Relationship between plasma SP-A expression level and disease stage in silicosis patients / 上海预防医学

ObjectiveTo investigate the relationship between plasma surfactant protein⁃A （SP⁃A） expression level and silicosis progression， and to provide early evidence for exploring whether SP⁃A can be used as a biomarker for clinical monitoring of silicosis disease progression. MethodsWe recruited 187 silicosis patients in Guangdong Province hospital for occupational disease prevention and treatment between November， 2019 and November，2020. Their peripheral venous blood samples were collected for the plasma isolation. The level of pulmonary SP⁃A was detected by enzyme-linked immunosorbent assay. ResultsThere was a statistically significant difference in the level of SP⁃A among the silicosis groups （P<0.05）， and the plasma SP-A level of the silicosis patients in stage Ⅲ was higher than that in stage Ⅰ and stage Ⅱ （P<0.05）. Smoking had effect on plasma SP⁃A levels， Age， working years and drinking had no effect on plasma SP⁃A levels. ConclusionThe expression level of SP⁃A in the plasma of silicosis patients is increased， which has a certain correlation with the disease stage， and plays a certain early warning role in the occurrence and development of silicosis， and may be a potential biomarker for the diagnosis and prognosis of silicosis.

The role of surfactant associated protein-A in silicosis / 中国职业医学

Objective: To investigate the role of surfactant associated protein-A (SP-A) in the development and progression of silicosis, and its mechanism. Methods: Homozygous and heterozygous mice of SP-A knockout of specific pathogen free (SPF) grade were selected for mating, and mice with SP-A-/- genotype were selected for subsequent experiments. SP-A wild-type (SP-A+/+) and SP-A-/- mice were divided into SP-A+/+ control group, SP-A-/- control group, SP-A+/+ silicosis group and SP-A-/- silicosis group with six mice in each group by random number table method. Mice in both silicosis groups were given 20.0 μL 250 g/L silica suspension by tracheal exposure, and mice in both control groups were injected with 0.9% sodium chloride solution at the same volume. On the 28th day after modeling, mice were sacrificed. Lung tissues were used for lung histopathology examination. The apoptosis of alveolar type Ⅱ epithelial cells of mice was detected by TUNEL method. The mRNA expression of B-lymphoblastoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cysteinyl aspartate specific proteinase (Caspase)-3 and Caspase-9 in lung tissues of mice was detected by quantitative real-time polymerase chain reaction. Results: The histopathological result of mice showed that thickened alveolar septum, scattered silicon nodule and collagen fiber formation were observed in the mice lungs of SP-A+/+ silicosis group, and a large number of inflammatory cells were observed in silicosis nodule, after exposure to silica dust. SP-A-/- silicosis group resulted in a more severe pulmonary inflammation and interstitial fibrosis compared to SP-A+/+ silicosis group. The apoptosis of alveolar type Ⅱ epithelial cells and the mRNA relative expression levels of Bax, Caspase-3 and Caspase-9 in lung tissues of mice in each silicosis groups were increased compared with their control groups (all P<0.05). The above four indexes of mice in SP-A-/- silicosis group were higher than those in SP-A+/+ silicosis group (all P<0.05). There was no significant difference in the expression of Bcl-2 mRNA in lung tissues of these four groups (P>0.05). Conclusion: Knockout of SP-A can aggravate inflammation and pulmonary fibrosis in silicosis model mice, and promote apoptosis of alveolar type Ⅱ epithelial cells. The mechanism may be related to the Bcl-2/Bax/Caspase-3 signaling pathway which affects the apoptosis of mitochondrial pathway.

FOXA1 in prostate cancer / 亚洲男科学杂志(英文版)

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.

The efficacy comparison of sakubatril valsartan and valsartan in the treatment of patients with chronic cardiac insufficiency and the influence on zinc finger protein A20 and nuclear factor-κB in peripheral blood mononuclear cells / 中国医师进修杂志

