ObjectiveTo explore the correlation between the blood stasis score of coronary heart disease（CAD） and mild cognitive impairment（MCI）， as well as the changes in plasma metabolic profile of blood stasis in patients with CAD combined with MCI（CADMCI） through a cross-sectional study， and further explore the impact of different degrees of blood stasis on the plasma metabolite profile of CADMCI patients. MethodsAccording to the diagnostic criteria of CAD and CAD blood stasis， patients hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from October 2022 to October 2023 were continuously included. According to the Montreal Cognitive Assessment（MoCA） scale score， the enrolled patients were divided into CADMCI blood stasis group and CAD blood stasis group. The association between blood stasis score and MCI was analyzed by multivariate Logistic regression model. The receiver operating characteristic（ROC） curve was drawn， and the area under the curve（AUC） was calculated to evaluate the sensitivity and specificity of the model. According to the blood stasis score， the first 30 patients in the CADMCI blood stasis group and CAD blood stasis group were divided into mild blood stasis and severe blood stasis. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect plasma metabolites in each group of patients. The differential metabolites were screened according to variable importance in the projection（VIP） value≥1， fold change（FC）<0.67 or >1.5， and P<0.05. ROC curve analysis was further used to evaluate the discriminatory efficiency of the screened differential metabolites for each group of samples. ResultsA total of 266 CAD patients were included in this study. Multivariate Logistic regression analysis showed that the CAD blood stasis score was significantly correlated with MCI［odds ratio（OR）=1.619， 95% confidence interval（CI） 1.223-2.142， P<0.001， ROC curve AUC was 0.615（95% CI 0.547-0.683， P=0.001）］， indicating that the CAD blood stasis score has a certain predictive value for MCI. Plasma non-targeted metabolomics analysis showed that the main differential metabolites between CAD blood stasis and CADMCI blood stasis were lipid metabolites， among which phosphatidylcholine［20∶4（5Z， 8Z， 11Z， 14Z）/P-18∶1（11Z）］ had the best discriminatory efficiency（ROC curve AUC=0.867， 95% CI 0.754-0.942）. Further analysis of the differential metabolites between mild and severe blood stasis showed that lipid metabolites were also the main differential metabolites between mild and severe blood stasis. Among them， 1α，25-dihydroxy-2β-（2-hydroxyethoxy） vitamin D₃ had the best efficacy in distinguishing mild and severe CAD blood stasis（AUC=0.813， 95% CI 0.649-0.951）， and phosphatidylcholine 34∶2 had the best efficacy in distinguishing mild and severe CADMCI blood stasis（AUC=0.819， 95% CI 0.640-0.941）. ConclusionThere is a significant correlation between CAD blood stasis score and MCI. Phosphatidylcholine metabolites play an important role in the pathogenesis of CADMCI blood stasis and severe blood stasis. The CAD blood stasis score combined with the detection of phosphatidylcholine metabolites can provide a reference for the development of early and efficient identification strategies for CADMCI.

ObjectiveTo explore the spatial distribution patterns of flavonoid glycosides in Epimedium sagittatum and the influences of environmental factors on the accumulation of these components. MethodsThe spatial statistical analysis and GeoDetector model were used to analyze the distribution patterns of epimedin A，epimedin B，epimedin C，icariin，and total flavonoid glycosides in E. sagittatum samples from 92 different production areas in 36 cities of 13 provinces/municipalities/autonomous regions of China，as well as the effects of 28 environmental factors on the accumulation of each component. ResultsThe average content of flavonoid glycosides 64 （69.56%） producing areas and 30 （83.33%） cities met the quality standard of no less than 1.50% of total flavonoid glycosides in the 2020 edition of Chinese Pharmacopoeia.Epimedin A，epimedin B，epimedin C，icariin，and their sum showed significantly high accumulation.The hot spots regions of epimedin A and epimedin B were similar with each other，mainly located in western Hunan，eastern Hubei，eastern Guizhou，and northern Guangxi.The common hot spot areas of epimedin C and total flavonoid glycosides were in western and southwestern Hunan，southern Henan，northern Anhui，eastern Guizhou，and southern Chongqing.The hot spots areas of icariin were in southern Chongqing，western Hunan，and eastern and northeastern Guizhou.The interactions between environmental factors had stronger explanatory power for the accumulation of components than single factors.The strongest single factor and interactive factor affecting the accumulation of epimedin C were precipitation of wettest quarter （q=0.16） and its interaction with temperature seasonality （q=0.35），respectively.The strongest single factor influencing both the accumulation of icariin and total flavonoid glycosides was the precipitation of coldest quarter （q equals 0.15 and 0.22，respectively）.The strongest interactions were observed between precipitation of coldest quarter and gravel content （q=0.34），as well as between precipitation of coldest quarter and aspect （q=0.35）. ConclusionThirteen cities，including Zhumadian and Nanyang in Henan，Huaihua，Shaoyang，and Zhangjiajie in Hunan，and Zunyi，Qiandongnan，and Tongren in Guizhou，were hot spots of total flavonoid glycosides in E.sagittatum.Precipitation，gravel content，temperature seasonality，and aspect significantly influence the accumulation of flavonoid glycosides in E.sagittatum.This study provides reference for the utilization and production zoning of E.sagittatum.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

