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Multicollinearity is an important issue affecting the results of regression analysis. LASSO developed in recent years has great advantages in selecting explanatory variables, processing high-dimensional data, and solving multicollinearity problems. This method adds a penalty term to the model estimation, which can compress the regression coefficients of some unnecessary variables to zero and then remove them from the model to achieve the purpose of variable screening. This paper focuses on the LASSO method and compares it with optimal subsets, ridge regression, adaptive LASSO, and elastic net results. It is found that both LASSO and adaptive LASSO have good performance in solving independent variable multicollinearity problems and enhancing model interpretation and prediction accuracy.
Subject(s)
Humans , Regression AnalysisABSTRACT
Morus alba, a traditional economic crop, is also a significant medicinal plant. The branches(Mori Ramulus), leaves(Mori Folium), roots and barks(Mori Cortex), and fruits(Mori Fructus) of M. alba are rich in chemical components, such as alkaloids, flavonoids, flavanols, anthocyanins, benzofurans, phenolic acids, and polysaccharides, and possess hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, anti-microbial, liver protective, immunoregulatory, and other pharmacological activities. This study analyzed the sources, classification, and functions of the main chemical components in M. alba and systematically summarized the latest research results of essential active components in M. alba and their pharmacological effects to provide references for in-depth research and further development as well as utilization of active components in M. alba.
Subject(s)
Anthocyanins , Flavonoids/pharmacology , Morus , Plant Extracts/pharmacology , Plant LeavesABSTRACT
The study evaluates the lipolysis rate and extent of type Ⅲ lipid formulations using testosterone undecanoate as a model drug after digestion with in vitro lipolysis model, and studies the digestive regularity with optical microscope and electrical conductivity. The results showed that for testosterone undecanoate type Ⅲ lipid formulations with castor oil as oil phase and Transcutol HP as latent solvent, the lipolysis rate and extent were increased with the increase of oil phase proportion and were decreased with excessive proportion of surfactant, in which can see liquid crystal phase during lipolysis process. The lipolysis rate of type ⅢB lipid preparations with different surfactant were ordered as Labrasol > Tween 80 > Cremophor EL, but the rate of type ⅢA is different in quick digestion phase and slow digestion phase. The lipolysis extent of type Ⅲ lipid formulations with different surfactant were ordered as Cremophor EL > Tween 80 > Labrasol. These may be related to the digestive effect of pancreatic lipase on different surfactants. This study implied that the lipolysis rate and extent of type Ⅲ lipid formulations are greatly influenced by the proportion of oil phase and surfactant, and the surfactant structure. These factors will affect the in vivo digestion and should be taken into account when screening type Ⅲ lipid formulations.
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The Chinese folk medicinal herb Hypericum japonicum, also known as Tianjihuang or Diercao in Chinese, has been widely used for clearing heat and removing toxin, hemostasis and detumescence, and for the treatment of acute and chronic hepatitis, and gastrointestinal disorders. In recent decades, several main types of chemical constituents such as phloroglucinols, flavonoids, xanthonoids, pyranones, and dipeptides have been reported. Modern pharmacology studies have shown that the extracts or secondary metabolites of the herb possess a variety of bio-activities such as hepatoprotective, antioxidant, anti-tumorous, antiviral, anti-bacterial, and anti-malarial activities as well as effects on cardiovascular diseases. In this paper, we presented the main metabolites and pharmacological activities of the plant in recent 30 years, which should be helpful for the further development and utilization of the herb resources of H. japonicum.
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To understand the awareness, treatment, and control of hypertension in residents aged 35-75 years in eastern China, analyze the treatment mode for antihypertensive agents while identifying those factors affecting awareness, treatment and control. The data collected in eastern China from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project were used to obtain the information about the awareness, treatment and control of hypertension in the residents and the antihypertensive medication treatment mode in this area. Multilevel mixed-effects model was used to explore the association of the demographic characteristics of hypertension patients with the rates of awareness, treatment and control of hypertension. A total of 640 539 participants aged 35-75 years, mean age (56.9±9.6) years, were included in the analysis, women accounted for 59.7 and 318 741 (49.8) of the participants suffered from hypertension. Among those hypertensive patients, 46.5 were aware of their condition, 38.1 were taking prescribed antihypertensive medications, and 11.1 had achieved the control of hypertension, the differences were significant among provinces, between urban area and rural area and among different demographical groups. Calcium-channel blockers was the most commonly used medication (45.1), and 78 735 hypertension patients (86.2) took only one type of medication. Older age, higher household income, higher level of education, and histories of myocardial infarction, stroke and diabetes were associated with higher awareness, treatment and control of hypertension (<0.05). The rates of awareness, treatment and control of hypertension were low in residents in eastern China. The differences in hypertension management were significant among provinces and between urban area and rural area. Further efforts are needed to enhance the system of hypertension prevention, screening, diagnosis and treatment.
