OBJECTIVETo provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.

METHODTolbutamide, chlorzoxazone, coumarin, nifedipine, and phenacetin were as probe substrates of rat CYP2C9, CYP2E1, CYP2A6, CYP3A4, and CYP1A2, and were incubated in rat liver microsomes with astragaloside IV. Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture. The K(i) values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition, noncompetitive inhibition, noncompetitive inhibition, and mixed-type inhibition.

RESULTIC50 and K(i) values were estimated, and the types of inhibition were determined. Among the five probe substrates, astragaloside IV might not significantly affect CYP2E1, CYP2A6 and CYP1A2-mediated metabolism in rats, but was a competitive inhibitor of CYP2C9 (IC50 35.40 micromol x L(-1), K(i) 42.88 micromol x L(-1)), and was a uncompetitive inhibitor of CYP3A4 (IC50 88.24 micromol x L(-1), K(i) 33.31 micromol x L(-1)).

CONCLUSIONThese results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4, which provided useful information for safe and effective use of astragaloside IV.

Animals ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Kinetics ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Triterpenes ; pharmacology

Objective To investigate the effect and mechanism of miR-27a-3p on nerve cell apoptosis induced by oxygen glucose deprivation/reoxygenation(OGD/R)through regulation of Rho family GTPase 3(Rnd3)expression.Methods PC12 neurons were cultured in vitro and reoxygenated for 3,6,9 h and 12 h after 2 h oxygen glucose deprivation.Cell viability,miR-27a-3p expression and Rnd3 mRNA expression were assessed at each time point and the optimal reoxygenation time point was screened.After transfection of miR-27a-3p Mimic,miR-27a-3p Inhibitor and their negative control,transfection of shRnd3 and its negative control,or co-transfection of shRnd3 and miR-27a-3p Inhibitor through lentivirus,CCK-8 assay was used to detect cell activity.The apoptosis rate of the cells was detected using flow cytometry.Expression of miR-27a-3p and Rnd3 mRNA was detected by RT-qPCR.Expression of apoptosis-related protein and Rnd3 protein was detected by Western blot.The dual luciferase reporter assay confirmed the targeting relationship between miR-27a-3p and Rnd3.Results Upregulation of miR-27a-3p increased cell viability,decreased total cell apoptosis rate,suppressed pro-apoptotic proteins Cleaved Caspase-3(C-caspase-3)and Bax,and promoted expression of anti-apoptotic protein Bcl-2(P<0.05);The opposite result was found when down-regulating miR-27a-3p.The double luciferase reporter gene assay showed that Rnd3 was the target gene of miR-27a-3p.Down-regulation of Rnd3 increased cell viability,decreased the total rate of apoptosis,suppressed the pro-apoptotic protein C-caspase-3,Bax,and promoted expression of the anti-apoptotic protein Bcl-2(P<0.05).However,miR-27a-3p Inhibitor reversed the protective effect of shRnd3.Conclusion miR-27a-3p alleviates OGD/R-induced damage to PC12 neurons by targeting Rnd3 to inhibit cell apoptosis.

Ferroptosis is a newly cell death mode discovered in recent years,involving in a variety of pathophysiological processes,such as ischemia reperfusion injury,neurodegenerative diseases and tumors,etc.At present,there is a lack of effective method to prevent and treat ischemic stroke worldwide,and ferroptosis which is involved in cerebral ischemia reperfusion injury.50 articles were included in this paper after searching the related literature,which published in databases such as PubMed,Wanfang,VIP and CNKI in recent years.Discussing the iron metabolism and the concept,mechanism and regulation of ferroptosis,the role of ferroptosis in the mechanism of cerebral ischemia reperfusion injury,and the method of inhibiting ferroptosis,this paper attempts to provide reference for finding a new potential treatment for ischemic stroke from the direction of inhibiting ferroptosis.

