Effects of dagliflozin on atrial tachyarrhythmia in rats with pulmonary arterial hypertension related right heart failure and its mechanisms / 中国药理学通报

Aim To investigate the effects of dagliflozin (DAPA) on atrial tachyarrhythmia (AT) in rats with right heart failure (RHF) due to pulmonary arterial hypertension (PAH) and the underlying mechanisms. Methods Sixty male SD rats were randomly divided into four groups: control group (CTL group), model group (MCT group), MCT + low-dose DAPA intervention group (MCT + LD group) and MCT + high-dose DAPA intervention group (MCT + HD group). After 35 days of continuous intervention, the model and cardiac function evaluation, atrial structural remodelling assessment, inflammatory factor detection, and in vivo cardiac electrophysiology experiments were completed. Results DAPA reduced menn pulmonaryarterial pressure (mPAP) and menn right ventricular pressure (mRVP) in the model rats (P <0.05), attenuated the inflammatory response (P < 0.05), reduced right atrial fibrosis (P <0.05), reduced AT induction rate (P < 0.05) and mean atrial tachyarrhythmia duration (MATD) (P < 0.05), the extent of which was more pronounced in the high-dose DAPA intervention group. Conclusions DAPA can reduce AT susceptibility in PAH-induced RHF rats, and the mechanisms may be related to the inhibition of systemic inflammation and anti-atrial fibrosis by DAPA.

Research progress on the relationship between lifestyle and dry eye in children / 国际眼科杂志(Guoji Yanke Zazhi)

Dry eye is a multifactorial ocular surface disease characterized by tear film dyshomeostasis, producing eye discomfort and visual impairment that seriously affects people's quality of life and quality of work. In recent years, the incidence of dry eye in children has been increasing year by year with the changes of environment and lifestyle, which has caused many concerns. Both genetic and non-genetic factors can affect the development of dry eye. However, non-genetic factors, such as lifestyle factors, can be improved by human intervention. Lifestyle modification is economical, safe and effective. It has proven to be efficient for preventing dry eye, so it is important to investigate the association between lifestyle and dry eye in children. Related studies analyzed the relationships between lifestyles such as video terminal, contact lens, low concentration of atropine eye drops, sleep, diet and dry eye in children. In this review, the above findings were summarized and relevant preventive measures were proposed, providing a new theoretical basis for preventing dry eye in children and delaying disease progression.

Influence of E-cadherin methylation on prognosis in children with acute lymphoblastic leukemia / 中国当代儿科杂志

OBJECTIVES@#To study the significance of E-cadherin and the association between E-cadherin methylation status and prognosis in children with acute lymphoblastic leukemia (ALL) by examining the mRNA and protein expression of E-cadherin and its gene methylation status in bone marrow mononuclear cells of children with ALL.@*METHODS@#The samples of 5 mL bone marrow blood were collected from 42 children with ALL who were diagnosed for the first time at diagnosis (pre-treatment group) and on day 33 of induction chemotherapy (post-treatment group). RT-qPCR, Western blot, and methylation-specific PCR were used to measure the mRNA and protein expression of E-cadherin and the methylation level of the E-cadherin gene. The changes in each index after induction chemotherapy were compared.@*RESULTS@#The mRNA and protein expression levels of E-cadherin in the post-treatment group were significantly higher than those in the pre-treatment group (P<0.05), while the positive rate of E-cadherin gene methylation in the post-treatment group was significantly lower than that in the pre-treatment group (P<0.05). At the end of the test, the children with negative methylation had significantly higher overall survival rate and event-free survival rate than those with positive methylation (P<0.05).@*CONCLUSIONS@#E-cadherin expression is associated with the development of ALL in children, and its decreased expression and increased methylation level may indicate a poor prognosis.

