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.

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.

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.

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*

BACKGROUND: Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. RESULTS: Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group. CONCLUSION: Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state. TRIAL REGISTRATION Chictr.org, ChiCTR2000039799.
Humans ; Quality of Life ; China ; Arthritis, Rheumatoid/drug therapy* ; Piperidines/therapeutic use* ; Treatment Outcome ; Antirheumatic Agents/therapeutic use* ; Pyrroles/therapeutic use*

In recent years,cortisol has been used as a biomarker to assess stress in dogs.To evaluate the welfare of dogs,we reviewed cortisol levels and changes in dogs under various stresses.We explored the influential factors that relieve stress in accordance with variations in cortisol levels,to improve the measures which reduce stress in dogs.It is recommended to apply cortisol measurement and behavioral observation comprehensively to evaluate stress in dogs more accurately.

ObjectiveTo investigate the clinical and epidemiological features of patients with bacterial liver abscess during the outbreak of coronavirus disease 2019 （COVID－19） in Changchun， China. MethodsA retrospective analysis was performed for 37 411 patients who were discharged from The First Hospital of Jilin University from March 1 to June 30 in 2022， and finally 135 patients with bacterial liver abscess were included for analysis. Related clinical data were collected to summarize their clinical features， and these patients were compared with the patients with bacterial liver abscess in 2019－2021 in terms of disease onset and pathogen. The Kruskal－Wallis H test was used for comparison of continuous data between multiple groups， and the chi－square test was used for comparison of categorical data between multiple groups. ResultsThe patients with bacterial liver abscess accounted for 0.36% of the patients admitted to our hospital during the same period of time， which showed varying degrees of increase compared with the previous years （χ²=32.081， P<0.001）. The 135 patients with bacterial liver abscess had a mean hospital stay of 11 （6－18） days， which was longer than that in the previous years （H=9.223， P=0.026）. The patients with bacterial liver abscess had higher levels of white blood cell count and C－reactive protein （CRP） than the previous years （H=14.150 and 8.736， P=0.003 and 0.033）. Among the 135 patients， 69 （51.11%） received blood culture， and the results showed sterile growth （59.42%）， Klebsiella pneumoniae （30.43%）， Escherichia coli （4.35%）， Bacteroides fragilis （1.45%）， Enterococcus faecium （1.45%）， Staphylococcus epidermidis （1.45%）， and Klebsiella oxytoca （1.45%）. Among the 135 patients， 90 （66.67%） received pus culture， and the results showed Klebsiella pneumoniae （72.22%）， sterile growth （14.44%）， Escherichia coli （4.44%）， Enterococcus faecium （2.22%）， Pseudomonas aeruginosa （2.22%）， Acinetobacter baumannii （1.11%）， Klebsiella aerogenes （1.11%）， Klebsiella oxytoca （1.11%）， and Enterococcus casseliflavus （1.11%）. Of all 135 patients， 127 （94.07%） were improved and cured after anti－infective therapy and ultrasound－guided abscess puncture and drainage， and 3 patients （2.22%） died during hospitalization. ConclusionDuring the outbreak of COVID－19 in Changchun， there are increases in the number of patients with liver abscess in our hospital， the length of hospital stay， and the levels of white blood cell count and CRP， with Klebsiella pneumoniae as the main pathogen， and most patients are improved after treatment.

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

Objective: To investigate the prevalence of dyslipidemia and the level of blood lipids among Tajik people in Pamir Plateau, Xinjiang, and explore the related factors of dyslipidemia. Methods: It is a retrospective cross-sectional study. A multi-stage cluster random sampling survey was conducted among 5 635 Tajiks over 18 years old in Tashkorgan Tajik Autonomous County, Xinjiang Province from May to October 2021. Data were collected through questionnaire survey (general information, medical history, and personal history), physical examination (height, weight, waist, and blood pressure) and blood test (total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density cholesterol (HDL-C)) to analyze the dyslipidemia and its risk factors among Tajiks. Results: The age of Tajik participants was (41.9±15.0) years, including 2 726 males (48.4%). The prevalence of borderline high TC, high LDL-C and high TG levels were 17.2%, 14.7% and 8.9%, respectively. The prevalence of high TC, high LDL-C, high TG and low HDL-C were 4.1%, 4.9%, 9.4% and 32.4%, respectively, and the prevalence of dyslipidemia was 37.0%. There is a positive correlation between male,higher education level, higher body mass index (BMI) value,waist circumference, living in town, smoking and dyslipidemia. Conclusions: The low prevalence of high TC, high LDL-C, high TG and high prevalence of low HDL-C was a major characteristic of Tajik people in Pamir Plateau of Xinjiang. The lower rates of overweight and obesity may be one of the reasons for the lower prevalence of dyslipidemia among Tajik.
Adult ; Humans ; Male ; Middle Aged ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Cross-Sectional Studies ; Dyslipidemias/epidemiology* ; Hypercholesterolemia/epidemiology* ; Hypertriglyceridemia/epidemiology* ; Prevalence ; Retrospective Studies ; Female