OBJECTIVE To investigate the mechanisms of adrenal dysfunction among adult offspring rats caused by prenatal ethanol exposure(PEE)aggravated by high-fat diet(HFD)and unpredictable chronic stress(UCS).METHODS Pregnant rats were randomly divided into the control group(saline,ig,once)and PEE group(4 g·kg-1,ig,once)from gestational day(GD)11 until delivery.At postnatal week 4(PW4),offspring rats from the control group and PEE group were randomly assigned to three sub-groups:the normal diet(ND)group,HFD group,and HFD-UCS group(n=20 per subgroup,at an equal male-to-female ratio).The rats in each group were given a corresponding diet until PW24.The HFD-UCS group received HFD until PW24,with additional UCS treatment initiated at PW21 and continued for 3 weeks.Serum adrenocorticotropic hormone(ACTH)levels were measured by radioimmunoassay,and corticosterone(CORT)levels were quantified via enzyme-linked immunosorbent assay(ELISA).Adrenal mRNA expressions of steroidogenic factor 1(Sf1),steroidogenic acute regulatory protein(Star),cyto-chrome P450 cholesterol side chain cleavage(P450scc),3β-hydroxysteroid dehydrogenase(3β-Hsd),steroid 21-hydroxylase(P450c21),steroid 11β-hydroxylase(P450c11),11β-hydroxysteroid dehydrogenase type 1(11β-Hsd1),11β-Hsd 2,mineralocorticoid receptor(Mr),glucocorticoid receptor(Gr),insulin-like growth factor 1(Igf1),IGF1 receptor(Igf1r),and serine/threonine kinase 1(Akt1)were determined using real-time quantitative PCR.Protein expressions of Akt1 and phosphorylated Akt1(p-Akt1)were analyzed via immunohistochemistry.RESULTS In male offspring,HFD/PEE significantly reduced serum ACTH and CORT levels,downregulated Star,P450scc,3β-Hsd and P450c11 mRNA,decreased 11β-Hsd1 mRNA expressions and 11β-Hsd1/11β-Hsd2 ratio,but increased Igf1,Igf1r mRNA,and p-Akt1 protein.Conversely,HFD-UCS/PEE elevated ACTH,CORT,P450scc,3β-Hsd and P450c11 mRNA,increased 11β-Hsd1 and 11β-Hsd1/11β-Hsd2 ratio while suppressing Igf1 mRNA,and p-Akt1 protein.In females,HFD/PEE decreased ACTH but upregulated Igf1,Akt1 mRNA,and p-Akt1 protein.HFD-UCS/PEE increased ACTH,CORT,Sf1,Star,P450scc and P450c11 mRNA,and 11β-Hsd1/11β-Hsd2 ratio,but reduced lgf1 and Igf1r mRNA.CONCLUSION HFD/UCS can aggravate PEE-induced adrenal dysfunction in adult offspring.The adrenal"GC-IGF1 axis"is an endocrine negative feedback one,and its decompensation may increase the susceptibility of a wide range of GC-related adult chronic diseases,such as diabetes.

OBJECTIVE To compare the efficacy and safety of dupilumab versus thalidomide in the treatment of refractory prurigo nodularis （PN） in adults. METHODS A retrospective analysis was conducted on the clinical data of 123 adult patients with refractory PN admitted to Wuhan First Hospital from May 2021 to June 2024. Among them， 63 patients who received dupilumab comprised the observation group and 60 patients who received thalidomide comprised the control group. Clinical efficacy indicators [Investigator Global Assessment （IGA） score， Pruritus Numerical Rating Scale （P-NRS） score， Patient-Oriented Eczema Measure （POEM） score， and Dermatology Life Quality Index （DLQI） score]， allergic biomarkers [eosinophil （EOS） count in peripheral blood and serum total immunoglobulin E （IgE） level]， psychological scores [Hospital Anxiety and Depression Scale （HADS）] before and after treatment， as well as the occurrence of adverse drug reaction during treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences between the two groups in above clinical efficacy indicators， allergic biomarkers， or psychological scores （P＞0.05）. At 4， 8， 12 and 16 weeks after treatment， both groups showed significant decreases in IGA score （except for the control group 4 weeks after treatment）， IGA activity score （except for the control group 4 weeks after treatment）， P-NRS score， POEM score， DLQI score （except for the control group 4 weeks after treatment）， serum EOS count， and serum total IgE level compared with baseline （P＜0.05）； at 12 and 16 weeks after treatment， scores on both the HADS-anxiety subscale and HADS-depression subscale were also significantly lower than baseline in both groups （P＜0.05）； the observation group was significantly lower than the control group （P＜0.05）. The overall incidence of adverse events was 12.70% in the observation group， which was significantly lower than 28.33% in the control group （P＜0.05）. CONCLUSIONS Dupilumab treatment in adults with refractory PN demonstrates superior efficacy compared with thalidomide in improving skin lesions， relieving pruritus， reducing peripheral EOS counts and serum total IgE， and improving quality of life and psychological status， while showing a more favorable safety profile.

