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.

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.

With increasing aging， cognitive impairment in elderly coronary heart disease is a "disease group" with high morbidity and mortality in the senior population， which seriously affects the health and quality of life of the elderly. This paper takes the "cardio-cerebral circuit" as the basis of co-morbidity， and under the guidance of the cardio-cerebral homoeopathy， based on the temporal sequential characteristics of the evolution of the disease mechanism of cognitive impairment in elderly coronary heart disease， we construct a “disease-syndrome-phase” prevention and treatment strategy based on the time-sequential characteristics of the pathogenesis of the disease mechanism of "deficiency-blood stasis-toxicity"， from the perspective of pathogenicity of the disease mechanism in time-phase and the spatial multidimensionality of cardio-cerebral homoeopathy. The prevention and treatment strategy of the "disease-syndrome-phase" is constructed from the perspective of the temporal phase of the disease mechanism and the multidimensionality of the space of cardio-cerebral homoeopathy. In the earlier stage， "kidney deficiency and brain emptiness are the foundation"， in the attack stage， "turbid stasis and brain injury are the key"， and in the progression stage， "toxicity and brain damage are the changes". It is emphasized that replenishing the deficiency and benefiting the kidneys to restore the smooth flow of collaterals， eliminating blood stasis and removing turbidity to promote the enrichment of blood， and detoxifying and clearing the heart to tranquilize the spirit and benefit the brain， the spatiotemporal thinking of cognitive impairment of coronary heart disease in the elderly is initially constructed with the spatial dimension to identify the location of the disease， and the temporal dimension to determine the stage of the disease， which will provide a theoretical basis for the spatiotemporal diagnostic and treatments for the heart and brain co-morbidities of TCM.

Objective To investigate the potential effect and mechanism of curcumin in inhibiting synaptic injury in the cortex of rats with cerebral ischemia-reperfusion. Methods Sprague-Dawley rats were divided into sham-operated group, model group, low-dose curcumin (50 mg/kg) group, and high-dose curcumin (100 mg/kg) group. A model of middle cerebral artery occlusion for 2 hours and reperfusion for 24 hours was constructed, and curcumin was administered. Based on the neurological function score, the effects of curcumin on cerebral infarct volume, synaptic ultrastructure changes, inflammatory cell infiltration, and the expression of NLRP3, Caspase-1, Synapsin1, and CAMKⅡ were observed after the end of the animal treatment. Results The neurological function scores were 0, 3.25±0.43, 2.50±0.50, and 1.50±0.50 for the sham-operated group, model group, low-dose curcumin group, and high-dose curcumin group, respectively. The percentage of cerebral infarct volume was 0, (38.89±2.21)%, (33.48±1.77)%, and (23.69±2.19)%, respectively. Compared with the sham operation group, the model group had severe synaptic ultrastructure damage, extensive inflammatory cell infiltration, significantly increased expression of Caspase-1 and NLRP3 (P < 0.5), and significantly decreased expression of Synapsin1 and CAMKⅡ (P < 0.5). Curcumin treatment significantly inhibited synaptic damage, reduced inflammatory cell infiltration, decreased the expression of Caspase-1 and NLRP3 (P < 0.5), and increased the expression of Synapsin1 and CAMKII (P < 0.5), when compared with the model group. Conclusion Ischemia-reperfusion-mediated synaptic injury in rat brain triggers an inflammatory response in cortical nerve cells, and curcumin alleviates synaptic damage and reduces brain injury by inhibiting inflammatory factor levels.

Objective To investigate the mechanism of tea polyphenols(TP)for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice.Methods Sixty C57BL/6 mice were randomly assigned into sham-operated,cecal ligation and puncture(CLP)and CLP+TP treatment groups,and survival of the mice was recorded after modeling in each group.The lung wet/dry weight ratio and myeloperoxidase(MPO)activity were determined,and lung injury of the mice was evaluated using HE staining and acute lung injury score.The expressions of IL-1β,TNF-α,IL-6,NLRP3,caspase-1 p10,ASC,MPO,and caspase-8 in the lung tissue were detected using ELISA,Western blotting,or immunohistochemical staining.MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress.Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4.Results The postoperative mortality rate at 72 h,lung wet/dry weight ratio,MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group(P<0.05).Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors(P<0.05)and lowered MDA and H2O2 levels in the lung tissue of the septic mice(P<0.05).Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group.Conclusion TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

