Traditional Chinese ancient prescriptions have been used for treatment of liver cancer for a long history and the scientific and rational compatibility is a great wealth for modern research and development (R&D) of new drugs. The research and development of new drugs are often accompanied with a large investment, a long cycle and a high risk, especially for the anti-tumor drugs R&D which are facing more risks and lower successful rate. In this research, the regularity of compatibility of drugs was analyzed from 124 anti-hepatoma ancient prescriptions by computer program. The results can offer help to the R&D of anti-hepatoma new drugs and reduce the risk of drug screening. In addition, we surveyed 22 companies in this field from six provinces such as Beijing, Shanghai, Tianjin and so on and obtained 240 risk assessment questionaires. Then we used qualitative analysis method to interpret the greatest impacts for the risks in the process of R&D, production and sales of anti-hepatoma new drugs. The study provides a basis for anti-liver cancer drugs R&D researchers, who can take effective measures to reduce the R&D risks and improve successful rate.
Carcinoma, Hepatocellular ; drug therapy ; history ; China ; Drug Discovery ; history ; Drug Incompatibility ; Drug Prescriptions ; history ; Drugs, Chinese Herbal ; history ; therapeutic use ; History, Ancient ; Humans ; Liver Neoplasms ; drug therapy ; history ; Research ; history

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.
Animals ; CD36 Antigens ; antagonists & inhibitors ; genetics ; metabolism ; CHO Cells ; Cells, Cultured ; Cricetulus ; Dose-Response Relationship, Drug ; Foam Cells ; cytology ; High-Throughput Screening Assays ; Humans ; Lipoproteins, LDL ; metabolism ; Macrophages ; cytology ; metabolism ; Mice ; Molecular Structure ; Plasmids ; Receptors, Scavenger ; antagonists & inhibitors ; Sf9 Cells ; Spodoptera ; Transfection

Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5'-methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4-Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N-[2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4-hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11). Among them, compounds 1 and 2 were new natural products. In the preliminary assays, none of the compounds exhibited obvious inhibition of HIV-1 protease activity (IC50 > 10 micromol x L(-1)).
Culture Media ; chemistry ; metabolism ; HIV Protease ; analysis ; HIV Protease Inhibitors ; chemistry ; isolation & purification ; Molecular Structure ; Spectrometry, Mass, Electrospray Ionization ; Streptomyces ; chemistry ; metabolism

To investigate the neuronal mechanism of retrieval of long-term digital memory in healthy volunteers, functional magnetic resonance imaging (fMRI) technique was used in the study. Twenty-two right-handed volunteers were subjected to a long-term digital memory test with block-design. The memory task and control task were adopted in the experiment alternatively. The fMRI data were recorded by a Siemens 1.5T MR machine and analyzed by SPM99. The activated brain regions were shown in the Talairach coordinate. The results showed that the Brodmann's area (BA) 9 region in left middle frontal gyrus was the most activated cortex during the long-term digital memory task. The left medial frontal gyrus, left inferior frontal gyrus, right inferior frontal gyrus, cingulate gyrus, left inferior parietal lobule, left superior parietal lobule, right superior parietal lobule, right middle temporal gyrus, left lingual gyrus, left middle occipital gyrus, right middle brain, cerebellum and right caudate nucleus tail were also involved. The activation in cortices showed obvious left predominance. It is suggested that a series of brain regions with left predominance are involved in long-term digital memory. Left lateral frontal cortex would be the most important structure for information extraction, while the other cortices and their connections may be important for processing and long-term storage of digital information.
Adolescent ; Brain ; physiology ; Female ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Memory, Long-Term ; physiology ; Parietal Lobe ; physiology ; Young Adult

AIMTo investigate whether NR2B-pERK1/2-pElk-1 signaling contributes to the Y-maze learning and memory of rat brain.

METHODS45 adult male SD rats were divided into 4 groups: (1) Ifenprodil peritoneal injection group (Ifenprodil ip, n = 14); (2) DMSO peritoneal injection group(DMSO ip, n = 15); (3) Ifenprodil cerebral ventricle injection group (Ifenprodil ic, n = 8); (4) DMSO cerebral ventricle injection group(DMSO ic, n = 8). Y-maze training and test were used as an learning and memory enhancing stimulus. Immunohistochemical and Western blotting methods were used for detecting pERK1/2 and pElk-1 expression intensity of different brain regions.

RESULTSCompared with the DMSO ip group, the ifenprodil ip group showed no change on the Y-maze learning score (P > 0.05), but its Y-maze memory score tested 24 after learning decreased (P < 0.05). Ifenprodil peritoneal injection made brain pERK1/2 and pElk-1 expression decreased generally. In hippocampus, marginal division of striatum(MrD), amygdala,these changes were more significant (P < 0.05). Compared with the DMSO ic group, the reconsolidation of Y-maze memory tested 6 hours after ifenprodil injection was impaired in ifenprodil ic group (P < 0.05). The OD value of pERK1/2 and pElk-1 positive bands in ifenprodil ic group attenuated generally. The pElk-1 positive bands of caudate putamen and MrD almost disappeared in ifenprodil ic group.

CONCLUSIONNR2B is essential for the formation of long-term memory, reconsolidation of Y-maze memory. The deactivation of NR2B by ifenprodil will impair these courses. Meanwhile, the deactivation of NR2B attenuates pERK1/2 and pElk-1 expression of learning and memory related regions after Y-maze learning and memory reconsolidation test. In MrD and caudate putamen, the pElk-1 expression are completely blocked by ifenprodil after memory reconsolidation test.

