OBJECTIVE To investigate the effect and mechanism of self-assembled nanoparticles from Shaoyao gancao decoction （SGD-SAN） on the intestinal absorption behavior of its main active components. METHODS SGD-SAN was prepared and characterized. Using an in-situ single-pass intestinal perfusion model in rats， the absorption characteristics of five active components （albiflorin， paeoniflorin， liquiritin apioside， liquiritin， glycyrrhizic acid） from SGD-SAN in the jejunum and ileum were studied， with the absorption rate constant （ K a ） and apparent permeability coefficient （ P eff ） as indicators， and compared with free drugs. In the intestinal segment with optimal absorption， the effects of drug concentration and efflux transporter inhibitors （P-glycoprotein inhibitor verapamil， multidrug resistance-associated protein 2 inhibitor indomethacin， breast cancer resistance protein inhibitor reserpine） on the intestinal absorption characteristics of these components were examined. RESULTS The obtained SGD-SAN exhibited a spherical shape with uniform sizes， an average particle diameter of （155.57±2.65） nm， a polydispersity index of 0.34±0.03， and a Zeta potential of （－9.30±1.12） mV. The average total content of five active components， including albiflorin， was 12.26%， and remained unaffected by enzymatic degradation and intestinal physical absorption. Compared with the free drug group， the five active components in the SGD-SAN group exhibited higher absorption rates in the ileal segment， with significantly elevated K a and P eff values （except for the P eff value of glycyrrhizic acid in the ileal segment） （ P ＜0.05 or P ＜0.01）. Their absorption demonstrated a concentration-dependent trend. In the free drug groups， the absorption of each component was regulated by corresponding inhibitors （ P ＜0.05 or P ＜0.01）； whereas in the SGD-SAN groups， except for albiflorin and paeoniflorin， the absorption of the remaining components was not affected by the inhibitors （ P ＞0.05）. CONCLUSIONS SGD-SAN significantly enhances the intestinal absorption efficiency of active components. The above absorption-enhancing effect may be related to the avoidance of efflux transporter influence and the presence of a mixed absorption mode.

BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

BACKGROUND:In recent years,more and more studies have confirmed that ferroptosis of dopaminergic neurons is involved in the pathogenesis of Parkinson's disease,and verbascoside has been confirmed to have antioxidant,anti-inflammatory and neuroprotective effects. OBJECTIVE:To investigate the protective effect of verbascoside on Erastin-induced ferroptosis of MN9D cells and its action mechanism. METHODS:MN9D cells were divided into control group,model group(20 μmol/L Erastin group),Erastin+1 μg/mL verbascoside group,Erastin+5 μg/mL verbascoside group,and Erastin+10 μg/mL verbascoside group.MN9D cells were cultured in a CO2 incubator for 24 hours,then pretreated with different mass concentrations of verbascoside for 8 hours,and induced with 20 μmol/L Erastin for 24 hours.The levels of reduced glutathione,superoxide dismutase,total iron ion,and malondialdehyde were detected by ELISA.The expression of tyrosine hydroxylase was detected by immunohistochemistry.The expressions of tyrosine hydroxylase,nuclear factor erythrocyte-2-associated factor 2,heme oxygenase-1,and glutathione peroxidase 4 were detected by western blot assay. RESULTS AND CONCLUSION:(1)Compared with the control group,the levels of reduced glutathione and superoxide dismutase were significantly decreased(P<0.05),and the levels of malondialdehyde and total iron ion were significantly increased in the model group(P<0.05).Compared with the model group,the levels of reduced glutathione and superoxide dismutase were significantly increased(P<0.05),and the levels of malondialdehyde and total iron ionized water were decreased in 1,5,10 μg/mL verbascoside groups(P<0.05).(2)Compared with the control group,the area of tyrosine hydroxylase positive cells in the model group was significantly reduced(P<0.05).Compared with the model group,the area of tyrosine hydroxylase positive cells was significantly increased in 1,5,10 μg/mL verbascoside groups(P<0.05).(3)Compared with the control group,the protein expressions of tyrosine hydroxylase,nuclear factor erythrocyte-2-associated factor 2,heme oxygenase-1 and glutathione peroxidase 4 were significantly decreased in the model group(P<0.05).Compared with the model group,the protein expression levels of tyrosine hydroxylase,nuclear factor erythrocyte-2-associated factor 2,heme oxygenase-1,and glutathione peroxidase 4 were significantly increased in 1,5,10 μg/mL verbascoside groups(P<0.05).The results suggested that verbascoside could inhibit Erastin-induced ferroptosis in MN9D cells,possibly by activating nuclear factor erythrocyte-2-associated factor 2/heme oxygenase-1/glutathione peroxidase 4 pathway.

