ObjectiveTo investigate the effect of dexmedetomidine postconditioning on mitochondria injury during myocardial ischemia-reperfusion (I/R) in isolated rat hearts.Methods Healthy female Wistar rats weighing 220-250 g were anesthetized with intraperitoneal 3％ pentobarbital 50 mg/kg and heparin 500 U/kg.Their hearts were excised and perfused in a Langenorff apparatus with modified K-H solution saturated with 95％ O2-5％ C02 at 37 ℃.Forty isolated rat hearts were randomly divided into 5 groups( n =8 each): I/R group(group A),dexmedetomidine 10 nmol/L group ( group B),dexmedetomidine 100 nmol/L group ( group C ),atractyloside ( the mitochondrial permeability transitionpore (mPTP) opener) group (group D)and dexmedetomidine 100 nmol/L + atractyloside group(group E).Myocardial I/R injury was induced by 40 min of global ischemia followed by 60 min of reperfusion.10 nmol/L dexmedetonidine( group B),100 nmol/L dexmedetonidine (group C),20 μmol/L atractyloside(group D) or 100 nmol/L dexmedetomidine + 20 μmol/L atractyloside (group E) was added into K-H solution and perfused for 10 min at the beginning of reperfusion.The myocardial tissues were obtained and mitochondria were isolated at the end of reperfusion for determination of activity of SOD,Na+ -K+ -ATPase,and Ca2+ -ATPase and content of MDA and Ca2+.ResultsThe activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase was significantly higher and MDA and Ca2+ content lower in groups B and C than in group A( P ＜ 0.05).The activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase was lower and MDA and Ca2+ content higher in groups E and D than in group C (P ＜ 0.05).There was no significant difference in activity of SOD,Na+ -K+ -ATPase and Ca2+ -ATPase and MDA and Ca2+ content between groups B and C,and between groups A and D( P ＞ 0.05).Conclusion Dexmedetomidine postconditioning can reduced mitochondria injury during myocardial I/R in isolated rat hearts through inhibiting of mPTP opening.

Objective To investigate the role of mitochondrial ATP-sensitive potassium(mito-KATP)channels in attenuation of ischemia-reperfusion(I/R)injury by lidocaine pretreatment in the isolated rat heart.Methods Adult female Wistar rats weighing 220-250 g were anesthetized with intraperitoneal 3% pentobarbital 35 mg/kg.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O2-5%CO2 at 37 ℃.Twenty-four isolated rat hearts with I/R injury were randomly divided into 3 groups(n = 8 each):group I/R,lidocaine group(group L)and lidocaine + glibenclamide group(group LG).After 10 min of equilibration,group C,L and LG received 20 min of perfusion with K-H solution,K-H solution containing lidocaine 2.5 mg/L and K-H solution containing lidocaine 2.5 mg/L + glibenclamide(a blocker of mito-KATP channels)10 μmol/L,respectively,then subjected to 30 min of ischemia followed by 60 min of reperfusion.HR,left ventricular developed pressure(LVDP),+ dp/dtmax and - dp/dtmax were recorded at the end of equilibration(T0)and at 15,30,45 and 60 min of reperfusion(T1-4).Coronary effluent was collected at T0 and T4 for determination of lactate dehydrogenase(LDH)and creatine kinase(CK)activities.Myocardial tissues were obtained from cardiac apex at T4 for determination of Na+ -K+ -ATPase and SOD activities and MDA and Ca2+ contents.Results Compared with group I/R,HR,LVDP,+ dp/dtmax and - dp/dtmax were significantly increased,CK and LHD activities were decreased,Na+ -K+-ATPase and SOD activities were increased,and MDA and Ca2+ contents were decreased in group L(P ＜0.05).Compared with group L,HR,LVDP,+ dp/dtmax and -dp/dtmax were significantly decreased,CK and LHD activities were increased,Na+ -K+ -ATPase and SOD activities were decreased,and MDA and Ca2+ contents were increased in group LG(P＜0.05).Conclusion The mechanism by which lidocaine pretreatment attenuates I/R injury to the isolated rat heart is related to mito-KATP channel opening.

Objective To discuss the cause and treatment strategy for open laryngotracheal trauma.Methods The clinical data of 38 cases with open laryngotracheal trauma admitted from 1998 to 2012 were collected and analyzed.Of them,one patient died in emergency department despite energetic resuscitation,37 were hospitalized and given advanced treatment after life support measures in emergency department.They were treated with tracheotomy before or during operation.Of them,32 patients were regularly followed up for imaging studies.Result Except 1 patient died of exsanguination from carotid artery rupture,the other 37 survived after successful treatment.Twenty patients were treated with debridement and suture of the wounds and laryngoplasty (20/37,54.1％),8 patients were operated with laryngoplasty plus intraluminal stents implanted (8/37,21.6％) ; the rest 9 patients (9/37,24.3％) were separately given placement of nickel-titanium shape memory alloy stent (n =2),laryngofissure with rubber gloves throat models implanted and laryngoplasty (n =3),linear silicone tube implanted and laryngoplasty with trans-cervical approach (n =1) and tracheoesophageal fistula neoplasty with laryngoplasty and laryngofissure (n =3).The operated patients were followed-up for 0.5 to 3 years after discharge.Of them,35 patients (35/37,94.6％) had successful decannulation,breathing smoothly and swallowing normally,23 patients (23/37,62.2％) had almost normal pronunciation,12 patients (12/37,32.4％) had different degrees in hoarseness of voice,and 2 patients (2/37,5.4％) were referred to other hospital because of failure in extubation with severe stenosis of laryngotrachea.Conclusions When the patients with open laryngotracheal trauma were treated,the essential strategy was to prevent shock,hemorrhage,and asphyxia.In the case of patent respiratory tract and stable vital signs,laryngotracheal reconstruction should be carried out as soon as possible to prevent complications,thereby obtaining good therapeutic effect.

