Clinical and molecular genetic analysis of Angelman syndrome with oculocutaneous albinism type 2: A case report and literature review / 北京大学学报(医学版)

To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome (AS) complicated with oculocutaneous albinism type 2 (OCA2), and to review the literature. "Angelman syndrome" "P gene" and "Oculocutaneous albinism type 2" were used as keywords to search at CNKI, Wanfang, and PubMed databases (from creation to December 2019). Then all the patients were analyzed. The patient in this study was a girl aged 1 year. After birth, she was found to present as white body, yellow hair, and nystagmus. She could raise her head at the age of 2 months and turn over at the age of 7 months. The head circumference was 42 cm and she could not sit alone or speak at present. Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del (p.Gln58ArgfsTer44) in the P gene, and her father was heterozygous and her mother was wild-type. The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region (P gene located in this region) in the patient. Until December 2019, a total of 4 cases in the 4 literature had been reported. Adding our case here, the 5 cases were summarized and found that all the cases showed white skin, golden hair, and shallow iris after birth. Comprehensive developmental delay was found around 6 months of age after birth, and the language remained undeveloped in 2 cases till follow-up into childhood. Seizures occurred in 4 patients. Two cases had ataxia. All the 5 cases had acquired microcephaly. Two cases had a family history of albinism. Electroencephalogram monitoring was completed in 3 cases and the results were abnormal. Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region. Four cases carried mutation of P gene on paternal chromosome. And 1 case was clinically diagnosed as OCA2 without P gene test. AS combined with OCA2 is relatively rare. OCA2 is easily diagnosed based on the obvious clinical manifestations after birth. When combined with clinical manifestations such as neurodevelopmental delay, it might indicate the possibility of AS that is hardly diagnosed clinically at an early stage. Genetic tests can reveal the cross-genetic phenomenon of AS and OCA2 and the complex of them can be eventually diagnosed.

Research progress on the methods of observation and analysis of dental bonding interfaces / 口腔疾病防治

@#Dental bonding technology and materials have been used widely in dentistry because of their excellent properties. The development of novel bonding technology and materials is constantly being performed to improve the effect of dental bonding restorations. Observation and analysis of the dental bonding interface is one of the most important methods for laboratory evaluation of bonding efficiency. This paper aims to review the methods of observation and analysis of dental bonding interfaces to provide a reference for the selection of evaluation methods in dental bonding research. The features of 6 methods, including scanning electron microscopy (SEM), transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), Raman spectroscopy (RS), optical coherence tomography (OCT) and atomic force microscopy (AFM), were described and summarized. Among these methods, SEM and TEM are used most often in the analysis of fine structures; CLSM and OCT are used for the acquisition of characteristic image signals, such as microleakage and exogenous and endogenous fluorescence; and RS and AFM can test chemical composition and mechanical properties.

A New Model of Multi-Terminal and Interractive Drug Approval Based on WeChat Platform / 医学信息学杂志

Taking Zhenjiang First Peopls's Hospital as an example,the paper analyzes the advantage of mulit-terminal and interactive durg approval based on WeChat platform,dilates upon realization method of the mode from the three aspects of logic architecture,physical archtecture and business process and poinst out that the mode is able to realize informatization management of the mixed approval of drugs.

Study on the Buliding of New Medical Insurance Mobile Payment Platform / 医学信息学杂志

Mobile medical service for patients is realized through Alipay hospital service window based on the new medical insurance mobile payment platform.The paper introduces overall business architecture of the platform and payment procedure realizing scheme,platform implementation and offline procedure to adapt to the platform,realizing real-time payment,optimizing the procedure of outpatient medical treatment,improving patients' experiences of being treated and enhancing their satisfaction.

