ObjectiveTo observe the effect of Yifei Jianpi prescription on the of signal transducer and activator of transcription protein 1 （STAT1）/interferon regulatory factor 3 （IRF3） signaling pathway in a pneumonia model induced by lipopolysaccharide （LPS） and to explore the mechanism of Yifei Jianpi prescription in improving lung immune and inflammatory responses. MethodsSixty male SPF SD rats were used in this study. Ten rats were randomly assigned to the normal control group， and the remaining 50 were instilled with LPS in the trachea to establish a pneumonia model. After successful modeling， the rats were randomly divided into the model group， dexamethasone group （0.5 mg·kg^-1）， and Yifei Jianpi prescription high-dose （12 mg·kg^-1）， medium-dose （6 mg·kg^-1）， and low-dose （3 mg·kg^-1） groups， with 10 rats in each group. Treatment was administered once daily， and the normal control and model groups received the same volume of normal saline. After 14 days， flow cytometry was used to detect the classification of whole blood lymphocytes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of immunoglobulin G （IgG）， immunoglobulin A （IgA）， immunoglobulin M （IgM）， and the content of tumor necrosis factor-α （TNF-α）， interleukin-8 （IL-8）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in alveolar lavage fluid （BALF）. Hematoxylin-eosin （HE） staining was used to observe lung tissue pathology and score the damage. Thymus weight， spleen weight， and wet-to-dry weight ratio （W/D） were recorded. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of STAT1， IRF3， IL-6， and interferon-alpha （IFN-α） in lung tissues， while Western blot was performed to assess the protein expression of STAT1， IRF3， IL-6， and IFN-α. ResultsCompared with the normal control group， the model group showed significantly increased proportion of B lymphocytes in peripheral blood， decreased proportions of NK cells and CD4⁺/CD8⁺ （P<0.05， P<0.01）， decreased serum levels of IgG and IgA， significantly increased IgM levels （P<0.01）， significantly elevated content of TNF-α， IL-6， and IL-8 in BALF， and significantly decreased IL-10 levels （P<0.01）. Lung tissue damage was evident， with significant increases in thymus and spleen weights and a higher W/D ratio （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly upregulated （P<0.05，P<0.01）. Compared with the model group， the Yifei Jianpi prescription groups showed significantly reduced proportions of B lymphocytes in peripheral blood， increased proportions of NK cells and CD4⁺/CD8⁺ ratios （P<0.05， P<0.01）， significantly increased serum levels of IgG and IgA， significantly decreased IgM levels （P<0.05， P<0.01）， significantly reduced levels of TNF-α， IL-6， and IL-8 in BALF， and significantly increased IL-10 levels （P<0.01）. Lung tissue damage was alleviated， thymus and spleen weights were significantly reduced， and the W/D ratio was markedly decreased （P<0.01）. The mRNA and protein expression of STAT1， IRF3， IFN-α， and IL-6 in lung tissues was significantly downregulated （P<0.05， P<0.01）. ConclusionYifei Jianpi prescription can alleviate lung tissue damage and improve immune and inflammatory responses in LPS-induced pneumonia rats. The mechanism may be related to the inhibition of STAT1/IRF3 signaling pathway activation.

Arginine methylation is a critical post-translational modification that plays multifaceted biological functions. However, the manipulation of protein arginine methylation largely depends on genetic or pharmaceutic inhibition of the regulatory enzymes, protein arginine methyltransferases (PRMTs), or non-methylation substitution of corresponding arginine residue to lysine or alanine of protein of interest (POI), which inevitably affects other substrates, or disrupts the structure of POI. Thus, it urges an approach to specifically modulate the arginine methylation of a POI under physiological conditions. To this end, we report the discovery of a methylation tagging system (MeTAG), that enables targeted modification of protein arginine methylation. Through bridging the methyltransferase PRMT5 proximity to a POI, MeTAG facilitates the arginine methylation of POIs, including known arginine methylated proteins, androgen receptor (AR) and protein kinase B (AKT), as well as a neo-substrate E1A binding protein (p300), in a reversible and PRMT5-dependent manner. Moreover, MeTAG can regulate downstream signaling in a methylation dependent manner, leading to downregulation of PSMA mRNA level and activation of AKT. Therefore, MeTAG represents a feasible approach to modulate protein methylation and thereby perturbs protein function in biological and therapeutic contexts.

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.

