Phillyrin promotes autophagosome formation in A53T-αSyn-induced Parkinson's disease model via modulation of REEP1.

BACKGROUND: The preservation of autophagosome formation presents a promising strategy for tackling neurological disorders, such as Parkinson's disease (PD). Mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) serve not only as a focal point linked to various neurological disorders but also play a crucial role in supporting the biogenesis of autophagosomes. PURPOSE: This investigation aimed to elucidate the neuroprotective properties of phillyrin against PD and its underlying mechanisms in promoting autophagosome formation. METHODS: ER and mitochondria co-localization was assessed via fluorescent staining. Annexin V-fluorescein isothiocyanate (FITC) fluorescence was employed to quantify accessible cardiolipin (CL) on mitochondrial surfaces. The levels of CL within the MAM fraction of SH-SY5Y cells were evaluated using a CL probe assay kit. Monodansylcadaverine staining was utilized to detect autophagosome formation in SH-SY5Y cells. In an A53T-alpha-synuclein (αSyn)-induced PD mouse model, the anti-PD properties of phillyrin were assessed using open field, pole climbing, and rotarod tests, as well as immunohistochemistry staining of TH+ neurons in the brain sections. RESULTS: In A53T-αSyn-treated SH-SY5Y cells, phillyrin facilitated autophagosome formation by suppressing CL externalization and restoring MAM integrity. Phillyrin enhanced the localization of receptor expression-enhancing protein 1 (REEP1) within MAM and mitochondria, bolstering MAM formation. Increased REEP1 levels in mitochondria, attributed to phillyrin, enhanced the interaction between REEP1 and NDPK-D, thereby reducing CL externalization. Furthermore, phillyrin exhibited a dose-dependent enhancement of motor function in mice, accompanied by an increase in the abundance of dopaminergic neurons within the substantia nigra. CONCLUSIONS: These findings illuminate phillyrin's ability to enhance MAM formation through upregulation of REEP1 expression within MAM, while concurrently attenuating CL externalization via the REEP1-NDPK-D interaction. These mechanisms bolster autophagosome biogenesis, offering resilience against A53T-αSyn-induced PD. Thus, our study advances the understanding of phillyrin's complex mechanisms and underscores its potential as a therapeutic approach for PD, opening new avenues in natural product pharmacology.

Ginsenoside Rg3 Restores Mitochondrial Cardiolipin Homeostasis via GRB2 to Prevent Parkinson's Disease.

Regulating cardiolipin to maintain mitochondrial homeostasis is a promising strategy for addressing Parkinson's disease (PD). Through a comprehensive screening and validation process involving multiple models, ginsenoside Rg3 (Rg3) as a compound capable of enhancing cardiolipin levels is identified. This augmentation in cardiolipin levels fosters mitochondrial homeostasis by bolstering mitochondrial unfolded protein response, promoting mitophagy, and enhancing mitochondrial oxidative phosphorylation. Consequently, this cascade enhances the survival of tyrosine hydroxylase positive (TH+) dopaminergic neurons, leading to an amelioration in motor performance within PD mouse models. Using limited proteolysis-small-molecule mapping combined with molecular docking analysis, it has confirmed Growth Factor Receptor-Bound Protein 2 (GRB2) as a molecular target for Rg3. Furthermore, these investigations reveal that Rg3 facilitates the interaction between GRB2 and TRKA (Neurotrophic Tyrosine Kinase, Receptor, Type 1), thus promotes EVI1 (Ecotropic Virus Integration Site 1 Protein Homolog) phosphorylation by ERK, subsequently increases CRLS1 (Cardiolipin Synthase 1) gene expression and boosts cardiolipin synthesis. The absence of GRB2 or CRLS1 significantly attenuates the beneficial effects of Rg3 on PD symptoms. Finally, Tenofovir Disoproxil Fumarate (TDF) that also promotes the binding between GRB2 and TRKA is further identified. The identified compounds, Rg3 and TDF, exhibit promising potential for the prevention of PD by bolstering cardiolipin expression and reinstating mitochondrial homeostasis.

