Object To investigate the chemical constituents from the whole plant of Notoseris gracilipes Shih Methods Compounds were isolated by various column chromatography and identified by spectral analysis Results Eight sesquiterpene lactones and four other compounds were isolated and identified as jacquilenin (Ⅰ), scorzoside (Ⅱ), ixerisoside D (Ⅲ), austricin (Ⅳ), notoserolide A (Ⅴ), crepidiaside A (Ⅵ), crepidiaside B (Ⅶ), and lactuside B (Ⅷ) The other four were 6, 7 dihydroxycoumarin (Ⅸ), cichoriin (Ⅹ), luteolin 7 glucoside (Ⅺ), and daucosterol ( ⅩⅡ ) Among them, compounds Ⅰ and Ⅱ showed antibacterial activity against Bacillu cereus AS 1 1688 Conclusion All compounds were isolated from this plant for the first time

Objective To investigate the clinical effectiveness of extended care on coronary intervention therapy in patients with acute myocardial infarction. Methods 90 patients with acute myocardial infarction who had been through coronary intervention therapy successfully in our hospital from June 2014 to April 2015 were divided into study group and control group with 45 patients in each according random number table. Patients in control group were treated with routine nursing care intervention while patients in study group were treated with additional extended care. Clinical effectiveness of nursing care in two groups were observed. Results After the intervention of extended care, there were 2 cases with nonfatal myocardial infarction (4. 4％), 3 patients undergoing revascularization for a second time (6. 7％) and one death (2. 2％) in study group, which were significantly fewer than those in control group, the difference was statistically significant(P＜0. 05). 30 cases were satisfied with extended care and 11 cases were somewhat satisfied in study group after intervention. The satisfactory rate in study group was 91. 1％, which was significantly higher than those in control group (66. 7％), the difference was statistically significant (P＜0. 05). According to the results of follow-up visit, nursing compliance of diet, exercise, medication and review in patients of study group was better than that in control group, the differences were statistically significant(P＜0. 05). Conclusion Extended care on coronary intervention therapy in patients with acute myocardial infarction could reduce the incidence of adverse reaction, improve the satisfactory rate of nursing care and improve patients ' quality of life. It was worth promotion.

Hypomyelinating leukodystrophies (HLDs) are a group of neurodegenerative diseases characterized by decreased myelination in the central nervous system, with diverse clinical manifestations like psychomotor retardation and dyskinesia.Some HLDs patients have epilepsy, microcephaly and other clinical manifestations.At present, there is no specific treatment of HLDs, and the prognosis is usually poor.At present, with the wide application of gene screening in clinical practice, many pathogenic genes related to HLDs have been found.It is particularly important to clarify the pathogenesis and clinical phenotypic changes of HLDs.

Objective As a signaling molecule,NO regulates key physiological processes and is closely related to periodontitis.To investigate the effect of flavonoid NO donor composite nanoparticles(G10@HAP/MSN@ZnO@COS)on osteogenic differentiation of periodontal ligament stem cells(PDLSCs)by regulating macrophage polarization.Methods The novel NO donor drug G10 was loaded on hydroxyapatite/mesoporous silicanant particles(HAP/MSN),filled with zinc oxide(ZnO),and then coated with chitosan(COS)to prepare composite nanoparticles(G10@HAP/MSN@ZnO@COS).The best concentration of G10@HAP/MSN@ZnO@COS was screened to promote cell proliferation by CCK-8 cell experiment.After the mouse mononuclear macrophages were stimulated by lipopo-lysaccharide,the mice were divided into four groups:Control group,G10 group,HAP/MSN@ZnO@COS group and G10@HAP/MSN@ZnO@COS group.Each group was cultured with fresh medium,5 μg/mL G10,5 μg/mL HAP/MSN@ZnO@COS and 5 μg/mL G10@HAP/MSN@ZnO@COS for 72 h respectively.ELISA and RT-qPCR were used to detect the expression of cytokines(TNF-α,IL-6,IL-1β,iNOS,IL-10)and mRNA expression in each group,and the phenotypic changes of M1/M2 were evaluated.The supernatant of each culture medium was used as conditioned medium to culture PDLSCs,and the osteogenic ability and cell miner-alization were evaluated by alkaline phosphatase activity test and alizarin red staining.Results CCK-8 experiment showed that G10@HAP/MSN@ZnO@COS of 5 μg/mL could significantly promote the proliferation of PDLSCs.The results of ELISA showed that compared with Control group,the expression of M1 type marker IL-1β,IL-6,TNF-α and iNOS in G10@HAP/MSN@ZnO@COS group was significantly decreased(P＜0.000 1),while the expression of M2 type marker IL-10 was significantly increased(P＜0.000 1).The results of RT-qPCR were consistent with those of ELISA,which showed that the expression of M1-related genes in G10@HAP/MSN@ZnO@COS group decreased significantly(P＜0.01).The results of alizarin red staining and alkaline phosphatase activity test showed that the number of mineralized nodules and alkaline phosphatase activity in G10@HAP/MSN@ZnO@COS-CM group were significantly higher than those in other groups(P＜0.000 1).Conclusion Composite nanoparticles(G10@HAP/MSN@ZnO@COS)can effectively inhibit the polarization of macrophages to M1 phenotype and promote it to M2 phenotypic polarization.The anti-inflammatory microenvironment regulated by G10@HAP/MSN@ZnO@COS can en-hance the osteogenic differentiation of PDLSCs.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

