Objective To determine whether acute withdrawal of simvastatin treatment in healthy normocholesterolemic men impairs the brachial artery endothelial function.Methods The study was performed on 16 healthy,young male subjects with desirable serum levels of cholesterol.They were administered with simvastatin(20 mg/d)for 4 weeks.Endothelial dependent flow-mediated vasodilation (FMD)was assessed on the brachial artery using high-resolution ultrasound,and fasting serum lipid profiles as well as vasoactive substances[NO,endothelin(ET)and 6-keto-PGF1α] were measured.The parameters mentioned above were obtained at indicated time points before and after simvastatin treatment. Resuts Simvastatin treatment for 4 weeks significantly improved FMD and reduced low density LDL-C and total TC levels.Withdrawal of simvastatin.however,resulted in dramatic impairment of endothelium- dependent relaxation on the first day after with drawal [(4.6±0.48)%and(10.9±0.89)%,P＜0.01 ], Furthermore,FMD decreased significantly as compared with baseline level[(4.6±0.48)%vs(6.4±0.47)%,P＜<0.01].Serum NO level varied according to the change of endothelial-dependent relaxation(γ=0.496,P＜0.01).After discontinuing simvastatin therapy,plasma ET increased and plasma 6-keto-PGF1α decreased progressively.In addition,serum TC and LDL-C were not significantly modified during the initial 2 days.No correlation was shown between FMD and serum LDL-C level(γ=-0.172,P=0.101). Conclusions Withdrawal of simvastatin not only abrogates the beneficial effect on endothelial function of healthy normocholesterolemic men rapidly,but also induces further endothelial deterioration as compared with pretreatment status.This adverse effect is independent of serum cholesterol.The underlying mechanism may be related to the suppression of endothelial NO production.

OBJECTIVE Dynamics of serum and urine metabolites in hepatic injury rats induced by ethanolic extract from Rhizoma Dioscoreae Bulbiferae(RDB)was investigated by 1H-NMR-based metabo?nomic methods in order to discover early biomarkers of liver toxicity induced by RDB. METHODS Rats were ig adminisetred with RDB at a dose of 5 g·kg-1 for 28 d. Rats were sacrificed 3,7,14 and 28 d af?ter RDB administration,as well as after a recovery period,respectively. Blood was taken for routine bio?chemical analysis by an automatic biochemical analyzer. Liver/body mass indexes were calculated ,and liver pathological changes were observed with hematoxylin-eosin staining. Urine samples were collected before and 3,7,14 and 28 d after RDB administration,respectively,as well as after withdrawal. Metabo?nomic analysis was carried out for serum and urine samples. Principal component analysis and orthogonal partial least squares-discriminant analysis were used for screening and identifiying early biomarkers. RESULTS Compared with the control group,total bilirubin (TB) and total cholesterol (TC) values were increased in 3-28 d in RDB group(P<0.05,P<0.01). Total bile acid(TBA)was elevated in 7-28 d (P<0.05,P<0.01). TB,TC and TBA became normal after discontinuation with RDB. There was no significant difference between RBD-treated group and control group in the activity of glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase,and the content of glucose also was not different between the two groups. The ratio of liver/body mass was elevated at 3-28 d(P<0.01)but returned to normal after withdraval of RDB. The enlargement and necrosis of hepatocytes were observed 7 d after RDB administration,and lesion degree was aggravated with the extension of RDB delivery time. Meta?bonomic analysis showed that the serum lipids (low density lipoprotein/very low density lipoprotein (LDL/VLDL),glutamic acid,choline phosphate and glycerolphosphatecholine were increased in the early stage. Pyruvate and N-acetylglutamate were decreased in urine. These metabolites became normal 7 d after discontinuation with RDB. CONCLUSION The serum lipids (LDL/VLDL),glutamic acid,glycerol phosphate choline,as well as urine pyruvic acid salt and N-acetyl glutamate may be used as the early biomarkers for liver toxicity induced by RDB.