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@#In this study, the effect of pH regulator meglumine(MEG)on the dissolution behavior of indomethacin(IND)amorphous solid dispersions was evaluated. The amorphous solid dispersion was prepared by hot-melt extrusion using IND and Kollidon® VA64 at a weight ratio of 1∶4, and extrudates were characterized using differential scanning calorimetry(DSC)and X-ray powder diffraction(PXRD). The dissolution behaviors of solid dispersions with or without MEG were investigated in three kinds of pH media. The effect of infiltration rate of media, microenvironmental pH(pHM)and recrystallization of drugs on drug dissolution were evaluated by designing the appropriate experiments. The results showed that the presence of MEG could accelerate the dissolution of IND from solid dispersions through providing an alkaline microenvironment, but in different dissolution media, the intensity and duration of alkaline microenvironment, recrystallization of local drug molecules and infiltration rate of media showed an obvious difference, and the above factors simultaneously affected the dissolution behavior of drugs from solid dispersions.
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Objective:To investigate the effect of different dosage forms of gonadotropin-releasing hormone agonist(GnRH-a) on in vitro fertilization-embryo transfer(IVF-ET) in patients with mild endometriosis.Methods:Totally 269 cycles(175 cases) of IVF-ET were included,which was divided into three groups:pro-long protocols (long acting 3.75 mg group,102 cycles),long protocols (long acting 1.875 mg group,87 cycles) and short protocols(short-acting 0.1 mg group,80 cycles).The clinical results were compared among groups.Results:The amount of gonadotropin(Gn) were significantly higher in pro-long protocol than the other ones.The implantation rate and clinical pregnancy rate were significantly higher in long acting 1.875mg group than the other two protocols (P ＜ 0.05).Conclusions:Long protocol (long acting GnRH-a down-regulation,1o 875 mg) may be more beneficial to improve the implantation rate and clinical pregnancy rate of in vitro fertilization-embryo transfer(IVF-ET) in patients with endometriosis.
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Objective To study the prokaryotic expression and immune protection of triosephosphate isomerase(TPI)of Toxoplasma gondii in mice. Methods Total RNA was extracted from toxoplasma tachyzoites,and TPI fragment was amplified by PCR and cloned into the prokaryotic expression vector pET-28a(+). The target protein was induced with IPTG and purified by Ni-NTA affinity chromatography. The mice were immunized 4 times by emulsified TPI with adjuvant,and the last time was the strengthen immunization. At the same time,an adjuvant group and a normal group were set as controls. The blood samples were got from the tail vein of the mice,and the serum antibody titres were detected. All the mice were challenged with 400 toxo-plasma tachyzoites to observe the survival time. Results The TPI gene was amplified from T. gondii cDNA by PCR. The recom-binant vector TPI/pET-28a(+)was usefully constructed,and the TPI protein was expressed and purified. The serum antibody ti-tre could be more than 100 thousand. After infected with toxoplasma tachyzoites,the survival time of the mice in the experimen-tal group was longer than that of the mice in the control groups. Conclusion The TPI protein of T. gondii could trigger the im-munoprotection against T. gondii challenge in the mice.
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Objective To summarize the present development by analysis of projects in schistosomiasis funded by National Science Foundation of China(NSFC). Methods Based on the ISIS database of NFSC,the projects in the studies of schistoso-miasis from 2005 to 2016 were analyzed. The distributions of sponsored numbers,amounts,types,agencies,disciplines and changes in research topics by means of network profiles were described. Results During the study period,198 projects were funded by NSFC totally with 76.05 million yuan in which the general and youth projects were main types. The main sponsored agencies were research institutes and medical colleges. The top three fields sponsored were medical pathogenic microbes and in-fection,veterinary and medical immunology. Conclusion The funding on schistosomiasis researches has a downward trend, but studies are continuing in depth. In this situation,innovative and interdisciplinary researches need to be encouraged to pro-mote the development of schistosomiasis.
