OBJECTIVES: The neurotoxicity of carbon monoxide (CO) to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Our previous study found that retinoic acid (RA) can suppress the neurotoxic effects of CO. This study further explores, in vivo and in vitro, the molecular mechanisms by which RA alleviates CO-induced central nervous system damage. METHODS: A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO, and a DEACMP animal model was established in adult Kunming mice. Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Annexin V/propidium iodide (PI) double staining. The transcriptional and protein expression of each gene was detected using real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Long noncoding RNA (lncRNA) SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes. In DEACMP mice, SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression. RESULTS: RA at 10 and 20 μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes, downregulation of SNHG15 and LINGO-1, and upregulation of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) (all P<0.05). Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity (all P<0.05). Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels (all P<0.05). Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP (all P<0.05). CONCLUSIONS RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes, thereby reducing central nervous system injury and exerting neuroprotective effects. LncRNA SNHG15 and LINGO-1 are key molecules mediating RA-induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway. These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.
Animals ; RNA, Long Noncoding/physiology* ; Brain-Derived Neurotrophic Factor/genetics* ; Carbon Monoxide Poisoning/complications* ; Mice ; Tretinoin/pharmacology* ; Nerve Tissue Proteins/metabolism* ; Membrane Proteins/metabolism* ; Apoptosis/drug effects* ; Hippocampus/cytology* ; Receptor, trkB/metabolism* ; Neurons/drug effects* ; Male ; Brain Diseases/etiology* ; Oligodendroglia/drug effects* ; Signal Transduction ; Cell Line

Neural loops are formed by interconnections between neurons through synaptic structures,which are the basic units of information transmission and processing in the brain and play an important role in the regulation of neural functions.After stroke,neural connections between the infarct and peri-infarct regions and the remote area are damaged,resulting in patients being at risk of neurological dysfunction or even disability.However,with advances in detection technology,an increasing number of studies are demonstrating that patients with stroke can undergo some functional recovery during the chronic phase,possibly via a mechanism related to the re-establishment of synaptic connections and neural circuits.Therefore,the development of specific technology to identify and manipulate neuronal activity patterns,as well as the use of high-resolution temporal and spatial imaging strategies to decipher these neurological processes,will allow us to understand the whole-brain network dynamics of stroke recovery and the mechanisms by which neural loop reestablishment occurs.Furthermore,we may be able to neurobiologically comprehend the closed-loop mechanisms that underlie the development of stroke pathology and their relationship to behavioral outcomes.Current technologies used for studying neural circuits include optogenetics,chemical genetics,in vivo calcium imaging,and functional magnetic resonance imaging.This article introduces the working principles of these four major technologies and focuses on summarizing the result of their respective application in resolving neural remodeling after stroke.We briefly analyze the application scenarios,advantages and disadvantages,and future development trends of each technique.This paper will help clinical and basic researchers to use these technologies to discover new therapeutic strategies and evaluate the effectiveness of rehabilitation strategies.

Objective:To establish a microwave digestion and inductively coupled plasma mass spectrometry(ICP-MS)for determination on calcium content of Xiao'er Magan granules and discuss the effect of decocting gypsum into medicine on calcium content.Methods:ICP-MS was adopted to determine the calcium content in the preparation,and the difference of calcium content in the small preparation and Xiao'er Magan granules prepared by different pul-verization degree gypsum and different alcohol precipitation processes were compared.Results:The consistency of calcium content between different enterprises and batches of the same enterprise was poor.The results showed that the larger the particles,the lower the calcium transfer rate.The smaller the particles,the higher the calcium trans-fer rate.Conclusion:The transfer rate of gypsum decocted calcium is related to its degree of comminution to ensure consistency of preparation quality.It is suggested to unify the comminution degree of gypsum.The method can pro-vide guidance for the optimization on preparation technology of Xiao'er Magan granules.