Objective:To compare the efficacy of sakubatril valsartan and valsartan in the treatment of patients with chronic cardiac insufficiency and the influence on zinc finger protein A20 and nuclear factor-κB (NF-κB) in peripheral bloodmononuclear cells (PBMCs).Methods:Ninety-senven patients with chronic cardiac insufficiency admitted to the Affiliated Hospital of Jining Medical College from February 2019 to January 2020 were continuously selected and randomly divided into the control group (48 cases) and the observation group (49 cases). Both groups received routine anti-heart failure according to the guidelines. The control group added with valsartan and the observation group added with sakubatril valsartan treatment. Before the treatment and after 3 months of treatment, the changes of cardiac function indexes and the changes of inflammatory markers such as hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP-9), and N-terminal pro B-type natriuretic peptide (NT-proBNP) were compared. PBMCs was extracted to detect zinc finger protein A20 and NF-κB levels. The incidence of adverse reactions in the two groups was recorded, and the relationship between zinc finger proteins A20, NF-κB and the myocardial injury marker NT-proBNP were analyzed.Results:After 3 months of treatment, the changes of cardiac function indexes in the observation group were better than those in the control group and the levels of hs-CRP, TNF-α, MMP-9, NT-proBNP in the observation group were lower than those in the control group: (1.96 ± 0.57) mg/L vs. (2.87 ± 0.79) mg/L, (7.11 ± 1.46) μg/L vs. (8.24 ± 1.57) μg/L, (110.14 ± 10.63) μg/L vs. (129.52 ± 17.96) μg/L, (716.91 ± 105.78) ng/L vs. (965.25 ± 97.41) ng/L, there were statistical differences ( P<0.05). After 3 months of treatment, the levels of finger protein A20, NF-κB in the observation group were lower than those in the control group: (3.57 ± 1.13) % vs. (4.41 ± 1.32) %, (29.87 ± 6.58) ng/L vs. (35.71 ± 10.02) ng/L, there were statistical differences ( P<0.05). Finger protein A20 and NF-κB in patients with chronic cardiac insufficiency were positively correlated with NT-proBNP ( r = 0.487, 0.738, P<0.01). Conclusions:On the basis of conventional treatment, compared with valsartan, the addition of sakubatril valsartan, can improve the cardiac function of patients with chronic cardiac insufficiency, reduce the body′s inflammatory response, reduce the expression of myocardial injury marker NT-proBNP, inhibit the activation of PBMCs NF-κB, and reduce the level offinger protein A20.

Effects of dexmedetomidine on nuclear factor-KB inhibitor protein kinase/ nuclear factor-KB inhibitor protein a/nuclear factor-KB pathway and cognitive dysfunction in rats with post-traumatic stress disorder / 解剖学报

Objective To investigate the effects of dexmedetomidine (DEX) on the nuclear factor-KB inhibitor protein kinase (IKK)/nuclear factor-KB inhibitor protein a (IKB(X)/nuclear factor-KB (N F - K B) pathway and cognitive dysfunction in rats with post-traumatic stress disorder (PTSD) . Methods Rats were randomly divided into control group, model group, positive group and DEX group. Except for the control group, the PTSD model was constructed by single prolonged stress method (SPS), and the corresponding drugs were given after the completion the model. Open field test and Morris water maze method were used to detect the autonomous activity, learning and memory ability of rats; HE staining was used to observe the morphological characteristics of cerebral cortex and hippocampus; ELISA and Western blotting were used to detect the contents of interleukin (IL)-1(3, IL-6, tumor necrosis factor a (TNF-a) and the expression levels of IKK, IKB(X, purinergic ligand-gated ion channel 7 receptor (P2X7R), leucine-rich repeat domain protein 3(NALP3) in hippocampus; the NF-KB activity was assessed by electrophoretic mobility shift assay (EMSA). Results Compared with the control group, the cerebral cortex and hippocampal CA1 region of model group were in structural disorders, nuclear pyysis and other pathological changes happend, learning and memory ability of rats decreased (P < 0. 05), contents of IL-lp, IL-6 and TNF-a, expression levels of IKK, IKB(X, P2X7R and NALP3, NF-KB activity in hippocampus increased (P<0. 05); Compared with the model group, the pathological phenomena in cerebral cortex and hippocampal CA1 area of rats in positive group and DEX group were in alleviated, and the changes of the above indexes were opposite to those of model group (P<0. 05) . Conclusion DEX can significantly improve the autonomous activity ability and learning and memory ability in PTSD rats, reduce inflammatory reaction in hippocampus and improve cognitive dysfunction, which may be related to the down-regulation of IKK/TKBQ!/NF-KB pathway.

Immunolocalización de s100a4 y α-sma en tejidos gingivales de pacientes con hipertrofia gingival por tratamiento ortodóntico: estudio preliminar / Immunolocalization of s100a4 and α-sma in gingival tissues of patients with gingival hypertrophy due to orthodontic treatment: preliminary study

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics.GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed.The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics. GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed. The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

A case report of staphylococcal protein A immunoadsorption therapy for refractory myasthenia gravis / 中华神经科杂志

Staphylococcal protein A (SPA) has a high affinity for human immunoglobulin, and SPA immunoadsorption can specifically reduce the titer of autoantibodies and quickly relieve the clinical symptoms of myasthenia gravis (MG). Recent studies have suggested that immunoadsorption has better clinical efficacy and a lower incidence of adverse reactions than plasma exchange. A case of refractory MG with poor response to corticosteroids, intravenous immunoglobulins and immunosuppressive therapy was reported. The patient had low immune function and progressive pulmonary infection in the later stage of the disease. Respiratory muscle weakness was relieved quickly after four times of immunoadsorption therapy. The value of immunoadsorption in the treatment of refractory MG was explored with literature review.

