Objective:To investigate the application effect of research-assisted teaching mode in histology teaching by taking the construction of rat spinal cord injury model as an example.Methods:A convenient sampling method was used to select 52 freshmen majoring in clinical medicine of grade 2020 in our school as the research subjects.They were randomly divided into the conventional teaching group and the research-assisted teaching group,with 26 students in each group.The conventional teaching group received traditional classroom teaching combined with experimental teaching.On this basis,research elements were added to the experimental teaching in the research-assisted teaching group to provide more in-depth research methods and experimental design,so as to cultivate students'research abilities.The theoretical assessment and practical skills assessment of histology course were compared between the two groups.A subjective evaluation questionnaire on experimental animal models teaching was used to evaluate the advantages of teaching programs in three dimensions:psychological quality training,technical skill enhancement,and theoretical knowledge expansion.The research abilities of the two groups were compared.Pearson correlation analysis was used to analyze the correlation between research ability scores and comprehensive scores.Results:The usual score and comprehensive score in the research-assisted teaching group were significantly higher than those in the conventional teaching group(P＜0.05).The scores of adaptability to challenging tasks,determination and perseverance in problem-solving,communication skills in teamwork,literature reading,integration of practical experience with theoretical knowledge,practical application value of the course,and innovation of teaching resources in the research-assisted teaching group were higher than those in the conventional teaching group(P＜0.05).The scores in experimental design ability,background knowledge in literature review,communication and reporting skills,awareness of evidence-based medicine,and overall research ability in the research-assisted teaching group were higher than those in the conventional teaching group(P＜0.05).The total score of students'research abilities was positively correlated with comprehensive scores(r=0.716,P＜0.01).Conclusions:The application of research-assisted teaching significantly improved students'research abilities in histology teaching.The enhancement of research abilities can promote the mastery of theoretical knowledge and the improvement of experimental skills.

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.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Dementia in traditional Chinese medicine （TCM） mainly presents amnesia and dullness. Alzheimer's disease and vascular dementia belong to the category of dementia in TCM. These progressive neurological diseases have a complex etiology and a long course， and the drugs that can reverse the disease course remain to be developed. Therefore， early intervention plays a vital role in delaying the disease progression. Apathy refers to a lack of motivation that leads to the attenuation or disappearance of goal-directed behaviors， cognitive functions， and emotional responses. Clinical studies have suggested that apathy exists in the early stage of a variety of neurodegenerative diseases， being one of the key symptoms to the early diagnosis of dementia. The severity of apathy is related to the severity of dementia. Therefore， early diagnosis and treatment of apathy are of great significance to the prevention and treatment of dementia. The preclinical research on apathy in dementia is still in its infancy， and the systematic evaluation method has not been prescribed. The clinical diagnosis and treatment are also in the exploratory stage， and the complex pathophysiological mechanisms of apathy and dementia development have not been fully elucidated. This article reviews the research progress of apathy in dementia， the apathetic behaviors of dementia animal models， the behaviors of patients with apathy， and the treatment methods in recent years and summarizes the research status of apathy in dementia. This review aims to provide a theoretical basis for exploring the behavior of apathy in dementia and conducting preclinical research and evaluation of the pathogenesis and to lay a foundation for the treatment of apathy in dementia.

Traditional Chinese medicine （TCM） has a long history of application in China and has consistently played a vital role in treating diseases and saving lives. TCM prescriptions （compounds） constitute the primary form of clinical TCM treatment and significantly differ from western medicine （chemicals） due to the diverse composition and chemical constituents of TCM （compounds）. Nevertheless， the potential multi-component， multi-target， and multi-pathway action characteristics of TCM prescriptions also demonstrate their possible （complementary） therapeutic advantages when compared with single-component chemical drugs. Therefore， driven by the development of modern science and technology and the demands of the modernization and internationalization of TCM， modern theories regarding the complexity of TCM prescription effects have been continuously proposed： Different from the abstract language of traditional prescription theory， the modern TCM prescription theory is more inclined to illustrate the connotation of prescription compatibility concretely and vividly from an experimental and scientific perspective. In this paper， new theories on the complexity of TCM prescriptions proposed in recent years are summarized to provide research references and ideas for the greater role of TCM prescriptions and a better scientific understanding.

Eubhorbia neriifolia L. is a plant of Euphorbia family.Five known lignans were isolated from the aerial parts of E. neriifolia L. by silica gel for column chromatography and preparative high-performance liquid chromatography (HPLC).Their potential antitumor activities were evaluated in vitro.Compound 2 exhibited proliferation inhibition and cytotoxicity against esophageal squamous cancer cells, especially KYSE-410 and KYSE-450 cells.Further analyses showed that compound 2 could significantly induce apoptosis through the activation of caspase 3/9 and down-regulation of the Bcl-2/Bax protein ratio.These results suggested that compound 2 had a significant inhibitory effect on the esophageal squamous cancer cells, especially KYSE-410, which deserves further research as a potential antitumor agent.

