OBJECTIVE To explore the effects of limonin on renal lesions， glucose metabolism， inflammation， and oxidative stress in gestational diabetic rats and its possible mechanisms. METHODS The model of gestational diabetic rats was established by intraperitoneal injection of streptozotocin. The diabetic rats were divided into the model group （intragastrical administration and tail vein injection of equal volume of normal saline）， limonin low-， medium-， and high-dose groups （intragastrical administration of limonin， at doses of 12.5， 25.0 and 50.0 mg/kg， and equal volume of normal saline into the tail vein）， and combination group [intragastrical administration of limonin 50.0 mg/kg + tail vein injection of c-Jun N-terminal kinase （JNK） activator Anisomycin 2 mg/kg ]， with 12 rats in each group. In addition， 12 pregnant rats were selected as the control group （intragastrical administration and tail vein injection of equal volume of normal saline）. They were given relevant medicine， once a day， for 14 consecutive days. After the last administration， fasting blood glucose （FBG）， the levels of fasting insulin （FINS）， interleukin-1β （IL-1β）， IL-6， and tumor necrosis factor-α （TNF-α） in the serum were detected； the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， blood urea nitrogen （BUN）， and creatinine （Cr） in the renal tissue were detected； the pathological changes of renal tissue were observed； the expressions of proteins related to the JNK/nuclear factor-κB （NF-κB） signaling pathway in the renal tissue were detected. RESULTS Compared with control group， in model group， the rats showed pathological injuries in the kidney tissue， such as glomerular atrophy， edema of renal tubular epithelial cells； the levels of FBG， FINS， IL-1β， IL-6， TNF-α， MDA， BUN and Cr， HOMA-IR， as well as the phosphorylation levels of JNK and NF-κB 0453-6602005。E-mail：mcvi45@163.com p65 proteins were increased significantly （P＜0.05）， while the levels of SOD and GSH-Px were decreased significantly （P＜0.05）. Compared with model group， in each dose group of limonin， the degree of renal tissue lesions in rats was alleviated， and the above-mentioned indicators were significantly improved （P＜0.05）， showing an obvious dose-effect relationship （P＜0.05）. Compared with high-dose limonin group， in the combination group， the degree of renal tissue lesions in rats was relatively aggravated， and the changes in the above-mentioned indicators were significantly reversed （P＜0.05）. CONCLUSIONS Limonin has a certain improvement effect on renal lesions， glucose metabolism， inflammation， and oxidative stress in pregnant rats with gestational diabetes. Its mechanism may be related to the inhibition of the JNK/NF-κB signaling pathway.

