[Objective]To investigate the protective effect of Zhuangtongyin on the Middle Cerebral Artery Occlusion(MCAO)model by modulating ferroptosis through the Nrf2-SCL7A11/xCT-Gpx4 pathway and its underlying mechanism.[Methods]C57BL/6J mice were randomly divided into Sham operation group(Sham),model group(MCAO),low-dose Zhuangtongyin group(ZTY-L),high-dose Zhuangtongyin group(ZTY-H),with 5 mice in each group.The MCAO group was modelled by silica gel embolization,the middle cerebral artery of mice was embolized for 1h,then the silica gel was pulled out and reperfusion was performed after 72 h;and the other operations in the Sham group were the same as those in the MCAO group except that the thread plug was not inserted.The neural function of mice was evaluated by Zea-Longa method.TTC staining was used to evaluate the volume of cerebral infarction.The level of brain injury was evaluated by HE staining and Nissl staining.Prussian blue staining and the expression of iron transport-related carrier receptors TfR1 and DMT1 on mRNA level was detected by qPCR to evaluate the iron ion deposition level in mice brain.The expression of lipid peroxidation-related gene ACSL4 on mRNA level was detected by qPCR,and the content of 4-HNE was detected by ELISA kit to evaluate the lipid peroxidation level of mice brain.The expressions of ferroptosis marker PTGS2 mRNA level was detected by qPCR.The expressions of Nrf2,SCL7A11/xCT,Gpx4 in mice brain tissue were detected by Western-blot and immunofluorescence.[Results]Zhuangtongyin improved the nerve function of mice after MCAO(P＜0.05)and the cerebral infarction volume of mice(P＜0.05)and alleviate the pathological injury of cerebral cortex cells after MCAO operation.Zhuangtongyin attenuated the accumulation of trivalent iron ions in the brain tissue of mice following MCAO.Additionally,Zhuangtongyin downregulated the expression of TfR1 and DMT1 mRNA(P＜0.001),a transporter associated with cellular iron ion uptake,in the brains of post-MCAO mice.Furthermore,Zhuangtongyin reduced levels of lipid peroxidation product 4-HNE(P＜0.001)and suppressed ACSL4 mRNA expression in brain tissue post-MCAO(P＜0.001).Besides,Zhuangtongyin downregulated the expression of PTGS2 mRNA(P＜0.001),in the brains of post-MCAO mice.Zhuangtongyin increased the expression of nrf2 into the nucleus(P＜0.001),and increased the expression of xCT and Gpx4 in neurons after MCAO(P＜0.001).[Conclusion]Zhuangtongyin can enhance the nerve function and reduce cerebral infarction volume in MCAO/R mice,alleviate the pathological damage of cerebral cortex cells,and modulate the expression of key signaling molecules in the Nrf2-SCL7A11/xCT-Gpx4 pathway.Therefore,it is suggested that the mechanism by which Zhuangtongyin improves MCAO/R injury in mice may involve regulating ferroptosis through the Nrf2-SCL7A11/xCT-GPX4 pathway.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective To investigate the changes in the expression of complement C3,high mobility group protein B1(HMGB1),and glutathione peroxidase 4(GPX4)in brain tissue at different time points after cerebral ischemia-reperfusion injury in rats.Methods A total 72 SPF male SD rats were randomly divided into a sham operation group(36 rats)and a model group(36 rats).A rat model of middle cerebral artery occlusion was established using thread occlusion,and then the rats from the model group were further assigned into 4 subgroups with reperfusion time for 3,6 and 24 h and 3 d,respectively,with 9 rats in each subgroup.Zea Longa scoring was used to assess neu-rological function.R2StarMap imaging,diffusion-weighted imaging(DWI),T1 weighted imaging,and T2 weighted imaging were performed on all the rats.The volume of abnormal DWI signals were detected and the volume of cerebral infarction was measured.The original R2StarMap images were post-processed to generate R2*pseudo color images,and then the R2*values of the areas with blood supply from bilateral middle cerebral artery were measured to detect iron deposition in the brain.The protein expression of C3,HMGB1,and GPX4 was detected by Western blotting.Results The sham operation group showed no neurological damage,while the model group had a significant increase in neurological function scores at 3,6 and 24 h and 3 d after modeling when compared to the sham surgery group(P＜0.05).While the size of right cerebral infarct was in-creased significantly at 3,6 and 24 h and 3 d in the rats of the model group(P＜0.05).The R2*value of the area with blood supply from the right middle cerebral artery in the model group was significantly higher than that in the left side at 3,6 and 24 h and 3 d(P＜0.05,P＜0.01),and it was also obviously higher than that in the right side of the sham operation group at these time points(P＜0.05,P＜0.01).The R2*ratio of the right and left blood supply areas in the model group at 3,6 and 24 h and 3 d was also statistically higher than that in the sham operation group at corresponding time points(1.82±0.82 vs 1.12±0.31,P＜0.05;1.31±0.26 vs 1.04±0.14,P＜0.05;1.94±0.74 vs 1.06±0.10,P＜0.01;1.99±0.39 vs 1.02±0.11,P＜0.01).Compared with the sham operation group,the expression levels of C3 and HMGB1 was significantly increased in the model group at 3,6 and 24 h and 3 d,while that of GPX4 was notably reduced(P＜0.01).Conclu-sion Cerebral ischemia-reperfusion injury impairs the neurological function of rats and signifi-cantly affects the cerebral expression of complement C3,HMGB1,and GPX4.