Effect and potential molecular mechanism of FOXA2 on cell proliferation, migration and invasion of hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To investigate the effect of forkhead box protein A2(FOXA2) on cell proliferation, migration and invasion of hepatocellular carcinoma and the potential molecular mechanism.Methods:From January 2019 to December 2020, 10 cases of hepatocellular carcinoma patients from Zhongnan Hospital of Wuhan University were collected for study, including 7 males and 3 females, with an average age of 53 years. FOXA2 expression was detected in human liver cancer cell line, and the highest expression of FOXA2 was found in HepG2 cells transfected with FOXA2 overexpression plasmid. Immunohistochemistry and qRT-PCR were used to detect the expression of FOXA2. Western blot was used to detect the expression of FOXA2, hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial growth factor A (VEGFA), B-cell lymphofactor-2 (Bcl-2), matrix metalloproteinase (MMP) 7, and glucose transporter (GLUT) 1. EdU assay was used to study cell proliferation, and Transwell chamber assay was used to study cell migration and invasion.Results:The relative expression of FOXA2 in liver cancer tissues were lower than those in adjacent tissues both at mRNA and protein levels, with statistical significance (both P<0.05). FOXA2 overexpression group showed lower cell proliferation rate (30.0±3.2)%, migration rate (10.6±1.1), and invasion rate (12.8±0.8) comparing with negative control group (67.0±3.6)%, (81.0±5.4), (74.8±4.5). The difference was statistically significant (all P<0.05). Expression of HIF-1α and its downstream targets VEGFA, MMP7, GLUT1 and Bcl-2 was decreased after over-expression of FOXA2 in HepG2 cells. Conclusion:FOXA2 inhibits proliferation, migration, and invasion in hepatocellular carcinoma by regulating HIF-1α signaling pathway, suggesting that FOXA2 is a potential target for the treatment of hepatocellular carcinoma.

Clinical significance of Clara cell secreted protein 16 and pulmonary surfactant protein-A in early diagnosis of neonatal acute respiratory distress syndrome / 中国小儿急救医学

Objective:To investigate the clinical significance of changes of serum Clara cell secretory protein(CC16) and pulmonary surfactant protein A(SP-A) in neonates with acute respiratory distress syndrome(ARDS).Methods:The data of 30 neonates with ARDS who needed mechanical ventilation in neonatal intensive care unit of Xi′an Children′s Hospital from January 2016 to November 2018 were collected as observation group, including 12 cases in mild group, 10 cases in moderate group and 8 cases in severe group.The data of healthy newborns during the same period were taken as control group.The serum levels of CC16 and SP-A were detected by ELISA.The serum levels of CC16 and SP-A among different groups were compared.Results:The levels of serum CC16 and SP-A in ARDS group were (59.35±3.67)mg/L and(75.38±6.27)mg/L respectively, (11.26±1.32)mg/L and(18.15±2.69)mg/L in healthy group.The difference was significant( P<0.05). And the differences of serum CC16 and SP-A levels among different degree ARDS groups were significant( P<0.05). The levels of serum CC16 in mild, moderate and severe subgroup were(38.27±16.01)mg/L, (51.25±15.63)mg/L, (84.76±13.12)mg/L and SP-A were(47.02±7.18)mg/L, (73.12±7.98)mg/L, (96.45±12.50)mg/L, which increased with disease severity. Conclusion:Serum CC16 and SP-A are increased and correlated with the severity of neonatal ARDS, which may be used as the index for evaluating the severity of neonatal ARDS in the future.

Effects of CENP-A on invasion and migration of ovarian cancer cells by regulating PI3K/AKT/NF-κB signaling pathway / 中华内分泌外科杂志