Metastatic dissemination is the major cause of death from breast-cancer (BC). Fusobacterium nucleatum (F.n) is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis. Here, with an experimental model, we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes. Therefore, the F.n may be a potential target to prevent metastasis. Given the fact that cancer-associated fibroblasts (CAFs) are abundant in BC and located near blood vessels, we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37, with the characteristics of biosafety and freely intercellular trafficking, for depleting intratumoral F.n, leading to a 72.1% reduction in lung metastatic nodules number without affecting the balance of the systemic flora. Notably, mild photothermal treatment was found that could normalize CAF, contributing to synergistically inhibiting BC metastasis. In addition, the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor. Together, our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

Objective To develop the "Questionnaires on the Knowledge, Attitudes, and Practices of College Students in Response to Public Health Emergencies" and validate its reliability and validity. Methods The initial questionnaire was developed according to literature review, expert consultations, and one-on-one interviews with students and educators. A total of 43 college students were selected as the pre-test subjects using the convenience sampling method. The final version of the questionnaire was developed using item analysis and expert consultations. A total of 682 college students were selected as the validation subjects using the cluster sampling method. The exploratory factor analysis and confirmatory factor analysis were used to assess the reliability and validity of the questionnaire. Results The final version of the questionnaire consisted of three dimensions: knowledge, practice, and attitude, with 5, 10, 7 items, respectively. The KMO test value for the questionnaire was 0.804, with Bartlett′s test of sphericity showing a chi-square value of 2 000.557 (P<0.01). The content validity index for each item ranged from 0.894 to 1.000, with the overall content validity index for the questionnaire being 0.966 and 0.973. The exploratory factor analysis identified three common factors, with a cumulative variance contribution rate of 54.1%. The result of confirmatory factor analysis showed good model fit, with model fit index, comparative fit index, normed fit index, incremental fit index, Tucker-Lewis Index, root mean square error of approximation of 2.960, 0.930, 0.940, 0.930, 0.950 and 0.070, respectively. The Cronbach's α coefficient for the questionnaire was 0.772, split-half reliability was 0.604, and test-retest reliability was 0.905. Conclusion The "Questionnaires on the Knowledge, Attitudes, and Practices of College Students in Response to Public Health Emergencies" demonstrates good reliability, and it is suitable for widespread application.

Objective:To explore the correlation between the level of T-lymphocyte subsets in peripheral blood and the progression of Alzheimer′s disease (AD).Methods:A cross-sectional study was conducted, including 30 cases of amnestic mild cognitive impairment (aMCI; aMCI group), 30 cases of mild AD (Mi-D; Mi-D group), 30 cases of moderate AD (Mo-D; Mo-D group), who were diagnosed in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from January to December 2023, and 30 normal controls (normal control group) matched by age and gender. The levels of T cell subsets in peripheral blood were detected by flow cytometry, and the subpopulations of CD4 +T cells, Th cells, were examined. Binary Logistic regression was used to explore the correlation between factors affecting patients′ cognitive function and the onset of AD, and Spearman′s correlation analysis was applied to assess the association between the level of peripheral blood immune cells and the severity of AD. Results:There were no statistically significant differences in peripheral blood CD4 +T cells ( F=1.762, P=0.158), CD8 +T cells ( F=0.370, P=0.775), CD4 +/CD8 +ratios ( F=1.976, P=0.121), and regulatory T cells (Tregs) levels ( F=0.232, P=0.874) among the aMCI group, Mi-D group, Mo-D group, and normal control group in the intergroup comparisons (all P>0.05). The study subjects were stratified according to gender, age, body mass index, and years of education affecting the cognitive function of AD patients, and the peripheral blood CD4 +T cells, CD8 +T cells, CD4 +/CD8 + ratios and Tregs levels showed no statistically significant differences among groups (all P>0.05). The results of binary Logistic regression analysis showed that the peripheral blood CD8 +T-cell level ( OR=1.131, 95% CI 1.009-1.268, P=0.035) was a risk factor for the onset of AD. Further analysis of peripheral blood CD4 +T cell subsets revealed that Th1 cell levels were lower in the aMCI group compared to the Mi-D group ( t=-2.354, P=0.036), and the Mo-D group ( t=-2.079, P=0.026). The results of the Spearman′s correlation analysis showed that peripheral blood Th1 cell level was positively correlated with AD progression ( r=0.192, P<0.05). Conclusions:AD patients show peripheral immune imbalance, peripheral blood CD8 +T-cell level is a risk factor for the onset of AD, and peripheral Th1 cell level is positively correlated with the severity of AD. Monitoring the changes in peripheral blood Th1 cell level may have a predictive value for the progression of AD.