Objective To explore the feasibility and efficacy of endoscopic balloon dilation in treatment of esophageal stenosis caused by operation of congenital esophageal atresia. Methods A retrospective analysis was performed on data of 218 children with type Ⅲ esophageal atresia, who underwent surgery in Zhengzhou Children' s Hospital from January 2009 to December 2017. The occurrence of postoperative complications and efficacy of endoscopic balloon dilation in treatment of esophageal stenosis was analyzed. Results Among the 218 patients with congenital esophageal atresia, 92 were type Ⅲa and 126 were type Ⅲb. Postoperative anastomotic leakage occurred in 46 cases (21. 1％), including 29 (31. 5％) of type Ⅲa and 17 (13. 5％) of type Ⅲb. Postoperative anastomotic stenosis occurred in 53 cases (24. 3％), including 29 ( 31. 5％) of type Ⅲa and 24 ( 19. 0％) of typeⅢb. The incidence of anastomotic leakage and anastomotic stenosis in different types was significantly different (χ2=10. 383, P=0. 001; χ2=4. 497, P=0. 034). The 53 cases of anastomotic stenosis underwent 123 times of endoscopic balloon dilation, with mean time of 3. 5±1. 6, and were finally clinically recovery. No esophagus perforation occurred. Among them, 29 cases of type Ⅲa underwent 73 times with mean of 4. 0±1. 8, and 24 cases of type Ⅲb underwent 50 times with mean of 2. 5±0. 7. The difference between the two types was statistically significant (t=-4. 053, P=0. 027). Conclusion Children with type Ⅲa esophageal atresia has a higher incidence of anastomotic stenosis and leakage, and more times of esophageal dilation. Endoscopic balloon dilation is safe and effective in treatment of esophageal stenosis after surgery for patients with congenital esophageal atresia.

Objective:To evaluate the value of magnetic resonance imaging (MRI) in differentiating Brucella spondylitis from tuberculosis spondylitis. Methods:A retrospective analysis method was used to include Brucella spondylitis patients and tuberculous spondylitis patients who had undergone MRI examination at the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2017. All patients data of MRI examination (all had T1WI, T2WI, STIR images) were collected and compared. The differences in lesion location, MRI signal, vertebral body destruction, vertebral wedge, kyphosis deformity, attachment destruction, dead bone, bone hyperplasia, intervertebral space change, abscess location, and abscess range were analyzed. Results:A total of 91 patients with brucella spondylitis were selected, including 36 women and 55 men, with an average age of 49.40 years old; 112 patients with tuberculous spondylitis selected in the same examination, including 48 women and 64 men, with an average age of 47.15 years old. There was no statistically significant difference in gender and age between the two groups (χ 2 = 0.225, t = 1.387, P > 0.05). Brucella spondylitis was more common in lumbar spine [72.53% (66/91)], and tuberculosis spondylitis was more common in thoracic spine [47.32% (53/112)]. Brucella spondylitis patients showed higher T2WI hyperintensity than tuberculosis spondylitis patients [51.65% (47/91) vs 24.11% (27/112), P <0.05]; and showed lower T2 hyperlipidemia than patients with tuberculosis spondylitis [59.34% (54/91) vs 72.32% (81/112), P < 0.05]; the incidence rates of mild destruction of vertebral body, bone hyperplasia, normal intervertebral space, paravertebral abscess, and abscess not exceeding the range of vertebral body were higher than those of patients with tuberculosis spondylitis [81.32% (74/91), 93.41% (85/91), 37.36% (34/91), 71.43% (65/91), 38.46% (35/91) vs 20.54% (23/112), 28.57% (32/112), 1.79% (2/112), 30.36% (34/112), 1.79% (2/112), P < 0.01]; the incidence rates of vertebral body severe destruction, vertebral wedge less than 1/2, kyphosis deformity, dead bone, inter vertebral space narrowing, inter vertebral space vanishing, psoas abscess, abscess beyond the range of vertebral body were lower than those of patients with tuberculous spondylitis [12.09% (11/91), 18.68% (17/91), 2.20% (2/91), 2.20% (2/91), 61.54% (56/91), 1.10% (1/91), 2.20% (2/91), 1.10% (1/91) vs 75.89% (85/112), 72.32% (81/112), 29.46% (33/112), 46.43% (52/112), 79.46% (89/112), 18.75% (21/112), 66.96% (75/112), 74.11% (83/112), P < 0.01]. Conclusions:MRI signs can be used to differentiate Brucella spondylitis from tuberculosis spondylitis through analysis of bone hyperplasia, vertebral body destruction, vertebral wedge, kyphosis deformity, dead bone, abnormal intervertebral space, and paravertebral abscess and psoas abscess.

