OBJECTIVE To investigate the ameliorative effect and mechanism of short-acting exenatide on diabetic cognitive dysfunction. METHODS Spontaneously diabetic db / db mice were randomly divided into model group （normal saline） and exenatide group （50 μg/kg）， with db / m mice as the normal control group （normal saline）， with 8 mice in each group. Mice in each group were subcutaneously injected with corresponding drugs or normal saline twice daily for 8 consecutive weeks. Body weight and fasting blood glucose were measured at a fixed time every week. Cognitive function was evaluated by Morris water maze test. The levels of oxidative st ress indicators [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH） ] ， cyclic adenosine monophosphate （cAMP） and protein kinase A （PKA） were detected in hippocampus tissue of mice. The hippocampal neuronal HT22 cells of mice were divided into control group （25 mmol/L glucose）， high glucose group （125 mmol/L glucose）， high glucose+exenatide group （125 mmol/L glucose+20 nmol/L exenatide）， high glucose+exenatide+H89 （PKA inhibitor） group （125 mmol/L glucose+20 nmol/L exenatide+10 μmol/L H89）， and high glucose+H89 group （125 mmol/L glucose+10 μmol/L H89）. After 48 h of intervention with corresponding solutions/culture medium， the levels of oxidative stress indicators， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and the phosphorylation level of dynamin-related protein 1 （Drp1） were measured. RESULTS Animal experiments showed that compared with the normal control group， the model group exhibited significantly increased body weight， fasting blood glucose and MDA level in the hippocampus （ P ＜0.05）， as well as significantly prolonged escape latency （ P ＜0.05）； swimming speed significantly slowed down， the time spent in the target quadrant， the number of platform crossings， and the levels of SOD， GSH， cAMP and PKA in the hippocampus were significantly decreased （ P ＜0.05）. Compared with model group， all the above indicators （except for swimming speed） in the exenatide group were significantly reversed （ P ＜0.05）. Cell experiments showed that compared with high glucose group， the high glucose+exenatide group had significantly decreased MDA level （ P ＜0.05）， and significantly increased levels of SOD， GSH， cAMP and PKA， the activities of mitochondrial respiratory enzymes Ⅱ and Ⅳ， and phosphorylation level of Drp1 （ P ＜0.05）. Compared with high glucose+exenatide group， the above indicators in the high glucose+exenatide+H89 group were significantly reversed （ P ＜0.05）. CONCLUSIONS Short-acting exenatide can activate the cAMP/PKA pathway， promote Drp1 phosphorylation， and increase the activities of mitochondrial respiratory enzymes， thereby maintaining mitochondrial stability， reducing oxidative stress injury， and ultimately improving diabetic cognitive dysfunction.

Objective To investigate the expression of serum microRNA(miR)-16a and mir-15b in patients with early-onset neonatal sepsis(EONS)and its value in clinical diagnosis and prognosis evaluation.Methods 114 children diagnosed with EONS admitted to the Department of Neonatology,Baoding Hospital of Beijing Children's Hospital Affiliated to Capital Medical University from October 2020 to October 2023 were selected as the EONS group,and 114 healthy newborns in the hospital during the same period were selected as the control group.Follow up was conducted on all EONS patients for a period of 6 months,including 34 cases in the poor prognosis group and 80 cases in the good prognosis group.The relative expression levels of miR-16a and miR-15b were measured within 6h of admission using real-time fluorescence quamtitative PCR(qRT-PCR).ROC curve was applied to analyze the diagnostic and prognostic value of serum miR-16a and miR-15b for EONS.Multivariate Logistic regression was applied to analyze the factors that affected the poor prognosis of EONS.Results Compared with the reference group,the birth weight of children in the EONS group(3.44±0.35kg/m2 vs 3.89±0.40kg/m2)was obviously reduced,and there was a obvious difference(35/114,1/114)in pathological jaundice between the two groups,and the differences were statistically significant(t=9.040,χ2=35.922,all P＜0.05).Compared with the reference group,the serum levels of miR-16a and miR-15b in the EONS group were obviously increased,and the differences was statistically significant(t=7.699,8.606,all P＜0.05).The area under the curve(AUC)of the ROC curve for the combined diagnosis of EONS by serum miR-16a and miR-15b was higher than that of miR-16a and miR-15b alone,and the differences were statistically significant(Z=2.619,2.157,all P<0.05).Compared with the good prognosis group,the poor prognosis group had a obvious decrease in body weight at birth,and a obvious increase in serum levels of miR-16a and miR-15b,and the differences were statistically significant(t=5.434,6.308,all P＜0.05).The AUC of serum miR-16a and miR-15b combined for prognostic evaluation was higher than that of miR-16a and miR-15b evaluated separately,and the differences were statistically significant(Z=2.364,2.073,all P＜0.05).Birth weight,miR-16a,miR-15b expression level was a prognostic factor of EONS(Wald χ2=33.459,16.146,49.797,all P<0.05).Conclusion MiR-16a and miR-15b are highly expressed in the serum of children with EONS,and they have certain diagnostic and prognostic value for EONS.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Stent entrapment is a rare complication of percutaneous coronary intervention.In recent years,with the development of distal radial artery puncture technology,the rare complications related to distal radial artery have been gradually understood.This article describes a patient who underwent coronary intervention through a distal radial approach,and the stent was dislodged and trapped in the far radial artery.The patient came to our hospital for stent implantation because of acute extensive anterolateral myocardial infarction.During the intervention,the balloon could not be filled when the stent was released from the left anterior descending artery,and the retracting stent could not be used to remove the guide catheter.The stent was dislodged and embedded in the distal vessel.The sheath was inserted through the proximal radial reverse puncture,and the stent was captured with a snare and removed.