Objective:To investigate the effects of centromere protein-A (CENP-A) on the invasion and migration of ovarian cancer (OC) cells and explore the related mechanism.Methods:OC cell line A2780 was cultured in vitro, and they were divided into Ng Group (Blank Control Group) , pcDNA group (negative transfection group:PCDNA vector plasmid) , pcDNA-CENP-A group (over-expression Group: pcDNA-CENP-A Vector Plasmid) and pathway inhibitor group (TRANSFECTION-CENP-A+ PI3K pathway inhibitor LY294002) . The cell proliferation was detected by CCK-8 method; the cell migration and invasion was detected by Scratch test and Transwell test; the expression of CENP-A, E-cadherin, N-cadherin and phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-kappa B (PI3K/AKT/NF-κB) pathway related proteins was detected by Western blot.Results:A2780 cells were successfully transfected. After 24 hours, with the extension of culture time, compared with that in NG group [ (0.50±0.07) , (0.72±0.11) , (0.99±0.14) ] and pcDNA group [ (0.55±0.08) , (0.78±0.12) , (1.02±0.15) ], the viability of A2780 cells in pcDNA-CENP-A group [ (0.78±0.12) , (1.03±0.15) , (1.67±0.25) ] and pathway inhibitor group [ (0.63±0.09) , (0.87±0.13) , (1.39±0.20) ] increased significantly ( P<0.05) , compared with that in the pcDNA-CENP-A group, the viability of A2780 cells in the pathway inhibitor group was significantly decreased ( P<0.05) , in a time-dependent manner. Compared with those in NG group [ (15.83±1.46) %, (105.32±15.78) individual] and pcDNA group [ (16.79±1.46) %, (108.98±16.35) individual], the migration rate [ (37.96±5.80) %, (25.15± 2.19) %] and invasion number [ (327.87±49.18) individual, 206.53±30.97) individual] of A2780 cells, protein expression of CENP-A, N-cadherin, Vimentin, p-PI3K/PI3K, p-AKT/AKT, NF-κB, interleukin (IL-1β) , tumor necrosis factor-α (TNF-α) in pcDNA-CENP-A group and pathway inhibitor group were significantly higher ( P<0.05) , the expression of E-cadherin was significantly lower ( P<0.05) ; compared with those in the pcDNA-CENP-A group, the migration rate and invasion number of A2780 cells, protein expression of CENP-A, N-cadherin, Vimentin, p-PI3K/PI3K, p-AKT/AKT, NF-κB, interleukin (IL-1β) , tumor necrosis factor-α (TNF-α) in pathway inhibitor group were significantly lower ( P<0.05) , and the expression of E-cadherin was significantly higher ( P<0.05) . Conclusion:Overexpression of CENP-A can promote the proliferation, invasion and migration of ovarian cancer cells, which may be achieved by activating PI3K/AKT/NF-κB signaling pathway.

Research progress of anti-Alzheimer′s disease drugs targeting Aβ oligomers / 中国药科大学学报

@#Alzheimer''s disease (AD) is the most common cause of senile dementia, accounting for an estimated 60% to 80% of cases, but there are no approved drugs to slow or stop the progressive clinical decline in the past years.Amyloid cascade hypothesis is recognized as the major etiologic basis for AD, however, the failures of several amyloid plaque-targeted programs have led many to dismiss the amyloid beta (Aβ) hypothesis of AD. Several reports show that soluble oligomers of Aβ (AβOs), which appear in brains more than 10 years before the clinical syndrome, are more toxic than Aβ plaque, causing synaptic dysfunction and neuronal apoptosis. Some agents that can effectively inhibit Aβ oligomer formation or block their toxicity made significant efficacy in clinical 2 and 3 trials, with the potential to be approved for the treatment of AD. This article reviews the recent development of AD drugs targeting Aβ oligomers, analyzes their structural characteristics, mechanism of action, preclinical and clinical data, and discusses the future direction of AD treatment, thus providing new strategies for AD drug research.

Low expression S100 calcium ion binding protein A6 promoting the proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells / 解剖学报

Objective To explore the effect of S100 calcium ion binding protein A6 (S100A6) on proliferation and migration of esophageal adenocarcinoma SK-GT-4 cells. Methods Lenti viruses were used to construct stable transfected cell lines (shNC and shS100A6). Real-time PCR was used to detect the mRNA expression of S100A6. The inverted microscope and MTT were used to detect cell proliferation. The Transwell assay was used to detect cell migration. Western blotting was used to detect the expression of S100A6, p-ERK, p-Akt and its downstream molecular involved in proliferation and migration. Using U0126 ( inhibitor of MER1/2) and LY294002 ( inhibitor of PI3K) to detect the effect of these two inhibitors on cell proliferation and migration and the expression of p-ERK, p-Akt and its downstream molecular involved in proliferation and migration in shS100A6 cells. Results Stable cell lines of knockdown S100A6 were constructed. Knockdown S100A6 promoted cell proliferation and migration. Western blotting result displayed that in shS100A6 cells, the levels of p-Akt and p-ERK increased, p21 decreased, cyclinDl increased, and the expression of β-catenin and vimentin, increased. U0126 and LY294002 inhibited the migration of shS100A6 cells. U0126 had no effect on the proliferation of shS100A6 cells, however LY294002 could inhibit the proliferation of shS100A6 cells. U0126 treatment on shS100A6 cells could decrease p-ERK and β-catenin expression. After shS100A6 cells treated with LY294002, p-Akt and β-catenin expression decreased, p21 expression increased and the expression of cyclinDl decreased. Conclusion Low expression of S100A6 promotes cell proliferation and migration, which may be mediated by activation of p-Akt regulating cell cycle progression to promote cell proliferation and by activation of p-Akt/p-ERK to regulate β-catenin to promote cell migration.

