Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

Simultaneous quantitative analysis of multi-compounds by a single marker in Radix Astragali by using serum HPLC-MS feature.

Using the serum pharmacochemistry method for Chinese Medicine, the material basis of Radix Astragali (RA) for "regulating and enriching blood" was studied. By compared with blank blood sample as a positive control in adult Wistar rats, four original saponinsas the material basis for "regulating and enriching blood" were absorbed into the blood after oral administration of RA. They were identified as astragaloside, astragaloside, astragaloside and astragaloside by HPLC-MS. According to the constituents absorbed into blood, the extracts of RA were prepared. In addition, the present patterns of quality control are limited to industrial application because most of the natural standard ingredients are very expensive and unavailable. Therefore, a quantitative analysis method of multi-components with a single marker (QAMS) was established and used to simultaneously measure four saponins from RA absorbed into the blood (Astragaloside, astragaloside, astragaloside and astragaloside). We used astragaloside I as the reference, the relative correction factors (f) of the other three saponins were measured by HPLC-MS. Within the linear ranges, the values of f of astragaloside I to astragaloside IV, astragaloside III and astragaloside II were 0.533, 0.779 and 0.934, respectively. According to the f values, we simultaneously determined four saponins using only one marker. The results of QAMS method were validated compared to that of external standard method, and no significant difference was observed.

Ultrasound-driven secondary self-assembly of amphiphilic ß-cyclodextrin dimers.

The controlled secondary self-assembly of amphiphilic molecules in solution is theoretically and practically significant in amphiphilic molecular applications. An amphiphilic ß-cyclodextrin (ß-CD) dimer, namely LA-(CD)2 , has been synthesized, wherein one lithocholic acid (LA) unit is hydrophobic and two ß-CD units are hydrophilic. In an aqueous solution at room temperature, LA-(CD)2 self-assembles into spherical micelles without ultrasonication. The primary micelles dissociates and then secondarily form self-assemblies with branched structures under ultrasonication. The branched aggregates revert to primary micelles at high temperature. The ultrasound-driven secondary self-assembly is confirmed by transmission electron microscopy, dynamic light scattering, (1) H NMR spectroscopy, and Cu(2+) -responsive experiments. Furthermore, 2D NOESY NMR and UV/Vis spectroscopy results indicate that the formation of the primary micelles is driven by hydrophilic-hydrophobic interactions, whereas host-guest interactions promote the formation of the secondary assemblies. Additionally, ultrasonication is shown to be able to effectively destroy the primary hydrophilic-hydrophobic balances while enhancing the host-guest interaction between the LA and ß-CD moieties at room temperature.

Cross-resistance and biochemical resistance mechanisms of avermectin resistant population of Dendrolimus punctatus.

To identify the resistance risk and the resistance mechanism of avermectin against Dendrolimus punctatus, we examined the cross-resistance of avermectin resistance population (AV) to multiple tested insecticides and the synergism of piperonyl butoxide (PBO), triphenyl phosphate (TPP) and diethyl maleate (DEM) to AV, Qin-ling Jieguanting (JGT) and susceptible (S) popultions, by leaf dipping method. The activities of carboxylesterase (CarE), glutathione S-transferases (GST) and mixed-functional oxidases (MFOs) in AV, JGT and S populations of D. punctatus was measured with spectrophotometry. The results showed that the AV population of D. punctatus had medium level of cross-resistance to emamectin benzoate (resistance ratio, RR50=25.0), chlorpyrifos (RR50=19.0), and cyhalothrin (RR50=15.4), and low level of cross-resistance to chlorfenapyr (RR50=8.1), but no cross-resistance to spinetoram, spinosad and chlorantraniliprole. Both PBO and TPP had significant synergism of avermectin to AV, JGT, and S populations, while DEM had no synergism to all the three populations. Compared with the S population, the AV population had higher content of MFOs cytochromes P450(3.5-fold) and b5(3.1-fold) and the activities of O-demethylase (4.1-fold) and CarE (2.2-fold). There was no significant difference in the activities of GST between AV and S populations. The increasing mixed-functional oxidases and CarE played an important role in the resistance of D. punctatus to avermectin. Spinetoram, spinosad, chlorantraniliprole, and avermectin were recommended to control D. punctatus.

