Circadian rhythm is an essential biological process that regulates the sleep-wake cycle，hormone secretion，and metabolism，and the stability of circadian rhythm is crucial for maintaining normal cognitive function. Melatonin （MT），a key hormone secreted by the pineal gland，is involved in the regulation of circadian rhythm and thus has a significant impact on cognitive function. This article systematically reviews the multiple mechanisms by which MT regulates cognitive function through circadian rhythm，including improving sleep quality，promoting the clearance of metabolic waste by the glymphatic system，exerting antioxidant and anti-inflammatory effects，and regulating neuronal activity and the improvement of synaptic plasticity. In addition，this article also discusses the association between circadian rhythm disorders and neurodegenerative diseases. Future studies are needed in the future to further clarify the neuroprotective mechanisms of MT，in order to provide new insights for the prevention and treatment of cognitive impairment.
Melatonin

OBJECTIVES: To investigate the subcellular localization and biological functions of transmembrane protein 240 (TMEM240). METHODS: NCBI BLAST and TMHMM bioinformatics software were used for protein sequence analysis and prediction of transmembrane domain of TMEM240. Brain tissues from male C57BL/6 mice (18-20 days old) were examined for distribution of TMEM240 using in situ hybridization, and qPCR and Western blotting were used to detect TMEM240 expression in different mouse tissues and in cortical neurons at different time points (n=3). In the in vitro experiment, HepG2 and Neuro-2a cells were transfected with plasmids for overexpression of TMEM240, and subcellular localization of TMEM240 was analyzed using cell imaging. In primary cultures of cortical neurons isolated from C57BL/6 mice, TMEM240 expression and its biological functions were investigated using qPCR, Western blotting, and immunofluorescence staining. RESULTS: Human and mouse TMEM240 proteins share a 97.69% similarity in the protein sequences, and both are transmembrane proteins with two transmembrane domains. TMEM240 mRNA and protein were highly expressed in mouse brain tissues and cortical neurons. In isolated mouse cortical neurons, TMEM240 expression reached the peak level after primary culture for 9 days and distributed in scattered spots within the cells. In HepG2 cells, TMEM240 was characterized as intracellular membrane structures and showed 80% colocalization with peroxisomes. In Neuro-2a cells, TMEM240 overexpression caused significant enhancement of the expressions of Rho GDP dissociation inhibitor β (ARHGDIB) at both the mRNA and protein levels. CONCLUSIONS TMEM240 is a novel intracellular subcellular structure specifically expressed in neurons with significant potential for targeted cellular function regulation.
Animals ; Humans ; Mice ; Peroxisomes/metabolism* ; Membrane Proteins/genetics* ; Mice, Inbred C57BL ; Neurons/metabolism* ; Male ; rho-Specific Guanine Nucleotide Dissociation Inhibitors ; Hep G2 Cells ; Brain/metabolism*

Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities. Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed. Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system. Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

Objective With the aging of the population and the deepening of research on neuropsychiatric disor-ders,cognitive impairment has become a hot focus in the field of neuroscience in recent years.The successful establish-ment and evaluation of appropriate animal models are crucial for conducting experimental research.At present,rodent models have been widely used in basic and medicine research due to their high genetic homology with humans,fast repro-duction,and easy accessibility.This article provides a systematical summary and preliminary discussions about the evalu-ation methods for rodent cognitive impairment models,aiming to provide a reference for the selection of model evaluation methods.

Intracerebral hemorrhage（ICH）is a cerebrovascular disease with high morbidity，mortality，and disability. As hematoma is the key driver of brain injury after ICH，early removal of hematoma components is crucial for preventing and reducing early brain damage following ICH. Existing treatments for ICH are limited in effectiveness，and recent preclinical trials have revealed some exciting findings，including an interesting new target—nuclear factor erythroid 2-related factor 2（Nrf2）. Nrf2 is a transcription factor that may play a neuroprotective role by activating cellular repair mechanisms through different pathways，and its therapeutic potential has attracted great interest in research. This article summarizes the role of Nrf2 and its agonists in post-ICH hematoma clearance and neuroprotection and the underlying mechanism.

