OBJECTIVE To explore the mechanism by which Cuscuta chinensis flavonoids （CCF） promote decidualization and improve recurrent spontaneous abortion （RSA）. METHODS HTR-8/SVneo cells in logarithmic growth phase were randomly divided into blank group， lipopolysaccharide （LPS） group， CCF group， SGK2 inhibitor （GSK650394， abbreviated as “GSK”） group and CCF+GSK group. Each group was treated with the corresponding agents accordingly. HTR-8/SVneo cells with SGK2 knockdown were randomly divided into small interfering RNA of SGK2 （siSGK2） group and siSGK2+CCF group； additionally， blank group and LPS group were established； each group was treated with the corresponding agents accordingly. The cell survival rate， expression levels of WNK signaling pathway- and decidualization-related proteins and mRNAs， as well as mitochondrial membrane potential levels， were assessed in each group before and after SGK2 knockdown. RSA mice model was constructed and randomly divided into model group， CCF low-dose group， CCF high-dose group， GSK group， and combined dosing group， with 4 mice in each group. Other 4 normal pregnant female mice were selected as the control group. The number of implanted embryos， viable fetuses， and lost embryos in mice was recorded. The morphological changes of endometrium and decidualization were observed， and WNK signaling pathway- and decidualization-related proteins and mRNAs expressing levels as well as mitochondrial membrane potential levels were all detected. RESULTS Compared with the blank group， the cell survival rate， as well as the protein and mRNA expression levels of SGK2， WNK1， WNK4， prolactin， insulin-like growth factor- binding protein-1， oxidative stress responsive kinase 1， and Ste20-like proline-/alanine-rich kinase were significantly reduced in the LPS group （P＜0.05）； compared with the LPS group， the cell survival rate and the expression levels of the above- mentioned proteins and mRNAs were significantly increased in the CCF group， while the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly decreased in the GSK group （P＜0.05）； compared with the CCF group， the cell survival rate and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the CCF+GSK group （P＜0.05）. After knocking down SGK2， compared with the LPS group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly reduced in the siSGK2 group （P＜0.05）； compared with the siSGK2 group， the cell survival rate， red/green fluorescence intensity ratio， and the expression levels of the above-mentioned proteins and mRNAs were significantly increased in the siSGK2+CCF group （P＜0.05）. The in vivo experimental results showed that CCF treatment can significantly improve the number of implanted embryos and viable fetuses in RSA model mice and reduce lost embryos， the expression levels of the above-mentioned proteins and mRNAs in endometrial tissue were significantly increased， and the red/green fluorescence intensity ratio was significantly increased （P＜ 0.05）； the combined dosing group could reverse the effect of CCF （P＜0.05）. CONCLUSIONS CCF can activate SGK2， up- regulate the WNK signaling pathway， promote endometrial decidualization， and improve RSA.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

Objective:To evaluate the relationship between gluten-free diet and rheumatoid arthritis (RA).Methods:Data were obtained from large-scale genome-wide association studies (GWAS), and genetic loci that are independent of gluten-free diet and RA of people of Europe2 were selected as instrumental variables. The gluten-free diet GWAS data included 64 949 individuals and 9 851 867 controls. Data were obtained from GWAS of 58 284 RA patients and 13 108 512 controls. The inverse variance weighted (IVW), MR Egger, weighted median method and weighted model were used to conduct two sample Mendelian randomization (MR) analysis. Cochran Q test and mendelian randomness pleiotropy residual sum and outlier (MR-PRESSO) were used to assess SNP heterogeneity. Applying the MR Egger intercept to test the level pleiotropy of SNP. The sensitivity analysis of the "leave one method" that evaluates whether MR studies were influenced by a single SNP. Results:After matching GFD and RA data, three SNPs were included as instrumental variables in the study. IVW showed that GFD could significantly reduce the risk of RA ( β=-60.83, s x=3.82, P<0.001). The weighted median method and weighted pattern also showed that the gluten free diet could reduce the risk of RA ( β=-57.97, s x=4.41, P<0.001; β=-55.81, s x=5.10, P=0.008). Sensitivity analysis of the correlation between GFD and RA showed that there might be heterogeneity between SNPs (Cochran Q test, Q=12.80, P=0.002). The MR-PRESSO results showed that no abnormal SNP was detected ( P=0.174). The forest map showed that SNPs was closely related to GFD and RA stability. The method comparison chart showed that the results of multiple testing methods were basically consistent. The funnel plot showed that SNPs were basically symmetrical, indicating that there was no pleiotropy in MR analysis. The MR Egger intercept test showed no horizontal pleiotropy in MR analysis (intercept value was-0.24, P=0.174). The sensitivity analysis of the "leave one method" is suggested that no single SNP had a significant impact on the overall results. Conclusion:Gluten free diet is related to the risk reduction of RA.

