Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Objective To investigate the effect of mitochondrial unfolded protein response(UPRmt)on lipid metabolism in human kidney 2(HK-2)cells.Methods Lipid accumulation was induced by palmitic acid(PA)in HK-2 cells.The cells were pretreated with siRNA or CDDO respectively.The intracellular lipid accumulation was observed by oil red staining;mitochondrial membrane potential(MMP)was measured by JC-1.The contents of reactive oxygen species(ROS)in mitochondria were measured by Mito-SOX,and the expressions of HSP60,LONP1,CLPP,ACOX1,PPARα,PGC1α and CPT1α were detected by Western blotting.Results PA induced lipid aggregation,MMP decrease,ROS generation in mitochondria and the decreased expression of UPRmt proteins(e.g.,HSP60 and LONP1)in HK-2 cells.Pretreatment of HK-2 cells with siRNA could aggravate lipid aggregation,MMP decrease and ROS generation induced by PA,and further decrease the expression of HSP 60and LONP1.Pretreatment of HK-2 cells with CDDO alleviated lipid aggregation,MMP decrease,ROS generation and decreased HSP60 and LONP1 expressions induced by PA.Conclusion Lipid aggregation in HK-2 cells induced by PA may be related to mitochondrial dysfunction and UPRmt has a protective effect on HK-2 cells in the process.

Objective·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein(COMP)in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment.Methods·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS(GEO)database,and differentially expressed genes(DEGs)were obtained via GEO2R.The molecular functions and signaling pathways related to differential genes were summarized.The most correlated key genes(hub genes)were acquired by Weighted Gene Co-Expression Network Analysis(WGCNA)and the protein-protein interaction network(PPI)of DEGs was constructed with STRING database.The enrichment analysis was performed again.Conditionally immortalized mouse podocyte cells were cultured in vitro.After being fully differentiated,they were stimulated with high glucose,and the expressions of COMP,mammalian target of rapamycin(mTOR),microtubule-associated protein 1 light chain3(LC3)and other proteins in podocytes were detected by Western blotting.The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP,and the stable cell strains were screened by puromycin.The expression of COMP,mTOR,and LC3 of stable strains were detected by Western blotting,in order to observe the effect of COMP on autophagy.Results·A total of 362 DEGs were filtered for subsequent analysis.Among these DEGs,284 genes were up-regulated and 78 genes were down-regulated.The results of Gene Onotology(GO)term analysis showed that DEGs in diabetic nephropathy(DN)were mainly enriched in cell surface receptor signaling pathway,receptor binding,etc.The main enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways included phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway,extracellular matrix(ECM)-receptor interaction,etc.Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes,and the hub genes with significantly increased or decreased expression were sifted.The hub genes were annotated with KEGG again,and it was found that most of the hub genes were enriched in"ECM-receptor interaction"and"PI3K/AKT signaling pathway".The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway,and COMP was absolutely overexpressed(logFC>2)in the 64 hub genes,suggesting that it may affect autophagy through this pathway.Western blotting showed that compared with the mannitol control group and the low glucose group,the expression of COMP in podocytes was significantly increased under high glucose stimulation.Compared with the control group,the expression of LC3-Ⅱ in the high glucose group was significantly decreased,indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment.Compared with the negative control,the expression of LC3-Ⅱ in renal podocytes of mice with knockdown of COMP was significantly increased,and the mTOR decreased with the decrease of the expression of COMP,indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes.Conclusion·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway.Autophagy in mouse renal podocytes is inhibited under high glucose conditions,and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition.Inhibiting COMP helps to restore autophagy in mouse renal podocytes.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective To observe the impairment effect of retinol binding protein 4(RBP4) on neurocognitive function in diabetic nephropathy(DN) patients with silent cerebral infarction(SCI) and to explore its mechanism.Methods Sixty patients with newly diagnosed DN and 30 healthy volunteers were selected as the study subjects and the DN cases were divided into the complicating SCI group(SCI,n=30) and non-complicating SCI group(NSCI,n=30) according to the imaging results.The degrees of neurological function deficit and Montreal cognitive assessment(MoCA) were evaluated.Serum RBP4 level was determined by ELISA and expressions of Lp-PLA2 and C-X-C chemokine receptor type 4(CXCR4) were determined by Western blot.Results Compared with the NSCI group,the neurocognitive function in the SCI group was subsided,the expression levels of RBP4,Lp-PLA2 and CXCR4 were increased(P＜0.05).The RBP4 level was positively correlated with the neurocognitive function impairment in SCI patients,moreover,there existed a regression correlation between them.Conclusion Serum RBP4 may serve as the predictive factor of DN complicating SCI and is positively correlated with neurocognitive dysfunction.Lp-PLA2/CXCR4 pathway activation may be one of its pathogenesis.

