Objective To investigate the feasibility and early efficacy of transapical transcatheter aortic valve replacement (TAVR) combined with transcatheter mitral valve edge-to-edge repair (TEER) in patients with high-risk aortic valve lesions combined with severe mitral regurgitation. Methods The clinical data of patients who underwent "one-stop" transapical TAVR+TEER in our hospital from August 2022 to October 2023 were retrospectively analyzed. Results Five patients were collected, including 3 males and 2 females with a mean age of 66.6±1.8 years. Four patients had aortic valve insufficiency combined with mitral regurgitation and one had aortic valve stenosis and insufficiency combined with mitral regurgitation. All patients successfully completed transapical TAVR+TEER, and the immediate postoperative echocardiographic results revealed that none of them had more than mild perivalvular leakage and mitral regurgitation, and the prosthetic valves were in good position and function. At 1 week postoperatively, echocardiographic results showed 5 patients with no displacement of the prosthetic valve, detachment of the mitral clip, or damage to the leaflets. At 1 month postoperatively, cardiac function was improved to varying degrees in 4 patients, and 1 patient died of multiorgan failure. At 2 months postoperatively, 1 patient died of cerebrovascular accident, and at 3 months postoperatively the echocardiographic results of the remaining 3 patients revealed that there was no more than mild perivalvular leakage or mitral regurgitation, and the patients' postoperative cardiac function and daily life ability were significantly improved. Conclusion In high-risk aortic valve lesions combined with severe mitral regurgitation, "one-stop" transapical TAVR+TEER is feasible with favorable early efficacy and safety.

AIM:To investigate the effect of a disintegrin and metalloproteinase(ADAM)domain-like decy-sin 1(ADAMDEC1)knockdown on the proliferation,migration and invasion of pancreatic carcinoma cells.METHODS:Expression levels of ADAMDEC1 in pancreatic carcinoma tissues were analyzed using the GEPIA and UALCAN online da-tabases.Western blot analysis was employed to detect the protein expression levels of ADAMDEC1 in pancreatic carcino-ma cell lines(MIA PaCa-2 and PANC-1)and pancreatic ductal cell line(hTERT-HPNE).The effects of ADAMDEC1 knockdown on cell proliferation,migration and invasion were evaluated using CCK-8,colony formation,wound-healing and Transwell assays.Additionally,Western blot analysis was used to detect the effects of ADAMDEC1 knockdown on the expression levels of migration and invasion markers,as well as Wnt/β-catenin signaling pathway-related proteins in pancre-atic carcinoma cells.Furthermore,a recovery experiment was conducted to assess the role of Wnt/β-catenin signaling path-way agonist CHIR-99021 in ADAMDEC1 knockdown-induced inhibition of pancreatic carcinoma cell growth and migra-tion.RESULTS:(1)ADAMDEC1 was highly expressed in pancreatic carcinoma cells.(2)Knockdown of ADAMDEC1 led to a significant reduction in the proliferation,migration and invasion of pancreatic carcinoma cells.(3)Knockdown of ADAMDEC1 resulted in increased E-cadherin protein expression and decreased levels of matrix metalloproteinase 9,N-cadherin and vimentin proteins,alongside a reduction in the expression of Wnt/β-catenin signaling pathway-related pro-teins.(4)Co-treatment of pancreatic carcinoma cells with CHIR-99021 and ADAMDEC1 small interfering RNA reversed the inhibitory effects of ADAMDEC1 knockdown on cell proliferation,migration,and invasion.CONCLUSION:ADAMDEC1 is highly expressed in pancreatic carcinoma.Targeted silencing of ADAMDEC1 has the potential to inhibit the prolifera-tion,migration and invasion of pancreatic carcinoma cells by regulating the Wnt/β-catenin signaling pathway.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective To establish a human tonsil organoid model and investigate the immunological effects of this tonsil organoid infected by influenza virus.Methods Human tonsil tissue removed by adenoid hypertrophy surgery were subjected to gradient centrifugation,and then the obtain cells were cultured in vitro with using a 2.5D-Transwell chamber in combination with IL-2 and B cell activating factor(Baff)to construct a human tonsil organoid.Single cell transcriptome sequencing(scRNA-seq)was used to analyze the distribution of influenza virus receptors in different cell subsets of the tonsil organoid.Immunofluorescence assay and flow cytometry were applied to detect the immunological effects of the tonsil organoid in 48 h after influenza virus infection.Results The tonsil organoids were established successfully using this 2.5D-Transwell culture technique.scRNA-seq analysis showed that the receptors for influenza virus were extensively distributed in nearly all of cell subsets of tonsil organoids.In 48 h after influenza virus infection,the tonsil organoids could generate a large amount of plasma cells and memory B cells to produce specific IgG antibodies.In addition,direct infection of the virus promoted the production of TNF-α and IL-2 from CD8+T cells and the secretion of TNF-α,IFN-γ and IL-2 by CD4+T cells.Conclusion The tonsil organoids can be established successfully and reach maturity at about the 6th day after culture.The receptors for influenza virus are widely distributed in human tonsil organoids.Influenza virus directly infects human T cells,leading to T cell activation and cytokine releasing.Moreover,influenza virus infection also promotes B cells differentiate into plasma cells and induce the secretion of IgG as well as the formation of memory B cells.

