The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice.

The purpose of the present study was to evaluate the protective effect of Palmatine on LPS-induced depressive like behavior and explore its potential mechanism. The mice were intragastrically treated with Fluoxetine or Palmatine once daily for 1 week. After the last drug administration, the mice were intraperitoneally challenged with LPS and suffered for Sucrose preference test, Tail suspension test, Forced swimming test and Open field test. The pro-inflammatory biomarkers were measured by ELISA, qPCR, WB and immunofluorescence. As a result, the administration of Palmatine effectively lessened depressive-like behavior. Palmatine could decrease the levels of pro-inflammatory cytokines TNF-α, IL-6, the expressions of CD68, iNOS mRNA, as well as increase the levels of anti-inflammatory cytokines IL-4, IL-10, the expressions of CD206, Arg1 mRNA, Ym1 mRNA both in LPS-induced mice and in LPS-induced BV2 cells. The beneficial effect of Palmatine might be attributed to the suppression of M1 microglia polarization and the promotion of M2 microglia polarization via PDE4B/KLF4 signaling. The similar results were observed in CUMS-induced depressive mice. The transfection with PDE4B SiRNA or KLF4 SiRNA indicated that PDE4B and KLF4 were both involved in the Palmatine-mediated microglia polarization. Molecular docking indicated that Palmatine could interact with PDE4B. In conclusion, this research demonstrated that Palmatine attenuated depressive like behavior by modulating microglia polarization via PDE4B/KLF4 signaling.

A 2-Year-Old Child with Late-Onset Pompe Disease: a Case Report.

BACKGROUND: Pompe disease is an inherited neuromuscular disease caused by a deficiency of lysosomal acid alphaglucosidase (GAA) leading to glycogen accumulation in muscle and motor neurons. METHODS: We retrospectively collected the clinical information on the case of a 2-year-old child admitted to the emergency department with respiratory failure and generalized hypotonia. RESULTS: Chest radiograph, cerebral and spinal magnetic resonance imaging, muscle biopsy, etc. were all examined. The 2-year-old child was later diagnosed with Pompe disease. Systematic assessment and effective sedation management were applied. CONCLUSIONS: Differential diagnosis, systematic assessment, and effective sedation management are important for Pompe disease patients.

Clinical manifestations of severe enterovirus 71 infection and early assessment in a Southern China population.

BACKGROUND: Enterovirus 71 (EV-A71) shows a potential of rapid death, but the natural history of the infection is poorly known. This study aimed to examine the natural history of EV-A71 infection. METHODS: This was a prospective longitudinal observational study performed between January 1st and October 31st, 2012, at three hospitals in Guangdong, China. Subjects with positive EV-A71 RNA laboratory test results were included. Disease progression was documented with MRI, autopsies, and follow-up. Symptoms/signs with potential association with risk of death were analyzed. RESULTS: Among the 288 patients, neurologic symptoms and signs were observed (emotional movement disorders, dyskinesia, involuntary movements, autonomic dysfunction, and disturbance of consciousness). Some of them occurred as initial symptoms. Myoclonic jerks/tremors were observed among >50% of the patients; nearly 40% of patients presented fatigue and 25% were with vomiting. Twenty-eight patients (9.7%) presented poor peripheral perfusion within 53.4 ± 26.1 h; 23 patients (8.0%) presented pulmonary edema and/or hemorrhage within 62.9 ± 28.6 h. Seventeen (5.9%) patients were in a coma. Seven (2.4%) patients died within 62.9 ± 28.6 h. Seventy-seven survivors underwent head and spinal cord MRI and 37.7% (29/77) showed abnormalities. Two fatal cases showed neuronal necrosis, softening, perivascular cuffing, colloid, and neuronophagia phenomenon in the brainstem. CONCLUSIONS: Patients with EV-A71 infection showed high complexity of symptoms and onset timing. Death risk may be indicated by autokinetic eyeball, eyeball ataxia, severe coma, respiratory rhythm abnormality, absent pharyngeal reflex, ultrahyperpyrexia, excessive tachycardia, pulmonary edema and/or hemorrhage, and refractory shock and ataxic respiration. Early assessment of these symptoms/signs is important for proper management.

Preparation of cellulose-based porous adsorption materials derived from corn straw for wastewater purification.

