Factors associated with malnutrition in infants with congenital heart disease within one year after surgery / 中华儿科杂志

Objective: To explore the risk factors of malnutrition in infants with congenital heart disease within one year after surgery. Methods: This retrospective cohort study selected 502 infants with congenital heart disease who underwent surgical treatment in Guangzhou Women and Children's Medical Center from February 2018 to January 2019. Their basic information and clinical data were analyzed, and their nutrition status after the surgery was followed up by questionnaire survey. Weight-for-age Z score (WAZ)≤-2 one year after operation was defined as malnutrition group, and WAZ>-2 was non-malnutrition group. The perioperative indicators and complementary food advancement were compared between the two groups by chi-square test, t-test, and Kruskal-Wallis test. The risk factors of malnutrition were analyzed by Logistic regression. Results: A total of 502 infants were selected, including 301 males and 201 females, with the age of 4.1 (2.0, 6.8) months. There were 90 cases in malnutrition group and 412 cases in non-malnutrition group. The body length and weight at birth in the malnutrition group were lower than those in the non-malnutrition group ((47.8±3.8) vs. (49.3±2.5) cm, (2.7±0.6) vs.(3.0±0.5) kg, both P<0.001). The proportion of paternal high school education or above and the proportion of family per capita income of 5 000 yuan or above in the malnutrition group were lower than those in the non-malnutrition group ((18.9% (17/90) vs. 30.8% (127/412), 18.9% (17/90) vs. 33.7% (139/412), both P<0.05). Compared to the non-malnutrition group, the proportion of complex congenital heart disease in the malnutrition group was higher (62.2% (56/90) vs. 47.3% (195/412), P<0.05). The postoperative mechanical ventilation time, postoperative intensive care unit (ICU) stay time, postoperative hospital stay, total length of ICU stay and total hospital stay in the malnutrition group were significantly longer than those in non-malnutrition group (all P<0.05). The proportion of egg and fish supplementation over 2 times/week within one year after the surgery was also lower in the malnutrition group (both P<0.05). Logistic regression analysis showed that mother's weight at delivery (OR=0.95,95%CI 0.91-0.99), the pre-operative WAZ≤-2 (OR=6.04, 95%CI 3.13-11.65), the complexity of the cardiac disease (OR=2.23, 95%CI 1.22-4.06), the hospital stay after the surgery over 14 days (OR=2.61, 95%CI 1.30-5.26), the types of complementary food<4 (OR=2.57, 95%CI 1.39-4.76), and the frequency of meat and fish<2 times/week (OR=2.11, 95%CI 1.13-3.93) were the risk factors associated with malnutrition within one year after the surgery. Conclusion: Mother's weight at delivery pre-operative nutritional status, complexity of cardiac disease, postoperative hospital stay, types of daily supplements and frequency of fish are risk factors associated with malnutrition within one year after surgery in children with congenital heart disease.

The Physiological Significance of A-Waves in Early Diabetic Neuropathy: Assessment of Motor Nerve Fibers by Neurophysiological Techniques.

Objective: This study aimed to investigate how early A-waves could occur in type II diabetes, and what it implied functionally. Methods: We performed conduction velocity distribution (CVD) test in peroneal nerves of 37 type II diabetic patients with normal nerve conduction study (NCS) and 22 age-matched controls. The electrophysiological data and clinical information were analyzed. Results: A-waves were observed in 45.9% of diabetic patients and only in 1 person in healthy controls, all detected in the tibial nerves. The diabetic patients with A-waves showed faster conduction velocity in all quartiles in the motor peroneal nerves compared to the patients without A-waves, and their CVD histograms were shifted to the right side, consisting of a significantly larger percentage of fast conducting fibers. There was no significant difference in the CVD values of the upper extremity nerves among the patients with and without A-waves and the healthy controls. Conclusion: A-waves could occur in type II diabetes as early as when NCS showed normal, and represented as a sign of neuropathy as well as a sign of rescued motor nerve function.

Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation.

