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.

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.

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 To develop a time-resolved fluorescent immunoassay kit for the rapid,accurate and quantitative detection of S100B protein in serum and to evaluate its performance.Methods The test strip was prepared using time-resolved fluorescent microsphere-labeled anti-S100B polyclonal antibody and rabbit IgG antibody,labeling pads,sample pads,S100B nitrocellulose films and absorbent paper,and an S100B time-resolved fluorescence immunoassay kit was obtained by assembling the cartridge.The performance of the kit developed was evaluated by standard curve,accuracy,minimum detection limit,linear interval,specificity,reproducibility and stability.The reference intervals of 199 pieces of healthy human serum and plasma samples from a certain region were detected with the kit,and the clinical performance of the kit and Roche Elecsys S100 kit was tested by synchronous blind method to assess the consistency of the results of the two kits for 142 samples.Results The S100B time-resolved fluorescence immunoassay kit had the standard curve beingy=(1.133 02+1.752 24)/[1+(x/1.082 20)×(-0.603 52)]-1.752 24,R2=0.999 08 and the linear range being[0.05,30]ng/mL,which met the requirements of the relative deviation of the accuracy within±15％,the minimum detection limit not hgier than 0.05 ng/mL,the relative deviation of specificity within±15％and the coefficient of variation of intra-and inter-batch difference less than 15％.The stability test results indicated that the kit was valid for 12 months at 2-30 ℃ conditions.The reference intervals of serum and plasma samples measured by the kit were both lower than 0.3 ng/mL.Clinical trials showed that the results by the kit and Roche Elecsys S100 Assay Kit were in high agreement(Kappa=0.906 1＞0.80)and met the requirements.Conclusion The kit developed detects the concentration of S100B protein in serum quickly,accurately and quantitatively,and provides references for the diagnosis and treatment of neurological diseases,autoimmune diseases,cerebrovascular diseases and etc.[Chinese Medical Equipment Journal,2024,45(1):47-55]

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

OBJECTIVE: To explore correlation between femoral mechanical axis and Blumensaat line (FMBL) angle of knee joint (angle between Blumensaat line and femoral mechanical axis), α angle (angle between Blumensaat line and axis of distal femur in sagittal plane) on EOS biplane imaging and non-contact anterior cruciate ligament(ACL) injury, and evaluate angle for its accuracy in predicting the populations prone to non-contact ACL injury. METHODS: From February 2018 to October 2020, EOS imaging and clinical data from 88 patients (176 knees) with unilateral non-contact ACL injury were retrospectively analyzed, including 53 males and 35 females, aged from 18 to 45 years old with an average of (30.3±6.2) years old, 48 patients on the left side and 40 patients on the right side. The patients were divided into ACL-affected group and ACL-health group according to side of ACL injuries, and 51 patients (51 knees) with non-ACL identified from EOS database were included in normal control group, including 28 males and 23 females, aged from 20 to 44 years old with an average of (31.6±5.5) years old, 26 patients on the left side and 25 patients on the right side. Full-length EOS imaging of skeleton extremitatis inferioris among three groups were reconstructed to 3D images of skeletal system with EOS software, and then FMBL angle and α angle were measured on the images. Univariate binary Logistic regression analysis was performed to determine the influence of the univariate(FMBL angle or α angle) on ACL status(normal or torn). And the angle cutoff value for univariate was selected based on receiver operating characteristics curve (ROC) to got the best accuracy. RESULTS: There was no statistically significant difference in age, gender and side distribution between ACL-injured group and normal control group(P>0.05). Statistical analyses (one-way ANOVA) indicated no significant difference in FMBL angle between ACL-injured knee group (32.8±2.3)° and ACL-injured contralateral knee group(32.5±2.3)°(P>0.05), but the values between two groups were significantly lower than that in normal control group (37.0±2.0)°(P<0.001). There was no statistically significant difference in α angle among three groups (P>0.05). Univariate binary Logistic regression analysis demonstrated that FMBL angle was risk factor for non-contact ACL injury[OR=0.433, 95%CI(0.330, 0.569), P<0.001]. The area under ROC curve for FMBL angle was 0.909[95%CI(0.861, 0.958), P<0.001], and the sensitivity and specificity were 70.5% and 98.0% respectively, cut-off value was 33.7°. CONCLUSION FMBL angle formed by Blumensaat line and femoral mechanical axis is one of the risk factors for non-contact ACL injury and has good predictive accuracy. The general population with FMBL angle below 33.7° may be increased risk for ACL injury.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Anterior Cruciate Ligament Injuries/diagnostic imaging* ; Retrospective Studies ; Imaging, Three-Dimensional ; Magnetic Resonance Imaging/methods* ; Anterior Cruciate Ligament/diagnostic imaging* ; Knee Joint/diagnostic imaging*

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].