Various methods have been used to cope with heavy metal ion contamination in wastewater, which caused serious hazards to ecological and human health. Adsorption is one of the most frequent, economical and effective methods for removing these contaminants. Herein, a porous and amino-rich cellulose-based composite adsorbent (PEI-PCS) with anisotropic property was successfully prepared by covalently cross-linking polyethyleneimine on delignified corn straw. Combined with the porosity of straw substrate and the chelating ability of amino group to metal ions, the as-prepared PEI-PCS exhibited universality (various metal ions), rapid adsorption behavior (within 180 min achieve adsorption equilibrium), high adsorption capacity (85.47 mg g-1 for Cu(II)), and good durability (70 % of adsorption efficiency after 5 cycles). In addition, the adsorption process was conformed to pseudo-second-order dynamics and the Langmuir isotherm models. Lastly, the adsorption mechanism was also elucidated. This study provides a sustainable pathway for the manufacture of efficient biomass-based adsorbents and confirms that functionalized corn straw is a promising material for the treatment of heavy metal ions.

Magnetic, self-heating and superhydrophobic sponge for solar-driven high-viscosity oil-water separation.

In this work, a novel oil-adsorption sponge with superhydrophobicity was fabricated using polymer-assisted electroless deposition and dip-coating techniques for depositing a rough polydopamine layer, magnetic particles, and low surface energy polydimethylsiloxane onto the surface of a sponge skeleton. The as-prepared superhydrophobic sponge (WCA > 150° and SA < 5°) exhibited rapid adsorption behavior, large adsorption capacity (up to 50.6 times its own dry weight or above 90% of its own volume), excellent durability (above 80% of the adsorption capacity after 80 recycles), and a self-cleaning property owing to sufficient open-cell pores and superelasticity provided by the melamine-formaldehyde host as well as the hierarchical roughness and convenient magnetic recovery enabled by the polymer-assisted electroless deposition approach. The pump-, gravity-, and solar-driven oil-water separation devices based on the fabricated cubic composites were also demonstrated, particularly the separation of high-viscosity oil-water mixtures via the solar-driven mode, demonstrating the broad prospects of such modified sponges in actual applications. This study provides a new avenue for rationally designing novel oil adsorption and separation materials.

Less is More: A Novel Feature Extraction Method for Heart Sound Classification via Fractal Transformation.

Cardiovascular diseases (CVDs) are the leading cause of death globally. Heart sound signal analysis plays an important role in clinical detection and physical examination of CVDs. In recent years, auxiliary diagnosis technology of CVDs based on the detection of heart sound signals has become a research hotspot. The detection of abnormal heart sounds can provide important clinical information to help doctors diagnose and treat heart disease. We propose a new set of fractal features - fractal dimension (FD) - as the representation for classification and a Support Vector Machine (SVM) as the classification model. The whole process of the method includes cutting heart sounds, feature extraction, and classification of abnormal heart sounds. We compare the classification results of the heart sound waveform (time domain) and the spectrum (frequency domain) based on fractal features. Finally, according to the better classification results, we choose the fractal features that are most conducive for classification to obtain better classification performance. The features we propose outperform the widely used features significantly (p < .05 by one-tailed z-test) with a much lower dimension.Clinical relevance-The heart sound classification model based on fractal provides a new time-frequency analysis method for heart sound signals. A new effective mechanism is proposed to explore the relationship between the heart sound acoustic properties and the pathology of CVDs. As a non-invasive diagnostic method, this work could supply an idea for the preliminary screening of cardiac abnormalities through heart sounds.

pH-Dependent intestine-targeted delivery potency of the O-carboxymethyl chitosan - gum Arabic coacervates.

Bovine serum albumin (BSA)-loaded microcapsules were prepared at pH 3.0, 4.5, and 6.0 through O-carboxymethyl (O-CMC) - gum Arabic (GA) coacervation followed by genipin crosslinking to explore the effects of coacervation acidity on the intestine-targeted delivery potency of resultant microcapsules. Confocal laser scanning microscope observation revealed that microcapsules with the multilayer structure were successfully prepared. As the coacervation pH rose from 3.0 to 6.0, the amount of O-CMC deposited on the microcapsule surface and the particle size increased accordingly. Swelling and BSA release results indicated that coacervation at higher pH conferred greater stability against simulated gastric fluid and better intestine-targeted delivery potency to the microcapsules. Circular dichroism analysis demonstrated that the structural integrity of entrapped BSA was well maintained during microencapsulation and incubation in simulated gastrointestinal fluids. Hence, genipin-crosslinked O-CMC - GA coacervates could be used to deliver nutraceuticals to the intestine and its delivery performance could be tailored by varying the coacervation pH.

[Expression of fibroblast growth factor receptor-4 in fetal kidneys and pathological kidneys of children].