Objective To investigate the clinical and magnetic resonance imaging(MRI)features of Trousseau's syndrome(TS)with acute cerebral infarction,so as to improve the accuracy of diagnosis of this disease.Methods Fifty-three cases of TS with clinically confirmed acute multiple brain infarction(AMBI)and 52 cases of TS without AMBI were enrolled,and the head MRI,primary tumor imaging and clinical data of the patients were retrospectively analyzed.The clinical and MRI features and thrombus types of the 2 groups were compared.Results There were significant differences in the types of thrombus between the 2 groups(P=0.001),while there were no significant differences in gender,age,whether they had hypertension,diabetes mellitus,hyperlipidemia,basic cardiovascular diseases or not,preventive medication use,abnormal coagulation function,or D-dimer level(all P＞0.05).The primary tumor type of 105 TS patients was mainly adenocarcinoma.MRI of the head of 53 TS with AMBI patients showed that the distribution area of acute and subacute infarct foci was bilateral anterior circulation in 16 cases,bilateral anterior circulation+bilateral posterior circulation in 17 cases,bilateral anterior circulation+unilateral posterior circulation in 4 cases,and unilateral anterior circulation in 16 cases.Enhancement scans were performed in 23 cases,of which 11 cases showed some infarct foci appeared enhanced and 12 cases did not show significant enhancement.Twenty-eight cases did not show meaningful stenosis of the cerebral arteries,4 cases showed stenosis occlusion of the cerebral arteries,and all lesions did not conform to cerebrovascular distribution.Twenty-four cases of arterial thrombosis(10 cases of carotid artery thrombosis,3 cases of lower-extremity arterial thrombosis,5 cases of cerebral arterial ring thrombosis,1 cases of pulmonary artery thrombosis,1 case of renal artery thrombosis,and 4 cases of subclavian artery thrombosis)and 3 cases of venous thrombosis(deep vein thrombosis of the lower extremities)were found among the patients with visualized thrombosis.The D-dimer level was increased in different degrees.Conclusion Multiple speckled and patchy acute anterior and posterior cerebral infarcts involving bilateral cerebral and cerebellar cortex,subcortical areas and hemi-oval centers with lesions not conforming to cerebrovascular distribution are the characteristic manifestations of MRI of the head in the combination of malignant tumors with TS.Adenocarcinoma is the main malignant tumor,and the combination of D-dimer index can improve the accuracy of diagnosis.

