Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Objective:To explore the best treatment for local ablation of colon cancer liver metastases (CRLM) by meta-analysis.Methods:The electronic databases of PubMed, Web of Science, Embase, CNKI and the Cochrane Library were searched from the establishment to August 22, 2022, and studies that report outcomes with comparison between microwave ablation (WMA) and radiofrequency ablation (RFA) in CRLM treatment were selected by inclusion and exclusion criteria. Furthermore, the perioperative and survival data were statistically summarized and analyzed by Review Manager 5.3 software.Results:A total of 5 retrospective studies were included with a total sample size of 648 cases, including 316 cases (48.8%) in the WMA group and 332 cases (51.2%) in the RFA group. The results of meta-analysis showed that locoregional recurrence rate in WMA group was significantly lower than that in RFA group. The 1-year and 2-year disease-free survival (DFS) of the WMA group was significantly better than that of the RFA group with HR of 1.77 ( P=0.04, 95% CI: 1.04-3.02) and 1.60 ( P=0.02, 95% CI: 1.09-2.35), respectively. Conclusion:The local control rate and 1-year and 2-year DFS of WMA were superior to RFA.

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

OBJECTIVE: To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism. METHODS: Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq). RESULTS: Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level. CONCLUSION LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
Acetylation ; Animals ; Inflammation Mediators ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Mice ; Tumor Necrosis Factor-alpha/metabolism*

ObjectiveTo explore the mechanism of Fangji Fulingtang in the treatment of acute kidney injury （AKI） induced by ischemia-reperfusion based on network pharmacology and experimental verification. MethodActive components of Fangji Fulingtang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and previous report and targets of these components were predicted by SwissTargetPrediction. The targets of AKI were searched from GeneCards， Online Mendelian Inheritance in Man （OMIM）， the database of gene-disease associations （DisGeNET）， and Therapeutic Target Database （TTD）. Protein-protein interaction （PPI） network was constructed by STRING. Metascape was used for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment of core targets. Cytoscape was employed to construct the "medicinal-active component-target-disease" network and “active component-target-pathway” network. AutoDock was applied for molecular docking. Finally， animal experiment was carried out to validate the mechanism of Fangji Fulingtang in treatment of AKI. ResultA total of 137 active components and 858 targets of Fangji Fulingtang， 1 294 targets of AKI， and 267 targets of Fangji Fulingtang in the treatment of AKI were screened out. Phosphoinositide-3-kinase regulatory subunit 1 （PIK3R1）， phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA）， proto-oncogene tyrosine protein kinase （SRC）， protein kinase B1 （Akt1）， and mitogen-activated protein kinase 3 （MAPK3） were the key anti-AKI targets of Fangji Fulingtang， which were involved in 1 609 GO terms， particularly cell response to lipids， membrane rafts， and protein kinase activity， and 140 KEGG pathways such as PI3K/Akt signaling pathway， chemokine signaling pathway， and Toll-like receptor signaling pathway. Molecular docking showed that the core active components had strong binding affinity to the key targets. The hematoxylin and eosin （HE） staining results indicated that Fangji Fulingtang can significantly improve the pathological state and the serological results suggested that the levels of serum creatinine （SCr） and blood urea nitrogen （BUN） were significantly reduced. ConclusionThis study clarified the mechanism of Fangji Fulingtang in the treatment of AKI and found that Fangji Fulingtang had the multi-component， multi-target， and multi-pathway characteristics in the treatment of AKI. The result lays a foundation for further study of its specific mechanism.

In this study, 24 copies of samples of Chrysanthemum morifolium and soil from two main production towns in Macheng city were collected, and the contents of 13 mineral elements, 5 effective components and 14 soil nutrient factors in Ch. morifolium were determined. The enrichment characteristics of available soil nutrients by mineral elements were analyzed and the dominant factors affecting the effective components of Ch. morifolium were screened. The results showed that the content of mineral elements and soil nutrients and effective components are very different, and variation of soil fertility was much greater than that of inorganic elements in chrysanthemum plants. In general, the level of element content in Ch. morifolium from different producing areas is K>N>P>Mg>Ca>Fe>Mn>Zn>Cu>Ni>Cr>Pb>Cd. The content of K, N and Mg is higher than that of common crops, and the content of Cu, Cd and Pb in Ch. morifolium from various producing areas does not exceed the relevant standards. The N, P and K enrichment capacity in soil was stronger than that of other elements, and the Ca enrichment ability was the worst. The content of AvCu in the soil was positively correlated with the contents of N, Mg, K, Fe and Cu elements in Ch. morifolium. The contents of chlorogenic acid, luteolin, 3,5-O-dicaffeoylquinic acid reached the pharmacopoeia standard. The percentage of chlorogenic acid and 3,5-O-dicaffeoylquinic acid in Ch. morifolium that from Huangtugang town in the active components were generally higher than that from Futianhe town, and the diffe-rences of luteolin contents in the two producing areas were relatively small. The correlation and regression analysis showed that the contents of Cu, Zn and Cr in Ch. morifolium were positively correlated with the active components, while the contents of Fe, Mn and Ni were negatively correlated with the contents of AvP, AvK, TK, AvMn and AvCu in soil. In general, Zn and Ca fertilizer should be added to the ecological planting of Ch. morifolium, K fertilizer should be added, and N and P fertilizer should be applied appropriately.
Chrysanthemum ; Fertilizers ; Minerals ; Nutrients ; Soil

