Lirispirolides A-L (1-12), twelve novel sesquiterpene-monoterpene heterodimers featuring distinctive carbon skeletons, were isolated from the branches and leaves of Chinese tulip tree [Liriodendron chinense (L. chinense)], a rare medicinal and ornamental plant endemic to China. The structural elucidation was accomplished through comprehensive spectroscopic analyses, quantum-chemical calculations, and X-ray crystallography. These heterodimers exhibit a characteristic 2-oxaspiro[4.5]decan-1-one structural motif, biosynthetically formed through intermolecular [4 + 2]-cycloaddition between a germacrane-type sesquiterpene and an ocimene-type monoterpene. The majority of the isolated compounds demonstrated significant anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced BV-2 microglial cells by reducing the production of pro-inflammatory mediators, specifically tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Further investigation revealed that the lirispirolides' inhibition of NO release correlated with decreased messenger ribonucleic acid (mRNA) expression of inducible NO synthase (iNOS).
Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Animals ; Mice ; Tumor Necrosis Factor-alpha/genetics* ; Nitric Oxide/immunology* ; Microglia/immunology* ; Molecular Structure ; Liriodendron/chemistry* ; Monoterpenes/isolation & purification* ; Plants, Medicinal/chemistry* ; Cell Line ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; China

BACKGROUND:Prosthesis loosening and wear are still the main problems in the failure of total ankle replacement,which are closely related to the micro-motion of the implant-bone interface,the contact stress of the articular surface and joint motion.The design of artificial joint components,including insert and tibial/talar stem prosthesis,is a key factor affecting the force,motion,and micromotion of the contact interface of the ankle joint.The development of new inserts is of great significance to improve the survival rate of artificial ankle joints. OBJECTIVE:The finite element model of the total ankle replacement model was constructed to detect the biomechanical properties of the porous structure-optimized inserts,and the effect of the porous structure-optimized inserts on reducing prosthesis micromotion and improving the contact behavior of the articular surface was analyzed. METHODS:Based on the CT scan data of the right ankle joint of a healthy adult and the INBONE Ⅱ system product manual,a three-dimensional model including bone and artificial joint system was established,and the total ankle replacement model(model A)was obtained after osteotomy and prosthesis installation,and then through four new types of inserts,G50,G60,D50,and D60,were obtained by transforming the porous structure of the original insert,and the original one was replaced with different inserts to establish an optimized total ankle replacement model(models B-E)corresponding to the inserts.The gait loads were applied on the five models to simulate the gait conditions.The differences in micromotion and articular surface contact behaviors at the implant-bone interface of all five models were compared. RESULTS AND CONCLUSION:(1)In the gait cycle,the micromotion of the prosthesis of the four optimized total ankle replacement models was lower than that of the original model.Compared with model A,the micromotion of the prosthesis in models B-E decreased by 5.4%,10.1%,8.1%,and 20.9%,respectively.The high micromotion area of t ??he tibial groove dome in the optimized model was significantly smaller than that of the original model.(2)The four optimized models obtained a larger articular surface contact area.Compared with model A,the average contact area of t ??he inserts in models B-E increased by 11.8%,14.7%,8.1%,and 32.6%,respectively.(3)Similar to the effect of increasing the contact area,compared with the original model,the contact stress of the optimized model decreased in varying degrees,and the value of model E decreased the most significantly(P<0.05),it is due to good mechanical properties and large porosity of the Diamond lattice that constitutes the D60-type insert.(4)The research results show that the use of porous structure to improve the inserts can improve the elasticity of the inserts and increase its ability to absorb joint impact,for favorable conditions are created for reducing micromotion at the implant-bone interface and improving joint contact behavior.