Chinese Medicine Shensong Yangxin Capsule () Ameliorates Myocardial Microcirculation Dysfunction in Rabbits with Chronic Myocardial Infarction / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Chinese compound Shensong Yangxin Capsule ( , SSYX) on myocardial microcirculation in myocardial-infarcted rabbits.@*METHODS@#Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. Thirty rabbits were randomly divided into the control group, the MI group (model), and the MI treated with SSYX group (MI+SSYX) by a random number table method. After 4 weeks of administration, low-energy real-time myocardial contrast echocardiography (RT-MCE) was conducted to assess the microcirculatory perfusion. Immunofluorescence double staining was used to detect the capillary density. The endothelial ultrastructure was observed with a transmission electron microscope. The mRNA expression levels of vascular endothelial growth factor (VEGF), endothelin 1 (ET-1), prostaglandin I2 (PGI2) and endothelial nitric oxide synthase (eNOS) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). The plasmic levels of ET-1, thromboxane A2 (TXA2), nitric oxide (NO) and von willebrand factor (vWF) were examined with enzyme-linked immunosorbent assays (ELISA).@*RESULTS@#SSYX significantly improved the myocardial blood volume, myocardial micro bubble velocity, and myocardial inflow according to the examination of RT-MCE, and it visibly ameliorated the capillary endothelial structure. Furthermore, compared with the MI group, the plasma levels of TXA2, ET-1 and vWF contents significantly decreased in the MI+SSYX group, and the ET-1 mRNA expression levels of myocardium in the border zone significantly decreased, and the VEGF, PGI2 and eNOS mRNA expression levels significantly increased (all P<0.05).@*CONCLUSIONS@#SSYX has favorable advantages in ameliorating the impaired myocardial microcirculation following MI. The mechanisms of the effect are related to the ability of SSYX in balancing the endothelial-derived vasodilators and vasoconstrictors, and up-regulating the expression of VEGF and eNOS.

The effects of stelleta ganglion resection on heart failure in response to pressure overload / 中华心血管病杂志

Objective: To observe the impact and difference of resection of left stellate ganglion (LSG) or right stellate ganglion (RSG) on rats with heart failure. Methods: Thirty male SD rats were divided into 3 groups (n=10 each) by random number table method: control group, LSG group, RSG group. All three groups underwent TAC surgery to establish a pressure-overloaded heart failure model. Then, LSG and RSG were bluntly separated and removed in rats assigned to the LSG group or RSG group by surgery, while rats in the control group underwent sham operation. The changes in blood pressure and heart rate before operation, 30 minutes and 10 weeks after operation were recorded; echocardiography was performed before operation and 10 weeks after operation to detect the thickness of the ventricular septum, left ventricle posterior wall diameter, left ventricular end diastolic diameter, left ventricular end diastolic volume, and calculate the left ventricular fractional shortening and left ventricular ejection fraction. HE staining and Masson staining were performed to observe the degree of myocardial hypertrophy and myocardial fibrosis, and to judge the ventricular remodeling. Results: The heart rates of the three groups of rats were (352.4±4.3), (320.3±4.0) and (297.9±5.9) beats/min, and the blood pressure was (142.8±2.3), (123.4±2.7) and (129.6±2.9) mmHg(1 mmHg=0.133 kPa) at thirty minutes after surgery; the heart rates of the three groups of rats were (352.9±4.0), (321.6±3.4) and (301±4.1) beats/min, and the blood pressure was (145.6±1.9), (124.8±1.7) and (130.4±4.4) mmHg at 10 weeks after surgery. The heart rate and blood pressure in the LSG group and RSG group at 30 min and 10 weeks after surgery were significantly lower than those in the control group; at 10 weeks after surgery, the heart rate in the RSG group was significantly lower than that in the LSG group (P both<0.001). After 10 weeks, rats in the control group developed severe left ventricular dilatation. Degree of left ventricular hypertrophy was significantly reduced in the LSG group and RSG group than in the control group, the thickness of the ventricular septum was (3.2±0.3), (2.5±0.1) and (2.5±0.1) mm; the left ventricular end-diastolic diameters were (7.5±0.3), (5.5±0.3) and (5.7±0.2) mm; the left ventricular end-diastolic volume was (9.5±0.3), (4.5±0.2) and (4.8±0.2) ml; the left ventricular fractional shortening was (21.6±1.3)%, (49.1±3.9)% and (47.4±1.5)%; and the left ventricular ejection fraction was (50.9±2.5)%, (81.9±2.1)% and (80.0±2.3)%, respectively in the control group, LSG group and RSG group. Compared with the control group, the left ventricular posterior wall diameter, left ventricular end-diastolic diameter and left ventricular end-diastolic volume were significantly lower and the left ventricular fractional shortening and left ventricular ejection fraction were significantly higher in the LSG group and RSG group (all P<0.001). 10 weeks after operation, the values of type Ⅰ collagen in the control group, LSG group, and RSG group were (0.354±0.013), (0.211±0.012) and (0.243±0.013), respectively. Ratio of type Ⅰ/Ⅲ collagen was (1.109±0.065), (0.737±0.055) and (0.839±0.075), respectively. Compared with the control group, the ratio of type Ⅰcollagen and ratio of type Ⅰ/Ⅲ collagen were significantly lower in the LSG group and RSG group (P<0.001). Conclusion: Both left and right stellate ganglion resection can similarly reduce ventricular remodeling caused by pressure overload and delay the progression of heart failure in tis TAC rat model.