Humans ; Asthma/drug therapy* ; Biological Therapy

Objective To explore the effects of heparinase(HPSE)on myocardial apoptosis,inflamma-tory response and oxidative damage in myocardial ischemia reperfusion(MI/R)rats.Methods Sixty SD rats were randomly assigned(1∶1∶1∶1)tocontrol group,I/R group,I/R+shRNA-NC group and I/R+Heparanase-shRNA group.The control group was only threaded without ligation after thoracotomy,and the MI/R model was prepared by ligation of the left anterior descending branch of coronary artery.The western blot assay(WB)was used to detect heart function and markers of heart damage in each group.HE staining and TUNEL staining were used to observe the myocardial pathology.The expression of apoptosis-related proteins(Caspase-3,Bax,Bcl-2)and UPRmt marker proteins(LonP1,HSP70)were detected by WB.The contents of superoxide dismutase(SOD)and malondi-aldehyde(MDA)were detected by kit.The levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in peripheral blood were detected by enzyme-linked immunosorbent assay(ELISA).Results HE staining results showed that the myocardium,epimyma and myocardial fibers were intact and normal in control group.However,the myocardial fibers were bent,myoglobin was dissolved,myocardial muscle nucleus was pyknotic and dissolved,and muscle bundle membrane was ruptured in I/R group and I/R+shRNA-NC group.The epimyocardium was intact in I/R+Heparanase-shRNA group.Moreover,the myocardial fiber bending was significantly improved in I/R+Heparanase-shRNA group.Additionally,compared with the control group,the expression levels of CK-MB,cTnI,Mb,Caspase-3 protein,Bax protein,MDA,IL-6,TNF-α and HSP70 in I/R group were significantly increased.And the difference was statistically significant.Furthermore,the expression levels of HR,LVEF,LVWT,Bcl-2 protein,SOD and LonP1 protein were significantly decreased.Additionally,compared with the I/R+shRNA-NC group,the expression levels of CK-MB,cTnI,Mb,Caspase-3 protein,Bax protein,MDA,IL-6 and TNF-α in I/R+ Heparanase-shRNA group were significantly decreased.And the difference was statistically significant.However,the expression levels of HR,LVEF,LVWT,Bcl-2 protein,SOD,LonP1 and HSP70 were significantly increased.And the difference was statistically significant.Conclusion Down-regulation of HPSE alleviates myocardial injury in ischemia-reperfusion rats by inhibiting oxidative stress,inflammation,and apoptosis.The mechanism may be related to the inhibition of UPRmt signaling pathway.