Overexpression of SMS in the tumor microenvironment is associated with immunosuppression in hepatocellular carcinoma.

Disorders of polyamine metabolism may contribute to the development of hepatocellular carcinoma (HCC), but the precise mechanism remains unknown. This study reports that spermine synthase (SMS), an enzyme involved in polyamine biosynthesis, is overexpressed in HCC and not associated with hepatitis virus infection in HCC patients. The results of analyzing the clinical data of HCC patients showed that SMS level as a categorical dependent variable was related to clinicopathological features of poor prognosis. Furthermore, the Kaplan-Meier survival analysis and ROC curve indicated that increased SMS level is associated with poor survival rate in HCC and may be a potential biomarker to discriminate HCC tissues. However, SMS overexpression limited the therapeutic effect of immune checkpoint blockade (ICB), which seemed to be related to the immunosuppressive effect of the HCC immune microenvironment formed by higher mRNA transcript levels of immune checkpoints and higher infiltration levels of immunosuppressive cells. In samples with high and low SMS expression, functional enrichment analysis of the differentially expressed genes (DEGs) showed that SMS may be linked to the occurrence and development of HCC by affecting a variety of immune-related pathways, such as Intestinal immune network for IgA production, Fc gamma R-mediated phagocytosis, Antigen processing and presentation, Th1 and Th2 cell differentiation. Subsequently, analysis of the co-expression network of SMS in the liver hepatocellular carcinoma (LIHC) cohort revealed that SMS has a broad impact on multiple important immune- and metabolic-related processes in HCC. In summary, SMS is a promising biomarker to differentiate the prognosis, immune characteristics, and holds promise as a potential target for ICB therapy to improve HCC.

Ganoderic Acid A Promotes Amyloid-ß Clearance (In Vitro) and Ameliorates Cognitive Deficiency in Alzheimer's Disease (Mouse Model) through Autophagy Induced by Activating Axl.

Alzheimer's disease (AD) is thought to be caused by amyloid-ß (Aß) accumulation in the central nervous system due to deficient clearance. The aim of the present study was to investigate the effect of ganoderic acid A (GAA) on Aß clearance in microglia and its anti-AD activity. Aß degradation in BV2 microglial cells was determined using an intracellular Aß clearance assay. GAA stimulated autophagosome formation via the Axl receptor tyrosine kinase (Axl)/RAC/CDC42-activated kinase 1 (Pak1) pathway was determined by Western blot analyses, and fluorescence-labeled Aß42 was localized in lysosomes in confocal laser microscopy images. The in vivo anti-AD activity of GAA was evaluated by object recognition and Morris water maze (MWM) tests in an AD mouse model following intracerebroventricular injection of aggregated Aß42. The autophagy level in the hippocampus was assayed by immunohistochemical assessment against microtubule-associated proteins 1A/1B light-chain 3B (LC3B). Intracellular Aß42 levels were significantly reduced by GAA treatment in microglial cells. Additionally, GAA activated autophagy according to increased LC3B-II levels, with this increased autophagy stimulated by upregulating Axl and Pak1 phosphorylation. The effect of eliminating Aß by GAA through autophagy was reversed by R428, an Axl inhibitor, or IPA-3, a Pak1 inhibitor. Consistent with the cell-based assay, GAA ameliorated cognitive deficiency and reduced Aß42 levels in an AD mouse model. Furthermore, LC3B expression in the hippocampus was up-regulated by GAA treatment, with these GAA-specific effects abolished by R428. GAA promoted Aß clearance by enhancing autophagy via the Axl/Pak1 signaling pathway in microglial cells and ameliorated cognitive deficiency in an AD mouse model.

Administration of isoliquiritigenin prevents nonalcoholic fatty liver disease through a novel IQGAP2-CREB-SIRT1 axis.

Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.

