Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
Animals ; Humans ; Mice ; Disease Models, Animal ; Fibroblasts/metabolism* ; Fibrosis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3/metabolism* ; Myocardial Infarction/metabolism* ; Receptors, Cytokine/metabolism* ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology*

Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ²=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ²=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ²=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ²=15.611, P<0.001). Conclusions In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.

Objective To evaluate the role of combination of multiple MRI sequences in the differential diagnosis of esophagus cancer and to assess the accordance among radiologists with different experience. Methods Thirty?fifty patients underwent conventional MRI including T2 weighted (T2) sequences, gadolinium fat?suppressed T1 weighted sequences (post?contrast T1), and DWI sequences. Three radiologists with different experience determined the possibility of local recurrence (LR) on T2, T2+post?contrast T1, T2+DWI, and T2+post?contrast T1+DWI. ROC and Kappa were used. Results In total, 13 patients had LR. On T2WI, the ROC curve (AUC) achieved by the senior,intermediate and junior groups were 0.701, 0.407, and 0.584, respectively. Compared with simple T2WI sequences, DWI and T1 Gd significantly improved the AUC value for the intermediate radiologist. The great difference was observed between radiologists of different experience (Kappa coefficient was from 0.227 to 0.884). Combination of multiple sequences significantly reduced the diagnostic differences between radiologists with different experience for the senior radiologists particularly. Conclusions The addition of DWI and T1 post?contrast MRI increased diagnostic ability for LR of esophagus cancer and reduced the diagnostic differences between radiologists with different experience compared to T2WI.

Objective: To evaluate the role of combination of multiple MRI sequences in the differential diagnosis of esophagus cancer and to assess the accordance among radiologists with different experience. Methods: Thirty-fifty patients underwent conventional MRI including T₂ weighted (T₂) sequences, gadolinium fat-suppressed T₁ weighted sequences (post-contrast T₁), and DWI sequences. Three radiologists with different experience determined the possibility of local recurrence (LR) on T₂, T₂+post-contrast T₁, T₂+DWI, and T₂+post-contrast T₁+DWI. ROC and Kappa were used. Results: In total, 13 patients had LR. On T₂WI, the ROC curve (AUC) achieved by the senior,intermediate and junior groups were 0.701,0.407,and 0.584, respectively.Compared with simple T₂WI sequences, DWI and T₁ Gd significantly improved the AUC value for the intermediate radiologist. The great difference was observed between radiologists of different experience (Kappa coefficient was from 0.227 to 0.884). Combination of multiple sequences significantly reduced the diagnostic differences between radiologists with different experience for the senior radiologists particularly. Conclusions The addition of DWI and T₁ post-contrast MRI increased diagnostic ability for LR of esophagus cancer and reduced the diagnostic differences between radiologists with different experience compared to T₂WI.

OBJECTIVE: To investigate the value of real-time ultrasound guided placement of permanent internal jugular vein (IJV) catheterization in maintenance hemodialysis patients, and analyze its technical success and complication rate. METHODS: We prospectively analyzed 63 patients (39 males, 24 females) who underwent permanent IJV cannulation with real-time ultrasound guidance from January to October in 2012. Under the real-time guidance of Logiq 5 color Doppler, we placed the tunneled cuffed catheters into the jugular vein by Seldinger technique. The number of needle punctures, technical success, the operation time, and complications were recorded. The patients were divided into a normal-risk group and a high-risk group: those who suffered multiple catheter insertions, previous difficulties during catheterization, poor compliance, obesity, impaired consciousness, skeletal deformity, disorder of haemostasis were regarded as high-risk patients. RESULTS: Cannulation of IJV was done in all patients. Of the 63 catheters, 20 (31.7%) were placed in the high-risk patients; 60 (95.2%) were successfully placed at the first attempt, with the average number of punctures of (1.23±0.21) (range 1-3); Only 3 immediate complications (4.7%) developed; 3 (4.7%) catheter infections occurred in the course of using. Cannulation of IJV took longer time in the high-risk group than that in the normal-risk group [(30.6±0.11) min vs (19.1±0.09) min, P<0.05]. The number of needle punctures, percent of successful cannulation, and the frequency of immediate complications were similar in the high- and normal-risk groups. It was more likely to form catheter thrombosis during long-term use in the high-risk group (4/20, 20%) which might cause poor blood flow. CONCLUSION Permanent IJV cannulation under real-time ultrasound guidance is very safe with high success rates. Nephrologists can use this technique with ease and with minimal complications in both normal- and high-risk patients.
Catheterization, Central Venous ; methods ; Female ; Humans ; Jugular Veins ; diagnostic imaging ; Male ; Prospective Studies ; Renal Dialysis ; Ultrasonography

Objective To compare the dosimetry and treatment efficiency between a multi-ple partial volumetric-modulated arcs therapy (MP-VMAT)and double-arc volumetric modulated arc therapy (DA-VMAT)for patients with breast cancer mastecomy.Methods 19 patients with breast cancer treated by mastecomy and requiring postoperative radiotherapy were collected.MP-VMAT and DA-VMAT plans were applied for each patient respectively.Dosimetry parameters for target volume and organ of risks (OARs)were compared.Machine unite and delivery times were compared.Results MP-VMAT plans had a more uniform target dose distribution with average Conformation Index (CI )andHomogeneity Index (HI )of0 .5 6 and 1 .0 6 compared to 1 .0 6 and 1.14 of the DA-VMAT plans(P <0.05).MP-VMAT plans predicted a reduction of 5.53% in V20 of contralateral lung,3.74 Gy in mean dose,6.27% in V5 and 5.53% in V20 of ispleratal lung respectively (P <0.05).MP-VMAT plans predicted a reduction of 10.33% and 7.82% in V5 and V10 of heartrespectively (P <0.05),MP-VMAT plans predicted a reduction of 9.14%, 2.72% and 0.06% inV5,V10 and V15 of contralateral breast respectively (P <0.05)plans. However,MP-VMAT plans improved monitor units 7 4 5 .9 MU and treatment time 3 0 4 .6 s compared with DA-VMAT 524.4 MU and 196.7 s (P <0.05).Conclusion MP-VMAT plans generate more uniformity in the target dose and decreased the dose of most of organs of risk com-pared to the DA-VMAT,But improved monitor units and treatment time.In clinical application, different techniqies are chosen based on the situation of every patient.

