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.

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 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.

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 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.

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.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Aim To investigate the effects of multi-gly-cosides of Tripterygium wilfordii(GTW)on mitochon-drial dynamics-related proteins and the mechanism of nephroprotective effects in IgA nephrophathy(IgAN)rats.Methods SPF grade male SD rats were random-ly divided into the Control group,modelling group,prednisone group(6.25 mg·kg·d-1)and GTW group(6.25 mg·kg·d-1).The IgAN rat model was established by the method of"bovine serum albumin(BSA)+carbon tetrachloride(CCl4)+lipopolysac-charide(LPS)".The total amount of urinary protein(24 h-UTP)and erythrocyte count in urine were meas-ured in 24 h urine.Blood biochemistry of serum albu-min(ALB),alanine aminotransferase(ALT),urea ni-trogen(BUN),and creatinine(Scr)were measured in abdominal aorta of the rats;immunofluorescence and HE staining were used to observe the histopathology of the kidneys;RT-PCR and Western blotting were used to detect the mRNA and protein expression levels of key proteins regulating mitochondrial division and fu-sion:dynamin-related protein 1(Drp1),mitochondrial fusion protein 1(Mfn1),and mitochondrial fusion pro-tein 2(Mfn2),and PTEN-induced putative kinase 1(Pink1),in the kidney tissue of rats.Results GTW significantly reduced urinary erythrocyte count and 24 h-UTP,decreased serum ALT,BUN and Scr levels,in-creased serum ALB levels,improved renal histopatho-logical status in IgAN rats,increased the protein and mRNA expression levels of Mfn1,Mfn2,and Pink1,and decreased the protein and mRNA expression levels of Drp1 in renal tissues.Conclusions GTW may regu-late mitochondrial structure and maintain the dynamic balance of mitochondrial dynamics by promoting the ex-pression of Mfn1,Mfn2,Pink1 and decreasing Drp1.This may result in a reduction in urinary erythrocyte counts and proteinuria,and an improvement in renal function.