ObjectiveTo explore the role and molecular mechanism of Weifuchun （WFC） in inhibiting inflammation and alleviating gastric precancerous lesions （GPL）. MethodHuman gastric mucosal epithelial cells （GES-1） were stimulated with N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPL （MC cells）， with Caspase-3 inhibition by Z-DEVD-FMK. MC cells were divided into control （20% blank serum）， WFC （15% and 20% WFC-containing serum）， and caspase-3 inhibitor groups. The cell counting kit-8 （CCK-8） was used to examine the viability of GES-1 cells or MC cells. The Transwell assay and 5-acetylidene-2′-deoxyuridine （EdU） staining were employed to examine cell invasion and proliferation， respectively. Flow cytometry was employed to determine the level of reactive oxygen species. Real-time PCR was conducted to determine the mRNA levels of interleukin （IL）-1， IL-6， and tumor necrosis factor （TNF）-α. Gene Expression Omnibus （GEO） was used to analyze the role of pyroptosis in gastric cancer progression. Western blotting was employed to determine the protein levels of nuclear factor-κB （NF-κB） p65， gasdermin E （GSDME）， and Caspase-3. Immunofluorescence staining was employed to detect the NF-κB p65 protein level and nuclear translocation. Hematoxylin-eosin staining was carried out to observe the pathological changes in the gastric mucosa before and after WFC treatment in the patients. ResultCompared with the control group， MC cells presented enhanced proliferation and invasion energy （P<0.01）. Compared with the blank serum group， WFC-containing serum inhibited the proliferation and invasion of MC cells （P<0.01）， down-regulated the mRNA levels of IL-1， IL-6， and TNF-α， and lowered the level of reactive oxygen species （P<0.05， P<0.01）. The transcriptome data at different stages of gastric cancer showed that pyroptosis was involved in gastric cancer progression， and the GSDME level was significantly higher in GPL patients than in the normal group. Compared with the blank serum， WFC-containing serum lowered the level of NF-κB and inhibited the nuclear translocation of NF-κB （P<0.05）， and it inhibited pyroptosis by suppressing the cleavage of Caspase-3 on GSDME （P<0.05， P<0.01）. The analysis of patient specimens further demonstrated that WFC treatment down-regulated the NF-κB level and GSDME cleavage （P<0.01）， inhibited pyroptosis， and alleviated gastric mucosal inflammation and intestinal epithelial metaplasia. ConclusionPyroptosis is involved in the progression of gastric cancer， and WFC inhibits pyroptosis via the NF-κB/GSDME pathway， thereby alleviating gastric mucosal inflammation in GPL.

Objective:To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis.Methods:It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups.Results:A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference ( χ2=0.004, P=0.952). Kaplan-Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion:The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.

Acute-on-chronic liver failure(ACLF)is a group of clinical syndromes related to severe acute liver function damage and multiple organ failure caused by various acute inducing factors on the basis of chronic liver disease.Due to its serious condition,rapid progression and high mortality,it has attracted more and more attention.Recent studies have shown that the pathogenesis of ACLF mainly includes direct injury and immune injury.As the main immune cells in the liver,the immunoregulatory role of liver macrophages in ACLF has been increasingly recognized.Liver macrophages have excellent phenotype conversion function and plasticity characteristics under the influence of epigenetic reprogramming or local microenvironment.This adaptive expression ability can use key mediators to promote the early conversion of anti-inflammatory phenotype to alleviate liver injury.A large number of studies have shown that liver macrophages have a certain potential in reversing the process of ACLF.Therefore,from the perspective of the plasticity characteristics of liver macrophages,this paper expounds the role of liver macrophages in ACLF and the research on the intervention of ACLF disease process,and summarizes its potential significance in the treatment of ACLF.