Effect of Compound Phylanthus urinaria Ⅱ in Regulating Expression of lncRNA CCAT1 in Hepatocellular Carcinoma HepG2 Cells / 中国实验方剂学杂志

Objective:To explore the anti-hepatoma effect of compound <italic>Phylanthus urinaria</italic> Ⅱ （ CPU Ⅱ） by inhibiting the expression of the long non-coding RNA （lncRNA） colon cancer associated transcript-1 （CCAT1） and restoring the expression of microRNA let-7a. Method:Real-time fluorescence quantitative polymerase chain reaction （PCR） was used to detect the expression of lncRNA CCAT1 in normal liver cells （LO2 cells） and hepatocellular carcinoma HepG2 cells， and the differences in expression between these two types of cells were compared. The methylthiazolyl tetrazolium（MTT） assay was used to detect the proliferation of HepG2 cells after treatment with different concentrations of CPU Ⅱ and 5-fluorouracil（5-FU） for 24， 48 and 72 h. Hepatocellular carcinoma HepG2 cells were cultured <italic>in vitro </italic>and set into three gropes： cell control group， CPU Ⅱ low-dose group （0.8 g·L^-1） and high-dose group （1.6 g·L^-1）. Real-time PCR was used to detect the mRNA expression of lncRNA CCAT1， microRNA let-7a and its target genes high mobility group protein A2（HMGA2）， and N-RAS in each grope. Western blot was used to detect the protein expression of HMGA2， and Cyclin D₁ in each grope. Result:As compared with LO2 cells， expression of lncRNA CCAT1 in HepG2 cells was significantly up-regulated （<italic>P</italic><0.05）. Results of MTT assay showed that the 50% inhibiting concentration（IC₅₀）of CPU Ⅱ and 5-FU on hepatocellular carcinoma HepG2 cells was 1.649， 0.044 648 g·L^-1respectively. As compared with the control group， CPU Ⅱ high-and low-dose groups （1.6， 0.8 g·L^-1） significantly inhibited the proliferation of HepG2 cells （<italic>P</italic><0.05）， and the effect was most remarkable in CPU Ⅱ high-dose group （<italic>P</italic><0.05）. The results of Real-time PCR showed that as compared with control group， the expression of lncRNA CCAT1 mRNA was significantly inhibited in CPU Ⅱ high-and low-dose groups （<italic>P</italic><0.05）， and the expression of microRNA let-7a mRNA was obviously up-regulated in high-dose group （<italic>P</italic><0.05）， but the expression of HMGA2 mRNA in CPU Ⅱ high-and low-dose groups as well as the expression of N-RAS mRNA in CPU Ⅱ low-dose group were down-regulated （<italic>P</italic><0.05）. Western blot results showed that as compared with the cell control group， the protein expression of HMGA2 and Cyclin D₁ in CPU Ⅱ high-and low-dose groups （1.6， 0.8 g·L^-1） was significantly down-regulated （<italic>P</italic><0.05）. Conclusion:CPU Ⅱ can inhibit the expression of lncRNA CCAT1， recover the expression of microRNA let-7a， and suppress the mRNA and protein expression of related downstream target genes in hepatoma cells line HepG2， thereby inhibiting the proliferation of hepatocellular carcinoma cells and exerting anti-hepatocellular carcinoma effect.

Role of surfactant proteins in viral keratitis / 国际眼科杂志(Guoji Yanke Zazhi)

@#Innate immunity plays an important role in viral keratitis. Recently, it has been found that surfactant proteins(SP)A and D in the innate immune system are essential in viral keratitis. SP can inhibit virus adhesion to host cells and further promote phagocytosis of virus through high affinity for virus ligands. In order to ensure the normal function of tissues in the early stage of virus infection, SP regulates immune cells to maintain a non-inflammatory state. However, when pathogen invasion increases, SP promoted inflammation and increased the immune cells to kill the pathogens. SP-A and SP-D could be expressed in cornea, conjunctiva. To play the role of anti-adenovirus, herpes simplex virus, cytomegalovirus and other major eye pathogenic viruses, SP-A and SP-D combine with the virus to prevent entry into cells, promote phagocytosis, and directly kill the virus. SP-A and SP-D may be used as clinical diagnostic tools for viral infection. In the future, recombinant SP is expected to be used as an important means for the treatment of viral keratitis. Here, we review the innate immune function of SP-A and SP-D in ocular viral infection.

