Objective To observe the effects of Angelica Sinensis Radix and Astragali Radix extract(ASR-AR)on HUVEC pyroptosis;To explore its mechanism of treating coronary microvascular disease.Methods HUVEC were divided into blank group,model group,MCC950 group,ASR-AR low-,medium-and high-dosage groups.After modeling and treatment with drug containing serum,cell viability was detected by CCK-8 method,and cell apoptosis was detected by flow cytometry,phalloidin staining was used to detect cytoskeletal morphology,immunofluorescence staining was used to detect the expressions of VEGF,eNOS,Ang-2,ROS,ET-1 and TXA2,ELISA was used to detect the contents of IL-1β and IL-18 in cell supernatant,Western blot was used to detect the expressions of NLRP3,ASC,Caspase-1 and GSDMD protein in cells.Results Compared with the blank group,the model group showed a decrease in HUVEC cell viability(P<0.01)and an increase in cell apoptosis rate(P<0.01),cellular microfilament structure was in disorder and knotting,the expressions of VEGF and eNOS decreased,and expressions of Ang-2,ROS,ET-1 and TXA2 increased,the contents of IL-1β and IL-18 in cell supernatant increased(P<0.01),and the expressions of NLRP3,ASC,Caspase-1 and GSDMD protein in cells increased(P<0.01).Compared with the model group,ASR-AR low-,medium-and high-dosage containing serum could increase cell viability(P<0.05),decrease cell apoptosis rate(P<0.05),improve cell microfilament structure,elevate VEGF and eNOS expressions,decrease Ang-2,ROS,ET-1,TXA2 expressions,reduce IL-1β and IL-18 contents in cell supernatant(P<0.05),and decrease NLRP3,ASC,Caspase-1 and GSDMD protein expressions(P<0.05).ASR-AR medium-dosage group was more obvious(P<0.05).Conclusion ASR-AR can inhibit pyroptosis of HUVEC induced by AngⅡ,attenuate endothelial cell dysfunction,thus treating coronary microvascular disease,and its mechanism may be related to the inhibition of the assembly of NLRP3 inflammasome.

AIM:To explore the potential targets and mechanisms of Angelica sinensis and Astraga-lus membranaceus ultrafiltration(RAS-AM)in the treatment of radiation induced myocardial fibrosis(RIMF)through network pharmacology combined experimental validation.METHODS:Using the TC-MSP database TCM@TAIWAN The Taiwan Tradition-al Chinese Medicine Database and TCMID Tradition-al Chinese Medicine Database screen the compo-nents and targets of RAS-AM,and use the Swiss Target Prediction database for target prediction.Obtain RIMF disease targets from Gene Cards and OMIM databases,obtain intersection targets of dis-eases and drugs through Wayne's online tool,ob-tain protein interaction relationships(PPIs)through STRING database,and use Cytoscape 3.9.1 soft-ware to construct a visualized network topology di-agram of"drug component target disease".Con-duct GO and KEGG enrichment analysis on core tar-gets through the David database,and use the mi-crobiome platform for mapping.Experimental veri-fication:Sixty Wistar rats were randomly divided in-to a blank group,a model group,a positive drug group,a RAS-AM low-dose group,a RAS-AM medi-um dose group,and a RAS-AM high-dose group.A RIMF model was established using a 38Gy dose of radiation induction,and was administered orally for 4 weeks.The general condition of the rats was also observed.After blood and heart collection in rats,HE staining was used to observe the morpho-logical changes of myocardial tissue,and ELISA and Western blot methods were used to detect key tar-gets for network pharmacology prediction.RE-SULTS:Network pharmacology analysis revealed 34 active components and 705 targets of Angelica si-nensis and Astragalus membranaceus ultrafiltra-tion,with a total of 154 targets,with IL-6,VEGFA,MMP2,MMP9,and ACE as the top five core tar-gets;GO enrichment analysis screened a total of 153 entries,and KEGG enrichment had 25 path-ways.Experimental part:HE staining results showed that the degeneration and necrosis of myo-cardial cells improved in each medication group,the infiltration of inflammatory cells in the myocar-dial interstitium decreased,and the proliferation of fibrous connective tissue in the myocardial intersti-tium decreased.ELISA and Western blot results showed that compared with the normal group,the expression of IL-6,VEGFA,and MMP-9 in the mod-el group increased.Compared with the model groupthe expression of IL-6,VEGFA,and MMP-9 in each medication group decreased to varying de-grees,in a dose-dependent manner.CONCLUSION:RAS-AM may inhibit RIMF by downregulating core targets such as IL-6,VEGFA protein,MMP-9 pro-tein,and regulating inflammatory pathways,colla-gen degradation,and other processes.