Objective:To evaluate the clinical efficacy and adverse events of 192Ir high-dose rate brachytherapy (HDR-BT) in the treatment of locally recurrent non-small cell lung cancer (NSCLC). Methods:Clinical data of 22 cases of recurrent NSCLC after radiotherapy admitted to our hospital from September 2013 to March 2018 were retrospectively analyzed. 192Ir HDR-BT was adopted for reradiotherapy. The prescription dose was 30Gy for 1 fraction. CT scan was reviewed every 1 month in the first 3 months after treatment and every 3 months after 3 months. Local control rate and adverse events were evaluated. The 1-and 2-year overall survival (OS) rates of re-treatment after relapse were calculated. Results:All the 22 patients completed the treatment successfully. The 1-, 3-and 6-month complete response (CR) rates were 9%, 14% and 14%, 82%, 82% and 82% for the partial response (PR) rates, 5%, 0% and 0% for the stable disease (SD) rates, 5%, 5% and 5% for the progressive disease (PD) rates, 91%, 96% and 96% for the objective response rates (ORR), respectively. The 1-and 2-year OS rates of re-treatment after relapse were 59% and 27%. Five patients (23%) experienced acute radiation-induced pneumonitis (3 cases of grade 1 and 2 cases of grade Ⅱ), 4 cases (18%) of radiation-induced bone marrow suppression (3 cases of grade I leukopenia and 1 case of grade I thrombocytopenia) and 1 case of postoperative pneumothorax. All these adverse events were mitigated after symptomatic treatment.Conclusion:192Ir HDR-BT is an efficacious and safe treatment of locally recurrent NSCLC.

Objective:To study the optimal surgical strategy for patients with hepatocellular carcinoma (HCC) presenting with spontaneous rupture and hemorrhage.Methods:The electronic databases of PubMed, Web of Science, Embase, and Cochrane Library were searched, and studies reporting on survival outcomes comparing emergency resection (ER) and transarterial embolization followed by hepatectomy (SH) were included by using predetermined inclusion and exclusion criteria. The perioperative and survival data were compared using the Review Manager 5.3 software.Results:Eight retrospective studies were included. The total sample size was 556, with 285 (51.3%) in the ER group and 271 (48.7%) in the SH group. Perioperative blood loss ( WMD=683.61, 95% CI: 283.36-1 083.86, P=0.0 008) and blood transfusion volume ( WMD=453.43, 95% CI: 250.27-656.58, P<0.0 001) in the SH group were significantly less than those in the ER group. There were no significant differences in operative time, incidences of complications, mortality and recurrence rates of tumors between the two groups (all P>0.05). The 1-, 2-, 3-year overall survival and 1-, 2-, 3-, 5-year disease-free survival of the ER group were not significantly different from those of the SH group (all P>0.05). The 5-year overall survival rate of the ER group was significantly lower than that of the SH group ( HR=1.52; 95% CI: 1.14-2.03, P=0.005). Conclusions:There was no significant difference in short-term outcomes in treatment of ruptured HCC, SH was superior to ER in long-term survival outcomes.

Aging is one of the most important risk factors for human diseases such as cancer, cardiovascular diseases, diabetes and neurodegenerative diseases, and many aging diseases are related to cellular aging. Cells show profound phenotypic changes during aging, which are driven by changes in metabolism, chromatin organizationand transcriptional activity. A significant feature of aging is the secretion of inflammatory mediators, including various cytokines, chemokines, extracellular matrix proteins and growth factors, collectively known as the aging-related secreted phenotype (SASP). By secreting SASP, senescent cells have important effects on many biological processes, such as wound healing, tissue repair, tumor formation, or in vivo reorganization. In addition, the inflammatory response associated with SASP is considered to be the basis of aging-related diseases, and the discovery of new targets to control the response of aging effects is crucial. Recent scientific advances have shown that innate immune responses, particularly those involving the cGAS-STING pathway, trigger SASP. In this article, we review the biological function and regulatory mechanism of SASP through the cGAS-STING signaling pathway in aging diseases.

Objective: To investigate the efficacy and feasibility of ¹⁹²Ir high-dose rate brachytherapy for recurrent intrapulmonary oligometastasis after colorectal cancer surgery. Methods: Patients from May 2013 to October 2017 with intrapulmonary oligometastasisafter colorectal cancer surgery in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital were enrolled. A total of 15 lesions were obtained from 10 patients, which were treated with CT-guided high dose rate of ¹⁹²Ir. The implant needles were inserted into the tumor and were adjusted to appropriate positions under the guidance of CT. Then the images after transplanting were uploaded to the planning system to delineate the target area and the organ at risk volume. Patients underwent a single radiation dose of 20 Gy. Results: All 10 patients were successfully treated. Grade 1 adverse events were observed for 30% of patients. Of the 10 patients, one patient had a mild cough, and two had bloody sputum. There was no serious adverse events occurred. The local control rate (LC) of the patients at 1 year after treatment was achieved in 93.3%. Only one developed local advancement after six months, who received the secondary brachytherapy. The median progression-free survival(PFS) was 8.5 months and the median overall survival(OS) was 14.7 months. Conclusions High dose rate brachytherapy is effective in terms of recurrent lung metastases after surgery for colorectal cancer, with a moderate rate of adverse reactions and a favorable local tumor control rate.