Expression and Clinical Significance of Cytokeratin-19 and Thymidine Kinase-1 in Advanced Gastrointestinal Cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As the clinical value of cytokeratin-19 (CK19) and thymidine kinase-1 (TK1) in advanced gastrointestinal cancer remains controversial, we investigated their expression and clinical significance in this disease.</p><p><b>METHODS</b>A total of 171 advanced gastrointestinal cancer patients were prospectively enrolled in this study. The mRNA level of CK19 was detected using quantitative real-time reverse transcription-polymerase chain reaction (PCR) in all patients, along with a control group of fifty healthy individuals. Furthermore, detection of TK1 protein was carried out in 96 patients using a chemiluminescence dot blot assay. The primary endpoint was overall survival (OS) time.</p><p><b>RESULTS</b>Positive CK19 mRNA expression was detected in 74 (43.3%) of the 171 patients and positive TK1 expression was detected in 66 (68.8%) of the 96 patients. Furthermore, of the 96 patients, 36 (37.5%) were positive for both TK1 protein and CK19 mRNA, 30 (31.3%) were negative for TK1 protein, and 15 (15.6%) were negative for TK1 protein and positive for CK19 mRNA. The results indicated that patients who were positive for CK19 mRNA expression had significantly shorter OS times than those who were negative for it (median OS 7.7 vs. 9.7 months, respectively; P = 0.02). Moreover, patients who were positive for CK19 mRNA and TK1 protein expression had shorter OS times (median OS 6.1 months) than those who were positive for CK19 mRNA and negative for TK1 protein expression (median OS 9.1 months; P = 0.028). Positive CK19 mRNA expression was significantly associated with shorter OS in the univariate analysis (P = 0.027). Based on a multivariate Cox regression analysis, CK19 mRNA together with TK1 protein expression (P = 0.024) was an independent predictor for OS in gastrointestinal cancer patients.</p><p><b>CONCLUSIONS</b>Our results suggest that positive expression of CK19 mRNA and TK1 protein is closely correlated with poor prognosis in advanced gastrointestinal cancer. Furthermore, both CK19 and TK1 are possible gastrointestinal cancer biomarkers.</p>

The role of tumor-associated macrophages in remodeling tumor immune microenvironment / 肿瘤

Majority of experimental and clinical studies have shown a pro-tumoral function of tumor-associated macrophages (TAMs) which occupy a large part in matrix cells. TAMs promote tumor cell invasion and migration, and their number is related to malignant degree and poor prognosis. Macrophages plasticity makes it possible to change the tumor microenvironment and remodel tumor immune in cancer immunotherapy. Increasing researches have revealed the TAMs' effect on tumor microenvironment and put forward tumor immune treatments aiming at TAMs. Here this review presents the recent research of TAMs in remodeling tumor immune microenvironment and immune targeted therapies, such as the origin of TAMs, the immunosuppression effect of TAMs on tumor microenvironment, tumor extracellular matrix remodeling, and promotion of angiogenesis and lymphangiogenesis Copyright © 2013 by TUMOR.

Synthesis and characterization of protocatechuic acid derivants / 中国中药杂志

To explore the effects of protocatechuic acid (PCA) and its derivants on angiogenesis of the chick embryo chorioallantoic membrane (CAM) and scavenging DPPH radical in vitro. The protection of benzyl and alkaline hydrolysis of benzyl ester were employed. The structures of PCA-1, PCA-2 and PCA-3, the derivates of PCA, were elucidated by 1H, 13C-NMR and MS data The bioactivity of PCA and its derivants was evaluated on the models of DPPH radical and chick embryo chorioallantoic membrane (CAM), respectively. PCA and PCA-1 showed the best activity of scavenging DPPH radical among all the compounds. In contrast to PCA-2, PCA and PCA-3 displayed inhibition to angiogenesis (P < 0.001). Pyrocatechol hydroxyl is the active site of PCA on scavenging DPPH radical in vitro. PCA with carboxyl and without pyrocatechol hydroxyl seems to show promotion to angiogenesis, but it needs more evidences.

Inhibitive Effect of Cremophor RH40 or Tween 80-based Self-microemulsiflying Drug Delivery System on Cytochrome P450 3A Enzymes in Murine Hepatocytes / 华中科技大学学报（医学）（英德文版）

This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate. The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium. In vitro release was detected by a dialysis method in reverse. The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes. The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique. The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting. Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500. The MDZ was completely released in 10 h. A significant decrease in the formation of 1'-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed. A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250. This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.

Stereoselective HPLC Assay of TJ0711 Enantiomers by Precolumn Derivatization with GITC Using UV Detection and Its Application in Pharmacokinetics in Rats / 华中科技大学学报（医学）（英德文版）

the quantitative determination of TJ0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.

