Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder(PTSD).Methods Totally 40 C57BL/6J male mice were randomly divided into by control group(Ctrl)and PTSD group,the PTSD group was divided into a no-exercise group(PTSD),a low-intensity exercise group(L)and a high-intensity exercise group(H).The PTSD model mice were constructed by combining conditioned plantar-foot shock(CF)and single-session sustained stress(SPS).After the exercise intervention,the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test;Subsequently,the densities of the newborn mature neurons in dentate gyrus(DG)of hippocampus were detected by immunofluorescent double-labelling staining,and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology.The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points;Meanwhile,the concentration level of adiponctin(APN)in the hippocampal area was determined by ELISA.Results The result showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test,and in the elevated cross maze experiment,the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group,while the residence time and the number of entries in the closed arm were significantly reduced.In addition,both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice,and high-intensity exercise significantly increased the number of dendritic branching points,and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group.At the same time,the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group,and it was more significant in the H group.Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice,and at the same time,it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice,suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion,and the improvement effect is better with high-intensity exercise.

Objective:To analyse the 3D-Flair MRI manifestations of the inner ear, vestibular function status, and their correlation with hearing treatment outcomes in patients with severe sudden sensorineural hearing loss (SSNHL), and to explore potential prognostic indicators for sudden deafness.Methods:The clinical data of adult patients with unilateral profound sudden sensorineural hearing loss were retrospectively analyzed in Otorhinolaryngology Department of Shandong Provincial ENT Hospital from March 2018 to August 2020. Patients were categorized based on the results of their inner ear 3D-Flair MRI into two groups: the normal MRI group and the abnormal MRI group. The abnormal group was further divided into three subgroups: those with non-absorbed high signal in the inner ear, those with absorbed high signal, and those with destruction of the blood-labyrinth barrier. SPSS 26.0 statistical software was applied to analyze the differences in hearing efficacy, caloric tests, vestibular evoked myogenic potentials (VEMP), video head impulse tests (vHIT), and the incidence of dizziness/vertigo among various patient groups.Results:A total of 191 patients with complete data were collected (97 males and 94 females, aged from 13 to 69 years old). There were 50 cases in the normal inner ear 3D-Flair MRI group. A total of 141 cases were found in the group with abnormal 3D-Flair MRI, including 50 cases of high signal unabsorbed, 71 cases of absorption high signal and 20 cases of blood labyrinth barrier destruction. There were no significant differences in age, sex, lateral ratio of hearing loss and course of disease among four groups (all P>0.05).The significant efficiencies of hearing recovery, in the group with normal 3D-FLAIR MRI were better than those in the abnormal group ( P<0.05) after treatment. Among the four groups, there were significant differences in the apparent efficiency and total effective rate between the normal group and the inner ear high signal absorption group ( χ2=4.007, P=0.045; χ2=6.925, P=0.009). The abnormal rates of bithermal caloric test, vHIT results and dizziness/vertigo symptoms in the abnormal group were higher than those in the normal group ( P<0.05). There were significant differences in oVEMP abnormality rate, vHIT abnormality rate and incidence of dizziness/vertigo among the three groups with 3D-FLAIR MRI abnormality ( P<0.05). There were significant differences in caloric test, oVEMP, vHIT abnormality rate and incidence of dizziness/vertigo among the four groups ( P<0.05). The positive rates of caloric test, cVEMP test and vHIT test in patients with dizziness/vertigo were higher than those in patients without dizziness/vertigo ( P<0.05). The abnormal rates of posterior semicircular canal and horizontal semicircular canal in patients with dizziness/vertigo were significantly increased ( P<0.05) than patients without dizziness/vertigo. The recovery rate, effective rate and total effective rate of patients without dizziness/vertigo were significantly better than those with dizziness/vertigo ( P<0.05). Conclusions:The 3D-Flair MRI of the inner ear and vestibular function tests have reference value for the prognosis assessment of patients with severe sudden sensorineural hearing loss. Abnormal 3D-FLAIR MRI of the inner ear, especially absorption high signal, is associated with high incidence of vestibular dysfunction and dizziness/vertigo, with poor prognosis. Patients with severe sudden sensorineural hearing loss who have symptoms of dizziness/vertigo are more likely to exhibit abnormal results in vestibular function tests, with a higher susceptibility to involvement of the posterior and horizontal semicircular canals.

