This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective The mouse autologous tumor model H22 is more valuable for tumor immunological-related research.This paper aims to establish mouse hepatic tumor cell line(H22-luc2-tdT)that stably express the tan-dem-dimer tomato(tdTomato)and luciferase genes.Establish an in vivo imaging model of cell line derived trans-planted tumors.Methods Using transplanted H22 tumor tissue,primary culture and continuous passage in vitro were performed to establish a continuous cell line.Cell proliferation,chromosome analysis,organoid culture,tumorigenicity,HE and ICH of aFP,CK7,CK15 were performed to charaterize the cell line.Then the luc2-tdT plasmid was transfected into H22 cells of P22,flow cytometry and in vitro/in vivo imaging were employed to screen and verify fluorescence expression.Mycoplasma detection and species verification of the established cell lines were performed.Results The H22 cells had been continuously passaged over 50 times.The cells of passsge 22(P22)were transplanted subcutaneously and intraperitoneally into C57 and Kunming mice,with a 100%tumor formation.The HE morphology of subcutaneous transplanted tumor were consistent with the original tumor.CK+/AFP+proved that it was of liver cancer origin.The H22 cells were hypo-triploid with a modal number of 40-44 chromosomes and telocentromeres,verifing its mouse origin.The latent phase for in vitro growth of H22 lasted from d0 to d3,while the exponential phaes d3 to d5,and reach plateou at d6.Successful transfection of H22 cells with the luc2-tdT were observed with in vitro/in vivo 100%fluorescence positivity,thus named H22-luc2-tdT.The transplanted tumor tissue of H22 cells could be primarily cultured to form organoids.The detection of Mycoplasma was negative,and its mouse origin confirmed by PCR.Conclusions H22 and H22-luc2-tdT cell lines are established and characterized,which can be used for the establishment and application of in vitro and in vivo liver cancer research and metastatic cell tracking.These cell lines are deposited at and can obtain from the National Biomedical Cell Resource Center(http://www.cellresource.cn).

The integration of traditional Chinese and Western medicine is a crucial contemporary medical model widely utilized today.Modern medicine is intricately linked to"data"and"calculation".The key to the high-quality development of integrated Chinese and Western medicine is to realise the in-depth integration of information technology and modern medicine,including tackling the three major scientific problems(algorithm establishment,queue creation and data quality),introducing laws and policies,fostering cross-innovation talents in integrated Chinese and Western medicine,and regulating standards.At the same time,adhering to the principle of integrity and innovation,and being firm in cultural self-confidence are important factors in promoting the healthy,rapid and sustainable development of the cause of integrative Chinese and Western medicine and traditional Chinese medicine.

The integration of traditional Chinese and Western medicine is a crucial contemporary medical model widely utilized today.Modern medicine is intricately linked to"data"and"calculation".The key to the high-quality development of integrated Chinese and Western medicine is to realise the in-depth integration of information technology and modern medicine,including tackling the three major scientific problems(algorithm establishment,queue creation and data quality),introducing laws and policies,fostering cross-innovation talents in integrated Chinese and Western medicine,and regulating standards.At the same time,adhering to the principle of integrity and innovation,and being firm in cultural self-confidence are important factors in promoting the healthy,rapid and sustainable development of the cause of integrative Chinese and Western medicine and traditional Chinese medicine.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Helicobacter pylori （Hp）， a spiral-shaped microaerophilic Gram-negative bacterium that has been classified as a class Ⅰ carcinogen by the World Health Organization， is associated with a variety of digestive system diseases. With the popularization of antibiotic therapy， Hp resistance has become the main reason for the failure of the eradication treatment of Hp. A variety of Chinese medicines have been proved to have anti-Hp effects， which are expected to serve as new options for the eradication of Hp. By reviewing the recent literature in China and abroad， we summarized the understanding of Chinese medicines in the treatment of Hp infection and elaborated on the mechanisms from two aspects： direct killing and indirect inhibition. On the one hand， Chinese medicines can directly kill Hp by inhibiting the growth， respiration， and metabolism of Hp， destroying the morphological structure of Hp， and inhibiting the formation of Hp biofilm. On the other hand， Chinese medicines can inhibit Hp by reducing Hp adhesion and colonization， regulating Hp-caused immune response， inhibiting Hp-caused inflammation， and alleviating the Hp-caused oxidative stress and gastric mucosal injury. Specifically， the indirect inhibition of Hp can be achieved via the following ways. Chinese medicines can reduce Hp adhesion and colonization by reducing Hp motility， inhibiting urease activity and the expression of related genes， and decreasing the production of adhesion proteins. They can regulate the Hp-caused immune responses by enhancing the immune protective response， modulating lysosomal function and immune cytokines， avoiding the immune evasion of Hp， and maintaining the balance between immunity and inflammation. Chinese medicines can inhibit Hp-caused inflammatory responses by inhibiting the release of inflammatory cytokines， down-regulating the expression of virulence factors， and regulating the targets and signaling pathways in the treatment of inflammation. In addition， Chinese medicines can alleviate the Hp-caused oxidative stress and gastric mucosal injury by improving the activities of antioxidant enzymes and oxidases， regulating the generation of reactive oxygen species and reactive nitrogen， and inhibiting inflammatory mediators. This article systematically introduces the mechanisms of Chinese medicines against Hp， aiming to provide a theoretical and scientific basis for the research and clinical application of Chinese medicines against Hp.