Objective:To evaluate the effect of lower limb neuromuscular electrical stimulation (NMES) on mechanical ventilation patients in intensive care unit (ICU).Methods:Databases including the Cochrane Library, PubMed, Web of Science, Embase, SinoMed, CNKI, VIP and Wanfang database were searched from inception to May 2021. Randomized controlled trails (RCT) about the influence of NMES of lower limbs in patients with mechanical ventilation in ICU were collected. Routine rehabilitation measures were implemented in the control group, while the combination of routine rehabilitation and NMES on the lower limbs was implemented in the observation group. The literature screening, data extracting, and bias risk assessment of included studies were conducted independently by two reviewers. RevMan 5.3 software was used to perform Meta-analysis. Funnel plot was used to test publication bias.Results:A total of 8 RCT were eventually enrolled. The literature quality evaluation results showed that 1 study was grade A and 7 studies were grade B, suggesting that the quality of the included literature was relatively high. The Meta-analysis results showed that NMES in the lower extremities could effectively shorten the duration of mechanical ventilation in ICU patients [standardized mean difference ( SMD) = -0.51, 95% confidence interval (95% CI) was -0.72 to -0.31, P < 0.000 01], increase the maximum inspiratory pressure [MIP; mean difference ( MD) = 14.19, 95% CI was 9.30 to 19.09, P < 0.000 01], and improve the functional status of critically ill patients [functional status score for ICU (FSS-ICU); MD = 10.44, 95% CI was 3.12 to 17.77, P = 0.005] with statistically significances. However, there were no significant advantages in increasing the Medical Research Council (MRC) score ( MD = 2.13, 95% CI was -1.38 to 5.63, P = 0.23), reducing ICU mortality [relative risk ( RR) = 0.80, 95% CI was 0.51 to 1.24, P = 0.31], shortening length of ICU stay ( MD = -0.54, 95% CI was -3.67 to 2.59, P = 0.74), and the combined effect was not statistically significant. Funnel plot based on the duration of mechanical ventilation showed that the distribution of included articles was basically symmetrical, and no publication bias was detected. Conclusions:NMES of the lower limbs can not only shorten the ventilation duration effectively, but also improve the MIP and functional status of mechanically ventilated patients in ICU. However, it has no significant effect on the MRC score, ICU mortality and length of ICU stay of patients with mechanical ventilation. In the future, high-quality, large sample size and multi-center RCT are needed to verify the effects of NMES.

Objective To screen items of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome;To provide reference for the formulation and improvement of the scheme.Methods The Delphi method was used to distribute two rounds of questionnaires to 60 experts in cerebropathy or neurology across the country.Statistical analysis was performed on the questionnaire results of the scheme's items,including the disease names,etiology and pathogenesis,syndrome characteristics,rules and regulations,representative prescriptions,acupuncture and other therapies,and preventive care.Results Totally 42 and 50 valid questionnaires were collected.The experts reached the consensus for the importance of etiology and pathogenesis,rules and regulations,acupuncture and other therapies,and preventive care.In the section on syndrome characteristics,items with low relevance or causing ambiguity were removed.Items that were no longer used in modern times and different prescriptions with the same name were removed from the representative prescriptions.The names of syndromes,rules and regulations were unified.Conclusion The experts generally reached the consensus for the importance of the Clinical Aided Decision Scheme for Stroke Simultaneous Treatment of Disease,Pulse and Syndrome.However,there are still some limitations that require further study and discussion.

