Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Purpose/Significance To construct a Chinese medical knowledge Q&A corpus dataset as a standardized evaluation bench-mark for large language models(LLMs)in the medical domain,so as to improve the accuracy and efficiency of LLMs in handling Chinese medical questions.Method/Process Chinese medical paper knowledge,medical terminology explanations and supplementary questions are acquired from the Chinese medical licensing examination,and open-source Chinese medical Q&A datasets are encompassed in the developed Q&A datasets.Result/Conclusion The Chinese medical knowledge Q&A corpus datasets enrich the sources of existing datasets and promote the objective and comprehensive quantitative evaluation of large models in the medical field.In the near future,additional data such as electronic medical records and those from online health communities will be used to strengthen the support of artificial intelli-gence for the Healthy China strategy.

Objective:To observe the neuroprotective effect of wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) in combination with Panax ginseng total saponin (PNS) on cerebral ischemia-reperfusion rats; To elucidate the mechanism of "wind medicine increasing effect".Methods:Totally 140 male SD rats were divided into sham-operation group, model group, PNS group, Puerariae Lobatue Radix group, Acori Tatarinowii Rhizoma group, Puerariae Lobatue Radix + PNS group, Acori Tatarinowii Rhizoma + PNS group according to the random number table method, with 20 rats in each group. Except for the sham-operation group, the cerebral ischemia/reperfusion rat model was established using the modified Longa line bolus method in the remaining groups. After 7 d of administration of the appropriate pharmacologic intervention in each group, neurological dysfunction was evaluated by Zea-longa score after final administration, cerebral infarct volume was determined by TTC staining; blood brain barrier (BBB) permeability of brain tissue on the ischemic side was detected by Evans blue content; BBB ultrastructure of each group of rats was observed by transmission electron microscopy; Claudin 5 protein expression level was detected by immunohistochemistry; Zonula occludens-1 (ZO-1), major facilitator supeffamily domain-containing protein 2a (Mfsd2a), Occludin, P-glycoprotein (P-gp), Monocarboxylate Transporters-1 (MCT1) and breast cancer resistance protein (BCRP) protein expression levels were detected by Western-blot.Results:Compared with the model group, the rat neurological function scores were reduced in each administration group ( P<0.05), infarct volume was reduced ( P<0.05), EB content of brain tissue decreased ( P<0.05), protein expressions of Claudin 5, ZO-1, Mfsd2a and Occludin in brain tissue were elevated ( P<0.05), the protein expressions of P-gp, BCRP and MCT1 were reduced ( P<0.05), and the protein expressions of Claudin 5, Mfsd2a, and Occludin was higher in the Puerariae Lobatue Radix + PNS group and Acori Tatarinowii Rhizoma + PNS group than that of each group of medication alone ( P<0.05), and the protein expression of MCT1 was lower than that of each group of medication alone ( P<0.05); the protein expression level of ZO-1 in the Puerariae Lobatue Radix + PNS group was higher than that of the group of medication alone ( P<0.05); P-gp protein expression was lower in Acori Tatarinowii Rhizoma + PNS group than in the PNS group and Acori Tatarinowii Rhizoma group ( P<0.05). Conclusion:Wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) may potentiate the neuroprotective effect of PNS on cerebral ischemia-reperfusion rats, and the mechanism may be related to the protection of BBB structural integrity and maintenance of central barrier properties, while regulating substance transport proteins and increasing the intracerebral content of the drug.

All-trans retinoic acid(ATRA)is able to induce promyelocytic differentiation effectively.However,its role in the process of erythroid differentiation remains unclear.To investigate the role of AT-RA in the process of erythroid differentiation and its epigenetic regulatory mechanism,we established an induced leukemia cell K562 model in this study.Firstly,hemin was used to induce the differentiation of K562 cells into erythroid cells.The results of flow cytometry showed that ATRA affected the lineage changes of cells during erythroid differentiation and blocked the process of cell differentiation.After AT-RA treatment of differentiating cells,the expression level of erythroid differentiation-related genes de-creased.Through chromatin conformational capture(3C),formaldehyde-assisted separation of regulatory elements(FAIRE),chromatin immunoprecipitation(ChIP)techniques,the epigenetic mechanism was explored and it was found that after ATRA treatment of cells,the chromatin accessibility within the β-glo-bin family gene locus decreased,and the frequency of interaction between the locus control region(LCR)and its target gene promoter decreased.The decrease in the chromatin accessibility of the gene locus led to a decrease in the enrichment frequency of erythroid-related transcription factors GATA binding protein 1(GATA1),LIM domain binding 1(LDB1),LIM domain only 2(LMO2),and BHLH transcription factor 1(TAL1)at the promoter regions of the LCR and the gene locus of the globin family.The above results indicate that the ATRA treatment of differentiating cells leads to a decrease in the chromatin acces-sibility of erythroid differentiation-related genes,and a more closed chromatin structure hinders the bind-ing of LCR-recruiting transcription factors to the promoter regions of genes,thereby further repressing the expression of β-globin family genes.This dynamic process elucidates the epigenetic mechanism of ATRA in regulating erythroid differentiation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.

Child ; Humans ; Inflammatory Bowel Diseases ; Organic Anion Transporters/genetics*

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective:To explore the ability of sequential immunization regimen inducing neutralizing antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Wuhan-Hu1 and Omicron variants in mice.Methods:Groups of 6-8-week-old BALB/c mice were primed with two doses of Wuhan-Hu-1 inactivated vaccine, and then boosted with Omicron or Wuhan-Hu-1 inactivated vaccine, respectively. Binding antibodies were tested by enzyme linked immunosorbent assay; and neutralizing antibodies against Wuhan-Hu1 and Omicron variants were analyzed by vesicular stomatitis virus pseudovirus assay system; SARS-CoV-2 specific cellular immune responses were quantified by enzyme-linked immunosorbent spot assay.Results:IgG antibodies against Wuhan-Hu1, Delta and Omicron RBD were enhanced after the second dose of Wuhan-Hu1 inactivated vaccine. Compared with Wuhan-Hu1 inactivated vaccine, the group boosted with Omicron inactivated vaccine improved Wu-RBD and Omic-RBD specific IgG antibodies 1.41 and 1.26 times, and serum neutralizing antibodies against BA.1, BA.2, BA.4/5 and BF.7 were elevated 4.5, 3.4, 12.1 and 6.5 folds, respectively, by sequential immunization. After booster immunization with inactivated Wuhan-Hu1 or Omicron vaccines, Wu-RBD IgA titer was significantly higher than that of one dose inactivated Wuhan-Hu1 vaccine ( P=0.005 7, P=0.006 1). Conclusions:Neutralizing antibodies against Omicron variants were enhanced by sequential immunization with Omicron inactivated vaccine. Specific IgA was significantly enhanced after the third dose of inactivated vaccine.