Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2A^APP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

With the optimization of surgical technologies and postoperative management regimens, the number of lung transplantation has been significantly increased, which has become an important treatment for patients with end-stage lung disease. However, due to the impact of comprehensive factors, such as bronchial ischemia and immunosuppression, the incidence of airway stenosis after lung transplantation is relatively high, which severely affects postoperative survival and quality of life of lung transplant recipients. In recent years, with the improvement of perioperative management, organ preservation and surgical technologies, the incidence of airway stenosis after lung transplantation has been declined, but it remains at a high level. Early diagnosis and timely intervention play a significant role in enhancing clinical prognosis of patients with airway stenosis. In this article, the general conditions, diagnosis, treatment and prevention of airway stenosis after lung transplantation were reviewed, aiming to provide reference for comprehensive management of airway stenosis after lung transplantation and improving clinical prognosis of lung transplant recipients.

Objective:To construct core medical skill index system for helicopter medical rescue personnel by Delphi expert consensus method.Methods:This study combined literature review and two rounds of Delphi expert correspondence to construct the core skill index system. Total of 22 experts from relevant disciplines were selected purposively to conduct Delphi expert consultation.Results:The effective questionnaire recovery rates of the two rounds of Delphi expert correspondence was 100%; the authority coefficient of experts was 0.87; the Kendall coordination coefficients of the importance of the first and second level indexes were 0.380 and 0.338 in the first round of correspondence, and then 0.415 and 0.357 in the second round. the Kendall coordination coefficients of the feasibility of the second level indexes were 0.347 in the first round of correspondence and 0.354 in the second round. The final core skill index system for helicopter medical rescue personnel includes 4 primary indicators: core medical skill for diseases or trauma in respiratory system, circulatory system, sports system and other system, and 32 secondary indicators.Conclusions:The core medical skill index system for helicopter medical rescue personnel constructed through two rounds of Delphi expert correspondence is scientific and reasonable, which can provide a scientific basis to accurately understand, describe, analyze, and evaluate the competence level of helicopter medical rescue personnel, as well as serve as a content framework for training programs.

BACKGROUND:MRI is important for the diagnosis of early knee osteoarthritis.MRI image recognition and intelligent segmentation of knee osteoarthritis using deep learning method is a hot topic in image diagnosis of artificial intelligence. OBJECTIVE:Through deep learning of MRI images of knee osteoarthritis,the segmentation of femur,tibia,patella,cartilage,meniscus,ligaments,muscles and effusion of knee can be automatically divided,and then volume of knee fluid and muscle content were measured. METHODS:100 normal knee joints and 100 knee osteoarthritis patients were selected and randomly divided into training dataset(n=160),validation dataset(n=20),and test dataset(n=20)according to the ratio of 8:1:1.The Coarse-to-Fine sequential training method was used to train the 3D-UNET network deep learning model.A Coarse MRI segmentation model of the knee sagittal plane was trained first,and the rough segmentation results were used as a mask,and then the fine segmentation model was trained.The T1WI and T2WI images of the sagittal surface of the knee joint and the marking files of each structure were input,and DeepLab v3 was used to segment bone,cartilage,ligament,meniscus,muscle,and effusion of knee,and 3D reconstruction was finally displayed and automatic measurement results(muscle content and volume of knee fluid)were displayed to complete the deep learning application program.The MRI data of 26 normal subjects and 38 patients with knee osteoarthritis were screened for validation. RESULTS AND CONCLUSION:(1)The 26 normal subjects were selected,including 13 females and 13 males,with a mean age of(34.88±11.75)years old.The mean muscle content of the knee joint was(1 051 322.94±2 007 249.00)mL,the mean median was 631 165.21 mL,and the mean volume of effusion was(291.85±559.59)mL.The mean median was 0 mL.(2)There were 38 patients with knee osteoarthritis,including 30 females and 8 males.The mean age was(68.53±9.87)years old.The mean muscle content was(782 409.18±331 392.56)mL,the mean median was 689 105.66 mL,and the mean volume of effusion was(1 625.23±5 014.03)mL.The mean median was 178.72 mL.(3)There was no significant difference in muscle content between normal people and knee osteoarthritis patients.The volume of effusion in patients with knee osteoarthritis was higher than that in normal subjects,and the difference was significant(P<0.05).(4)It is indicated that the intelligent segmentation of MRI images by deep learning can discard the defects of manual segmentation in the past.The more accuracy evaluation of knee osteoarthritis was necessary,and the image segmentation was processed more precisely in the future to improve the accuracy of the results.