Progress in the research on multi-target-directed drugs against Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and one of the earliest sings of AD is deficit in short term memory. Till now, the pathogenesis of AD has not been elucidated and the present one-drug-one-target paradigm of anti-AD-drug treatment seems not to be effective in clinic. Multi-target-directed anti-AD-drugs are those agents that may act on two or more targets implicated in AD. Based on the brief introduction of progress in the development of present anti-AD-drugs, the paper mainly focused on the advances in the field of multi-target-directed drug development both home and abroad, especially those studies on selective estrogen receptor modulators.

Two-dimensional electrophoresis analysis of hydrophobic membrane proteome in mouse hepatocarcinoma cell H22 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To compare the membrane protein profile of mouse hepatocarcinoma cell H22 with that of normal liver cell.</p><p><b>METHODS</b>The membrane proteins in mouse hepatocarcinoma cell H22 and normal liver cell were extracted and their concentrations were determined by Bradford method. The proteins were separated by two-dimensional electrophoresis, and then stained with silver. The 2-DE maps were scanned and analyzed by Image Master 2D Platinum software. The differential expression protein spots were cut out from the gels, and the peptide fingerprinting was determined by MALDI-TOF-MS (Matrix-Assisted Laser Desorption/ Ionization Time of Flight Mass Spectrometry), followed by matching to Swiss-Prot protein database by Aldente software with experimental pI and MW data.</p><p><b>RESULTS</b>Compared to normal liver cells, 8 membrane proteins, including sulfatase-modifying factor 2, protein kinase C and casein kinase II substrate protein 3, sorting and assembly machinery component 50 homolog, macrophage scavenger receptor types I/II, uncharacterized protein C9 or f135 homolog, tight junction protein ZO-2, 3-hydroxy-3- methylglutaryl-coenzyme A reductase, and vacuolar protein sorting-associated protein 52 homolog were upregulated in H22 cells.</p><p><b>CONCLUSION</b>The membrane proteins involved in cell metabolism, proliferation, signal transduction, and skeleton, which are highly expressed in mouse hepatocarcinoma H22 cells, are probably related to the proliferation, invasion and migration of this tumor cell line.</p>

Different effects of isoflurane and sevoflurane on cytotoxicity / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Isoflurane, a commonly used inhaled anesthetic, induces apoptosis in primary rat cortical neurons of rat in a concentration- and time-dependent manner by an unknown mechanism. We hypothesized that isoflurane induced apoptosis by causing abnormal calcium release from the endoplasmic reticulum (ER) via activation of inositol 1, 4, 5-trisphosphate (IP(3)) receptors. Sevoflurane has a reduced ability to disrupt intracellular calcium homeostasis and is a less potent cytotoxic agent. This study examined and compared the cytotoxic effects of isoflurane and sevoflurane on rat primary cortical neurons and their relationship with disruption of intracellular calcium homeostasis and production of reactive oxygen species (ROS).</p><p><b>METHODS</b>Primary rat cortical neurons were treated with the equivalent of 1 minimal alveolar concentration (MAC) of isoflurane and sevoflurane for 12 hours. MTT reduction and LDH release assays were performed to evaluate cell viability. Changes of calcium concentration in the cytosolic space, [Ca(2+)](c), and production of ROS were determined after exposing primary rat cortical neurons to isoflurane and sevoflurane. We also determined the effects of IP(3) receptor antagonist xestospongin C on isoflurane-induced cytotoxicity and calcium release from the ER in primary rat cortical neurons.</p><p><b>RESULTS</b>Isoflurane at 1 MAC for 12 hours induced cytotoxicity in primary rat cortical neurons, which was also associated with a high and fast elevation of peak [Ca(2+)](c). Xestospongin C significantly ameliorated isoflurane cytotoxicity in primary cortical neurons, as well as inhibited the calcium release from the ER in primary cortical neurons. Isoflurane did not induce significant changes of ROS production in primary rat cortical neurons. Sevoflurane, at equivalent exposure to isoflurane, did not induce similar cytotoxicity or elevation of peak [Ca(2+)](c) in primary rat cortical neurons.</p><p><b>CONCLUSION</b>These results suggested that isoflurane induced elevation in [Ca(2+)](c), partially via elevated activity of IP(3) receptors, which rendered cells vulnerable to isoflurane neurotoxicity. ROS production was not involved in isoflurane-induced neurotoxicity. Sevoflurane, at an equivalent exposure to isoflurane, did not induce similar elevations of [Ca(2+)](c) or neurotoxicity in primary cortical neurons of rat.</p>