AIM:To investigate the effects of Balanophora involucrata Hook.f.(BIH)extracts on bile acid metabolism and liver injury in mice with metabolic dysfunction-associated fatty liver disease(MAFLD)through the gut mi-crobiota-farnesoid X receptor(FXR)axis,and to explore the underlying mechanisms.METHODS:Forty C57BL mice were randomly divided into control group,MAFLD model group,medium-dose BIH group,and high-dose BIH group.The mice in control group received a regular diet,while those in other groups were fed with high-fat diet for 12 weeks to induce MAFLD.The mice in medium-and high-dose BIH groups received 0.598 and 0.299 g/kg BIH solution,respectively,while those in control and MAFLD groups received an equivalent volume of normal saline.Serum levels of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were measured using an automatic biochemical analyzer.Liver morphology,steatosis and fibrosis were assessed by HE,oil red O and Masson staining.Levels of TC,tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in liver tissues,and bile acids in serum and ileum tissues were measured by ELISA.Protein expression of FXR and fibroblast growth factor 15(FGF15)in ileum tissues,and FXR,small heterodimer partner(SHP)and cholesterol 7α-hydroxylase(CYP7A1)in liver tissues were analyzed by Western blot.Intestinal microbiota changes were assessed by 16S rRNA gene sequencing.RESULTS:(1)The MAFLD mice exhibited increased serum TC,TG,LDL-C and bile acid levels,liver TC,TNF-α and IL-6 levels,and lipid deposition.However,BIH intervention improved these factors and increased FXR and SHP pro-teins,but decreased CYP7A1 expression in the liver.The protein levels FXR and FGF15 in the ileum were also elevated.(2)Intestinal flora analysis demonstrated that BIH intervention improved the abundance and diversity of intestinal flora in MAFLD mice.Specifically,there was an increase in Bacteroidetes/Firmicutes ratio and a decrease in Proteobacteria and Verrucomicrobia.At the genus level,abundance of Duncaniella,Muribaculum and Paramuribaculum increased,while He-licobacter decreased.CONCLUSION:Treatment with BIH regulates intestinal flora,decreases FXR levels,enhances CYP7A1 expression,promotes bile acid synthesis,reduces hepatic cholesterol accumulation,and attenuates liver steato-sis and inflammation in MAFLD mice,indicating potential therapeutic effects.

Objective:To investigate the clinical characteristics and gene sequencing results of NDM, so as to provide evidence for clinical diagnosis and treatment .Methods:Clinical data of 1 child diagnosed with NDM in Hebei People's Hospital in January 2021 were retrospectively analyzed, and DNA gene sequencing was performed in the peripheral blood of the child, and relevant literatures were reviewed.Results:The child was born with a weight of 2.2kg. On the second day after birth, blood glucose significantly increased and insulin and C-peptide levels decreased. After 14 days of insulin treatment, hyperglycemia was still present, which was consistent with the diagnosis of NDM. Genetic testing indicated that there were missense mutations of newborn compound heterozygote in ABCC8 gene: c. 752G > A (p.G251E), c. 772A > G (p.R258G). The mutation of c. 772A > G in ABCC8 gene had not been reported before, and sulfonylureas were effective for the treatment of the child.Conclusion:NDM is a rare monogenic genetic disease with a lack of specificity in clinical manifestations. For children diagnosed or suspected of NDM, genetic testing should be actively carried out, which is of great significance for clinical diagnosis, treatment and prognosis.

Objective:To investigate the effect of trifluoperazine (TFP) on the proliferation of mesangial cells through FoxO1 pathway and its protective effect on lupus nephritis (LN) mice.Methods:In vitro, MTT assay was used to detect the effect of different concentrations of trifluoperazine on the proliferation of mesangial cells. Flow cytometry was used to detect the effect of different concentrations of TFP on the mesangial cell cycle. Western blotting method (WB method) was used to detect the effect of different concentrations of TFP on the expression of FoxO1 and cyclinD1 proteins in mesangial cells, and the expression of TFP on mesangial cells, cyclinD1 and P21 after enhancing or inhibiting the expression of FoxO1. The effect of TFP on the proliferation of MRL/LPR mouse mesangial cells and the expression of FoxO1 was detected by HE staining, immunohistochemistry and WB method, and the effect of TFP on renal function in LN mice was detected by ELISA method in vivo. WB method was used to detect the effect of TFP on mesangial cell fibrosis, that is, the protein expression levels of FN and Col1. Repeated measures analysis of variance and One-way analysis of variance were used to compare measurement data between groups, and further pairwise comparisons were made using the Bonferroni method. Results:Trifluoperazine inhibits the proliferation of mesangial cells, and the interaction effects was concentration dependence and were statistically signifiant between groups, time ( Fgroup=162.58, Ftime=50.84, Finteraction=19.12, P<0.001). Flow cytometry results showed that after mesangial cells were treated with trifluoperazine at different concentrations, the percentage of cells in the G 0/G 1 phase gradually increased, while the cells in the S phase gradually decreased. This effect was dose-dependent, the difference was statistically significant ( P<0.05). Results of WB test proved that trifluoperazine inhibited the expression of cyclinD1 protein (2.17±0.34, 1.49±0.20, 1.11±0.27, 0.15±1.55, F=33.60 , P<0.001) and up-regulated the expression of FoxO1 (0.81±0.45, 2.31±0.81, 3.51±0.52, 5.13±10.07, F=35.63, P<0.001), and also in a dose-dependent patten. In vivo experimental results showed that trifluoperazine could inhibit the proliferation of mesangial cells and promote the expression of FoxO1 in mice with lupus nephritis, and the difference wsa statistically significant ( F=8.47, P=0.007). ELISA test results showed that trifluoperazine had a protective effect on renal function [serum creatinine: normal group(144±23)μmol/L, LN group (237±14)μmol/L, LN+TFP(211±36)μmol/L, Fvalue=20.47, P<0.001, urea nitrogen: normal group (22.84±0.56)μmol/L, LN group (19.99±0.92)μmol/L, LN+TFP (13.57±0.25)μmol/L, F=331.96, P<0.001] and it was proved by WB method that trifluoperazine could inhibit Fn and Col1 expression, the difference was statistically significant ( FFN=1 312.83, FCol1=171.16, P<0.001). Conclusion:Trifluoperazine blocks the mesangial cell cycle in G 0/G 1 phase by increasing the expression of FoxO1 and inhibits cell proliferation, which may have a therapeutic effect on lupus nephritis nephritis.