Comparative outcomes of subcutaneous and transvenous cardioverter-defibrillators / 中华医学杂志(英文版)

BACKGROUND@#The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD.@*METHODS@#The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups.@*RESULTS@#The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups.@*CONCLUSIONS@#The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.

Risk factors for hepatocellular carcinoma in hepatitis B cirrhosis patients given treatment with human umbilical cord mesenchymal stem cells / 中国组织工程研究

BACKGROUND: With the continuous development of mesenchymal stem cell therapy, it has been reported that stem cell therapy is likely to cause the occurrence and development of tumors. OBJECTIVE: To investigate the potential risks of hepatocellular carcinoma (HCC) in patients with hepatitis B cirrhosis after receiving human umbilical cord mesenchymal stem cells (hUC-MSCs) transplantation. METHODS: The study collected the information of patients with hepatitis B cirrhosis treated with hUC-MSCs, admitted at the Infectious Disease Department of the 105thHospital of PLA from January 2011 to December 2013. The following investigation lasted 36 months. The follow-up was terminated at the time of diagnostic confirmation. The risk factors that may affect the occurrence of HCC were analyzed by univariate Logistic and multivariate unconditional Logistic regression analyses. RESULTS AND CONCLUSION: (1) A total of 386 patients were followed up, including 171 patients who received hUC-MSCs transplantation as the observation group and 215 patients only given general internal medicine treatment as the control group. (2) At the follow-up of 12 months, the incidence of HCC in the observation group was significantly higher than that in the control group (P < 0.05). At the follow-up of 36 months, the incidence of HCC was 11.7% in the observation group and 9.8% in the control group (P > 0.05). (3) Univariate Logistic regression analysis showed that the HCC patients had higher age, alpha-fetoprotein (AFP), alpha-fetoprotein variants (AFP-L3), AFP-L3 ratio (AFP-L3%), and Golgi glycoprotein 73 (GP73) than those with no HCC in both control and observation groups (P < 0.05). Multivariate unconditional Logistic regression analysis showed that only APF-L3% was an independent risk factor for HCC in patients with hepatitis B cirrhosis undergoing hUC-MSCs transplantation. Overall, hUC-MSCs transplantation does not increase the HCC incidence in patients with hepatitis B cirrhosis within 3 years, but it may lead to an early onset of HCC. AFP-L3% can be used as an early predictor of HCC in patients with hepatitis B cirrhosis undergoing hUC-MSCs transplantation.

Effect of the Shensong Yangxin Capsule on Energy Metabolism in Angiotensin II-Induced Cardiac Hypertrophy / 中华医学杂志(英文版)