Neuroprotection and neurotrophism effects of liquiritin on primary cultured hippocampal cells / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the neuroprotective and neurotrophic effects ofliquiritin (LQ) on rats primary cultured hippocampal neuronal damage induced by Abeta25-35.</p><p><b>METHOD</b>The rats hippocampal neuronal damage model by Abeta25-35 was established. The protective effects of LQ to the cells were observed through the MTU assay. The apoptosis of neurons was detected by flow cytometer and the concentration of intracellular calcium by fluorescence probe dying. LQ' s neurotrophic effects were observed through measuring the neurite outgrowth induced by LQ in primary cultured hippocampal neurons and the differentiation of LQ on hippocampal stem cells to cholinergic neurons was assayed by flow cytometry.</p><p><b>RESULT</b>Treatment of the cells with 10 micromol x L(-1) Abeta25-35 could induce a significant decrease of cell viability, enhance the level of intracellular [Ca2+] and increase the percentage of apoptosis to 28%. However, pretreatment with LQ (0.1, 1, and 10 micromol x L(-1)) for 6 hours exhibited cytoprotective effects, inhibited the cells' s death induced by Abeta25-35, prevented the accumulation of [Ca2+], and decreased the apoptosis neurons significantly to 10%, 15% and 9%, which meaned that LQ could antagonize Abeta25-35 induced apoptosis. LQ together with NGF had a dramatic prolonged effect on the neurite of the primary cultured hippocampal neurons, which was blocked by a specific MAPK kinase inhibitor to some extent. In addition, LQ could induce the differentiation of hippocampal stem cells to cholinergic neurons in vitro.</p><p><b>CONCLUSION</b>These results demonstrate that LQ has the neuroprotective capacity to cell damage iduced by Abeta25-35 in primary cultured hippocampal neurons, and also has the neurotrophic effects.</p>

Effect of recombinant microplasmin on acute cerebral infarction in rats / 药学学报

The effect of recombinant microplasmin (micro-plasmin) on acute cerebral infarction was evaluated in rats, and compared with recombinant tissue plasminogen activator (rt-PA). After the model of middle cerebral artery occlusion (MCAO) was established by autologous blood clots, different doses of micro-plasmin (2.5, 5, and 10 mg x kg(-1)) were administered into the thrombus intra-arterial. Twelve hours after administration of micro-plasmin, the neurological deficit score of rats was recorded and the infarct volumes were determined. Bleeding time (BT), fibrin degradation product (FDP) concentration in serum and thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB) concentration in plasma were tested after administration. Intra-arterial administration of micro-plasmin could reduce significantly neurological deficit score and infarct volumes in MCAO rats. FDP concentration increased significantly as compared with model group. There were no significant differences in TT, PT and BT. FIB concentration reduced markedly as compared with model group, but had no significant difference as compared with sham group. The results suggest that micro-plasmin is effective in treatment of rat acute cerebral infarction, and has no significant influence on fibrinolytic system and blood clotting system, indicating that micro-plasmin may be useful for treatment of acute cerebral infarction, and not lead to hemorrhage. Micro-plasmin seems to be distinguished from clinical used rt-PA by its no hemorrhage effect.

Advances in studies on absorption, distribution, metabolism of flavonoids / 中国中药杂志

Plenty of data and tests suggested that flavonoids have strong physiological and pharmacological activities. In this paper, the absorption, distribution and metabolism of flavonoids in gaster, gut and liver were introduced. The research of absorption, distribution and metabolism on flavonoids will provide theoretical basis for developing new drugs of flavoniods.

Protective effect of madecassoside against reperfusion injury after regional ischemia in rabbit heart in vivo / 药学学报

