"MS/MS spectrum to structure"plays a critical role in the confirmative identification of complicated matrices and is currently regarded as an extremely challenging endeavor.MS/MS information provides vital clues to structural identification.In this study,a strategy was proposed to facilitate unambiguous identification through matching MS3 with MS2 spectra.Initially,MS3 spectra of the featured ions(c-and y-type ions)generated by the decomposition of ester functional group in esters and the MS2 spectrum of the structural unit([M-H]-)were all captured on the Qtrap-MS platform equipped with two tandem-in-space collision cells,including the second quadrupole cell(q2)and linear ion trap(LIT)chambers(actually the third quadrupole unit).Subsequently,the MS/MS spectrum matching between MS3 spectra of the ester compound and MS2 spectra of the structural unit(s)were achieved.As a result,the findings corresponding to MS3 and MS2 spectra matching were summarized.Finally,based on HR-MS/MS information of total salvianolic acid derivatives(TSA),36 kinds of compounds were preliminarily identified through matching with literature information and database retrieval.The applicability of MS3 and MS2 spectra matching strategy was further justified by the confirmative identification of phenolic acid compounds(Rosmarinic acid and salvianolic acid B)in TSA.Above all,MS3 and MS2 spectra matching strategy was quite meaningful towards advancing"MS/MS spectrum to structure"analysis through recognizing and identifying featured fragment ions,and also provided inspiration and new insights for the structural characterization.

This study utilized a chiral liquid chromatography-mass spectrometry (LC-MS)-guided isolation strategy to accurately capture angular-type pyranocoumarins (APs) in Peucedani Radix (Chinese name: Qianhu). Sixteen APs were successfully purified from the ethyl acetate extract of Peucedani Radix through deploying various techniques such as silica gel, ODS, Sephadex LH-20, and achiral (chiral) semi-preparative liquid chromatography. After extensive structural measurements, such as ¹H and ¹³C NMR spectroscopy, their structures were identified as (3′S)-3′-(2-methyl-butyroyl)-4′-oxo-3′,4′-dihydroseselin (1A), (3′R)-3′-(2-methyl-butyroyl)-4′-oxo-3′,4′-dihydroseselin (1B), (3′S)-3′-isovaleryl-4′-oxo-lomatin (2A), (3′R)-3′-isovaleryl-4′-oxo-lomatin (2B), (3′S)-3′-angeloyloxy-4′-oxo-3′,4′-dihydroseselin (3A), (3′R)-3′-angeloyloxy-4′-oxo-3′,4′-dihydroseselin (3B), (3′S,4′S)-praeruptorin B (4A), (3′R,4′R)-praeruptorin B (4B), (3′S,4′S)-praeruptorin E (5A), (3′R,4′R)-praeruptorin E (5B), 3′-isovaleryl-4′-angeloyl-cis-khellactone (6), 3′-angeloyl-4′-(2-methyl-butyroyl)-cis-khellactone (7), (3′S,4′S)-praeruptorin A (8A), (3′R,4′R)-praeruptorin A (8B), (3′S,4′S)-khellactone (9A), and (3′R,4′R)-khellactone (9B), respectively. Thereof, compounds 1A and 1B were new compounds, while compound 2A represents a new configuration for a known planar structure. Compounds 2A and 2B were isolated for the first time from Peucedani Radix. Above all, chiral LC-MS-guided isolation strategy is advantageous at rapid capturing new compounds from herbal medicines, providing an effective means for the separation of novel structures, especially new enantiomers.

The risks related to the essential performance were analyzed with considerations on the concept of the essential performance in GB 9706.1-2020 Medical electrical equipment-Part 1:General requirements for basic safety and essential performance,and the determination process for the essential performance of medical electrical equipment was summarized.The essential performance of the example equipment was clarified with the semi-quantitative risk analysis,and the influences of the arrangement of the electromagnetic compatibility test on the determination of the essential performance were explored with the conducted immunity test and conventional test.References were provided for standard users to understand and determine the essential performance effectively.[Chinese Medical Equipment Journal,2024,45(11):72-76]

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Aim To explore the improvement effect of Bazi Bushen capsule on thymic degeneration in SAMP6 mice and the possible mechanism.Methods Twenty 12 week old male SAMP6 mice were randomly divided into the model group(SAMP6)and the Bazi Busheng capsule treatment group(SAMP6+BZBS).Ten SAMR1 mice were assigned to a homologous control group(SAMR1).The SAMP6+BZBS group was oral-ly administered Bazi Bushen capsule suspension(2.8 g·kg-1)daily,while the other two groups were orally administered an equal amount of distilled water.After nine weeks of administration,the morphology of the thymus in each group was observed and the thymus in-dex was calculated;HE staining was used to observe the structural changes of thymus tissue;SA-β-gal stai-ning was used to detect thymic aging;flow cytometry was used to detect the proportion of thymic CD3+T cells in each group;Western blot was used to detect the levels of p16,Bax,Bcl-2,and cleaved caspase-3 proteins in thymus;immunofluorescence was applied to detect the proportion of cortical thymic epithelial cells in each group;ELISA was employed to detect IL-7 lev-els in thymus.Results Compared with the SAMP6 group,the thymic index of the SAMP6+BZBS group significantly increased(P＜0.05);the disordered thy-mic structure was significantly improved;the positive proportion of SA-β-gal staining significantly decreased(P＜0.01);the proportion of CD3+T cells apparently increased(P＜0.05);the level of p16 protein signifi-cantly decreased(P＜0.05);the level of Bcl-2 pro-tein significantly increased(P＜0.05),while the lev-el of cleaved caspase-3 protein markedly decreased(P＜0.05);the proportion of cortical thymic epithelial cells evidently increased;the level of IL-7 significantly increased(P＜0.01).Conclusions Bazi Bushen capsule can delay thymic degeneration,inhibit cell ap-optosis in thymus and promote thymic cell development in SAMP6 mice,which may be related to increasing the proportion of cortical thymic epithelial cells and promoting IL-7 secretion.