AIM: To study the dominant role of parasympathetic inputs at cellular level of baroreflex afferent pathway and underlying mechanism in neurocontrol of blood pressure regulation. METHODS: Whole-cell patch-clamp and animal study were conducted. RESULTS: For the first time, we demonstrated the spontaneous activities from resting membrane potential in myelinated A- and Ah-type baroreceptor neurons (BRNs, the 1st-order), but not in unmyelinated C-types, using vagus-nodose slice of adult female rats. These data were further supported by the notion that the spontaneous synaptic currents could only be seen in the pharmacologically and electrophysiologically defined myelinated A- and Ah-type baroreceptive neurons (the 2nd-order) of NTS using brainstem slice of adult female rats. The greater frequency and the larger amplitude of the spontaneous excitatory postsynaptic currents (EPSCs) compared with the inhibitory postsynaptic currents (IPSCs) were only observed in Ah-types. The ratio of EPSCs:IPSCs was estimated at 3:1 and higher. These results confirmed that the afferent-specific spontaneous activities were generated from baroreflex afferent pathway in female-specific subpopulation of myelinated Ah-type BRNs in nodose and baroreceptive neurons in NTS, which provided a novel insight into the dominant role of sex-specific baroreflex-evoked parasympathetic drives in retaining a stable and lower blood pressure status in healthy subjects, particularly in females. CONCLUSION: The data from current investigations establish a new concept for the role of Ah-type baroreceptor/baroreceptive neurons in controlling blood pressure stability and provide a new pathway for pharmacological intervention for hypertension and cardiovascular diseases.

Osteoblast-oriented differentiation of BMSCs by co-culturing with composite scaffolds constructed using silicon-substituted calcium phosphate, autogenous fine particulate bone powder and alginate in vitro.

Autogenous bone graft is the best for spinal fusion in clinics, however, lacking sources, bleeding and infection are limited its practice. Seeking alternative materials are urgent for orthopaedic surgeon. Here, we evaluated osteoblast-oriented differentiation of rabbit BMSCs by co-culturing with composite scaffolds constructed using silicon-substituted-CaP-fine particulate bone powder-alginate. Using CCk8-kit, biocompatibility was evaluated by testing BMSCs proliferation; morphology and survival of osteoblasts within scaffolds were observed using EM and HE staining; growth factors and related genes were detected using RT-PCR. HE staining showed spindle-shaped BMSCs after the 3rd passage; EM data showed that uneven surface and longitudinal section were observed with scattered distribution of 5-100 mm interspaces, which leave enough space for BMSCs adhesion and growth. Interestingly, at 14-day culture with HE staining, osteocytes within the scaffolds grew well with regular shape and integrate structure. RT-PCR results showed that expression levels of BMP2, TGF-b and COL-I, ALP, OPN were increased significantly and time-dependently. Collectively, all mentioned effects were more obvious in co-culture BMSCs with scaffolds than those with other components. Immunohistochemistry showed that positive OPN expression was detected at 7-day co-culturing BMSCs with scaffold, rather than other situations. These results suggest that composite scaffolds constructed with Si-CaP-fine particulate bone powder-alginate have a certain degree of biocompatibility and bioactivity to promote osteoblast-oriented BMSCs differentiation.

Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts.

BACKGROUND/AIMS: Promyelocytic leukemia (PML) protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα) to contribute to the initiation of acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) upregulates expression of TGF-ß1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-ß1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-ß1 protein expression. METHODS: Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-ß1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. RESULTS: ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-ß1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-ß1 expression, and collagen synthesis. CONCLUSION: These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts.

Protective Effects of Modeled Superoxide Dismutase Coordination Compound (MSODa) Against Ischemia/Reperfusion Injury in Rat Skeletal Muscle.