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Objective To study the association of Hp infection and insulin resistance (IR) with vascular dementia (VaD).Methods Eighty-six elderly VaD patients admitted to our hospital from April 2015 to April 2016 served as a VaD group and 52 healthy subjects undergoing physical examination served as a control group in this study.The patients in VaD group were further divided into Hp-positive group (n =50) and Hp-negative group (n =36).Their fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured with positive C13 urea breath test as the diagnostic index of Hp infection.HOMA-IR=FINS× FBG/22.5 was calculated according to the self balance model analysis.Results The positive Hp rate,serum FBG and FINS levels,and HOMA-IR were significantly higher in VaD group than in control group (58.14％ vs 28.58％,x2=10.273,P=0.002;5.53±0.60 mmol/L vs 5.19±0.38 mmol/L,P=0.0004;10.29±4.95 μIU/L vs 8.77±4.02 μIU/L,P=0.0317;2.57±1.34 vs 2.06±0.96,P=0.0179).The serum FBG and FINS levels and HOMA-IR were significantly higher in Hp-positive group than in Hp-negative group (P＜0.05,P＜0.01).Conclusion Hp infection and IR are closely associated with VaD,and can thus lead to the occurrence or progression of VaD by inducing or aggravating IR.
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@#Hot-melt extrusion technology was used to prepare solid dispersion of posaconazole for improving its dissolution. Solubility parameter, glass transition temperature and melting method were utilized to screen polymers. Using KollidonVA64, Soluplus, Eudragit L100 and combined carrier KollidonVA64-Eudragit L100 as polymer carrier, solid dispersion was prepared by hot-melt extrusion technology and characterized by drug dissolution. The formulation and process factor affecting dissolution were studied. The state of posaconazole in solid dispersion was characterized by differential scanning calorimetry and preliminary analysis of the stability was studied by influencing factors experiments. When using KollidonVA64-Eudragit L100(2 ∶8)as the carrier, 10 % triethyl citrate as the plasticizer and extrusion temperature of 150 °C, the dissolution of posaconazole was improved significantly. Drug was molecular or amorphous form in the carrier. Proportion of Eudragit L100 and KollidonVA64, temperature, drug loading and plasticizer influenced dissolution of posaconazole. Solid dispersion was stable for high temperature and strong light but sensitive to high humidity. Solid dispersion using hot-melt extrusion technology can significantly improve the dissolution of posaconazole.
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This study is to report the evaluation of the micromeritic properties of LubriTose AN, which is expected to provide preliminary theoretical basis for the direct compression technology. From the aspects of flowability, compressibility and dilution potential, the angle of repose, flow velocity, the Carr' index, tensile strength, elastic recovery, yield pressure and the lubricating ability of LubriTose AN were determined. Also, model drugs were selected to investigate the dilute potential under the desirable compressing performance. Compared to the physical mixtures, the flowability of LubriTose AN was better, and the deformation mechanism was the same with anhydrous lactose, both brittle deformation. The compressibility and compaction of LubriTose AN was slightly better than that of physical mixtures under low and moderate pressure. The dilution potential of LubriTose AN were high for most of hydrophobic drugs. The lubricate ability was desirable under different rotational speeds. LubriTose AN is an excellent co-processed excipient, which is helpful for the promotion and improvement of the tablet manufacturing level.
Subject(s)
Drug Compounding , Elasticity , Excipients , Chemistry , Glycerides , Chemistry , Ibuprofen , Chemistry , Lactose , Chemistry , Lubricants , Chemistry , Lubrication , Particle Size , Pressure , Technology, Pharmaceutical , Methods , Tensile StrengthABSTRACT
Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities. But the clinical use is limited by its low bioavailability. The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use. The transport characteristics and mechanisms of limonin in rat were studied by in situ intestine perfusion and in vitro Caco-2 cells method. The intestinal absorption of limonin was probably via a facilitated diffusion pathway which was poor and without segment-selection. Verapamil and ketoconazole improved the absorption remarkably according to the result of in vitro Caco-2 cells study; however, probenecid had no significant effect on the absorption. The P-gp efflux and CYP3A4 metabolism were involved in the poor intestinal absorption and low bioavailability of limonin. The exploration of the intestinal absorption mechanism is crucial to the design of dosage form and clinical use of limonin.
Subject(s)
Animals , Humans , Male , Rats , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Biological Availability , Biological Transport , Caco-2 Cells , Cytochrome P-450 CYP3A , Metabolism , Dose-Response Relationship, Drug , Intestinal Absorption , Ketoconazole , Pharmacology , Limonins , Pharmacokinetics , Perfusion , Probenecid , Pharmacology , Verapamil , PharmacologyABSTRACT
Limonin existed in citrus fruits has been shown to have anti-bacterial, anti-viral, anti-feedant, anti-nociceptive, anti-inflammatory activities and anti-carcinogenic activities. But the clinical use is limited by its low bioavailability. The aim of this study is to observe the absorption and secretion transport mechanisms of limonin in intestine which can pave the way for the further study and clinical use. The transport characteristics and mechanisms of limonin in rat were studied by in situ intestine perfusion and in vitro Caco-2 cells method. The intestinal absorption of limonin was probably via a facilitated diffusion pathway which was poor and without segment-selection. Verapamil and ketoconazole improved the absorption remarkably according to the result of in vitro Caco-2 cells study; however, probenecid had no significant effect on the absorption. The P-gp efflux and CYP3A4 metabolism were involved in the poor intestinal absorption and low bioavailability of limonin. The exploration of the intestinal absorption mechanism is crucial to the design of dosage form and clinical use of limonin.