ObjectiveTo analyze the effects of Danggui Shaoyaosan （DSS） on the gut microbiota of the Alzheimer's disease （AD） model in SAMP8 mice based on 16S rDNA sequencing. MethodTwenty-four SAMP8 mice aged seven months were randomly divided into low-， medium-， and high-dose DSS groups （14.4， 28.8， 57.6 g·kg^-1·d^-1） and a model group according to a random number table， with six rats in each group. Six SAMR1 mice of the same age were assigned to the normal group. After intragastric administration for eight consecutive weeks， 16S rDNA sequencing was performed to detect the gut microbiota of feces in mice. Morris water maze was employed to assess the directional navigation and space exploration ability of mice. Nissl staining was performed to observe the pathological changes of neurons in the hippocampal CA1 area. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the protein content of hippocampal amyloid β-protein （Aβ） and hyperphosphorylated Tau （p-Tau）. ResultCompared with the normal group， the model group presented a declining α diversity （P<0.05）， markedly altered β diversity， prolonged escape latency （P<0.05）， reduced number of platform crossings and cumulative duration in the targeted quadrant （P<0.05）， decreased neurons and Nissl bodies in the CA1 hippocampal area， and up-regulated Aβ and p-Tau expression （P<0.05）. However， DSS intervention enhanced the α diversity， and medium- and high-dose DSS， especially the medium-dose DSS， could result in α diversity similar to the control group. Moreover， at the phylum level， the abundance of Firmicutes increased （P<0.05）， while the abundance of Bacteroidetes and Proteobacteria decreased （P<0.05）. At the genus level， the abundance of Lactobacillus and other genera increased （P<0.05）， while the abundance of Bacteroides， Helicobacterium， Rikenella， Parabacteroides， Sutterella， and Mucilaginibacter decreased （P<0.05）. The DSS groups also showed shortened escape latency （P<0.05）， increased number of platform crossings and cumulative duration in the targeted quadrant （P<0.05）， increased Nissl bodies （P<0.05）， and reduced Aβ and p-Tau content （P<0.05）. Pearson correlation analysis showed that the abundance of Mucilaginibacter， Bacteroides， and Sutterella was negatively correlated with the cognitive ability of SAMP8 mice， while the abundance of Lactobacillus and Butyricimonas was positively correlated with the cognitive ability of SAMP8 mice. ConclusionDSS can improve the cognitive ability of SAMP8 mice， and its mechanism may be related to the regulation of gut microbiota diversity and community composition.

Objective:To explore the classification performance of combined model constructed from CT signs combined with radiomics for discriminating COVID-19 pneumonia and other viral pneumonia.Methods:The clinical and CT imaging data of 181 patients with viral pneumonia confirmed by reverse transcription-polymerase chain reaction in 15 hospitals of Yunnan Province from March 2015 to March 2020 were analyzed retrospectively. The 181 patients were divided into COVID-19 group (89 cases) and non-COVID-19 group (92 cases), which were further divided into training cohort (126 cases) and test cohort (55 cases) at a ratio of 7∶3 using random stratified sampling. The CT signs of pneumonia were determined and the radiomics features were extracted from the initial unenhanced chest CT images to build independent and combined models for predicting COVID-19 pneumonia. The diagnostic performance of the models were evaluated using receiver operating characteristic (ROC) analysis, continuous net reclassification index (NRI) calibration curve and decision curve analysis.Results:The combined models consisted of 3 significant CT signs and 14 selected radiomics features. For the radiomics model alone, the area under the ROC curve (AUC) were 0.904 (sensitivity was 85.5%, specificity was 84.4%, accuracy was 84.9%) in the training cohort and 0.866 (sensitivity was 77.8%, specificity was 78.6%, accuracy 78.2%) in the test cohort. After combining CT signs and radiomics features, AUC of the combined model for the training cohort was 0.956 (sensitivity was 91.9%, specificity was 85.9%, accuracy was 88.9%), while that for the test cohort was 0.943 (sensitivity was 88.9%, specificity was 85.7%, accuracy was 87.3%). The AUC values of the combined model and the radiomics model in the differentiation of COVID-19 group and the non-COVID-19 group were significantly different in the training cohort ( Z=-2.43, P=0.015), but difference had no statistical significance in the test cohort ( Z=-1.73, P=0.083), and further analysis using the NRI showed that the combined model in both the training cohort and the test cohort had a positive improvement ability compared with radiomics model alone (training cohort: continuous NRI 1.077, 95 %CI 0.783-1.370; test cohort: continuous NRI 1.421, 95 %CI 1.051-1.790). The calibration curve showed that the prediction probability of COVID-19 predicted by the combined model was in good agreement with the observed value in the training and test cohorts; the decision curve showed that a net benefit greater than 0.6 could be obtained when the threshold probability of the combined model was 0-0.75. Conclusion:The combination of CT signs and radiomics might be a potential method for distinguishing COVID-19 and other viral pneumonia with good performance.