[Objective]To clarify the associations between plasma fibrinogen(Fbg)and volumetric bone mineral density(vBMD)as well as osteoporosis measured by quantitative computed tomography(QCT),and to explore the role of plasma Fbg in early screening and diagnosis of osteoporosis.[Methods]Patients with hypertension who were hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to June 2022 and underwent QCT examinations were included for cross-sectional analysis.The study analyzed the correlation between plasma Fbg and osteoporosis in patients.The diagnostic efficacy of plasma Fbg for osteoporosis was evaluated by the area under the receiver operating characteristic(ROC)curve(AUC).[Results]Totally 441 subjects were included in the analysis,with an average age of 46.0±14.5 years and a prevalence of osteoporosis of 6.4%(28/441).As the level of plasma fibrinogen increased,the incidence of osteoporosis significantly increased(P<0.000 1)while the average bone mineral density of L1 and L2 were significantly decreased(P<0.05).Compared with the first quartile of plasma Fbg(1.99g/L-2.37g/L),the risk of osteoporosis in the fourth quartile of plasma Fbg(3.67g/L-4.46g/L)increased by 8.85 times after adjusting for related confounding factors.[Conclusion]This study found a negative correlation between plasma fibrinogen levels and bone density in patients with hypertension.Plasma fibrinogen levels may serve as a potential screening indicator for osteoporosis,aiding in early diagnosis and therapeutic monitoring.This discovery offers a new perspective for the study of bone metabolic diseases and warrants further investigation.

Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective:To investigate the dynamic changes of serum long non-coding ribonucleic acid antisense non-coding RNA in the INK4 locus (LncRNA ANRIL), long non-coding ribonucleic acid maternally expressed gene 3 (LncRNA MEG3) and inflammatory factors [interferon-γ (IFN-γ), interleukin-6 (IL-6), interleukin-18 (IL-18) and interleukin-1β (IL-1β)] in patients with acute ischemic stroke and their correlation with neurological impairment.Methods:This prospective study included fifty-two patients with acute ischemic stroke admitted to the Central Hospital of Dalian University of Technology were included, and the neurological impairments of the patients were scored using the National Institutes of Health stroke scale (NIHSS) on the first day of the onset of the disease, and serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factors (IFN-γ, IL-6, IL-18 and IL-1β) were detected using enzyme-linked immunosorbent assay (ELISA) at the first, second and seventh day of the onset of the disease. The correlation between serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factor levels and neurological impairment at each time point was analyzed by Spearman correlation analysis.Results:Among 52 patients, mild group had 22 cases (NIHSS score <5 scores), and moderate-to-severe group had 30 cases (NIHSS score ≥5 scores). In acute ischemic stroke patients with moderate-to-severe group, the expression level of LncRNA MEG3 was higher than in the mild group, but the intergroup difference did not reach statistical significance ( P>0.05). LncRNA ANRIL, LncRNA MEG3, IFN-γ, IL-18 and IL-1β peaked at the same time point in acute ischemic stroke patients, all within second day of the onset of the disease. Spearman correlation analysis showed that the serum LncRNA MEG3 level on the first day of the onset of the disease was significantly positively correlated with NIHSS score ( P = 0.006), and serum LncRNA ANRIL level on seventh day was significantly positively correlated with NIHSS score ( P = 0.049). Conclusions:Serum LncRNA ANRIL, LncRNA MEG3 and inflammatory factors (IL-18, IL-1β and IFN-γ) are highly expressed in patients with acute ischemic stroke, peaking on the second day of onset. LncRNA MEG3 levels on the first day of onset and LncRNA ANRIL levels on the seventh day of onset are helpful in determining the degree of neurological impairment in patients with acute ischemic stroke.

Autoimmune oophoritis is a rare cause of primary ovarian insufficiency(POI), and some patients may also have concurrent adrenal insufficiency. This condition significantly impairs reproductive function and is often difficult to distinguish from common causes of POI, leading to missed or incorrect diagnoses. This paper reports a case of autoimmune oophoritis treated in our department and provides an updated summary of recent advances in the understanding of this condition, with the aim of raising clinical awareness and improving diagnostic accuracy among healthcare professionals.