BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.

Objective: To analyze the epidemiological characteristics and changing trends of non suicidal self injury (NSSI) behaviors among middle school students in Jiading District of Shanghai, from 2015 to 2023, so as to provide a basis for the development of NSSI prevention and control measures among students. Methods: Using a stratified cluster random sampling method, a total of five times for Shanghai Adolescent Health Risk Behavior Surveys were conducted for every two years in Jiading District of Shanghai from 2015 to 2023. A total of 5 231 middle school students from junior high schools and senior high schools were selected for questionnaire surveys. Intergroup comparisons were performed using the x 2 test or the χ 2 trend test, and the JointPoint 5.0 software was used to analyze the changing trends, with the annual percent change (APC) used for evaluation. A binary Logistic regression model was employed to analyze the related factors of NSSI behavior among middle school students. Results: In 2023, the reported NSSI rate among middle school students in Jiading District was 14.2%. The rate was significantly higher among junior high school students (17.1%) than that among senior high school students (11.1%), and higher among females (19.2%) than that among males (10.0%) ( χ 2=10.04, 23.21, both P <0.01). From 2015 to 2023, the overall reported NSSI rate showed an increasing trend, rising from 8.6% in 2015 to 14.2% in 2023 ( χ 2 trend =22.25), with an APC of 6.64% ( t =3.49), and the APC for girls was 9.79 % ( t =3.20) (all P <0.05). Among students reporting NSSI, the proportion experiencing ≥6 episodes increased from 10.8% in 2015 to 19.2% in 2023 ( χ 2 trend =6.57, P <0.05). Multivariate Logistic regression analysis indicated that girls, junior high school students, those with insomnia, depressive emotion and drinkers had higher risks of NSSI, compared to boys, senior high school students, those without insomnia, non depressive emotion students and non drinkers ( OR =1.71, 1.96, 3.44, 4.76, 1.77, all P < 0.05 ). Conclusions The reported rate of NSSI among middle school students in Jiading District of Shanghai, increased annually from 2015 to 2023, and the proportion of repeated NSSI also showed an upward trend. Early intervention measures targeting middle school students, especially junior high school students and females, should be implemented to prevent and control its occurrence and development.

Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective:To investigate the role of CD8 + T cells in lethal Plasmodium yoelii 17XL ( Py 17XL) infection. Methods:BALB/c mice and C57BL/6 mice were infected with Py 17XL-infected red blood cells (1×10 6 cells/0.1 ml) through intraperitoneal injection to establish the mouse models of Py 17XL infection. Parasitemia (the percentage of erythrocytes infected with Py 17XL) and the survival rates of the mice was observed dynamically. Flow cytometry was used to detect the number of effector T cells (T EFF) and central memory T cells (T CM) of CD8 + T cell subpopulations, the expression of IFN-γ and granzyme B (GB) levels, and the expression of surface chemokine receptors CXCR3, CXCR6 and CX3CR1. FTY720 blocking experiment was conducted on Py 17XL-infected C57BL/6 mice to analyze the impact of CD8 + T cell migration on Py 17XL infection. Results:The parasitemia of BALB/c mice increased rapidly 5 d after infection and reached the peak on 8 d [(79.57±3.82)%]. Besides, the parasitemia was higher in BALB/c mice than in C57BL/6 mice 5-8 d after infection ( P<0.000 1). All BALB/c mice died on 9 d. The parasitemia of C57BL/6 mice reached the peak on 14 d [(48.19±3.19)%] and then decreased to 0 on 26 d. There was statistically significant difference in the survival rate between the two groups ( P<0.000 1). Flow cytometry results showed that compared with the BALB/c mice, the absolute number of CD8 + T cells in spleen and liver tissues and the number of CD8 + T EFF and CD8 + T CM cells in spleen and lymph nodes of C57BL/6 mice increased significantly ( P<0.05). Compared with the BALB/c mice, the levels of GB, IFN-γ and chemokines expressed by CD8 + T cells in spleen and liver tissues of C57BL/6 mice increased significantly ( P<0.05). The FTY720 blocking experiment showed that the survival rate, the absolute number of CD8 + T cells in liver and spleen, and the number of CD8 + CXCR3 + T cells decreased significantly in the experimental group ( P<0.05). Conclusions:CD8 + T EFF and CD8 + T CM cells contribute to resistance against Py 17XL infection by secreting GB and IFN-γ. The chemokine receptor CXCR3 plays an important role in mediating the chemotaxis of CD8 + T cells to spleen and liver.