Objective:To evaluate the efficacy and safety of 532-nm picosecond laser in the treatment of early-stage facial seborrheic keratosis.Methods:A total of 95 patients with early-stage facial seborrheic keratosis were prospectively enrolled from the Department of Dermatology, General Hospital of Ningxia Medical University between December 2020 and September 2022. All the patients received a session of 532-nm picosecond laser treatment, and were followed up for 6 months. A 4-point scale was used to evaluate the overall improvement of skin lesions for assessing the clinical efficacy. A VISIA skin detector was used to quantitatively determine the characteristic counts, absolute scores, and percentiles of brown spots before and after treatment, and the paired sample t-test was used to compare the quantitative indicators of brown spots before and after treatment. The patients′ pain grades were evaluated, and adverse reactions were recorded. Results:All the 95 patients with early-stage facial seborrheic keratosis received a session of 532-nm picosecond laser treatment, and completed a 6-month follow-up. All the patients achieved over 25% regression of skin lesions in the treatment area, of whom 10 received mild improvement, 17 received favorable improvement, and 68 received marked improvement, with the response rate being 89.47% (85/95). The examination with the VISIA skin detector showed that the characteristic counts (195.19 ± 51.06) and absolute scores (28.80 ± 6.20 points) of brown spots significantly decreased, while the percentiles of brown spots (38.48% ± 10.80%) significantly increased at 6 months after treatment compared with the corresponding baseline indicators (211.48 ± 50.94, 35.16 ± 6.84 points, 30.61% ± 10.27%, t = 12.73, 16.90, -15.73, respectively, all P < 0.001). All the patients experienced varying degrees of pain during the treatment, with the pain scores being 2 - 6 (3.64 ± 1.67) points, but all of them could tolerate the pain and completed the treatment. Temporary postinflammatory hyperpigmentation and hypopigmentation occurred in 9 (9.47%) and 4 (4.21%) patients respectively, and the skin color restored to normal during the 6-month follow-up. Conclusion:The 532-nm picosecond laser was safe and effective for the treatment of early-stage facial seborrheic keratosis.

Myocardial infarction （MI） is a common cardiovascular disease in clinical practice and one of the main causes of cardiovascular mortality. Its pathogenesis is complex and associated with oxidative stress reactions. Nuclear factor E₂-related factor 2 （Nrf2） is a key factor in regulating oxidative stress reactions. It can regulate the expression of heme oxygenase-1 （HO-1）， playing a role in maintaining the oxidative-reductive homeostasis in the body. During the course of MI， the biological activity and levels of Nrf2 and HO-1 decrease， leading to weakened tissue antioxidant and anti-inflammatory capabilities， endothelial damage in myocardial blood vessels， release of vascular cell adhesion factors， and impaired endothelial function. In recent years， many basic research studies have explored the role and mechanisms of traditional Chinese medicine （TCM） in treating MI by modulating the Nrf2/HO-1 signaling pathway. The results have indicated that the Nrf2/HO-1 signaling pathway is an important potential target for TCM in the treatment of MI. This article reviewed the mechanism of the Nrf2/HO-1 signaling pathway in MI and the research progress of TCM in targeting and regulating this pathway， aiming to provide a theoretical basis for the prevention and treatment of MI and further drug development.

Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the "trophectoderm (TE)-like structure" of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Pregnancy ; Female ; Animals ; Mice ; Tetraploidy ; Blastocyst ; Embryo, Mammalian ; Cell Differentiation ; Embryonic Development

AIM: To study the mechanism of Ginseng Yixin granules (QSYXG) in treating ejection fraction preserved heart failure (HFpEF) based on network pharmacology. METHODS: Effective chemical composition information of QSYXG particles was collected through TCMSP database; DisGeNET, GeneCards, OMIM database for obtaining HFpEF related targets; Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF; STRING Construction and analysis of the database PPI network; Cytoscape3.7.2 Software construction network diagram; Docking of the major active components to the core target with the AutoDock Vina software molecules, the results were visualized and analyzed with pymol. RESULTS: A total of 66 components and corresponding targets were obtained, HFpEF corresponds to 1 931 targets, The intersection of 127 targets, the main active ingredients are quercetin, kaempferol, β-sitosterol, etc.; TNF, AKT1, IL-6, P53 and JUN as the core targets, Good docking of the key components with the core targets; Mainly involving the positive regulation of gene expression, signal transduction, negative regulation of apoptotic process, positive regulation of cell proliferation and senescence, hypoxia response, negative regulation of gene expression, inflammatory response and so on, PI3K-Akt, AGE-RAG, MAPK, TNF, IL-17, and HIF-1 are the main associated signaling pathways. CONCLUSION: QSYXG may treat HFpEF by activating targets of TNF, AKT1, IL-6, P53, JUN, and regulating apoptotic process, cell proliferation, hypoxia response, and inflammatory response.

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.

