Objective To investigate the effect of selective phosphatase inhibitors Salubrinal on autophagy and apoptosis in the lung tissue of rats with acute paraquat (PQ) poisoning,and to explore its mechanism.Methods 200 Wistar rats were randomly divided into four groups by randomized arrangement table formed by computer,with 50 rats in each group.PQ poisoning model was reproduced by one time gastric lavage with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline (NS) once a day.The rats in control group were lavaged once with 1 mL of NS followed by intraperitoneal injection of 1 mL NS twice a day.The rats in Sal 0.5 and Sal 1.0 groups were intraperitoneal injected with 1 mL Salubrinal 0.5 mg/kg or 1.0 mg/kg on the 1st,3rd,and 5th day after PQ poisoning once a day.The lung tissue was harvested on the 7th day after poisoning,and the changes in histomorphology were observed using hematoxylin and eosin (HE) staining.The positive expression of autophagy-related protein LC3-Ⅱ in lung tissue was observed after immunohistochemistry staining,and LC3-Ⅱ and caspase-3 protein expressions were determined by Western Blot.Results HE staining results showed partial abnormal pulmonary structure in the PQ poisoning group:collapse of pulmonary alveoli,enlargement of the cavity,local infiltration of inflammatory cells,increasing thickness in the alveoli wall and obvious bleeding in the local lung tissue.Compared with the PQ poisoning group,the above changes in Sal 0.5 and Sal 1.0 groups were obviously relieved.It was shown by immunohistochemistry staining that compared with control group,the positive expression of LC3-Ⅱ was obviously decreased in the PQ poisoning group,Sal 0.5,and Sal 1.0 groups (A value:78.34 ± 10.71,76.52 ± 8.21,77.48 ± 9.11 vs.117.58 ± 15.26,all P＜0.05).There was no significant difference in positive expression of LC3-Ⅱ between each of the later three groups (all P＞0.05).Western Blot results showed:compared with the control group,the protein expressions of LC3-Ⅱ and caspase-3 were significantly increased in PQ poisoning group [LC3-Ⅱ (A value):0.22 ±0.05 vs.0.14 ±0.03,caspase-3 (A value):0.115 ± 0.013 vs.0.023 ± 0.006,both P＜0.05].Compared with PQ poisoning group,the protein expressions of LC3-Ⅱ and caspase-3 were obviously decreased in the Sal 0.5 and Sal 1.0 groups [LC3-Ⅱ (A value):0.19 ±0.05,0.18 ±0.04 vs.0.22 ±0.05; caspase-3 (A value):0.078 ±0.012,0.076 ±0.010 vs.0.115 ±0.013,all P＜0.05].Conclusions The endoplasmic reticulum stress-autophagy is activated in the pulmonary cell of acute PQ poisoning rats.Salubrinal can decrease the autophagy and apoptosis in the lung of rats with acute PQ poisoning,which play a role in the treatment.

