[Coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance].

Objective: To investigate the clinical value of coefficient of variation of heart rate and blood pressure in rapid identification of children with suspected orthostatic intolerance(OI). Methods: This was a retrospective study. The medical records of 379 children with OI were collected, who were admitted to the Department of Pediatrics of Qilu Hospital of Shandong University from January 2015 to January 2020. Another 20 out-patient children without syncope or syncope aura were selected as control. According to the results of standing test and head-up tilt test (HUTT), all the patients with OI were divided into the following 4 groups: vasovagal syncope (VVS) group, postural tachycardia syndrome (POTS) group, POTS combined with VVS (POTS+VVS) group and HUTT negative group. Then, coefficient of variation of systolic pressure (SBPCV), coefficient of variation of diastolic pressure (DBPCV) and coefficient of variation of heart rate (HRCV) in standing test and HUTT were calculated. Kruskal-Wallis test was used for comparison among the five groups, and Dunnett's T3 method for comparison between two groups. Paired t test was used to compare the coefficient of variation between supine and erect position and tilt position in each group. The predictive values of HRCV,SBPCV and DBPCV for negative HUTT were evaluated by receiver operating characteristic (ROC) curve. Results: Among the 379 children, there were 79 in HUTT negative group, 208 in VVS group, 52 in POTS group, and 40 in POTS+VVS group. The SBPCV of supine-erect position of the control group, HUTT negative group, VVS group, POTS group, POTS+VVS group were (3.8±1.0)%, (5.3±2.2)%, (6.6±3.4)%, (5.9±3.6)%, (6.9±2.8)%, respectively. Similarly, the SBPCV of supine, erect and head-up tilt position were (4.5±0.8)%, (6.0±1.9)%, (7.1±2.6)%, (6.0±2.1)%, (7.3±2.5)%; the DBPCV of supine-erect position were (7.3±1.2)%, (9.1±3.7)%, (9.1±4.9)%, (9.1±4.8)%, (11.6±4.6)%; the DBPCV of supine, erect and tilt position were (7.4±1.1)%, (9.4±2.9)%, (10.1±3.8)%, (9.2±3.3)%, (11.0±4.7)%; the HRCV of supine-erect position were (7.6±2.6)%, (12.9±3.7)%, (16.2±4.3)%, (21.2±5.9)%, (24.9±5.3)%; and the HRCV of supine, erect and tilt position were (8.1±1.6)%, (10.1±2.7)%, (14.1±4.3)%, (15.6±3.7)%, (18.9±4.0)%, respectively. All the indexes showed significant differences among the five groups (χ2=21.91, 25.47, 19.82, 14.65, 104.52, 92.51, all P<0.05). ROC curve analysis showed that when the SBPCV and HRCV of supine-erect position reached 4.4% and 10.5%, the area under the curve of ROC were 0.713 and 0.877, the sensitivity of predicting negative HUTT were 58.2% and 78.5%, and the specificity were 80.0% and 95.0%, respectively. Conclusions: Coefficient of variation of heart rate and blood pressure may serve as potential diagnostic indexes in evaluating autonomic function of OI patients. SBPCV ≥ 4.4% or HRCV ≥ 10.5% of supine-erect position could be an indication of HUTT.

Initial metal-metal bond breakage detected by fs X-ray scattering in the photolysis of Ru3(CO)12 in cyclohexane at 400 nm.

Using femtosecond resolution X-ray solution scattering at a free electron laser we were able to directly observe metal-metal bond cleavage upon photolysis at 400 nm of Ru3(CO)12, a prototype for the photochemistry of transition metal carbonyls. This leads to the known single intermediate Ru3(CO)11(µ-CO)*, with a bridging ligand (µCO) and where the asterisk indicates an open Ru3-ring. This loses a CO ligand on a picosecond time scale yielding a newly observed triple bridge intermediate, Ru3(CO)8(µ-CO)3*. This loses another CO ligand to form the previously observed Ru3(CO)10, which returns to Ru3(CO)12via the known single-bridge Ru3(CO)10(µ-CO). These results indicate that contrary to long standing hypotheses, metal-metal bond breakage is the only chemical reaction immediately following the photolysis of Ru3(CO)12 at 400 nm. Combined with previous picosecond resolution X-ray scattering data and time resolved infrared spectroscopy these results yield a new mechanism for the photolysis of Ru3(CO)12.

Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells.

Autophagic activity reflects cellular response to drug treatment and can be regulated by STAT3 signaling. Resveratrol inhibits STAT3 activation and causes remarkable growth arrest and cell death of ovarian cancer (OC) cells. However, the autophagic status and its relevance with resveratrol's anti-OC effects remain unclear. We analyzed the states of autophagic activities, the nature of autophagosomes and the levels of autophagy-related proteins (LC-3, Beclin 1 and STAT3) in resveratrol-treated CAOV-3 and OVCAR-3 OC cells using multiple approaches. We elucidated the correlation of STAT3 inhibition with autophagic activity by treating OC cells with an upstream inhibitor of STAT proteins, AG490. Resveratrol efficiently suppressed growth, induced apoptosis and inactivated STAT3 signaling of the two OC cell lines. We found enhanced autophagic activity accompanied with Beclin-1 upregulation and LC3 enzymatic cleavage in resveratrol-treated OC cells. Immunofluorescent (IF) microscopic and IF-based confocal examinations demonstrated the accumulation of cytoplasmic granules co-labeled with LC3 and cytochrome C in resveratrol- or AG490-treated OC cells. Using electron microscopy, we confirmed an increase in autophagosomes and mitochondrial spheroids in either resveratrol- or AG490-treated OC cells. This study demonstrates the abilities of resveratrol to enhance apoptotic and autophagic activities in OC cells, presumably via inactivating STAT3 signaling. Resveratrol or the selective JAK2 inhibitor also leads to mitochondrial turnover, which would be unfavorable for OC cell survival and sensitize OC cells to resveratrol.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells.

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

Adrenomedullin and adrenotensin regulate collagen synthesis and proliferation in pulmonary arterial smooth muscle cells

To understand the pathophysiological mechanisms of pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular-matrix accumulation in the development of pulmonary hypertension and remodeling, this study determined the effects of different doses of adrenomedullin (ADM) and adrenotensin (ADT) on PASMC proliferation and collagen synthesis. The objective was to investigate whether extracellular signal-regulated kinase (ERK1/2) signaling was involved in ADM- and ADT-stimulated proliferation of PASMCs in 4-week-old male Wistar rats (body weight: 100-150 g, n=10). The proliferation of PASMCs was examined by 5-bromo-2-deoxyuridine incorporation. A cell growth curve was generated by the Cell Counting Kit-8 method. Expression of collagen I, collagen III, and phosphorylated ERK1/2 (p-ERK1/2) was evaluated by immunofluorescence. The effects of different concentrations of ADM and ADT on collagen I, collagen III, and p-ERK1/2 protein expression were determined by immunoblotting. We also investigated the effect of PD98059 inhibition on the expression of p-ERK1/2 protein by immunoblotting. ADM dose-dependently decreased cell proliferation, whereas ADT dose-dependently increased it; and ADM and ADT inhibited each other with respect to their effects on the proliferation of PASMCs. Consistent with these results, the expression of collagen I, collagen III, and p-ERK1/2 in rat PASMCs decreased after exposure to ADM but was upregulated after exposure to ADT. PD98059 significantly inhibited the downregulation by ADM and the upregulation by ADT of p-ERK1/2 expression. We conclude that ADM inhibited, and ADT stimulated, ERK1/2 signaling in rat PASMCs to regulate cell proliferation and collagen expression.

Impulsive solvent heating probed by picosecond x-ray diffraction.