PKCδ promotes the invasion and migration of colorectal cancer through c-myc/NDRG1 pathway.

Objective: Colorectal cancer (CRC) is the third cause of expected cancer deaths both in men and women in the U.S. and the third most commonly diagnosed cancer in China Targeted therapy has been proven to improve overall survival for unresectable metastatic CRC. But the location of the primary tumor or the presence of various core driver gene mutations that confer resistance may limit the utility of targeted therapy. Therefore, it is of great significance to further elucidate novel mechanisms of invasion and metastasis of CRC and find potential novel therapeutic targets. Protein Kinase C Delta (PKCδ) plays an important role in various diseases, including tumors. In CRC, the function of PKCδ on proliferation and differentiation is mostly studied but various research results were reported. Therefore, the role of PKCδ in CRC needs to be further studied, especially in tumor invasion and metastasis in CRC which few studies have looked into. Methods: The expression of PRKCD was analyzed by the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases and Immunohistochemical (IHC). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) enrichment analysis were used to explore the biological functions and pathways related to PRKCD. Lentivirus transfection was used to construct CRC cell lines with overexpression and knock-down of PKCδ or N-myc Downstream Regulated Gene 1 (NDRG1). Cell invasion and migration assay, wound healing assay were used to detect the function of PKCδ and NDRG1 in the invasion and migration of cells. Flow cytometry analysis was used to detect the influence of PKCδ on the CRC cell cycles .Immunofluorescence histochemistry ,Immunoprecipitation Assay and qPCR were used to detect the relationship of PKCδ and NDRG1. Xenograft model was used to verify the role of PKCδ in vivo. Results: PKCδ is overexpressed in CRC and could promote Epithelial-Mesenchymal Transition (EMT) and the invasion and migration of CRC in vitro. We confirmed that PKCδ and the tumor suppressor factor NDRG1 had a co-localization relationship in CRC. PKCδ inhibited NDRG1 transcription and protein expression. Overexpressing NDRG1 could inhibit the function of PKCδ in promoting tumor invasion and migration. PKCδ could regulate c-Myc, one transcription factor of NDRG1, to down-regulate NDRG1. In vivo, overexpressing PKCδ could promote xenograft growth and volume. Thus, our results showed that PKCδ reduced the expression of NDRG1 through c-Myc, promoting the invasion and migration of CRC through promoting EMT. Conclusion: The increased expression of PKCδ in CRC tumor tissue could promote the invasion and migration of tumor cells, and one of the mechanisms may be regulating c-Myc to inhibit the expression of NDRG1 and promote EMT.

[Therapeutic effect of metformin for clomiphene-resistant infertility patients with polycystic ovary syndrome: a systematic analysis].

OBJECTIVE: To evaluate the efficacy of metformin (MTF) in treatment of clomiphene (CC)-resistant patients with polycystic ovary syndrome (PCOS). METHODS: The published articles of randomized controlled trial (RCT) of comparison of MTF combined with CC and CC alone in treatment of CC-resistant PCOS were searched in PubMed, EMBASE, OVID, EBSCO databases and Cochrane Library, and these studies were screened under inclusion and exclusion criteria. The quality of included studies and extract data of comparison of ovulation rates and pregnancy rates were evaluated. And the Meta-analysis using statistic software RevMan 5.0 was completed. RESULT: Total of 333 patients in total 8 trials were included. Meta analysis showed that MTF plus CC led to a significantly higher clinical ovulation rate (OR = 7.31, 95%CI: 2.57 - 20.76, P < 0.05) and pregnancy rate (OR = 7.93, 95%CI: 2.45 - 25.63, P < 0.05) than that of CC alone. CONCLUSION: MTF can increase ovulation and pregnancy rates of CC-resistant PCOS women.