Efecto de la lente fáquica ACR-128 sobre la tensión ocular y el endotelio corneal en las altas miopías / Effect of the ACR-128 phakic lens on ocular tension and the corneal endothelium in high myopia

RESUMEN Objetivo: Describir los efectos sobre la tensión ocular y el endotelio corneal con el implante de la lente fáquica ACR-128 para la corrección de la alta miopía. Métodos: Se realizó un estudio descriptivo, observacional, longitudinal y prospectivo en 60 ojos de 32 pacientes con miopía corregida con lente fáquica ACR-128. Se determinaron las complicaciones trans y posoperatorias, la presión intraocular, la densidad de las células endoteliales, el coeficiente de variabilidad y la hexagonalidad, así como la posición de la lente. El análisis estadístico se realizó con la Prueba T para datos pareados, con una significación del 95 por ciento. Resultados: La edad media fue de 27,41 ± 5,91 años y el 68,75 por ciento correspondió al sexo femenino. El equivalente esférico preoperatorio promedio fue de -11,54 ± 3,20 dioptrías. Resultó sin complicaciones transoperatorias el 100 por ciento; las posoperatorias inmediatas fueron de 93,33 por ciento y las mediatas y tardías del 95,00 por ciento. No hubo diferencias significativas entre el pre y el posoperatorio en la tensión ocular (p=0,2570); la densidad endotelial fue p= 0,0928; el coeficiente de variación p= 0,889 y la hexagonalidad (p= 0,0957). Conclusiones: El implante de la lente fáquica ACR-128 para la corrección de las altas miopías es un procedimiento seguro, al ofrecer escasas complicaciones y mínimos efectos en la tensión ocular y en el endotelio corneal(AU)

ABSTRACT Objective: Describe the effects of ACR-128 phakic lens implantation for high myopia correction on ocular tension and the corneal endothelium. Methods: An observational descriptive longitudinal prospective study was conducted of 60 eyes of 32 patients with myopia corrected with the ACR-128 phakic lens. Determination was made of intra- and postoperative complications, intraocular pressure, endothelial cell density, variability and hexagonality quotient, and lens position. Statistical analysis was based on the paired T-test with a significance level of 95 percent. Results: Mean age was 27.41 ± 5.91 years and 68.75 percent of the patients were female. Mean preoperative spherical equivalent was -11.54 ± 3.20 diopters. Complications were none in the intraoperative period, 93.33 percent in the immediate postoperative period and 95.00 percent mid- or long-term. No significant differences were found between the pre- and postoperative periods concerning ocular tension (p= 0.2570). Endothelial cell density was p= 0.0928, the variability quotient p= 0.889 and hexagonality p= 0.0957. Conclusions: ACR-128 phakic lens implantation for correction of high myopia is a safe procedure causing few complications and minimal effects on ocular tension and the corneal endothelium(AU)

Resultados visuales en la corrección de la alta miopía con implante de lente fáquica ACR-128 / Visual results of correction of high myopia with ACR-128 phakic lens implantation

RESUMEN Objetivo: Describir los resultados visuales en la corrección de la alta miopía con implante de lente fáquica ACR-128. Métodos: Se realizó un estudio descriptivo, observacional longitudinal y prospectivo en 60 ojos de 32 pacientes con miopía corregida con lente fáquica ACR-128. Se determinó el componente esférico esperado y observado, el cilindro queratométrico, las agudezas visuales sin corrección y mejor corregidas en el pre y en el posoperatorio y el astigmatismo inducido. El análisis estadístico se realizó con la Prueba T para datos pareados, con una significación del 95 por ciento. Resultados: La edad media fue 27,41 ± 5,91 años, el equivalente esférico preoperatorio -11,54 ± 3,20 dioptrías y el 68,75 por ciento eran femeninas. El componente esférico en dioptrías esperado (-0,53 ± 0,37) y observado (-0,42 ± 0,47) sin diferencias (p= 0,0742). Entre ± 1,00 el 91,67 por ciento y entre ± 0,50 el 70 por ciento. Ningún ojo quedó por encima de +0,50 dioptrías. El cilindro queratométrico en dioptrías, pre (1,44 ± 0,76) y posoperatorio (1,49 ± 0,84) sin astigmatismo inducido (p= 0,6377). El 100 por ciento tenía agudeza visual sin corrección preoperatoria ≤ 0,1 y posoperatoria ≥ 0,3. Después de la cirugía el 10 por ciento alcanzaba 1,0 y 71,6 por ciento ≥ 0,5. Solo el 28,33 por ciento tenía la unidad en el preoperatorio, y el 70 por ciento en el posoperatorio (98,33 por ciento ≥ 0,7). Conclusiones: El implante de lente fáquica ACR-128 proporciona corrección refractiva y predictibilidad favorables para el paciente, al reducir el componente esférico al deseado, no inducir astigmatismo y mejorar la agudeza visual, todo lo que se traduce en un adecuado resultado visual(AU)

