolymphatic hydrops using uCS 3D-FLAIR sequence between the two doctors were 0.725 and 0.756, respectively (P＜0.001). Conclusions ACS 3D-FLAIR could provide higher SNR and CNR than uCS 3D-FLAIR, and is more suitable for intravenous gadolinium contrast-enhanced magnetic resonance imaging of the inner ear; the endolymphatic hydrops grades using ACS 3D-FLAIR is similar to use uCS 3D-FLAIR.

BACKGROUND:Ferroptosis is closely associated with the pathogenesis of ischemic stroke,and targeting ferroptosis is a promising regimen for the treatment of ischemic stroke,but the specific regulatory targets are unclear. OBJECTIVE:To screen ferroptosis-related characterized genes in ischemic stroke by bioinformatics and machine learning methods and validate them by cellular experiments to investigate the role of ferroptosis in ischemic stroke. METHODS:Eligible ischemic stroke-related datasets and ferroptosis expression datasets were selected based on GEO database and FerrDb database,and ferroptosis-related differential genes were screened by t-test.GO functional enrichment analysis with KEGG signaling pathway enrichment analysis was performed for ferroptosis-related differential genes.Characterized genes for ferroptosis in ischemic stroke were screened by PPI network analysis and machine learning.The reliability and biological functions of the characterized genes were explored using ROC analysis and GSEA analysis,followed by cell experiment.HT22 cells were divided into control and ischemic stroke groups.No intervention was made in the control group,and 0.1 mM H2O2 was added to the ischemic stroke group for 24 hours to simulate cellular oxidative stress injury and ferroptosis.The ferroptosis and the expression of characterized genes were verified by real-time fluorescence quantitative polymerase chain reaction(RT-PCR)and western blot assay. RESULTS AND CONCLUSION:(1)Forty-five ferroptosis-associated differential genes were obtained,and GO and KEGG enrichment analyses revealed that the differential genes were closely associated with oxidative stress,autophagy,ferroptosis,adipocytokine signaling pathway,and mitochondrial metabolism.(2)A total of one ferroptosis characterized gene,nuclear factor erythroid 2-related factor 2(NFE2L2),was identified by the MCODE plugin and cytoHubba plugin in the PPI network with the LASSO algorithm and SVM-RFE algorithm in machine learning.(3)Receiver operating characteristic curve analysis of NFE2L2 revealed that the diagnostic prediction models constructed in the training and validation sets had good accuracy and specificity.GSEA analysis of NFE2L2 revealed that the characterized gene was involved in the regulation of ischemic stroke pathogenesis through immunity,inflammatory response,amino acid metabolism,and neurofactor regulation.(4)RT-PCR and western blot analyses showed that the acyl coenzyme A synthetase long chain family,member 4(ACSL4)mRNA and protein expression levels were significantly higher in the ischemic stroke group compared with the control group(P<0.05),and the glutathione peroxidase 4(GPX4)mRNA and protein expression levels were significantly lower in the ischemic stroke group(P<0.05).Compared with the control group,the mRNA and protein expression levels of the characterized gene NFE2L2 were significantly higher in the ischemic stroke group(P<0.05).(5)It suggests that ischemic stroke is closely related to ferroptosis,and targeting the characterized gene NFE2L2 may provide certain ideas and directions for the study and treatment of ischemic stroke.

ObjectiveTo explore the current situation and influencing factors of humanistic care experience among patients visiting traditional Chinese medicine （TCM） outpatient clinics in China， and to provide a basis for optimizing TCM-characterized services in both TCM and Western medicine hospitals. MethodsA multi-center cross-sectional study was conducted using convenience sampling to select 35 hospitals across 13 provinces in China （including 3 TCM hospitals and 32 TCM outpatient clinics in general hospitals）. A total of 3，430 patients were surveyed using the general information questionnaire and the Outpatient Humanistic Care Experience Questionnaire， with data collected via Questionnaire Star. Univariate analysis and multiple linear regression were employed to examine the impacts of patient characteristics， visit characteristics， hospital type （TCM hospital/general hospital）， and geographic region （eastern/central/western） on humanistic care experience. ResultsThe total score of humanistic care experience was 194 （188， 233）. Univariate analysis showed that gender， educational level， current residence， per capita monthly household income， location attribute of medical institutions， number of previous visits to this hospital， payment method of medical expenses， previous hospitalization history in this hospital， frequency of outpatient visits within the past 12 months， self-rated disease severity， familiarity with the outpatient procedures， implementation of the follow-up service provided by the hospital， satisfaction with follow-up services， the grade of the hospital visited， geographical region of the hospital visited， and the department visited had an impact on the humanistic care experience during outpatient visits （P<0.05）. Multivariate analysis demonstrated that educational level （β=0.609， P=0.011）， self-rated disease severity （β=-0.646， P=0.047）， familiarity with outpatient procedures （β=4.784， P<0.001）， satisfaction with follow-up services （β=6.365， P<0.001）， and the grade of the hospital visited （β=-5.487， P<0.001） affected the humanistic care experience in outpatient medical treatment， explaining 24.4% of the total variation. ConclusionHumanistic care experience in TCM outpatient clinics is influenced by multiple factors. It is recommended to optimize the medical treatment process， strengthen doctor-patient communication training， and establish a precise follow-up mechanism， with a focus on improving care perceptions among patients with lower education levels and those attending primary-level hospitals， to refine the TCM-characterized service system.