ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells （BMSCs） co-cultured with bone marrow-derived M2 macrophages （M2-BMDMs）， named as BMSC^M2， on a rat model of liver cirrhosis induced by carbon tetrachloride （CCl₄）/2-acetaminofluorene （2-AAF）. MethodsRat BMDMs were isolated and polarized into M2 phenotype， and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSC^M2. The rats were given subcutaneous injection of CCl₄ for 6 weeks to establish a model of liver cirrhosis， and then they were randomly divided into model group （M group）， BMSC group， and BMSC^M2 group， with 6 rats in each group. A normal group （N group） with 6 rats was also established. Since week 7， the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl₄. Samples were collected at the end of week 10 to observe liver function， liver histopathology， and hydroxyproline （Hyp） content in liver tissue， as well as changes in the markers for hepatic stellate cells， hepatic progenitor cells， cholangiocytes， and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group， the M group had significant increases in the activities of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in ALT and AST （P<0.01）， and the BMSC^M2 group had significantly better activities than the BMSC group （P<0.05）. Compared with the N group， the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin （α-SMA） in the liver （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in Hyp content and the expression of α-SMA （P<0.05）， and the BMSC^M2 group had a significantly lower level of α-SMA than the BMSC group （P<0.01）. Compared with the N group， the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 （P<0.01） and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb （P<0.01）； compared with the M group， the BMSC and BMSC^M2 groups had significant reductions in the mRNA expression levels of EpCam， Sox9， CK7， and CK19 （P<0.05） and significant increases in the mRNA expression levels of HNF-4α and Alb （P<0.05）， and compared with the BMSC group， the BMSC^M2 group had significant reductions in the mRNA expression levels of EpCam and CK19 （P<0.05） and significant increase in the expression level of HNF-4α （P<0.05）. ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl₄/2-AAF-induced liver cirrhosis in rats， which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.

Objective To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.Methods KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues,4 gastric adenocarcinoma cell lines(MKN-28,HGC-27,CRL-5822,and SNU-1)and normal human gastric mucosal GES-1 cells.In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression,cell proliferation,migration,invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay,Transwell migration and invasion assays,and Western blotting.In BALB/c-nude mice,HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.Results Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells.In HGC-27 cells,KHSRP knockdown significantly inhibited cell proliferation,migration and invasion,while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells.In nude mice,inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight,slower cell proliferation rate and fewer lung metastatic foci,and KHSRP-overexpressing SNU-1 cells produced the opposite results.KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3,which were obviously increased in KHSRP-overexpressing SNU-1 cells.Conclusion High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

Traditional Chinese medicine is a treasure of Chinese civilization,which has undergone thousands of years of precipitati-on and clinical verification.According to the theory of traditional Chinese medicine,ancient doctors used natural medicines and natural means to promote self-regulation and damage repair of the body.In recent years,as an important tool to repair body damage,stem cells have set off a research upsurge.With the continuous deepening of stem cell research and the continuous expansion of the fields in-volved,the potential correlation between traditional Chinese medicine and stem cells has attracted more and more domestic and foreign researchers to invest in research.This paper expounds regenerative medicine and stem cells,the advantages of Chinese medicine in regulating stem cells,and the opportunities and challenges faced by Chinese medicine and regenerative medicine,and reviews the cur-rent research trends and frontier trends in this field,in order to provide useful references for subsequent studies.