Recent studies have demonstrated that bitter taste receptors are distributed not only in oral cavity but also in non-gustatory systems,such as the respiratory,digestive,reproductive and cardiovascular systems.The physiological role of bitter taste receptors is to recognize bitter substances or bacterial secretions,to trigger the immune response and to maintain the internal environmental homeosta-sis.In addition,oral bitter taste receptors are expressed not only in taste buds,perceiving bitter taste,but also in many other parts of periodontal tissues,which is the potential treatment target for oral infectious diseases.This review summarized the expression and distri-bution of oral bitter taste receptors which was off the taste buds and their roles in regulating oral inflammation and oral bacteria,dis-cussed the effects of genetic polymorphism of bitter taste receptor 38 subtype(TAS2R38)on innate immunity and its relationship with the susceptibility of dental caries and periodontal,aimed to provide novel ideas for the better prevention and treatment of dental caries and periodontal diseases.

Objective:To explore the impact of artificial intelligence compressed sensing technology (CS-AI) on image quality in three-dimensional proton density weighted imaging (3D PDWI) of the unilateral hip joint.Methods:High-resolution unilateral hip imaging was conducted on 67 healthy volunteers at West China Hospital of Sichuan University from January to July 2023. Imaging was performed by using CS-AI 3D PDWI sequence with acceleration factors (AF) of 4, 6, 8, and 10, respectively. According to the AF, all subjects were divided into 4 groups: CS-AI 4, CS-AI 6, CS-AI 8 and CS-AI 10, with CS-AI 4 serving as a reference. Recording the scan time, the signal and noise intensity of the femoral head, muscle, and subcutaneous fat were measured by a senior radiologist and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were then calculated. Additionally, two observers provided ratings for overall image quality and artifacts in the 4 groups, and statistical analysis was performed using the Friedman rank-sum test.Results:The acquisition times for CS-AI 4, CS-AI 6, CS-AI 8, and CS-AI 10 were 5 min 49 s, 3 min 54 s, 2 min 56 s and 2 min 22 s, respectively. Compared to CS-AI 4, the scanning time for CS-AI 6, CS-AI 8, CS-AI 10 were reduced by 32.95%, 50.14%, 59.31%, respectively. The objective evaluation revealed that the SNR and CNR of the femoral head and muscle in groups CS-AI 6, CS-AI 8, and CS-AI 10 were slightly lower than those in group CS-AI 4 ( P<0.05), and the differences were statistically significant. However, no statistically significant differences were found among the 3 groups ( P>0.05). The subjective evaluation indicated that the overall image quality scores of group CS-AI 8 [3 (3,4)] did not significantly differ from those of group CS-AI 4 and CS-AI 6( P>0.05); The mean scores of group CS-AI 4 and CS-AI 6 were 4 (4, 4); Scores of group CS-AI 10 was 3(3, 3), which statistically significant differ from those of the other groups ( P<0.05). The artifacts rating for groups CS-AI 4, CS-AI 6, CS-AI 8 and CS-AI 10 were 4 (4, 4), 4 (4, 4), 3 (3, 4), and 2 (2, 3) respectively. When AF was set to 10, the images exhibited the most severe artifacts ( P<0.05). For other AF values, artifact ratings did not differ significantly ( P>0.05). Conclusion:The CS-AI 3D-PDWI sequence with acceleration factor 8 can acquire high-resolution images of the unilateral hip joint that meet clinical diagnostic requirements while reducing scanning time.