This study is to investigate if madecassoside can protect against myocardial reperfusion injury in rabbit heart in vivo. The ischemia reperfusion model was established. Left ventricular function and ECG were monitored at the ischemia and reperfusion period. The infarct areas were expressed as percentage. The levels of LDH, CK, MDA and SOD were measured and C-reactive protein (CRP) in serum was measured by ELISA kit. Cardiomyocyte apoptosis were measured by TUNEL staining. A monoclonal rabbit anti-goat Bcl-2 proteins as primary antibody was used for Bcl-2 immunohistochemical staining. Treatment with madecassoside (3.2, 1.6 and 0.8 mg x kg(-1)) i.v. during ischemia reperfusion injury attenuated myocardial damage, that is, characteristic of decreasing infarct size, decreasing LDH and CK release. Activities of SOD were diminished and MDA level increased obviously in control group whereas pretreatment with madecassoside significantly blunted the decrease of SOD activity, markedly reduced the levels of MDA, CRP and cardiomyocyte apoptosis, and upregulated the expression of Bcl-2. Madecassoside has the protective effect against myocardial ischemia reperfusion injury, and effects of anti-lipid peroxidation, enhancement of SOD activity, anti-inflammation and anti-apoptosis.

An analysis of the features of HBx protein distributed in liver cells and its expression in E. coli / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the features of HBx protein distributed in liver cells and its expression in E. coli.</p><p><b>METHODS</b>The expression vectors encoding the full length HBx and its mutants were constructed by the routine molecular cloning method. HBx protein expression was detected using Western blotting. The distribution feature of HBx protein in liver cells was examined using the fluorescence confocal microscopy. A series of purified HBx fusion proteins were obtained by glutathione-sepharose 4B affinity chromatography.</p><p><b>RESULTS</b>The expression vectors were successfully constructed for the full length HBx and its mutants. HBx was found distributed uniformly in the nuclei but granularly in the cytoplasm of the liver cells. Under optimal conditions, the mutant GST-HBx (72-120aa) was easily degraded.</p><p><b>CONCLUSION</b>This study may provide a basis for further study on the biological function of HBx at the protein level.</p>

Establishment of a reporter gene-based cell screening model for discovering new agonists of estrogen receptor beta subtype / 药学学报

<p><b>AIM</b>To establish a sensitive and efficient reporter gene-based screening model for finding agonists of estrogen receptor beta subtype.</p><p><b>METHODS</b>A recombinant vector pTAL-ERE-SEAP was constructed by inserting a synthetic sequence composed of five estrogen responsive elements in front of promoter of pTAL-SEAP vector. pTAL-ERE-SEAP was then transfected into human embryonic kidney (HEK293) cells. G418 (200 microg x mL(-1)) was added to select positive clones that can be induced by E2 to express reporter gene SEAP. The speciality was tested by several ligands of relative nuclear receptors of the same family. The stability of the model, the time-effect relationship, the dose-response relationship, and the immunocytochemistry staining of ERbeta expression after transfection were observed. 2 622 compounds were screened by using this model.</p><p><b>RESULTS</b>Stably transfected clones were obtained. The expression levels of reporter gene SEAP of positive clones was induced by E2 in a dose-response and time-effect relationship manners. The Z' factor value was 0.7. The expression levels of dexamethasone and other ligands were low. The result of immunocytochemistry staining showed the expression of ERbeta. E2 had no proliferating effects on stably transfected clones.</p><p><b>CONCLUSION</b>Stably transfected positive clones transfected with recombinant vector pTAL-ERE-SEAP were obtained. The positive clones may be used to screen for agonists of estrogen receptor beta subtype by measurement of luminescent value of expressed SEAP in wells of microlitre plate.</p>

XBP-1 interacts with estrogen receptor alpha (ERalpha) / 生物工程学报

Estrogen receptor alpha (ERalpha) has been a primary target of treatment as well as a prognostic indicator for breast cancer. The level of human X-box binding protein 1 (XBP-1) mRNA was related with that of ERalpha in breast tumors and was over-expressed in some breast tumors. These previous studies suggested that XBP-1 may interact with ERalpha. XBP-1 has two isoforms, XBP-1S and XBP-1U, as the result of unique splicing. GST pull-down assay showed that both XBP-1S and XBP-1U bound to ERalpha in vitro. The binding of XBP-1S to ERalpha was stronger than that of XBP-1U to ERalpha. Co-immunoprecipitation revealed that the binding was in a ligand-independent manner. XBP-1S and XBP-1U interacted with the region of ERalpha that contains a DNA-binding domain. The ERalpha-interacting regions on XBP-1S and XBP-1U have been mapped to two regions, the N-terminal basic region leucine zipper domain (bzip) and the C-terminal activation domain. These findings suggest that XBP-1S and XBP-1U may participate in ERalpha signaling pathway through the mediation of ERalpha.