ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Objective:To investigate expression levels of various myeloid suppressor cells(MDSCs)in bone marrow of patients with chronic myeloid leukemia(CML),and the difference and correlation of expression levels of BCR-ABL fusion gene and WT1 in CML patients at different stages,and explore its clinical significance.To analyze and compare the distribution differences of various MDSCs in CML with different remission depths after treatment.Methods:Proportions of various MDSCs in 58 CML patients were de-tected by flow cytometry.Relative expressions of WT1 and BCR-ABL were detected by RQ-PCR.Iron deficiency anemia patients were served as control group,differences of the distribution of MDSCs in CML patients with different BCR-ABL expression,different WT1 expression,different CD34+cell numbers and different disease course,and expressions of various types of MDSC at 3,6,12 and 24 months after treatment in patients with chronic phase of CML were analyzed.At the same time,changes of cellular immune status in CML patients at different stages were detected,and correlations between the changes of lymphocyte subsets and MDSCs were compared.Results:Proportions of G-MDSC and e-MDSC in chronic phase of CML were significantly higher than that in normal control group(P<0.05).Proportions of G-MDSC and e-MDSC in CML patients in accelerated phase and blast crisis phase were significantly higher than that in CML patients in chronic phase(P<0.05).However,the difference in proportion of M-MDSC between accelerated phase of CML and chronic phase of CML had no statistical significance.Proportion of G-MDSC in CML patients was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.558 7,0.530 7,0.598 1),proportion of M-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.132 1,0.144 6,0.157 8).Proportion of e-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.604 3,0.620 7,0.625 9).G-MDSC was significantly lower in the best response group than that in warning/failure group at all stages of treatment.e-MDSC was differential in the best response and warning/failure groups at only 3 months of treatment.M-MDSC was not statistically significant in the best response and warning/failure groups at all stages of treatment.And only G-MDSC cell ratio was positively correlated with its BCR-ABL ratio(r=0.798 1).Per-centage of T lymphocyte in CML blast crisis phase was significantly lower than that in accelerated and chronic phases,while percentage of NK cells was higher.Only the proportion of G-MDSC was negatively correlated with the proportion of T lymphocyte(r=-0.815 2).Conclusion:Various MDSCs are positively correlated with BCR-ABL,WT1 gene and CD34+cells,and positively correlated with the tumor burden of CML patients,while the correlation of M-MDSC is weaker than that of G-MDSC and e-MDSC.With the remission of CML,G-MDSC decreases,while M-MDSC does not change.e-MDSC only shows differences in the early 3-month of treatment.Change of G-MDSC ratio may predict the effect of CML treatment.MDSCs can inhibit the proliferation of T lymphocyte,and inhibitory effect of G-MDSC is stronger than that of M-MDSC and e-MDSC.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

Objective:To investigate the relationship between macrophage activation related factors and clini-cal symptoms of schizophrenia(SCZ).Methods:Outpatient or inpatient SCZ patients(n=166)and normal con-trols(n=71)meeting the diagnostic criteria of DSM 4th edition were selected as subjects.The psychopathological symptoms were assessed by the Positive and Negative Syndrome Scale(PANSS),and the concentrations of α-Na-Galases,MAF and IL-18 were determined by enzyme-linked immunosorbent assay(ELISA).The correlation be-tween biological indicators and clinical symptoms was analyzed and the mediation effect was tested.Results:The concentrations of α-NaGalases(P＜0.001)and MAF(P＜0.01)in SCZ group were lower than those in normal control group.In SCZ group,IL-18 was negatively correlated with α-NaGalases concentration(r=-0.24,P＜0.01).α-NaGalases was positively correlated with MAF concentration(r=0.67,P＜0.001),and the total score of PANSS positive symptom scale was positively correlated with IL-18(r=0.21,P＜0.05)and MAF concentration(r=0.22,P＜0.01).The mediating effect of α-NaGalases and MAF was statistically significant,and the relative mediating effect accounted for 25.47％.Conclusion:The increase of IL-18 level may indicate the occurrence of positive symptoms of schizophrenia,and α-NaGalases and MAF may negatively regulate the inflammatory damage effect of IL-18 on SCZ,thereby reducing the positive symptoms.