OBJECTIVE To investigate the mechanisms of adrenal dysfunction among adult offspring rats caused by prenatal ethanol exposure(PEE)aggravated by high-fat diet(HFD)and unpredictable chronic stress(UCS).METHODS Pregnant rats were randomly divided into the control group(saline,ig,once)and PEE group(4 g·kg-1,ig,once)from gestational day(GD)11 until delivery.At postnatal week 4(PW4),offspring rats from the control group and PEE group were randomly assigned to three sub-groups:the normal diet(ND)group,HFD group,and HFD-UCS group(n=20 per subgroup,at an equal male-to-female ratio).The rats in each group were given a corresponding diet until PW24.The HFD-UCS group received HFD until PW24,with additional UCS treatment initiated at PW21 and continued for 3 weeks.Serum adrenocorticotropic hormone(ACTH)levels were measured by radioimmunoassay,and corticosterone(CORT)levels were quantified via enzyme-linked immunosorbent assay(ELISA).Adrenal mRNA expressions of steroidogenic factor 1(Sf1),steroidogenic acute regulatory protein(Star),cyto-chrome P450 cholesterol side chain cleavage(P450scc),3β-hydroxysteroid dehydrogenase(3β-Hsd),steroid 21-hydroxylase(P450c21),steroid 11β-hydroxylase(P450c11),11β-hydroxysteroid dehydrogenase type 1(11β-Hsd1),11β-Hsd 2,mineralocorticoid receptor(Mr),glucocorticoid receptor(Gr),insulin-like growth factor 1(Igf1),IGF1 receptor(Igf1r),and serine/threonine kinase 1(Akt1)were determined using real-time quantitative PCR.Protein expressions of Akt1 and phosphorylated Akt1(p-Akt1)were analyzed via immunohistochemistry.RESULTS In male offspring,HFD/PEE significantly reduced serum ACTH and CORT levels,downregulated Star,P450scc,3β-Hsd and P450c11 mRNA,decreased 11β-Hsd1 mRNA expressions and 11β-Hsd1/11β-Hsd2 ratio,but increased Igf1,Igf1r mRNA,and p-Akt1 protein.Conversely,HFD-UCS/PEE elevated ACTH,CORT,P450scc,3β-Hsd and P450c11 mRNA,increased 11β-Hsd1 and 11β-Hsd1/11β-Hsd2 ratio while suppressing Igf1 mRNA,and p-Akt1 protein.In females,HFD/PEE decreased ACTH but upregulated Igf1,Akt1 mRNA,and p-Akt1 protein.HFD-UCS/PEE increased ACTH,CORT,Sf1,Star,P450scc and P450c11 mRNA,and 11β-Hsd1/11β-Hsd2 ratio,but reduced lgf1 and Igf1r mRNA.CONCLUSION HFD/UCS can aggravate PEE-induced adrenal dysfunction in adult offspring.The adrenal"GC-IGF1 axis"is an endocrine negative feedback one,and its decompensation may increase the susceptibility of a wide range of GC-related adult chronic diseases,such as diabetes.