ABSTRACT Objective: Describe the visual results of correction of high myopia with ACR-128 phakic lens implantation. Methods: An observational descriptive longitudinal prospective study was conducted of 60 eyes of 32 patients with myopia corrected with the ACR-128 phakic lens. Determination was made of the expected and observed spherical component, the keratometric cylinder, uncorrected and best corrected visual acuity in the pre- and postoperative periods, and induced astigmatism. Statistical analysis was based on the paired T-test with a significance level of 95 percent. Results: Mean age was 27.41 ± 5.91 years, preoperative spherical equivalent was -11.54 ± 3.20 diopters, and 68.75 percent of the patients were female. Spherical component in diopters expected (-0.53 ± 0.37) and observed (-0.42 ± 0.47) without differences (p= 0.0742). Between ± 1.00 diopters 91.67 percent and between ± 0.50 diopter 70 percent. No eye was above +0.50D. Keratometric cylinder in diopters, preoperative (1.44 ± 0.76) and postoperative (1.49 ± 0.84) without induced astigmatism (p=0.6377). In 100 percent visual acuity without correction ≤ 0.1 preoperative and ≥ 0.3 postoperative. After surgery 10 percent reached 1.0 and 71.6 percent ≥ 0.5. Only 28.33 percent had the unit corrected in the preoperative period and 70 percent in the postoperative period (98.33 percent ≥ 0.7). Conclusions: ACR-128 phakic lens implantation provides patients with favorable refractive correction and predictability. This is achieved by reducing the spherical component to desired values, not inducing astigmatism and improving visual acuity, all of which leads to an adequate visual result(AU)

Administration of methyl palmitate prevents non-alcoholic steatohepatitis (NASH) by induction of PPAR-α.

BACKGROUND AND AIMS: The lack of valid therapeutic approach that can ameliorate the manifestations of NASH is a barrier to therapeutic development. Therefore, we investigate the novel role of Methyl Palmitate (MP) in preventing NASH and the possible mechanism involved. METHODS: 50 Male C57BL/6 J mice were randomly divided into 5 groups (n = 10). The control group was fed control diet; model group was fed MCD diet; MP 1 group was fed MCD diet supplemented with MP (75 mg/kg/day); MP 2 group was fed MCD plus MP diet (150 mg/kg/day); and MP 3 group was fed MCD plus MP diet (300 mg/kg/day). Histological staining's, and commercially available kits for serum ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. RESULTS: Mice fed MCD diet developed NASH, which was markedly improved by MP in a dose-dependent manner. MP treatment improved hepatic content of TG, TC, MDA, SOD and GSH and serum levels of ALT and AST. In vivo studies showed that MP treatment activated PPARα expression, that in turns, promoted ß-oxidation protein and gene expressions, suppressed TNFα, MCP1, TGFß1 and Colla1 protein and gene expression levels, contributing to the prevention of NASH. CONCLUSIONS: Our results indicated that MP could successfully prevent NASH. This effect of MP was mediated through induction of PPARα pathway. This study provides a novel therapeutic target that plays pivotal role in the prevention of NASH.