The time-resolved diffraction signal from a laser-excited solution has three principal components: the solute-only term, the solute-solvent cross term, and the solvent-only term. The last term is very sensitive to the thermodynamic state of the bulk solvent, which may change during a chemical reaction due to energy transfer from light-absorbing solute molecules to the surrounding solvent molecules and the following relaxation to equilibrium with the environment around the scattering volume. The volume expansion coefficient alpha for a liquid is typically approximately 1 x 10(-3) K(-1), which is about 1000 times greater than for a solid. Hence solvent scattering is a very sensitive on-line thermometer. The decomposition of the scattered x-ray signal has so far been aided by molecular dynamics (MD) simulations, a method capable of simulating the solvent response as well as the solute term and solute/solvent cross terms for the data analysis. Here we present an experimental procedure, applicable to most hydrogen containing solvents, that directly measures the solvent response to a transient temperature rise. The overtone modes of OH stretching and CH3 asymmetric stretching in liquid methanol were excited by near-infrared femtosecond laser pulses at 1.5 and 1.7 microm and the ensuing hydrodynamics, induced by the transfer of heat from a subset of excited CH3OH* to the bulk and the subsequent thermal expansion, were probed by 100 ps x-ray pulses from a synchrotron. The time-resolved data allowed us to extract two key differentials: the change in the solvent diffraction from a temperature change at constant density, seen at a very short time delay approximately 100 ps, and a term from a change in density at constant temperature. The latter term becomes relevant at later times approximately 1 mus when the bulk of liquid expands to accommodate its new temperature at ambient pressure. These two terms are the principal building blocks in the hydrodynamic equation of state, and they are needed in a self-consistent reconstruction of the solvent response during a chemical reaction. We compare the experimental solvent terms with those from MD simulations. The use of experimentally determined solvent differentials greatly improved the quality of global fits when applied to the time-resolved data for C2H4I2 dissolved in methanol.

Ultrafast x-ray diffraction of transient molecular structures in solution.

We report direct structural evidence of the bridged radical (CH2ICH2.) in a polar solution, obtained using time-resolved liquid-phase x-ray diffraction. This transient intermediate has long been hypothesized to explain stereo-chemical control in many association and/or dissociation reactions involving haloalkanes. Ultrashort optical pulses were used to dissociate an iodine atom from the haloethane molecule (C2H4I2) dissolved in methanol, and the diffraction of picosecond x-ray pulses from a synchrotron supports the following structural dynamics, with approximately 0.01 angstrom spatial resolution and approximately 100 picosecond time resolution: The loss of one iodine atom from C2H4I2 leads to the C-I-C triangular geometry of CH2ICH2.. This transient C2H4I then binds to an iodine atom to form a new species, the C2H4I-I isomer, which eventually decays into C2H4 + I2. Solvent dynamics were also extracted from the data, revealing a change in the solvent cage geometry, heating, and thermal expansion.

Loss of phospholipids asymmetry in red blood cells contributes to anemia in uremic patients.

Anemia is common in dialysis patients. Change in phospholipids asymmetry in red blood cells (RBCs) may affect the removal of RBCs from the circulation and thus shorten the lifespan of RBCs. In the present study, we investigated phospholipids asymmetry in RBCs in uremic patients and its relationship with anemia. We studied 34 continuous ambulatory peritoneal dialysis (CAPD) patients (age: 51 +/- 15 years), 73 hemodialysis (HD) patients (age: 48 +/- 12 years), 8 pre-dialysis renal-failure patients (age: 42 +/- 21 years), and 16 healthy controls (age: 32 +/- 9 years). All patients were clinically stable. Phospholipids asymmetry as measured by phosphatidylserine exposure was determined by a flow-cytometric annexin V-binding assay. Hemoglobin levels were 93 +/- 20 g/L, 83 +/- 17 g/L, 78 +/- 21 g/L, and 145.8 +/- 12.5 g/L for CAPD patients, pre-dialysis patients, HD patients, and healthy controls respectively. Phosphatidylserine exposure in RBCs was significantly higher in uremic patients as compared with healthy controls, especially in HD patients--whose values were significantly higher than values seen in CAPD patients and pre-dialysis patients. No significant difference was seen in RBC phosphatidylserine exposure between pre-dialysis patients and CAPD patients. Cells positive for annexin V binding were 1.58%, 1.40%, 2.11%, and 0.71% for CAPD patients, pre-dialysis patients, HD patients, and healthy controls respectively. Significant reverse correlations were seen between annexin V and hemoglobin (r = -0.381, p < 0.001), and between annexin V and hematocrit (r = -0.355, p < 0.001). Our results suggest that (1) anemia is common in our uremic patients, especially in HD patients; and (2) anemia in uremic patients may be partly related to the loss of phospholipids asymmetry in RBCs.

CD40 ligand expression on macrophages during peritonitis in continuous ambulatory peritoneal dialysis patients.