Objective:To analyze the clinical effects of the pre-expanded internal mammary artery perforator flap in large chest keloids surgical treatment.Methods:Patients with large chest keloid were treated with the pre-expanded internal mammary artery perforator flap between January 2017 and September 2021. The surgical treatment was divided into two different phases. In the first phase, a tissue expander was implanted beneath the skin within the angiosome of the internal mammary artery perforator. The expander was injected with normal saline once a week. In the second phase, the expander and the keloid tissue were removed, and a pre-expanded internal mammary artery perforator flap was designed to cover the wound. Radiotherapy and hyperbaric oxygen therapy were performed in the postoperative period. The treatment effect was followed up. The postoperative complications were analyzed, and the recurrence and patient satisfaction rates were recorded.Results:A total of 41 patients were enrolled, including 20 male and 21 female patients. The patients’ age ranged from 24 to 64, with a mean disease history of 11.9 years. The mean size of the keloid was 9 cm × 8 cm. Some patients were treated with one expander, but four expanders were needed in some extensive cases. The volume of the expander ranged from 80 to 600 ml. The mean volume was 300 ml, with a mean expansion time of 3 months. The mean flap size was 9 cm × 8 cm. Two cases with distal necrosis were observed. Five cases suffered from partial incision scar hyperplasia. No recurrence occurred during the followed-up period. Thirty-six patients (87.8%) were satisfied with the operation effect, and five (12.2%) thought the effect was acceptable.Conclusions:The pre-expanded internal mammary artery perforator flap is an effective treatment for the large chest keloid. It can provide sufficient skin tissue for wound repair, with a stable blood supply and an excellent curative effect.

Objective To investigate the mechanism underlying gasdermin E(GSDME)-mediated pyroptosis in radiation-induced intestinal injury and to find out whether gasdermin(GSDM)family members regulate pyroptosis through similar signaling pathways.Methods Human normal colon epithelial cells(NCM460)and human colon cancer cells(HT-29)were exposed to radiation of different doses and durations before pyroptosis indicators were evaluated by observing pyroptotic bubbles,cell survival,and the cleavage of pyroptosis execution proteins.HT-29 cells overexpressing GSDME were subjected to radiation,followed by enrichment analysis of pyroptosis-related differentially expressed genes using RNA-seq.Results Radiation induced substantial pyroptosis in NCM460 cells.Overexpression of GSDME in HT-29 cells resulted in substantial radiation-induced pyroptosis.The pyroptosis state of human intestinal cells was simulated in the HT-29 model cell line.Overexpressions of GSDME-N and GSDMD-N resulted in the expression of more than 50％ of the differentially expressed genes in the pyroptosis state.Sequencing analysis showed that the genes in the pyroptosis state were mainly overrepresented in immune response,inflammatory response,and Rapl signaling pathway.Conclusion GSDME activation can mediate radiation-induced pyroptosis by producing GSDME-N fragments.GSDM family members participate in pyroptosis in a similar mode of regulation.Furthermore,radiation-induced activation of GSDME/D may regulate pyroptosis through immune response,inflammatory response,and Rap1 signaling pathway.

Objective To investigate the protective effect and mechanism of glutathione peroxidase 3-(GPx3)modified mesenchymal stem cells(MSC)against radiation-induced lung injury(RILI).Methods GPx3-modified MSCs were injected into the tail vein of mice whose lungs were irradiated with 20 Gy.Lung tissues were collected and sections were stained to observe pathological changes.The expression levels of inflammation-related factors were detected by real time quantitative PCR(qPCR),while the levels of malondialdehyde(MDA),H2O2,and 8-hydroxyguanine(8-OHG)were detected via biochemical experiments.Additionally,RNA damage was assessed by reverse transcription blocking combining with double primer PCR.Results GPx3-modified MSCs significantly improved the pathological damage in post-radiation lung tissues and inhibited the fibrosis process and inflammatory response.GPx3-modified MSCs were able to scavenge reactive oxygen species(ROS)more effectively,resulting in a reduction of lipid peroxidation products such as MDA and oxidative damage to RNA formation of 8-OHG.Conclusion By decreasing ROS accumulation,GPx3-modified MSCs can potentially reduce oxidative damage and attenuate RILI.GPx3-modified MSCs can improve the therapeutic efficacy against RILI.