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<p><b>OBJECTIVE</b>To map the susceptibility gene of developmental dysplasia of the hip(DDH) in chromosome 17q21 region.</p><p><b>METHODS</b>According to the number of alleles (≥ 5), heterozygosity (≥ 0.70) and polymorphic information content (PIC≥ 0.5), 11 STR markers in the 17q21 region were chosen for transmission disequilibrium test (TDT). STR markers were amplified by PCR and genotypes were analyzed by capillary electrophoresis in 103 trio families. TDT was used to locate the susceptibility gene in 17q21 region.</p><p><b>RESULTS</b>Because of a low genetic polymorphism, D17S810 and D17S931 loci were removed from the TDT. Transmission disequilibrium was detected at D17S855, D17S858, D17S806, D17S1877, D17S941, D17S752 and D17S790, which overlapped 11.7 cM in 17q21. However, no transmission disequilibrium was found at D17S1787 and D17S787. Thus, the susceptibility gene for DDH was located in the chromosome region between D17S855 and D17S790.</p><p><b>CONCLUSION</b>The susceptibility gene for DDH is narrowed to an 11.7 cM region of 17q21.31-17q22, between STR loci D17S855 and D17S790.</p>
Subject(s)
Child , Child, Preschool , Female , Humans , Infant , Male , Chromosome Mapping , Methods , Chromosomes, Human, Pair 17 , Genetics , Cloning, Molecular , Genetic Predisposition to Disease , Genetics , Hip Dislocation, Congenital , Genetics , Linkage Disequilibrium , Genetics , Microsatellite Repeats , Genetics , Polymorphism, Genetic , GeneticsABSTRACT
OBJECTIVE@#To establish a new method of SNP typing.@*METHODS@#Based on the principle of allele specific PCR and capillary electrophoresis technique, 11 diallelic SNP loci were selected and two forward primers with different length were designed for each SNP, with their 3' ends matched to the two alleles, respectively. An artificially mismatched base was also introduced into the third or fourth base in the 3' end area of the two forward primers in order to enhance the specificity of amplification. A common reverse primer was designed 100-300 bp away from the forward primers, and labeled with fluorescence. The PCR products were separated and analyzed by ABI Prism 310 Genetic Analyzer after all of the 11 SNPs were multiply amplified.@*RESULTS@#A single product peak was observed while the SNP was homozygous, and two product peaks with different height were observed while the SNP was heterozygous. The length of PCR products was different with the different SNPs. According to the length of the products and the number of the product peaks, the genotypes of the 11 SNPs can simultaneously be analyzed, and the results were in accordance with the direct sequencing.@*CONCLUSION@#Fragment length discrepant allele specific fluorescence labeled multi-PCR (FLDASFLM-PCR) is a simple, rapid and efficient new method for SNP typing.
Subject(s)
Humans , Alleles , Electrophoresis, Capillary/methods , Forensic Genetics , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide/geneticsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the application of fluorescence in-situ hybridization (FISH) in detection of gene translocation in paraffin-embedded tissue samples of synovial sarcoma.</p><p><b>METHODS</b>Interphase FISH was carried out in paraffin-embedded tissue of 42 cases of synovial sarcoma and 9 cases of non-synovial sarcoma, using a LSI SYT (18q11.2) dual color break-apart probe. In all of the cases studied, the gene fusion product SYT-SSX was also analyzed by reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Positive signals were detected in 37 cases (88.1%) of synovial sarcoma by FISH, as compared with 35 cases (83.8%) by RT-PCR and 39 cases (92.9%) by both techniques. Of the 39 positive cases, 33 cases (78.5%) revealed SYT gene translocation.</p><p><b>CONCLUSIONS</b>FISH may serve as an adjunctive diagnostic tool in problematic cases of synovial sarcoma and can be applied in paraffin-embedded tissue samples. As compared with RT-PCR, FISH is also sensitive and reliable. The methodology is less labor intensive and time consuming. FISH has great potential in molecular diagnosis of soft tissue tumors.</p>