Objective To explore the inhibitory effect of Xinhui tangerine peel polysaccharides on the mouse skin fibroblasts so as to understand the underlying molecular mechanism.Methods We separated and purified the components of tangerine peel polysaccharides from Xinhui tangerine peel.C57BL/6 mouse skin fibroblasts were isolated and cultured for the cellular experimental study.We set up a blank control group(normal culture)and low-,medium-and high-dose experimental groups(50,100 and 200 μg/mL tangerine peel polysaccharides).After 24 hours of treatment,cell survival rate was assessed by CCK-8 assay.The mRNA and protein expression levels of collagen type Ⅰ(Col1a1),collagen type Ⅲ(Col1a3),TGF-β1 and ACTA2 in fibroblasts were examined by RT-qPCR and Western blotting.Smad3 was examined by Western blotting.Results The cell survival rate in the blank control group,the medium-and high-dose experimental groups was 100％,(90.54±6.74)％,and(78.90±4.24)％,respectively.The relative expression level of Col1a1 protein was 1.13±0.15,0.57±0.16,and 0.48±0.05,respectively;the relative expression level of Col3a1 protein was 0.81±0.13,0.49±0.11 and 0.50±0.03;the relative expression level of TGF-β1 protein was 1.11±0.15,0.60±0.13,and 0.33±0.11;the relative expression level of p-Smad3/Smad3 proteins was 0.96±0.05,0.75±0.06 and 0.71±0.03.The mRNA expression level of Col1a1 was 1.01±0.17,0.58±0.11,and 0.52±0.12;the mRNA expression level of Col3a1 was 1.01±0.12,0.56±0.19,and 0.65±0.14;the expression level of ACTA2 mRNA was 1.01±0.13,0.24±0.04,and 0.22±0.07;the mRNA expression level of TGF-β1 was 1.00±0.09,0.50±0.10,and 0.49±0.15.The relative expression levels of p-Smad3/Smad3 proteins were 0.86±0.06,0.66±0.06,0.55±0.13,0.43±0.09,0.35±0.06,and 0.27±0.12,respectively,after time-related treatment with high-dose tangerine peel polysaccharides.The above indicators in medium-and high-dose tangerine peel polysaccharide groups showed statistically significant differences compared to those in the blank control group(P＜0.05).Conclusion Tangerine peel polysaccharides can inhibit the cell proliferation and the synthesis of keloid-related genes on fibroblasts by inhibiting TGF-β1/Smad3 signaling pathway.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Objective:To prepare rabbit polyclonal antibody against human FAM21 and analyze antibody specificity.Methods:Using the plasmid encoding human FAM21 full-length gene as a template,the nucleotide sequence of its 2 431～3 006 base was amplified by PCR and connected to the pGEX-6p-1 prokaryotic expression vector to construct pGEX-6P-1-FAM21 recombinant plasmid expressing the 811～1 002 amino acid fragment of FAM21.The recombinant plasmid was transformed into BL21(DE3)compe-tent Escherichia coli and was expressed inductively,and the protein was purified using GST fusion protein purification magnetic beads.The purified GST fusion protein was used as an antigen to immunize New Zealand rabbits,and the collected antiserum was purified by an agarose column containing GST protein.The specificity of antibody was detected by Western blot and immunofluorescence assay in stable FAM21 knockdown HeLa cells.Results:The pGEX-6p-1-FAM21 prokaryotic expression plasmid was successfully constructed and induced to express in BL21(DE3)competent Escherichia coli.The purified GST fusion protein had a molecular weight of approxi-mately 50 kD,and the purified antibody titer from immunized New Zealand rabbits was greater than 1∶128 000,with high specificity.Conclusion:The pGEX-6p-1-FAM21 prokaryotic expression plasmid is successfully constructed,and the rabbit polyclonal antibody against human FAM21 is prepared for Western blot and immunofluorescence assay.