Objective:To screen the differentially expressed immune-related genes(DEIRGs)in in-stent restenosis(ISR),and to analyze the immune cell infiltration in ISR,and to clarify the mechanism of occurrence and development of ISR.Methods:The mRNA gene expression data of GSE46560 dataset samples were downloaded from the Gene Expression Omnibus(GEO),and divided into ISR group and non-ISR group.The"Limma"package in R software was used to identify the differentially expressed genes(DEGs)which were then intersected with immune-related genes(IRGs)to identify the DEIRGs in ISR;R software was used for Gene Ontology(GO)functional enrichment andalysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis on DEIRGs;the STRING database was used to construct the protein-protein interaction(PPI)network,which was visualized and analyzed for Hub genes by Cytoscape software;the receiver operating characteristic(ROC)curve of the Hub genes were plotted,and the area under the curve(AUC)was calculated and the diagnostic value was evaluated;CIBERSORT software was used to analyze the immune cell infiltration in ISR;Pearson correlation analysis was used to analyze the relationships between the immune cells and the relationships between the immune cells and key genes.Results:A total of 331 DEGs were identified(P<0.05,|log2FC|>1),including 176 upregulated genes and 155 downregulated genes,and 38 DEIRGs were obstained.The GO functional enrichment analysis results showed that the DEIRGs were mainly enriched in biological processes(BP)such as defense response,immune response,and immune system;in cellular components(CC),the DEIRGs were located primarily in the extracellular region and cytoplasmic membrane;and in molecular functions(MF),the DEIRGs were mainly involved in regulating signaling receptor binding and cytokine receptor activity.The KEGG signaling pathway enrichment analysis results indicated that the DEIRGs in ISR were primarily enriched in the phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and transforming growth factor-β(TGF-β)signaling pathways.In the PPI network,CD19 had the highest node among the top 10 Hub genes.Compared with non-ISR group,the expression level of the CD19 gene in the samples in ISR group was increased(P<0.05).The AUC value in the ROC curve of CD19 gene expression was 0.92(P<0.05).The immune cell infiltration analysis results showed that compared with non-ISR group,the infiltration level of T lymphocyte follicular helper(Tfh)cells in the patients in ISR group were increased(P<0.05),the infiltration levels of immature B lymphocytes,CD8+T lymphocytes,naive CD4+T lymphocytes,and M0 macrophages were increased,but the differences were not statistically significant(P>0.05),while the infiltration levels of memory B lymphocytes,activated memory CD4+T lymphocytes,regulatory T cells,resting natural killer(NK)cells,activated NK cells,monocytes,resting mast cells,and neutrophils were decreased,but the differences were not statistically significant(P>0.05).There were positive correlations between Tfh cells and M0 macrophages and resting mast cells(r=0.88,P<0.05;r=0.68,P<0.05),and there were negative correlations between Tfh cells and monocytes and neutrophils(r=-0.49,P<0.05;r=-0.42,P<0.05).Conclusion:CD19 may influence the occurrence and development of ISR by regulating the activation of the PI3K-AKT signaling pathway to affect the Tfh and B lymphocytes.CD19 can serve as a biomarker for the diagnosis of ISR.

This paper reviews the research progress on live-cell super-resolution fluorescence microscopy, discusses the current research status and hotspots in this field, and summarizes the technological application of super-resolution fluorescence microscopy for live-cell imaging. To date, this field has gained progress in numerous aspects. Specifically, the structured illumination microscopy, stimulated emission depletion microscopy, and the recently introduced minimal photon fluxes microscopy are the current research hotspots. According to the current progress in this field, future development trend is likely to be largely driven by artificial intelligence as well as advances in fluorescent probes and relevant labelling methods.
Artificial Intelligence ; Microscopy, Fluorescence ; Fluorescent Dyes ; Technology

Colorectal cancer is one of the most common malignant tumors of digestive tract. In 2020， 1.93 million new cases of colorectal cancer were diagnosed globally， ranking third in the global incidence spectrum， and 930 000 new deaths were reported， ranking second in the global cause of death spectrum. Meanwhile， the medical cost of metastatic colorectal cancer is the highest among all stages. A large number of studies have demonstrated that traditional Chinese medicine（TCM） treatment can bring clinical benefits to patients with metastatic colorectal cancer with unique efficacy. In order to further standardize the TCM diagnosis and treatment for metastatic colorectal cancer and improve the level of TCM diagnosis and treatment， Xiyuan Hospital， China Academy of Chinese Medical Sciences， together with other relevant units in China， according to the guideline development process of the World Health Organization Handbook for Guideline Development and the relevant requirements of the Clinical Evidence Grading Criteria on TCM Based on Evidence Body， the Regulations for Group Standards of China Association of Chinese Medicine and others， combined with the characteristics of TCM diagnosis and treatment and the actual situation in China， the Guidelines for TCM Diagnosis and Treatment of Metastatic Colorectal Cancer was developed in accordance with the Catalogue of TCM Diagnosis and Treatment Plans for 105 Diseases in 24 Specialties issued by Department of Medical Administration of National Administration of TCM.

In order to carry out the " Healthy China 2030″ initiative, accelerate the cloud-based transformation of hospital information platforms, promote the construction of smart hospitals, and improve hospital informatization service capabilities, a tertiary hospital launched a comprehensive cloud-based practice for hospital operations in November 2020. A high-availability medical cloud platform designed for large general hospitals was built, by renting from carriers the Internet data center, installing highly scalable infrastructure, building multi-loop self-healing fiber-optic private network, applying the cloud-based software architecture using microservices and distributed storage, and implementing distributed systems′ full-link log and performance monitoring. In February 2021, the hospital migrated its medical care and operation management services on the cloud, achieving unified management of multiple hospital campuses, and reducing manpower and capital investment in computer room constructions. This practice ensured the continuity of hospital business, promoted the regional medical cooperation and the sinking of high-quality medical resources, and provided a reference for speeding up the promotion of nationwide hospital business to the cloud.