Objective To investigate the effects of ulinastatin on autophagy and apoptosis of lung cells in rats with acute paraquat poisoning.Methods A total of 150 Wistar rats were randomly (random number) divided into three groups.The rats in control group had stomach lavaged once with 1 mL of normal saline followed by intraperitoneal injection of 1 mL normal saline twice a day.PQ poisoning model was produced by stomach lavaged once with 1 mL of 40 mg/kg PQ solution followed by intraperitoneal injection of 1 mL normal saline once a day.In PQ + ulinastatin (PU) group,UTI in dose of 12 000 U/kg was intraperitoneally injected in rats twice a day.The lung tissue was obtained on the 7th day after modeling,and the histopathological changes were observed under microscope after hematoxylin and eosin (HE) staining.The positive expressions of autophagy-related LC3 protein LC3 and Bcl-2 pretein in lung tissue were observed after immunohistochemistry staining,and the levels of LC3、Bax 、Bcl-2 proteins were determined by Western blot.Results HE staining Results showed:it was observed from the PQ poisoning group that the abnormal cellular structure,enlargement in the pulmonary alveoli,leaking a lot of inflammatory cells,increased thickness of the alveoli wall and bleeding in the local area of lung tissue.Compared with the PQ poisoning group,the above changes in ulinastatin groups were relieved.Western blot Results showed:compared with the control group,the protein expressions of LC3-A/B were significantly increased in PQ poisoning group [LC3-A/B expression (A scale):0.22 ± 0.05 vs.0.14 ± 0.03,F =22.48,P ＜ 0.01].compared with PQ group,the expression of LC3 A/B obviously increased in the group of PU [LC3-A/B expression (A scale):0.36 ± 0.08 vs.0.22 ± 0.05,F =22.78,P ＜ 0.01].compared with Con group,the expression of Bcl-2/Bax obviously decreased in the group of PQ [Bcl-2/Bax expression (A scale),0.11 ±0.04 vs.0.83 ± 0.09,F =154.43,P ＜ 0.01].Compared with PQ poisoning group,the protein expressions of Bcl-2/Bax were obviously increased in PU groups [Bcl-2/Bax expression (A scale):(0.63 ± 018) vs.(0.11 ±0.04),F =154.43,P ＜0.01].Immunohistochemistry result:compared with Con group,the expression of LC3 and Bcl-2 obviously decreased in the group of PQ [LC3expression (A scale):(78.34±10.71) vs.(117.58±15.26),F=31.63,P＜0.01) (Bcl-2 expression (A scale):(62.54±9.74)vs.(130.52 ± 9.86,F =118.44,P ＜ 0.01).Compared with PQ poisoning group,the protein expressions of LC3 and Bcl-2 were obviously increased in PU groups [LC3expression (A scale):(162.58 ± 25.76) vs.(78.34 ± 10.71),F=31.63,P＜0.01]; [Bcl-2 expression (A scale):(145.56±10.26) vs.(62.54±9.74),F=118.44,P ＜ 0.01].Conclusions Theendoplasmic reticulum stress-autophagy is activated in the lung cells of rats with acute PQ poisoning.UTI can adjust endoplasmic reticul um stress,increased the expression of Bcl-2 and enhance the proportion of Bcl-2/Bax to protect the lungs of rats from acute PQ poisoning.

Objective: To study the relationship between dilated cardiomyopathy and nuclear lamina protein (LMNA) gene mutation in Kazak ethnics at Xinjiang area.
Methods: A Kazak familial dilated cardiomyopathy (FDCM) with 31 members was studied. In addition, 160 patients with idiopathic dilated cardiomyopathy (IDCM) with 160 healthy controls were enrolled in our study, and they were divided into 4 groups: IDCM-Kazak, IDCM-Han and Control-Kazak, Control-Han.n=80 in each group. Peripheral blood DNA were extracted, 12 exons with nearby introns of LMNA gene were detected by PCR and the ampliifed products were sequenced and compared with the standard template of CHROMAS and BLAST software to identify mutation sites. LMNA mutation in both Kazak and Han IDCM patients were investigated.
Results: A novel LMNA mutation (insC, CGG→CCG) at exon 7 was identiifed in a FDCM proband, it caused an amino acid substitution as Arg to Pro, and a known LMNA polymorphism loci rs4641 (c.1362C>T His454His) was fund at exon 10. In addition, LMNA polymorphism loci rs4641 genotype distribution (χ2=5.16,P=0.036) and allele frequency (χ2=4.50,P=0.034) were statistically different between IDCM-Kazak group and Control-Kazak group; while such differences were no statistic meaning between IDCM-Han group and Control-Han group. Logistic regression analysis indicated that LMNA polymorphism loci rs4641 was related to IDCM occurrence in Kazak ethnics (P=0.025, OR=0.412, 95% CI 0.189-0.896).
Conclusion: LMNA polymorphism loci rs4641 was related to IDCM in Kazak ethnics at Xinjiang area, which might be susceptible loci for IDCM occurrence.