Objective:To observe expression changes of PHD2 and HIF-1α, and to investigate the effect of β-AR on the regulation of PHD2/HIF-1α pathway on heart failure after myocardial infarction.Methods:Acute myocardial infarction model in rats were established by ligation of left anterior descending coronary artery. The experiment was randomly (random number)divided into three groups: sham operation group, model group and propranolol group. The changes of electrocardiogram before and after coronary artery ligation were recorded, and cardiac function was detected by echocardiography 12 weeks later. Also, the mRNA and protein expression of PHD2 and HIF-1α were detected by PCR and Western Blot.Results:The ST segment of the ECG showed a significant elevation after the coronary artery was ligated. After 12 weeks of ligation, compared with model group, the ejection fraction (EF) in sham operation group [(79.45 ± 2.86)% vs (61.10 ± 2.78)% , P <0.05] and in propranolol group was higher [(67.33 ± 2.66)% vs (61.10 ± 2.78)%), P <0.05].The mRNA and protein expression of PHD2 decreased significantly in the model group( P <0.05), while the propranolol group increased significantly compared with the model group ( P <0.05). The mRNA and protein expression of HIF-1α increased significantly in the model group ( P <0.05), while the propranolol group decreased significantly compared with the model group ( P <0.05). Conclusions:PHD2/HIF-1α pathway may play an important role in the development of heart failure after myocardial infarction in rats. Activation of β-adrenal system after myocardial infarction may promote the occurrence of heart failure by regulating PHD2/HIF-1α pathway.

Objective:To observe the changes of rapidly activated delayed rectifier potassium channel (IKs) and slowly activated delayed rectifier potassium channel (IKs) in cardiac hypertrophy and to evaluate the effects of IKs and IKs blocker on the incidence ofventricular arrhythmias in guinea pigs with left ventricular hypertrophy (LVH).Methods:Guinea pigs were divided into a sham operation group and a left ventricular hypertrophy (LVH) group.LVH model was prepared.Whole cell patch-clamp technique was used to record IKr and IKs tail currents in a guinea pig model with LVH.The changes of QTc and the incidence rate of ventricular arrhythmias in LVH guinea pigs were observed by using the IKr and IKs blockers.Results:Compared with cardiac cells in the control group,the interventricular septal thickness at end systole (IVSs),left ventricular posterior wall thickness at end systole (LVPWs),QTc interval and cell capacitance in guinea pigs with LVH were significantly increased (P＜0.05);while IKs densities were significantly reduced [+60 mV:(0.36±0.03) pA/pF vs (0.58±0.05) pA/pF,P＜0.01].However,LVH exerted no significant effect on IKr densities.IKr blocker markedly prolonged the QTc interval (P＜0.01) and increased the incidence of ventricular arrhythmias in guinea pigs with LVH compared with the control guinea pigs.In contrast,IKs blocker produced modest increase in QTc interval in guinea pigs of control group with no increase in LVH animals.IKs blocker did not induce ventricular arrhythmias incidence in either control or LVH animals.Conclusion:The cardiac hypertrophy-induced arrhythmogenesis is due to the down-regulation of IKs.

Intravascular ultrasound (IVUS) is an invasively tomograhpic techology. As a adjunct to angiography, IVUS has important application value for percutaneous coronary intervention (PCI) . IVUS allows to assess the degree of area stenosis, optimize PCI strategy and improve clinical outcomes. Although lacking randomized trials, the currently nonrandomized studies support that IVUS-guided PCI of the left main coronary artery stenoses reduce the rate of the major adverse cardiac events (MACE, including cardiac death,myocardial infarction,and target vessel revacularization) and improve long-term outcomes compared with angiography-guided PCI.

Objective To evaluate the effect of tirofiban injection in coronary artery occlusion by suction catheter on the opening time of the coronary artery occlusion , the improvement of the blood flow and the incidence of adverse events in 30 days. Methods A total of 97 patients with acute myocardial infarction in recent 4 years were included , whose culprit vessels were subtotal occlusion or total occlusion by angiography and were randomly divided into thrombus aspiration group (group A) and tirofiban injection in occlusion and thrombus aspiration group (group B). The opening time of the coronary artery, the improvement of the blood flow and the incidence of adverse events in 30 days were compared between two groups. Results The opening time of the coronary artery occlusion in group A was shortened when compared with group B but the blood flow arriving TIMI III grade in group B was shorter (P < 0.05). No-reflow incidence in group B was lower while the proportion of blood flow arriving TIMI III grade was higher than that in group A in early phase (P < 0.05). The incidence of adverse events in 30 days was decreased in group B when compared with group A ,but the difference wasn't statistically significant (P > 0.05). Conclusion Direct tirofiban injection in coronary artery occlusion could effectively shorten the opening time of the coronary artery occlusion reduce no-reflow incidence , and improve coronary perfusion but could not decrease the incidence of adverse cardiovascular events in 30 days.

Objective: To analyze influencing factors of percutaneous coronary intervention (PCI) on therapeutic effect in patients with coronary chronic total occlusions (CTO). Methods: Clinical data, lesion features and PCI therapeutic results of 65 patients with 72 CTO lesions, who received PCI in our hospital from Jan 2010 to Dec 2012, were retrospectively analyzed. Results: PCI success rate of CTO lesion was 91.67% (66/72); compared with patients with CTO occlusion 3~12 months, there was significant decrease in PCI success rate (97.78% vs. 81.48%) in those with CTO occlusion >12 months; compared with patients with occlusion length ≤15mm, there was significant decrease in PCI success rate (97.96% vs. 78.26%) in those with occlusion length >15mm; compared with patients with mouse tail-like broken ends, there was significant decrease in PCI success rate (96.55% vs. 71.43%) in those with knife cut-like broken ends, P<0.05 all; PCI failed in six lesions, in which four because guidewire failed to pass through lesions and two because balloon failed to pass through lesions; incidence rate of complications was 7.69% during PCI, there were no major adverse cardiovascular events during admission in all patients; symptoms relieving rate of angina pectoris was 90.16% after PCI. Conclusion: Success rate of percutaneous coronary intervention is related to lesion features, CTO occlusion duration etc.

Aim To investigate the effects of β1-ad-renergic receptor (β1-AR ) on rapid component of the delayed rectifier potassium current ( IKr ) in ventricular
myocytes of guinea pigs with chronic heart failure ( CHF) . Methods The CHF model of guinea pigs was established by descending thoracic aortic banding .
Whole-cell patch-clamp technique was used to record IKr in ventricular myocytes. The effects ofβ1-AR on IKr in CHF ventricular myocytes were detected and its mechanisms were studied by pretreatment with protein kinase A ( PKA ) inhibitor and calmodulin kinase II( CaMK II) inhibitor. Results In CHF ventricular myocytes, xamoterol, the selectiveβ1-AR agonist, de-creased IKr by (52±8)% and prolonged action poten-tial duration. These effects were completely abolished by pretreatment of myocytes with CGP20712A, a selec-tive β1-AR antagonist. íamoterol only decreased IKr
by (28±3)% by pretreatment of CHF myocytes with specific PKA inhibitor KT5720 . KN93 , an inhibitor of CaMKII, did not attenuate the inhibitory effect on CHF ventricular myocytes. Conclusion IKr is inhibi-ted by β1-AR activation in CHF ventricular myocytes. PKA, but not CaMKII signaling pathway is involved in, at least in part, the inhibitory effect ofβ1-AR acti-vation on IKr.

Aim To research the changes of myocardial endoxin level in rats with myocardial ischemia reperfusion (MIR) and the protevtive effects of anti digoxin antiserum, an endoxin specific antagonist, on MIR injury. Methods Myocardial ischemia reperfusion injury models were obtained by ligating left anterior descending coronary artery 30 min followed by 45 min reperfusion. Sprauge Dawley rats were randomly divided into seven groups each with 10 rats. There were sham group, MIR group, normal saline group, verapamil group, low dose anti digoxin antiserum group, middle dose anti digoxin antiserum group, and high dose anti digoxin antiserum group. After reperfusion of left ventricular myocardium, sample of ischemia were processed immediately. Myocardial endoxin levels, Na +, K + ATPase activities, and intramitochondrial Ca 2+ contents were measured. The myocardial morphology were observed. Results Myocardial endoxin levels were significantly increased; Na +, K + ATPase activities were remarkably decreased; intramitochondrial Ca 2+ contents were remarkably raised. Meanwhile, myocardial morphology injury were remarkable in light microscope and electric microscope. Middle and high dose of anti digoxin antiserum intervention, myocardial endoxin levels were remarkably decreased; Na +, K + ATPase activities were drastically increased; intramitochondrial Ca 2+ declined. The myocardial histological morphology was significantly improved. Conclusion Antidigoxin antiserum, an endoxin antagonist, had protective effect against MIR. The mechanism maybe related to antagonizing endoxin, restoring energy metabolism, attenuating intracellular Ca 2+ overload.