AIM To study the chemical constituents from the methanol fraction of Premna fulva Craib leaves and their anti-inflammatory activities.METHODS The methanol fraction from P.fluva were isolated and purified by TLC,column chromatography,and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Twelve compounds were isolated and identified as vitexin(1),balanophonin(2),inotodisaccharide(3),4-allyl-2,6-dimethoxyphenol-β-D-glucopyranoside(4),dehydrovomifoliol(5),loliolide(6),(E)-4-((1S,3R,4R)-1-hydroxy-4,5,5-trimethyl-7-oxabicyclo[4.1.0]heptan-1-yl)but-1-en-3-o-ne(7),(E)-4-hydroxyphenylprop-7-ene 4-O-β-D-glucopyranoside(8),4-O-β-D-glucopyranosylbenzoic acid(9),vicenin(10),oleanicacid(11),sesamin(12),respectively.Compounds 1,2,5,7,10,and 12 showed good inhibitory activities against NO,and the IC50 values were(26.42±2.5)、(21.24±2.2)、(25.88±1.9)、(29.72±2.1)、(8.90±1.1)、(9.73±0.7)μmol/L,respectively.CONCLUSION Compounds 2,4-8 are isolated from Premna genus plants for the first time.Compounds 1,2,5,7,10,12 have anti-inflammatory activities.

Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.

Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.

Objective:To explore the medication law and core TCM prescriptions of Jia Yuejin in the treatment of coronary heart disease (CHD) complicated with depressive disorder (DD) by analyzing target-based network and mining clinical data.Methods:The targets of CHD complicated with DD were obtained by GeneCards, OMIM, TTD and other databases, and then the protein-protein interaction network of the two disease targets was constructed and then screened out the core targets. The Metascape platform was used to perform GO and KEGG pathway enrichment analysis on the intersection targets respectively to analyze the mechanism of action of CHD complicated with DD. Then TCMSP was used to query the active components acting on the targets and the Chinese materia medica containing these active components, and the data were imported into Cytoscape 3.9.0 to construct the core target-active component-Chinese materia medica network for network topology analysis. The outpatient clinical data of Jia Yuejin from January 1, 2015 to January 1, 2021 were collected, and data mining was conducted by using the Ancient and Modern Medical Case Cloud Platform (V2.3.5) to obtain his commonly used prescriptions. The results were fitted with the core TCM prescriptions obtained by target network analysis, and the drugs in the core prescriptions were analyzed.Results:Totally 1 501 intersection targets were obtained by protein interaction network analysis of CHD complicated with DD, which could be divided into 4 core target clusters, including inflammation cause, subclass tumor cause, subclass lipid metabolism factor, and fibrosis factor; a total of 480 active components were obtained by TCMSP, which belonged to 181 types of Chinese materia medica, including 8 core components: quercetin, kaempferol, luteolin, carotene, beta-carotene, acacetin, formononetin and ellagic acid. GO enrichment analysis yielded 61 results, mainly including positive regulation of protein phosphorylation, signal receptor agonist activity, side of membrane , etc.; KEGG pathway enrichment analysis yielded a total of 20 results, mainly including cancer pathways, lipid and atherosclerosis, JAK-STAT signaling pathway, etc. Clinical data mining included 120 cases and 148 prescriptions, including 135 types of Chinese materia medica; the properties were mainly mild, warm, slightly cold and cold; the tastes were mainly sweet, bitter and light, and the medicine mainly belongs to the lung, spleen, liver, heart, stomach, kidney and other meridians; drug association analysis, cluster analysis and complex network analysis were used to synthesize common prescriptions. The core TCM prescriptions obtained from common prescription and target network analysis were fitted: Pinelliae Rhizoma, Glycyrrhizae Radixet Rhizoma, Bupleuri Radix, Cyperi Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, Corydalis Rhizoma, Codonopsis Radix, Astragali Radix, Acori Tatarinowii Rhizoma. Conclusion:The medication law of Jia Yuejin in the treatment of CHD complicated with DD is in accordance with core TCM prescriptions. This study can provide guidance for clinical treatment and further research of CHD complicated with DD.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.