Objective:To explore the application value of histogram and texture feature analysis based on CT images in distinguishing long bone osteosarcoma (OS) from Ewing sarcoma (ES).Methods:A retrospective collection of 25 patients with long bone osteosarcoma and 25 patients with Ewing sarcoma confirmed by surgery and pathology in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Qilu Hospital of Shandong University and Nanjing Drum Tower Hospital, Nanjing University Medical School, from March 2018 to May 2023 was conducted. All patients were randomly divided into a training set (21 cases of OS and 19 cases of ES) and a validation set (4 cases of OS and 6 cases of ES) in an 8∶2 ratio. The region of interest (ROI) on CT images to extract texture feature parameters was manually sketched. Random forest and least absolute shrinkage and selection operator (LASSO) algorithm were used for feature screening. Logistic regression (LR), random forest (RF), support vector machine (SVM) and K-nearest neighbor (KNN) classifiers were used to establish models respectively. Receiver operating characteristic (ROC)curve was drawn and area under the curve (AUC) was calculated to evaluate the diagnostic efficiency of the four models.Results:A total of 100 texture parameters were extracted from CT images, and 8 feature parameters (maximum 3D diameter, 10th percentile, kurtosis, maximum pixel intensity value, inverse normalization, grayscale level variance, long range high grayscale emphasis, and low grayscale area emphasis) were obtained through screening. Four classifiers were used to establish models, and the AUC values of the four models (LR, RF, SVM, KNN) in the validation group were 0.92, 0.79, 0.83, and 0.73, respectively. LR and SVM classifier algorithm trains models had high diagnostic efficiency, with an accuracy of 90%, sensitivity of 83%, specificity of 100%, and AUC of 92% for the LR classifier validation set; the accuracy of SVM classifier validation set was 80%, sensitivity was 67%, specificity was 100%, and AUC was 83%.Conclusions:LR and SVM models have high value in distinguishing OS and ES.

Malignant tumors are one of the main causes of human death worldwide and pose a serious threat to human health. The current treatment methods are mainly the combination of chemotherapeutics， surgery， radiotherapy， or hormone therapy. The treatment process has limitations such as multidrug resistance， non-selective targeting of cancer cells， and drug toxicity. With the development and application of traditional Chinese medicine （TCM）， Chinese medicine has the characteristics of multi-angle and multi-mechanism coordination and slight toxic and side effects. It can effectively inhibit tumor proliferation， differentiation， and metastasis， and avoid drug resistance， serving as the focus of current tumor treatment research. Hedysari Radix， one of the genuine medicinal materials in Gansu province， is a tonic Chinese medicine with a wide range of pharmacological effects such as anti-inflammation， immune regulation， anti-oxidation， prevention and treatment of diabetic complications. In the majority of the ancient works on herbs of the past dynasties， Hedysari Radix was included under the item of Astragali Radix and used as Astragali Radix. Hedysari Radix is superior to Astragali Radix in enhancing immunity， scavenging free radicals， and resisting liver fibrosis. Studies have found that the effective components of Hedysari Radix have a prominent anti-tumor effect and a significant inhibitory effect on various malignant tumors such as liver cancer， bladder cancer， gastric cancer， breast cancer， and colorectal cancer. They can also combine with clinical anti-cancer drugs to reduce the toxic and side effects of chemotherapy drugs and improve the tolerance of patients during chemotherapy. On the basis of current research， this study summarized the mechanism of Hedysari Radix active components in inducing cell apoptosis， blocking cell cycle， inhibiting tumor cell proliferation， migration， and invasion， regulating micro mRNA （miRNA）， inducing cell autophagy， enhancing immune regulation， as well as reducing toxicity and enhancing efficiency and sensitization with clinical chemotherapeutics， and systematically explained the anti-tumor mechanism of Hedysari Radix active components， aiming to provide a basic reference for the further exploration of the anti-tumor mechanism of Hedysari Radix and the further development and utilization of its effective components.

OBJECTIVE: To compared the effect of different drying methods on drying characteristics, water effective diffusion coefficient and biased activation energy of Codonopsis Radix and to definite 3 different drying methods of varying temperature(45-55-60, 60-55-45, 60-45-60℃) and 3 constant temperature(45, 55, 60℃) on drying characteristic curves of different commercial grades of Codonopsis Radix. METHODS: Used R2, χ2 and RMSE as evaluation indexes, 10 typical drying kinetic models were selected to fit the drying curve of Codonopsis Radix, and the effective moisture diffusion coefficient and biased activation energy under different drying method were calculated. RESULTS: It was found that the Midilli model could well describe the drying process of different commercial grades of Codonopsis Radix, the water ratio of Codonopsis Radix showed an exponential downward trend. If the initial drying temperature was set above 55℃, the maximum drying rate could be reached within 2 h. And commercial grades temperature had certain influence on the effective water diffusion coefficient of Codonopsis Radix. Under the same temperature condition, the average speed of moisture migration during drying of Codonopsis Radix was:first-class> second-class>third-class, and the Deffwere 10.433 9×10-8, 5.545 2×10-8, 2.249 6×10-8·m2·s, respectively. The calculated bias activation energy of Codonopsis Radix was 2.943×104-4.378×104 J·mol-1, the order of bias activation energy of different drying methods was as follows:60-55-45℃ variable temperature<60-45-60℃ variable temperature<45-55-60℃ variable temperature<55℃ constant temperature<60℃ constant temperature <45℃ constant temperature, which indicated that the moisture in the medicinal materials was more likely to evaporate and overflow and consumes less energy than the constant temperature drying. In particular, the bias activation energy of 60-55-45℃ drying method was 77.54% and 81.86% of the other 2 variable temperature drying methods, which were 67.22%, 75.13% and 74.26% of the 3 kinds of constant temperature drying. CONCLUSION The use of cooling mode in the drying process can save more time and energy, and can provide experimental basis for the improvement of drying technology and optimization of drying process of Codonopsis Radix.