OBJECTIVE To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method for determination and comparison of 26 components in different parts of two base plants of Shiliang tea(Chimonanthus salicifolius S.Y.Hu and Chimonanthus zhejiangensis M.C.Liu), and screen quality markers of different parts. METHODS The UHPLC method was performed on an Agilent RRHD Eclipse Plus C18 (2.1 mm×50 mm, 1.8 μm) column with a gradient elution of methanol and 0.1% formic acid in water at a flow rate of 0.3 mL·min−1, the column temperature was 35 ℃, and the injection volume was 0.5 μL; the multiple reaction monitoring mode was employed for the quantification of 26 components with electrospray ionization(ESI) source polarity in negative and positive mode. RESULTS Good linear relationship(r >0.999) were observed in the test ranges for 26 compounds, and the average recovery was 88.5%−111.7% with RSD was 3.4%−9.8%. There was no significant difference between the two base plants of Shiliang tea, and all of these samples were divided into two categories by hierarchical cluster analysis. The main components in leaves was flavonoids, among them, the content of kaempferol 3-O-rutinoside was the highest, reaching 12.902 mg.g−1; the main components in stems and roots was coumarins, and the content of alkaloids in roots was higher, relatively; 7 quality markers of difference were screened by OPLS-DA, which were kaempferol 3-O-rutinoside, chimonanthine, rutin, fraxetin, calycanthoside, scopolin, neochlorogenic acid. CONCLUSION These study elucidates the differences of chemical components in the different parts of two base plants of Shiliang tea, which providing basis for the research of pharmacodynamic substances and references for the comprehensive utilization of Chimonanthus salicifolius S.Y. Hu and Chimonanthus zhejiangensis M.C.Liu resources.

OBJECTIVE To establish a ultra-high-performance liquid chromatography-mass spectrum/mass spectrum(UPLC-MS/MS) method for the determination of anlotinib in human plasma and assessment of clinical application. METHODS Zanubrutinib was used as internal standard and the extraction process was performed through protein precipitation method using acetonitrile, followed by separation on an Ultimate XB-C18(100 mm×2.1 mm, 3.0 μm) column using acetonitrile and 10 mmol·L−1 ammonium acetate-0.1% formic acid step-elution gradient. The flow rate was 0.6 mL·min−1 and injection volume was 5 μL. The mass analysis was performed by positive ion electrospray ionization in multiple-reaction monitoring mode, and the mass spectrometer was set at m/z 408.1→339.1 for anlotinib and m/z 472.2→290.1 for internal standard, respectively. The specificity, standard curve and lower limit of quantification, precision and recovery, matrix effect and stability of the method and clinical application were investigated. RESULTS The method was validated over the concentration range of 1.0−100.0 ng·mL−1, with R2=0.998 4. The precision RSD was<9%, the recovery and matrix effect were 104.81%−107.32% and 102.54%−105.26%, respectively, and this method had good stability and was not affected by matrix effect. The method had been used for determined 52 advanced non-small cell lung cancer patients treated with anlotinib. The trough plasma concentration (Ctrough) was measured on day 43 after initiation of anlotinib treatment. Anlotinib Ctrough were higher than lower limit of quantitation (1.0 ng·mL−1) from 52 patients. The plasma concentration of anlotinib Ctrough was (11.38±4.29)ng·mL−1 with 37.66% coefficients of variation, which were shown large inter-patient variability. CONCLUSION This method is high sensitivity, specificity and accurate, and suitable for determination of anlotinib in human plasma.

【Objective】 To monitor the effectiveness and accuracy of the blood transfusion compatibility test system by self-made weakly positive internal quality control products. 【Methods】 Red blood cells from DAT(-) healthy subjects were selected, and B/RhD(-)E(-) red blood cells were selected as tube 1. A/RhD(+ )E(+ ) was selected as tube 2 to prepare blood group quality control products according to the principle of blood group antigen compatibility, and red blood cell preservation solution and corresponding ABO blood group reagent antibody were added to make the agglutination intensity of microcolumn gel method in reverse blood typing reach a low positive value (1+ ). Tube 3 and tube 4 were prepared with five different preservation media: plasma, serum, antibody diluent, mixture of equal plasma and antibody diluent, and mixture of equal serum and antibody diluent, respectively. IgM anti-E antibody was added to tube 3, and IgG anti-D antibody was added to tube 4, so that the agglutination intensity of microcolumn gel method reached a low positive value (1+ ). 【Results】 Comparison between the 5 different preservation media showed that the preservation medium of antibody diluent was the most stable for weakly positive antibody (F=11.35, P<0.05), Agglutination intensity 1+ is assigned 5 points by AABB Technical Manual, and its score was 5.25±1.75 points. 【Conclusion】 The use of self-made weakly positive quality control products can improve the effectiveness, accuracy and sensitivity of the monitoring system, thus achieving internal quality control and ensuring the safety of clinical blood use.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To empirically analyze the status quo of high-quality development of public hospitals in S Province,provides reference for promoting high-quality development of public hospitals.Methods SPSS 26.0 soft-ware and text analysis method were used to process the high-quality development monitoring data of tertiary public hospitals in S Province,and the qualitative interview results obtained by field investigation were comprehensively ana-lyzed.Results In terms of capacity improvement,public hospitals actively take measures such as the construction of medical union and the reform of payment methods to improve their capacity.Specialized hospitals and maternity and child care hospitals need to be improved in some indicators.In terms of structural optimization,the quality of medi-cal services is high in all regions.The proportion of medical service revenue and the proportion of high-grade surgery still need to be increased.In terms of innovation and efficiency improvement,the application level of electronic medi-cal records has made remarkable progress in various regions.There are differences in the funding of scientific re-search projects.In terms of cultural cohesion,patient satisfaction was higher.There is improvement room in the satisfaction of medical staff.Conclusion Third-level public hospitals in S province have achieved certain results in high-quality de-velopment,but there are still problems,such as the need to further integrate party building work with hospital busi-ness work,the lack of connection between performance incentive and performance evaluation index system,and the need to improve the satisfaction of medical staff.It is necessary to solve the problem and improve the quality and efficiency of medical service.