AIM: To investigate the protective effect of Jianpi Bushen Yishi Formula on dry age-related macular degeneration(dARMD)induced by sodium iodate in mice and its mechanism.METHODS: A total of 27 SPF male C57BL/6 mice were randomly divided into blank, model and traditional Chinese medicine groups, with 9 in each group, the structure and morphology of the retina were observed by Hematoxylin-Ehong(HE)staining, and the intracellular reactive oxygen species(ROS)in the retina were observed by fluorescence staining with dihydroethidium(DHE). In addition, malondialdehyde(MDA)and superoxide dismutase(SOD)expression levels in mouse retina were detected by biochemical kit, and expression levels of silent information regulator type 1(SIRT1)and peroxisome proliferator-activated receptor-γ coactivator 1-α(PGC-1α)protein in mouse retina were detected by Western blot.RESULTS: Retinal structure and morphology of the model group showed a slight or mild decrease in the number of cells in the outer nuclear layer, a localized thinning of the outer nuclear layer, an inconspicuous demarcation between the outer and outer membranes, a slight or mild swelling of retinal pigment epithelial cells, and a slight or mild disturbance in the arrangement of retinal cells; while retinal pigment epithelial cells and photoreceptor layers in the traditional Chinese medicine group were significantly improved. DHE staining fluorescence results showed that the ROS level in the model group was significantly higher than that in the blank group at 14 d after modeling(P<0.01); the ROS level in the traditional Chinese medicine group was significantly lower than that in the model group(P<0.001). ELISA showed that the SOD level of the model group was significantly lower than that of the blank group at 14 d after modeling(P<0.01), and the MDA level was significantly increased(P<0.01)in the model group compared with the blank group; the SOD level was significantly higher(P<0.01), and the MDA level was significantly lower(P<0.01)in the traditional Chinese medicine group compared with the model group. Western blot results showed that the expression of SIRT1 and PGC-1α in the model group was significantly lower compared with that in the blank group(P<0.01), and the expression of SIRT1 and PGC-1α in the traditional Chinese medicine group was significantly higher compared with that in the model group at 7 and 14 d after modeling(P<0.01).CONCLUSION: The Chinese herbal medicine, which strengthens the spleen, tonifies the kidney and benefits the eyesight, can improve the oxidative stress state of the retina induced by sodium iodate in mice and reduce the damage to the retinal tissues, which may exert the anti-oxidative stress effect through the PGC-1α/SIRT1 signaling pathway.

Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.

Objective To identify the risk factors of patients with frequent acute exacerbations of chro-nic obstructive pulmonary disease(AECOPD)and construct a prediction model based on the clinical data,provi-ding a theoretical basis for the clinical prevention and treatment.Methods A total of 25 638 COPD patients ad-mitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic(ROC)curve.Results In the patients with frequent AECOPD,male percentage(P＜0.001),age(P＜0.001),urban residence(P＜0.001),smoking(P＜0.001),length of stay(P＜0.001),total cost(P＜0.001),antibiotic cost(P＜0.001),diabetes(P=0.003),respiratory failure(P＜0.001),heart disease(P＜0.001),application of systemic glucocorticoids(P＜0.001),white blood cell count(P＜0.001),neutrophil percentage(P＜0.001),C-reactive protein(P＜0.001),total cholesterol(P＜0.001),and brain natriuretic peptide(BNP)(P＜0.001)were all higher than those in the patients with infre-quent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabe-tes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,re-spiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899(95％CI=0.892-0.905),the sensitivity of 85.30％,and the specificity of 79.80％.Conclusions Frequent AECOPD is associated with smoking,heart disease,ap-plication of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevat-ed BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide the-oretical support for the treatment and risk factor management of the patients.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

The deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.