Novel hepatoprotective role of Leonurine hydrochloride against experimental non-alcoholic steatohepatitis mediated via AMPK/SREBP1 signaling pathway.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and is characterized by steatosis, inflammation, and fibrosis. We aim to characterize the hepatoprotective effects of Leonurine hydrochloride (LH) and the possible pathway in a cell and rodent model of diet-induced steatohepatitis (NASH). METHODS: For in vitro studies, Palmitic acid (PA) and free fatty acid (FFA) induced HepG2 and HL7702 steatosis cell models were used. For in vivo studies, NASH was induced by feeding mice MCD diet. These mice received either placebo or LH at three different doses (50、100、200 mg/kg/day) for 6 weeks. Histological staining's, and commercially available kits for ALT and AST and hepatic contents of TG, TC, MDA, SOD, and GSH were used to assess NASH. Furthermore, relative liver protein and gene expression levels were determined by Western Blot and qPCR, respectively. RESULTS: After establishing NASH models, LH treatment improved lipid accumulation, hepatic contents of TG, TC, and expression levels of ALT and AST in dose-dependent manner. Also, LH improved MDA, SOD, and GSH expression levels. The results of RT-PCR and Western blotting showed that LH upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes expression level. CONCLUSIONS: Our data reveal the promising role of Leonurine hydrochloride in the prevention and treatment of NASH, in vitro and in vivo. This effect may be partially mediated by the AMPK/SREBP1 pathway. These findings provide a novel therapeutic target for the clinical treatment of NASH.

[In-Situ Analysis of Solid Steel Samples with Remote Double-Pulse Laser-Induced Breakdown Spectroscopy System].

In order to realize real-time, online monitoring of the component of steel and other metal smelting process, we designed a remote double-pulse laser-induced breakdown spectroscopy (LIBS) analysis system which can realize non-contact remote measurement and component analysis for long distance sample. The paper first tests the system on solid standard steel samples, which provides basis for online monitoring the component of molten steel. The experimental results show：laser focal spot is about 1mm in long distance; double-pulse ablation depth is deeper than single pulse's; the optimum delay of double-pulse is non-consistent in different distances; the enhancement effect of double- pulse in 3.1 m is better than that in 2.1 m，and the maximum enhancement is 5.19 of Ti(Ⅰ) 319.99 nm; the calibration curve of R2 is about 0.99, RSD being less than 5%, RMSE being less than 0.021%, LOD being less than 500 ppm for most elements in 2.1 m, which is better than that in 3.1 m.

[Quantitative analysis of alloy steel based on laser induced breakdown spectroscopy with partial least squares method].

In the present paper both the partial least squares (PLS) method and the calibration curve (CC) method are used to quantitatively analyze the laser induced breakdown spectroscopy data obtained from the standard alloy steel samples. Both the major and trace elements were quantitatively analyzed. By comparing the results of two different calibration methods some useful results were obtained: for major elements, the PLS method is better than the CC method in quantitative analysis; more importantly, for the trace elements, the CC method can not give the quantitative results due to the extremely weak characteristic spectral lines, but the PLS method still has a good ability of quantitative analysis. And the regression coefficient of PLS method is compared with the original spectral data with background interference to explain the advantage of the PLS method in the LIBS quantitative analysis. Results proved that the PLS method used in laser induced breakdown spectroscopy is suitable for quantitative analysis of trace elements such as C in the metallurgical industry.

Potential study perspectives on mechanisms and correlations between adiposity and malignancy.

Adiposity is a well-recognized risk factor of type 2 diabetes and cardiovascular disease, and recently there is increasing evidence that excess body weight is an avoidable cause of cancer, including gastrointestinal, endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal malignancies. The mechanisms whereby adiposity is associated with tumor development remains not well understood. There are some most studied hypothesized mechanisms such as, high levels of insulin and free levels of insulin-like growth factors, sex hormones, adipocytokines, and inflammatory cytokines, adiposity-induced hypoxia, and so on. The potential mechanisms and conclusions in adiposity associated with increased risk for developing malignancy, and the underlying cellular and molecular mechanisms will be studied very well in the near future.

