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.

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.

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

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.

Objective:To explore the effect of perioperative whole-course closed-loop temperature management system for prevention of hypothermia in elderly patients with femoral neck fracture.Methods:A retrospective case-control study was conducted to analyze the clinical data of 120 elderly patients with femoral neck fracture admitted to Chengdu First People's Hospital from January 2020 to December 2020. There were 48 males and 72 females, aged 60-79 years［（68.3±5.0）years］. All patients underwent total hip arthroplasty. Heat warming with the whole-course closed-loop temperature management system was applied in 40 patients（closed-loop group）, with the medical heating mattress in 40 patients（heat preservation group）, and with the quilt in 40 patients（control group）. The core body temperature of the three groups was recorded 8 minutes after wearing the temperature sensor（T0）, immediately after induction of anesthesia（T1）, 30 minutes after induction of anesthesia（T2）, 60 minutes after induction of anesthesia（T3）, at the end of surgery（T4）, and 20 minutes after entering the postanesthesia care unit（PACU）（T5）. The thrombin time（TT）, prothrombin time（PT）and activated partial thromboplastin time（APTT）were compared among groups before operation and at T4. The incidence of intraoperative hypothermia, incidence of shivering during PACU, incidence of surgical site infection, extubation time（from the day of drug withdrawal to the time of tracheal tube removal）, length of hospital stay（from the day of operation to the time of discharge）and adverse reactions related to the devices were compared among groups.Results:There was no statistically significant difference in core body temperature among three groups at T0（ P>0.05）. The core body temperature in closed-loop group［（36.61±0.28）℃］was higher than that in heat preservation group［（36.45±0.28）℃］and control group［（36.44±0.27）℃］at T1（ P<0.05）, but no statistically significant difference was found in core body temperature between heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group［（36.46±0.28）℃,（36.40±0.30）℃,（36.45±0.37）℃,（36.50±0.27）℃］was higher than that in heat preservation group［（36.32±0.31）℃,（36.24±0.26）℃,（36.28±0.30）℃,（36.24±0.31）℃］and control group［（36.12±0.30）℃,（35.98±0.28）℃,（35.73±0.31）℃,（35.81±0.32）℃］at T2-T5（ P<0.05）, and a higher temperature was found in heat preservation group than control group（ P<0.05）. The core body temperature in closed-loop group was increased at T1 compared to that at T0（ P<0.05）, while there was no statistical difference at T0 and T1 in heat preservation group and control group（ P>0.05）. The core body temperature in closed-loop group showed no significant difference at T2-T5 and T0（ P>0.05）, while the core temperature in heat preservation group and control group was decreased at T2-T5 compared to that at T0（ P<0.05）. The core body temperature in closed-loop group was within the set target temperature range. There was no statistically significant difference in TT, PT and APTT among the three groups before operation（ P>0.05）. At T4, the levels of TT, PT and APTT in closed-loop group［（18.9±1.7）seconds,（11.9±0.7）seconds,（35.5±3.3）seconds］and heat preservation group［（18.8±1.7）seconds,（11.6±0.8）seconds,（32.8±2.7）seconds］were shorter than those in control group［（20.9±1.3）seconds,（13.0±0.8）seconds,（35.7±3.4）seconds］（ P<0.05）. At T4, the levels of APTT in closed-loop group and heat preservation group were longer than those before operation（ P<0.05）. At T4, the levels of TT, PT and APTT in control group were longer than those before operation（ P<0.05）. There was no significant difference in the incidence of intraoperative hypothermia or shivering during PACU between closed-loop group［18%（7/40）, 3%（1/40）］and heat preservation group［33%（13/40）, 8%（3/40）］（ P>0.05）, which were lower than those in control group［75%（30/40）, 33%（13/40）］（ P<0.05）. There was no significant difference in the extubation time between closed-loop group［（12.5±3.6）minutes］and heat preservation group［（13.2±3.9）minutes］（ P>0.05）, which was shorter than that in control group［（16.6±4.0）minutes］（ P<0.05）. The incidence of surgical site infection and length of hospital stay were statistically insignificant among the three groups（ P>0.05）. No adverse reactions such as allergic reaction or pressure ulcers occurred in the three groups. Conclusion:For the elderly patients with femoral neck fracture, the perioperative whole-course closed-loop temperature management system can effectively maintain the core body temperature, improve coagulation function, prevent hypothermia, reduce shivering and shorten the extubation time, without increasing the risk of other adverse events, so the system can be safely used in clinical practice.

Accurate determination of drug concentration in blood samples is a necessary prerequisite for therapeutic drug monitoring (TDM) and the implementation of precise drug treatment, and it is also one of the important tasks of clinical laboratories.TDM plays an important role in clinical treatment in immunosuppressants (cyclosporine A, tacrolimus), psychotropic drugs (valproic acid, carbamazepine) and other drugs that require monitoring of drug concentration. There are many types of methods used for TDM for the detection of drug concentration in blood samples. At present, only a few immuno-assay methods were approved for marketing with detection systems and kits, most methods used for TDM are high performance liquid chromatography or liquid chromatography-tandem mass spectrometry which belong to laboratory developed tests (LDTs). Detection of TDM samples has many problems, such as incomparable testing results and large bias between different testing systems, including the biasbetween both different methods and different laboratories using the same method. There are several reasons:(1) the traceability chain has not been established, (2) the methods have not yet been standardized, (3) the coverage of the EQA plan is insufficient, (4) the awareness of TDM laboratories to participate in the EQA plan is insufficient, (5) TDM standardization is still in its infancy. These problems restrict the clinical application of TDM and the development of related research work. In order to solve these problems, it is necessary to: (1) Establish a reference system to realize the traceability of the test results; (2) While gradually increasing the TDM EQA plan items, the Trueness evaluation plan should be carried out as soon as possible; (3) Standardized TDM sample testing Technology; (4) Strengthen laboratory management and establish a complete quality management system.