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.

Objective To explore the correlation between platelet to lymphocyte ratio(PLR),neutrophil to lymphocyte ratio(NLR)and carotid atherosclerotic(CAS)plaque in patients with type 2 diabetes(T2DM),and the predictive value of PLR and NLR for T2DM complicated with CAS plaque.Methods A total of 369 T2DM patients admitted to the Department of Endocrinology,the Third Affiliated Hospital of Xinxiang Medical University from September 2019 to November 2021 were se-lected as research subjects.The clinical data such as gender,age,course of disease,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),personal history,and history of past illness of patients were collected by searching the electronic medical record system.Neutrophil(NC)count,lymphocyte count(LC)and platelet(PLT)count were detected by fully automated blood routine analyzer,and PLR,NLR were calculated;the levels of fasting blood glucose(FBG),total cholesterol(TC),triglycerides(TG),high-density lipoprotein-cholesterol(HDL-C)and low-density lipoprotein-cholesterol(LDL-C)were detected by biochemical analyzer;the level of glycosylated hemoglobin(HbA1c)were detected by high-performance liquid chromatography.The T2DM patients were divided into T2DM uncomplicated with CAS plaque group(n=94)and T2DM complicated with GAS plaque group(n=275)based on whether they complicated with CAS plaque or not;the general clinical data,blood indicators,and PLR,NLR of patients were compared between the two groups.The T2DM patients were divided into non plaque group(group A,n=94),1 plaque group(group B,n=79),2 plaque group(group C,n=89),and 3 or more plaques group(group D,n=107)based on the number of CAS plaques;the indicators with statistical differences between T2DM uncomplicated with CAS plaque group and T2DM complicated with CAS plaque group of patients were compared among the four groups.According to the PLR quartile,the patients were divided into P1 group(PLR≤94.87,n=93),P2 group(94.87＜PLR≤117.30,n=91),P3 group(117.30＜PLR ≤ 148.53,n=93),and P4 group(PLR＞148.53,n=92),and the detection rate of CAS plaques of patients was compared among the four groups;according to the NLR quartile,the patients were divided into N1 group(NLR≤1.59,n=92),N2 group(1.59＜NLR≤1.93,n=92),N3 group(1.93＜NLR≤2.50,n=93),and N4 group(NLR＞2.50,n=92),and the detection rate of CAS plaque of patients was compared among the four groups.The risk factors of T2DM complicated with CAS plaque was analysed by multivariate logistic regression analysis,and the predictive efficacy of PLR and NLR for T2DM complicated with CAS plaque were evaluated by receiver operating characteristic(ROC)curve.Results The age,course of T2DM,proportion of patients combined with hyper-tension,SBP,PLR,and NLR of patients in the T2DM complicated with CAS plaque group were significantly higher than those in the T2DM uncomplicated with CAS plaque group,while LC and TG levels were significantly lower than those in the T2DM uncomplicated with CAS plaque group(P＜0.05);there was no significant difference in gender,proportion of patients com-bined with hyperlipidemia,proportion of smoking history,proportion of drinking history,and the levels of DBP,BMI,NC,PLT,TC,HDL-C,LDL-C,FBG,HbA1c between the T2DM uncomplicated with CAS plaque group and T2DM complicated with CAS plaque group(P＞0.05).The age,proportion of patients combined with hypertension,course of T2DM,SBP,PLR,and NLR of patients in group B,group C,and group D were significantly higher than that in group A,while LC level was significantly lower than that in group A(P＜0.05).The TG level of patients in group D was significantly lower than those in group A(P＜0.05);there was no statistically significant difference in TG level of patients among group A,group B,and group C(P＞0.05).The age,proportion of patients combined with hypertension,and course of T2DM of patients in group C and group D were significantly higher than those in group B,while the SBP of patients in group D was significantly higher than that in group B(P＜0.05);there was no statistically significant difference in SBP of patients between group C and group B(P＞0.05).The age,proportion of patients combined with hypertension,course of T2DM,and SBP of patients in group D were significantly higher than those in group C(P＜0.05).There was no statistically significant difference in the levels of LC,TG,and PLR of patients among group B,group C,and group D(P＞0.05).The NLR of patients in group D was significantly higher than that in group B(P＜0.05);there was no statistically significant difference in NLR of patients between group C and group B(P＞0.05),and there was no statistically significant difference in NLR of patients between group D and group C(P＞0.05).The detection rate of CAS plaques of patients in P1 group,P2 group,P3 group,and P4 group showed a significant increase trend(x2=30.610,P=0.000);and the detection rate of CAS plaques of patients in N1 group,N2 group,N3 group,and N4 group showed a significant increase trend(x2=35.170,P=0.000).Multivariate logistic regression analysis showed that age,PLR,and NLR were independent risk factors for T2DM complicated with CAS plaque(odds ratio=1.107,1.017,1.940;P＜0.05).The opti-mal cutoff value of PLR in predicting T2DM complicated with CAS plaque was 119.95,with an area under the curve of 0.680,a sensitivity of 54.7％,and a specificity of 76.3％;the optimal cutoff value of NLR in predicting T2DM complicated with CAS plaque was 1.97,with an area under the curve of 0.698,a sensitivity of 56.5％,and a specificity of 79.6％.Conclusion PLR and NLR are associated with T2DM complicated with CAS plaque,which are independent risk factors for T2DM compli-cated with CAS plaque,and have certain predictive value for T2DM complicated with CAS plaque.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Objective To investigate the main dietary patterns of children in urban areas of Maanshan City, and to explore the association between dietary patterns and subthreshold autism trait (SAT), attention-deficit/hyperactivity disorder (ADHD) symptoms and comorbid behaviors in 3-year-old children. Methods Based on the birth cohort of Maanshan Maternal and Infant Health from June 2015 to June 2016，regular physical examinations were conducted from 4 to 2 to 1, and follow-up was conducted until the age of 3. A semi-quantitative food frequency questionnaire was employed to assess dietary intakes. SAT and ADHD symptoms were assessed by Clancy autism behavior scale (CABS) and the 10-item Chinese version of the Conners Abbreviated Symptom Questionnaire (C-ASQ). Social-demographic information was also collected. Results The detection rates of SAT, ADHD symptoms, and comorbidity were 11.03%, 5.28%, and 2.71%, respectively. The older the father, the higher the mother's education level, and the higher the per capita monthly income of the family, the lower the SAT detection rate (P<0.05). The higher the father's educational level, the lower the detection rate of ADHD symptoms (P<0.05). The older the mother and the higher the education level, the lower the detection rate of comorbid behavior in their children (P <0.05). After adjusting for demographic influencing factors, the low intake level was used as a reference. The vegetarian type with moderate intake level was negatively correlated with SAT, while the processed food type with high intake level was positively correlated with SAT. The vegetarian type with high intake level was negatively correlated with ADHD symptoms, while the snack type with high intake level was positively correlated with ADHD symptoms. The vegetarian type with high intake level was negatively correlated with comorbidity. Conclusion Unhealthy dietary patterns are related to children's SAT and ADHD symptoms. Correcting children's unhealthy eating patterns may help reduce children's behavior problems.