[Detection and clinical significance of platelet derived growth factor-BB and microvessel density in clear cell renal cell carcinoma].

OBJECTIVE: To investigate the expression of platelet derived growth factor-BB (PDGF-BB) and microvessel density (MVD) marked with CD34 in clear cell renal cell carcinoma (CCRCC) and explore their relevance to clinicopathologic features and prognoses of patients. METHODS: Expressions of PDGF-BB and CD34 in the tissue samples of 100 clear cell renal cell carcinomas were detected by immunohistochemical (IHC) SP staining. The microvessel density (MVD) was counted using Weidner's method. For PDGF-BB assessment, the staining intensity and the proportion of positive tumor cells were analyzed. Staining was considered immunoreactive when brown granules were identified in the cytoplasm or nuclei of tumor cells. Staining intensity and the proportion of positively stained tumor cells in lesions was scored for further analysis. Statistical analysis was performed using the software SPSS 18.0. RESULTS: The MVD value marked by CD34 in the 100 cancer tissues was (105.49 ± 37.95) profiles/HPF. The median value of MVD in the entire cohort was used as the cut-off point for low MVD group (42 cases) and high MVD group (58 cases). The MVD of the low and high MVD groups was (75.12 ± 22.41) profiles/ HPF and (135.86 ± 22.91) profiles/HPF, respectively, with a statistically significant difference (P < 0.001). MVD was significantly correlated with the tumor T staging, histopathological grading and postoperative metastasis in CCRCC (P < 0.05, respectively). Among the 100 CCRCC cases, there were 38 cases with low PDGF-BB expression and 62 cases with high PDGF-BB expression, and the expression of PDGF-BB was significantly correlated with tumor diameter, T staging, histopathological grading and postoperative metastasis in the CCRCC (P < 0.05, respectively). Kaplan-Meier survival analysis showed that the cancer specific survival (CSS) in CCRCC patients with high expression of MVD and PDGF-BB was significantly better than that in the group with low MVD and low PDGF-BB expression (P < 0.001, respectively). Expression of PDGF-BB protein was positively associated with the MVD assessed by Spearman's correlation and factor analysis (r = 0.461, P < 0.001). CONCLUSION: Significantly increased MVD and PDGF-BB expression detected in CCRCC patients indicate a better tumor grading and staging, and a longer survival time.

[Dynamic changes of lung function in infant of different gestational ages].