Objective To analyse the quality of Xiao'er Magan granules by the combination of chemometrics and difference analysis of component content.Methods The ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry(UPLC-Q-TOF/MS)method was used to study the characteristic spectrum of basic components.The partial least squares discriminant analysis was used to quantify and screen the markers of quality difference,the methods of muti-component quantification for differential components and fingerprint were established,and the principal component analysis was used to calculate the comprehensive scores of principal components.Results The 12 common peaks were identified by the characteristic spectrum,which were attributed to 6 medicinal herbs,namely Rhizome,Mulberry bark,Bitter almond,Licorice,Perilla seed and Scutellaria.Taking the variable importance projection value＞1 as the criterion,4 characteristic components of quality differences(mulberry A,amygdalin,rosmarinic acid and baicalin)were screened out.The fingerprints similarity of 45 batches of samples were 0.867-0.997.14 components were calibrated,and 8 components were identified,which were mulberroside A,L-amygdalin,amygdalin,rosmarinic acid,baicalin,oroxindin,baicalein and wogonin.The scores of principal component 1 of each enterprise were as follows:G＞H＞A＞C＞E＞D＞F＞I＞B.The scores of principal component 2 were as follows:F＞G＞H＞B＞E＞D＞C＞A＞I.The ranking of the comprehensive scores was as follows:G＞H＞C＞A＞E＞F＞D＞I＞B.Conclusion The preparation quality of enterprise G and H is the best.The established fingerprint and quantitative method of quality differential components are accurate and reliable,which can provide reference for the quality analysis of Xiaoer Magan granules.

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

Objective:Delayed encephalopathy after acute carbon monoxide poisoning(DEACMP)is the most severe complication of carbon monoxide poisoning,which seriously endangers patients'quality of life.This study aims to investigate the efficacy of hyperbaric oxygen(HBO2)on improving dementia symptoms in patients with DEACMP. Methods:A retrospective analysis was performed on DEACMP patients,who visited Xiangya Hospital,Central South University from June 2014 to June 2020.Among them,patients who received conventional drug treatment combined with HBO2 treatment were included in an HBO2 group,while those who only received conventional drug treatment were included in a control group.HBO2 was administered once daily.Patients in the HBO2 group received 6 courses of treatment,with each course consisting of 10 sessions.The Hasegawa Dementia Scale(HDS)was used to diagnose dementia,and the Clinical Dementia Rating(CDR)was used to grade the severity of dementia for DEACMP.The Alzheimer's Disease Assessment Scale-Cognitive Section(ADAS-Cog),the Functional Activities Questionnaire(FAQ),the Neuropsychiatric Inventory(NPI),and the Clinician's Interview-Based Impression of Change-Plus Caregiver Input(CIBIC-Plus)were performed to assess cognitive function,ability to perform activities of daily living(ADL),behavioral and psychological symptoms,and overall function.The study further analyzed the results of objective examinations related to patients'dementia symptoms,including magnetic resonance imaging detection of white matter lesions and abnormal electroencephalogram(EEG).The changes of the above indicators before and after treatment,as well as the differences between the 2 groups after treatment were compared. Results:There was no significant difference in the HDS score and CDR grading between the 2 groups before treatment(both P＞0.05).After treatment,the score of ADAS-Cog,FAQ,NPI,and CIBIC Plus grading of the 2 groups were significantly improved,and the improvement of the above indicators in the HBO2 group was greater than that in the control group(all P＜0.05).The effective rate of the HBO2 group in treating DEACMP was significantly higher than that of the control group(89.47% vs 65.87%,P＜0.05).The objective examination results(white matter lesions and abnormal EEG)showed that the recovery of patients in the HBO2 group was better than that in the control group. Conclusion:Hyperbaric oxygen can significantly relieve the symptoms of dementia in patients with DEACMP.

Objective To analyze the impact of health education on osteoporosis after fracture patients with osteoporosis awareness, self-efficacy and fracture efficacy. Methods All 142 osteoporotic fracture patients were randomly divided into observation group and control group 71 cases, the implementation of comprehensive health education observation group were compared osteoporosis knowledge questionnaire (OKT), osteoporosis self-efficacy scale (OSES), lumbar spine bone mineral density and fractures situation. Results After 3 and 6 months in the observation group were signifi-cantly higher OKT score(P<0.05), exercise performance after 3 and 6 months in the observation group OSES of calci-um and performance scores were significantly higher(P<0.05),after 3 and 6 months in the observation group were sig-nificantly higher lumbar spine BMD(P<0.05), after three months in the observation group fractures was significantly better than the control group(P<0.05). Conclusion Osteoporosis is adversely affected by the patient fractures and osteo-porosis-related health education helps to enhance patient awareness of osteoporosis and self-efficacy, improved bone density and fractures.