Objective:To study the influencing factors of postoperative complications in patients with malignant biliary obstruction treated by endoscopic radiofrequency ablation(RFA).Methods:Data of patients with malignant biliary obstruction who underwent endoscopic RFA at the Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine from January 2010 to June 2021 were retrospectively analyzed. There were 62 males and 48 females, with age (74.1±11.1) years. Based on occurrence of postoperative complications, these patients were divided into the complication group ( n=18) and the control group ( n=92). Univariate and multivariate logistic regression analysis were used to analysis the influencing factors of complications. Results:RFA was successfully performed in 110 patients with malignant biliary obstruction, and the technical success rate was 100.0% (110/110). Postoperative complications occurred in 18 patients (16.4%), including 12 patients with of biliary tract infection (8 patients with acute cholangitis, 4 patients with acute cholecystitis) and 6 patients with acute pancreatitis. All these patients responded well to treatment. The proportion of patients who developed complications having associated diabetes, bile duct stenosis length >2.5 cm, fractional RFA for bile duct stenosis, and single stent drainage were significantly higher than those in the control group (all P<0.05). Multivariate logistic regression analysis showed that the risk of complications after endoscopic RFA was significantly increased in patients with diabetes ( OR=6.967, 95% CI: 1.256-38.658) and fractional RFA of bile duct stenosis ( OR=8.297, 95% CI: 1.526-45.122), while the risk of complications after multiple stents drainage ( OR=0.037, 95% CI: 0.008-0.169) was significantly decreased (all P<0.05). Conclusion:Diabetes and fractional RFA of bile duct stenosis were risk factors for complications after endoscopic RFA of malignant biliary obstruction. Multiple stents drainage was a protective factor. Better clinical attention should be paid to the patients with high risk factors.

Objective:To investigate breast ultrasound imaging and pathological characteristics of patients with hereditary breast cancer-ovarian cancer syndrome (HBOC).Methods:A total of 12 patients with HBOC admitted to Shanxi Province Cancer Hospital from January 2012 to 2021 April were retrospectively analyzed. All patients were pathologically diagnosed as invasive breast cancer based on the preoperative puncture or surgical specimens, including 3 patients with double primary cancers of breast and ovary. The clinical, breast ultrasound imaging and pathological data of patients were analyzed.Results:The ultrasound imaging of HBOC usually showed regular morphology in 8 cases, clear border in 9 cases, no burr sign in 10 cases, no calcification in 10 cases, rear echo in 10 cases; the maximum blood flow velocity was (0.21±0.09) m/s, the vascular resistance index was 0.72±0.17, and aspect ratio ≤ 1 in 8 cases. Among 12 cases of HBOS, 9 cases were invasive ductal carcinoma, 3 cases were breast cancer with medullary features; histological grade: 7 cases of grade Ⅱ, 5 cases of grade Ⅲ; molecular classification: Luminal B type in 2 cases, human epithelial receptor 2 (HER2) type in 4 cases, and triple-negative type in 6 cases. The histological types of 3 patients with double primary cancers of breast and ovary were all high-grade serous carcinoma.Conclusions:HBOC is a type of neoplastic disease with a special genetic background. Ultrasound and pathological manifestations have certain characteristics. Sonographers should improve the understanding of the disease and pay attention to the medical history and family history in order to reduce the rate of misdiagnosis and increase the rate of diagnosis.

Dysregulated crosstalk between different signaling pathways contributes to tumor development, including resistance to cancer therapy. In the present study, we found that the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase (ERK) signaling. In particular, the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling pathways. Furthermore, the combination of the two inhibitors resulted in a reduced tumor burden in mice. Our evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC) cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.

December of 2019 witnessed the outbreak of new coronavirus pneumonia in Wuhan city and a few localities. As a designated hospital, Tongji Hospital is designated as a hospital for the diagnosis and treatment of numerous patients of such a disease. Based on the medical cloud platform, the hospital has initiated a regional remote diagnosis center; based on its IT system, the hospital to operate its epidemic prevention and management mechanism, set up the self-service system for patients at the fever clinic, launched its online diagnosis and treatment services, and established a hospital epidemic supervision platform. By strengthening the informational support needed for epidemic prevention and control, the hospital has enhanced its efficiency of epidemic prevention and control, reducing the risk of cross-infection, and ensuring data security. Its experiences offer references for informationization support for other regions and hospitals in China.