OBJECTIVE: To explore the dynamic changes of lung function in infants born at different gestational ages without respiratory complications. METHODS: A total of 110 cases of hospitalized neonatal patients were retrospectively recruited and analyzed at Shenzhen Children's Hospital from July 2010 to August 2012. By gestational age they were divided into 3 groups of full term (37-40 weeks, n = 55, 29 males and 26 females) with an average birth weight (3.1 ± 0.3) kg, late preterm group (34- < 37 weeks, n = 30, 18 males and 12 females) with an average birth weight (2.1 ± 0.3) kg and early preterm (<34 weeks, n = 25, 16 males and 9 females )with an average birth weight (1.4 ± 0.3) kg. At Days 1, 14 and 28, lung function parameters of functional residual capacity (FRC) and lung clear index (LCI) were measured by multiple breath washouts with an ultrasonic flow meter and tidal breathing. One-way ANOVA was used for each index. RESULTS: Tidal expiratory flow 75% remaining tidal volume (TEF75), tidal expiratory flow 50% remaining tidal volume (TEF50) and tidal expiratory flow 25% remaining tidal volume (TEF25) gradually increased at Days 1, 14 and 28 in 3 groups. However respiratory rate (RR) gradually decreased. Compared with full term and late preterm, the early preterm infants had lower TEF75, TEF50 and TEF25, lower the ratios of time to peak expiratory flow and expiratory time (TPTEF/TE), lower ratios of volume to peak expiratory flow and expiratory volume (VPEF/VE) ((71 ± 21) and (66 ± 16) vs (55 ± 19)ml/s, (70 ± 20) and (62 ± 17) vs (51 ± 16)ml/s, (54 ± 17) and (51 ± 13) vs (38 ± 10)ml/s, 37% ± 8% and 34% ± 9% vs 29% ± 6%, 38% ± 6% and 33% ± 8% vs 28% ± 7%, F = 5.82, 8.74, 11.30, 7.72, 16.40, all P < 0.01), higher RR and LCI at Day 28((49 ± 6) and (51 ± 8) vs (56 ± 7)/min, 8.6 ± 2.7 and 8.9 ± 2.2 vs 10.8 ± 2.0,F = 10.09, 7.15, both P < 0.05). At a matched post-menstrual age of 40 weeks, compared with full term and late preterm, the early preterm group had lower TEF50, TEF25, TPTEF/TE, VPEF/VE ((65 ± 21) and (62 ± 12) vs (50 ± 17)ml/s,(51 ± 13) and (47 ± 10) vs (39 ± 10)ml/s, 36% ± 8% and 31% ± 7% vs 30% ± 6%, 37% ± 10% and 32% ± 8% vs 29% ± 6%,F = 4.41, 8.23, 9.08, 7.35, all P < 0.05). CONCLUSIONS: Lung function improves with the elongation of days. The parameters of lung function in early infants are worse than those in full and late-preterm counterparts. At a corrected gestational age of 40 weeks, early preterm infants fail to achieve catch-up growth in lung function. Dynamic monitoring of lung function in preterm infants of different gestational ages is of vital importance for gauging respiratory maturity and assessing lung development especially for preterm infants.

[Characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia].

OBJECTIVE: To explore the characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia(BPD). METHODS: There were 407 infants (278 males and 129 females) were recruited from Shenzhen Children' Hospital between January 2011 and October 2012.Among them 188 term infants (term group)and 113 preterm infants (non-BPD preterm group) were selected as controls. A total of 106 BPD infants from the observation group were divided into mild(n = 48), moderate (n = 42) and severe(n = 16) sub-groups according to the definition of BPD. Infants with diseases interfering with lung function, such as congenital heart disease, congenital diaphragmatic hernia, or thoracic wall deformities, were excluded. Lung function was tested at a postmenstrual age (PMA) of 44 weeks.q test, Dunnett C test and Spearman analysis were used for statistical analysis. RESULTS: The age range was 17-116 d, test weight range 1.83-7.00 kg and test height range 40.0-64.0 cm.In non-BPD preterm group, the respiratory rate (RR) was higher than that in term group ((50 ± 13) vs (44 ± 10) times/min,P < 0.01) ,while the tidal volume(TV), ratio of time to peak tidal expiratory time and expiratory time (Tpef/Te) and peak expiratory flow(TPEF) were all less than those in term group ((25 ± 9) vs (29 ± 7)ml,29% ± 9% vs 33% ± 8%, (59 ± 23) vs (65 ± 25)ml/s,all P < 0.05) .Neither functional residual capacity(FRC) nor lung clearance index (LCI) had significant statistical difference between two groups ((20 ± 5) vs (19 ± 5)ml/kg, 8.4 ± 2.8 vs 8.7 ± 3.4, all P > 0.05)) . In moderate and severe BPD groups, RR ((57 ± 9), (58 ± 10) times/min) were both higher than that in non-BPD group(both P < 0.05) while RR in mild group ((53 ± 13)times/min)had no statistical significant difference with non-BPD group (P > 0.05). The values of TV and LCI in mild, moderate and severe BPD groups have no statistical significance with non-BPD group (all P > 0.05). Except for mild BPD group(24% ± 13%, (18 ± 5)ml/kg), Tpef/Te and FRC in both moderate and severe groups (20% ± 9% and 18% ± 5%, (15 ± 3)and (15 ± 4)ml/kg)were less than those in non-BPD group(all P < 0.05). Only in severe BPD group ((85 ± 11)ml/s), TPEF was higher than that in non-BPD group(P < 0.05). Correlation analysis showed that, except for LCI, all of these parameters were significantly associated with the degree of BPD(all P < 0.05). CONCLUSIONS: For BPD and non-BPD preterm infants, there are various changes in respiratory rhythm, lung volume, ventilation inhomogeneity, ventilatory efficiency and small airway resistance. The increases of pulmonary elastic recoil and degree of major airway constriction are obvious in moderate and severe BPD infants.