Objective: To observe the clinical characteristics and current treatment status in patients with chronic heart failure (CHF) at different grade hospitals in Xinjiang Area.
Methods: A total of 5357 patients with CHF diagnosis discharged from 20 different grade hospitals in Xinjiang area from 2011-01 to 2012-02 were enrolled. The age, gender, nationality, etiology of CHF, cardiac function, complications and current medication status in all patients were systemically studied.
Results:①There were 2295/5357 (42.8%) patients with Han nationality, 2255 (42.1%) with Uyghur nationality and 8.07 (15.1%) with other nationalities. The average age of patients was at (64.60 ± 12.77) years.②The etiology of CHF were, in turn, as: coronary artery disease (CAD) 50.8%, hypertension (31.8%), dilated cardiomyopathy (7.2%).③ The ratios of patients with NYHA III-IV in county hospital 440/682 (64.5%), in regional hospital 1180/1557 (75.8%) were higher than that that in grade A class 3 hospital 967/3118 (31.0%), ( =1390.362,P=0.000).④The patients in county hospital, regional hospital showed increased left atrial diameter (44.7 ± 8.8) mm, (39.5 ± 8.1) mm and left ventricular end-diastolic diameter (60.6 ± 11.1) mm, (56.9 ± 11.1) mm than those in grade A class 3 hospital (37.3 ± 7.1) mm and (53.8 ± 9.7) mm; while decreased LVEF (41.9 ± 10.5) %, (42.3 ± 13.0) % than that in grade A class 3 hospital (46.5 ± 12.8), allP<0.001.⑤The medication status in different grade hospitals as ACEI/ARB, β-blocker, aldosterone antagonist, diuretics, digitalis were at 72.8%, 66.8%, 46.6% , 45.5% and 26.8% respectively. The application of ACEI/ARB and β-blocker in county hospital (61.4% and 51.5%) and in regional hospital (72.3% and 58.3%) were lower than those in grade A class 3 hospital (75.6% and 74.3%); while the application of aldosterone antagonist in county hospitals (57.9%) and in regional hospital (73.8%) were higher than that in grade A class 3 hospital (30.6%), allP<0.001.
Conclusion: The etiology of CHF were mainly as CAD and hypertension in Xinjiang area, the patients in county and regional hospitals had more severe conditions than that in grade A class 3 hospital, which implying the distance between the guideline standard and real practice especially in basic level hospitals.

Objective: To explore the relationship between atrial MMP-9 with its inhibitor (TIMP-1), anti-apoptosis gene (BCL-2) with apoptosis gene (BAX) and the aging with atrial remodeling in experimental dog model during atrial ifbrillation (AF), in order to better deal with the aging caused AF.
Methods: The experimental dogs were divided into 4 groups: ①Adult with sinus rhythm (ASR) group, ②Elder with sinus rhythm (ESR) group and③Adult with AF (AAF) group,④Elder with AF (EAF) group. n=7 in each group. Chronic AF model was induced by rapid and persistent atrial pacing. The mRNA and protein expressions of MMP-9, TIMP-1 and BCL-2, BAX were measured by real time quantitative RT-PCR and Western blot analysis. The cellular ultra structural remodeling was examined by optical/electron microscopy, and the apoptosis index was determined by TUNEL method,
Results: Compared with adult dogs, the elder dogs showed obviously increased expressions of MMP-9, BAX, and decreased expressions of TIMP-1, BCL-2, all P<0.05. Compared with SR gods, the AF dogs presented up-regulated expressions
of MMP-9, BAX, all P<0.05, and down-regulated expressions of TIMP-1, BCL-2, all P<0.05, such changes were most obvious in elder AF dogs. Accompanying with the aging and AF, the degree of atrial ifbrosis, cellular ultra structure and the apoptosis index were changed with the statistic meaning.
Conclusion: The abnormal expressions of MMP-9/TIMP-1 and BCL-2/BAX might be one of the molecular mechanisms for aging caused AF in experimental dog model.

Objective To evaluate the association between LDL-C and ischemic stroke in patients with nonvalvular atrial fibrillation (AF).Method A total of 2 470 patients with nonvalvular AF were included in the present study.The clinical data and laboratory examination results of the patients in the hospital were collected.The subjects were either divided into the ischemic stroke history (n =560),and non-ischemic stroke history groups (n =1 910),or divided into the low-middle risk (n =566) and high risk groups (n =1 904) based on CHA2 DS2-VASc score.Results There were significant differences in the proportion of Han,the ratio of gender,age,hemoglobin,hematocrit,ALT,serum uric acid,HDL-C and LDL-C between the patients with ischemic stroke history and without (all P ＜ 0.05).Similarly,there were significant differences in the proportion of Han,the ratio of gender,age,white blood cell count,hemoglobin,hematocrit,platelet count,ALT,albumin,TG and LDL-C between subjects in the low-middle risk group and those in the high risk group (all P ＜ 0.05).A logistical regression analysis showed that LDL-C was an independent risk factor for both the ischemic stroke history (OR 2.089,95％ CI 1.860-2.347,P ＜0.05),and future ischemic stroke risk (OR 1.270,95％ CI 1.079-1.494,P ＜ 0.05) in patients with nonvalvular AF.Conclusion LDL-C is associated with ischemic stroke in patients with nonvalvular AF,and it is also an independent risk factor for future ischemic stroke in these patients.