<p><b>Background</b>Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy.</p><p><b>Methods</b>We used 2 μl (10 mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR). Therefore, it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed. Then, NRCMs were treated with 1 μl of different concentrations of SSYX (0.25, 0.5, and 1.0 μg/ml) for another 24 h. To explore the time-depend effect of SSYX on energy metabolism, 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h. Mitochondria was assessed by MitoTracker staining and confocal microscopy. mRNA and protein expression of mitochondrial biogenesis-related genes - Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), energy balance key factor - adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor - carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor - glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis.</p><p><b>Results</b>With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml), an increased mitochondrial density in AngII-induced cardiomyocytes was found compared to that of those treated with AngII only (0.25 μg/ml, 18.3300 ± 0.8895 vs. 24.4900 ± 0.9041, t = 10.240, P < 0.0001; 0.5 μg/ml, 18.3300 ± 0.8895 vs. 25.9800 ± 0.8187, t = 12.710, P < 0.0001; and 1.0 μg/ml, 18.3300 ± 0.8895 vs. 24.2900 ± 1.3120, t = 9.902, P < 0.0001; n = 5 per dosage group). SSYX also increased the mRNA and protein expression of PGC-1α (0.25 μg/ml, 0.8892 ± 0.0848 vs. 1.0970 ± 0.0994, t = 4.319, P = 0.0013; 0.5 μg/ml, 0.8892 ± 0.0848 vs. 1.2330 ± 0.0564, t = 7.150, P < 0.0001; and 1.0 μg/ml, 0.8892 ± 0.0848 vs. 1.1640 ± 0.0755, t = 5.720, P < 0.0001; n = 5 per dosage group), AMPK (0.25 μg/ml, 0.8872 ± 0.0779 vs. 1.1500 ± 0.0507, t = 7.239, P < 0.0001; 0.5 μg/ml, 0.8872 ± 0.0779 vs. 1.2280 ± 0.0623, t = 9.379, P < 0.0001; and 1.0 μg/ml, 0.8872 ± 0.0779 vs. 1.3020 ± 0.0450, t = 11.400, P < 0.0001; n = 5 per dosage group), CPT-1 (1.0 μg/ml, 0.7348 ± 0.0594 vs. 0.9880 ± 0.0851, t = 4.994, P = 0.0007, n = 5), and GLUT-4 (0.5 μg/ml, 1.5640 ± 0.0599 vs. 1.7720 ± 0.0660, t = 3.783, P = 0.0117; 1.0 μg/ml, 1.5640 ± 0.0599 vs. 2.0490 ± 0.1280, t = 8.808, P < 0.0001; n = 5 per dosage group). The effect became more obvious with the increasing concentration of SSYX. When 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h, the expression of AMPK (6 h, 14.6100 ± 0.6205 vs. 16.5200 ± 0.7450, t = 3.456, P = 0.0250; 12 h, 14.6100 ± 0.6205 vs. 18.3200 ± 0.9965, t = 6.720, P < 0.0001; 24 h, 14.6100 ± 0.6205 vs. 21.8800 ± 0.8208, t = 13.160, P < 0.0001; and 48 h, 14.6100 ± 0.6205 vs. 23.7400 ± 1.0970, t = 16.530, P < 0.0001; n = 5 per dosage group), PGC-1α (12 h, 11.4700 ± 0.7252 vs. 16.9000 ± 1.0150, t = 7.910, P < 0.0001; 24 h, 11.4700 ± 0.7252 vs. 20.8800 ± 1.2340, t = 13.710, P < 0.0001; and 48 h, 11.4700 ± 0.7252 vs. 22.0300 ± 1.4180, t = 15.390; n = 5 per dosage group), CPT-1 (24 h, 15.1600 ± 1.0960 vs. 18.5800 ± 0.9049, t = 6.048, P < 0.0001, n = 5), and GLUT-4 (6 h, 10.2100 ± 0.9485 vs. 12.9700 ± 0.8221, t = 4.763, P = 0.0012; 12 h, 10.2100 ± 0.9485 vs. 16.9100 ± 0.8481, t = 11.590, P < 0.0001; 24 h, 10.2100 ± 0.9485 vs. 19.0900 ± 0.9797, t = 15.360, P < 0.0001; and 48 h, 10.2100 ± 0.9485 vs. 14.1900 ± 0.9611, t = 6.877, P < 0.0001; n = 5 per dosage group) mRNA and protein increased gradually with the prolongation of drug action time.</p><p><b>Conclusions</b>SSYX could increase myocardial energy metabolism in AngII-induced cardiac hypertrophy. Therefore, SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.</p>