MicroRNAs (miRNAs) are a new class of endogenous, single-strand, noncoding small RNAs. MiRNAs play an important regulatory role in a variety of pathological and physiological process, such as cell proliferation and apoptosis, organ development and differentiation and tumorigenesis and so on. It has been found that circulating miRNAs are also stably and specially expressed in serum or plasma and other body fluids. Circulating miRNAs could be taken as noninvasive and new biomarkers for evaluating the drug-induced target organ injury, which may play a vital role in monitoring the drug toxicity at the early stage.
Animals ; Biomarkers ; metabolism ; Diagnosis ; Disease ; genetics ; Drug Monitoring ; instrumentation ; methods ; Drug-Related Side Effects and Adverse Reactions ; Humans ; MicroRNAs ; genetics ; metabolism

The incidence and mortality rate of heart failure (HF) are increasing annually, resulting in a huge medical and economic burden worldwide. B-type natriuretic peptide (BNP) is the gold standard biomarker of HF recommended by national and international guidelines for the diagnosis and prognosis evaluation of HF. Recent studies suggest that BNP can be truncated in multiple forms by different enzymes rather than complete fragments in circulation, which can be contributing to the diagnosis and classification of HF. The immunoassay mostly used in clinics are unable to distinguish different truncated BNP forms due to cross-reactivity of antibody, while mass spectrometry is more accurate because it can easily distinguish through their mass-to-charge ratios. With the maturation of ambient ionization mass spectrometry and ion mobility mass spectrometry, it can help to simplify sample pre-treatment and improve the separation efficiency, in order to explore the clinical value of the heterogeneity of BNP truncated forms.

Objective To evaluate the objective sleep status of patients with chronic insomnia by cardiopulmonary coupling (CPC) technique, and evaluate the characteristics of cognitive dysfunction to explore the correlation between objective sleep and cognitive dysfunction in patients with chronic insomnia. Methods Forty-three patients with chronic insomnia, admitted to our hospital from October 2017 to April 2019, were enrolled in our study;15 age-, gender-and education-matched healthy volunteers were recruited as control group. All subjects followed their daily routine at home and completed CPC examination. Montreal Cognitive Assessment (MoCA), Auditory Vocabulary Learning Test (AVLT), Trail Making Test (TMT) and Stroop Color Word Test were used to evaluate the general and single cognitive functions, respectively. The correlation of objective sleep with cognitive function was analyzed. Results (1) As compared with those in the control group, high frequency coupling (stable sleep) ratio was significantly decreased, low frequency coupling (un-stable sleep) ratio and extremely low frequency coupling (rapid-eye-movement sleep/waking) ratio were significantly increased, and latency of high frequency coupling was significantly prolonged in chronic insomnia group (P<0.05). (2) Chronic insomnia group had significantly lower MoCA total scores than control group (P<0.05), specifically manifested as decrement of visuospatial ability and execution and attention abilities; specific cognitive test showed that chronic insomnia group performed worse in immediate recall, and had delayed recall of AVLT, longer time consumption in TMT-B, smaller number of wired arrival numbers, and longer time consumption in Stroop color word test than the control group, with significant differences (P<0.05). (3) There was a correlation between CPC sleep structure and Cognitive Function Scale scores in patients with chronic insomnia. Conclusion In patients with chronic insomnia, stable sleep is reduced, un-stable sleep and rapid-eye-movement sleep/waking are increased; the impaired cognition domains are visual space and executive function, attention and memory; disturbed sleep structure aggravates the memory and execution impairment of patients with chronic insomnia.

