BACKGROUND:A large number of studies have confirmed that the therapeutic effectiveness of mesenchymal stem cell secretome is comparable to that of mesenchymal stem cells,but the mechanism of its action is still unclear. OBJECTIVE:To summarize the research progress of mesenchymal stem cell secretome in recent years,to investigate the molecular mechanism of its therapeutic effect,to analyze the current problems and to look forward to the future development. METHODS:The terms"exosomes,mesenchymal stem cells secrete,extracellular vesicles,mesenchymal stem cells,mechanism"were used as English search terms in the PubMed database.Articles that were not related to the research purpose of the article and duplicated articles were excluded.At the same time,we combined the method of literature tracking.Finally,109 articles that met the criteria were incuded for the review. RESULTS AND CONCLUSION:(1)The mesenchymal stem cell secretome promotes tissue repair and regeneration through delivering genetic material,immunomodulatory factors,growth factors,etc.to target cells,by activating anti-apoptotic,regulating angiogenesis,modulating fibrosis and pro-survival pathways in target cells.(2)The potential of mesenchymal stem cell secretome in disease therapy has also been confirmed.Numerous research results have shown that mesenchymal stem cell secretome can be used as a new cell-free treatment for inflammatory and degenerative diseases.(3)Mesenchymal stem cell secretome has been engineered to have more efficient therapeutic effects in recent years.However,due to the heterogeneity of the mesenchymal stem cell secretome and the complexity of its components,the exact mechanism of its therapeutic effect is still unclear.(4)At present,further research is needed to identify the key targets of mesenchymal stem cell secretome,and innovative specific and enhanced mesenchymal stem cell secretome should be developed by combining with engineering and genetic engineering technologies in the future.

Objective To investigate the underlying mechanisms of the effect of Fufang Changtai Decoction(FFCT)in inhibiting colorectal cancer(CRC)through the ferroptosis pathway using network pharmacology combined with experimental validation.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Swiss Target Prediction databases were employed for the systematic screening of potent active ingredients and therapeutic targets of FFCT.In addition,the identification of CRC-associated genes and ferroptosis-related genes(FRGs)was accomplished using the Gene Cards and FerrDb databases,respectively.Venn diagrams,coupled with Cytoscape software,facilitated the comprehensive analysis of key FRGs involved in FFCT's intervention in CRC by mapping the TCM compound-therapeutic target network.Transmission electron microscopy was used to examine the mitochondrial ultrastructure of SW480 and HCT116,2 Human CRC cell lines,after treatment with FFCT-containing serum.Intracellular reactive oxygen species(ROS)levels were measured using a ROS detection kit.To assess the role of ferroptosis,ferroptosis inhibitor liproxstatin-1(Lip-1)was co-administered with FFCT-containing serum.The effects on cancer cell viability and proliferation were evaluated using CCK-8 and colony formation assays.Key molecular targets involved in the regulatory effects of FFCT on the expression of FRGs were further analyzed using PCR Array and Western blot.The findings were then validated with human CRC tissue microarrays.Results A total of 103 active ingredients of FFCT,739 therapeutic targets,9 101 disease-related genes,and 564 FRGs were identified.Venn diagram analysis identified 81 FRGs associated with FFCT intervention.Network analysis revealed that NQO1,TP53,and PTGS2 served as hub nodes in the regulatory network.Findings from the in vitro experiments showed that FFCT induced ferroptosis changes,including mitochondrial condensation,membrane thickening,and cristae reduction,in SW480 and HCT116 cells.FFCT treatment significantly increased intracellular ROS levels in a dose-dependent manner(P<0.05)and reduced cancer cell viability and proliferative capacity(P<0.01).These inhibitory effects were partially reversed by Lip-1,suggesting that FFCT's antitumor activity was closely associated with the ferroptosis pathway.PCR Array and Western blot analyses further confirmed that FFCT significantly downregulated NQO1 mRNA and protein expression in cancer cells(P<0.001),which was consistent with network pharmacology predictions.Immunofluorescence analysis of clinical CRC tissue microarrays revealed that NQO1 expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.001).Conclusion FFCT may induce intracellular ferroptosis by downregulating the oncogenic gene NQO1,thereby exerting anti-CRC effects.

Objective To explore the economic toxicity perceptions and experiences of caregivers of colorectal cancer patients from the perspective of social ecological systems theory.Methods Using purposive sampling,18 caregivers of colorectal cancer patients hospitalized in the gastrointestinal sur-gery and oncology departments of a tertiary grade A hospital in Yangzhou were selected for semi-struc-tured interviews.The Colaizzi 7-step analysis method was employed to organize and analyze the data.Results Three main themes and nine sub-themes were extracted regarding the economic toxicity expe-riences and needs of caregivers of colorectal cancer patients.Microsystem included multiple negative experiences,impacted individual health,and difficulties in surrogate decision-making;mesosystem in-cluded heavy family financial burden,altered family lifestyle,and tense family atmosphere;macrosys-tem included needs for the scope and intensity of medical insurance reimbursement,needs for medical resources and services,and a desire for social support.Conclusion The ecological system of caregiv-ers of colorectal cancer patients is not optimistic,and is generally affected by economic toxicity.Inter-vention strategies can be sought from multiple aspects,including alleviating the negative experiences of caregivers,strengthening social support,and paying attention to the needs of caregivers,aiming to re-duce the level of economic toxicity among caregivers of colorectal cancer patients.