ObjectiveThis study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease （IBD） from the perspectives of the peroxisome proliferator-activated receptor γ （PPARγ） signaling pathway and T-cell immunity， providing reference for the treatment of IBD with traditional Chinese medicine. MethodThe study involved administering 2，4，6-trinitrobenzenesulfonic acid （TNBS） enemas to 35 rats to induce acute IBD. After 24 hours， the animals were divided into the following groups： normal group， model group， Wujiwan treatment group， and positive drug control group. Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index （DAI） of the rat colon tissue， the colon mucosal damage index （CMDI）， and the spleen index. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） in the serum. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of T-bet （T-box expressed in T cells） and Gata3 （Gata-binding protein-3） in the colon tissue. Western blot analysis was conducted to detect the protein expression levels of PPARγ， T-bet， and nuclear factor-κB p65 （NF-κB p65） in the rat colon. ResultThe rat model of IBD was successfully established. Compared with the model group， the Wujiwan treatment group showed reduced DAI， CMDI， and spleen index， decreased content of TNF-α in the serum（P<0.01）， significantly increased content of IL-10（P<0.01）， and elevated mRNA content of T-bet and Gata3（P<0.05） in the colon tissue. The expression of PPARγ protein was augmented（P<0.05）， and the expression of T-bet and NF-κB p65 protein was decreased（P<0.05，P<0.01）. ConclusionWujiwan activates or upregulates PPARγ expression in IBD rats to inhibit the generation of pro-inflammatory factors， participates in the inflammatory immune process， and alleviates inflammatory reactions. Its mechanism may involve regulating the NF-κB pathway through PPARγ， enhancing Th2 cell transcription expression， and reducing Th1 cell transcription.

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:The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment.Methods:In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed.Results:Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased ( P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased ( P<0.05) . After 72 h, MV in the long range group was significantly decreased ( P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance ( P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased ( P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion:Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.

Objective:The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment.Methods:In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed.Results:Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased ( P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased ( P<0.05) . After 72 h, MV in the long range group was significantly decreased ( P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance ( P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased ( P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion:Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.

Fractures are frequently occurring diseases that endanger human health. Crucial to fracture healing is cartilage formation, which provides a bone-regeneration environment. Cartilage consists of both chondrocytes and extracellular matrix (ECM). The ECM of cartilage includes collagens and various types of proteoglycans (PGs), which play important roles in maintaining primary stability in fracture healing. The PG form of dentin matrix protein 1 (DMP1-PG) is involved in maintaining the health of articular cartilage and bone. Our previous data have shown that DMP1-PG is richly expressed in the cartilaginous calluses of fracture sites. However, the possible significant role of DMP1-PG in chondrogenesis and fracture healing is unknown. To further detect the potential role of DMP1-PG in fracture repair, we established a mouse fracture model by using a glycosylation site mutant DMP1 mouse (S89G-DMP1 mouse). Upon inspection, fewer cartilaginous calluses and down-regulated expression levels of chondrogenesis genes were observed in the fracture sites of S89G-DMP1 mice. Given the deficiency of DMP1-PG, the impaired IL-6/JAK/STAT signaling pathway was observed to affect the chondrogenesis of fracture healing. Overall, these results suggest that DMP1-PG is an indispensable proteoglycan in chondrogenesis during fracture healing.