[A meta-analysis of tubeless versus standard percutaneous nephrostolithotomy].

OBJECTIVE: To systematically review the advantages of tubeless percutaneous nephrolithotomy. METHODS: The randomized controlled trials (RCTs) of tubeless and standard percutaneous nephrolithotomy were retrieved and their included references investigated. Data analyses of literatures fulfilling the inclusion criteria were performed with the Cochrane ColLaboration's RevMan 5.0 software. RESULTS: Seven literatures were finally retrieved after screening. A total of 1365 patients were included for a meta-analysis. The results showed that, as compared with the control group (standard percutaneous nephrolithotomy), the patients in the trial group (tubeless percutaneous nephrolithotomy) had the following features. (1) There was no significant difference in mean operative duration and change of hemoglobin (95%CI -15.16 to 0.13, P = 0.05; 95%CI -0.16 to 0.19, P = 0.90 respectively). (2) The hospitalization stay was shortened an average of 23.86 hours (95%CI -32.35 to -15.36, P = 0.000). (3) The postoperative analgesic dose was lowered by 69.02 mg (95%CI -107.67 to -30.36, P = 0.000). (4) There was a remarkable improvement of the stone-free rate (95%CI 1.25 to 2.95, P = 0.003). CONCLUSION: Tubeless percutaneous nephrolithotomy may shorten the hospitalization stay, lower the postoperative analgesic dose and improve the stone-free rate. It is significantly superior to standard percutaneous nephrolithotomy.

[Effect of recombinant hIFN-alpha-2b-BCG on mouse bladder tumor MB49 cells in vitro].

OBJECTIVE: To investigate the antitumor effect of recombinant IFN-alpha-2b-BCG on mouse bladder cancer MB49 cells in vitro, and to explore its antitumor mechanisms. METHODS: MB49 cells were co-cultured with recombinant BCG or wild BCG, and than were examined by light and transmission electron microscopy. The cell growth was assessed by MTT assay, and apoptosis rate and MHC-I of the MB49 cells was detected by flow cytometry using AO and Hoechst33258 fluorescence immunostaining. RESULTS: The hIFN-alpha-2b-BCG-treated tumor cells showed slow growth, detachment of some cells, and various degree of degeneration. Light microscopy revealed organelle disorganization, chromatin aggregation, nuclear pyknosis, and cytolysis in some cells. Cellular membrane bulged and some bubbles were seen under fluorescence microscope using AO staining. Hoechst33258 assay also depicted frequent apoptosis in the tumor cells. The MTT assay showed that rBCG more actively than the wild BCG inhibited the proliferation of MB49 cells. The apoptosis rate of the recombinant BCG group was 19.7% and 46.6% at the time point of 24 h and 48 h, respectively, significantly higher than 10.8% and 20.9%, respectively, in the wild BCG group. The results of flow cytometry indicated that both types of BCG enhanced the expression of MHC-I in the MB49 cells, but more effective in the recombinant BCG group. CONCLUSION: The recombinant hIFN-alpha-2b-BCG has more strong immuno-modulatory properties, anti-tumor effect on MB49 cells and induces apparent cytotoxicity in the bladder cancer cells in vitro.

Synthesis and characterization of core-shell acrylate based latex and study of its reactive blends.

Techniques in resin blending are simple and efficient method for improving the properties of polymers, and have been used widely in polymer modification field. However, polymer latex blends such as the combination of latexes, especially the latexes with water-soluble polymers, were rarely reported. Here, we report a core-shell composite latex synthesized using methyl methacrylate (MMA), butyl acrylate (BA), 2-ethylhexyl acrylate (EHA) and glycidyl methacrylate (GMA) as monomers and ammonium persulfate and sodium bisulfite redox system as the initiator. Two stages seeded semi-continuous emulsion polymerization were employed for constructing a core-shell structure with P(MMA-co-BA) component as the core and P(EHA-co-GMA) component as the shell. Results of Transmission Electron Microscopy (TEM) and Dynamics Light Scattering (DLS) tests confirmed that the particles obtained are indeed possessing a desired core-shell structural character. Stable reactive latex blends were prepared by adding the latex with waterborne melamine-formaldehyde resin (MF) or urea-formaldehyde resin (UF). It was found that the glass transition temperature, the mechanical strength and the hygroscopic property of films cast from the latex blends present marked enhancements under higher thermal treatment temperature. It was revealed that the physical properties of chemically reactive latexes with core-shell structure could be altered via the change of crosslinking density both from the addition of crosslinkers and the thermal treatment.