We reported a 54-year-old female patient with severe tricuspid regurgitation, who received mechanic valve in the mitral position 15 years ago. The patient’s Society of Thoracic Surgeons score was 8.27%, and was intolerant to open heart surgery, so she was recommended for transcatheter tricuspid valve replacement via right vena jugularis interna. The procedures were guided by echocardiography and X ray fluoroscopy on November 13, 2021, the prosthesis was implanted successfully, and the patient was recoved without any adverse events. After 1 month follow-up, her general condition was apparently improved.

Objective To analyze the clinical efficacy of transcatheter tricuspid valve replacement (TTVR) in cardiac implantable electronic lead-related tricuspid regurgitation (TR). Methods The patients with severe TR who underwent LuX-Valve TTVR in 9 Chinese medical centers from June 2020 to August 2021 were retrospectively enrolled. They were divided into a cardiac implantable electronic device (CIED) group and a non-CIED group based on whether they had pre-existing CIED implantation. Success of the procedure was defined as safe implantation of the LuX-Valve and complete withdrawal of the delivery system. Prognostic improvement was defined as a decrease of TR grade to≤2+ and an improvement of cardiac function by≥2 grades. Surgical success and postoperative prognosis were compared between the two groups. Results A total of 190 patients were collected, including 50 males and 140 females with a mean age of 66.2±7.8 years. There were 29 patients in the CIED group, and 161 patients in the non-CIED group. In the CIED group, 28 patients were implanted with a permanent pacemaker and 1 patient with a cardioverter-defibrillator. Preoperative New York Heart Association (NYHA) cardiac function class, TR degree, left ventricular ejection fraction, tricuspid annular plane systolic excusion, and cardiac risk scores were comparable between the two groups (P>0.05). Postoperative TR was reduced to≤2+ in all patients, and there was no statistical difference in the incidence of perivalvular leakage between the two groups (P=0.270). Postoperative CT of CIED patients showed the valve was in place, and the lead was not extruded, twisted, or deflected. The in-hospital mortality of the two groups were 10.3% and 1.9%, respectively, and the difference was statistically significant (P=0.047). In addition, there was no statistical difference between the two groups in terms of postoperative improvement of cardiac function and mortality in the 1- and 2-year follow-up. Conclusion TTVR is feasible, safe, and effective in patients with CIED implantation, and the pre-existing lead has no significant effect on the clinical efficacy.

OBJECTIVE To explore standardized evaluation process for clinical comprehensive evaluation of blood lipid- regulating drugs and perform rapid assessment of clinical comprehensive evaluation of blood lipid-regulating drugs with different mechanisms so as to provide reference for the drug catalogue selection and rational drug use of medical institutions. METHODS Referring to guidelines and consensus such as the guideline for the management of comprehensive clinical evaluation of drugs， the methods such as literature research， expert interviews， and Delphi expert consultation were used to establish a multi-dimensional and multi-criteria clinical comprehensive evaluation index system and quantitative scoring table for blood lipid-regulating drugs around the two main lines of technical evaluation and policy evaluation. Then 13 blood lipid-regulating drugs with different mechanisms in 21 third-grade class-A medical institutions from five provinces and regions of Northwest China were scored from both technical and policy dimensions to form a comprehensive evaluation result. RESULTS The clinical comprehensive evaluation index system and corresponding rapid evaluation quantitative scoring table were constructed for blood lipid-regulating drugs in the five northwest provinces and regions. The technicalevaluation section included 6 primary indicators， 13 secondary indicators， and 34 tertiary indicators， totaling 110 points. The policy evaluation section included 4 primary indicators and 6 secondary indicators， with a total score of 40 points （30 points for some drugs） and a total score of 150 points （or 140 points）. The scoring results showed that the highest score was atorvastatin， followed by rosuvastatin and simvastatin. CONCLUSIONS Statins are still the cornerstone of drug therapy for patients with dyslipidemia； the rapid evaluation quantitative scoring table constructed in this study is comprehensive， systematic and operable. The evaluation process in this study can provide empirical references for other groups to exploring the standardized path and quality control mechanism of clinical comprehensive evaluation of drugs.