Effects of Traditional Chinese Medicine Shensong Yangxin Capsules on Heart Rhythm and Function in Congestive Heart Failure Patients with Frequent Ventricular Premature Complexes: A Randomized, Double-blind, Multicenter Clinical Trial / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pharmacological therapy for congestive heart failure (CHF) with ventricular arrhythmia is limited. In the study, our aim was to evaluate the effects of Chinese traditional medicine Shensong Yangxin capsules (SSYX) on heart rhythm and function in CHF patients with frequent ventricular premature complexes (VPCs).</p><p><b>METHODS</b>This double-blind, placebo-controlled, multicenter study randomized 465 CHF patients with frequent VPCs to the SSYX (n = 232) and placebo groups (n = 233) for 12 weeks of treatment. The primary endpoint was the VPCs monitored by a 24-h ambulatory electrocardiogram. The secondary endpoints included the left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) classification, 6-min walking distance (6MWD), Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores, and composite cardiac events (CCEs).</p><p><b>RESULTS</b>The clinical characteristics were similar at baseline. SSYX caused a significantly greater decline in the total number of VPCs than the placebo did (-2145 ± 2848 vs. -841 ± 3411, P < 0.05). The secondary endpoints of the LVEF, NYHA classification, NT-proBNP, 6MWD, and MLHFQ scores showed a greater improvements in the SSYX group than in the placebo group (ΔLVEF at 12th week: 4.75 ± 7.13 vs. 3.30 ± 6.53; NYHA improvement rate at the 8th and 12th week: 32.6% vs. 21.8%, 40.5% vs. 25.7%; mean level of NT-proBNP in patients with NT-proBNP ≥125 pg/ml at 12th week: -122 [Q1, Q3: -524, 0] vs. -75 [Q1, Q3: -245, 0]; Δ6MWD at 12th week: 35.1 ± 38.6 vs. 17.2 ± 45.6; ΔMLHFQ at the 4th, 8th, and 12th week: -4.24 ± 6.15 vs. -2.31 ± 6.96, -8.19 ± 8.41 vs. -3.25 ± 9.40, -10.60 ± 9.41 vs. -4.83 ± 11.23, all P < 0.05). CCEs were not different between the groups during the study period.</p><p><b>CONCLUSIONS</b>In this 12-week pilot study, SSYX was demonstrated to have the benefits of VPCs suppression and cardiac function improvement with good compliance on a background of standard treatment for CHF.</p><p><b>TRIAL REGISTRATION</b>www.chictr.org.cn, ChiCTR-TRC-12002061 (http://www.chictr.org.cn/showproj.aspx?proj=7487) and Clinicaltrials.gov, NCT01612260 (https://clinicaltrials.gov/ct2/show/NCT01612260).</p>

Effect of Shensong Yangxin on the Progression of Paroxysmal Atrial Fibrillation is Correlated with Regulation of Autonomic Nerve Activity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity.</p><p><b>METHODS</b>Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration.</p><p><b>RESULTS</b>Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms 2 , P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P < 0.001). The atrial effective refractory period (AERP) was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing.</p><p><b>CONCLUSIONS</b>SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway.</p>

Shensong Yangxin (SSYX) ameliorates disordered excitation transmission by suppressing cardiac collagen hyperplasia in rabbits with chronic myocardial infarction / 华中科技大学学报（医学）（英德文版）

The traditional Chinese medicine Shensong Yangxin (SSYX) can improve the clinical symptoms of arrhythmia in an integrated manner. This study aimed to investigate the electrophysiological effect of SSYX on the hearts of myocardial-infarcted rabbits and further explore the mechanism by which SSYX alleviates myocardial fibrosis. Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. The rabbits were treated with SSYX (0.5 g/kg/d) or saline for 8 weeks by oral administration. Microelectrode array (MEA) technology was used in vivo for extracellular electrophysiological recordings of the infarct border zone. Masson's trichrome staining was used to observe myocardial fibrosis. Western blotting was performed to evaluate the protein expression levels of collagen I (COL I) and collagen III (COL III). Quantitative real-time polymerase chain reaction (real-time PCR) was performed to evaluate the TGF-β1 and MMP-2 mRNA expression levels. The results showed that the total activation time (TAT) and the dispersion of TAT were significantly increased and the excitation propagation markedly disordered after MI. SSYX could significantly decrease TAT and the dispersion of TAT, and significantly ameliorate the chaotic spread pattern of excitation. Furthermore, SSYX treatment could significantly decrease COL I and COL III protein levels and down-regulate TGF-β1 and MMP-2 mRNA expression levels in MI rabbits. It was concluded that SSYX may ameliorate cardiac electrophysiological abnormalities in infarcted hearts by decreasing the protein levels of COL I and COL III, down-regulating the mRNA expression levels of TGF-β1 and MMP2, and thereby reducing adverse cardiac remodeling.

Serial Thyroglobulin Variation Trend Shortly after Radioiodine Therapy in Poorly to Moderately Differentiated Recurrent Thyroid Cancer / 中国医学科学院学报