Objective·To further clarify the mechanism of podocyte damage by studying the expression of cartilage oligomeric matrix protein(COMP)in glomerular podocytes and its relationship with podocyte autophagy under high glucose environment.Methods·The gene expression dataset GSE104948 was downloaded from the GENE EXPRESSION OMNIBUS(GEO)database,and differentially expressed genes(DEGs)were obtained via GEO2R.The molecular functions and signaling pathways related to differential genes were summarized.The most correlated key genes(hub genes)were acquired by Weighted Gene Co-Expression Network Analysis(WGCNA)and the protein-protein interaction network(PPI)of DEGs was constructed with STRING database.The enrichment analysis was performed again.Conditionally immortalized mouse podocyte cells were cultured in vitro.After being fully differentiated,they were stimulated with high glucose,and the expressions of COMP,mammalian target of rapamycin(mTOR),microtubule-associated protein 1 light chain3(LC3)and other proteins in podocytes were detected by Western blotting.The shRNA constructed by lentiviral vector was further used to infect podocytes to inhibit the expression of COMP,and the stable cell strains were screened by puromycin.The expression of COMP,mTOR,and LC3 of stable strains were detected by Western blotting,in order to observe the effect of COMP on autophagy.Results·A total of 362 DEGs were filtered for subsequent analysis.Among these DEGs,284 genes were up-regulated and 78 genes were down-regulated.The results of Gene Onotology(GO)term analysis showed that DEGs in diabetic nephropathy(DN)were mainly enriched in cell surface receptor signaling pathway,receptor binding,etc.The main enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways included phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway,extracellular matrix(ECM)-receptor interaction,etc.Sixty-four hub genes were refined through the intersection of WGCNA and PPI hub genes,and the hub genes with significantly increased or decreased expression were sifted.The hub genes were annotated with KEGG again,and it was found that most of the hub genes were enriched in"ECM-receptor interaction"and"PI3K/AKT signaling pathway".The PI3K/AKT/mTOR signaling pathway is a classic autophagy pathway,and COMP was absolutely overexpressed(logFC>2)in the 64 hub genes,suggesting that it may affect autophagy through this pathway.Western blotting showed that compared with the mannitol control group and the low glucose group,the expression of COMP in podocytes was significantly increased under high glucose stimulation.Compared with the control group,the expression of LC3-Ⅱ in the high glucose group was significantly decreased,indicating that the autophagy initiation of podocytes was inhibited under the high glucose environment.Compared with the negative control,the expression of LC3-Ⅱ in renal podocytes of mice with knockdown of COMP was significantly increased,and the mTOR decreased with the decrease of the expression of COMP,indicating that inhibiting COMP contributed to the recovery of autophagy in podocytes.Conclusion·COMP is highly expressed in DN patients and highly enriched in ECM receptor and PI3K/AKT signaling pathway.Autophagy in mouse renal podocytes is inhibited under high glucose conditions,and the high expression of COMP induced by high glucose may be a key factor in autophagy inhibition.Inhibiting COMP helps to restore autophagy in mouse renal podocytes.

