Effects of autologous SCF- and G-CSF-mobilized bone marrow stem cells on hypoxia-inducible factor-1 in rats with ischemia-reperfusion renal injury.

To explore the mechanism whereby stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) jointly mobilize bone marrow stem cells (BMSCs) and promote kidney repair, male Sprague-Dawley rats were randomly assigned into 4 groups. In the treatment control group, rats were administered SCF (200 µg·kg(-1)·day(-1)) and G-CSF (50 µg·kg-1·day-1) for 5 days. In the treatment group, RIRI models were established, and 6 h later, SCF (200 µg·kg(-1)·day(-1)) and G-CSF (50 µg·kg(-1)·day(-1)) were administered for 5 days. In the model and treatment groups, tubular epithelial cell degeneration and necrosis were noticed, but the extent of repair in the treatment group was significantly better than in the model group. Five days after the operation, renal tissue CD34+ cells significantly increased in the model and treatment groups compared with the control and treatment control groups. HIF-1α, VEGF, and EPO expression in treatment groups increased significantly compared with the other groups. HIF- 1α, VEGF, EPO expression in the treatment control group increased significantly compared with the control group. Joint use of SCF and G-CSF increased the number of BMSCs in damaged kidney tissue and reduced the degree of renal tissue damage. BMSCs promote increased HIF-1α expression in renal tissue. Increased kidney tissue HIF- 1α and its target gene products VEGF and EPO expression possibly induce SCF and G-CSF to promote acute tubular necrosis repair.

[Predictive value of serum ferritin and a new predictive model for intravenous immunoglobulin resistance in Kawasaki disease].

Objective: To evaluate the predictive value of serum ferritin (SF) and construct a novel predictive model for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) (IVIGRKD). Methods: The clinical data of 422 children with KD from January 2017 to December 2019 in Quanzhou Women's and Children's Hospital were retrospectively analyzed. According to the response to IVIG, they were divided into IVIG-resistant group and IVIG-sensitive group. Forty-one clinical indicators including general characteristics and laboratory results were compared between the two groups. Comparisons between groups were performed with unpaired Student t test or Mann-Whitney U test or chi-square test. Receiver operating characteristic (ROC) curve was applied to evaluate the predictive value of SF for IVIGRKD. Binary Logistic regression analysis was used to test whether SF was an independent risk factor for IVIGRKD. Meanwhile, a novel predictive scoring system was established. The comparisons between the new predictive scoring system with four commonly used prediction scoring systems were conducted. Results: A total of 422 KD cases (285 males and 137 females, 17.0 (9.0,29.0) years of age) were enrolled and divided into IVIG-resistant group (n=57) and IVIG-sensitive group (n=365). Seventeen clinical indicators differed significantly between the two groups. SF level of the IVIG-resistant group was significantly higher than that of the sensitive group (245.0 (131.0, 519.0) vs. 145.0 (92.5, 232.5) µg/L, Z=-5.109, P<0.05). ROC curve showed that the Youden index of SF for predicting IVIGRKD was 0.326 (cutoff value 403.5 µg/L). Binary logistic regression analysis showed that SF, days of illness at initial IVIG treatment, cervical lymphadenopathy, pleomorphic rash, white blood cell, C-reactive protein (CRP), activated partial thromboplastin time (APTT), alanine transaminase (ALT) and creatinine were independent risk factors for IVIGRKD. A novel prediction model was constructed, and the cutoff points and score points were as follows: pleomorphic rash, 2 points; cervical lymphadenopathy, 1 point; SF≥ 403.5 µg/L, 1 point; white blood cell ≥ 18.3×109/L, 1 point; CRP≥83.1 mg/L, 1 point; APTT≥25.3 s, 1 point; ALT≥37.5 U/L, 1 point. And patients with scores of 4 or more were at high-risk for IVIGRKD. The Youden index of the four commonly used scoring systems ranged from 0.315 to 0.512. However, the Youden index of the new scoring system was 0.695 (sensitivity 0.772, specificity 0.923) and was the highest among the five scoring systems. Conclusions: SF shows well predictive efficiency for IVIGRKD and is an independent risk factor for IVIGRKD. SF can be used as a new predictor of IVIGRKD.