Dilated cardiomyopathy is a main disease that causes heart failure and exhibits etiological heterogeneity.Nearly a quarter of dilated cardiomyopathy in patients is related to genetics,and ventricular dilation and myocardial systolic dysfunction are the main characteristics of the disease.LMNA mutation is a major cause of hereditary dilated cardiomyopathy,and arrhythmia is a major clinical manifestation of hereditary dilated cardiomyopathy with LMNA mutation.In recent years,establishment of a dilated cardiomyopathy model in C57/B6 mice and its treatment by focused gene therapy has been a research focus,and some important conclusion have been drawn from the establishment of large animal models in dogs and pigs.However,large animals,especially non-human primates,are closer to humans.At present,dilated cardiomyopathy is not involved in the heart disease model of non-human primates.Therefore,this article reviews studies on rodent and large animal models of dilated cardiomyopathy at the genetic level and proposes the idea of developing a dilated cardiomyopathy model in a non-human primate.It also provides new ideas to study the pathogenesis and clinical treatment.

Heart failure is a common frequently-occurring disease, and it is the terminal stage of the development of various heart diseases. The pathogenesis is very complex and seriously endangers human health. A large number of studies have shown that Ca2+/Calmodulin dependent protein kinase II(CaMKII) plays an important role in the occurrence and development of heart failure. Traditional Chinese medicine has unique advantages and good prospects in the prevention and treatment of heart failure. Among them, there are many compound and their active ingredients can target and regulate CaMKII. This paper mainly expounds the mechanism of the CaMKII signaling pathway in the failing heart and the research progress of traditional Chinese medicine in preventing and treating heart failure by targeting the regulation of CaMKII signaling in recent years, in order to provide reference and expand ideas for clinical traditional Chinese medicine prevention and treatment in heart failure.

Objective:To determine the expression of silent information regulator 1 (Sirt1) , Sirt3 and hypoxia-inducible factor 1α (HIF-1α) in cutaneous squamous cell carcinoma (CSCC) tissues and cells, and to explore their role in the occurrence and development of CSCC.Methods:From January 2019 to December 2020, 30 lesional skin tissues were obtained from patients with histopathologically confirmed poorly-, moderately- or well-differentiated CSCC, and 30 normal skin tissues were obtained from patients with non-cancerous diseases in Department of Dermatology, General Hospital of Ningxia Medical University. A CSCC cell line A431 and a human keratinocyte cell line HaCaT were cultured. Immunohistochemical study, Western blot analysis and real-time quantitative PCR (RT-PCR) were performed to determine the protein and mRNA expression of Sirt1, Sirt3 and HIF-1α in CSCC tissues of different grades of differentiation and normal skin tissues, cytochemical and immunofluorescence staining and RT-PCR were conducted to determine the protein and mRNA expression of Sirt1, Sirt3 and HIF-1α in A431 and HaCaT cells, respectively. Comparisons of measurement data among multiple groups were performed by using one-way analysis of variance, and comparisons between two groups by using t test. Results:Immunohistochemical study showed that the expression level of Sirt3 (expressed as the average optical density) was 100 ± 12.12, 117.72 ± 26.23, 127.32 ± 24.45, 132.71 ± 31.61 in the normal skin tissues and well-, moderately- and poorly-differentiated CSCC tissues respectively, and there was a significant difference among these groups ( F = 20.14, P < 0.001) ; the expression of Sirt1 and HIF-1α increased in turn from the normal skin tissues to the well-, moderately- and poorly-differentiated CSCC tissues, and significantly differred in these groups ( F = 174.50, 225.00, respectively, both P < 0.001) . As Western blot analysis revealed, the expression level of Sirt3 significantly differed among the normal skin tissues, well-, moderately- and poorly-differentiated CSCC tissues (expressed as relative gray value: 1.000 ± 0.132, 1.403 ± 0.411, 1.387 ± 0.393, 1.677 ± 0.683, respectively; F = 34.97, P < 0.001) , and so did the expression levels of Sirt1 and HIF-1α ( F = 69.29, 199.90, respectively, both P < 0.00l) , with a gradually increasing trend in their expression levels from the the normal skin tissues to well-, moderately- and poorly-differentiated CSCC tissues. RT-PCR showed that the mRNA expression of Sirt3, Sirt1 and HIF-1α was sequentially increased from the normal skin tissues to well-, moderately- and poorly-differentiated CSCC tissues, and significant differences were observed among these groups ( F = 113.00, 174.50, 50.33, respectively, all P < 0.001) . The protein expression levels of Sirt3, Sirt1 and HIF-1α were significantly higher in the A431 cells than in the HaCaT cells ( t = 16.75, 18.34, 27.76, respectively, all P < 0.001) , and so were their mRNA expression levels ( t= 14.22, 9.62, 16.86, respectively, all P < 0.001) . Conclusion:Increased expression of Sirt3, Sirt1 and HIF-1α was observed in CSCC tissues and cells, which may promote the occurrence and development of CSCC.