Objective:To develop a quality control model for anal sphincter ultrasound images and validate its diagnostic performance across multiple centers.Methods:A retrospective analysis was conducted on anal sphincter ultrasound images from seven medical centers in China between May 2019 and June 2022. A total of 7 040 images from 3 116 patients were included and divided into a training set（4 912 images）and a validation set（2 128 images）. The images were classified as standard or non-standard images by three experts. Three models were developed based on different image feature extraction methods：a single-branch model，a multi-branch weighted model，and a multi-branch ensemble model. The diagnostic performance of each model was evaluated using the area under the ROC curve（AUC），sensitivity，specificity，accuracy，positive predictive value，and negative predictive value，respectively. The optimal model was selected and compared with the performance of 4 doctors with varying experience levels. Sixty days later，the images with the assistance of the model's output were reassessed by the doctors to evaluate its impact on manual quality control.Results:① Among the 3 models，the multi-branch ensemble model demonstrated the highest AUC and sensitivity，with an AUC of 0.966（95% CI=0.958 - 0.974），a sensitivity of 91.83%，and a specificity of 91.41%. This model was named M quality. ② M quality's AUC was slightly lower than that of Senior A and B（0.966 vs. 0.976，0.976，and P<0.05），its sensitivity was slightly lower than that of Senior A（91.83% vs. 95.61%， P<0.001）but comparable to Senior B（91.83% vs. 92.89%， P=0.315），its specificity was slightly lower than Senior A and B（91.41% vs. 94.44%，98.18%，and P<0.05）. However，M quality significantly outperformed Junior A and B in AUC and sensitivity（AUC：0.966 vs. 0.850，0.818；sensitivity：91.83% vs. 84.90%，61.46%；all P<0.001），its specificity was higher than that of Junior A（91.41% vs. 80.28%， P<0.001）but lower than that of Junior B（91.41% vs. 95.96%， P<0.001）. ③ With model assistance，Senior B's sensitivity（92.89% vs. 94.20%， P=0.001）and Senior A's specificity（94.44% vs. 96.56%， P<0.001）improved significantly. Junior A and B showed significant improvements in AUC and sensitivity（AUC：0.931 vs. 0.850，0.914 vs. 0.818；sensitivity：91.83% vs. 84.90%，89.53% vs. 61.46%；all P<0.001）. After model assistance，Junior A's specificity increased（93.62% vs. 80.28%， P<0.001），while Junior B's specificity decreased（91.60% vs. 95.96%， P=0.013）. Conclusions:This study develops a quality control model for anal sphincter ultrasound images with robust diagnostic performance，approaching the level of seniors. The model significantly enhances the image quality assessment capabilities of juniors，demonstrating promising clinical application potential.

Gynecological diseases have a high prevalence and severely impact women's health and quality of life. Ultrasonography is the first-line imaging modality for assessing gynecological diseases. However，its diagnostic results are highly dependent on clinical experience and are subject to significant interobserver variability. In recent years，the rapid development of artificial intelligence technology has led to the construction of models based on ultrasonic images，which have demonstrated high accuracy in the identification of uterine，ovarian，and pelvic floor structures，as well as in the diagnosis，classification，and prognosis of diseases. These models hold great promise for clinical application.

Over the past 40 years,gynecological ultrasound in China has evolved from two-dimensional imaging to multi-modal imaging,quantitative analysis,artificial intelligence analysis and minimally invasive treatment,playing more and more important role in diagnosis and treatment of gynecological diseases.The development of diagnostic and therapeutic gynecological ultrasound techniques and relative clinical application advances in China were reviewed,and the future development prospects were looked forward to in this article.