[A systematic review of anti-interleukin-17 antibody in the treatment of plaque psoriasis].

OBJECTIVE: To evaluate the efficacy and safety of anti-interleukin-17 antibody in the treatment of plaque psoriasis. METHDOS: Randomized controlled trials (RCT) of anti-interleukin-17 antibody (Secukinumab, Brodalumab, and Ixekizumab) in the treatment of plaque psoriasis published between January, 2000 and March, 2017 were searched from PubMed, Cochrane Library, EBSCO, EMbase, CBM, CNKI, VIPdetabase, and Wangfang database. The quality of the retrieved trials was evaluated and the results of studies were analyzed using RevMan 5.0 software. RESULTS: Thirteen RCTs were included involving a total of 11 203 patients. Meta-analysis showed a significant differences between anti-interleukin-17 antibody and placebo (or positive drug) in terms of PASI75 and sPGA (P<0.05). The total incidence of adverse events differed significantly between anti- interleukin-17 antibody and placebo, but no significant differences were found between them in the incidence of serious adverse events and discontinuation rate due to adverse events (P>0.05). CONCLUSION: Anti-interleukin-17 antibody is safe and effective for treatment of plaque psoriasis.

pH-responsive amphiphilic hydrogel networks with IPN structure: a strategy for controlled drug release.

A pH-responsive amphiphilic hydrogel with interpenetrating polymer networks (IPN) structure for controlled drug release was proposed. The IPN was constructed with hydrophilic poly(acrylic acid) (PAA) and hydrophobic poly(butyl acrylate) (PBA). Using drug N-acetyl-5-methoxytryptamine (melatonin, MEL) as a model molecule, the controlled drug release behaviors of the IPN were investigated. It is found that not only the release of MEL from the IPN can respond to change in pH, but also the presence of hydrophobic network can overcome disadvantageous burst effect of hydrophilic network. This may be a result of hydrophobic aggregation encapsulating MEL molecules.

The design and application of DNA chips for early detection of SARS-CoV from clinical samples.

BACKGROUND: SARS coronavirus has been identified as the cause of severe acute respiratory syndrome (SARS). Few tests allow confirmation or exclusion of SARS within the first few days of infection. A gene chip is a useful tool for the study of microbial infections mainly for its capability of performing multi-target analysis in a single test. OBJECTIVES: Investigate the possibility of early detection of SARS virus from clinical samples using the gene chip-based method. STUDY DESIGN: We purified RNA from SARS-CoV obtained from routinely collected peripheral blood and sputum samples of 34 patients who had been identified as probable SARS patients by following the interim U.S. case definition. Four segments of the SARS-CoV were amplified using reverse transcription-nested PCR and the products examined using the 70-mer gene chips for SARS-CoV detection. RESULTS: A blind-test of both peripheral blood and sputum specimens lead to the positive detection of SARS-CoV in 31 out of 34 patients. SARS-CoV was not found in peripheral blood or sputum specimens from three patients. Two of the 34 patients were only 3 days post-onset of symptoms and were subsequently confirmed to be SARS positive. Our results indicate that the gene chip-based molecular test is specific for SARS-CoV and allows early detection of patients with SARS with detection rate about 8% higher than the single PCR test when the sputum sample is available.

Synthesis, properties and controlled release behaviors of hydrogel networks using cyclodextrin as pendant groups.