OBJECTIVE: To investigate the role of platelet-rich plasma (PRP) in inducing the M2 macrophage polarization via regulating AMPK singling pathway. METHODS: The expressions of M1 marker CD11c and M2 marker CD206 in macrophages of blank control group, LPS group, LPS+PRP group, and LPS+PRP+Compound C group were detected by flow cytometry. Western blot was used to observe the effects of PRP on the expression of AMPK-mTOR signaling pathway-related proteins at different times (12 h, 18 h and 24 h) after LPS treatment. RNA interference technology was used to silence the expression of AMPK in macrophages, and the expression of TGF-β protein was subsequently examined by Western blot. RESULTS: LPS significantly reduced the expression of CD206 and increased the expression of CD11c (P <0.05). After the addition of PRP, the expression of CD206 was significantly increased (P <0.05), while the expression of CD11c was significantly decreased (P <0.05). Compared with LPS group, PRP treatment significantly increased the expressions of p-AMPK and p-ULK1 proteins at 12 h, 18 h and 24 h, while significantly decreased the expression of p-mTOR protein (P <0.05). After the addition of AMPK inhibitor Compound C, the expression of CD206 was significantly reduced (P <0.05) and the expression of CD11c was significantly increased compared with LPS+PRP group (P <0.05). After silencing the expression of AMPK in macrophages, the promotion effect of PRP on TGF-β was significantly reduced (P <0.05). CONCLUSION PRP can stimulate the transformation of macrophages to M2 type via AMPK signalling pathway.
Humans ; AMP-Activated Protein Kinases/pharmacology* ; Lipopolysaccharides/pharmacology* ; Macrophages/metabolism* ; Transforming Growth Factor beta/metabolism* ; Platelet-Rich Plasma/metabolism*

Objective:To study the effect of PAD (presentation-assimilation-discussion) class applied in the standardized residency training of dermatovenereology on improving residents' practical operation ability.Methods:A total of 120 residents taking the standardized residency training of dermatovenereology in the Affiliated Hospital of North Sichuan Medical College from November 2018 to December 2020 were selected as the research objects and divided into two groups according to the time order of admission, among which, 60 residents enrolled from November 2018 to November 2019 were selected as the control group, and 60 residents enrolled from December 2019 to December 2020 were selected as the experimental group. The control group adopted the traditional standardized residency training mode, and the experimental group adopted the teaching mode of PAD class. SPSS 22.0 statistical software was used for data analysis. The results of theoretical knowledge assessment and skill operation assessment were compared between the two groups by t test, the evaluation of teaching effect was compared between the two groups by chi-square test, and the satisfaction of teaching was compared between the two groups by rank sum test. Results:The theoretical knowledge [(45.38±4.14) points], skill operation [(42.35±4.32) points] and total score [(88.74± 7.69) points] of the experimental group were higher than those of the control group [(39.62 ± 4.15) points, (36.25±4.27) points, (77.96±7.52) points, respectively], with statistical significance ( P<0.05). The evaluation of teaching effect in the experimental group showed that 49 residents (81.67%) believed that their learning interest had been stimulated; 51(85.00%) improved their self-learning ability; 47(78.33%)improved their ability of analyzing and solving problems; 50(83.33%) improved their doctor-patient communication ability; 49(81.67%) improved their clinical thinking ability; 52(86.67%) improved their teamwork ability; and 50(83.33%) improved their literature retrieval ability. The results of satisfaction showed that the experimental group was significantly higher than the control group in sense of responsibility, teaching methods, teaching contents and self-evaluation. Conclusion:The application of PAD class in the standardized residency training of dermatovenereology plays a positive role in mobilizing the learning enthusiasm of residents and cultivating their independent learning ability, and can significantly improve the practical operation and theoretical awareness of residents.

Cartilage stem cells (CSCs) are cells that self-proliferate, have surface antigen expression, and have multidirectional differentiation potential in the articular cartilage. CSCs, as an ideal source of stem cells, has a good application prospect in stem cell therapy. This article reviews the CSCs markers, cartilage differentiation signaling pathway, and clinical treatment of osteoarthritis.
Cartilage, Articular ; Cell Differentiation ; Chondrocytes ; Humans ; Osteoarthritis ; Stem Cells

Based on the principle of magnetic anastomosis technique, the design of magnetic anastomosis system for endoscopic tissue clamping is proposed. The system includes a semi-ring magnet, a special structure transparent cap and a detachable push rod. With the help of the existing digestive endoscopy and endoscopic tissue gripper, the endoscopic close clamping and anastomosis of the bleeding or perforated tissue can be completed. After the anastomosis, the magnet falls off and is discharged through the digestive tract. Animal experiments showed that the system was easy to use, the fistula was clamped firmly, the magnet was discharged for 7~21 days, and there was no magnet retention and digestive tract obstruction. Further safety verification, optimization of endoscopic operation, the system can be used in clinical trial.
Anastomosis, Surgical ; Animals ; Constriction ; Endoscopy, Gastrointestinal ; Magnetics ; Magnets

Objective:To compare the activity difference of the high affinity humanized CD19 chimeric antigen receptor (CAR)-T cells and murine CD19 CAR-T cells.Methods:Peripheral venous blood T cells from 8 healthy volunteers were collected and infected with humanized and murine CD19 CAR lentivirus. Human and murine CD19 CAR-T cells were prepared and cell proliferation was detected by cell counting kit-8 (CCK-8) method. The cytotoxicity of CD3 + T cells, humanized and murine CD19 CAR-T cells to NALM-6 cells was detected by lactate dehydrogenase assay. Thirty BAL B/c nude mice transplanted with NALM-6 cells were randomly divided into 3 groups with 10 mice in each group and injected humanized CD19 CAR-T cells, mouse CD19 CAR-T cells and control CD3 + T cell via tail vein, respectively. The proportion of NALM-6 cells in peripheral blood and the proportion of CD19 CAR-T cells in T cells from the vein of the inner canthus were detected by flow cytometry. The overall survival of BAL B/c nude mice was observed. Results:The proliferation of mouse and humanized CD19 CAR-T cells were (68.50±0.93)% and (80.63±1.41)%, respectively ( t=20.353, P<0.001) after cultured in vitro for 24 hours, and were (91.38±1.41)% and (148.13±1.25)%, respectively ( t=85.364, P<0.001) after cultured for 48 hours. When the effect to target ratio was 1∶1, there was no difference between the humanized and murine CD19 CAR-T cell group after co-culture for 24 hours ( P=0.169), while the killing activity of humanized CD19 CAR-T cells against NALM-6 cells was higher than that of murine CD19 CAR-T cells ( P<0.01) after 48 hours of co-culture. When the effect to target ratio was 4∶1, the cytotoxicity of humanized CD19 CAR-T cells against NALM-6 cells was higher than that of murine CD19 CAR-T cells in co-culture for 24 and 48 hours ( P<0.01). On the seventh day of CD19 CAR-T cell therapy, the proportion of NALM-6 cells in the peripheral blood of BAL B/c nude mice decreased to the lowest level in the humanized CD19 CAR-T cell group and the murine CD19 CAR-T cell group. After 21 days, the proportion of NALM-6 cells in the murine CD19 CAR-T cell group was higher than that in the humanized CD19 CAR-T cell group ( P21 d=0.001, P28 d<0.001, P35 d<0.001). The proportion of humanized and murine CD19 CAR-T cells in the peripheral blood reached the peaks after 7 days of therapy, and the proportion of humanized CD19 CAR-T cells was higher than that of murine CAR-T cells ( P7 d=0.002). The CD19 CAR-T cells disappeared in the peripheral blood in the murine CD19 CAR-T cell group after 14 days of therapy, while in the humanized CD19 CAR-T cell group it disappeared after 21 days of therapy. The median survival of BAL B/c nude mice in the murine CD19 CAR-T cell group and the humanized CD19 CAR-T cell group was 42 days and 63 days, respectively ( χ2=15.382, P<0.001). Conclusions:High affinity humanized CD19 CAR-T cells have stronger proliferation, higher cytotoxicity and longer survival time compared with those of murine CD19 CAR-T cells. The results indicate that the clinical efficacy of humanized CD19 CAR-T cells would be better than that of murine CD19 CAR-T cells.