Objective:To investigate expression levels of various myeloid suppressor cells(MDSCs)in bone marrow of patients with chronic myeloid leukemia(CML),and the difference and correlation of expression levels of BCR-ABL fusion gene and WT1 in CML patients at different stages,and explore its clinical significance.To analyze and compare the distribution differences of various MDSCs in CML with different remission depths after treatment.Methods:Proportions of various MDSCs in 58 CML patients were de-tected by flow cytometry.Relative expressions of WT1 and BCR-ABL were detected by RQ-PCR.Iron deficiency anemia patients were served as control group,differences of the distribution of MDSCs in CML patients with different BCR-ABL expression,different WT1 expression,different CD34+cell numbers and different disease course,and expressions of various types of MDSC at 3,6,12 and 24 months after treatment in patients with chronic phase of CML were analyzed.At the same time,changes of cellular immune status in CML patients at different stages were detected,and correlations between the changes of lymphocyte subsets and MDSCs were compared.Results:Proportions of G-MDSC and e-MDSC in chronic phase of CML were significantly higher than that in normal control group(P<0.05).Proportions of G-MDSC and e-MDSC in CML patients in accelerated phase and blast crisis phase were significantly higher than that in CML patients in chronic phase(P<0.05).However,the difference in proportion of M-MDSC between accelerated phase of CML and chronic phase of CML had no statistical significance.Proportion of G-MDSC in CML patients was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.558 7,0.530 7,0.598 1),proportion of M-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.132 1,0.144 6,0.157 8).Proportion of e-MDSC was positively correlated with values of BCR-ABL,WT1 genes and proportion of CD34+cells(r=0.604 3,0.620 7,0.625 9).G-MDSC was significantly lower in the best response group than that in warning/failure group at all stages of treatment.e-MDSC was differential in the best response and warning/failure groups at only 3 months of treatment.M-MDSC was not statistically significant in the best response and warning/failure groups at all stages of treatment.And only G-MDSC cell ratio was positively correlated with its BCR-ABL ratio(r=0.798 1).Per-centage of T lymphocyte in CML blast crisis phase was significantly lower than that in accelerated and chronic phases,while percentage of NK cells was higher.Only the proportion of G-MDSC was negatively correlated with the proportion of T lymphocyte(r=-0.815 2).Conclusion:Various MDSCs are positively correlated with BCR-ABL,WT1 gene and CD34+cells,and positively correlated with the tumor burden of CML patients,while the correlation of M-MDSC is weaker than that of G-MDSC and e-MDSC.With the remission of CML,G-MDSC decreases,while M-MDSC does not change.e-MDSC only shows differences in the early 3-month of treatment.Change of G-MDSC ratio may predict the effect of CML treatment.MDSCs can inhibit the proliferation of T lymphocyte,and inhibitory effect of G-MDSC is stronger than that of M-MDSC and e-MDSC.

ObjectiveTo examine the inhibitory effects of berberine compounds， including columbamine， on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier （BBB） permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration （IC₅₀） of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters （K_off） of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds （including medicinal herbs and compound formulas） was conducted using ultra performance liquid chromatography-high resolution mass spectrometry （UPLC-HRMS）. ResultBerberine compounds， including columbamine， exhibited strong inhibition of acetylcholinesterase， with IC₅₀ values in the nanomolar range. Moreover， they displayed better drug-target binding kinetics characteristics （with smaller K_off values） than the positive control of donepezil hydrochloride （P<0.01）， indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer， as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance， this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease， providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.

ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus（SCF） based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism， intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration， and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC Q-Exactive Orbitrap MS） was used to analyze and compare the differences in the spectra of SCF extract， blank plasma， administered plasma， blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column（2.1 mm×100 mm， 1.7 µm）， the mobile phase was acetonitrile（A）-0.1% formic acid aqueous solution（B） for gradient elution（0-7 min， 95%B； 7-12 min， 95%-35%B； 12-17 min， 35%-15%B； 17-20 min， 15%-12%B； 20-22 min， 12%-5%B； 22-23 min， 5%B； 23-25 min， 5%-95%B； 25-28 min， 95%B）. And heated electrospray ionization（HESI） was used with positive and negative ion modes， the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time， characteristic fragments， molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF， including lignans， flavonoids， amino acids， tannins， and others， of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation， methylation， demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats， it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.

BACKGROUND:Scoliosis mainly refers to sequence abnormalities in the coronal,sagittal,and axial positions of the spine,with a Cobb angle of≥10°.The patients may experience symptoms such as unequal shoulder height and back asymmetry.Severe cases may affect the patient's cardiopulmonary function,thereby affecting their daily life.Conservative treatment can control the progression of scoliosis and avoid later surgery.Scoliosis orthosis is currently a commonly used and effective treatment measure in conservative treatment. OBJECTIVE:To summarize and analyze the current research status,hotspots,and trends of scoliosis orthoses both domestically and internationally,providing reference for related research. METHODS:Using bibliometrics and visual analysis as tools,and using a comparison between China and foreign countries as a method,this paper analyzes the literature on scoliosis orthosis journals in the past decade.Based on bibliometrics,the current status of research on scoliosis orthoses is determined.Citespace software is used to analyze key words and identify the current hotspots and future trends in scoliosis orthosis research. RESULTS AND CONCLUSION:(1)At present,the number of literature on scoliosis orthoses is still on a fluctuating upward trend.China and the United States are the main countries for research,with a literature share of over 40%.However,the average citation rate of foreign language literature by Chinese scholars is relatively low.(2)The basic fields of domestic research are mainly surgery and pediatrics,while orthotics and clinical neurology are mainly studied abroad.Among them,there is also a certain number of documents in domestic Chinese medicine,indicating that China is also engaged in the combination of Chinese and Western treatment of scoliosis.The National Natural Science Foundation of China has the highest proportion in the aspect of Chinese and foreign literature,reflecting the importance of the fund attaches to the research of scoliosis orthosis.(3)The authors with the highest number of publications are Qiu Yong and Negrini Stefano,and the most published institutions are the Spinal Surgery Department of Gulou Hospital affiliated to Nanjing University Medical College and UDICE-French Research University.Domestic and foreign authors and institutions have certain communications about this,but not closely,which requires relevant institutions and scholars to further explore and study.(4)From the research hotspots and future trends,the main treatment type is adolescent idiopathic scoliosis,while the production method of the short-column side bending orthosis is three-dimensinoal printing,and the main treatment index is convex progression.The ultimate purpose of treatment is to improve the quality of life of the patients.