Objective To observe the effect of different doses of octreotide acetate on the clinical efficacy of patients with severe acute pancreatitis (SAP).Methods Ninety patients with SAP were admitted to the Department of First Aid Medicine Second Section of the First Hospital of Jilin University from September 2013 to January 2016, and according to difference in drug doses, they were divided into octreotide small dose, moderate dose and large dose groups, 30 cases in each group. All the three groups were given the basic treatment, and in the mean time octreotide 0.2, 0.3, 0.4 mg respectively was dissolved in 0.9 % sodium chloride 100 mL, then the low, moderate and high dose solutions were intravenously continuously infused by a micro pump into the veins of patients in respective small, medium and large dose groups, once every 12 hours, for a total of 20 days. The times of improvement of clinical symptoms (such as abdominal pain, nausea, vomiting), blood amylase recovery time, hospitalization time and clinical efficacy, the incidence of shock, renal insufficiency and other complications were compared among the three groups.Results With the increase of drug dosage, the symptom improvement time (days) was gradually decreased (5.0±1.2, 3.0±1.2, 2.8±1.2) in small, medium and large dose groups, the recovery time of blood amylase and hospitalization time were the shortest in medium dosage group, less than those in large and small dosage groups [blood amylase recovery time (days): 4.5±1.0 vs. 6.0±1.0, 4.6±1.0, hospitalization time (days) 12.0±1.5 vs. 15.0±1.5, 12.5±1.5], the total effective rate was the highest in the middle dosegroup, higher than those in the large and small dose groups [96.7% (29/30) vs. 93.3% (28/30), 83.3% (25/30)]; the incidence of complications was the highest in the lowdose group, higher than those in the middle and large dose groups [26.67% (8/30) vs. 10.0% (3/30), 13.3% (4/30)].Conclusions When using micro infusion pump for intravenous infusion of octreotide, the efficacy of moderate dose is better than that of small dose, but compared with the efficacy in large dose group, no significant difference is seen.

Objective: Present study analyzed the association betwen the postassium voltage-gated channel KQT-like subfamily member 1 gene (KCNQ1) mutation and the clinical and the electrocardiographic features in 2 pedigrees with congenital long QT syndrome type 1 (LQT1) in Xinjiang Uygur Autonomous Region. Methods: Three family members were diagnosed as LQT1 patients in 2 Uygur congenital LQT1 families, these 3 LQT1 patients served as long QT group, 24 Uygur healthy volunteers served as control group. Electrocardiogram (ECG) and the gene detection were applied to compare the ECG and molecular genetic features between the long QT group and control group, and to explore the relationship between the KCNQ1 gene mutation and the clinical and the electrocardiographic features in these 2 families with congenital long QT syndrome type 1. Results: The LQT1 was diagnosed in 3 cases of the 2 pedigrees. The common features of ECG were QTc>480 ms, prolonged ST segment, and delayed T wave. The gene test evidenced a polymorphism of KCNQ1 gene exon 13:47G➝A(R16R). The mutation of 133G➝A9(G45S) of exon 16 resulted in the change of the original glycine (G) to serine (s). The ECG of the control group were normal, and there were no KCNQ1 gene mutations in control group. Conclusion The exon sequencing results of KCNQ1 gene in 2 Xinjiang Uygur congenital long LQT1 families showed that exon16 missense changes (133G to A (G45S)) can lead to amino acid mutation, this mutation may be a pathogenic mutation. Subsequent validation of the expanded sample will provide a reference for revealing the relationship between the KCNQ1 gene and the pathogenesis of LQT1.

OBJECTIVETo establish the canine model of new-onset atrial fibrillation (AF) after acute myocardial infarction (AMI), and explore the relationship between new-onset AF and sympathetic neural remodeling in this model.

METHODSTwenty four adult mongrel dogs were randomly divided into 4 groups by applying random number table. Group A (n=6): ligate the left circumflex artery (LCX). Group B (n=6): ligate the LCX and right atrial anterior artery and right atrial middle artery. Group C (n=6): ligate left anterior descending artery.Group D (n=6): sham operation.Sequential electrophysiology study was performed in all dogs to determine the AF induction rate, AF duration, effective refractory period (ERP), the density of tyrosine hydroxylase (TH) and norepinephrine transporter (NET) before AMI or sham operation, and at 30 min, 2 hours and 4 hours after AMI or sham operation.

