Stroke is one of the leading causes of disability and mortality worldwide. Research into its mechanisms and the development of therapeutic strategies heavily rely on animal models that accurately replicate the pathological features of human disease. An ideal animal model for stroke should not only reproduce the neurological deficits and pathological changes observed in clinical patients but also demonstrate good reproducibility and translational value. This review focuses on the preparation and evaluation methods of ischemic stroke animal models. Firstly, it elaborates on the selection criteria, advantages, and disadvantages of experimental animals, including rodents (rats, mice) and non-rodents (non-human primates, miniature pigs, rabbits, zebrafish). Secondly, it provides a detailed overview of the modeling principles, key procedures, and application scopes for ischemic stroke models and hemorrhagic stroke models. Furthermore, the review summarizes advances in the applications of emerging technologies—including gene editing [e.g., clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing], multimodal imaging (e.g., two-photon microscopy, photoacoustic imaging), artificial intelligence, optogenetics, 3D bioprinting, organoid models, and multi-omics–in model optimization, precise assessment, and mechanistic investigation. Finally, based on a systematic analysis of relevant domestic and international literature from 2019 to 2024, this review discusses model selection strategies based on research objectives, a multidimensional evaluation system encompassing behavioral, imaging, and molecular pathological assessments, and envisions future directions involving technological integration to achieve model precision and individualization. This article aims to provide a comprehensive methodological reference to help researchers select appropriate animal models of stroke according to specific scientific questions.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

AIM: To compare the efficacy of different intraocular lens(IOL)fixation in aphakic patients lacking capsule support.METHODS:Retrospective study. Totally 120 cases(120 eyes)of aphakia patients who lacked capsule support admitted to our hospital from June 2019 to June 2024 were selected as the study subjects and randomly assigned into group A and group B, with 60 cases in each group. Group A underwent subcapsular IOL deep scleral fixation, while group B underwent IOL suture suspension fixation in the ciliary groove. The surgery time, uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), intraocular pressure(IOP), corneal endothelial cell density(CECD), corneal endothelial cell loss rate, and postoperative complications were compared between the two groups before and at 1, 3, 6 mo after surgery.RESULTS:The operation time of the group A was lower than that of the group B(24.69±2.69 vs. 32.75±3.75 min, t=11.937, P<0.05). The UCVA and BCVA in both groups were better than those before operation, and the group A was better than the group B(all P<0.05). The loss rates of corneal endothelial cells in the group A were lower than those in the group B at 1, 3 and 6 mo after surgery, the IOP in the group A was lower than that in the group B at 1 mo after surgery, and the CECD in the group A was higher than the group B(all P<0.05). The 3 eyes(5.0%)of the postoperative IOL ectopic in the group A were less than 11 eyes in the group B(18.3%, P=0.023).CONCLUSION:Subcapsular IOL deep scleral fixation has prominent curative effects on aphakic patients who lack capsule support. It helps improve vision, with less operation time, and fewer postoperative complications.

ObjectiveThis paper proposes a novel real-time bedside pulmonary ventilation monitoring method for the diagnosis of chronic obstructive pulmonary disease (COPD), based on electrical impedance tomography (EIT). Four indicators—center of ventilation (CoV), global inhomogeneity index (GI), regional ventilation delay inhomogeneity (RVDI), and the ratio of forced expiratory volume in one second to forced vital capacity (FEV₁/FVC)—are calculated to enable the spatiotemporal assessment of COPD. MethodsA simulation of the respiratory cycles of COPD patients was first conducted, revealing significant differences in certain indicators compared to healthy individuals. The effectiveness of these indicators was then validated through experiments. A total of 93 subjects underwent multiple pulmonary function tests (PFTs) alongside simultaneous EIT measurements. Ventilation heterogeneity under different breathing patterns—including forced exhalation, forced inhalation, and quiet tidal breathing—was compared. EIT images and related indicators were analyzed to distinguish healthy individuals across different age groups from COPD patients. ResultsSimulation results demonstrated significant differences in CoV, GI, FEV₁/FVC, and RVDI between COPD patients and healthy individuals. Experimental findings indicated that, in terms of spatial heterogeneity, the GI values of COPD patients were significantly higher than those of the other two groups, while no significant differences were observed among healthy individuals. Regarding temporal heterogeneity, COPD patients exhibited significantly higher RVDI values than the other groups during both quiet breathing and forced inhalation. Moreover, during forced exhalation, the distribution of FEV₁/FVC values further highlighted the temporal delay heterogeneity of regional lung function in COPD patients, distinguishing them from healthy individuals of various ages. ConclusionEIT technology effectively reveals the spatiotemporal heterogeneity of regional lung function, which holds great promise for the diagnosis and management of COPD.

Objective: Negative symptoms in schizophrenia indicate a poor prognosis. However, the mechanisms underlying the development of negative symptoms remain unclear. This study investigated the relationship between negative symptoms in schizophrenia and frontal alpha asymmetry (FAA). Methods: The study used a 32-channel electroencephalography to acquire alpha power in 4 target-paired sites in each patient. Regional alpha asymmetry was calculated based on the alpha power using EEGLAB Frontal Alpha Asymmetry Toolbox. Results: Sixty schizophrenia patients with predominant negative symptoms (PNS), 72 stabilized schizophrenia (SS) patients, and 73 healthy control (HC) participants were enrolled in this study. No significant differences were observed in FAA between the PNS and SS groups, although both groups exhibited reduced P3-P4 alpha asymmetry compared to HCs. A positive correlation was found between F7-F8 alpha asymmetry and illness duration. Additionally, a predictive model based on P3-P4 alpha asymmetry scores was able to differentiate schizophrenia patients from HCs, achieving a sensitivity of 71.2% and a specificity of 72.6%. Conclusion This study highlighted that parietal alpha asymmetry could serve as a valuable diagnostic tool for schizophrenia.

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude