This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

Objective To evaluate the effectiveness of CT angiography(CTA)imaging and fluoroscopic fusion navigation techniques in left atrial appendage closure(LAAC).Methods A total of 82 patients underwent LAAC in this prospective study and were matched(1:1)according to whether they underwent image fusion or not.The fusion group(41 cases)consisted of patients who received LAAC with the support of CTA and X-ray fluoroscopy fusion technology;The non fusion group(41 cases)consisted of patients who underwent surgery using traditional surgical methods without the support of this technology.Record the intraoperative indicators,perioperative complications,and postoperative follow-up outcomes of both groups.Results The surgical time in the fusion group was significantly shorter than that in the non fusion group[(50.23±25.23)min vs.(65.71±29.15)min,P=0.012],The difference is statistically significant.Compared with the non fusion group,the fusion group significantly reduced the total radiation dose[(195.15±205.59)mGy vs.(351.08±196.54)mGy],dose area product[(22.47±20.05)Gy·cm2vs.(38.12±19.38)Gy·cm2],and X-ray fluoroscopy time[(9.03±3.58)min vs.(13.35±4.23)min].Correspondingly to the radiation dose,the amount of contrast agent used in the fusion group was also relatively reduced[(59.32±24.65)ml vs.(93.12±35.08)ml],and the differences were statistically significant(all P＜0.001).There was a significant difference in the rate of repeated interval puncture(2.44％vs.12.20％,P=0.090),but the difference was not statistically significant.Occluder implantation success rates were identical(100.00％vs.100.00％).No statistically significant differences in procedural complications were observed between the groups.Conclusions Three-dimensional CTA and fluoroscopic fusion navigation techniques are not only feasible and safe but also enhance the efficiency of LAAC procedures.

Biofilm is one of the important reasons for bacterial resistance and persistent infection in Staphylococcus aureus,which poses a significant threat to the dairy farming industry in southern Xinjiang.Although quercetin has antibacterial properties,its poor hydrophilicity and low solubility limit its clinical application.Therefore,quercetin nanogel was prepared by the electrostatic interac-tion between guar gum(positive charge)and hyaluronic acid(negative charge)under the action of sodium tripolyphosphate in this study.Using encapsulation efficiency and loading capacity as indi-cators,the optimal formula was screened through single factor experiments and response surface methodology,and characterized.The minimal inhibitory concentration(MIC)and minimal mem-brane inhibitory concentration(MBIC)of quercetin nanogel against Staphylococcus aureus were determined by micro broth dilution method and micro plate semi quantitative method.The results showed that the optimal formulation of quercetin nanogel was 11.6 g/L guar gum,10.0 g/L hyalu-ronic acid and 50.0 g/L sodium tripolyphosphate.The encapsulation efficiency and loading capacity were 79.4％and 7.6％,respectively.The particle size and Zeta potential were(396.0±4.2)nm and(-25.0±0.8)mV,respectively,indicating that the nanogel had good dispersion,high stability and excellent drug loading capacity.The MIC and inhibitory rate of quercetin nanogel against Staphy-lococcus aureus were 8.0 mg/L and 83.8％,respectively.The MBIC and inhibitory rate of quercetin nanogel against Staphylococcus aureus were 8.0 mg/L and 38.3％,respectively.Therefore,the pre-pared quercetin nanogel solved the problems of low solubility and poor hydrophilicity of quercetin,improved the inhibitory effect of quercetin on the membrane of Staphylococcus aureus,and was expected to be further applied to the treatment of cow bacterial diseases in southern Xinjiang.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

Objective To evaluate the effectiveness of CT angiography(CTA)imaging and fluoroscopic fusion navigation techniques in left atrial appendage closure(LAAC).Methods A total of 82 patients underwent LAAC in this prospective study and were matched(1:1)according to whether they underwent image fusion or not.The fusion group(41 cases)consisted of patients who received LAAC with the support of CTA and X-ray fluoroscopy fusion technology;The non fusion group(41 cases)consisted of patients who underwent surgery using traditional surgical methods without the support of this technology.Record the intraoperative indicators,perioperative complications,and postoperative follow-up outcomes of both groups.Results The surgical time in the fusion group was significantly shorter than that in the non fusion group[(50.23±25.23)min vs.(65.71±29.15)min,P=0.012],The difference is statistically significant.Compared with the non fusion group,the fusion group significantly reduced the total radiation dose[(195.15±205.59)mGy vs.(351.08±196.54)mGy],dose area product[(22.47±20.05)Gy·cm2vs.(38.12±19.38)Gy·cm2],and X-ray fluoroscopy time[(9.03±3.58)min vs.(13.35±4.23)min].Correspondingly to the radiation dose,the amount of contrast agent used in the fusion group was also relatively reduced[(59.32±24.65)ml vs.(93.12±35.08)ml],and the differences were statistically significant(all P＜0.001).There was a significant difference in the rate of repeated interval puncture(2.44％vs.12.20％,P=0.090),but the difference was not statistically significant.Occluder implantation success rates were identical(100.00％vs.100.00％).No statistically significant differences in procedural complications were observed between the groups.Conclusions Three-dimensional CTA and fluoroscopic fusion navigation techniques are not only feasible and safe but also enhance the efficiency of LAAC procedures.

Biofilm is one of the important reasons for bacterial resistance and persistent infection in Staphylococcus aureus,which poses a significant threat to the dairy farming industry in southern Xinjiang.Although quercetin has antibacterial properties,its poor hydrophilicity and low solubility limit its clinical application.Therefore,quercetin nanogel was prepared by the electrostatic interac-tion between guar gum(positive charge)and hyaluronic acid(negative charge)under the action of sodium tripolyphosphate in this study.Using encapsulation efficiency and loading capacity as indi-cators,the optimal formula was screened through single factor experiments and response surface methodology,and characterized.The minimal inhibitory concentration(MIC)and minimal mem-brane inhibitory concentration(MBIC)of quercetin nanogel against Staphylococcus aureus were determined by micro broth dilution method and micro plate semi quantitative method.The results showed that the optimal formulation of quercetin nanogel was 11.6 g/L guar gum,10.0 g/L hyalu-ronic acid and 50.0 g/L sodium tripolyphosphate.The encapsulation efficiency and loading capacity were 79.4％and 7.6％,respectively.The particle size and Zeta potential were(396.0±4.2)nm and(-25.0±0.8)mV,respectively,indicating that the nanogel had good dispersion,high stability and excellent drug loading capacity.The MIC and inhibitory rate of quercetin nanogel against Staphy-lococcus aureus were 8.0 mg/L and 83.8％,respectively.The MBIC and inhibitory rate of quercetin nanogel against Staphylococcus aureus were 8.0 mg/L and 38.3％,respectively.Therefore,the pre-pared quercetin nanogel solved the problems of low solubility and poor hydrophilicity of quercetin,improved the inhibitory effect of quercetin on the membrane of Staphylococcus aureus,and was expected to be further applied to the treatment of cow bacterial diseases in southern Xinjiang.

Objective:To compare the preliminary efficacy and adverse events of chemoradiotherapy (CRT) with or without immunotherapy in bladder preservation therapy for localized muscle-invasive bladder cancer (MIBC) confined to the pelvis.Methods:Clinical data of 60 patients with MIBC who received CRT with or without immunotherapy for bladder preservation at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2016 to June 2024 were retrospectively analyzed. Patients were divided into CRT plus immunotherapy group and CRT-alone group. Survival outcomes, bladder function preservation, recurrence and metastasis, as well as early and late radiation toxicities were evaluated. The Mann-Whitney U test was used for between-group comparisons. Overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method, and survival rates were compared by the log-rank test. Results:In the CRT plus immunotherapy group ( n=23), the median follow-up was 20 months. The median OS and median PFS were not reached. The 2-year OS, PFS, LRFS, and DMFS rates were 95.7%, 70.7%, 70.7%, and 92.9%, respectively, and 22 patients (96%) preserved normal bladder function. Patients with programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 had significantly higher 1-year PFS rate than those with CPS <1 (100% vs. 66.7%, P=0.004). In the CRT-alone group ( n=37), the median follow-up was 37 months, with median OS and PFS of 68 and 19 months, respectively. The 2-year OS, PFS, LRFS, and DMFS rates were 92.0%, 41.1%, 60.9% and 81.5%, respectively, and 33 patients (89%) preserved normal bladder function. Compared with the CRT-alone group, the CRT plus immunotherapy group showed a significant improvement in PFS ( χ2=4.38, P=0.036), while no significant differences were observed in OS, LRFS, or DMFS (all P>0.05). The incidence of acute hematologic toxicity in the CRT plus immunotherapy group and CRT-alone group were 52% (12/23), 27% (10/37) respectively, and late genitourinary toxicity was 22% (5/23), 8% (3/37), respectively, with no significant differences in overall acute or late toxicities (all P>0.05). Conclusions:For localized MIBC, bladder preservation with CRT combined with immunotherapy significantly improves PFS compared with CRT alone, while maintaining comparable safety. The PD-L1 status may serve as a favorable predictor for immunotherapy efficacy.

In this paper, the antitussive and expectorant activity of platycodin D (PD) were studied by constructing a mouse cough induced by concentrated ammonia water and a mouse trachea phenol red excretion model. The mechanism of antitussive and expectorant effect of PD was studied by metabolomics. The animal experiment was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (approval number: JZLLSC-20220739). Then mice were randomly divided into the normal, model, positive drug, PD low-dose, PD medium-dose and PD high-dose group. The antitussive and expectorant effects of PD were evaluated using a cough mouse model induced by concentrated ammonia water and a mouse tracheal phenol red excretion model, respectively. UHPLC-LTQ-Orbitrap-MS was used to identify the metabolites of mouse lung tissue, and multivariate statistical analysis method of orthogonal partial least squares discriminant analysis (OPLS-DA) was used for metabolites profile analysis. The differential metabolites were screened by variable projected importance value (VIP) and t-test results. Pathways for enrichment of differentiated metabolites were analyzed using the MetaboAnalyst platform. The comparative method was applied to analyze the differences in mechanisms of PD, Deapio-platycodin D (DPD) and total platycosides fraction. The results showed that PD at different concentrations could significantly prolong (P < 0.05) the incubation period of cough mice induced by ammonia water, reduce the coughs frequency, and significantly increase (P < 0.05) the amount of phenol red excretion in phenol red excretion model mice. PD could regulate 6 metabolic pathways of phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, glycerophospholipid metabolism, and tyrosine metabolism to exert antitussive effect. It could also regulate 8 metabolic pathways of linoleic acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, glycerol phospholipid metabolism, citric acid cycle and arachidonic acid metabolism to exert an expectorant effect. However, only linoleic acid metabolism and glycerophospholipid metabolism could be regulated by the PD, total platycosides fraction and DPD, which may be ascribed to the structural difference of the platycosides and the interaction between platycosides and the intestinal microbiota. Functional analysis showed that these metabolic pathways are closely related to the regulatory mechanisms of anti-inflammatory response, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and cell apoptosis. This study shows that PD possesses good antitussive and expectorant activities. In addition, the mechanism difference of PD, total platycosides fraction and DPD imply that the apiose in PD and the interaction between PD and intestinal microbiota could exert an important effect on the antitussive and expectorant mechanism of the platycosides.

The identification of the components absorbed in serum of platycosides in total saponins fraction of Platycodonis Radix is great significance, but there are still great challenges. In this study, 8 types of 44 primordial components from Platycodon saponins were firstly identified using the ultra-performance liquid chromatography-linear ion trap electrostatic field orbitrap high resolution mass spectrometry (UPLC-LTQ-Orbitrap-MS) equipped with the software of Compound Discoverer 3.2 and Trace finder 2.1. Then, the platycosides and their deglycosylated metabolites were used as the template molecules to construct the intestinal microbiota mediated method to identify the primary components and the prototypes in serum. As results, 57 components originating from 44 prototypes of platycosides were identified from drug-containing plasma. Those compounds consist of 12 prototypes of platycosides and 45 metabolites, while the prototypes in serum are also deglycosylated metabolites of other platycosides. The results showed that the intestinal microbiota mediated method could be applied to identify the metabolites of platycosides in total saponins fraction of Platycodonis Radix; and reveal the potential existing forms of prototypes of platycosides in plasma; In addition, it could clearly illustrate the one to many and many to one network of the prototypes and metabolites of platycosides. All animal protocols were approved by the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (No.JZLLSC-202100322).

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.