RESULTS(1) The highest AF induction rate of right atrium and left auricle was 96.7%(58/60) and 95.0%(57/60) in group B, 81.7%(49/60) and 38.3%(23/60) in group A, 28.3%(17/60) and 35.0%(21/60) in group C, 20.0%(12/60) and 33.3%(20/60) in group D. (2) At 4 hours after AMI, AF duration was significantly prolonged in group B(193.50±54.67) s, compared with group A(53.83±9.37) s, group C(45.00±19.50) s, and group D(16.67±4.50) s (all P<0.05). (3) In group B, the ERP of AF was prolonged at 30 minutes after AMI and shortened at 2 hours and 4 hours after AMI compared with baseline level(all P<0.05). (4) The TH density of left atrium ((3 485±694) µm2/mm2) and left auricle((2 645±454) µm2/mm2) in group A and the TH density of left atrium ((7 873±1159) µm2/mm2) and left auricle((3 070±605) µm2/mm2) in group B were significantly higher than those in group C ((1 474±475) µm2/mm2, (1 177±277) µm2/mm2) and group D ((678±206) µm2/mm2, (489±125) µm2/mm2) (all P<0.05), and the TH density of right atrium and right auricle in group B were higher than group A (all P<0.05). The NET density of left atrium((476±75) µm2/mm2) and left auricle ((414±52) µm2/mm2) in group A and the NET density of left atrium((527±81) µm2/mm2) and left auricle((429±85) µm2/mm2) in group B were lower than that in group C ((1 044±105) µm2/mm2, (867±67) µm2/mm2) and group D ((1 438±60) µm2/mm2, (1 027±119) µm2/mm2) (all P<0.05).

CONCLUSIONSLigating the LCX, right atrial anterior artery and right atrial middle artery at the same time can significantly increase the success rate in establishing the canine model of new-onset atrial fibrillation after acute myocardial infarction and can also increase the AF duration.Cardiac sympathetic remodeling after acute myocardial infarction is associated with induction and duration of AF.

Animals ; Anterior Wall Myocardial Infarction ; Atrial Fibrillation ; Disease Models, Animal ; Dogs ; Heart Atria ; Sympathetic Nervous System

OBJECTIVEDetect the relationship between TPM1 gene mutations and dilated cardiomyopathy (DCM) of Kazaks and Hans in Xinjiang.

METHODSTPM1 gene was screened from 31 family members in a Kazak family with familiar DCM (FDCM), 100 patients with idiopathic DCM (IDCM, 50 Kazaks and 50 Hans), and in 100 healthy controls (50 Kazaks and 50 Hans). All the samples were the inpatients or outpatients of First Affiliated Hospital of Xinjiang University from 2012 to 2014. PCR was used to amplify 9 exons and nearby introns of the TPM1 gene. The amplified products were sequenced and compared with the standard sequence with CHROMAS software and BLAST software in Pubmed to identify mutation sites. The relationship between TPM1 gene mutations in the Kazak IDCM and healthy volunteers, between Han and Kazak IDCM and healthy volunteers was analyzed. Tropomyosin was qualitatively and quantitatively detected by ELISA in all subjects.

RESULTSA novel variant (c.524 G > T) was identified in two FDCM patients at exon 3, this mutation caused an amino acid substitution, Gln111His. The FDCM, IDCM from Kazak and Han, healthy volunteers from Kazak and Han were founded a rs1071646 (c.644C > A, Ala151Ala). There was a significant difference in the genotype distribution (χ(2) = 13.36, P = 0.001) and allele frequency (χ(2) = 10.25, P = 0.001) between Kazaks with IDCM and Kazak controls of rs1071646, while these parameters were similar between Han IDCM patients and Han controls (all P > 0.05). The tropomyosin content of Kazak and Han IDCM patients were significantly lower than Kazak and Han controls ((1 764.2 ± 350.9) ng/L vs. (2 369.7 ± 345.9) ng/L, P = 0.001).

CONCLUSIONTPM1 gene of rs1071646 polymorphism is a possible independent risk factor for IDCM in Kazaks but not Han Chinese.

Cardiomyopathy, Dilated ; genetics ; Exons ; Gene Frequency ; Genotype ; Humans ; Mutation ; Polymorphism, Genetic ; Pyridines ; Risk Factors ; Tropomyosin