Objective To compare the dosimetry and treatment efficiency between a multi-ple partial volumetric-modulated arcs therapy (MP-VMAT)and double-arc volumetric modulated arc therapy (DA-VMAT)for patients with breast cancer mastecomy.Methods 19 patients with breast cancer treated by mastecomy and requiring postoperative radiotherapy were collected.MP-VMAT and DA-VMAT plans were applied for each patient respectively.Dosimetry parameters for target volume and organ of risks (OARs)were compared.Machine unite and delivery times were compared.Results MP-VMAT plans had a more uniform target dose distribution with average Conformation Index (CI )andHomogeneity Index (HI )of0 .5 6 and 1 .0 6 compared to 1 .0 6 and 1.14 of the DA-VMAT plans(P <0.05).MP-VMAT plans predicted a reduction of 5.53% in V20 of contralateral lung,3.74 Gy in mean dose,6.27% in V5 and 5.53% in V20 of ispleratal lung respectively (P <0.05).MP-VMAT plans predicted a reduction of 10.33% and 7.82% in V5 and V10 of heartrespectively (P <0.05),MP-VMAT plans predicted a reduction of 9.14%, 2.72% and 0.06% inV5,V10 and V15 of contralateral breast respectively (P <0.05)plans. However,MP-VMAT plans improved monitor units 7 4 5 .9 MU and treatment time 3 0 4 .6 s compared with DA-VMAT 524.4 MU and 196.7 s (P <0.05).Conclusion MP-VMAT plans generate more uniformity in the target dose and decreased the dose of most of organs of risk com-pared to the DA-VMAT,But improved monitor units and treatment time.In clinical application, different techniqies are chosen based on the situation of every patient.

Objective To investigate the clinical significance of velocity vector imaging(VVI)in evaluating the left ventricular(LV)segmental longitudinal systolic function in patients with coronary artery disease(CAD).Methods In 25 patients with myocardial ischemia,28 patients with myocardial infarction,26 patients with coronary lumen stenosis＜50%,according to coronary arteriography and electrocardiogram,the myocardial segments of LV were divided into 4 groups:ischemic segments group,infarcted segments group,non-ischemic segments group and normal segments group.Twenty-eight healthy subjects were selected as control group.Dynamic imaging of all subjects were collected,the systolic peak strain(Smax)and strain rate(SRmax),the time to peak strain(PTs)and the time to peak strain rate(PTsr)were measured respectively.Results Smax and SRmax of the ischemic segments and infracted segments were significantly lower than those of the control group respectively,PTs and PTsr of the ischemic segments and infracted segments were significantly longer than those of the control group respectively.Smax and SRmax of infarcted segments were significantly lower than those of the ischemic segments,there were no differences of PTs and PTsr between ischemic segments and infracted segments.Smax and SRmax cutoff of -14.08%,-0.83 s-1 for detecting ischemic segments and cutoff of -6.65%,-0.38 s-1 for detecting infracted segments,respectively,gave an optimal sensitivity and specificity.Conclusions VVI is a kind of novel noninvasive-tool to quantitatively assess LV regional systolic function in CAD patients.It is competent to differentiate between the ischemic segments and infarcted segments.

Objective To assess the characteristic of left ventricular(LV) twist changed from infancy to the elder,in order to determine the normal value of LV twist in different age group.Methods After acquired basal and apical LV short-axis images in 293 healthy volunteers (aged 15 days to 72 years) by 2-dimensional echocardiography, speckle tracking echocardiography was used to analysis LV twist motion offline.The peak apical rotation (PAr), peak basal rotation (PBr), peak LV twist (Ptw), peak LV twist normalized by LV length ( PtwN), peak untwisting velocity ( PutwV), isovolumic untwisting% ( Iutw% ) in different group were compared.Results Reliable LV twist measurements were obtained in 274 volunteers.Different LV twist values were noted according to age.Ptw increased gradually with advancing age, when normalized by LV length, PtwN showed higher values before 3 years old and 25 to 45 years old.PutwV increased with aging from infancy to 25 years old, and leveled off from 25 to 45 years old, then decreased with advancing age.Iutw% was lowest before 3 years old,and increased gradually from 25 to 45 years old,then decreased with aging.Conclusions speckle tracking echocardiography can be used to noninvasively and exactly assess LV twist with high feasibility.The effect of aging on LV twist may reflect the process of maturational and adaptive modulation of LV torsional biomechanics from infancy to the elder.

[Objective]To observe the relativity between congestive heart failure(CHF) differentiation types of TCM and thyroid gland hormone,BNP and heart function parameters.[Method] Divide CHF patients into 4 groups,measure their heart function parameters,BNP and thyroid hormone,compare it to that of control group(21 cases).[Result] In CHF combined with blood stasis group,T3 level is much more reduced than that of control group and groups of heart Qi deficiency and combination of Yin deficiency(P