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.

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.

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.

Objective:Using Mendelian randomization analysis to investigate the unidirectional causal effects of gut microbiota on gout and serum uric acid levels.Methods:The Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies (GWAS). The gut microbiota was used as the exposure factor, with gout and serum uric acid levels as the outcomes, utilizing the MiBioGen Consortium, FinnGen GWAS, and CKDGen Consortium meta-analysis databases. The analysis was performed using inverse variance weighted (IVW) method, MR-Egger, and weighted median (WM) approach. Additionally, sensitivity analysis was conducted by excluding heterogeneity and horizontal pleiotropy. This study used RStudio 4.3.1 software for analysis.Results:The IVW results confirmed that 17 microbiota taxa were associated with gout, including class Verrucomicrobiaceae [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], family Verrucomicrobiaceae [ OR(95% CI)=1.161(1.004, 1.344), P=0.044], genus Akkermansia [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], genus Collinsella [ OR(95% CI)=1.257(1.043, 1.516), P=0.016], genus Eubacterium hallii group [ OR(95% CI)=1.226(1.022, 1.471), P=0.027], genus Howardella [ OR(95% CI)=1.094(1.001, 1.195), P=0.046], genus Ruminococcaceae UCG010 [ OR(95% CI)=1.317(1.089, 1.593), P=0.004], order Clostridiales [ OR(95% CI)=1.182(1.007,1.387), P=0.041], order Verrucomicrobiales [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], class Melainabacteria [ OR(95% CI)=0.894(0.804, 0.994), P=0.038], family Streptococcaceae [ OR(95% CI)=0.851(0.727, 0.996), P=0.044], unknown family [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Streptococcus [ OR(95% CI)=0.836(0.710, 0.983), P=0.030], unknown genus [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Victivallis [ OR(95% CI)=0.857(0.736, 0.998), P=0.046], order Gastranaerophilales [ OR(95% CI)=0.890(0.800,0.989), P=0.030], and phylum Bacteroidetes [ OR(95% CI)=0.827(0.692, 0.989), P=0.037]. Additionally, 5 microbiota taxa were associated with serum uric acid levels: phylum Actinobacteria [ OR(95% CI)=0.963(0.925, 0.992), P=0.027], family ⅩⅢ [ OR(95% CI)=0.965(0.932, 1.008), P=0.035], genus Escherichia Shigella [ OR(95% CI)=1.047(1.005,1.089), P=0.034], genus Lachnospiraceae FCS020 group [ OR(95% CI)=0.974(0.941, 1.003), P=0.028], and genus Lachnospiraceae NC2004 group [ OR(95% CI)=0.966(0.943, 0.995), P=0.018]. No abnormalities in SNPs were found in the sensitivity analysis. Conclusion:An increase in the levels of class Verrucomicrobiae, family Verrucomicrobiaceae, genus Akkermansia, and genus Escherichia Shigella is associated with an increased risk of gout or serum uric acid levels, while an increase in the levels of class Melainabacteria, family Streptococcaceae, unknown family, phylum Actinobacteria, and family ⅩⅢ is associated with a decreased risk of gout or serum uric acid levels.

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.

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.

Objective:Acute kidney injury(AKI) is a common complication after cardiac surgery, and associated with increased risk of development of chronic kidney disease and mortality in the long term. Neutrophil percentage-to-albumin ratio(NPAR) is a new inflammatory marker that has been used to predict the poor prognosis of patients with cardiovascular disease or shock. However, the relationship between NPAR and AKI in patients with cardiac surgery has not been established. The aim was to evaluate the relationship between NPAR and AKI after cardiac surgery.Methods:Data of all adult patients underwent cardiac surgery with cardiopulmonary bypass from January 1, 2006 to December 31, 2018 were extracted from electronic medical record system of the Guangdong Provincial People's Hospital and retrospectively analyzed. The outcome of interest was AKI diagnosed by using the criteria of Kidney Disease Improving Global Outcomes. Logistic regression was used to assess the relationship between NPAR and postoperative AKI while adjust for potential confounders. In addition, restricted cubic spline(RCS) was utilized to provide a flexible description of the association of the preoperative NPAR and AKI. Results:Totally, 24 178 patients were analyzed. The incidence of AKI was 30.1%. Compared with patients without AKI, those with AKI were older and had higher rates of males, left ventricular ejection fraction(LVEF) less than or equal to 0.60, estimated glomerular filtration rate less than 90 ml·min -1·1.73 m -2, hypertension, diabetes, emergency surgery, preoperative critical illness, and reoperation. The baseline serum creatinine, serum uric acid, cardiopulmonary bypass time and postoperative mechanical ventilation time were higher or longer in AKI patients than those in none AKI patients. Then, patients were divided into four groups based on NPAR quartiles. After adjusting for confounding factors using logisitc regression, compared with patients with NPAR in group 3(1.551.97), respectively. The RCS showed a U-shaped nonlinear relationship( P for nonlinear less than 0.001) between NPAR and AKI after adjusting for potential confounding factors. RCS indicated the NPAR of 1.77 was the lowest risk for AKI. When NPAR less than 1.77, per 1-standard deviation(SD) increase in NPAR, the risk of AKI decreased by 23.2%( OR=0.768, 95% CI: 0.687, 0.859). Conversely, when NPAR above 1.77, per one SD increase in NPAR, the risk of AKI increased by 25.9%( OR=1.259, 95% CI: 1.166, 1.36). Conclusion:A U-shaped relationship between NPAR and AKI after cardiac surgery was shown. The appropriate value for NPAR might be 1.77. The risk of AKI might be increased, when less or above this value. NPAR might be used as an effective and economical tool to identify AKI risk among individuals with cardiac surgery, as well as to formulate individualized prevention and intervention strategy.

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.