Alzheimer's disease(AD)is common neurodegenerative diseases that is the main causes of cognitive dysfunction and behavioral abnormalities.Constructing animal models with similar characteristics to human patients is crucial for advancing investigations of AD,and to develop new therapeutic drugs.Combined with the latest research progress,this review classifies animal models of AD according to aging models,genetically modified models,and chemically induced models.This review systematically summarizes the commonly used animal models of AD,and elucidates the modeling mechanisms and pathological changes,and compares their advantages and limitation,with a view to provide method ological references for researchers in selecting appropriate animal model for AD investigation.

Alzheimer's disease(AD)is common neurodegenerative diseases that is the main causes of cognitive dysfunction and behavioral abnormalities.Constructing animal models with similar characteristics to human patients is crucial for advancing investigations of AD,and to develop new therapeutic drugs.Combined with the latest research progress,this review classifies animal models of AD according to aging models,genetically modified models,and chemically induced models.This review systematically summarizes the commonly used animal models of AD,and elucidates the modeling mechanisms and pathological changes,and compares their advantages and limitation,with a view to provide method ological references for researchers in selecting appropriate animal model for AD investigation.

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective To summarize the diagnosis and treatment experience of surgical site infection(SSI)after percutaneous endoscopic lumbar discectomy(PELD).Methods A retrospective analysis was made on 11 cases of postoperative SSI after PELD from January 2016 to December 2022.After PELD surgery,severe lower back or lower limb pain occurred in all the patients,with a Visual Analog Scale(VAS)score of 7-9(average,8.1).The erythrocyte sedimentation rate(ESR)was 17-114 mm/h(average,54.4 mm/h),and the level of C-reactive protein(CRP)was 8-151 mg/L(average,56.5 mg/L).The MRI showed changes of inflammatory signals in the intervertebral space of the surgical area.The SSI was diagnosed at 2-17 d(average,9.5 d)after PELD surgery.All the cases were treated with antibiotics(4 cases with empiric antibiotic therapy and 7 cases with sensitive antibiotic treatment),8 of which underwent combined surgery,including percutaneous endoscopic lesion removal,catheter irrigation and drainage in 4 cases,posterior lesion removal in 2 cases,and posterior lesion removal combined with internal fixation in 2 cases.Results The patients were followed up for 14-75 months(average,36.8 months).According to the modified MacNab criteria,5 cases were excellent,4 cases were good,and 2 cases were fair.Conclusions SSI after PELD is characterized by acute onset,recurrent severe lower back or lower limb pain,elevated inflammatory markers,and characteristic imaging features.Standardized antibiotic treatment combined with surgery can achieve good therapeutic effects.

Objective:To analyze the superficial retinal blood flow around the optic disc of optical coherence tomography angiography (OCTA) in non-arteritic anterior ischemic optic neuropathy (NA-AION) patients with affected eyes and contralateral healthy eyes, compared with healthy people.Methods:From May 2018 to may 2019, 30 patients with NA-AION in Xi′an No. 1 Hospital were selected. The changes of superficial retinal blood flow density and perfusion around the optic disc on OCTA of 30 patients with NA-AION, whose contralateral healthy eyes were compared. The pattern visual evoked potential (PVEP) of both eyes was also compared. 30 healthy people with no history of eye disease and history of eye surgery were selected as healthy control group, and differences between healthy control group and contralateral healthy eye group in NA-AION patients of the superficial retinal blood flow density and perfusion around the optic disc were compared.Results:The average values of serum homocysteine, apolipoprotein E and low density lipoprotein in 30 patients with NA-AION were higher than the normal reference range. Compared with the contralateral healthy eyes, the effected eyes of NA-AION patients had lower retinal blood flow density and perfusion in the center, inner layer and complete area of the optic disc, with significantly difference ( P<0.05); there was no significant difference in the latency and amplitude of PVEP-P100 between the two groups ( P>0.05). There was no significant difference in the density and perfusion of superficial retinal blood flow in the center, inner layer and complete area of the optic disc between the contralateral healthy eyes of NA-AION patients and healthy control ( P>0.05). Conclusions:OCTA is a safe, rapid and non-invasive test, and it can detect blood perfusion defects promptly, which can be used as the most commonly test method for patients with NA-AION in order to make auxiliary diagnosis and gain time for clinical treatment.

Objective To investigate the sleep quality and daytime sleepiness between naval afloat and ashore personnel.Methods Sleep quality and daytime sleepiness of 50 naval afloat personnel and 50 naval ashore personnel were evaluated by using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS).Results The incidence of sleeping disorder among the afloat or shipboard naval personnel accounted for 57.14％, which showed statistical significance as compared with 29.17％ of the ashore personnel (P ＜ 0.05).Statistical significance could be seen in sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorder as well as daytime dysfunction, when comparisons were made between the 2 groups (P＜0.05).The incidence of daytime sleepiness in the naval afloat personnel was 61.22％, which was of statistical significance, as compared with 27.08％ of the ashore personnel (P ＜ 0.05).Conclusions The sleep quality of the afloat naval personnel was poorer than that of the ashore personnel, while daytime sleepiness was severer.

Objective To investigate the sleep quality and daytime sleepiness between naval afloat and ashore personnel.Methods Sleep quality and daytime sleepiness of 50 naval afloat personnel and 50 naval ashore personnel were evaluated by using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS).Results The incidence of sleeping disorder among the afloat or shipboard naval personnel accounted for 57.14％, which showed statistical significance as compared with 29.17％ of the ashore personnel (P ＜ 0.05).Statistical significance could be seen in sleep quality, sleep latency, sleep time, sleep efficiency, sleep disorder as well as daytime dysfunction, when comparisons were made between the 2 groups (P＜0.05).The incidence of daytime sleepiness in the naval afloat personnel was 61.22％, which was of statistical significance, as compared with 27.08％ of the ashore personnel (P ＜ 0.05).Conclusions The sleep quality of the afloat naval personnel was poorer than that of the ashore personnel, while daytime sleepiness was severer.

Objective To observe the effects of electroacupuncture on the expressions of autophagy related protein Beclin-1 and apoptosis related protein p53 of hippocampus in rats;To explore the mechanism of electroacupuncture on Alzheimer's disease (AD).Methods The rats were randomly divided into the normal group, the sham-operation group, the model group, and the electroacupuncture treatment group. “Baihui” and “Yongquan” points were taken for electroacupuncture treatment and the treatment course was 7 days. The rats were treated once a day for 4 courses. Changes in morphology and number of Nissl positive cells were examined by Nissl staining in hippocampal CA1 regions. Expressions of Beclin-1 and p53 protein were determined by Western blot analysis.Results Number of Nissl positive cells in CA1 region of the model group was significantly less than that of normal group (P<0.01). After electroacupuncture treatment, number of pyramidal cells and expression of Nissl body significantly increased (P<0.05). Expression of Beclin-1 decreased, while expression of p53 increased in the hippocampus of the model group, compared with that in the normal group (P<0.05). However, electroacupuncture treatment could significantly upregulate the expression of Beclin-1 protein (P<0.01), but downregulate the level of p53 (P<0.05).Conclusion Electro-acupuncture treatment could fight against Aβ-induced neuronal apoptosis, and improve the morphological changes of AD’s hippocampus.