Objective To promote the building of the hospital mobile applications architecture in a scientific,user-centered,and needs-oriented way.Methods Function points from mobile applications were rounded up for classification and ranking by means of Kano model and double factor questionnaire survey,for the purpose of qualitative and quantitative analysis of 12 hospitals and identifying the core needs of patients.Statistical methods such as descriptive analysis were used to analyze the data.Results 16 function points of mobile applications were rounded up from 12 hospitals,finding that 12 of their 16 App functions were located in the upper half of the quartile graph,namely appointment and result inquiry.These 12 functions if well met will upgrade patient satisfaction.Conclusions High focus on mobile applications is imperative to upgrade hospital's intelligent medical services,improve the medical efficiency and satisfaction.

Objective The effect of Asperosaponin Ⅵ(ASAⅥ)on adipocyte differentiation and the involvement of Wnt signal pathway was investigated. Methods The murine bone marrow stromal cell line ST-2 were divided into 6 groups:control group, adipocyte differentiation group, and 4 different doses of ASAⅥgroups. Control group was exposed to the vehicle, adipocyte differentiation group was exposed to adipogenic reagent, and those 4 ASAⅥgroups were treated with different concentration(10-7, 10-6, 10-5, 10-4 mol/L)of ASAⅥafter adipocyte differentiation induction. 5 days later, oil red O staining was performed to calculate adipocyte rate. Then mRNA transcription levels of PPARγ, FABP4 genes andβ-catenin that were Wnt/β-catenin signaling pathway proteins were examined by FQ-PCR. Then Wnt pathway inhibitor DKK1 was supplemented into ST-2 cells treated with 10-4 mol/L ASAⅥfor 5 days. After that FQ-PCR was used to detect whether tran?scription levels of PPARγ, FABP4 andβ-catenin in ST-2 cells were changed. Results Compared with adipocyte differenti?ation group 10-5 mol/L and 10-4 mol/L ASAⅥtreatments greatly down-regulated the number of lipid droplets and markedly inhibited transcription levels of adipocyte characterization transcription factors included PPARγ, FABP4 while up-regulat?ed transcription level ofβ-catenin in ST-2 cells. DKK1 can reverse the inhibitory effect of ASAⅥon adipocyte differentia?tion in ST-2 adipocyte. The transcription levels of PPARγand FABP4 were up-regulated significantly while transcription level ofβ-catenin was inhibited. Conclusion ASAⅥblocks adipocyte differentiation in ST-2 cells which might be medi?ated through activating Wnt/β-catenin signaling pathway.

ObjectiveTo study the pharmacokinetics of sufentanil in patients undergoing different cardiac surgeries with or without CPB.MethodsSixteen ASA Ⅱ or Ⅲ patients aged 56-64 yr weighing 52-78 kg undergoing cardiac surgery were divided into 2 groups ( n ＝ 8 each):group Ⅰ off-pump coronary artery bypass grafting and group Ⅱ valve replacement.Radial artery and peripheral vein were cannnlated.A bolus of sufentanil 5μg/kg was administered iv after induction of anesthesia.Blood samples were obtained from radial artery at 1,3,5,10,20,30,60,120,180,240,360 min after sufentanil injection.Plasma was immediately separated and stored at - 80 C for determination of plasma sufentanil concentration by liquid c hromatography-mass spectrometry.Pharmacokinetic parameters were calculated by 3P97 pharmacological program.ResultsThe pharmacokinetic profile of sufentanil was best described by a three-compartment open model.The 3 exponential equations in group Ⅰ,before and during CPB in group Ⅱ were:Cp(t) ＝ 11.7 e-0.47t + 1.9 e0.043t + 0.27 e-0.0032t ; Cp(t) ＝ 33.4 e-1.87t + 7.1e-0.103t +2.0 e-0.0248t and Cp(t) ＝ 23.8 e-0.54t + 5.2 e0.054t + 0.15 e-0.0017t respectively.There was significant difference in most of the pharmacokinetic parameters between the 2 groups.ConclusionsThe pharmacokinetics of sufentanil in patients undergoing different cardiac surgeries can be described by ~compartment open model.Low cardiac function and CPB can reduce its drug metabolism rate and prolong the duration of action.

Objective To investigate the effects of trichostatin A(TSA)on the mice model of collagen induced arthritis(CIA).Methods Mice model of rheumatoid arthritis(RA)was induced in DBA/1 mice with type Ⅱ collagen.Paws were scored for histological severity of arthritis.The severity of inflammation of mouse joint was evaluated by histological examination.Real-time PGR was used to determine the cytokine mRNA expression.Cytokine production was measured by ELISA from serum,spleen cell culture or dendritic cell and T cell co-culture supematant.T cell proliferation was examined by MTT method.Results TSA can significantly suppress the severity of the arthritis in CIA.IFN-γ was elevated in CIA mice,but was inhibited significantly by TSA introduced either at the same time with immunization or at the onset of manifestation of arthritis.Collagen specific T cell proliferation was significantly suppressed by introduction of TSA.Increased level of IL-4 by T cells was observed in TSA treated group compared to that of control group.Conclusion IL-4 level was increased and played a critical role in the protective effects of TSA in CIA.TSA suppresses the progress of CIA by regulates the balance of Th1/Th2 differentiation.