Validación de la calculadora de la Fundación de Medicina Fetal para tamiz de preeclampsia adaptada a población mexicana / Validation of the Fetal Medicine Foundation calculator for pre-eclampsia screening test adapted to a Mexican population

Resumen OBJETIVO: Validar el rendimiento de la calculadora de la Fundación de Medicina Fetal 4.0 adaptada a población mexicana. MATERIALES Y MÉTODOS: Estudio de cohorte efectuado en embarazos con feto único, según el modelo de riesgos en competencia para preeclampsia en un centro de medicina fetal de la Ciudad de México. El riesgo a priori se calculó de acuerdo con la historia clínica. La presión arterial media, el índice de pulsatilidad medio de la arteria uterina y la proteína plasmática A asociada al embarazo se midieron a las 11 a 14 semanas de gestación con metodología estandarizada. El valor de cada marcador se transformó en múltiplos de la mediana adaptados a la población local. Se aplicaron la distribución normal multivariante y el teorema de Bayes para obtener las probabilidades posprueba individuales, que se utilizaron como clasificadores para el área bajo la curva de característica receptor-operador. RESULTADOS: La incidencia de preeclampsia fue del 5.0% (54/1078). El área bajo la curva de característica receptor-operador fue de 0.784 (0.712; 0.856) para preeclampsia a menos de 37 semanas y de 0.807 (0.762; 0.852) para preeclampsia global. CONCLUSIONES: La calculadora FMF 4.0 adaptada a población mexicana resultó válida. Si bien tuvo menor rendimiento al esperado para preeclampsia a menos de 37 semanas, el rendimiento para preeclampsia global fue satisfactorio. Se justifica desarrollar la calculadora local.

Abstract OBJECTIVE: To validate the performance of the Fetal Medicine Foundation 4.0 calculator adapted to the Mexican population. MATERIALS AND METHODS: Cohort study performed in singleton pregnancies, according to the competing risk model for preeclampsia in a fetal medicine center in Mexico City. The a priori risk was calculated according to the clinical history. Mean arterial pressure, mean uterine artery pulsatility index and pregnancy-associated plasma protein A were measured at 11 to 14 weeks of gestation with standardized methodology. The value of each marker was transformed into multiples of the median adapted to the local population. Multivariate normal distribution and Bayes' theorem were applied to obtain individual posttest probabilities, which were used as classifiers for the area under the receiver-operator characteristic curve. RESULTS: The incidence of preeclampsia was 5.0% (54/1078). The area under the receiver-operator characteristic curve was 0.784 (0.712; 0.856) for preeclampsia at less than 37 weeks and 0.807 (0.762; 0.852) for global preeclampsia. CONCLUSIONS: The FMF 4.0 calculator adapted to Mexican population proved valid. Although it had lower performance than expected for preeclampsia at less than 37 weeks, the performance for global preeclampsia was satisfactory. The development of the local calculator is justified.

Effect of first trimester maternal serum pregnancy associated plasma protein: a level on fetomaternal outcome

Background: Serum pregnancy-associated plasma protein-A (PAPP-A) levels fluctuate in continuation with the pregnancy and thus become an important standalone marker in monitoring the adverse outcomes that may occur in pregnancy.Methods: A prospective observational study was conducted in the department of obstetrics and gynaecology. A total of 240 pregnant women in their first trimester were included in the study. Serum PAPP-A levels were measured at 11-13+6week of gestation and were evaluated with respect to the feto-maternal outcome. The data was entered in MS excel spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0.Results: The mean age of the study population was 27 years. Among the maternal pregnancy parameters, PIH, pre-term labor and Emergency LSCS were significantly associated with low (<0.5 MoM) Serum PAPP-A levels, P<0.05. All the fetal outcome measures: IUGR, IUD, low birth weight, SGA babies, prematurity and NICU admissions, were significantly associated with low (<0.5 MoM) Serum PAPP-A levels, p <0.05.Conclusions: Serum PAPP-A in the early pregnancy showed significant correlation with feto-maternal outcome. Thus, it has the potential to be used as a prognostic factor and in the management of adverse outcomes by increasing surveillance for pregnant women with high-risk factors.

Protective Mechanism of Icariin on Nephrotic Syndrome Rats Based on RhoA/ROCK Pathway / 中国实验方剂学杂志