ObjectiveTo investigate the role of paraventricular nucleus (PVN) corticotropin releasing hormone (CRH) neurons in chronic restraint stress (CRS)-induced anxiety-like behavior. And whether exercise relieves chronic restraint stress-induced anxiety through PVN CRH neurons. MethodsTwenty 8-week-old male C57BL/6J mice were randomly divided into control (Ctrl) group and chronic restraint stress (CRS) group. The open field test (OFT) and elevated plus maze (EPM) were used to evaluate anxiety-like behavior of the mice. Food intake was recorded after CRS. Immunofluorescence staining was used to label the expression of c-Fos expression in PVN and calculate the co-expression of c-Fos and CRH neurons. We used chemogenetic activation of PVN CRH neurons to observed the anxiety-like behavior. 8-week treadmill training (10-16 m/min, 60 min/d, 6 d/week) were used to explore the role of exercise in ameliorating CRS-induced anxiety behavior and how PVN CRH neurons involved in it. ResultsCompared with Ctrl group, CRS group exhibited significant anxiety-like behavior. In OFT, the mice in CRS groups spent less time in center area (P<0.001). In EPM, the time in open arm in CRS group were significantly decreased (P<0.001). Besides, food intake was also suppressed in CRS group compared with Ctrl group (P<0.05). Compared with Ctrl group, CRS significantly increase c-Fos expression in PVN and most of CRH neurons co-express c-Fos (P<0.001). Chemogenetic activation of PVN CRH neurons induced anxiety-like behavior (P<0.05) and inhibited feeding behavior (P<0.01). Exercise relieves chronic restraint stress-induced anxiety (P<0.001) and relieved the anorexia caused by chronic restraint stress (P<0.05). Aerobic exercise inhibited the CRS labeled c-Fos in PVN CRH neurons (P<0.001). Furthermore, ablation of PVN CRH neurons attenuated CRS induced anxiety-like behavior. ConclusionCRS activated PVN CRH neurons, induced anxiety-like behavior and reduced food intake. 8-week exercise attenuated CRS-induced anxiety-like behavior through inhibiting PVN CRH neuron. Ablation of CRH PVN neurons ameliorated CRS-induced anxiety-like behavior. These finding reveals a potential neural mechanism of exercise-relieving CRS-induced anxiety-like behavior. This provides a new idea and theoretical basis for the treatment of anxiety and related mental disorders.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Molecularly imprinted polymers(MIPs)of colchicine(COL)were prepared by precipitation polymerization with COL as template,methacrylic acid(MAA)as monomer,ethylene glycol dimethacrylate(EGDMA)as crosslinking agent,azobisisobutyronitrile(AIBN)as initiator and chloroform as porogen.The basic structure of the prepared MIPs was characterized by scanning electron microscopy(SEM),transmission electron microscopy(TEM)and Fourier transform infrared(FT-IR)spectrometry,and the adsorption properties of MIPs were evaluated by kinetic adsorption,isothermal adsorption and selective adsorption experiments.The results indicated that the prepared MIPs had uniform particles size,with a maximum adsorption capacity of 62.61 mg/g for COL and an imprinting factor of 3.74,and was suitable for sample pretreatment in determination of COL blood concentration,enabling the enrichment and separation of trace or even ultra-trace target components,thereby improving analytical capabilities.

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

Purpose To demonstrate the advantages of non-contrast-enhanced whole-heart coronary magnetic resonance angiography(NCE-CMRA)in evaluating coronary arteries by comparing ultrasonography(US),and to explore the clinical value of NCE-CMRA in the diagnosis of coronary artery lesions of Kawasaki disease(KD)in children.Materials and Methods NCE-CMRA and US imaging data of 41 children with KD from June 2017 to June 2021 who were diagnosed clinically in Lanzhou University Second Hospital were analyzed retrospectively.The display ability of US and NCE-CMRA in coronary arteries were compared.At the same time,the imaging characteristics of NCE-CMRA were analyzed,and the imaging characteristics such as the range and degree of coronary artery lesions displayed by NCE-CMRA were summarized.Results The overall segment display rate of NCE-CMRA in 41 children with KD was 75.6%;the overall segment display rate of US was 46.3%,with statistical difference between the two techniques(χ2=59.04,P<0.001).Regarding the display of the middle and distal segments of coronary arteries,NCE-CMRA had a clear imaging advantage over US(χ2=57.98 and 161.47,P<0.001).In all cases,25 patients(200 segments)had coronary artery lesions,and 94 segments of coronary artery showed different degrees of dilatation,including 8 segments(8.6%)of giant coronary artery aneurysm,35 segments(37.2%)of medium coronary artery aneurysm,and 51 segments(54.2%)of small coronary artery aneurysm or coronary artery dilation.Conclusion NCE-CMRA technology can objectively and accurately display coronary artery in children,and it can specifically evaluate the degree of damage caused by KD.It has important clinical significance in the diagnosis and evaluation of coronary artery lesions in children with KD.