OBJECTIVE: To investigate the expression of fibroblast growth factor receptor-4 (FGFR4) in fetal kidneys and pathological kidneys of children in order to show the roles of fibroblast growth factor (FGF) and FGFR4 in the development of fetal kidneys and renal diseases. METHODS: The expression of FGFR4 was detected by immumohistochemistry in the normal fetal kidney at 8 to 34 weeks of gestation age (n=18) and 82 children with renal disease, including 28 cases of primary nephrotic syndrome (PNS), 12 acute glomerulonephritis (AGN), 20 Henoch-Schoenlein purpura nephritis (HSPN), and 22 isolated hematuria (IHU). A correlation analysis between renal pathological scores and FGFR4 expression was performed. RESULTS: 1) FGFR4 expression was weakly in renal vesicle and primitive tubules of S-shaped body, irrecognizable in urteric bud and podocytes of C-stage, and negative in mesenchyme and condensing mesenchyme. The immunostaining of FGFR4 was intense in distal tubules and collecting ducts, but was negative in mature glomeruli and proximal tubules. 2) FGFR4 was expressed in all pathological sections of various renal diseases. FGFR4 expression was intense in tubules but weak in glomeruli. It was principally expressed in distal tubules and partially in proximal tubules. The tubules with very strong expressions of FGFR4 presented abnormal structures including dilation and atrophy, especially in proximal tubules. 3) There were no significant differences in the FGFR4 expression in various parts of the kidney among various renal diseases. There were also no significant differences in the FGFR4 expression in renal tubules among the four different pathological types of renal diseases: focal segmental glomerularsclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis (MsPGN), and minimal change disease (MCD). The FGFR4 expression in podocytes in the MPGN group was noticeably higher than that of the other pathological type group (P < 0.05). 4) The FGFR4 expression in proximal tubules positively correlated with the pathological score of tubules (r=0.463682, P < 0.05) but negatively correlated with the pathological score of glomeruli (r=- 0.0277, P < 0.05). The FGFR4 expression in both distal tubules and podocytes negatively correlated with the pathological score of tubules or glomeruli (P < 0.05). CONCLUSIONS: The development of fetal kidneys in the early period could not be regulated by FGF-FGFR4 signal which takes part in the development of renal tubules and collecting duct in the mature period. The FGFR4 expression is related with renal pathology in children with PNS, AGN, HSPN or IHU. A proper increase of FGFR4 expression is beneficial to the recovery of renal tissues but an over-expression relates to a severe renal damage.

MiR-483-5p promotes IGF-II transcription and is associated with poor prognosis of hepatocellular carcinoma.

The human insulin-like growth factor-II (IGF-II) gene transcribes four mRNAs (P1 mRNA-P4 mRNA), and P3 mRNA overexpression contributes to hepatocarcinogenesis. IGF-II-derived miR-483-5p is implicated in the development of cancers. Here, we investigated the involvement of miR-483-5p in P3 mRNA overexpression regulation and its role in hepatocellular carcinoma. Our results showed that miR-483-5p up-regulated P3 mRNA transcription by targeting the 5'-untranslated region (5'UTR) of P3 mRNA in hepatocellular carcinoma. The mechanism was involved in recruiting of an argonaute 1(Ago1)-argonaute 2 (Ago2) complex to the P3 mRNA 5'UTR and the P3 promoter of IGF-II gene by miR-483-5p, accompanied by increased enrichment of RNA polymerase II and activating histone marks histone 3 lysine 4 trimethylation (H3K4me3), histone 3 lysine 27 acetylation (H3K27ac), and histone 4 lysine 5/8/12/16 acetylation (H4Kac) at the P3 promoter. High miR-483-5p expression was an independent predictor for shorter survival of HCC patients. The findings suggest that miR-483-5p promotes P3 mRNA transcription by recruiting the Ago1-Ago2 complex to the P3 mRNA 5'UTR and is associated with poor prognosis of HCC. Our results display a potential new model for miRNAs to up-regulate gene expression.

The mortality of patients in a pediatric emergency department at a tertiary medical center in China: An observational study.