Objective:To investigate different regulatory effects of S100A8/A9 expressed by keratinocytes in 3 common inflammatory skin injury modes: UVB-induced skin injury, allergic contact dermatitis, and psoriasis.Methods:Wild-type C57BL/6JGpt mice aged 6 to 8 weeks were selected for the following experiments: (1) mouse models of UVB-induced skin injury were established by single exposure to ultraviolet B (UVB) radiation on the shaved dorsal skin of mice (UVB group, n = 4), with the mice receiving no UVB radiation serving as a control group ( n = 4) ; (2) mouse models of allergic contact dermatitis were established by application of 2,4-dinitrochlorobenzene (DNCB) to the right ears of mice (DNCB group, n = 4), with the left ears of mice treated with a vehicle control serving as a control group ( n = 4) ; (3) mouse models of psoriasis-like skin inflammation were established by topical application of imiquimod cream to the depilated dorsal skin of mice (imiquimod group, n = 4), with the mice treated with vaseline serving as a control group ( n = 4). Hematoxylin-eosin (HE) staining was performed to assess histopathological changes in mouse skin tissues obtained from each group, and immunohistochemical study and Western blot analysis were performed to determine the expression of S100A8 and S100A9 in the mouse dorsal epidermis or ear skin lesions. In vitro cultured HaCaT cells were subjected to the following experiments: (1) cells in the UVB group were treated with a single UVB irradiation at a dose of 50 mJ/cm 2, and cells in the control group received no irradiation; (2) some cells were treated with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) (collectively referred to as TI), and named as the TI group, which simulated the inflammatory environment in allergic contact dermatitis, while cells treated with corresponding solvents served as the control group; (3) cells were treated with 5 cytokines (interleukin 17A [IL-17A], IL-22, IL-1α, oncostatin M, and TNF-α, collectively referred to as M5), and named as the M5 group, which simulated the inflammatory environment in psoriasis, while cells treated with corresponding solvents served as the control group. Real-time fluorescence-based quantitative PCR, Western blot analysis, and enzyme-linked immunosorbent assay were performed to determine the mRNA and protein expression of S100A8 and S100A9, and to detect the extracellular secretion level of S100A8/A9, respectively. Results:Immunohistochemical study and Western blot analysis revealed that S100A8 and S100A9 expression levels were significantly higher in the skin lesions of mouse models of UVB-induced skin injury, allergic contact dermatitis, and psoriasis-like skin inflammation than in their corresponding control groups; immunohistochemical study further demonstrated that the increase in the expression of the two proteins was more pronounced in the mouse models of psoriasis-like skin inflammation. In the in vitro cell experiments, the mRNA expression of S100A8 and S100A9 in HaCaT cells at 12 and 24 hours were markedly higher in the UVB group (e.g., at 24 hours, 6.14 ± 0.60 vs. 1.00 ± 0.08, 2.58 ± 0.06 vs. 1.02 ± 0.22, respectively, both P < 0.01), TI group (e.g., at 24 hours, 3.90 ± 0.75 vs. 1.00 ± 0.02, 2.42 ± 0.30 vs. 1.01 ± 0.13, respectively, both P < 0.05), and M5 group (e.g., at 24 hours, 157.59 ± 9.30 vs. 1.00 ± 0.11, 251.37 ± 6.63 vs. 1.00 ± 0.03, both P < 0.001) than in the corresponding control groups, so were the extracellular secretion levels of S100A8/A9 at 24 and 48 hours (all P < 0.001), with some differences observed in their response patterns; notably, the response was more pronounced in the mouse model of psoriasis-like skin inflammation. Additionally, the protein expression levels of S100A8 and S100A9 in HaCaT cells were significantly higher in the M5 group than in the control group ( t = 4.66, 4.63, respectively, both P < 0.01), but were significantly lower in the UVB group ( t = -3.75, -3.34, P = 0.020, 0.029, respectively) and TI group ( t = -3.30, -4.50, P = 0.030, 0.011, respectively) than in the control groups. Conclusion:Keratinocytes exhibited active responses following 3 common inflammatory skin injuries, with their effector molecules S100A8 and S100A9, as damage-associated molecular patterns, playing crucial roles in UVB-induced skin injury, allergic contact dermatitis, and psoriasis, and the response seemed to be more pronounced in psoriasis-like dermatitis.

Objective To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.Methods KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues,4 gastric adenocarcinoma cell lines(MKN-28,HGC-27,CRL-5822,and SNU-1)and normal human gastric mucosal GES-1 cells.In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression,cell proliferation,migration,invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay,Transwell migration and invasion assays,and Western blotting.In BALB/c-nude mice,HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.Results Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells.In HGC-27 cells,KHSRP knockdown significantly inhibited cell proliferation,migration and invasion,while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells.In nude mice,inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight,slower cell proliferation rate and fewer lung metastatic foci,and KHSRP-overexpressing SNU-1 cells produced the opposite results.KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3,which were obviously increased in KHSRP-overexpressing SNU-1 cells.Conclusion High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

In the central nervous system,CX3CL1 is a transmembrane chemokine expressed on neurons,and its specific receptor CX3CR1 is located on microglia.The combination of CX3CL1 and CX3CR1 is regarded as the bond of interaction between neurons and microglia.Bidirectional communication between microglia and neurons is essential for maintaining brain homeostasis and overcoming neuroinflammation,which is thought to play an important role in neurode-generative and cerebrovascular diseases.This article reviews the mechanisms of CX3CL1/CX3CR1 signaling pathway in the proliferation,metabolism,activation,polarization and regulation of synaptic plasticity of microglia,and uses this sig-naling pathway as a target to regulate the role of microglia in the disease process,which may provide a new target for the treatment of inflammation-related diseases.