[Treatment of 30 elderly patients with advanced myeloid neoplasm by allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for elderly patients with advanced myeloid neoplasm. Methods: From September 2014 to September 2017, 30 consecutive hospitalized 50-plus-year-old myeloid neoplasm patients were retrospectively analyzed. At the time of transplantation, 6 patients reached complete remission and the others remained no remission after treatment. The donors were identical sibling (12), matched unrelated (6) and haploidentical family member (12), respectively. 18 patients received RIC while 12 patients received MAC conditioning regiments consisted of Busulfan, cytarabine, fludarabine or clarithromycin±TBI, respectively. Results: Five patients died early in the conditioning stage, 24 patients successfully engrafted. The median time of neutrophil engraftment was 14(10-18) d, whereas platelet engraftment was 15(10-19) d. Six cases (25%) experienced aGVHD grades Ⅱ, 8 cases (32%) cGVHD, including moderate to severe cGVHD in 2 cases (8%). Seven, 7 and 5 cases developed CMV viremia, pneumonia and herpeszoster, respectively after transplantation, but no patients died of infections. The median follow-up time of the patients was 7(0.5-38) months. Twenty-one patients were still alive. The estimated 2 years OS and LFS were 62.5% (95% CI 39.2%-85.8%) and 59.2% (95% CI 26.9%-91.5%), respectively. Univariate analysis showed that HCT-CI was the only factor influencing OS. Conclusion: Allogeneic hematopoietic stem cell transplantation could improve the survival of elderly patients with myeloid neoplasm.

Effects of left ventricular asynchrony on time constant and extrapolated pressure of left ventricular pressure decay in coronary artery disease.

To elucidate the effects of ventricular asynchrony with or without myocardial ischemia on the time constant of left ventricular pressure decay and asymptote, that is, the level to which pressure would decrease if isovolumic pressure decrease continued infinitely, left ventriculography and pressure measurements were investigated in 14 normal subjects and 25 patients with coronary artery disease. Ventricular asynchrony was quantitated by the segmental area-time curve. This study consisted of two parts. 1) After a right atrial pacing stress test, the time constant and asymptote remained unchanged in eight normal subjects. In 18 patients with coronary artery disease and pacing-induced angina, asynchrony increased, the time constant was prolonged (64 +/- 13 to 94 +/- 17 ms, p less than 0.01) and the asymptote decreased (-22 +/- 10 to -46 +/- 20 mm Hg, p less than 0.01) after the pacing. 2) During right ventricular pacing at 80, 100 and 120 beats/min in the patients, asynchrony increased and the time constant was prolonged (55 +/- 7 versus 70 +/- 10, 47 +/- 11 versus 66 +/- 19, 36 +/- 7 versus 53 +/- 13 ms, respectively, p less than 0.01 versus right atrial pacing), whereas the asymptote was unchanged in six normal subjects compared with the value during right atrial pacing at each pacing rate. In seven patients with coronary artery disease, right ventricular pacing at 80, 100 and 120 beats/min also produced an increase in the time constant, while the asymptote was unchanged. Thus, prolongation of the time constant of left ventricular pressure decay may result from ventricular asynchrony even in the absence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired right ventricular filling in old myocardial infarction.

To evaluate ventricular filling and interactions between right and left ventricles in patients with old myocardial infarction, right and left ventricular time-volume curves were analyzed from a cineangiographic study of 10 normal subjects (Group 1), 10 patients with old anterior myocardial infarction (Group 2) and 10 patients with old inferior myocardial infarction (Group 3). Volumes of both ventricles were calculated from each frame over an entire cardiac cycle using Simpson's method. From time-volume curves, peak ejection rates, peak filling rates and atrial kick rates were obtained for both ventricles and these parameters were normalized by end-diastolic volume. All patients were in sinus rhythm with heart rates less than 80 beats/min. There were no significant differences among the 3 groups in end-diastolic pressure of both ventricles and mean pulmonary artery pressure. Left ventricular ejection fractions were significantly lower in Groups 2 and 3 than in Group 1 (p less than 0.001, p less than 0.005, respectively), although there were no significant differences in end-diastolic volume indexes of either ventricle among the 3 groups. Peak left ventricular ejection rate and peak filling rates of the left and right ventricles were lower in Group 2 than in Group 1 (p less than 0.01, p less than 0.05, p less than 0.01, respectively) and peak filling rate of the right ventricle in Group 2 correlated with the peak filling rate of the left ventricle and left ventricular ejection fraction (r = 0.64, r = 0.64, respectively). Peak filling rate of the right ventricle in Group 2 correlated inversely with left ventricular peak negative dp/dt (r = -0.72), but no correlation was found between peak filling rate of the right ventricle and left ventricular end-diastolic volume index or mean pulmonary artery pressure. Peak ejection rate of the left ventricle and peak filling rates of both ventricles in Group 3 were lower than in Group 1 (p less than 0.02, p less than 0.02, p less than 0.01, respectively) and no correlation was found between peak filling rates of both ventricles. Wall motion of the right ventricular septal portion was slightly reduced in 5 patients in Group 2. In all patients in Group 3, right ventricular wall motion centering around the right ventricular diaphragmatic portion was reduced. These results suggest that in old inferior myocardial infarction, right ventricular wall motion abnormality results in impaired right ventricular filling, whereas in old anterior myocardial infarction, right ventricular filling is reduced indirectly due to impaired left ventricular filling.