Based on inclusion character of beta-cyclodextrin (beta-CD) with drug molecule and low glass transition temperature of poly(2-hydroxyethyl acrylate) (PHEA), a series of hydrogels with different compositions were synthesized by the copolymerization of a monovinyl cyclodexrin monomer with 2-hydroxyethyl acrylate (HEA). The structure and properties of the hydrogels were characterized by FTIR, DSC, TGA and swelling measurements. It is found that swelling ratios of these beta-CD hydrogels can keep a relative stability in the range of pH from 1.4 to 7.4, and are not sensitive to change in NaCl concentration. Using drug N-acety-5-methoxytryptamine (melatonin, MEL) as a model molecule, the controlled drug release behaviors of these hydrogels were investigated. The results indicate that the diffusion and permeation of MEL from the hydrogels may be a dominant factor for its release. Owing to the formation of MEL/beta-CD retarding diffusion rate of MEL, a sustained release of MEL from hydrogel with high content of beta-CD can be obtained compared with hydrogel PHEA without beta-CD.

Mechanism of miR-21 via Wnt/ß-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice.

OBJECTIVE: To study the mechanism of effect of miR-21 via Wnt/ß-catenin signaling pathway in human A549 lung cancer cells and Lewis lung carcinoma in mice. METHODS: The effect of miR-21 on A549 cells were detected by MTT method. MiR-21 expression levels were overexpressed or inhibited in A549 cells by transfecting with miR-21 mimics or inhibitors. Correlation among key molecules (Wnt1, ß-catenin, CyclinD1 and miR-21) of mRNA and protein levels in Wnt/ß-catenin signaling pathway were studied by Real-time PCR and Western blot hybridization assay. Invasive ability of A549 cells was determined via Transwell chamber cell invasion assay; the role of miR-21 in A549 cells was explored via the Wnt/ß-catenin signaling pathway. A Lewis lung carcinoma animal model was established to detect miR-21 expressions in tumor animals and controlled animal tissues, and verify expression changes of the above molecules in the Wnt/ß-catenin signaling pathway was determined in the animal level. RESULTS: MTT assay results showed that miR-21 overexpression could markedly enhance cell absorbance value; that is, miR-21 could increase the ability proliferation of A549 cells. ß-catenin and CyclinD1 expression levels were significantly higher in miR-21 mimic transfected cells (P < 0.05), and Wnt1 gene had no significant change. Wnt1, ß-catenin and CyclinD1 gene expression showed no significant change when miR-21 expression was suppressed, compared with controls. After cells were transfected with miR-21 mimics, cell invasion assay revealed that the perforated cells was significantly higher than the perforated cells in the control group (P < 0.01). Lewis lung assay revealed that miR-21 expression levels in the Lewis lung carcinoma were significantly higher; and at the same time, Wnt1, ß-catenin and CyclinD1 gene expression levels were significantly increased, compared to controls. CONCLUSIONS: In A549 human lung cancer cells and Lewis lung carcinoma in mice, key molecules ß-catenin and CyclinD1of miR-21 expressions and the Wnt/ß-catenin signaling pathway are positively correlated.

[Effect of YM155 on Apoptosis and Autophagy of K562 Cells].

OBJECTIVE: This study was purposed to investigate the effect of YM155, a survivin inhibitor, on the apoptosis and autophagy of K562 cells. METHODS: K562 cells were treated with YM155 at different concentration. Cell survival was analyzed by CCK-8 assay, the cell apoptosis was detected by flow cytometry. Survivin, BCL-2 and beclin1 mRNA expressions were determined by RT-PCR. Survivin, BCL-2, caspase-3, PARP and LC-3 protein expressions were assayed by Western blot. RESULTS: YM155 inhibited the proliferation of K562 cells in a time- and dose-dependent manners. With the increasing of YM155 concentration and prolonging of action time, the expression levels of mRNA and protein of survivin and BCL-2 decreased, while the expression levels of caspase-3, PARP, beclin1 and LC-3 increased. Compared with the YM155 group, the protein levels of LC-3 and caspase-3 were lower in YM155 combined with 3-MA group. CONCLUSION: YM155 can inhibit K562 cell proliferation by inducing apoptosis and autophagy, while autophagy induction effect can enhance its cytotoxic effect.