Objective To dynamically observe the early change of thyroglobulin(Tg) levels after (131)I therapy in differentiated thyroid cancer(DTC) patients. Methods The study enrolled 22 post-total-thyroidectomy DTC patients and they were stratified as low to intermediate recurrence according to the 2009 American Thyroid Association Guidelines. The clinical data including pre-ablation stimulated Tg (ps-Tg),corresponding thyroid stimulating hormone(TSH),anti-thyroglobulin (TgAb) values,and the afterwards parameters were dynamically measured each week in the first month after (131)I therapy. Values collected at the first time were defined as Tg 0 and TSH0,while Tg1 and TSH1 were collected at the first week after (131)I therapy respectively. Then the variation trend curves of Tg were drawn,and factors influencing the variation of Tg were analyzed. Two groups were divided according to Tg levels:G1 (Tg≤0.1 ng/ml,n=9) and G2(Tg>0.1 ng/ml,n=13). Results The rates of negative Tg were 4.5%,18.0%,27.0%,36.0%,and 41.0%,respectively,exactly before (131)I therapy and the 1(st),2(nd),3(rd),and 4(th) week after the therapy. One-way analysis of variance showed that the two groups statistically differed in age (F=3.182,P=0.04) and remnant thyroid (U=4.849,P=0.026). Multivariate logistic regression analysis showed that early negative Tg was related to remnant thyroid tissue (OR:2.132;95%Cl:1.418- 6.532,P=0.009). Conclusions Negative Tg can be achieved in nearly half of DTC patients by the end of first month after (131)I therapy. The negative conversion is closely related with the volume of remnant thyroid tissue.

Shensong Yangxin (SSYX) ameliorates disordered excitation transmission by suppressing cardiac collagen hyperplasia in rabbits with chronic myocardial infarction / 华中科技大学学报（医学）（英德文版）

The traditional Chinese medicine Shensong Yangxin (SSYX) can improve the clinical symptoms of arrhythmia in an integrated manner. This study aimed to investigate the electrophysiological effect of SSYX on the hearts of myocardial-infarcted rabbits and further explore the mechanism by which SSYX alleviates myocardial fibrosis. Myocardial infarction (MI) was established in rabbits by ligation of the left circumflex coronary. The rabbits were treated with SSYX (0.5 g/kg/d) or saline for 8 weeks by oral administration. Microelectrode array (MEA) technology was used in vivo for extracellular electrophysiological recordings of the infarct border zone. Masson's trichrome staining was used to observe myocardial fibrosis. Western blotting was performed to evaluate the protein expression levels of collagen I (COL I) and collagen III (COL III). Quantitative real-time polymerase chain reaction (real-time PCR) was performed to evaluate the TGF-β1 and MMP-2 mRNA expression levels. The results showed that the total activation time (TAT) and the dispersion of TAT were significantly increased and the excitation propagation markedly disordered after MI. SSYX could significantly decrease TAT and the dispersion of TAT, and significantly ameliorate the chaotic spread pattern of excitation. Furthermore, SSYX treatment could significantly decrease COL I and COL III protein levels and down-regulate TGF-β1 and MMP-2 mRNA expression levels in MI rabbits. It was concluded that SSYX may ameliorate cardiac electrophysiological abnormalities in infarcted hearts by decreasing the protein levels of COL I and COL III, down-regulating the mRNA expression levels of TGF-β1 and MMP2, and thereby reducing adverse cardiac remodeling.

Correlation between Expression of Signal Transducer and Activator of Transcription 3 and Pituitary Adenoma Subtypes / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the correlation between signal transducer and activator of transcription 3 (STAT3) expression and pituitary adenoma subtypes.</p><p><b>METHOD</b>The STAT3 expression profiles in different pituitary adenomas from 74 patients were determined using quantificational real-time polymerase chain reaction,Western blot,and immunohistochemistry.</p><p><b>RESULTS</b>Expression of STAT3 was observed in all pituitary adenoma subtypes. The STAT3 expression level was highest in growth hormone adenoma when compared with other tumors including prolactin,follicle-stimulating hormone/luteinizing hormone-secreting adenoma,and adrenocorticotrophic hormone-secreting adenoma. The follicle-stimulating hormone/luteinizing hormone adenomas exhibited the lowest STAT3 expression levels.</p><p><b>CONCLUSION</b>STAT3 is differentially expressed in pituitary adenoma subtypes, suggesting the cell-specific features of STAT3 regulation,although further investigations are still warranted to clarify the underlying mechanisms.</p>