Assessment of left ventricular function in ischemic heart disease. The relation between pressure decay during the isovolumic relaxation phase and regional wall motion abnormality.

We examine whether regional wall motion abnormality (RWMA) could contribute to the slowed relaxation rate of the left ventricle (LV) in patients with coronary artery disease (CADpts). Simultaneous observations were made on the time constant (Tc) of the isovolumic pressure decay and left ventriculography at the control period and after right atrial pacing. Subsequently, the subjects investigated were divided into 3 groups, i.e. normal subjects (Group I, n = 8), CADpts with normal wall motion during the control period (Group II, n = 21), and CADpts with RWMA during the control period (Group III, n = 28). The latter two groups were further divided into two subgroups according to the presence (Group IIa and IIIa) or absence (Group IIb and IIIb) of pacing-induced RWMA. We measured Tc by a method of exponential analysis that could estimate the asymptote. During the control period, Tc was significantly prolonged in Group III (82 +/- 26 msec) than that in Group I (60 +/- 6 msec) and Group II (63 +/- 12 msec). Tc was prolonged in proportion to the extent of RWMA during the control period. Immediately after right atrial pacing, Tc was markedly prolonged in Group IIa (from 61 +/- 12 to 90 +/- 20 msec, p less than 0.001) and in Group IIIa (from 73 +/- 26 to 95 +/- 34 msec, p less than 0.001). The post-pacing prolongation of Tc was closely correlated with the extent of post-pacing RWMA. From these results, it is postulated that RWMA may play an important role as a causes of the altered LV relaxation in CADpts.

Effects of diltiazem and nitroglycerin on left ventricular diastolic properties in patients with coronary artery disease.

To determine the effects of diltiazem (DTZ) and nitroglycerin (NTG) on left ventricular (LV) diastolic relaxation and filling in patients with cornary artery disease (CADpts), LV graphy and time constant (Tc) of LV isovolumic pressure decay were studied before and 5 min after intravenous DTZ (10 mg) in 16 CADpts and sublingual NTG (0.3 mg) in 11 CADpts. Diastolic regional ventricular filling dynamics were quantitated by segmental area-time curves during early-, mid- and late-filling periods. After NTG, LV systolic pressure (LVSP), end-diastolic pressure (EDP) and end-diastolic volume (EDV) decreased. Early-filling rate (EFR) decreased (165 +/- 82 to 122 +/- 61 ml/sec/m2) due to a decrease in the regional early-filling rate in the normokinetic area and late-filling rate (LFR) increased (95 +/- 38 to 145 +/- 45 ml/sec/m2), while LV peak positive dp/dt, peak LVSP/end-systolic volume (ESV) ratio, Tc and mid-filling rate (MFR) were unchanged. After DTZ, LVSP decreased and EDV increased. EFR increased. EFR increased (127 +/- 54 to 166 +/- 60 ml/sec/m2) due to an enhanced regional early-filling rate in the mildly hypokinetic area, while EDP, LV peak positive dp/dt, peak LVSP/ESV ratio, Tc, MFR and LFR were unchanged. From these results, it was postulated that NTG caused a decrease in LV early filling and an increase in LV late filling, probably due to LV preload reduction. In contrast, DTZ caused significant improvement of LV early filling particularly in the mild hypokinetic area. Thus, DTZ but not NTG was able to relieve local myocardial dysfunction secondary to a stenosed coronary artery during the filling period, resulting in clinical improvement in CADpts.

A comparison of two exponential models of the time constant during left ventricular isovolumic pressure decay in coronary artery disease.

To make a comparison of two exponential models of the time constant (Tw: Weiss's method, Tc: exponential analysis with a variable asymptote) during left ventricular (LV) isovolumic relaxation, we assessed LV pressure decay in 104 patients with coronary artery disease (CADpts) and 21 normal subjects at rest and after pacing, and investigated the hemodynamic determinants of these two models using forward-backward stepwise multiple regression analysis. At rest, Tw was prolonged as the left ventricular minimal pressure (LVPmin), the left ventricular end-diastolic pressure (LVEDP) and the end-systolic volume (ESV) increased (multiple regression coefficient: R = 0.87), whereas Tc was prolonged as ESV and regional wall motion abnormality (RWMA) increased (R = 0.72). Pacing-induced changes in Tw were augmented as LVPmin and RWMA increased (R = 0.75), whereas changes in Tc were augmented as RWMA increased (R = 0.63). Thus, the changes in Tw may be due to an increase in LVPmin rather than to any direct effect of ischemia on the relaxation rate. The relaxation rate can be evaluated more reliably by Tc than by Tw, irrespective of associated pressure changes during ischemia in CADpts.