OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.

P-glycoprotein (P-gp) is a transmembrane protein widely involved in the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of drugs within the human body. Accurate prediction of P-gp inhibitors and substrates is crucial for drug discovery and toxicological assessment. However, existing models rely on limited molecular information, leading to suboptimal model performance for predicting P-gp inhibitors and substrates. To overcome this challenge, we compiled an extensive dataset from public databases and literature, consisting of 5,943 P-gp inhibitors and 4,018 substrates, notable for their high quantity, quality, and structural uniqueness. In addition, we curated two external test sets to validate the model's generalization capability. Subsequently, we developed a multimodal graph contrastive learning (GCL) model for the prediction of P-gp inhibitors and substrates (MC-PGP). This framework integrates three types of features from Simplified Molecular Input Line Entry System (SMILES) sequences, molecular fingerprints, and molecular graphs using an attention-based fusion strategy to generate a unified molecular representation. Furthermore, we employed a GCL approach to enhance structural representations by aligning local and global structures. Extensive experimental results highlight the superior performance of MC-PGP, which achieves improvements in the area under the curve of receiver operating characteristic (AUC-ROC) of 9.82% and 10.62% on the external P-gp inhibitor and external P-gp substrate datasets, respectively, compared with 12 state-of-the-art methods. Furthermore, the interpretability analysis of all three molecular feature types offers comprehensive and complementary insights, demonstrating that MC-PGP effectively identifies key functional groups involved in P-gp interactions. These chemically intuitive insights provide valuable guidance for the design and optimization of drug candidates.

Objective:To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics.Methods:This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children′s Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson′s chi-square test or Fisher′s exact probability method were used to compare the clinical characteristics between the groups. Results:A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions:Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.

Objective To investigate the predictive value of early efficacy of neoadjuvant chemotherapy(NAC)in patient with breast cancer via full quantitative parameters of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI).Methods Forty patients with breast cancer were selected.The 18 fluorodeoxyglucose positron emission tomography/computed tomography(18F-FDG PET/CT)and DCE-MRI were performed before and after two cycles of NAC.According to the decrease rate of maximum standardized uptake value(ΔSUVmax)of PET/CT before and after two cycles of NAC,all patients were divided into two groups,including good response group(24 cases)(ΔSUVmax>40%)and general response group(16 cases)(ΔSUVmax≤40%).The changes of full quantitative parameters of DCE-MRI between the two groups were observed and analyzed.Results There were statistically significant differences in changes of Ktrans and Kep between the two groups(P<0.05),however,there was no significant difference in the change of Ve between the two groups(P>0.05).There was a significant positive correlation between ΔKtrans and ΔSUVmax(r=0.850,P<0.001).There was a high positive correlation between ΔKtrans and ΔKep(r=0.727,P<0.001).Conclusion The full quantitative parameters of DCE-MRI are helpful to evaluate the early efficacy of NAC in breast cancer,which can reflect the changes of microcirculation in the lesion,further reflect the therapeutic effect of NAC,guide the clinical optimization of treatment plan in time,and achieve accurate evaluation and individualized treatment.

Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

Objective To establish a method to qualitatively identify and quantitatively determine a new impurity from beclomethasone propionate inhalation aerasol.Methods Ultra-performance liquid chromatography-Q-exactive orbitrap-mass spectrometry(UPLC-QE-MS)technology and Discovery Studio software were used to identify and predict the toxicity of a new impurity in beclomethasone propionate inhalation aerasol,and the content of this new impurity was determined by UPLC.Results The new impurity in beclomethasone propionate inhalation aerasol was polybutylene terephthalate(PBT)cyclic dimer.Discovery Studio software predicted that PBT dimer had potential developmental toxicity,with no mutagenicity,no ocular and skin irritancy and no rodent carcinogenicity.The content range of PBT dimer in 9 batches of beclomethasone propionate inhalation aerasol was 20.5-116.6 pg per bottle.Conclusion This study can realize the rapid identification and toxicity prediction of the new impurity in the preparation,and provide a theoretical basis for the quality control of the preparation by determining their content.

Inflammation, abnormal cholesterol metabolism, and macrophage infiltration are involved in the destruction of the extracellular matrix of the nucleus pulposus (NP), culminating in intervertebral disc degeneration (IDD). Whether nimbolide (Nim), a natural extract, can alleviate IDD is unclear. In this study, we demonstrated that Nim promotes cholesterol efflux and inhibits the activation of the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways by activating sirtuin 1 (SIRT1) in nucleus pulposus cells (NPCs) during inflammation. Thus, Nim balanced matrix anabolism and catabolism of NPCs. However, the inhibition of SIRT1 significantly attenuated the effects of Nim. We also found that Nim promoted the expression of SIRT1 in RAW 264.7, which enhanced the proportion of M2 macrophages by facilitating cholesterol homeostasis reprogramming and impeded M1-like macrophages polarization by blocking the activation of inflammatory signaling. Based on these results, Nim can improve the microenvironment and facilitate matrix metabolism equilibrium in NPCs. Furthermore, in vivo treatment with Nim delayed IDD progression by boosting SIRT1 expression, modulating macrophage polarization and preserving the extracellular matrix. In conclusion, Nim may represent a novel therapeutic strategy for treating IDD.

Objective:To investigate the biological characteristics of Kerstersia gyiorum and to support the rapid and accurate identification of Kerstersia gyiorum on mass spectrometry by using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) for self-built libraries. Methods:From November 2020 to February 2022, thirty-eight strains of Kerstersia gyiorum isolated from clinical patients of the General Hospital of Southern Theatre Command were collected and identified by the fully automated microbial analysis system (Vitek-2 Compact), the automatic microbial mass spectrometry detection system (Vitek-MS) and the 16S ribosomal RNA sequencing. Thirteen strains were randomly selected and mass spectra were obtained by using Vitek-MS. The SARAMIS software was used to construct a Kerstersia gyiorum library, and the remaining 25 strains were used to validate the constructed library. Results:The Vitek-2 Compact and Vitek MS were unable to identify Kerstersia gyiorum; 13 strains were successfully built into a self-built library of Kerstersia gyiorum by SARAMIS software, and 25 validated strains were identified as Kerstersia gyiorum with a confidence level of more than 99.0% and 100% (25/25) accuracy. Conclusion:Kerstersia gyiorum has unique mass spectrometry profile, which can be identified as species quickly and accurately by the establishment of the self-constructed library of profiles.

Objective:To construct the concept and its conceptual framework of hospital health literacy(HHL) for exploring the HHL promotion mechanism in the country.Methods:Based on the proceduralised grounded theory, twelve middle or senior managers of hospitals were selected for in-depth interviews and three hospitals were selected for field research from July 2021 to February 2022. Open coding, axial coding, and selective coding were used in data analysis, establishing the concept of HHL and its conceptual framework in China.Results:The conceptual framework of HHL was composed of an internal driver mechanism(hospitals improve their health literacy promotion management system, staff-led health literacy promotion, health literacy promoting physical environment construction), and an external driver mechanism(cooperate with external organizations and institutions to conduct health literacy promotion). The concept of HHL in China was derived as follows: the combination of supportive environments and human resources that health care organizations have in place can improve access and understandability of health information and simplify healthcare services to help patients of different health literacy levels more easily obtain, process, and understand health information as well as to make the most of medical services.Conclusions:Hospital health literacy promotion mechanism in China is a synergy between internal and external driver mechanisms.

Objective:To describe the current situation of health promotion and education in medical and health institutions in China, propose targeted improvement strategies and provide inspiration for medical and health institutions to implement the relevant content of the Health China Action.Methods:We searched China National Knowledge Infrastructure (CNKI) , WanFang Data, VIP China Science and Technology Journal Database, PubMed, Embase, Cochrane Library and so on. The retrieval time limit was from January 1, 2000 to December 30, 2021. The search content was the research on the theme of "health promotion and education in medical and health institutions".Results:A total of 20 articles were included. In the research on health promotion and education of medical and health institutions, the studies involved in "organization management" and "health education" were the most ( n=20) . There were 7 studies (35%) related to "smoke-free hospitals", 4 studies (20%) related to "work effect evaluation", and the studies on "healthy environment" was the least (15%, 3/20) . Conclusions:The work experience of attaching importance to organization management and health education, vigorously promoting the construction of smoke-free hospitals and institutions' health environment, and strengthening the effectiveness evaluation of health promotion and education can provide reference for medical and health institutions to implement the relevant content of health promotion in the Health China Action (2019-2030) .