Objective To investigate the effect and mechanism of sodium cantharidate on the proliferation,migration and invasion of esophageal carcinoma EC9706 cells.Methods Esophageal cancer EC9706 cells were randomly divided into blank control group,low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium canthari-date group and cisplatin group.The EC9706 cells in the low-,medium-and high-dose sodium cantharidate groups were given fi-nal mass concentration of 1.0,2.5 and 5.0 mg·L-1 sodium cantharidate intervention,respectively.The EC9706 cells in the cisplatin group were treated with the final mass concentration of 140 mg·L-1 cisplatin,and the cells in the control group was cultured in Dulbecco's modified Eagle's medium.The cell proliferation rate in each group was detected by cell counting reagent-8 method,the mobility of EC9706 cells in each group was detected by scratch test,the invasion rate of EC9706 cells in each group was detected by Transwell method,and the levels of Wnt3a and β-catenin mRNA in EC9706 cells in each group were detected by real-time quantitative polymerase chain reaction method,and the levels of Wnt3a and β-catenin protein in EC9706 cells in each group were detected by Western blot.Results At 24,48 and 72 h of cultivation,the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium canthari-date group and cisplatin group was significantly lower than that in the blank control group(P＜0.05);the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group and medium-dose of sodium cantharidate group was significantly higher than that in the high-dose sodium cantharidate group and cisplatin group(P＜0.05);the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group was significantly higher than that in the medium-dose sodium cantharidate group(P＜0.05);there was no significant difference in the proliferation rate of EC9706 cells between the high-dose sodium cantharidate group and cisplatin group(P＞0.05);the proliferation rate of EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium cantharidate group and cisplatin group was significantly decreased with the extension of culture time(P＜0.05).The mobility rate and invasion rate of EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium cantharidate group and cisplatin group were significantly lower than those in the blank control group(P＜0.05);the mobility rate and invasion rate of EC9706 cells in the low-dose sodium cantharidate group and medium-dose sodium cantharidate group were significantly higher than those in the high-dose sodium cantharidate group and cisplatin group(P＜0.05);the migration rate and invasion rate of EC9706 cells in the low-dose sodium cantharidate group were significantly higher than those in the medium-dose sodium cantharidate group(P＜0.05);there was no significant difference in the mobility rate and invasion rate of EC9706 cells between the high-dose sodium cantharidate group and cisplatin group(P＞0.05).The relative expression levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells in the low-dose sodium cantharidate group,medium-dose sodium cantharidate group,high-dose sodium cantharidate group and cisplatin group were significantly lower than those in the blank control group(P＜0.05);the relative expression levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells in the low-dose sodium cantharidate group and medium-dose sodium cantharidate group were significantly higher than those in the high-dose sodium cantharidate group and cisplatin group(P＜0.05);the relative expressions levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells in the low-dose sodium cantharidate group were significantly higher than those in the medium-dose sodium cantharidate group(P＜0.05);there was no significant difference in the relative expression levels of Wnt3a and β-catenin mRNA and protein in EC9706 cells between the high-dose sodium cantharidate group and cisplatin group(P＞0.05).Conclusion Sodium cantharidate can significantly inhibit the proliferation,migration and invasion of esophageal carcinoma EC9706 cells,and its mechanism may be related to the inhibition of the Wnt3a/β-catenin pathway.