Probing into the Supramolecular Driving Force of an Amphiphilic ß-Cyclodextrin Dimer in Various Solvents: Host-Guest Recognition or Hydrophilic-Hydrophobic Interaction?

Tuning of the morphology and size of supramolecular self-assemblies is of theoretical and practical significance. To date, supramolecular driving forces in different solvents remain unclear. In this study, we first synthesized an amphiphilic ß-cyclodextrin (ß-CD) dimer that consists of one hydrophobic ibuprofen (Ibu) and two hydrophilic ß-CD moieties (i.e., Ibu-CD2). Ibu-CD2 possesses double supramolecular driving forces, namely, the host-guest recognition and hydrophilic-hydrophobic interaction. The host-guest interaction of Ibu-CD2 induced the formation of branched supramolecular polymers (SPs) in pure water, whereas the hydrophilic-hydrophobic interaction generated spherical or irregular micelles in water/organic mixtures. The SP size increased with the increase in Ibu-CD2 concentration in pure water. By contrast, the size of micelles decreased with the increase in volume ratio of water in mixtures.

Release of chlorambucil from poly(N-isopropylacrylamide) hydrogels with beta-cyclodextrin moieties.

The present work is focused on investigating the behavior of controlled drug release poly(N-isopropylacrylamide) (PNIPA) hydrogels in the presence of beta-cyclodextrin (beta-CD). For this purpose, three types of NIPA hydrogels with beta-CD moieties were synthesized with different architectures according to our previous studies. An anti-cancer drug (chlorambucil, CLB), which can form an inclusion complex with beta-CD, was selected for loading and in vitro release studies. The drug was loaded into hydrogels via a swelling method. DSC was used to study the interactions between the CLB molecules and the polymers. The results indicate that the CLB-polymer interactions are at the molecular level. Loading CLB into these polymers can result in an evident decrease in the glass transition temperature (T(g)), and the variation of T(g) (DeltaT(g)) depends on the structures of the polymers and their beta-CD content. The controlled release experiments show that the presence of beta-CD can markedly enhance CLB release from shrunken PNIPA hydrogels and increase the ratio of CLB released in total drug loading content. Release profile of CLB from hydrogels 1a-c and 4 at pH 1.4 and 7.4, at 37 degrees C.

Genetic study of a large Chinese kindred with von Hippel-Lindau disease.

BACKGROUND: Von Hippel-Lindau (VHL) disease is a heraditary cancer syndrome caused by germline mutations of the VHL tumor on the suppressor gene. This study was to show the clinical characteristics of a large Chinese kindred with von Hippel-Lindau disease and to evaluate the role of the genetic test of VHL disease in the diagnosis of VHL disease and clinical screening of members of the VHL disease family. METHODS: DNA extracted from peripheral blood was amplified by PCR to three exons of the VHL gene in 27 members of a large kindred with VHL disease. PCR products were directly sequenced. The involvements of multi-organs in the kindred with VHL disease were confirmed by history taking and radiography. RESULTS: Of 47 members in the four generations of the kindred, 18 members were diagnosed as having VHL disease. Clinical manifestations of 18 patients included: central nervous system (CNS) hemangioblastoma (5), renal cell carcinoma and CNS hemangioblastoma (3), renal cell carcinoma and retinal angioma (3), renal cell carcinoma and multiple pancreatic cysts (1), renal cell carcinoma and retinal angioma and multiple pancreatic cysts (2), renal cell carcinoma and CNS hemangioblastomas and multiple pancreatic cysts (1), and multiple pancreatic cysts and multiple renal cysts (1), multiple pancreatic cysts (2). The common lesions of the 18 patients were renal cell carcinoma (55.6%), CNS hemangioblastoma (50.0%), retinal angioma (27.8%), and multiple pancreatic cysts (38.9%). Among the 27 members who volunteered for genetic analysis, 15 members including 9 affected family patients and 2 asymptomatic patients and 4 carriers, who are still alive, presented a codon 78 from Asn to Ser change at nucleotide 446 (A-->G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic patients were initially diagnosed by genetic testing and subsequently confirmed radiologically and surgically. Members without gene mutation had no clinical evidence of VHL disease. CONCLUSIONS: The large Chinese kindred with VHL disease was classified as type I. The main characteristics in the kindred were higher incidence of renal cell carcinoma and lower incidence of retinal angioma. Genetic test plays an important role in early detecting asymptomatic patients and the carriers in clinical screening of members of the families with VHL disease. It is also important to prevent the transmission of VHL disease to their offsprings in the kindred.