BACKGROUND: The quality of treatment for critically ill children varies widely at different hospitals. This study aimed to analyze the characteristics of mortality in a pediatric emergency department (PED) at a tertiary children's hospital in Guangzhou, China and to investigate the risk factors associated with the mortality. METHODS: The mortality of pediatric patients at the hospital from 2011 to 2013 was retrospectively analyzed using descriptive statistics. RESULTS: Altogether 466 919 patients visited the PED during the period and 43 925 of them were admitted for further observation. In 230 deaths, the ratio of boys to girls was 1.4:1, and their age ranged from 2 hours to 16 years (median, 5 months). The time from admission to death ranged from 0 to 216 hours (median, 1.5 hours). There were 92 (40%) patients who died within 24 hours after admission and 104 (45.2%) patients who died on arrival. The prominent causes of the deaths were respiratory diseases, neuromuscular disorders, cardiovascular diseases, and sepsis, most of which were ascribed to severe infection. Sixty-five deaths were associated with more than one concomitant problem. The top concomitant problems were congenital malformation, low gestational age, and severe birth asphyxia. CONCLUSIONS: In our center, 40% of the patients in the PED died of fatal acute diseases, and pneumonia was the first leading cause of the deaths. Almost half of the deaths occurred on arrival and the rest were due to end-stage malignant diseases. This study emphasized the importance of prevention of birth deficits by reducing deaths in infants and children.

[Primary abdominal aortoduodenal fistula: a case report].

OBJECTIVE: Abdominal aortoenteric fistula (AAEF) is a rare but life-threatening complication of abdominal aortic aneurysms, and is also an uncommon cause of gastrointestinal hemorrhage. We report a case of primary abdominal aortoduodenal fistula in a 74-year-old male patient, whose main clinical manifestations were abdominal pain, hematochezia, and hematemesis. Colonoscopy, abdominal enhanced computed tomography (CT) and three-dimensional reconstruction angiography confirmed the diagnosis. The patient recovered well after emergent surgical management.

A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis. Macroautophagy is a highly conserved cellular process that digests dysfunctional macromolecules and damaged organelles. Accumulating evidence indicates that macroautophagy (hereafter referred to as autophagy) is involved in alpha-synuclein degradation. Dysregulation of autophagy has been observed in the brain tissues from PD patients and animal models. We hypothesized that change expression levels of autophagy-related genes (ATG), including ATG5, may contribute to PD. In this study, we genetically and functionally analyzed the ATG5 gene promoter in groups of sporadic PD patients and ethnic-matched healthy controls. A novel heterozygous variant, 106774459T>A, was identified in one female patient, but in none of controls, which significantly enhanced transcriptional activities of the ATG5 gene promoter. Furthermore, ATG5 gene expression level in the PD patient was significantly elevated than that in controls. Four novel heterozygous variants, 106774423C>A, 106774418C>A, 106774382C>A and 106774206G>A, were only found in controls. The variant, 106774464C>T, and SNP-106774030A>G (rs510432) were found in PD patients and controls with similar frequencies. Collectively, the variant identified in PD patient may change ATG5 protein levels and alter autophagy activities, contributing to PD onset as a risk factor.

[Role of pulmonary stem cells labeled with bromodeoxyuridine and telomerase reverse transcriptase in hyperoxic lung injury in neonatal rats].

OBJECTIVE: To investigate characteristics of pulmonary stem cells labeled with bromodeoxyuridine (Brdu) and telomerase reverse transcriptase (TERT) in lung tissue, as well as the effects of proliferation and differentiation of the stem cells on lung development and repair of pulmonary injury. METHODS: A model of hyperoxia in neonatal rats was made by exposing the rats to 95% O2 for 7 d. Before sacrificing the rats, Brdu was injected through peritoneum, and immune staining positive cells were analyzed after the rats were sacrificed. TERT positive cells were stained by an immunohistochemical method. At the same time, the double staining for surfactant protein C (SPC) and Brdu or SPC and TERT were performed. Lung histologic study was done on HE stained tissue slices. RESULTS: (1) The lung with hyperoxic injury had thinner walls of alveoli, simple alveolar structure, fewer and larger alveoli, expanded and shrunken alveoli, and there were many fell-off alveolar epithelial cells in the alveolar cavities as well. (2) The cells positively stained with Brdu located in septa, mucosa and submucosa of various bronchi, scattering in epithelium of bronchi, and the number of positive cells was low, having a large nucleus. The TERT-positive cells were apparent in the septa and alveolar walls of peripheral lung tissue, characterized by uneven distribution in the lung lobes, the number of positive cells was less than that of Brdu-positive cells [integral of expression (1.61 +/- 0.83) vs. (0.62 +/- 0.55), P < 0.05]. The number of Brdu- and TERT-positive cells had no significant difference in hyperoxic rats compared to that in controls [integral of expression (1.43 +/- 0.85) vs. (1.61 +/- 0.83); (0.62 +/- 0.55) vs. (0.83 +/- 0.84), P > 0.05]. (3) After double staining, a few positive cells were found in double-stained tissues with SPC and Brdu or TERT. (4) The cells positively stained with SPC antibody had different size. The percentage of positive cells was not significantly different between the hyperoxia group (80.3%) and control group (78.6%). The Brdu positive staining located in nucleus of cells that had larger size than the cells not stained, round nucleus with intense staining (seldom, pole-shaped) and the number of such cells was less than that of the SPC positive cells. The percentage of positive cells was not significantly different between the hyperoxia group (28.5%) and control group (21.4%). (5) The TERT staining located in nucleus of cell that had smaller size than the cells not stained, various nuclear shape, including round intensively stained, round slightly stained, pole-shaped and divided shape. The percentage of positive cells was not significantly different between the hyperoxia group (2.3%) and control group (1.5%). CONCLUSIONS: (1) Brdu and TERT, as markers of stem cells having different capability of differentiation, possess special characteristics, respectively. The cells with Brdu could be transit amplifying cell (TAC) which retains characteristics of stem cells originated from differentiated stem cells, while, the cells stained with TERT especially reflects the characteristics of stem cells. (2) The proliferation and differentiation of pulmonary stem cells during hypoxic lung injury are limited and may be related with arrest of alveolization.