Objective:To investigate the effect of lappaconitine (LA) on neuropathic pain (NPP) mediated by retrograde transport of purinergic P2X3 receptor (P2X3R) in dorsal root ganglion (DRG) neurons of rats with chronic constriction injury (CCI) of the sciatic nerve.Methods:Seventy-two male healthy SD rats were selected to construct the NPP model following CCI of the sciatic nerve by ligating the right sciatic nerve. according to the random number table method. The rats were divided into CCI group, CCI+LA group and normal control group according to the random number table method, with 24 rats in each group. In normal control group, the right sciatic nerve was exposed without ligation. In CCI+LA group, the rats were given 2 g/L LA (ie, 4 mg/kg intravenously for once a day for one day only) after the same treatment as CCI group. Other two groups were injected with the identical amount of normal saline in the same way. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were evaluated before injury and at 2, 6, 12 and 24 hours after injury to evaluate the symptoms of neuralgia caused by nerve injury. The proximal and distal nerve fragments were collected in the three groups at 2, 6, 12 and 24 hours after injury. Western blotting was applied to analyze the expression of P2X3R at 2, 6, 12 and 24 hours after injury and the expression of neurotrophic factor (NGF) and tyrosine kinase receptor A (TrkA) at 24 hours after injury to evaluate the effect of LA on P2X3R, NGF and TrkA.Results:There were insignificant differences in MWT and TWL among all groups before injury (all P>0.05). Compared with normal control group, MWT and TWL were significantly decreased in CCI group and CCI+LA group at 2, 6, 12 and 24 hours after injury (all P<0.05 or 0.01). There were insignificant differences in MWT and TWL between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), while MWT and TWL were significantly higher in CCI+LA group than those in CCI group at 12 and 24 hours after injury (all P<0.05 or 0.01). In the proximal sciatic nerve segment, Western blotting showed similar levels of P2X3R among all groups at 2, 6, 12 and 24 hours after injury (all P>0.05). In the distal sciatic nerve segment, Western blotting showed higher expression of P2X3R in CCI group than that in normal control group at 2, 6, 12, 24 hours after injury (all P<0.01), higher expression of P2X3R in CCI+LA group than that in normal control group at 2, 6 and 12 hours after injury (all P<0.05), similar expression of P2X3R expression between CCI+LA group and normal control group at 24 hours after injury ( P>0.05), similar expression of P2X3R between CCI group and CCI+LA group at 2 and 6 hours after injury (all P>0.05), and lower expression of P2X3R in CCI+LA group than that in CCI group at 12 and 24 hours after injury ( P<0.05 or 0.01). In the proximal and distal nerve fragments, the expression of NGF was lower in normal control group than that in CCI group and CCI+LA group ( P<0.05 or 0.01), but was similar between CCI group and CCI+LA group at 24 hours after injury ( P>0.05). In the proximal and distal nerve fragments, there were insignificant differences in the expression of TrkA among all groups at 24 hours after injury (all P>0.05). Conclusion:Early LA treatment after injury can alleviate mechanical and thermal hyperalgesia in NPP rats, which may be related to the reduction of P2X3R retrograde transport in DRG neuron axonal.

COVID-19 represents the most serious public health event in the past few decades of the 21^st century. The development of vaccines, neutralizing antibodies, and small molecule chemical agents have effectively prevented the rapid spread of COVID-19. However, the continued emergence of SARS-CoV-2 variants have weakened the efficiency of these vaccines and antibodies, which brought new challenges for searching novel anti-SARS-CoV-2 drugs and methods. In the process of SARS-CoV-2 infection, the virus firstly attaches to heparan sulphate on the cell surface of respiratory tract, then specifically binds to hACE2. The S protein of SARS-CoV-2 is a highly glycosylated protein, and glycosylation is also important for the binding of hACE2 to S protein. Furthermore, the S protein is recognized by a series of lectin receptors in host cells. These finding implies that glycosylation plays important roles in the invasion and infection of SARS-CoV-2. Based on the glycosylation pattern and glycan recognition mechanisms of SARS-CoV-2, it is possible to develop glycan inhibitors against COVID-19. Recent studies have shown that sulfated polysaccharides originated from marine sources, heparin and some other glycans display anti-SARS-CoV-2 activity. This review summarized the function of glycosylation of SARS-CoV-2, discoveries of glycan inhibitors and the underpinning molecular mechanisms, which will provide guidelines to develop glycan-based new drugs against SARS-CoV-2.
Antibodies, Neutralizing ; Glycosylation ; Heparin ; Heparitin Sulfate ; Humans ; Polysaccharides/chemistry* ; Receptors, Mitogen/metabolism* ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/metabolism* ; COVID-19 Drug Treatment

Objective:To establish O-(2-[ 18F]fluoroethyl)- L-tyrosine( 18F-FET) PET radiomics features-based model and investigate its predictive efficacy for isocitrate dehydrogenase type 1 (IDH1) genotyping in untreated gliomas. Methods:From November 2017 to February 2019, 58 pathologically confirmed glioma patients (36 males, 22 females; age (41.8±15.1) years) with preoperative 18F-FET PET/CT imaging in Huashan Hospital, Fudan University were retrospectively enrolled. PyRadiomics software package was used to extract 105 radiomics features. Least absolute shrinkage and selection operator (LASSO) algorithm with 5-fold cross-validation was used to build the logistic regression model. And radiomic scores (RS) of each lesion were calculated according to their weighted coefficients. The area under the receiver operating characteristic (ROC) curve was used for evaluating the predictive efficacy for IDH1 prediction. The predictive efficacies of radiomics model and traditional semi-quantitative parameters including tumor-to-background ratio (TBR; maximum TBR (TBR max), mean TBR (TBR mean), peak TBR (TBR peak)), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU), were compared by Delong test. Results:Seven radiomics features including maximum 2-dimensional (2D) diameter slice, first order_maximum, first order_range, gray level co-occurrence matrix (GLCM)_joint energy, GLCM_inverse variance, gray level dependence matrix (GLDM)_dependence entropy and GLDM_large dependence low gray level emphasis were selected for the LASSO regression model building and RS calculation. ROC analysis results showed that the predictive accuracy of RS for IDH1 genotyping (mutation, n=20; wild-type, n=38) was 81.0%(47/58), with sensitivity of 65.0%(13/20), specificity of 89.5%(34/38), and area under curve (AUC) of 0.842, respectively. The traditional 18F-FET semi-quantitative parameter TLU ranked the second regarding the diagnostic performance, with accuracy of 60.3%(35/58), sensitivity of 85.0%(17/20), specificity of 47.4%(18/38), and AUC of 0.661( z=3.426, P<0.01). Conclusion:Radiomics analysis based on 18F-FET PET images can improve the predictive efficacy for IDH1 genotyping in untreated adult glioma patients.

Objective:To establish a nomogram prediction model for the prognosis of patients with septic cardiomyopathy (SCM) based on afterload-corrected cardiac performance (ACP), in order to identify septic patients with poor outcomes and treatment.Methods:The data of patients admitted to the department of critical medicine of the Second Affiliated Hospital of Guangzhou Medical University from June 2016 to June 2019 were analyzed. All patients were monitored by pulse indication continuous cardiac output (PiCCO) monitor more than 24 hours and diagnosed as SCM with ACP less than 80%. The predictors of 30-day death risk of SCM patients were screened by univariate Cox regression analysis. Multivariate Cox regression analysis was used to establish the prediction model for 30-day death risk of SCM patients, which was displayed by the nomogram. Finally, the discrimination and calibration of the model were analyzed by receiver operator characteristic curve (ROC curve) and consistency index (C-index).Results:A total of 102 patients with SCM were included and the 30-day mortality was 60.8% (62 cases). Among 102 patients with SCM, 57 patients (55.9%) had mild impairment of cardiac function (60%≤ACP < 80%), and the 30-day mortality was 43.9% (25/57); 39 patients (38.2%) had moderate impairment of cardiac function (40%≤ACP < 60%), and the 30-day mortality was 79.5% (31/39); 6 patients (5.9%) had severe impairment of cardiac function (ACP < 40%), and the 30-day mortality was 100% (6/6). There was significantly difference in mortality among the three groups (χ 2 = 24.156, P < 0.001). The potential risk factors for 30-day death of SCM patients screened by univariate Cox regression analysis were included in multivariate Cox regression analysis. The results showed that the independent risk factors for 30-day death of SCM patients were acute physiology and chronic health evaluation Ⅱ [APACHEⅡ, risk ratio ( HR) = 1.031, 95% confidence interval (95% CI) was 1.002-1.061, P = 0.039], vasoactive inotropic score (VIS, HR = 1.003, 95% CI was 1.001-1.005, P = 0.012), continuous renal replacement therapy (CRRT; HR = 2.106, 95% CI was 1.089-4.072, P = 0.027), and ACP ( HR = 0.952, 95% CI was 0.928-0.977, P < 0.001). The nomogram model was established based on the above independent risk factors and age, and the area under the curve (AUC) was 0.865 (95% CI was 0.795-0.935), P < 0.001; C-index was 0.797 (95% CI was 0.747-0.847), P > 0.05. Conclusions:The nomogram model based on age, APACHEⅡ score, VIS score, CRRT and ACP has a certain clinical reference significance for the prediction of 30-day mortality of SCM patients. The discrimination and calibration are good, however, further verification is needed.