Hangzhou Sijiqing Community Health Service Center has started the precise contract service mode with the characteristics of competitive contract,regional medical alliance and team service form 2016,which improved hypertensive and diabetic patients management in community.After adopting the precision contract service mode,the contracting rate of hypertensive and diabetic patients increased from 56.1％ (2 680/4 777)to 81.6％ (5 602/6 863),the rate of referral to regional medical alliance increased from 26.1％ (2 678/10 259)to 44.4％ (5 589/12 589),consultation rate of contracted doctor increased from 47.1％ (54 603/115 986) to 56.3％ (93 219/165 725),contract renewing rate increased from 41.3％ (5 794/10 822) to 67.2％ (7 282/10 838),and the rate of home nursing care in increased from 9.5％ (47/495) to 61.5％ (392/637).The precise family doctor contract service is an effective mode for primary care,which improves the management rate of hypertensive and diabetic patients,provides continuous medical service,facilitates referral and home nursing service,and promotes the continuity of contract service.

ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.

With intensified aging， Alzheimer's disease has become a serious problem in China's health field. In the field of traditional Chinese medicine （TCM）， Alzheimer's disease mainly describes cognitive deficits such as dementia and amnesia. After the inheritance and summary by medical experts of successive generations， the theory of "toxin damaging brain collaterals" has become a mature pathogenesis hypothesis of this disease. Blood stasis， as one of the main viral pathogens， is also closely related to the theory of Alzheimer's disease in modern pharmacology. Chuanxiong Rhizoma is used frequently in clinical prescriptions for Alzheimer's disease. As the main component of Chuanxiong Rhizoma， tetramethylpyrazine has a series of pharmacological effects on the cardiovascular system such as vasodilation， anti-platelet aggregation， anti-atherosclerosis， and anti-myocardial ischemia， which reflects the effects of Chuanxiong Rhizoma in activating blood circulation and removing blood stasis. However， few studies have focused on the effect of tetramethylpyrazine on the pathogenesis of Alzheimer's disease. From the perspective of TCM theory and modern pharmacology， this article discussed the effects of tetramethylpyrazine on the pathology and pathogenesis of Alzheimer's disease from the aspects of cardiovascular function， oxidative stress， inflammatory response， mitochondrial function， and cholinergic system and made prospects for the future application of tetramethylpyrazine to prevent and treat Alzheimer's disease.

Objective: To understand the dyslipidemia rate and trend of blood lipid level in an urban community in Hangzhou. Methods: A total of 1 485 urban community residents aged 24 years or older who had participated in health checkup over 6 years, from 2011-2016, were selected by random cluster sampling. Fasting blood Triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) levels were measured in all subjects. A χ² test was used to analyze the dyslipidemia rate trend, and an ANOVA of repeated measurement was conducted to observe the blood lipid level changes. Results: From 2011 to 2016, the total abnormal rates of blood lipids in 1 485 residents were 33.2% (493/1 485), 30.5% (453/1 485), 30.4% (452/1 485), 26.5% (394/1 485), 26.3% (391/1 485), and 25.1% (373/1 485), respectively, which showed a declining trend year-by-year (χ²=36.051, P<0.01). Among these results, however, the high TG rate did not significantly differ from year-to-year (χ²=10.081, P>0.05). The TG, TC, LDL-C, and HDL-C levels statistically differed over the 6 years (F=4.876, 33.033, 170.254, 58.442, respectively, all P<0.01). LDL-C was the highest in 2011 [(3.02±0.29) mmol/L] and the lowest in 2016 [(2.72±0.71) mmol/L], while HDL-C was the highest in 2016 (1.44±0.33 mmol/L) and the lowest in 2011 [(1.35±0.30) mmol/L]. Time-sex group interaction effect analysis: TC and HDL-C levels showed different trends over time between men and women (F=2.556, 4.982, respectively, all P<0.05), and the TC level in the male group was significantly lower than in the female group, since 2012. Interaction effect of time age group: TC and LDL-C levels showed different trends between age groups over time, and the declining trend of TC and LDL-C in the elderly group was more significant than in the young or middle age group (F=10.328, 3.085, respectively, all P<0.01). Conclusions The community population showed an overall improvement in blood lipid levels; however, there was no significant improvement in high TG levels. It is necessary to continue monitoring blood lipid levels in the community, especially to strengthen the prevention and control of high TG levels.