Objective:To investigate the current situation of water-borne endemic fluorosis in Anhui Province, and provide basic data for the adjusting the prevention and control measures.Methods:Using cross-sectional survey method, all villages in the water-borne endemic fluorosis areas were investigated in Anhui Province from 2019 to 2022. In water-borne endemic fluorosis village, the situation of water improvement project and the fluoride level of drinking water were investigated, and dental fluorosis of all children aged 8 - 12 was examined. The criteria for determining the achievement of control targets for water-borne endemic fluorosis in affected counties were based on the "Evaluation Measures for Control and Elimination of Key Endemic Diseases (2019 Edition)".Results:From 2019 to 2022, the rate of water improvement village in water-borne endemic fluorosis areas were 88.47% (1 527/1 726), 100% (1 726/1 726), 100% (1 726/1 726) and 100% (1 726/1 726), respectively. The qualified proportion of water fluoride in water-borne endemic fluorosis villages was 33.84% (584/1 726), 63.09% (1 089/1 726), 70.74% (1 221/1 726) and 74.33% (1 283/1 726), respectively. The prevalence rates of dental fluorosis in children aged 8 - 12 were 25.48% (45 461/178 440), 15.78% (27 959/177 200), 13.68% (23 505/171 880) and 12.66% (23 315/184 200), respectively. The proportion of affected counties that had achieved the control target of water-borne endemic fluorosis was 16% (4/25), 60% (15/25), 36% (9/25) and 40% (10/25), respectively.Conclusions:The water-borne endemic fluorosis areas in Anhui Province have improved the water fluoride qualification rate and reduced the incidence of fluorosis in children through prevention and control measures such as water improvement and fluoride reduction. However, the prevention and control efforts in key areas and counties need to be further improved.

Objective To explore the application value of MRI diaphragmatic navigation technology combined with three dimensional liver acquisition with volume acceleration-flexible(3D LAVA-FLEX)sequence in abdominal enhanced imaging of infants and young children.Methods A retrospective analysis was conducted on imaging data of 84 infants and young children who underwent abdominal enhanced MRI examination in our hospital between January 2021 and December 2023.All 84 infants and young children initially underwent conventional dynamic contrast-enhanced 3D LAVA-FLEX sequence scanning;the delayed phase images obtained were included in the dynamic enhancement group.Subsequently,diaphragmatic navigation combined with 3D LAVA-FLEX sequence examination was implemented,and the obtained images were included in the diaphragm navigation group.Subjective scoring was performed for images in both groups,while the signal to noise ratio(SNR),contrast to noise ratio(CNR),and artifact quantification(AQ)were measured and compared between the two groups.Results The respiratory motion artifacts,the clarity of liver parenchyma enhancement,the clarity of liver vascular enhancement,the clarity of spleen parenchyma enhancement and the overall image quality score in the diaphragm navigation group were higher than those in the dynamic enhancement group,and the differences were statistically significant(P<0.05).There were statistically significant differences in SNR and AQ between the two groups of images(P<0.000 1),while there was no statistically significant difference in CNR between the two groups of images(P>0.05).Conclusion Diaphragmatic navigation technology combined with 3D LAVA-FLEX sequence imaging can improve the image quality of abdominal MRI enhanced imaging in infants and young children,and provide a reference for clinical diagnosis and treatment.

Objective By observing and measuring the relevant data of the buccal branch of the facial nerve,the parotid duct and the facial artery,the positional relationship among the three was analyzed to avoid accidental injury to the buccal branch of the facial nerve and the parotid duct when ligaturing the facial artery during the operation.Methods Forty adult head and neck specimens were dissected to observe the relationship between the buccal branch of the facial nerve and the parotid duct,the course and positional relationship of the facial artery,and the relationship between the buccal branch of the facial nerve and the peripheral vascular network.The relevant diameters were measured with a vernier caliper.Results The buccal branch of the facial nerve was divided into the superior buccal branch and the inferior buccal branch,and there was no direct anastomosis or connecting fiber between the buccal branch of the facial nerve and the parotid duct.The superior buccal branch was relatively thick,and it has a relatively constant position,which was parallel to the parotid duct.The position of the inferior buccal branch was not constant and it ran on or slightly above the plane of angulus oris.The superior buccal branch was located(10.76±5.54)mm from the parotid duct,while the inferior buccal branch was positioned(6.84±4.06)mm away from the parotid duct.The course of the main trunk of the facial artery was relatively fixed.Moreover,if the branch of the facial artery was missing,other branches of the facial artery would extend to replace the missing branch artery.The main trunk of the facial artery had a diameter of(2.34±0.83)mm,and its branches formed anastomoses with the buccal branch of the maxillary artery,creating a vascular network in the parotid and buccal regions.There was a vascular network around the buccal branch of the facial nerve,which was mostly small branches of the facial artery and the superficial temporal artery.Conclusion The buccal branch of the facial nerve exhibits a consistent anatomic relationship with the parotid duct and the facial artery.During the ligation of the facial artery,the parotid duct can serve as a landmark to accurately locate the buccal branch of the facial nerve,thereby significantly reducing the risk of inadvertent injury to the buccal branch of the facial nerve and the parotid duct.