CD40-CD40 ligand (CD40L) interaction plays an important role in macrophage/monocyte-mediated inflammatory processes by up-regulating cytokine production by macrophages/monocytes and by preventing macrophage apoptosis at the inflammation sites. The present study investigated the possible regulation of CD40L expression in peritonitis during continuous ambulatory peritoneal dialysis (CAPD). We used fluorescence-activated cell sorter (FACS) analysis to detect CD40L expression on macrophages obtained from peritoneal dialysate. Our results showed that CD40L expression on macrophages was significantly increased in a peritonitis group (4.62 +/- 6.54) as compared to a control group (0.76 +/- 0.30, p < 0.01). The CD40L-positive cells were also significantly increased during peritonitis (97.86% +/- 1.67% in the peritonitis group as compared to 73.10% +/- 26.94% in the control group, p < 0.05). After successful treatment, the expression of CD40L was significantly reduced (3.66 +/- 1.12 vs 1.05 +/- 0.02, p < 0.05). We conclude that functionally expressed CD40L on macrophages may take part in acute inflammatory response during peritonitis in CAPD and may play an important role in the local defense against infection in the peritoneal cavity.

[Fetal umbilical arterial blood flow velocity waveforms as measured in the uterus by pulsed Doppler and B-mode ultrasound].

3.0 MHz Doppler ultrasound was used to measure the umbilical arterial blood flow velocity waveforms (FVW) in 174 fetuses between 22-42 weeks of gestation. The A/B ratio (systolic/diastolic), resistance index (RI), pulsatility index (PI) and impedance index (ImI) were used as indexes of placental flow resistance. In normal pregnancy (n = 152), 460 measurements were performed. Analysis of these waveforms demonstrated that the placental is an organ of low vascular resistance and that placental resistance to blood flow gradually declines with advancing gestational age. Our results indicated a significant negative correlation between each of the four indexes and gestational age. There was a small but significant decrease in all four indexes, from 22-42 weeks. 56 scans were performed on 22 fetuses with intrauterine growth retardation (IUGR). The sonograms from these IUGR fetuses showed different characteristics which implied a high distal impedance to the blood flow. 16 of these (72.7%) presented an abnormal increase in all four indexes.

Lymphonodovenous anastomosis in the treatment of chyluria.

Thirty cases of chyluria were treated by means of lymphonodovenous anastomoses according to the principles of lymphovenous shunt. A conical tissue of lymph node close to the greater saphenous vein in the inguinal region was removed and the remaining tunnel-shaped node was anastomosed to the vein to drain the lymph into the venous system. Twenty-one cases were followed up for six months after the operation. Among them, 16 (76.2%) showed disappearance of chyluria, and 2 (9.5%) were improved, giving an effective rate of 85.7%. This operation avoids damage to both the afferent and efferent lymphatic vessels, and affords a large anastomotic stoma for free passage of the lymph into the vein.

[Ultrasonographic study of trophoblastic neoplasms. A report of 185 cases].

B-scan ultrasonography was used in 94 cases of hydatidiform mole (benign group), 62 cases of invasive mole and 29 cases of choriocarcinoma (malignant group). A correct diagnosis was made in 91.5% of cases of the benign group and 91.3% of the malignant group. Chemotherapy was given to all patients with invasive mole or choriocarcinoma, and hysterectomy was done in 47 cases after chemotherapy. During chemotherapy a gradual regression of the intramural lesions was demonstrated by ultrasonography with fall of hCG titer. The authors suggest that the B-scan ultrasonography is a safe and useful method in monitoring the response of the trophoblastic tumors to chemotherapy.

Observations of Langerhans' cells in leprosy using monoclonal antibody OKT6.

Changes in the Langerhans' cells (LC) in seven cases of leprosy were observed using the monoclonal antibody OKT6. In the epidermis of the lesions of most of the leprosy cases, the processes of LC were reduced or diminished. Some LC were disintegrated. In two BT cases in the upgrading (type 1) reactional stage, either increased numbers and aggregation of OKT6-positive cells in clusters or their disintegration was seen in different areas of the epidermis.

Preliminary observation on Langerhan's cells in leprosy.

Langerhans' cells were enumerated in the skin of eight borderline and tuberculoid leprosy patients by the enzymatic histochemical demonstration of ATPase in these cells in epidermal sheets. The number of Langerhans' cells was significantly reduced in the skin lesions of these patients compared with normal appearing skin from the same patients. The morphological details of these cells were not clear under light microscopy; further study with electron microscopy is desirable.