Objective To analyze the correlation between inflammatory factors and bone mineral density(BMD)as well as β-C-terminal telopeptide of type I collagen(β-CTX)in postmenopausal patients with type 2 diabetes mellitus(T2DM),and to evaluate the diagnostic efficacy of the inflammatory factors in postmenopausal T2DM patients with osteoporosis(OP).Methods A total of 538 postmenopausal women with T2DM,hospitalized in the Department of Endocrinology at the Third People's Hospital of Yunnan Province from October 1,2023 to August 31,2024,were screened,and 181 were ultimately included in the study.Based on bone mineral density,they were divided into the osteopenia group(86 patients,-2.51,B>0),while BMI was an independent protective factor for the occurrence of OP(OR<1,B<0);(4)ROC curve analysis showed that CRP,IL-6,NLR,MLR,and SII all demonstrated diagnostic efficacy for postmenopausal T2DM patients with osteoporosis,among which the combined detection model of CRP,IL-6,and SII exhibited the highest diagnostic efficacy.Conclusion Inflammatory markers are correlated with bone mineral density and β-CTX levels,and may have predictive value for diagnosing osteoporosis in postmenopausal T2DM patients.

Lung cancer is the top cause of cancer deaths globally.Advances in immune checkpoint inhibitors(ICIs)have transformed cancer treatment,but their use in lung cancer has led to more side effects.This study examined if past pulmonary tuberculosis(TB)affects ICIs'effectiveness and safety in lung cancer treatment.We reviewed lung cancer patients treated with ICIs at Beijing Chest Hospital from January 2019 to August 2022.We compared outcomes and side effects between patients with and without prior TB.Of 116 patients(40 with TB history,76 without),prior TB didn't reduce treatment effectiveness but did increase severe side effects.Notably,older patients(≥65 years)faced a higher risk of severe side effects.Detailed cases of two patients with severe side effects underscored TB as a risk factor in lung cancer patients receiving ICIs,stressing the need for careful monitoring and personalized care.

Objective To investigate the expression of TXNIP and NLRP3 in atherosclerotic plaque of coronary artery and their relationship with secondary lesion of plaque and sudden death of coronary heart dis-ease.Methods A total of 105 cases of cardiac coronary samples extracted from autopsy anatomy and related data in the Forensic Judicial Appraisal Center of Guizhou Medical University from January 2019 to March 2022 were analyzed retrospectively.They were divided into the non-lesion group (n=20) and plaque group (n=85) according to whether or not having harden plaque in coronary artery.Then the plaque group was divided into the non-coronary heart disease sudden death group (n=25),coronary heart disease sudden death without sec-ondary lesion group (n=30) and coronary heart disease sudden death complicating secondary lesion group (n=30).The hematoxylin-eosin (HE) dyed section was prepared.The IPP6.0 image analysis software was used to measure the thickness of coronary intima and lesion,the thickness of fibrous cap,the thickness of nec-rotic lesion and the degree of lumen stenosis.Immunohistochemical method,Western blot and real-time fluo-rescent quantitative reverse transcription-PCR (qRT-PCR) were used to detect the distribution characteristics and expression levels of TXNIP and NLRP3 in coronary arteries.Results Compared with the non-lesion group,the thickness of the intima,lesion,fibrous cap and necrosis lesion in the other three groups was thicker,the stenosis degree of lumen was higher,and the differences were statistically significant (P<0.05).Com-pared with the coronary heart sudden death without secondary lesion group,the thickness of the intima,lesion and necrose lesion in the coronary heart disease sudden death complicating secondary lesion group was thic-ker,the necrosis degree of lumen was higher,and the differences were statistically significant (P<0.05).The TXNIP and NLRP3 proteins expressions were not seen in the coronary arterial wall of the no-lesion group.The strong positive expression rates of TXNIP and NLRP3 in the non-coronary sudden death group were 40.0% and 36.0%,the weak positive expression rates were 32.0% and 36.0%,and the weaker positive ex-pression rates were 28.0% and 28.0%.The strong positive expression rates in the coronary heart disease sud-den death without secondary lesion group were 50.0% and 43.3%,the stronger positive expression rates were 33.3% and 36.7%,and the weak positive expression rates were 16.7% and 20.0%;the strong positive ex-pression rates in the coronary heart disease sudden death complicating secondary lesion group were 73.3% and 76.7%,the stronger positive expression rates were 26.7% and 23.3%.The coronary artery TXNIP and NLRP protein and mRNA levels in the coronary heart disease sudden death complicating secondary lesion group were higher than those in the other three groups with statistical difference (P<0.05).TXNIP in coro-nary arterial plaque was positively correlated with the absorbance value of NLRP3 expression absorbance val-ue,protein and mRNA expression level (P<0.05).The TXNIP and NLRP3 expression levels were positively correlated with the intima and lesion thickness,and negatively correlated with the fibrous cap thickness (P<0.05).The necrosis lesion area of coronary artery was positively correlated with the TXNIP and NLRP3 (P<0.05).Conclu-sion TXNIP and NLRP3 could serve as the diagnostic indicators of coronary heart disease sudden death.