Objective To explore the effects of different doses of valproate on serum thyroxine(TSH),prolactin(PRL)and dopamine(DA)in patients with bipolar disorder(BPD)level of influence.Methods A total of 90 patients with BPD who received treatment in hospital from May 2020 to May 2022 were selected as the study objects.They were randomly divided into groups A,B and C,with 30 cases in all.Groups A,B and C were orally administered 10 mg/kg,15 mg/kg and 20 mg/kg sodium valproate every day,respectively.The clinical efficacy,scores of mental diseases before and after treatment,indexes related to blood drug concentration,serum levels before and after treatment,indexes related to liver function and incidence of adverse reactions were compared among the three groups.Results There was no significant difference in the total effective rate among the three groups after treatment(P>0.05).After treatment,the scores of the three groups were significantly improved compared with before treatment(P<0.05).There was significant difference in the time to reach the stable state serum concentration(P<0.05).There were no significant differences in TSH,PRL and DA levels among the three groups after treatment compared with before treatment(P>0.05).ALT and AST levels in the three groups after treatment were increased compared with those before treatment(P<0.05),and there were statistically significant differences in ALT and AST levels among the three groups after treatment(P<0.05).There was significant difference in the incidence of adverse reactions among the three groups(P<0.05).Conclusion Sodium valproate can effectively treat BPD patients and relieve the degree of mania or depression,but has no significant effect on the level of TSH,PRL and DA.Among them,small dose of sodium valproate can guarantee the thera-peutic effect and have less impact on liver function,and less adverse reactions,high safety,worthy of clinical promotion.

The innovation of integrating medical treatment and prevention mechanisms is a key task deployed by the government, aiming to promote the construction of a Healthy China and address the prevalent "treatment over prevention" mindset in healthcare services and society. Vaccination is an effective strategy for preventing and controlling infectious diseases; however, adult vaccination rates in China remain low due to insufficient awareness and enthusiasm among the public and healthcare professionals. In recent years, various regions have begun to explore the model of physicians in medical institutions prescribing vaccines to improve vaccination rates. This article analyzes the positioning, current implementation status, and challenges of vaccine prescriptions, and proposes recommendations advocating policy formulation, improving service models and supporting measures, improving funding mechanisms, and strengthening publicity and education to promote the widespread implementation and effectiveness of vaccine prescriptions.

Objective:To assess the utility of whole-genome sequencing (WGS) in predicting Mycobacterium tuberculosis resistance to fluoroquinolones (FQs) and to establish a quantitative relationship between resistant gene mutations and resistance levels. Methods:A total of 296 drug-resistant tuberculosis surveillance strains with various resistance profiles, preserved by the National Tuberculosis Reference Laboratory of the Tuberculosis Prevention and Control Center at the Chinese Center for Disease Control and Prevention between 2013 and 2020, were included as study subjects. The Sensititre? MYCOTBI microplate method and WGS were used to assess the phenotypic and genotypic drug sensitivity of Mycobacterium tuberculosis to ofloxacin and moxifloxacin. Sensitivity, specificity, and concordance (Kappa value) of WGS in predicting fluoroquinolone sensitivity were calculated using phenotypic drug susceptibility testing (DST) results as the gold standard. A summary analysis was conducted on the distribution of drug resistance mutation sites and resistance levels. The paired χ 2 test was used to compare the detection rates between the two methods, with P<0.05 indicating statistical significance. Results:Among the 296 Mycobacterium tuberculosis strains with different resistance profiles, 196 were rifampicin-resistant, 50 were resistant to other drugs, and 50 were fully sensitive. WGS identified 81 strains carrying FQs resistance-related mutations, primarily at gyrA codons 94, 90, and 91. Sensitivity, specificity, and consistency (Kappa value) of WGS in predicting ofloxacin resistance were 86.5%, 98.1%, and 0.87, respectively. For moxifloxacin resistance prediction, these values were 80.0%, 99.5%, and 0.83, respectively. There was no statistically significant difference between the phenotypic DST and WGS detection rates for ofloxacin resistance (30.1% vs 27.4%, χ 2=3.06, P=0.08). However, the phenotypic DST detection rate for moxifloxacin resistance (33.8%, 100/296) was significantly higher than that of WGS (27.4%, 81/296) (χ 2=15.43, P<0.01). Analysis of the distribution of resistance mutation sites and resistance levels showed that different mutation sites corresponded to different minimum inhibitory concentrations (MICs). Multiple mutation combinations, including gyrA_D94G, gyrA_D94Y, and gyrA_D94N were mainly associated with high-level resistance, while gyrA_D94A, gyrA_A90V, and gyrA_S91P were primarily linked to low-level resistance. Conclusion:WGS demonstrates favorable sensitivity, specificity, and consistency in predicting FQs resistance and can partially predict resistance levels.

Purpose To evaluate the added value of time of flight(TOF)and point spread dispersion(PSF)reconstruction in mediastinal lymph node metastasis of lung cancer in 18F-FDG PET/CT imaging.Materials and Methods Sixty-eight lung cancer patients with mediastinal lymph node metastasis who underwent PET/CT examination in the First People's Hospital of Foshan from March 9,2020 to July 23,2021 were analyzed retrospectively.The different methods,including ordered subsets estimation maximization(OSEM),OSEM+TOF,OSEM+PSF,OSEM+TOF+PSF,were used to reconstruct the images.The resolution of different reconstruction algorithms for mediastinal lymph node metastasis of lung cancer,as well as the differences of signal-to-noise ratio(SNR)and standard uptake value(SUV)were compared,respectively.Results The highest values of SUVmean,SUVmax and SNR were obtained via OSEM+TOF+PSF method,which increased by 21.99%,22.86%and 60.14%,compared with conventional OSEM method(t=28.321,19.11,11.059,all P<0.01).The difference percentage in smaller lesions that diameter≤22 mm was significantly higher than that in larger lesions that diameter>22 mm(24.1%vs.21.1%,25.3%vs.19.3%,70.6%vs.63.3%;Z=-3.658,-4.313,-2.154,all P<0.05),and the difference percentage in low contrast lesions that SNR≤15.31 was significantly higher than that in high contrast lesions that SNR>15.31(23.6%vs.21.4%,25.3%vs.21.1%,85.7%vs.46.0%;Z=-3.519,-2.336,-5.106,all P<0.05).Among the evaluation results of lesion detectability of different reconstruction algorithms,OSEM+TOF+PSF image showed the mediastinal lymph node metastasis most clearly(87.4%of the lesions were clearly existing),which was significantly higher than that of OSEM image(73.1%of lesions were clearly existing)(χ2=11.704,P=0.001),however,the proportion of lesions clearly existing in OSEM+PSF image did not significantly increase compared with OSEM image(73.1%vs.75.8%;χ2=0.361,P=0.548).Conclusion The combination of TOF and PSF can significantly improve the detection ability,SNR and SUV of mediastinal lymph node metastasis of lung cancer,especially in small and low contrast lesions.

Objective To analyze the medication law and academic thoughts of Professor Wang Junhong in the treatment of tic disorders(TD)in children.Methods The cases of children with TD diagnosed and treated by Professor Wang Junhong from January 2015 to November 2022 were selected.Excel 2016 was used to analyze the clinical information of children with TD.The frequency ranking,property,taste and meridian tropism,and changes of prescription drugs were analyzed in multiple dimensions.SPSS Modeler 18.0 was used to analyze the drug association rules of prescriptions in 2021 and 2022.Cytoscape 3.9.0 was used to analyze the complex network of drug-drug strong,medium and weak links obtained by SPSS Modeler 18.0.The drug groups were obtained in SPSS,and Excel 2016 was used to analyze the annual changes of high-frequency drugs.Results Totally 5586 prescriptions were included,involving 198 kinds of Chinese materia medica,with a total frequency of 108356 times.The top five kinds of high-frequency Chinese materia medica were Chrysanthemi Flos,Acori Tatarinowii Rhizoma,Coptidis Rhizoma,Crataegi Fructus,Polygalae Radix.The medicinal properties were mostly cold,warm and mild.The medicinal tastes were mainly bitter,sweet and pungent.The main meridians of drugs were liver,heart and lung meridians.The association rule analysis showed that the common couplet medicines were Chrysanthemi Flos-Acori Tatarinowii Rhizoma and Acori Tatarinowii Rhizoma-Scorpio.Commonly used triple combination was Chrysanthemi Flos-Scorpio-Acori Tatarinowii Rhizoma.Clustering analysis showed 4 drug groups,reflecting the characteristics of Professor Wang Junhong's treatment of calming liver and tranquilizing mind.According to the time-flow analysis,since 2020,the proportion of drugs such as Bupleuri Radix,Scutellariae Radix,Haliotidos Concha,Gastrodiae Rhizoma and Margaritifera Concha have gradually increased,indicating that more attention should be paid to treating the liver,resolving phlegm and calming the mind.Conclusion In the treatment of TD in children,Professor Wang Junhong takes heart,liver and lung as the center.The prescription medication is to relieve wind and phlegm,soothe the liver and tranquilize the mind.In recent years,it has attached importance to the role of regulating emotions and resolving phlegm in the treatment of children with TD.