The purpose of this paper is to optimize the course construction and teaching process of psychopharmacology， and analyze the problems in the course of teaching and assessment of psychopharmacology from many aspects. This article is to deeply excavate the space for improvement， and enrich the teaching links by using existing conditions， technology and personnel to enhance the teaching effect and improve the teaching quality， so as to provide references for the reform of similar course teaching.

Objective To know the prevalence of chronic obstructive pulmonary disease(COPD) in patients with obstructive sleep apnea-hypopnea syndrome(OSAHS) in Kunming Yunnan Province, and the clinical symptom of OS.Methods Retrospective study of 4 636 cases of patients with snoring, excluding COPD in addition to chronic respiratory disease and assess the patient`s condition.The test included AHI, BMI, Epworth sleepiness scale, lung function.The index of OS was confirmed by AHI>5 times/h and FEV1/FVC<70%.Results During the period of 2006 to 2012, he prevalence of COPD in patients with OSAHS was 10.1% [95% confidence interval (CI) 9.1%-11.1%] in Kunming Yunnan Province.And male`s OS prevalence rate is higher than the female(male 10.2%;female 9.7%).The OS patients` average age was 56.9±14.1, the mean AHI was (47.46±26.79) times/h, and the average FEV1/FVC was 60.09%±23.57%.Polysomnographyresults show that patients suffered obvious hypoxiaat night in both OSAHS group and OS group, but it was more significant in OS group.Pulmonary function test showed that OS patients have more serious chronic obstructive pulmonary disease.Conclusions The prevalence of COPD in OSAHS patients was high in Kunming, Yunnan Province, and the prevalence rate in old group reached more than 24%.In addition, the sympotms of patients with OS were more severe than those with only OSAHS or COPD in lung function and hyoxemia.

Objective To analyze the clinical characteristics of suspected acute aortic dissection with ST-segment elevation detected by inferior leads in order to avoid the misdiagnosis of acute aortic dissection facilitating an appropriate treatment strategy carried out in time.Methods A total of 14 patients with suspected acute aortic dissection with ST-segment elevation detected by inferior leads were enrolled.Their clinical presentation,ECG features,imaging findings,laboratory testing,coronary angiography results, treatment and outcome were retrospectively analyzed.Results Clinical characteristics of suspected acute aortic dissection with ST-segment elevation detected by inferior leads suggested that hypertension as a single risk factor accounted for 79%.The patients with normal blood pressure or high blood pressure in emergency visits accounted for 86%.The amplitude of ST elevation in lead Ⅲ was greater than that in lead Ⅱ,and lead Ⅲ accompanied with ST elevation in lead V1 or V4R accounted for 86%.Significantly elevated D-dimer >2 000 ng/mL was found in those patients.Coronary angiography showed that the opening of coronary artery not seen,normal coronary arteries or a simple right coronary artery proximal lesion.Transesophageal echocardiography and computed tomography angiography were used to identify the diagnosis with 100%accuracy.The mortality rate of this group was 50%.Conclusions Patients with acute aortic dissection evidenced by ST-segment elevation detected by inferior leads are in critical setting of high mortality. Emergency surgical treatment can significantly improve the survival rate of patients.