[Effect of lethal hyperoxia on pulmonary development and lung injury in neonatal rats].

OBJECTIVE: To study the effect of oxygen at lethal levels (95%) on pulmonary development and lung injury in neonatal rats and establish rat models of bronchopulmonary dysplasia. METHODS: Three-day-old and adult SD rats were assigned to experimental or control groups and subjected to 95% O(2) exposure and room air for 7 days. Body weight and length of the rats were recorded, and histological study of the lung tissue and radical alveoli count (RAC) were carried out. RESULTS: The mortality rate of the neonatal and adult rats was 12.5% and 35.2% in hyperoxia group, respectively. The newborn rats in hyperoxic group had lower body weight (18.02-/+0.68 vs 13.24-/+0.59 g) and length (8.83-/+0.25 vs 6.76-/+0.51 cm) than those in the control group (P<0.05), with also lower RAC (9.50-/+1.05 vs 13.00-/+1.79, P<0.05); RAC of the adult rats with hyperoxic exposure (12.67-/+2.25) was higher that of exposed neonatal rats, but not significantly different from that of the adult or neonatal rats in the control group (P>0.05). Structure configuration of the rats on the first 10 days of life resembled that of adulthood. The lung of hyperoxic neonatal rats showed thinner walls of alveoli, simple alveolar structure, fewer and larger alveoli, expanded and shrunk alveoli, while the lung of the adult rats displayed thicker septa, smaller space of alveoli, and cells in the space of the alveoli. CONCLUSION: Exposure of neonatal rats to 95% O(2) may result in mild pulmonary inflammation in addition to growth impediment and impaired lung development, which shares morphologic similarities to human bronchopulmonary dysplasia.

Role of PAX2 gene polymorphisms in Henoch-Schonlein purpura nephritis.

OBJECTIVE: To investigate the distribution of polymorphisms in the PAX2 gene in children with Henoch-Schonlein purpura with and without nephritis (HSPN and HSP, respectively), with particular attention to the relationship between PAX2 gene polymorphisms and the development of kidney pathology. METHODS: Genomic DNA was extracted from the peripheral leukocytes of 39 HSPN patients, 23 HSP patients without nephritis and 100 normal children, and three known single nucleotide polymorphisms (SNP), including 1410C>T, 1521A>C and 1544C>T in exon 8 and exon 9 of the PAX2 gene were studied as the candidate polymorphisms. The above two exons were amplified, the polymerase chain reaction (PCR) products were detected by denatured high-pressure liquid chromatography and direct DNA sequencing was performed for sequences with abnormal elution peaks. RESULTS: In all samples confirmed by direct sequencing, we identified two SNP, which present as complete linkage haplotype 1410C>T + 1521A>C, in exon 8. We did not identify any SNP in exon 9. The frequency of the PAX2 heterozygous genotype 1410CT/1521AC in the HSPN group (28.20%) was significantly higher than in the HSP without HSPN group (4.35%) or in the control group (12.00%) (P < 0.05). The odds ratio (OR) values for HSPN and HSP were 6.05 and 2.62, respectively, and the 95% confidence intervals (CI) were 1.23-29.78 and 1.09-6.30, respectively. However, no differences in the frequency distribution was found between the HSP without nephritis and normal groups. Furthermore, there was no significant correlation between the polymorphism and clinical manifestation or kidney pathology in the HSPN group (P > 0.05). CONCLUSION: The 1410CT/1521AC PAX2 genotype does not increase susceptibility for HSP, but is likely to increase the susceptibility of kidney involvement, resulting in a HSPN diagnosis.