Biliary stent has been widely used in the treatment of biliary stricture and obstruction, it can relieve the pain of patients effectively, but bacterial infection and stent obstruction are still troublesome after surgery. We introduce the mechanism of infection and stent blockage caused by bacterial invasion after biliary stent implantation, and expound the formation mechanism of bacterial biofilm and bile sludge in this review. Antibacterial biliary stent is an effective way to inhibit biliary tract infection, the literatures on antibacterial modification of biliary stent with different antibacterial methods in domestic and abroad are reviewed, and the research prospect of antibacterial biliary stent is summarized and prospected.
Anti-Bacterial Agents/pharmacology* ; Bile ; Biliary Tract ; Cholestasis ; Humans ; Stents

Estrogen receptor (esr) mediates the effects of estrogen on the expression of related genes, thereby regulating the growth and reproduction of mammals. To investigate the effect of retrotransposon insertion polymorphism (RIP) of the porcine esr gene on porcine growth performance, retrotransposon insertion polymorphism of the esr gene were predicted by comparative genomics and bioinformatics, and PCR was used to verify the insertion polymorphisms in different porcine breeds. Finally, the correlation analysis between the genotypes and performance of Large White pigs was conducted. The results showed that four retrotransposon polymorphic sites were identified in the esr1 and esr2 genes, which are esr1-SINE- RIP1 located in intron 2 of the esr1 gene, esr1-LINE-RIP2 and RIP3-esr1- SINE located in intron 5 of the gene, and esr2-LINE-RIP located in intron 1 of the esr2 gene, respectively. Among them, insertion of a 287 bp of SINE into intron 2 of the esr1 gene significantly affected (P<0.05) the live back fat thickness and 100 kg body weight back fat thickness of Large White pigs. Moreover, the live back fat thickness and back fat thickness at 100 kg body weight of homozygous with insertion (SINE+/+) was significantly greater than that of heterozygous with insertion (SINE+/-) and homozygous without insertion (SINE-/-). Therefore, esr1-SINE-RIP1 could be used as a molecular marker to assist the selection of deposition traits in Large White pigs.
Animals ; Genotype ; Introns/genetics* ; Phenotype ; Polymorphism, Genetic/genetics* ; Retroelements/genetics* ; Swine/genetics*

Objective:To investigate the current management of nosocomial infection at medical institutions of all levels in Changzhou, so as to provide basis for standardizing nosocomial infections control of hospitals within a medical alliance.Methods:An electronic questionnaire was customized for online survey of 91 hospitals affiliated to eight regional medical alliances in Changzhou city in March 2019. The survey covered such aspects as general conditions of the hospital, profile of nosocomial infection control administrators and other staffing, supervision of hospital nosocomial infection programs, and training needs, as well as outstanding problems and suggestions.Frequency number and percentage represent enumeration data, and χ2 test was used to analyze the in-group differences of medical institutions of three levels. Results:Tertiary public hospitals were superior to the secondary and primary hospitals in organizational structure, professional staffing and target monitoring, with the differences of statistical significance( P<0.05). The most urgent training needs of medical institutions at all levels were knowledge in determination and reporting of infectious diseases/nosocomial infection/infection outbreaks; top imperatives and recommendations were development of operation rules for primary medical institutions and standardization of workflows. Conclusions:Staff of primary medical institutions need capacity building in nosocomial infection control; primary hospitals are equipped with incomplete nosocomial infection control information platform; key departments in general lack homogenous management. Tertiary hospitals are encouraged to play leadership in medical alliances in achieving standardized, homogenous and informationized nosocomial infection control within the medical alliances.