Objective To analyze the achievement of target vancomycin concentration and the risk factors affecting the concentration to reach the target,providing a reference for the rational use of vancomycin and the implementation of therapeutic drug monitoring(TDM).Methods Patients who were hospitalized and received vancomycin TDM from January 2016 to June 2019 at Zhongshan Hospital,Fudan University were selected.Clinical data,vancomycin blood concentrations,and occurrences of acute kidney injury(AKI)during the hospitalization were collected.Factors affecting the attainment of target vancomycin concentrations were analyzed using logistic regression and grouped according to whether the target concentrations were attained.The correlation between drug concentration and the occurrence of AKI was analyzed.Results A total of 1 106 patients were included,with 70.7％being males and a median age of 60.0(IQR=20)years.Surgical departments accounted for 76.4％of the distribution.The median duration of vancomycin therapy was 10.8 d(IQR=9.0).A total of 21.6％of patients had their first concentration monitored before administration of doses 4 and 5.The drug concentration monitoring results of 46.8％(518/1 106)of patients were in the range between 10-20 μg·mL-1,reaching the target concentration range.The incidence of vancomycin-associated AKI was 25.9％.The incidence of AKI varied among patients with different vancomycin concentrations:when the concentrations are＜10,10-＜15,15-20,and＞20 μg·mL-1,the AKI rates are 15.8％,20.5％,25.8％,and 39.4％,respectively.Multivariate logistic regression analysis showed that target concentrations were more likely to be reached with a dosing course of＞7-14 d(OR=1.688,P=0.001)and＞14 d(OR=1.744,P=0.002)than with a dosing course of ≤7 d.Patients receiving conventional daily doses were more likely to achieve target concentrations than those receiving the non-conventional daily dose(OR=1.540,P=0.003).Conclusion The current status of vancomycin TDM in China still suffers from deficiencies,such as delayed timing of monitoring and low rate of target concentration attainment.Higher vancomycin concentrations are significantly associated with AKI,and the factors affecting the vancomycin concentration to reach the target mainly include treatment duration and the complexity of the dosing regimen.

Objective:Using real-world data to analyze whether the administration of carbapenems within 7 days before the treatment or during the treatment will reduce the effectiveness of sodium valproate in patients with status epilepticus (SE) and seizure clusters (SC).Methods:The clinical data of SE and SC patients who received intravenous administration of sodium valproate in the Department of Emergency of Zhongshan Hospital, Fudan University from 2017 to 2021 were collected. The main endpoint was the failure to terminate epileptic seizures after sodium valproate injection. Univariate analysis and multivariate Logistic regression model were used to analyze whether the carbapenems was an independent risk factor for the failure of sodium valproate treatment.Results:Finally, 142 SE patients and 181 SC patients were included. Univariate analysis revealed that the use of carbapenems within 7 days before or during the treatment was a risk factor for the failure of sodium valproate treatment in SC patients (χ 2=5.498, P=0.019), but was not a risk factor for the failure of sodium valproate treatment in SE patients (χ 2=3.015, P=0.082). Through multiple factor analysis, it was found that the use of carbapenems was an independent risk factor for the seizures not terminatd by sodium valproate in SC patients ( OR=3.462, 95% CI 1.180-10.157); the interval between onset and medication≥4 hours increased the risk of sodium valproate treatment failure in SE patients ( OR=4.591, 95% CI 1.443-14.607); simultaneously using benzodiazepines could reduce the risk of sodium valproate treatment failure in SE patients ( OR=0.300, 95% CI 0.128-0.703). Conclusions:The use of carbapenems by SC patients within 7 days before or during treatment may lead to the failure of sodium valproate treatment. In clinical practice, the use of sodium valproate as a medication to terminate seizures in SC patients can be determined based on their medication records.