Objective:To study the effect of icariin on renin homologous protein A (RhoA)/Rho-related kinase (ROCK) pathway in rats with nephrotic syndrome (NS) and its protective mechanism. Method:Totally 54 clean-grade male SD rats were tested and randomly divided into normal group, model group, RhoA inhibitor group (Rhosin, 40 mg·kg-1·d-1) and three doses of icariin groups (low, medium and high corresponding dose， 30, 60, 120 mg·kg-1·d-1). Adriamycin hydrochloride 6.5 mg·kg-1 was given in tail vein of rats to induce NS model in rats. After the model was established, peritoneal administration was carried out. The normal group and the model group were given saline 2.5 mL·d-1, and the inhibitor group and all of dose groups were given corresponding doses of Rhosin and icariin for intervention. Total urinary protein (Alb), creatinine (Cre), total urinary protein/creatinine ratio (A/C) kit were detected in rats, ultrastructure of kidney was identified by transmission electron microscopy (TEM), and Real-time fluorescent quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and proteins expressions of RhoA, ROCK1, ROCK2. Result:TEM showed that the basement membrane was intact and the foot process was regular in the normal group, in model group, basement membrane was damaged seriously, foot process disappeared, and fusion was serious, in the low-dose group, the basement membrane injury was alleviated, the number and density of foot process were improved, and the fusion was obvious， in the middle-dose group and the inhibitor group, the basement membrane thickening was alleviated, and the foot process was slightly fused, in the high-dose group, the basement membrane structure was more complete, and podocytes were longer and arranged tightly. Compared with the normal group, the levels of Alb, Cre and A/C in urine, and RhoA, ROCK1 and ROCK2 mRNA and protein expressions in kidney tissue of rats of the model group were significantly higher (P<0.05). Compared with model group, the levels of Alb, A/C in urine and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue in the inhibitor group and low, medium and high-dose groups, and Cre in urine in inhibitor group and high-dose group decreased significantly (P<0.05). Compared with the inhibitor group, the levels of Alb, Cre in urine and RhoA protein in kidney tissue in the high-dose group were significantly decreased (P<0.05), the levels of Alb, Cre, A/C in urine and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue of the low-dose group, and the levels of RhoA, ROCK1 and ROCK2 mRNA expressions in kidney tissue of the middle-dose group were significantly increased (P<0.05). Compared with the low-dose group, the levels of Alb, A/C in urine, and RhoA, ROCK1, ROCK2 mRNA and protein expressions in kidney tissue in the middle and high-dose groups, Cre in urine of the high-dose group were significantly decreased (P<0.05). Compared with the middle-dose group, the levels of Alb, Cre in urine, and RhoA, ROCK1, ROCK2 mRNA and protein expressions, ROCK2 mRNA expression in kidney tissue in the high-dose group were significantly decreased (P<0.05). Conclusion:Icariin may protect glomerular endothelium and podocyte by affecting RhoA/ROCK pathway in the treatment of NS rats.

Apatinib enhances the anti-tumor effect of cisplatin on gastric cancer by inhibiting HMGA2 / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of apatinib (APA) combined with cisplatin (DDP) on the proliferation, invasion and migration capacity of gastric carcinoma (GC) cells and its molecular mechanism. Methods: Cancer and para-cancerous tissue samples resected from 50 GC patients, who were surgically treated in Wuwei People's Hospital from January 2016 to June 2019, were collected for this study; in addition, GC cell lines MGC803 and SGC7901 were also collected. qPCR was used to detect the HMGA2 expression in tissues and mRNA expressions of molecules related to cell proliferation, migration and invasion in GC cell lines. MGC803 and SGC7901 cells were transfected with pcHMGA2 by liposome transfection technology. After treatment with DDP and APA at different concentrations, the cells were divided into NC, pcHMGA2, pcHMGA2+DDP and pcHMGA2+DDP+APA groups. Protein expression of HMGA2 in GC cells was detected by Western blotting, and proliferation, migration and invasion of the cells were detected by MTT and Transwell assay, respectively. Results: The mRNA expression of HMGA2 in GC tissues was higher than that in para-cancerous tissues (P<0.05), and the survival rate of GC patients in the high expression group was significantly reduced (P<0.01). DDP significantly inhibited the proliferation, invasion and migration of MGC803 and SGC7901 cells (all P<0.01); the proliferation, invasion and migration of MGC803 and SGC7901 cells in DDP+APA group significantly decreased (all P<0.01) as compared with DDP group; APA significantly enhanced the inhibitory effect of DDP on HMGA2 expression in GC cells (P<0.01); APA enhanced the anticancer activity of DDP against GC by down-regulating HMGA2 expression. Conclusion: APA promotes the anticancer activity of DDP against GC, and its molecular mechanism is the promotion of the inhibitory effect of DDP on HMGA2 expression.

Diagnostic value of lung injury biomarkers in neonatal acute respiratory distress syndrome / 国际儿科学杂志