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CX_AE, CX_AL, CX_PA and CX_PHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CX_AE, CX_AL and CX_PHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CX_AE and CX_PHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CX_PHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CX_PHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CX_PHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

{L-End}Objective To establish the construction of intelligent management system for equipment and supplies of medical rescue teams for provincial nuclear and radiation accidents, based on modern Internet+ Internet of Things. {L-End}Methods The current status and requirements of emergency equipment and supplies allocation and management of medical emergency teams for provincial nuclear and radiation accidents were analyzed. Utilizing technologies such as Internet of Things, low-power Bluetooth, and radio frequency identification, an intelligent management system for medical rescue teams, its equipment and supplies for provincial nuclear and radiation accidents was designed. {L-End}Results The intelligent management system for medical rescue teams, its equipment and supplies for nuclear and radiation accidents was able to perform the inventory warning, expiration date warning, maintenance alert, and warning for emergency personnel health status, based on dynamic management of rescue personnel, equipment and supplies. It provided an effective support for on-site commanders in making emergency decisions. {L-End}Conclusion The use of Internet+Internet of Things technology can achieve intelligent management for medical rescue teams and its equipment and supplies can effectively improve the level of personnel and equipment support for the rescue of nuclear and radiation accidents at the provincial level.

Objective:To study the morphology of hemophagocytosis (HPC) in bone marrow smears of patients with infection-associated hemophagocytic lymphohistiocytosis (IAHLH), and further analyse if there were differences in the clinical and laboratory features, the cytokines level and prognosisMethods:24 patients newly diagnosed with IAHLH from 2016-Dec-1 to 2021-Dec-31 in Beijing Friendship Hospital were included as study group, and 20 patients with infectious disease as non-HLH control group. In IAHLH group, mean age was 34±13 years, including 17(71%) males and7(29%) females. In Non-HLH group, mean agewas 43±16 years, including 14 (70%) males and6 (30%) females. Depending on re-checking phagocytic cell type on the initial bone marrow smear, the HPCs were divided into HPC-1, phagocytizing non-nucleated cells (mature erythrocyte or platelets), and HPC-2, phagocytizing nucleated cells. The differences in clinical presentations covered in HLH-2004 criteria, cytokines value(IL-6, IL-10, IL-18, IFN-γ) recommended in HLH-2022-China guideline, and the mortality within 1 year of diagnosis, were compared between IAHLH and non-HLH groups, between patients with or without HPC, and between patients with HPC-2 or only with HPC-1. For categorical variables, two groups were compared with the use of either the chi-square test or Fisher′s exact test. For non-normal distribution continuous variables, the difference between two groups variation was performed by using Mann-Whitney U test, and for normal distribution continuous variables, the difference was by the Independent Samples t-test.Results:The positive rates of fever, hepatomegaly and splenomegalyand the motrtality in IAHLH were 100% (24/24), 63% (15/24), 92% (22/24) and 46% (11/24), respectivelyin non-HLH were 55%(11/20),0(0/20),25% (5/20),0(0/20),and the differences between two groups were all statistically significant( P<0.01), but thedifferences between groups with and without HPC and between IAHLH patients with HPC-2 or only with HPC-1 were no statistically significanlly, ( P>0.05).In IAHLH group, IFN-γ in patients with HPC-2 was 400(246, 532)ng/L, significantly higher than 146(38, 180)ng/L in patients only with HPC-1 [ P=0.02, 95% CI was 233(75.8 to 397)], andthe other test parameters and cytokines level showed no obvious differences ( P>0.05).

AIM: To compare the results calculated by population pharmacokinetic analysis tools Phoenix NLME, Monolix, R nlmixr package and CPhaMAS cloud platform with the gold standard sofeware NONMEM. METHODS: Fifty sparse sampling data sets based on a one-compartment model and fifty dense sampling data sets based on a two-compartment model were simulated, and the above five analysis tools were used to calculate the population typical value, individual variability and individual pharmacokinetic parameters. RESULTS: The population typical value and individual variability calculated by CPhaMAS and Phoenix NLME had the highest matching degree with NONMEM, followed by nlmixr. Monolix had the lowest matching degree, but Monolix and nlmixr might be more robust. The correspondence between clearance and distribution volume was better than the absorption rate constant. Except the absorption rate constant calculated by Monolix and intercompartmental clearance calculated by nlmixr, the correlation coefficients of individual pharmacokinetic parameters calculated by all analytical tools were greater than 0.99. CONCLUSION: The results calculated by the above four population pharmacokinetic analysis tools are highly correlated with that of NONMEM.