To develop a rapid differential detection method for porcine epidemic diarrhea virus(PEDV)and transmissible gastroenteritis virus(PEDV),M gene sequences of PEDV and TGEV were compared,the inner and outer primer pairs and probes were designed according to the highly conserved region.PEDV-Probe was labeled with FAM at5'end and BHQ1 at 3'end.TGEV-Probe was labeled with CY5.5 at the 5'end and BHQ2 at the 3'end.After optimizing the reaction condi-tions and system,a dual fluorescent RT-LAMP assay for PEDV and TGEV rapid identification was established.The amplification could be completed within 60 min in a 63 ℃ water bath and then stopped at 85 ℃ for 10 min.Then the tubes were placed in a multicolor imaging system,and the re-sults could be observed under 520 nm and 690 nm dual channels.There was no cross-reaction when other common swine viral pathogens were detected by this method.The sensitivity of the assay was evaluated with a 10-fold diluted recombinant plasmid as templates.The lowest detection limit was 102 copies/μL recombinant plasmid,which was 10 times more sensitive than the conventional RT-PCR method.Seventy-two PEDV-positive samples,49 TGEV-positive samples,and 40 PEDV and TGEV co-infected samples were detected from 175 anal swab samples of diarrheic piglets by the established method,which were all higher than the detection rates of the conventional RT-PCR method.The dual fluorescent RT-LAMP method established in this study can be used to amplify the target gene in an ordinary water bath without gel electrophoresis,which provides technical sup-port for rapid and convenient differential diagnosis of PED and TGE and simultaneous detection of PEDV and TGEV co-infection.

Ziziphi spinosae semen mainly contains contents of saponins,flavonoids,alkaloids and aliphatic acids.Meanwhile,it has a variety of activities such as sedative-hypnotic,anti-anxiety,anti-depression,nerve protection,cardiovascular and cerebrovascular protection,liver protection,and antioxidant,which is widely used in medicine,food,health food and other fields.The chemical constituents,pharmacological action and clinical application of Ziziphi spinosae semen were systematically summarized in this paper by reviewing the literature,in order to provide theoretical guidance for the sustainable development of the resources and the rational use of Ziziphi spinosae semen.