Objective:To investigate the status and influencing factors of different types of cognitive frailty in aged inpatients with hypertension.Methods:Totally 300 aged patients with hypertension admitted to the Cardiology, Geriatrics, and Endocrinology Departments of Xuanwu Hospital, Capital Medical University, from April to October 2022 were selected by convenience sampling. Data were collected using a general information questionnaire, the Fried Frailty Phenotype (FP), the Mini-Mental State Examination (MMSE), the 9-item Subjective Cognitive Decline Questionnaire-9 (SCD-Q9), the Morisky Medication Adherence Scale (MMAS), the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression Scale (HADS), the Social Support Rating Scale (SSRS), and the Mini Nutritional Assessment (MNA) .Results:A total of 300 questionnaires were distributed and returned, yielding a 100.00% response rate. Among the 300 aged hypertensive patients, 74 were diagnosed with reversible cognitive frailty (RCF) and 98 with potentially reversible cognitive frailty (PRCF). Logistic vegression analysis showed that, factors influencing RCF included daily exercise habits and the use of thiazide diuretics ( P<0.05) ; factors influencing PRCF included age, pre-retirement occupation, daily exercise habits, sleep quality, Barthel Index score, and serum albumin levels ( P<0.05) . Conclusions:The status of both RCF and PRCF is relatively high among aged inpatients with hypertension. The influencing factors for different types of cognitive frailty vary. Targeted interventions based on both common and specific influencing factors should be developed to reverse or slow the progression of cognitive frailty in aged hypertensive patients.

Objective To investigate the independent influences on the occurrence of ICU Acquired Weakness(ICU-AW)in elderly patients undergoing third-and fourth-level surgeries,to construct a prediction model and draw a column-line diagram,and to internally validate the model.Methods A convenience sampling method was used to select 186 elderly patients undergoing tertiary and quaternary surgeries who were hospitalized in 3 tertiary A hospitals in Beijing from May to December 2022 as the study subjects.Single-factor and multifactor logistic regression were used to analyze the risk factors for ICU-AW in elderly patients undergoing third-and fourth-degree surgeries.A risk prediction model was established and the model was visualized by drawing a column-line diagram,and the receiver operator characteristic curve(ROC)and the Hosmer-Lemeshow tests were applied to verify the predictive effect of the model.Results ICU-AW occurred in 40 of 186 cases in the modeling group,with an incidence rate of 21.5％.The results of univariate analysis showed that the 2 groups of preoperative physiology score and surgical severity score included in the physiology and surgical severity scoring system,age,presence of cardiac disease,hemoglobin(within 24 h of admission to the ICU),blood urea nitrogen(within 24 h of admission to the ICU),blood creatinine(within 24 h of admission to the ICU),presence of braking,mode of establishment of mechanical ventilation,presence of nutritional therapy,number of sedative or analgesic drugs used,whether vasoactive drugs were used,whether diuretics were used,and the level of hemoglobin,blood urea nitrogen and blood creatinine within 24 h after admission to ICU the difference is statistically significant(P＜0.05).The results of multifactorial logistic regression analysis showed that preoperative physiology scores included in the physiology and surgical severity scoring system,the presence of cardiac disease,the presence of braking,the presence of nutritional therapy,and the number of sedative or analgesic medications used were the predictors of the occurrence of ICU-AW in elderly patients undergoing third-and fourth-degree surgeries(OR were 1.364,2.344,5.568,5.823,1.109,all P＜0.05).The above 5 factors were plotted as independent variables in a column-line graph,and the area under the ROC curve of the model was 0.859(95％CI 0.793～0.924),with an optimal critical value of 0.156,a sensitivity of 0.875,a specificity of 0.705,and a Hosmer-Lemeshow goodness-of-fit test of x2=3.906,P=0.865,Brier score of 0.109,and a decision analysis curve indicating that patients could benefit.Conclusion The predictive effect of the constructed model is good,and it can be used as a reference for early and rapid identification of the risk of ICU-AW in elderly patients undergoing third-and fourth-degree surgeries by clinical staff,and timely provision of preventive intervention programs.

Dental erosion is characterized by progressively destroyed teeth, which has no relation to bacteria but to chemicals. Some internal factors, such as gastroesophageal reflux induced by bulimia, anorexia, gastrointestinal diseases, or drugs, and external factors, such as diet, drugs, and occupational acid exposure, are considered promotive factors for this disease. This article presents a patient suffering from severe dental erosion in the whole dentition, especially in the maxillary teeth, due to gastroesophageal reflux induced by glucocorticoid therapy for optic neuritis. This article discusses the mechanism between optic neuritis glucocorticoid therapy and dental erosion.
Humans ; Glucocorticoids/therapeutic use* ; Tooth Erosion/therapy* ; Gastroesophageal Reflux/complications*