BACKGROUND/AIM: Ischemia/reperfusion (I/R) injury of skeletal muscles is common pathophysiology during surgeries and the superoxide dismutase (SOD) plays a critical role in this process. SOD-modeled coordination compound (MSODa) may simulate the protective effects as SOD. METHODS: Therefore, this study was designed to explore the protective effects and underlying mechanism of MSODa on malondialdehyde (MDA) and integrin-ß2 (CD11b/CD18) in plasma, myeloperoxidase (MPO) and intercellular cell adhesion molecule-1 (ICAM-1) in tissue, and morphological changes before and after I/R injury. The rat model of I/R in hind limb was established and randomly divided into sham, ischemia, I/R, I/R-treated with saline, SOD, and MSODa, respectively. RESULTS: These results showed that averaged values for MDA, MPO, CD11b/CD18, and ICAM-1 were significantly increased (P < 0.01 vs ischemia alone) in a time-dependent fashion along with marked tissue remodeling, such as abnormal arrangement of muscular fibers, interstitial edema, vasodilation with no-reflow, inflammatory cells adherent and infiltration, structural changes in mitochondrial, and decrease in glycogens as well. However, all parameter changes induced by I/R injury were reversed, at least partially, by MSODa and SOD treatments and intriguingly, the beneficial/protective effects of MSODa was superior to SOD with an early onset. CONCLUSION: This novel finding demonstrates that MSODa improves I/R injury of skeletal muscles due at least partially to inhibition of adherent molecule expression and reduction of oxygen free radical formation during I/R pathophysiological processes and this protective action of MSODa was superior to SOD, highlighting the bright future for MSODa in clinical management of tissue I/R injury.

Risk factors for extrauterine growth retardation at discharge in premature infants / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the incidence and risk factors for extrauterine growth retardation (EUGR) at discharge in premature infants.</p><p><b>METHODS</b>A retrospective analysis was performed on 596 premature infants who were admitted to the neonatal intensive care unit between 2006 and 2010. These subjects were classified into EUGR (n=217) and non-EUGR groups (n=379) based on the body weight at discharge. The risk factors for the occurrence of EUGR were studied by multivariate logistic regression analysis.</p><p><b>RESULTS</b>Based on the body weight, length, and head circumference, the incidence of EUGR at discharge was 36.4% (217 cases), 42.0% (250 cases), and 22.8% (136 cases), respectively. Low gestational age, low birth weight, intrauterine growth retardation (IUGR), delayed enteral feeding and complications of the respiratory system were identified as risk factors for EUGR (OR=6.508, 14.522, 5.101, 1.366, and 1.501, respectively).</p><p><b>CONCLUSIONS</b>The incidence of EUGR might be greatly decreased by strengthening the perinatal care, reducing the incidence of premature delivery and IUGR, undertaking early enteral feeding, and actively preventing postnatal complications.</p>

Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR).</p><p><b>METHODS</b>A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups.</p><p><b>RESULTS</b>The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well.</p><p><b>CONCLUSIONS</b>Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.</p>

Arsenic trioxide exerts a double effect on osteoblast growth in vitro.

Arsenic trioxide (ATO) is a promising antitumor agent used to treat acute promyelocytic leukemia (APL) and, recently solid tumor. The present study was designed to evaluate the effect of ATO proliferation of osteoblast that plays very important roles in maintaining the structure integrity and function of bone. Cell survives, apoptosis, collagen, and molecular targets were identified by multiple detecting techniques, including MTT assay, electron microscopy, collagen detecting kit, TUNEL kit, and western blot in hFOB1.19 human osteoblasts cell line. The results showed that low dose of ATO (0.25, 0.5, and 1µM) remarkably enhanced the viability of cultured osteoblasts in a concentration- and time-dependent manner. Intriguingly, a dual effect of high dose of ATO (5, 10, and 20µM) was also observed showing significant reduction in viability of culture osteoblasts at concentration- and time-dependent fashion. Moreover, low dose of ATO promoted secretion and synthesis of collagen, whereas high dose of ATO induced typical morphological characteristics of apoptosis in osteoblasts. Mechanically, western blot results demonstrated that low dose of ATO dramatically up-regulated TGF-ß1 protein and activated p-AKT proliferative signaling. And, high dose of ATO increased Bax/Bcl-2 ratio in a time-dependent fashion and activated caspase-3 apoptotic signaling. These results demonstrate at the first time that ATO exerts a double effect on osteoblast function depending upon the concentration and provide a clue to rationally use ATO for clinicians to pay more attention to protect bone from the adverse effects of therapeutic dose of ATO during tumor therapy.

A comparison of osteocyte bioactivity in fine particulate bone powder grafts vs larger bone grafts in a rat bone repair model.