Objective To investigate the mechanism of tea polyphenols(TP)for regulating NLRP3 inflammasomes and alleviating acute lung injury in septic mice.Methods Sixty C57BL/6 mice were randomly assigned into sham-operated,cecal ligation and puncture(CLP)and CLP+TP treatment groups,and survival of the mice was recorded after modeling in each group.The lung wet/dry weight ratio and myeloperoxidase(MPO)activity were determined,and lung injury of the mice was evaluated using HE staining and acute lung injury score.The expressions of IL-1β,TNF-α,IL-6,NLRP3,caspase-1 p10,ASC,MPO,and caspase-8 in the lung tissue were detected using ELISA,Western blotting,or immunohistochemical staining.MDA and H2O2 levels in the lungs were detected to evaluate the level of oxidative stress.Immunofluorescence assay was used to investigate the co-localization of NLRP3 and NOX4.Results The postoperative mortality rate at 72 h,lung wet/dry weight ratio,MPO level and acute lung injury scores were significantly lower in CLP+TP group than in CLP group(P<0.05).Treatment with TP significantly reduced the expressions of NLRP3-related inflammatory factors(P<0.05)and lowered MDA and H2O2 levels in the lung tissue of the septic mice(P<0.05).Immunofluorescence co-staining showed a lower level of NOX4 and NLRP3 co-localization in CLP+TP group than in CLP group.Conclusion TP inhibits NLRP3 inflammasome-associated inflammation to alleviate CLP-induced acute lung injury in mice through a regulatory mechanism that inhibits NOX4 expression and reduces oxidative stress in the lung tissue.

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 characteristics of electrocardiogram changes during nocturnal asymptomatic hypoglycemia in type 2 diabetes mellitus(T2DM)patients and early diagnosis of cardiac autonomic neuropathy(CAN).Methods A total of 150 patients with T2DM who were admitted to our hospital from June 2015 to June 2022 were retrospectively selected and given 72 h dynamic blood glucose and dynamic electrocardiogram monitoring.According to whether asymptomatic hypoglycemia occurred at night,they were divided into hypoglycemia group(n=62)and non-hypoglycemia group(n=88).According to the Ewing experiment,150 T2DM patients with T2DM were divided into T2DM group(n=90)and CAN group(n=60).Results Compared with the non hypoglycemic group,the hypoglycemic group had an increase in DM duration,LF/HF(P<0.05),HbA1c,average blood glucose,collected heart rate deceleration force(DC),QT dispersion(QTD),end of peak T value(Tp-e),Tp-e/QT,percentage of beats with a difference of more than 50 ms between adjacent normal RR intervals(pNN50),root mean square difference between adjacent normal RR intervals(rMSSD),standard deviation of 24-hour normal sinus RR interval(SDNN),and standard deviation of mean normal RR interval every 5 minutes(SDANN)and the average heart rate decreased within 24 hours decreased(P<0.05).Logistic regression analysis showed that the duration of DM was a risk factor for CAN in T2DM patients,and DC,QTD,and pNN50 were protective factors for CAN in T2DM patients.The characteristic curve analysis of the participants showed that the area under the curve for predicting CAN was 0.811,0.842,0.786,0.801,and 0.886 for the DM duration,DC,QTD and pNN50 respectively.The combined diagnostic performance of these four items was the best.After internal verification,it was found that the model has good discrimination and accuracy.Conclusion T2DM patients with nocturnal asymptomatic hypoglycemia may exhibit elevated,ECG LF/HF and decreased DC,QTD,Tp-e,Tp-e/QT,pNN50,rMSSD,SDNN,SDANN,and 24-hour average heart rate decrease;DM duration,DC,QTD and pNN50 can serve as effective indicators for early diagnosis of CAN in T2DM patients.

Objective:To compare the application value of the Braden-QD scale and the Braden-Q scale in assessing the risk of pressure injuries in pediatric intensive care unit (PICU) patients.Methods:A convenient sampling method was used to select 205 pediatric patients admitted to the First People’s Hospital of Lianyungang from December 2021 to September 2022 as the research subjects.The Braden-QD scale and the Braden-Q scale were used to evaluate the risk of pressure injuries.SPSS 25.0 and Python 2.7 softwares were used for statistical analysis. Inter-rater reliability of the scales was evaluated using intraclass correlation coefficient (ICC), internal consistency was evaluated using Cronbach's α, and the predictive power was compared using receiver operator characteristic curve (ROC), positive predictive value, negative predictive value, sensitivity, specificity and area under the ROC curve (AUC).Results:(1) A total of 24 (11.7%) out of 205 patients had pressure injury, predominantly in stage 1 (20 cases, 83.3%). (2)The ICC of Braden-QD scale and Braden-Q scale were 0.890 and 0.862, while the Cronbach's α were 0.891 and 0.710.(3) The AUC of the Braden-QD scale was 0.936. The optimal diagnostic cutoff value was 9.5, with a Youden index, sensitivity, specificity, positive predictive value and negative predictive value of 0.765, 0.875, 0.890, 0.512, 0.982, respectively.The AUC of the Braden-Q scale was 0.881. The optimal diagnostic cutoff value was 18.5, with a Youden index, sensitivity, specificity, positive predictive value, and negative predictive value of 0.626, 0.792, 0.834, 0.388, 0.968, respectively.Conclusion:Compared with the Braden-Q scale, the Braden-QD scale is more suitable for assessing the risk of pressure injuries in PICU children.

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.