Objective To investigate the effect of isorhyncophylline on cognitive impairment in rats with acute cerebral infarction and its corresponding mechanism.Methods SD rats were separated into acute cerebral infarction group,sham operation group,low-dose isorhyncophylline group,high-dose isorhyncophylline group,nimodipine group,and high-dose isorhyncophylline+ADU-S100 group,with 24 rates for each group.Except the sham operation group,the rats in other groups were treated with filament model to construct the model of acute cerebral infarction.In the sham operation group,only the right external carotid artery,common carotid artery and internal carotid artery were exposed,and the filament was not inserted.After successful modeling,the medication was administered once a day for 2 weeks.After the modeling was successful,the rats in the low dose group and the high dose group were given 5 mg/kg and 20 mg/kg respectively,and the same amount of isotonic saline was injected intraperitoneally.Nimodipine group rats were given 30 mg/kg nimodipine by intragastric administration,and the same amount of isotonic saline was also injected intraperitoneally.The rats in high dose isorhyncophylline+ADU-S 100 group were given 20 mg/kg isorhyncophylline by intragastric administration and 20 mg/kg ADU-S 100 intraperitoneally.Rats in sham operation group and acute cerebral infarction group were injected with 10 ml/kg isotonic saline by intragastric administration and intraperitoneal injection.The medication was administered once a day for 2 weeks.The Zela-Longa neurological function score was evaluated in all the rats 24 h after the final medication,and then Morris water maze test was conducted and their escape latency and the number of stays in the original platform quadrant were recorded.The levels of interleukin 6(IL-6)and tumor necrosis factor(TNF)α in serum were detected by enzyme-linked immunosorbent assay(ELISA).The water content of brain tissue was detected in each group.The volume of cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining.Evans blue was applied to detect blood-brain barrier permeability.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the expression of ZO-1 and occludin messenger RNA(mRNA)in brain tissue of each group.The expression of STING,phosphorylated tank-bound kinase 1(p-TBK1)and phosphorylated interferon regulatory factor 3(p-IRF3)in rat brain tissues was detected by western blot and compared between groups.Results Compared with sham operation group,the neurological function score([2.96±0.32]vs.0),brain tissue water content([86.9±3.2]％vs.[71.8±3.1]％),serum TNF-a([86.7±3.5]ng/L vs.[35.6±1.7]ng/L)and IL-6([167.8±6.1]ng/L vs.[50.2±2.2]ng/L)levels,cerebral infarction volume([28.6±1.3]mm3 vs.0 mm3),evans blue content([1.57±0.13]g/Lvs.[0.96±0.08]g/L),STING([1.83±0.16]vs.[0.86±0.08]),p-TBK1([0.89±0.07]vs.[0.41±0.03]),and p-IRF3([0.67±0.05]vs.[0.13±0.01])protein expression in brain tissue were increased,expression of ZO-1([0.45±0.04]vs.[1.00±0.00])and occludin mRNA([0.23±0.02]vs.[1.00±0.00])in brain tissue were decreased,the escape latency was prolonged([33.6±1.6]s vs.[12.3±0.5]s),and the number of stays in the original platform quadrant([5.9±0.2]times vs.[15.7±0.4]times)was decreased in the acute cerebral infarction group 24 h after last medication administration(all P＜0.05).(2)Compared with acute cerebral infarction group,the neurological function score([2.37±0.21],[1.14±0.17],[1.18±0.13]vs.[2.96±0.32]),brain tissue water content([81.8±3.0]％,[74.9±3.0]％,[74.3±2.9]％vs.[86.9±3.2]％),serum TNF-α([71.1±1.4]ng/L,[43.4±2.0]ng/L,[41.5±1.9]ng/L vs.[86.7±3.5]ng/L)and IL-6([129.8±5.4]ng/L,[81.2±3.8]ng/L,[80.0±3.6]ng/L vs.[167.8±6.1]ng/L)levels,cerebral infarction volume([21.7±1.0]mm3,[10.5±0.5]mm3,[10.7±0.5]mm3 vs.[28.6±1.3]mm3),evans blue content([1.39±0.12]g/L,[1.16±0.10]g/L,[1.18±0.19]g/L vs.[1.57±0.13]g/L),STING([1.50±0.14],[1.02±0.11],[1.01±0.09]vs.[1.83±0.16]),p-TBK1([0.75±0.05],[0.54±0.04],[0.52±0.05]vs.[0.89±0.07]),and p-IRF3([0.51±0.05],[0.25±0.02],[0.27±0.02]vs.[0.67±0.05])protein expression in brain tissue were decreased,expression of ZO-1([0.58±0.05],[0.87±0.07],[0.89±0.09]vs.[0.45±0.04])and occludin mRNA([0.36±0.03],[0.71±0.06],[0.69±0.05]vs.[0.23±0.02])in brain tissue were increased,the escape latency were shortened([28.6±1.0]s,[16.5±0.7]s,[16.4±0.7]s vs.[33.6±1.6]s),and the number of stays in the original platform quadrant([8.2±0.3]times,[12.8±0.5]times,[12.9±0.5]times vs.[5.9±0.2]times)were increased in the low-dose isorhyncophylline group,high-dose isorhyncophylline group,and nimodipine group(all P＜0.05).(3)Compared with high-dose isorhyncophylline group,the neurological function score([2.12±0.14]vs.[1.14±0.17]),brain tissue water content([78.7±3.2]％vs.[74.9±3.0]％),serum TNF-a([59.7±2.1]ng/L vs.[43.4±2.0]ng/L)and IL-6([118.9±4.6]ng/L vs.[81.2±3.8]ng/L)levels,cerebral infarction volume([16.6±0.4]mm3 vs.[10.5±0.5]mm3),evans blue content([1.36±0.10]g/L vs.[1.16±0.10]g/L),and STING([1.37±0.12]vs.[1.02±0.11]),p-TBK1([0.67±0.05]vs.[0.54±0.04]),and p-IRF3([0.39±0.03]vs.[0.25±0.02])protein expression in brain tissue were increased,expression of ZO-1([0.63±0.05]vs.[0.87±0.07])and occludin mRNA([0.46±0.05]vs.[0.71±0.06])in brain tissue were decreased,the escape latency was prolonged([23.4±1.0]svs.[16.5±0.7]s),and the number of stays in the original platform quadrant([9.6±0.3]times vs.[12.8±0.5]times)was decreased in the isorhyncophylline high-dose+ADU-S100 group(all P＜0.05).Conclusion Isorhyncophylline can inhibit inflammation,reduce blood-brain barrier damage,reduce cerebral edema,and improve cognitive impairment in rats with acute cerebral infarction,and the mechanism of which may be related to the inhibition of STING/TBK1/IRF3 pathway.