Objective:To study the clinical, imaging and genetic characteristics of two Chinese families with oculopharyngeal muscular dystrophy (OPMD).Methods:The clinical data of the two families found in our hospital in August 2016 and May 2018 were analyzed. All the members were investigated in detail, and the clinical and imaging data of the probands were analyzed. Blood samples were collected from 22 members of the two families and PABPN1 gene analysis was performed. Results:There were 4 patients in family 1 with four generations and 4 patients in family 2 with three generations. The two probands presented ptosis, dysphagia at the age of 50 and 55. The proband of family 1 also showed diplopia, amyotrophy, weakness of proximal limbs, neurogenic changes in electromyogram (EMG), muscle fibers with rimmed vacuoles in muscle pathology, aspiration pneumonia in chest CT, and brainstem symmetric white matter lesions in cranial MR imaging. The proband of family 2 also showed eye muscle paralysis and lateral limb weakness, myogenic changes in EMG, bilateral parietal and right frontal lacunar infarctions in cranial MR imaging. Analysis of PABPN1 gene showed that the repeated mutation of PABPN1 trinucleotide (GCN) in 2 families was amplified from normal (GCG) 6(GCA) 3(GCG) to (GCG) 6(GCA) 3(GCG) 2(GCA) 3(GCG). Conclusion:OPMD has clinical heterogenicity; symmetrical white matter lesions in the brainstem might be found in cranial MR imaging; Chinese patients with OPMD have PABPN1 gene mutation, specificly manifested as (GCG) 6(GCA) 3(GCG) 2(GCA) 3(GCG) repeat mutations.

Objective To analyze the clinical management of women with atypital squamous cells(ASC).Methods During Sep 2003 to Sep 2008,a totle of 956 women in our department were diagnosed with ASC by cytological test,they were further biopsied under the colposcope.The result of TCT,colposcopic test,biopsy and the highrisk factor were recorded and analysed;the based the biopsy were analyzed by the X~2-test;the high-risk factors and the odds Ratio(OR) were counted by SPSS10.0.Results Among the women with ASC,the rate of cervical intraepithelial neoplasia(CIN) diagnosed by the biopsy under the colposcope was 50.7% ,the rate of the high-grade lesion over CINII Was 13.3% ;if the colposcopic test were low-grade lesion,the rate of the cases which biopsys were the highgrade lesion over CINII,was 8.3% ;the high-risk factors which caused the cervical high-grade lesion were the number of sex-partners over 3,the age less than 20 yearold when the sex were made,the cervical erosion,the result of TCT with ASC-H.Conclusion Among the women with ASC,the biopsy shows multiformity;the rate of CIN and the highgrade lesion is also high;if TCT is ASC,the colposcopie test is advised;if the woman who has the high-risk factors,biopsy is advised.

Objective To investigate whether iron mass induces HO-1 overexpression and explore the role of HO-1 in rat intracerebral hemorrhage(ICH). Methods In this study,144 hydrated chloride aldehyde-anesthetized Sprague- Dawley rats were used,autologous blood were injected into the right caudate nucleus to establish the ICH model.Saline injection and health were served as controls.Deferoxamine(DFO)with an intraperitoneal injection served as intervention group.Enhanced Perl's reaction was used for iron staining and brain iron deposits were determined.Brain HO-1 level were examined by immunohistochemical analysis and reverse transcription polymerase chain reaction(RT-PCR). Results There was a 21-fold increase in iron deposits around the hematoma 7 days after the infusion of 100 μl of autologous blood.Markedly increased levels of perihematomal HO-1 immunoreactivity and HO-1 mRNA in all ICH rats were detected at 3-14 days.The addition of DFO significantly reduced iron deposits in the ipsilateral basal ganglia at 7-14 days after ICH.DFO also inhibited HO-1 overexpression at day 7,14.Correlations test showed that there were positive correlations of iron sediments with HO-1mRNA(r=0.647)and HO-1 immunopositive cells(r=0.209). Conclusions ICH causes iron accumulation in the brain.Iron overloading may induce HO-1 upregulation after ICH.Ratherly,the HO-1 moderate increasing possibly fits with the events,whereas HO-1 overexpression may result in its dysfunction.It may be prudent to intervene ICH with HO-1 inhibitor.

The paper set up a set of quality monitor measures from training important tache, beginning thesis, imposing advantage resource to strengthening practice ability to build a scientific quality monitor system for postgraduate training and ensure steadily improvement of the postgraduate training quality.

This article reviewed the experience of the reform of the graduate student course system in Capital Medical University(CCMU),which included three aspects:the reform of course setting,the reform of course management rule and the reform of course management means.Then,it gives some new opinions about the reform of course system in the future.