Objective:To analyze the characteristics and quantitative evaluation of Brucella spondylitis patients by magnetic resonance T2 mapping. Methods:A prospective clinical study was conducted to analyze the MRI data of 23 patients with brucellosis spondylitis diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to September 2018, and 25 healthy volunteers were selected as the control group. MRI was used to examine the vertebral bodies of the subjects, and T2 mapping map was automatically generated. Regions of interest (ROI) were selected on the T2 mapping map to generate T2 mapping values automatically. The T2 mapping values of diseased vertebrae, adjacent unaffected vertebrae, paravertebral abscess and healthy volunteers were analyzed.Results:Among 48 MRI examinees, 23 cases were Brucella spondylitis, including 17 males and 6 females, aged (38.5 ± 13.4) years; 25 healthy volunteers, including 15 males and 10 females, aged (35.1 ± 12.7) years. In 23 patients with Brucella spondylitis, 5 thoracic vertebrae, 40 lumbar vertebrae and 7 sacral vertebrae were involved, with a total of 52 vertebral bodies. Among them, 11 (21.2%) vertebral bodies showed bone marrow edema on MRI, 41 (78.8%) vertebral bodies showed bone marrow edema and vertebral bone destruction. T2 mapping values of the diseased vertebrae, adjacent unaffected vertebrae and paravertebral abscess in Brucella spondylitis patients and normal vertebrae in healthy volunteers were (115.62 ± 11.37), (75.21 ± 5.57), (240.26 ± 30.67) and (77.29 ± 4.19) ms, respectively. There were significant differences between the diseased vertebrae in Brucella spondylitis and adjacent unaffected vertebrae in Brucella spondylitis, and there were significant differences between the diseased vertebrae in Brucella spondylitis and normal vertebrae in healthy volunteers ( t = 26.78, 19.42, P < 0.05). Conclusion:Magnetic resonance T2 mapping can be used to evaluate the pathological tissues in Brucella spondylitis patients, and it has certain guiding significance for the quantitative description and qualitative diagnosis.

Micro/nanoplastics (MNPs), recognized as emerging environmental pollutants, are widely distributed in natural environments. Due to their small particle size and significant migratory capacity, MNPs can infiltrate diverse environmental matrices, then invade and accumulate in the organism via the skin, respiration, and digestion. Recently, concerns have grown over the detrimental effects and potential toxicity of MNPs on reproductive health. This review summarized published epidemiological and toxicological studies related to MNPs exposure and their effects on reproductive health. Firstly, this review critically examined the current landscape of epidemiological evidence and found that MNPs (e.g., polystyrene, polypropylene, polyvinyl chloride, polyethylene, etc.) are present in various biological specimens from both males and females, and their presence may be associated with an increased risk of reproductive disorders. Secondly, extensive toxicological studies revealed that MNPs exposure induces reproductive health damage through mechanisms such as disrupting the microstructure of reproductive organs and altering molecular-level expressions. Oxidative stress, inflammatory responses, and apoptosis are identified as potential links between MNPs exposure and reproductive damage. Finally, this review addressed the prevalent shortcomings in existing studies and proposed future directions to tackle the challenges posed by MNPs-induced reproductive harm. These insights aim to inform strategies for safeguarding public reproductive health and ecological security, providing a scientific foundation for mitigating risks associated with MNPs pollution.

ObjectiveTo investigate the application value of digital three-dimensional reconstruction in liver transplantation for hepatic alveolar echinocoecosis (HAE).MethodsClinical data of 21 patients with end-stage HAE undergoing liver transplantation (LT) and 6 living donors in the First Affiliated Hospital of Xinjiang Medical University between April 2012 and December 2014 were retrospectively studied. Among the 21 patients, 13 were males and 8 were females with the average age of (43±13) years old. Among the 6 donors, 4 were males and 2 were females with the average age of (40±9) years old. Fifteen cases underwent extracorporeal hepatectomy and autotransplantation and 6 cases underwent living donor LT. The informed consents of all patients and 6 living donors were obtained and the local ethical committee approval had been received. All patients and donors received computer tomography (CT) plain scan, 3-phase (arterial phase, portal venous phase and delayed phase) enhancement scan and computed tomography angiography (CTA). The total liver volume and the liver graft volume were measured according to the two-dimensional liver image. The digital three-dimensional liver reconstruction software was used to perform three-dimensional model reconstruction. The total liver volume and the liver graft volume were measured a second time. The liver section was designed and the individualized virtual surgery was performed. The actual total liver volume and the liver graft volume were measured during LT to assess the error rate of liver volume predicted before operation. The comparison of liver volume data was conducted usingt test and the comparison of the error rate of liver graft volume was conducted using Chi-square test.Results The intrahepatic anatomical relationship was clearly displayed by the three-dimensional model, which was in accordance with that observed during operation. The liver graft volume of 15 patients undergoing extracorporeal hepatectomy and autotransplantation and 6 patients undergoing living donor LT calculated by the digital three-dimensional reconstruction technology was (766±197) ml, which was signiifcantly smaller than (833±243) ml calculated by the two-dimensional measurement (t=-3.674,P<0.05). Compared with the actual liver graft volume of (955±194) ml measured during operation, the average error rate of the liver graft volume calculated by the three-dimensional reconstruction technology was (6±1) %, which was signiifcantly smaller than (13±2) % of that calculated by two-dimensional measurement (t=-14.346,P<0.05). The liver graft volume measured by the three-dimensional measurement was positively correlated with the actual liver graft volume measured during operation (r=0.967,P<0.05). All the operations were completed successfully. One patient died of acute renal failure 12 d after LT. No case was observed developing liver failure or hemorrhage or other severe complications. The growth of the liver graft was good and the anastomotic stoma of intrahepatic vessels was clear by CT reexamination and three-dimensional reconstruction after operation. ConclusionThe application of three-dimensional reconstruction technology in preoperative assessment and operation planning of LT for end-stage HAE can improve the precision and success rate and achieve good curative effect.

Objective To evaluate the value of intrathecal synthetic related markers in patients with mild cognitive impairment(MCI),Alzheimer's disease(AD),and other types of dementia.Methods Retrospec-tively collect the clinical data of 577 patients diagnosed with MCI(MCI group,178 cases),AD(AD group,131 cases),and other types of dementia(other types group,268 cases)from June 2019 to July 2023 in Beijing Tiantan Hospital,Capital Medical University.Oligoclonal zone electrophoresis(OCB)and 24 h intrathecal pro-tein synthesis rate(ISR)of each group were investigated,and the difference of different indexes among the groups was compared to evaluate the value of related indexes in the differential diagnosis of different diseases.Results Compared with AD group and other groups,AD group had a higher proportion of females,more patients were＞50-70 years old,and the incidence of abnormal lipid metabolism was higher,with statistical significance(P＜0.05).There were significant differences in OB(S),cerebrospinal fluid albumin,serum albumin and cerebrospinal flu-id IgG in different disease groups(P＜0.05).IgG index and ISR in patients with positive SOB(CSF)were higher than those in negative and weakly positive patients,and the differences were statistically significant(P＜0.001).IgG index was positively correlated with ISR(r=0.878,P＜0.001).Conclusion Intrathecal synthetic mark-ers such as IgG index,SOB(CSF)and 24 h ISR have synergistic effects in the diagnosis of cognitive dysfunction and various dementias,which can be collectively utilized in the diagnosis of diseases.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.