A new type of fluorescent gold nanoclusters (MU-Au NCs) was prepared by hydrothermal synthesis method using ammonium benzoate murexide (MU) as reducing agent and protecting agent.The synthesis method was simple and rapid.Based on the fluorescence quenching ability of spermine, a turn off type fluorescence analysis method was established for rapid and ultra sensitive detection of spermine.The linear range for detection of spermine was 0.003-300 μmol/L and the detection limit was 1 nmol/L (S/N=3).The established analytical method of spermine provided theoretical basis and reference for construction of spermine biosensor and actual sample detection.

Objective To investigate the effects of Lotensin on inflammatory factors, vascular endothelial function and heart function in patients with acute myocardial infarction. Methods 100 cases with acute myocardial infarction from March 2015 to January 2016 in the fifth central hospital of Tianjin were selected as the research object, which were randomly divided into the control group and the observation group. The control group were given routine treatment, at this basis, the observation group were given Lotensin. After treatment, the cardiac function, the levels of inflammatory factors, the blood vessel endothelial function, the serum NO and endothelin 1 and the therapeutic effect in the two groups were compared. Results LVESV, LVEDV (156.28±3.29、213.45±6.12) mL in the observation group were better than (162.98±4.16、202.83±7.16) mL in the control group (P<0.05). LVEF was (48.72± 2.13)% in the observation, which was higher than (40.62±3.29)% in the control group(P<0.05). Hs-CRP, IL-6 were (2.66±0.68) mg/L、(4.90±0.92) ng /L in the observation group , which were less than (6.35±1.50) mg/L、(9.38±2.01) ng/L in the control group (P<0.05). FMD(10.37±0.62)% in the observation group was bet er than (6.16±0.92)% in the control group (P<0.05)、 NO, ET-1 level (71.52±13.21) μmol/L、(56.27±7.10) ng/L in the observation group were bet er than (60.63 ±10.57) μmol/L、(69.72±9.50) ng/L in the control group (P<0.05). The total effective rate in the observation group was 94.00% (47/50), which was better than 62.00% (31/50) in the control group (P<0.05). Conclusion The effect is significant which Lotensin is used in the treatment of acute cerebral infarction, which can reduce inflammatory factors, improve endothelial function and cardiovascular function.

Objective To observe the effect of ATF6 on the apoptosis and proliferation of podocytes induced by palmitic acid (PA). Methods Podocytes were stimulated with different doses of PA for 24 h. The expression of cleaved-caspase3 was detected by Western blotting. The podocyte apoptosis was analyzed by flow cytometry (FCM), and the expression of ATF6 was tested by Western blotting and immunofluorescence staining. After the transfection of adenovirus siRNA against ATF6, the proliferation, the cell cycle and apoptosis of potocytes stimulated with PA were tested by MTT or FCM. Results The levels of cleaved - caspase3 and ATF6 of podocytes stimulated with PA were significantly increased by a dose-dependent manner compared with the control group (P<0.05). The apoptosis of podocytes stimulated with PA was increased (P<0.05). Compared with the podocytes stimulated with PA, the apoptosis of podocytes transfected by adenovirus siRNA against ATF6 with PA stimulation was significantly reduced (P<0.05). The proliferation of podocytes transfected by adenovirus siRNA against ATF6 and stimulated with PA, however, was obviously increased compared with the podocytes stimulated with PA (P<0.05). Conclusion ATF6 mediated the apoptosis of podocytes induced by palmitate acid.

OBJECTIVETo analyze potential mutation of chloride channel 7(CLCN7) gene in a patient with autosomal dominant osteopetrosis II (ADO II).

METHODSGenomic DNA was extracted from peripheral blood samples from the patient and 100 healthy subjects. The DNA was used as template of polymerase chain reaction (PCR) to amplify the exons of CLCN7. Then the PCR products were sequenced to detect the mutation.

RESULTSA novel heterozygous deletional mutation (c.2460delA) was detected in exon 25 of the CLCN7 gene in the patient, which has resulted in substitution of Gly residue for Arg at position 784 of the CLCN7 protein and caused frame shift of the following 28 amino acids (Arg784GlyfsX29). The same mutation was not found in the healthy subjects.

CONCLUSIONThe ADO II in the patient probably results from a Arg784GlyfsX29 mutation in the CLCN7 gene.

Base Sequence ; Chloride Channels ; genetics ; DNA Mutational Analysis ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Osteopetrosis ; diagnostic imaging ; genetics ; Radiography ; Young Adult