OBJECTIVETo establish a mouse model of H435Y mutation of gene using CRISPR/Cas9- mediated gene targeting.

METHODSThe single-stranded guide RNA (sgRNA) specific to the H435Y loci of gene was designed based on the sequence of gene. After activity assessment, the active sgRNA and Cas9 were transcribed into RNA and microinjected along with the donor DNA fragment with point mutations into fertilized mouse eggs. The microinjected eggs were transferred into pseudopregnant mice to obtain the F0 generation mice with the target gene mutation confirmed by PCR and gene sequencing. gene mutations in the offsprings of the F0 generation mice were analyzed.

RESULTSGene sequencing confirmed the successful establishment of mouse models carrying H435Y mutation of gene in 4 of the F0 generation mice. The positive F0 generation mice were crossed with wild-type C57BL/6J mice to obtain the F1 generation mice, and PCR confirmed the presence of H435Y mutations of gene in 6 of the F1 mice. Then F2 generation mice were obtained by F1 generation matting with each other. PCR showed that H435Y mutation of gene in F2 mice was found, indicating the mousemodel of gene mutation in H435Y was established and propagated successfully.

CONCLUSIONSWe successfully established gene H435Y mutant mouse models using CRISPR/Cas9 technique.

Objective:To evaluate the efficacy of the domestic D-Shant device for the treatment of patients with chronic heart failure (CHF) using echocardiography.Methods:Twenty-four CHF patients who were treated with domestic D-Shant device in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2020 to December 2021 were enrolled in the study. Pulmonary capillary wedge pressure (PCWP)/ left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure, interatrial septal gradient pressure, cardiac index and pulmonary/systemic blood flow ratio (Qp/Qs) were measured before and after implantation using right heart catheterization.Left atrial end-diastolic area index (LAEDAI), left atrial end-diastolic volume index (LAEDVI), left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular ejection fraction (LVEF), right atrial end-diastolic diameter, right ventricular end-diastolic diameter, tricuspid annular plane systolic excursion (TAPSE), right ventricular tractional area change (RVFAC), device shunt aperture, velocity and pressure, together with mitral and tricuspid regurgitation severity were measured using echocardiography before, and 1 month as well as 3 months after D-Shant device implantation. Clinical data were collected and analyzed including 6-minute walking test (6MWT), New York Heart Association (NYHA) classification and the Kansas City Cardiomyopathy Questionnaire (KCCQ). Spearman correlation analysis was used to determine the relation between the changes in PCWP/LAP as well as echocardiographic parameters before and 3 months after implantation and NYHA classification. Binary Logistic regression analysis was performed to determine the predictive factors of NYHA classification improvement at 3-month follow-up after D-Shant device implantation.Results:①D-Shant devices were successfully implanted in all patients. ②Compared with preoperative values, invasive PCWP/LAP systolic, diastolic and mean pressures, transatrial septal gradient, and pulmonary systolic, diastolic and mean pressures decreased significantly after implantation(all P<0.001); Qp/Qs increased significantly after implantation( P<0.001). ③Compared with preoperative values, TAPSE, RVFAC and pulmonary artery flow velocity increased at 1 month after implantation(all P<0.05), whereas a significant reduction in mitral regurgitation grade, and an increase in LVEF and pulmonary artery flow velocity at 3 months after implantation(all P<0.05). Right atrial end-diastolic diameter, right ventricular end-diastolic diameter, LAEDAI, LAEDVI, LVEDVI, LVESVI, ratio of early to late diastolic peak velocities of mitral inflow(E/A), systolic peak velocity of mitral annulus at septal site(S′), ratio of early diastolic peak velocity of mitral inflow to diastolic peak velocity of mitral annulus(E/e′), pulmonary artery diameter, inferior vena cava diameter and degree of tricuspid regurgitation did not change among before, and 1 month as well as 3 months after implantation. There were no significant changes in the device shunt aperture, velocity and pressure between 1 month and 3 months after implantation(all P>0.05). ④The significant improvements in NYHA classification, KCCQ scores and 6MWT were observed at 1 and 3 months after implantation compared with preoperative values (all P<0.01). ⑤NYHA classification at 3 months after implantation was correlated with LVEF pre-post, PCWP/LAP pre-post, TAPSE pre-post and RVFAC pre-post ( rs=0.738, -0.730, 0.738, 0.723; all P<0.001). Logistic regression analysis showed that LVEF pre-post was an independent predictor for NYHA classification improvement at 3 months after implantation ( OR=0.687, 95% CI=0.475-0.992, P=0.045) . Conclusions:Domestic D-Shant device can effectively improve the cardiac function and clinical symptoms in patients with CHF. Echocardiography is a feasible and effective method to evaluate the benefits of domestic D-Shant device for the treatment of CHF.