The osteogenic potential for bone grafts is based on numbers and activities of cells that survive transplantation. In this study, we compared the bioactivity of osteocytes in 300-500 µm fine particulate bone powder grafts to 2 mm larger bone grafts in a rat radial defect model. Expression levels of bone morphogenetic protein-2 (BMP-2), transforming growth factor-beta 1 (TGF-ß1), alkaline phosphatase (ALP), and collagen I were semi-quantified by both immunohistochemistry and RT-PCR at days 1 and 4, as well as weeks 1, 2, 4, 6 and 10 post-transplantation. Within two weeks post-transplantation, more cells stained positively for BMP-2, TGF-ß1, ALP, and collagen I within the bone grafts and in the surrounding tissues in the group transplanted with the fine particulate bone powder grafts than in those with larger bone grafts (P<0.05). The mRNA levels of all four markers in the group transplanted with fine particulate bone powder graft peaked earlier and were expressed more highly than in the larger bone graft group, suggesting that fine particulate bone powder grafts provide more viable and active osteocytes to accelerate bone defect healing than larger bone grafts.

Gender differences in histamine-induced depolarization and inward currents in vagal ganglion neurons in rats.

Evidence has shown gender differences regarding the critical roles of histamine in the prevalence of asthma, anaphylaxis, and angina pectoris. Histamine depolarizes unmyelinated C-type neurons without any effects on myelinated A-type vagal ganglion neurons (VGNs) in male rats. However, little is known if VGNs from females react to histamine in a similar manner. Membrane depolarization and inward currents were tested in VGNs isolated from adult rats using a whole-cell patch technique. Results from males were consistent with the literature. Surprisingly, histamine-induced depolarization and inward currents were observed in both unmyelinated C-type and myelinated A- and Ah-type VGNs from female rats. In Ah-type neurons, responses to 1.0 µM histamine were stronger in intact females than in males and significantly reduced in ovariectomized (OVX) females. In C-type neurons, histamine-induced events were significantly smaller (pA/pF) in intact females compared with males and this histamine-induced activity was dramatically increased by OVX. Female A-types responded to histamine, which was further increased following ovariectomy. Histamine at 300 nM depolarized Ah-types in females, but not Ah-types in OVX females. In contrast, the sensitivity of A- and C-types to histamine was upregulated by OVX. These data demonstrate gender differences in VGN chemosensitivity to histamine for the first time. Myelinated Ah-types showed the highest sensitivity to histamine across female populations, which was changed by OVX. These novel findings improve the understanding of gender differences in the prevalence of asthma, anaphylaxis, and pain. Changes in sensitivity to histamine by OVX may explain alterations in the prevalence of certain pathophysiological conditions when women reach a postmenopausal age.

Subtype identification in acutely dissociated rat nodose ganglion neurons based on morphologic parameters.

Nodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced ganglion preparation have provided valuable insights into the electrophysiological properties of nodose ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated nodose ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat nodose ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.

Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral ganglion neurons following ovariectomy in adult rats.

Hyperpolarization-activated currents (Ih) mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate excitability of myelinated A- and Ah-type visceral ganglion neurons (VGN). Whether alterations in Ih underlie the previously reported reduction of excitability of myelinated Ah-type VGNs following ovariectomy (OVX) has remained unclear. Here we used the intact nodose ganglion preparation in conjunction with electrophysiological approaches to examine the role of Ih remodeling in altering Ah-type neuron excitability following ovariectomy in adult rats. Ah-type neurons were identified based on their afferent conduction velocity. Ah-type neurons in nodose ganglia from non-OVX rats exhibited a voltage 'sag' as well as 'rebound' action potentials immediately following hyperpolarizing current injections, which both were suppressed by the Ih blocker ZD7288. Repetitive spike activity induced afterhyperpolarizations lasting several hundreds of milliseconds (termed post-excitatory membrane hyperpolarizations, PEMHs), which were significantly reduced by ZD7288, suggesting that they resulted from transient deactivation of Ih during the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih activation. OVX-induced Ih remodeling was accompanied by a flattening of the stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were reduced by ∼30% in nodose ganglia from OVX rats compared with their non-OVX counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly restored Ih density and accelerated Ih activation in Ah-type cells. In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats.