Objective To investigate the effect of hypert riglyceridemia on vascular endothelial function. Methods With high-resolution ultrasound, flow and nitroglycerin-induced dilatation of the brachial artery were determined in thirty hypertriglyceridemic patients and thirty healthy subjects as controls. Serum lipid and plasma endothelin (ET) were determined. Results In patients with hypertriglyceridemia,flow-induced vasodilatation was much reduced compared with that in the control subjects[(2.7±2.0)% vs (15.0±8.0)%, P<0.001］.However, vasodilatation in response to nitroglycerin were similar in both groups［(15.0±5.0)% vs (16.8±9.0)%, P>0.05].Plasma ET level in the hypertriglyceridemic group was significantly higher than that in the control group［(106.22±19.16) μg/L vs (72.37±14.06) μg/L, P<0.001].ConclusionEndothelium-dependent vasodilatation was impaired in patients with hypertriglyceridemia.

Aged ; Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Humans ; Male

Even though mutations in LMNA have been reported in patients with typical dilated cardiomyopathy (DCM) and atrioventricular block (AVB) previously, the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval. Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2, where the LMNA gene was located. Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA, which resulted in an E82K mutation. The E82K mutation co-segregated with all affected individuals in the family, and was not present in 200 normal controls. Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades. Ejection fractions were documented in 5 patients with DCM, but 4 showed a normal value of [Symbol: see text]50%. Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients. This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM. The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.

OBJECTIVETo investigate the effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia.

METHODSUsing high-resolution ultrasound, we measured flow- and nitroglycerin-induced dilatation of the brachial artery in 30 patients with hypertriglyceridemia before and after treatment with micronized fenofibrate at a dose of 200 mg once daily for 4 weeks. Simultaneously, both serum lipid and plasma endothelin (ET) levels were determined.

RESULTSAfter micronized fenofibrate therapy, serum triglyceride (TG) levels decreased significantly (P < 0.05). Plasma ET levels also decreased markedly [(82.66 +/- 15.46) microg/L vs. (106.22 +/- 19.16) microg/L, P < 0.001]. Flow-induced vasodilatation was much improved (11.0% +/- 9.0% vs 2.7% +/- 2.0%, P < 0.01). However, no significant changes in vasodilatation occurred in response to nitroglycerin (16.2% +/- 6.0% vs 15.0% +/- 5.0%, P > 0.05) in patients with hypertriglyceridemia.

CONCLUSIONSMicronized fenofibrate can improve impaired endothelium-dependent vasodilatation in patients with hypertriglyceridemia. Improving endothelial function may also be the mechanism responsible for the beneficial effects of micronized fenofibrate.

Adult ; Endothelium, Vascular ; drug effects ; physiology ; Female ; Fenofibrate ; pharmacology ; therapeutic use ; Humans ; Hypertriglyceridemia ; drug therapy ; Male ; Middle Aged ; Vasodilation ; drug effects

Objective To investigate the effects of dexmedetomidine injection at the Neiguan acupoint before general anaesthesia on neurocognitive disorder and sleep quality after non-cardiac major surgery in eld-erly people.Methods Elderly patients undergoing elective thoracic and laparoscopic surgery in this hospital from February 2023 to March 2024 were selected and divided into the dexmedetomidine Neiguan acupoint in-jection group(A),saline Neiguan acupoint injection group(B)and dexmedetomidine intravenous injection group(C)by the randomised numerical table method,40 cases in each group.The postoperative neurocognitive function and sleep-related condition in the three groups were observed.Results The incidence rate of postop-erative delirium(POD)on postoperative 1 d in the group A and C was significantly decreased compared with the group B,and the difference was statistically significant(P＜0.05);the incidence rate of POD on postoper-ative 2 d in the group A was significantly decreased compared with the group B(P＜0.05);the incidence rate of postoperative cognitive dysfunction(POCD)on postoperative 1 d in the group A and C was significantly de-creased compared with the group B,moreover which in the group A was lower than that in the group C,and the differences were statistically significant(P＜0.05);the incidence rate of POCD on postoperative 3,5 d in the group A was lower than that in the group B(P＜0.05).The MMSE score on postoperative 1,3,5 d in the group B and C was significantly decreased compared with preoperative 1 d(P＜0.05).The MMSE score on postoperative 1,3,5 d in the group A and C was higher than that in the group B.and the difference was statis-tically significant(P＜0.05).The PSQI score on postoperative 1,3,5 d in the group A and C was increased compared with preoperative 1 d(P＜0.05);compared with the group B,the PSQI score on postoperative 1,3,5 d in the group A and C was decreased,moreover the group A was lower the group C,and the differences were statistically significant(P＜0.05).The incidence rate of bradycardia in the group A and C was signifi-cantly higher than that in the group B(P＜0.05).The incidence rate of postoperative nausea and vomiting(PONV)in the group A was significantly lower than that in the group B and C(P＜0.05),and the difference between the group B and C had no statistical significance(P＞0.05).Conclusion Dexmedetomidine injection at the Neiguan acupoint before anaesthesia for minimally invasive surgery can significantly reduce periopera-tive neurocognitive dysfunction(PND)and improve the quality of sleep in elderly patients,moreover simulta-neously has the effect for preventing PONV.

Even though mutations in LMNA have been reported in patients with typical dilated cardio-myopathy(DCM)and atrioventricular block(AVB)previously,the purpose of this study was to disclose this novel genetic abnormality in one Chinese family with the atypical phenotype of progressive AVB followed by DCM with normal QRS interval.Genome-wide linkage analysis mapped the AVB gene in this family to a marker at chromosome 1q21.2,where the LMNA gene was located.Direct DNA sequence analysis revealed a heterozygous G to A transition at nucleotide 244 in exon 1 of LMNA,which resulted in an E82K mutation.The E82K mutation co-segregated with all affected individuals in the family,and was not present in 200 normal controls.Further clinical evaluation of mutation carriers showed that 5 of 6 AVB patients exhibited mild DCM with a late onset of age in the fourth and fifth decades.Ejection fractions were documented in 5 patients with DCM,but 4 showed a normal value of ≥50%.Echocardiography showed that atrial dilatation occurred earlier than ventricular dilatation in the patients.This study suggests that progressive AVB with normal QRS interval and accompanying DCM at later stages may represent a distinct type of DCM.The molecular mechanism by which the E82K mutation causes AVB as the prominent phenotype in DCM may be a focus of future studies.

SIRT6 belongs to the conserved NAD⁺-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD⁺. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC₅₀ of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.