Purpose To explore the feasibility of artificial intelligence compressed sensing(ACS)technique in ankle joint MRI.Materials and Methods From September to October 2023,32 healthy volunteers who underwent ankle joint scanning in Beijing Friendship Hospital,Capital Medical University were prospectively collected.MRI of the ankle joint based on ACS and parallel imaging(PI)technology was performed on 3.0T MR.The sagittal proton density weighted imaging(PDWI),coronary PDWI,transverse PDWI and sagittal T1WI were acquired,and all data were divided into test group and control group,with ACS to accelerate the multiples of 5(ACS 5.0)in test group,whereas PI speed ratio of 2(PI 2.0)in control group,respectively.The signal intensity of talus,achilles tendon and cartilage were measured,the signal intensity and standard deviation of the long hallux flexor were obtained,and the signal noise ratio(SNR)and contrast to noise ratio(CNR)were calculated via long hallux flexor as background noise.The data of objective and subjective evaluation of the two sequences were statistically analyzed,and the image quality of each sequence was evaluated via the standard reference of PI 2.0.Results SNR and CNR in ACS group were higher than those in PI group,and the anatomical structure of sagittal PDWI sequence between the two groups had statistical significance(t=-2.937,-1.981,-4.058,-3.879,P<0.05).There were significant differences in cartilage SNR and talus CNR in coronal PDWI sequence(t=-3.310,-3.567;P=0.002,P<0.001).In terms of axial PDWI sequence,there were statistically significant differences in talus CNR and cartilage CNR between ACS and PI groups(t=-4.270,-4.382,P<0.05).The subjective evaluation of the image quality scores of the two groups by the two diagnostic imaging doctors showed a strong observer consistency(Kappa=0.977,P=0.009).There was no significant difference in image quality scores between the two groups(Z=-0.248,-0.747,<0.001,-0.071,P>0.05).The total collection time of ACS group and PI group was 337 s and 610 s,respectively.Compared with PI group,the total scanning time of ACS group was shortened by 44.8%.Conclusion ACS based MRI of the ankle joint can not only shorten the scan time,but also ensure and further improve the image quality,with feasibility.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To explored the role and mechanism of antisense RNA of long non-coding RNA(LncRNA)GA binding protein transcrip-tion factor β subunit 1(GABPB1-AS1)in regulating the proliferation,invasion,migration,and apoptosis of acute myeloid leukemia(AML)cells by targeting the microRNA-497-5p/heat shock protein 8(miR-497-5p/HSPA8)axis.Methods:HL-60 cells were divided into the normal con-trol,si-NC,si-GABPB1-AS1,si-GABPB1-AS1+NC,and si-GABPB1-AS1+miR-497-5p inhibitor groups.Quantitative real time polymerase chain re-action(RT-qPCR)was used to detect the expression levels of LncRNA GABPB1-AS1,miR-497-5p,and HSPA8.Double luciferase reporter gene assay was used to verify the targeting relationship between LncRNA GABPB1-AS1,miR-497-5p,and HSPA8;MTT was used to detect cell viab-ility;while 5-ethynyl-2'-deoxyuridine(EdU)was used to detect proliferation.Transwell chamber experiments were used to detect invasion and migration while flow cytometry was used to detect apoptosis.Western blot was used to detect the levels of proliferating cell nuclear an-tigen(PCNA),HSPA8,metastasis-associated proteins(MTA2),homolog of yeast Atg6(Beclin-1),and Caspase-3 proteins.A mouse trans-planted tumor model was established to verify the effect of LncRNA GABPB1-AS1 on the growth of AML transplanted tumors.Results:Com-pared to human bone marrow monocytes,LncRNA GABPB1-AS1 was highly expressed[(1.29±0.10),(1.58±0.12),(2.02±0.17),(3.17±0.24)vs.(1.02±0.07)]while miR-497-5p was lowly expressed[(0.94±0.07),(0.75±0.03),(0.57±0.03),(0.25±0.01)vs.(1.05±0.09)]in different AML cells(THP-1,NB4,U-937,and HL-60,respectively).The HL-60 cell line was selected for functional verification experiments since LncRNA GABPB1-AS1 expression was highest in the HL-60 cells.Knockdown of LncRNA GABPB1-AS1 reduced HL-60 cell viability,the EdU positive rate,cell in-vasion and migration,the expression of HSPA8 mRNA,and HSPA8,PCNA,and MTA2 protein contents.It increased the apoptosis rate,and the expression of miR-497-5p,Caspase-3 and Beclin-1 protein(P<0.05).miR-497-5p had a targeting relationship with LncRNA GABPB1-AS1 and HSPA8;inhibiting the expression of miR-497-5p reversed the inhibitory effect of LncRNA GABPB1-AS1 knockdown on the malignant bio-logical behavior of HL-60 cells.Meanwhile,inhibiting the expression of LncRNA GABPB1-AS1 constrained the growth of transplanted tumors.Conclusions:Knockdown of LncRNA GABPB1-AS1 inhibits the progression of AML cells,which may be related to the upregulation of miR-497-5p expression and downregulation of HSPA8 expression.