Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism* ; Humans ; Central Nervous System/metabolism* ; Animals

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Air Pollution/analysis* ; Environmental Exposure/analysis* ; China/epidemiology* ; Air Pollutants/analysis* ; Particulate Matter/analysis* ; Environmental Monitoring

Objective: To preliminarily explore the mechanism of tensile stress regulating endochondral osteogenesis of condyle by analyzing the expression profiles of significantly different microRNAs (miRNAs) in exosomes of rat mandibular condylar chondrocytes (MCC) under quiescent and cyclic tensile strain (CTS) conditions. Methods: Rat condylar chondrocytes were cultured under static and CTS conditions respectively (10 SD rats, male, 2 weeks old), and exosomes were extracted. The two groups of exosomes were named as control group and CTS group respectively. The differential expression miRNAs were screened by high-throughput sequencing. Bioinformatics analysis and prediction of target genes related to osteogenesis were performed by TargetScan and miRanda website. Results: The exosomes of rat condylar chondrocytes cultured under tensile stress showed a "double concave disc" monolayer membrane structure, the expression of CD9 and CD81 were positive, and the particle size distribution accorded with the characteristics of exosomes, which was consistent with that of static cultured rat condylar chondrocytes. A total of 85 miRNAs with significantly different expression were detected by high-throughput sequencing (P<0.05). The main biological processes and molecular functions of differential miRNAs were biological processes and protein binding, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) database pathway enrichment analysis showed that there was significant enrichment in mammalian target of rapamycin (mTOR) signal pathway. The candidate target genes of miR-199a-5p include bone morphogenetic protein 3 (BMP3), endothelin converting enzyme 1, and miR-186-5p may target Smad8 and BMP3 to exert osteogenesis-related functions. Conclusions: Compared with static state, tensile stress stimulation can change the expression of miRNAs such as miR-199a-5p, miR-186-5p in the exocrine body of rat condylar chondrocytes, which can be considered as a mean to regulate the application potential of the exosomes.
Animals ; Male ; Rats ; Bone Morphogenetic Protein 3 ; Chondrocytes/metabolism* ; Mandibular Condyle ; MicroRNAs/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Stress, Mechanical

Objective:To evaluate the reliability of cardiac late iodine enhancement dual-energy CT (LIE-DECT) multiparameter post-processing technique for evaluating the presence, location, and extent of cardiac scars in patients with heart failure (HF), using cardiac MR (CMR) late gadolinium enhancement (LGE) as a reference standard.Methods:Thirty-nine HF patients who underwent cardiac LIE-DECT and LGE-CMR examinations in the Second Affiliated Hospital of Nantong University from November 2019 to November 2021 were prospectively collected, all enrolled HF patients underwent LIE-DECT post-processing to reconstruct monoenergetic plus (Mono+) map (40 keV), iodine map and Rho/Z map, to evaluate the enhancement degree, location and extent of left ventricular myocardial LIE on the left ventricular short-axis map, respectively, and compared with LGE-CMR. Cohen′s Kappa test was used to assess the intra-and inter-observer consistency of LIE by DECT multiparameter technique and the consistency of LIE presence and location by DECT multiparameter technique and by CMR. The diagnostic efficacy of DECT multiparameter technique in diagnosing myocardial scar was calculated.Results:Of the 39 patients included, 32 patients were detected by CMR with LGE in 147 segments, including 37 subendocardial patterns, 19 transmural patterns, 74 mid-wall patterns, and 17 epicardial patterns. The intra-observer consistency Kappa values of 40 keV Mono+map, iodine map and Rho/Z map were 0.878, 0.930 and 0.835 ( P all<0.001), respectively. The inter-observer consistency Kappa values were 0.838, 0.892 and 0.808 ( P all<0.001), respectively. The LIE of 40 keV Mono+map, iodine map and Rho/Z map were in good agreement with CMR, Kappa values were 0.903, 0.883 and 0.810 ( P all<0.001), respectively. For the per-patient analysis, the accuracies of 40 keV Mono+map, iodine map and Rho/Z map were 92.3% (36/39), 92.3% (36/39) and 82.1% (32/39), respectively. For the segment-based analysis, the accuracies of 40 keV Mono+map, iodine map and Rho/Z map accuracy were 96.1% (492/512), 95.3% (488/512) and 92.6% (474/512), respectively. In Bland-Altman analysis, the consistency bias between scar extent measured by 40 keV Mono+map, iodine map, Rho/Z map and that measured by LGE-CMR were -2.03%, -2.21%, -2.65%, and the 95% limit of agreement were -12.20%-8.14%, -12.69%-8.28% and -14.85%-9.58%, respectively. Conclusion:LIE-DECT multiparameter technique can detect myocardial scar in HF patients well, which is consistent with LGE-CMR.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Aim To study the effect of sodium pyruvate on apoptosis and autophagy of HT22 in mouse hippocampal neuronal cells under hypoxia conditions. Methods HT22 cells were incubated with different concentrations of sodium pyruvate to detect their cellular activity by MTS; iron staining was used to further observe the effect of sodium pyruvate on HT22 cells in mitochondrial metabolism; lysosomal staining was applied to detect the lysosomal changes of sodium pyruvate on HT22 cells; Western blot was used to detect the expression of Bcl-2, Bax and LC3-II/LC3- I proteins. Results To verify whether sodium pyruvate exerted neuroprotective effects on mouse hippocampal HT22 cells through affecting mitochondrial apoptosis and autophagy pathways, which were improved by administration of sodium pyruvate. Conclusions Sodium pyruvate administration under hypoxic conditions can reduce the neuroprotective effect of hypoxic injury by reducing apoptosis and activating autophagy in HT22 cells.

Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8+T cells in A A group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4+T cells and the CD4+/CD8+ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and0.001,respectively).Furthermore,the proportion of CD4+andCD8+activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8+naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and 0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4+and CD8+TA cells,memory Tregs and CD8+TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.

Glucagon-like peptide-1 (GLP-1) is expressed in retinal neurons, but its role in the retina is largely unknown. Here, we demonstrated that GLP-1 or the GLP-1 receptor (GLP-1R; a G protein-coupled receptor) agonist exendin-4 suppressed γ-aminobutyric acid receptor (GABAR)-mediated currents through GLP-1Rs in isolated rat retinal ganglion cells (GCs). Pre-incubation with the stimulatory G protein (G_s) inhibitor NF 449 abolished the exendin-4 effect. The exendin-4-induced suppression was mimicked by perfusion with 8-Br-cAMP (a cAMP analog), but was eliminated by the protein kinase A (PKA) inhibitor Rp-cAMP/KT-5720. The exendin-4 effect was accompanied by an increase in [Ca²⁺]_i of GCs through the IP₃-sensitive pathway and was blocked in Ca²⁺-free solution. Furthermore, when the activity of calmodulin (CaM) and CaM-dependent protein kinase II (CaMKII) was inhibited, the exendin-4 effect was eliminated. Consistent with this, exendin-4 suppressed GABAR-mediated light-evoked inhibitory postsynaptic currents in GCs in rat retinal slices. These results suggest that exendin-4-induced suppression may be mediated by a distinct G_s/cAMP-PKA/IP₃/Ca²⁺/CaM/CaMKII signaling pathway, following the activation of GLP-1Rs.

Objective : To investigate the effect of hypoxic preconditioning (HPC) on mitochondrial energy metabolism in mouse hippocampal HT22 cells and its possible mechanism. Methods : In this paper, mouse hippocampal nerve cells HT22 were divided into control group, hypoxia group, HPC group, and the levels of adenosine triphosphate (ATP) and reactive oxygen species (ROS) in each group were measured for observing the effect of HPC on cell mitochondrial metabolism. Western blot was used to detect the expression of target of rapamycin ( mTOR), phosphorylated mTOR protein and autophagy substrate P62 protein; cellular immunofluorescence was used to detect phosphorylated mTOR, and LysoTrackerTM probe was used to detect lysosomes. Results : Compared with the control group, the ATP level was significantly decreased and the ROS level was increased in the hypoxia group. Exposed to HPC, the ATP level was increased and the ROS level was decreased. Compared with the control group, the expression of phosphorylated mTOR was down⁃regulated and the expression of autophagy substrate P62 was down⁃regulated in the HPC group. Conclusion HPC may affect the energy metabolism of HT22 cells through the mTOR/autophagy signaling pathway, thereby exerting a protective effect on the HT22 cells.