Objective@#To investigate the role of E-selectin, Clara cell secretory protein 16 (CC-16), and pulmonary surfactant protein A (SP-A) in the diagnosis of neonatal ARDS.@*Methods@#Full-term newborn with ARDS in 9 hospitals of Jiangsu Province from March 1st 2015 to February 29th 2016 were selected as observation group.According to the lung oxygenation of the neonates, they were divided into three groups: mild, moderate and severe.In addition, 60 normal full-term newborns were selected as control group.In the observation group, venous blood samples were taken on the 1st, 3rd and 7th day of diagnosis and the control group within 7 days after birth.The level of E-selectin, CC-16 and SP-A were detected by double antibody sandwich enzyme-linked immunosorbent assay.The changes of the level of E-selectin, CC-16 and SP-A at different time points and in neonatus with different severity of ARDS were compare with control group and correlatively analyzed.@*Results@#The observation group included 60 newborns who met the diagnostic criteria of ARDS with male 38, female 22, day age (7.3 ±3.3) hours, gestational age (39.5 ±1.7) weeks and birth weight (3280 ±577) g. The control group included 60 normal full-term newborns, with male 30, female 30, day age (6.9 ±4.2) hours, gestational age (39.4 ±1.5) weeks and birth weight (3329 ±593) g. There was no significant difference between two groups.The levels of E-selectin[1 d, 3 d, 7 d: (36.36 ±8.32)μg/L, (45.51 ±9.26)μg/L, (57.15 ±6.84)μg/L], CC-16[1 d, 3 d, 7 d: (25.24 ±8.63)mg/L, (48.33±10.83)mg/L, (18.84±10.11)mg/L]and SP-A [1 d, 3 d, 7 d: (58.38±10.31)mg/L, (53.29±11.31)mg/L, (25.99±6.66)mg/L]in the blood of the observation group increased on the first day and reached the peak on the third day, which were significantly higher than those in the control group [E-selectin, CC-16, SP-A: (15.52 ±6.24)μg/L, (11.26 ±5.18)mg/L, (24.30 ±5.27)mg/L] (P<0.05). The levels of E-selectin [mild, moderate, severe are(30.07±6.10)μg/L, (33.39 ±6.64)μg/L, (41.63 ±7.36)μg/L], CC-16 [mild, moderate, severe are(12.61 ±5.80)mg/L, (25.22 ±6.77)mg/L, (30.61 ±4.69)mg/L]and SP-A [mild, moderate, severe are(49.67 ±8.26)mg/L, (7.11 ±7.94)mg/L, (63.19 ±11.45)mg/L]increased gradually in the blood of ARDS neonates with different severity (P<0.05), especially in moderate and severe degree.There was a significant negative correlation between E-selectin (r=-0.629 8), CC-16 (r=-0.679 3), SP-A (r=-0.458 8) and PaO2/FiO2 (P<0.05).@*Conclusion@#The levels of E-selectin, CC-16 and SP-A in the blood of ARDS neonates increased significantly and were closely related to the severity of the disease, which may be a biomarker of neonatal lung injury.

Dynamic expression of CCAAT enhancer binding protein A and its significance in rat lung development / 中华实用儿科临床杂志

Objective To investigate the role of CCAAT enhancer binding protein A (C/EBPα) in lung development by analyzing the relationship between dynamic expression of C/EBPα protein and cell differentiation in rat lung tissue.Methods According to the histological stages of rat lung development,lung tissues were collected on 15.5 d (the late pseudoglandular period),17.5 d (the canalicular period),19.5 d (the early saccular period) of embryonic age and at 12 h (the middle saccular period),on 4 d (the late saccular period),7 d (the alveolar period,the alveolar stage),14 d (the alveolar period,the equilibrium stage) of postnatal age.The lung morphologic appearance was observed by using HE staining.Western blot was used to detect the expressions of C/EBPα and surfactant Protein (SP)-A,SP-B,SP-C,SP-D.Phosphatidylcholine (PC) assay kit was utilized to analyze the secretion of PC.Periodic acid-schiff (PAS) staining was used to evaluate the amcunt of glycogen in lung tissue.Results (1) C/EBPαt and SP-A began to express on 15.5 d of embryonic age (0.36 ±0.02,0.01 ±0.01),while SP-B,SP-C and SP-D started to express on 17.5 d of embryonic age (0.33 ±0.06,0.01 ±0.01,0.11 ±0.08).All of them increased with the development of lung,and C/EBPα,SP-A,SP-C reached the highest level at 12 h of postnatal age (3.48 ±0.05,3.24 ± 0.19,1.26 ± 0.21),and SP-D on the postnatal 4 d (1.48 ± 0.10),then gradually decreased,while the expression of SP-B continued to rise.The levels of C/EBPα and SPs maintained stable on postnatal 14 d.The C/EBPα protein level was positively correlated with SPs at embryonic age of 15.5 d,17.5 d,19.5 d and postnatal age 12 h (r =0.999,0.991,0.982,0.951,all P ＜ 0.05).(2) The level of PC was very low at embryonic age of day 15.5 [(60.50 ± 1.30) μg/g].With the development of lung,the secretion of PC increased gradually,but there was no significant correlation between the expression of PC and C/EBPoα(all P ＞ 0.05).(3) The level of glycogen was high in the late pseudoglandular stage (15.5 d) (585.50 ± 2.20),the content of glycogen decreased with the development of lung,especially on the canalicular (embryonic day 17.5) and during early saccular period (embryonic day 19.5),and then it became stable during the alveolar period (postnatal age 7 d).The expression of C/EBPα had negative correlation with the content of glycogen in fetal lung(r =-1.000,P ＜ 0.01).Conclusion C/EBPα plays an important role in rat lung development,as it may promote lung maturation by regulating the synthesis and secretionof SPs and PC.