[Familial and genetic study in a large Chinese kindred with von Hippel-Lindau disease and gene mutation analysis].

OBJECTIVE: To report the clinical characterization of a large Chinese kindred with von Hippel-Lindau (VHL) disease and to evaluate the role of VHL genetic testing in diagnosis of VHL disease and clinical screening for members in VHL disease family. METHODS: A large kindred with VHL disease was studied. DNA extracted from peripheral blood was amplified by PCR to three exons of VHL gene in 27 members. PCR products were directly sequenced. The data on involvement of multi-organs in the VHL disease kindred were obtained by medical history taking and radiography. RESULTS: There were 47 members in the four generations of the Chinese VHL kindred; among them, 18 members were patients with diagnostically proven VHL disease. Their clinical manifestations included: central nervous system(CNS) hemangioblastoma (n=5), renal cell carcinomas and CNS hemangioblastoma (n=3), renal cell carcinomas and retinal angiomas (n=3), renal cell carcinomas and multiple pancreatic cysts (n=1), renal cell carcinomas and retinal angiomas and multiple pancreatic cysts (n=2), renal cell carcinomas and CNS hemangioblastomas and multiple pancreatic cysts (n=1), and multiple pancreatic cysts and multiple renal cysts (n=1), and multiple pancreatic cysts (n=2). The common lesions of 18 patients in the large kindred were: renal cell carcinomas (56%), CNS hemangioblastomas(50%),retinal angiomas(28%), and multiple pancreatic cysts(39%). Of the 27 members who volunteered for genetic analysis, all 11 affected family patients who are still alive, including 9 affected family patients and 2 asymptomatic patients, presented a codon 78 from Asn to Ser change at nucleotide 446(A to G) in exon 1. Four members were carriers with the same VHL gene mutation. Two asymptomatic cases were initially diagnosed by genetic testing and subsequently confirmed by radiological imaging and surgery. Members not having the gene mutation had no clinical evidence of VHL disease. CONCLUSION: The large Chinese kindred with VHL disease was classified as type . The main characteristics of the kindred are higher incidence of renal cell carcinomas and lower incidence of retinal angiomas. The genetic testing played an important role in early detecting asymptomatic patients and the carriers in clinical screening for members in the VHL families. Also, it is important to prevent the transmission of VHL disease to the offspring in the kindred.

Preparation and properties of cyclodextrin/PNIPAm microgels.

A two-stage precipitation polymerization in aqueous solution was used to prepare beta-cyclodextrin/poly(N-isopropylacrylamide) (beta-CD/PNIPAm) core-shell microgels. At the first stage, core microgels with CD moieties were synthesized by precipitation copolymerization of N-isopropylacrylamide (NIPAm) with a monovinyl beta-CD monomer. At the second stage, using the core particles as seeds, PNIPAm shell were further added onto the seeds by NIPAm polymerization. The microgels were characterized by means of Zetasizer Nano-ZS dynamic light scattering, TEM, IR, NMR, DSC, and TGA measurements. Using paeonol as a model drug molecule, the release behaviors of the microgels were investigated. The result indicates that the core-shell microgels could respond to change in temperature. Furthermore, the release of paeonol was related to supramolecular inclusion behavior of beta-CD and temperature sensitivity of PNIPAm.