Effects of miRNA-21 on paclitaxel-resistance in human breast cancer cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of miR-21 on paclitaxel-resistance in human breast cancer MCF-7/PR and SKBR-3/PR cells.</p><p><b>METHODS</b>Paclitaxel-resistant human breast cancer cell lines MCF-7/PR and SKBR-3/PR were established by stepwise selection in increasing concentration of paclitaxel. Cellular morphology, mRNA and protein level of MDR1, BCRP and MRP1 in MCF-7/PR and SKBR-3/PR cells were determined. The expression of Bax, Bcl-2 and miR-21 in parental and paclitaxel-resistant cells was detected by RT-PCR and Western blotting. The synthetic miR-21 inhibitor or miR-21 mimic were transfected into MCF-7/PR, SKBR-3/PR and MCF-7, SKBR-3 cells with Lipofectamine 2000. The miR-21 levels were determined by RT-PCR, and P-gp, Bcl-2 and Bax protein levels were examined by Western blotting. MTT assay was used to measure the cell viability, and flow cytometry was performed to analyze the cell cycle and apoptosis.</p><p><b>RESULTS</b>The levels of MDR1, BCRP, MRP1, Bcl-2/Bax and miR-21 in MCF-7/PR and SKBR-3/PR cells were significantly higher than those in MCF-7 and SKBR-3 cells. The protein levels of P-gp, Bcl-2 were up-regulated, and Bax was down-regulated compared with parental cells. MiR-21 was significantly down-regulated after miR-21 inhibitor was transfected; and the levels of MDR1, BCRP, MRP1 and Bcl-2/Bax (P <0.05) were also down-regulated. MiR-21 inhibitors significantly suppressed G0/G1 transition of the cell cycle, and induced cell apoptosis in MCF-7/PR and SKBR-3/PR cells. MTT results showed that miR-21 inhibitors induced sensitivity of MCF-7/PR and SKBR-3/PR cells to paclitaxel. And miR-21 mimic can increase the expression of MDR1, Bcl-2/Bax and change cell morphology from parental cells to resistant cells.</p><p><b>RESULTS</b>The established MCF-7/PR and SKBR-3/PR breast cancer cells show typical multidrug resistance characteristics, which can be used as the model for drug resistance study. Down-regulated miR-21 expression in MCF-7/PR and SKBR-3/PR breast cancer cells can enhance cell sensitivity to paclitaxel.</p>

Relationship between Variation of Pre-ablation Stimulated Thyroglobulin and Distant Metastasis in Patients with Differentiated Thyroid Cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship between the dynamic variation of pre-ablation stimulated thyroglobulin(sTg)and distant metastasis in patietns with differentiated thyroid cancer(DTC).</p><p><b>METHODS</b>DTC patients after total or near total thyroidectomy were divided into two groups as M1 group(n=38)and M0 group(n=130)according to the presence of distant metastases or not. Clinical data including pre-ablation sTg and the corresponding thyrotropin(TSH)values were dynamically measured. The pre-ablation sTg and corresponding TSH collected at the first time were defined as Tg1 and TSH1,while as Tg2 and TSH2 at the last time. χ(2) test was used to compare the variation tendency of sTg between these two groups. Tg1,Tg2,pre-ablation sTg variation(∆Tg),and ∆Tg/∆TSH ratio between M0 and M1 were compared by Mann-Whitney rank-sum test. The receiver operating characteristic(ROC)curves and diagnostic critical point(DCP)were employed to evaluate the predictive values of the above indicators.</p><p><b>RESULTS</b>Both Tg1 and Tg2 of M1 were significantly higher than those of M0(the Mann-Whitney rank-sum test:Tg1 P<0.001,Tg2 P<0.001). The corresponding areas under the ROC curve(AUC)to differentiate the two groups were 0.921 and 0.942,respectively. The cut-off value of Tg2,which was more accurate in predicting distant metastasis,was 24.3 ng/ml with a sensitivity of 92.11% and a specificity of 83.85%. Both ∆Tg and ∆Tg/∆TSH between these two groups were significantly different(the Mann-Whitney rank-sum test:∆Tg P=0.002,∆Tg/∆TSH P<0.001). ∆Tg/∆TSH worked better than Tg2 in predicting distant metastasis with both higher accuracy(87.50%)and higher specificity(86.92%).</p><p><b>CONCLUSIONS</b>Dynamically tracing pre-ablation sTg may improve the accuracy and specificity of distant metastases prediction in DTC patients. ∆Tg/∆TSH,which means the ratio of sTg variation to TSH variation,may be a useful diagnostic marker for predicting distant metastases in DTC.</p>

Diagnosis and Treatment of Pituitary Carcinoma / 中国医学科学院学报

The early diagnosis and treatment of pituitary carcinoma is difficult. The diagnosis is often delayed, and the confirmation of a diagnosis requires the presence of distant subarachnoid,brain or systemic metastasis from the primary pituitary tumor in the sella and also needs the evidences of pathology and imaging of the primary pituitary carcinoma and metastases. Treatment of pituitary carcinoma includes surgery, radiation therapy ,hormone therapy, chemotherapy, and molecularly targeted therapy; however, these methods are mainly palliative and can not prolong the survival. The prognosis remains poor. Efforts should be made to develop more effective diagnosis and treatment options.

Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effectiveness of treating giant pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques.</p><p><b>METHODS</b>A total of 72 patients who underwent neuroendoscopic surgery and 55 patients who underwent microscopic surgery for giant pituitary adenomas were enrolled in this retrospective analysis. Both groups received expanded endoscopic endonasal transsphenoidal approach, intraoperative application of navigation, and Doppler.The clinical data of two groups were compared.</p><p><b>RESULTS</b>The two groups were significantly different in total tumor removal rate, operation time, postoperative nasal patency, and postoperative recurrence rate (P=0.004, P=0.0003, P=0.000, and P=0.002, respectively), whereas the cerebrospinal fluid leakage, postoperative diabetes insipidus, and cranial nerve injury were not significantly different (P > 0.05).</p><p><b>CONCLUSIONS</b>Expanded neuroendoscopic endonasal transsphenoidal approach assisted by multiple techniques is the preferred surgical method for giant invasive pituitary adenomas invading cavernous sinus.The lateral cavernous sinus approach and the further molecular biology research will bring more options for the treatment of invasive pituitary adenomas.</p>

Effect of temperature on hospital admission among patients with chronic systolic heart failure / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the effect of temperature on hospital admission among patients with chronic systolic heart failure (CSHF).</p><p><b>METHODS</b>Data regarding in-hospital patients with CSHF were gathered from 12 hospitals in Hubei province, between 2000 and 2010. Patients with a history of congenital heart disease and the history of cancer from this series, were excluded. Chi-square (χ(2)) tests and t tests were used for descriptive analysis. Univariate and multivariate logistic regression methods were performed to determinate the risk of hospital admission of every month to compare with the previous one. We used 2-tailed 95% confidence interval (CI), and tests with P < 0.01 to consider the significant levels, statistically. We also used the SPSS 13.0 for Windows, release 15, 2006 (SPSS Inc, Chicago, Ill) for data analyses.</p><p><b>RESULTS</b>(1) 48 964 patients were enrolled in the present study. The numbers of admission increased 18.71%, 13.84%, -21.90%, -34.62%, -21.97%, -3.81%, -2.04%, 10.13%, -17.13%, -0.85%, 21.54% and 42.70% from January to December when compared to the average number of admission. (2) The odds ratios (ORs) (95% CI, P values) of hospital admission in January, February and December were 1.09 (0.96 - 1.23, 0.54), 0.98 (0.84 - 1.10, 0.46) and 0.96 (0.84 - 1.08, 0.59), respectively in females which did not show any significant differences when compared to the number in August. However the ratios were 0.61 (0.54 - 0.69, < 0.01), 0.80 (0.68 - 0.92, < 0.01) and 0.73 (0.64 - 0.83, < 0.01), respectively, in males that showed significant differences when, compared to the figures in August. (3) The OR of admission increased more when temperature got lower for patients with coronary artery disease, hypertension heart disease or rheumatic heart disease, but not with dilated cardiomyopathy. (4) The OR of admission showed a different impact on patients with different occupation, along with the change of temperature. Low or high temperature did not seem to have different effects on the OR of admission in patients who were free-lanced or unemployed.</p><p><b>CONCLUSION</b>Temperature seemed to have significant effects on the risk of admission, which related to gender, etiology or occupation.</p>

Advances in medical treatment of clinically nonfunctioning pituitary adenomas / 中国医学科学院学报

Clinically nonfunctioning pituitary adenomas are the most common types among pituitary adenomas. These tumors are usually diagnosed in their later stages due to the absence of clinical symptoms and detectable hormonal hypersecretion. Although these tumors are benign, they are hard to be completely removed during neurosurgery due to the massive invasion into the surrounding tissues at diagnosis. Furthermore, relapse is common. In recent years, medical treatment of pituitary adenomas has witnessed a rapid development. New medications have shown certain effectiveness in reducing the tumor size and improving the clinical symptoms.