Objective:To evaluate the risk factors for the formation of parastomal Hernias(PSH)using meta-analysis,and to provide a theoretical basis for the prevention and treatment of PSH.Methods:Case control or Cohort study of PSH risk factors were collected by searching PubMed,CNKI,Wanfang data and other databases.Extract relevant data and perform meta-analysis using RevMan 5.3.Results:The results included a total of 16 studies,with a total sample size of 2411 cases,including 670 in the PSH group and 1741 in the non PSH group.The results showed that advanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,and postoperative Hypoproteinemia could increase the risk of PSH(P＜0.05);Smoking,previous ab-dominal surgery history,preoperative radiotherapy/chemotherapy etc.,were not significantly asso-ciated with the occurrence of PSH(P＞0.05).Conclusion:The current evidence shows that ad-vanced age,female gender,BMI≥25,hypertension,COPD/chronic cough,diabetes,postoperative Hypoproteinemia are risk factors for PSH,and extraperitoneal stoma can reduce the occurrence of PSH.

The NiFe2O4-graphene oxide nanocomposite modified with polyethylenimine(GO@PEI-NiFe2O4)was prepared to purify and enrich phosphopeptides from biosamples.The Ni2+and Fe3+ions on its surface could coordinate with phosphate groups and then selectively adsorb phosphopeptides.PEI was conducive to the above combination due to its high hydrophilicity.The material showed good magnetic response properties and could be rapidly separated from samples with the aid of magnet.With tryptic digest of β-casein as sample,the enrichment property of the material to phosphopeptides was studied,which was compared with the results of GO@NiFe2O4,revealing the adsorption mechanism of GO@PEI-NiFe2O4.The static and dynamic binding properties of GO@PEI-NiFe2O4 were investigated using pTyr as a representative phosphopeptide,and the adsorption capacity was 36.2 μg/mg.The results showed that the material could remove the interference of nonphosphopeptides and effectively enrich phosphopeptides in complex matrix.After enrichment by GO@PEI-NiFe2O4,1535 phosphopeptides were identified from the tryptic digest of rat liver by mass spectrum and the enrichment effect of GO@PEI-NiFe2O4 greatly outperformed commercial Fe3+-IMAC kits.This work provided an efficient material for the enrichment of phosphopeptides,showing potential applications in phosphoproteomics research.

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.