[Dynamic change in respiratory mechanic dynamics and its clinical significance during mechanical ventilation in hyaline membrane disease of children].

OBJECTIVE: To explore the characteristics of changes in respiratory mechanic dynamics and clinical significance in hyaline membrane disease (HMD) under mechanical ventilation. METHODS: One hundred and twenty-six newborns with HMD undergoing mechanical ventilation were divided into two groups: complication group with 43 cases and no-complication group with 83 cases. The blood gases and indices of respiratory mechanic dynamics were monitored 2, 24, 48 and 72 hours after the first ventilation and before the first weaning from ventilation. RESULTS: Pulmonary compliance [(0.55+/-0.10) ml.cm H(2)O(-1).kg(-1), (0.43+/-0.10) ml.cm H(2)O(-1).kg(-1)] and minute volume [MV, (0.65+/-0.10) L/min, (0.62+/-0.30) L/min] were elevated compared with that after ventilation for 2-72 hours, however the oxygenation index [OI, (10.2+/-1.9)mm Hg vs. (13.6+/-4.3) mm Hg] significantly lower. The compliance and MV in no-complication group were higher than that in complication group 24 and 48 hours after ventilation. There were no differences in the airway resistance and lung inflation index between two groups. The pulmonary compliance was negatively correlated with OI (r=-0.208, P<0.01) and corrected with MV (r=0.218, P<0.01). In no-complication group, all cases ventilation was weaned successfully at once in all the patients,and their mean compliance and MV were (0.55+/-0.10) ml.cm H(2)O(-1).kg(-1) and (0.65+/-0.20) L/min respectively. However, in complication group, weaning failed 38 patients, their mean compliance and MV were (1.03+/-0.30) ml.cm H(2)O(-1).kg(-1) and (0. 33+/-0.30) L/min respectively. CONCLUSION: Respiratory mechanic dynamics monitoring is beneficial in evaluating the severity of hyaline membrane disease and complications, guiding mechanical ventilation management and weaning.

In vitro effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 cells.

AIM: To investigate the effects of chitosan nanoparticles on proliferation of human gastric carcinoma cell line MGC803 in vitro and the possible mechanisms involved. METHODS: Chitosan nanoparticles were characterized by particle size, zeta potential, and morphology. After treatment with various concentrations of chitosan nanoparticles (25, 50, 75, 100 microg/mL) at various time intervals, cell proliferation, ultrastructural changes, DNA fragmentation, mitochondrial membrane potential (MMP), cell cycle phase distribution and apoptotic peaks of MGC803 cells were analyzed by MTT assay, electron microscopy, DNA agarose gel electrophoresis, and flow cytometry. RESULTS: Chitosan nanoparticles exhibited a small particle size as 65 nm and a high surface charge as 52 mV. Chitosan nanoparticles markedly inhibited cell proliferation of MGC803 cells with an IC50 value of 5.3 microg/mL 48 h after treatment. After treatment with chitosan nanoparticles, the typical necrotic cell morphology was observed by electron microscopy, a typical DNA degradation associated with necrosis was determined by DNA agarose electrophoresis. Flow cytometry showed the loss of MMP and occurrence of apoptosis in chitosan nanoparticles-treated cells. CONCLUSION: Chitosan nanoparticles effectively inhibit the proliferation of human gastric carcinoma cell line MGC803 in vitro through multiple mechanisms, and may be a beneficial agent against human carcinoma.