BACKGROUND:Based on different algorithms of machine learning,how to carry out clinical research on lumbar disc herniation with the help of various algorithmic models has become a trend and hot spot in the development of intelligent medicine at present. OBJECTIVE:To review the characteristics of different algorithmic models of machine learning in the diagnosis and treatment of lumbar disc herniation,and summarize the respective advantages and application strategies of algorithmic models for the same purpose. METHODS:The computer searched PubMed,Web of Science,EMBASE,CNKI,WanFang,VIP and China Biomedical(CBM)databases to extract the relevant articles on machine learning in the diagnosis and treatment of lumbar disc herniation.Finally,96 articles were included for analysis. RESULTS AND CONCLUSION:(1)Different algorithm models of machine learning provide intelligent and accurate application strategies for clinical diagnosis and treatment of lumbar disc herniation.(2)Traditional statistical methods and decision trees in supervised learning are simple and efficient in exploring risk factors and establishing diagnostic and prognostic models.Support vector machine is suitable for small data sets with high-dimensional features.As a nonlinear classifier,it can be applied to the recognition,segmentation and classification of normal or degenerative intervertebral discs,and to establish diagnostic and prognostic models.Ensemble learning can make up for the shortcomings of a single model.It has the ability to deal with high-dimensional data and improve the precision and accuracy of clinical prediction models.Artificial neural network improves the learning ability of the model,and can be applied to intervertebral disc recognition,classification and making clinical prediction models.On the basis of the above uses,deep learning can also optimize images and assist surgical operations.It is the most widely used model with the best performance in the diagnosis and treatment of lumbar disc herniation.The clustering algorithm in unsupervised learning is mainly used for disc segmentation and classification of different herniated segments.However,the clinical application of semi-supervised learning is relatively less.(3)At present,machine learning has certain clinical advantages in the identification and segmentation of lumbar intervertebral discs,classification and grading of the degenerative intervertebral discs,automatic clinical diagnosis and classification,construction of the clinical predictive model and auxiliary operation.(4)In recent years,the research strategy of machine learning has changed to the neural network and deep learning,and the deep learning algorithm with stronger learning ability will be the key to realizing intelligent medical treatment in the future.

Objective To explore the safety and efficacy of portable ultrasound-guided sacroiliac joint injection in the treatment of sacroiliac joint pain caused by military training injuries of grass-roots officers and soldiers.Methods The clinical data of officers and soldiers with sacroiliac joint pain caused by military training injuries treated in The First Affiliated Hospital of Naval Medical University from April 2020 to April 2022 were collected.Necessary examinations were completed.Patient Health Questionnaire-9(PHQ9)and 7-item Generalized Anxiety Disorder Questionnaire(GAD7)were used to evaluate anxiety and depression.Portable ultrasound-guided sacroiliac joint injection with steroid hormone was adopted.Visual analogue scale(VAS)scores were recorded before treatment and 30 min,1 week and 4 weeks after treatment.Oswestry disability index(ODI)and self-rating scale of sleep(SRSS)were evaluated before treatment and 4 weeks after treatment.The clinical efficacy was evaluated by pain degree,mobility,sleep quality,and complications.Satisfaction survey was conducted 4 weeks after treatment.Results A total of 33 officers and soldiers were enrolled,and 3(9.10% )of them suffered from depression or anxiety.Portable ultrasound-guided sacroiliac joint injection was successfully completed.The scores of VAS,ODI and SRSS at the 4th week after treatment were significantly lower than those before treatment(6.27±0.80 vs.2.97±1.26,72.45±9.54 vs.37.64±10.99,40.70±6.47 vs.20.61±6.02,P<0.05).The overall satisfaction of officers and soldiers was 96.97% .Conclusion Portable ultrasound-guided sacroiliac joint injection is safe,effective,easy to operate.It is suitable for the treatment of sacroiliac joint pain after military training injuries,and clinical efficacy is good during follow-up.It can provide reference for medics in naval combat support ships and grass-roots units.

Animals ; Mice ; Corticotropin-Releasing Hormone/metabolism* ; Neurons/metabolism* ; Brain/metabolism*

OBJECTIVE: To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout. METHODS: The Sidt2 knockout (Sidt2^-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed. RESULTS: Sidt2^-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2^-/- HL7702 cells. CONCLUSION Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.
Humans ; Lysosome-Associated Membrane Glycoproteins/metabolism* ; Autophagy ; Apoptosis ; Hepatocytes ; Lysosomes/metabolism* ; Chloroquine/pharmacology* ; Nucleotide Transport Proteins/metabolism*