Animals ; Avoidance Learning ; physiology ; Dimethyl Sulfoxide ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Male ; Maze Learning ; physiology ; Memory ; physiology ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; ets-Domain Protein Elk-1 ; metabolism

Objective:To investigate the feasibility of real-time screening and diagnosing fundus diseases with Wild Field Imaging System (WFIS SW-8000) in the eyes with dense cataract patients.Methods:A series of case-observational study was carried out.Ninety-six dense cataractous eyes of 90 patients with suspected fundus diseases were included in Affiliated Hospital of Nantong University from April to July 2019.Lens phacoemulsification combined with intraocular lens implantation was performed after the opacity lens was removed, and fundus examination was performed with WFIS SW-8000.Super field lens, optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) was used to verify the fundus findings after surgery, which were compared with WFIS SW-8000.This study protocol was approved by Ethics Committee of Affiliated Hospital of Nantong University and followed the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical examination.Results:Among 96 eyes, fundus diseases were detected in 40 eyes with the detection rate of 41.67% by WFIS SW-8000 examination, including dry age-related macular degeneration (AMD) in 2 eyes, wet AMD in 3 eyes, polypoidal choroidal vasculopathy (PCV) in 1 eye, high myopia retinopathy (HMR) in 7 eyes, central retinal vein occlusion (CRVO) with macular edema (ME) in 1 eye, mild non-proliferative diabetic retinopathy (NPDR) in 12 eyes, moderate NPDR in 7 eyes, severe NPDR in 4 eyes and proliferative diabetic retinopathy (PDR) in 3 eyes.Fundus diseases were detected in 45 eyes with detection rate of 46.88% after surgery by a super field lens, OCT and FFA.The detectable rate of digital retinal camera examination and super field lens, OCT and FFA showed no significant difference between intraoperation and postoperation (χ 2=0.528, P=0.468). Twenty-two eyes with fundus neovascular disease or macular edema requiring drug intervention were identified intraoperatively, and intravitreal anti-inflammatory and/or anti-vascular endothelial growth factor (VEGF) drugs were injected in 11 eyes during the operation. Conclusions:WFIS SW-8000 is a useful tool for the accurate and convenient method in real-time fundus examination during phacoemulsification, which is feasible and helpful for timely intervention in and treatment of fundus diseases.

OBJECTIVETo observe the status of occult hepatitis B virus infection in chronic viral hepatitis patients with non-A to E hepatitis virus infection and explore the diagnostic value of fluorescence quantitative polymerase chain reaction (FQ-PCR) technique for occult hepatitis B virus infection.

METHODSThe amount of HBV-DNA in serum and liver tissue from 57 patients with non-A to E hepatitis virus infection who were diagnosed as chronic viral hepatitis by Menghini method liver biopsy were detected by using FQ-PCR technique, then the relation between the viral load of HBV DNA in liver tissue and hepatic inflammatory activity were analyzed.

RESULTSThirteen (22.81%), 22 (38.60%) patients were positive for HBV DNA in serum and liver tissue, respectively. The positive rate and the level of HBV DNA quantity in liver tissue were significantly higher than those in serum; HBV DNA was found positive in both serum and liver tissue in 13 cases, negative in both serum and liver tissue in 35, positive in liver tissue but negative in serum in 9, and in none of the cases HBV DNA was positive in serum but negative in liver tissue (P < 0.01). The logarithmic value of HBV DNA from 13 patients in liver tissue and in serum was respectively: (6.62 +/- 1.21) copies/g vs.(4.03 +/- 1.06) copies/ml, P < 0.01. The hepatic lesions of all HBV DNA positive patients were active pathologic changes, but the level of HBV DNA in liver tissue was not significantly correlated with the grade of hepatic inflammation activity (P > 0.05).

CONCLUSIONOccult HBV infection is the etiology of part of the chronic viral hepatitis patients with non-A-E hepatitis virus infection. Missed diagnosis will occur if diagnosis of hepatitis B is only based on detection of serum HBV markers. It is useful for improvement of the diagnostic level of HBV infection via detection of HBV DNA quantitatively in serum especially in liver tissue of chronic viral hepatitis patients with non-A-E hepatitis virus infection by using FQ-PCR technique. The chronic viral hepatitis patients with occult HBV infection should be also given effective anti-viral therapy.

Carrier State ; physiopathology ; DNA, Viral ; Hepatitis B ; physiopathology ; Hepatitis B Surface Antigens ; immunology ; Hepatitis B virus ; physiology ; Hepatitis C ; physiopathology ; Hepatitis D ; physiopathology ; Hepatitis E ; physiopathology ; Hepatitis, Viral, Human ; physiopathology ; Humans

OBJECTIVETo analyze and predict the incidence trends and burden of pancreatic cancer from 2008 to 2015.

METHODSRegistration data on pancreatic cancer of cancer registration in 1998 - 2007, were retrieved and utilized for analyzing the annual incidence of pancreatic cancer. Age-standardized rate by Chinese population (ASR) was calculated, using the direct method. JoinPoint software was applied for trend analysis. Bayesian Age-Period-Cohort Modeling Prediction Package was used to estimate age, period and cohort effects as well as to predict the incidence rates.

RESULTSFrom 1998 to 2007, the annual incidence for men and women in urban areas showed an increase of 1.86% and 2.1% per year, but the increasing trend on the age-standardized rate was not obvious in both men and women. However, the incidence rates for men and women in rural areas increased by 7.54% and 7.83% and the age-standardized rates increased by 4.82% and 5.48% per year.

RESULTSfrom the projection model showed that the trends were mainly caused by age, period and cohort effects. Based on the analysis, up to 2015, the annual new cases of pancreatic cancer would be 103 428 (60 500 for males and 42 928 for females), with 15 277 cases more than that of 2008.

CONCLUSIONThere appeared an increasing trend of pancreatic cancer incidence which was more significant in the rural areas than the slowly increasing trend in the urban areas. The increasing trend of pancreatic cancer would be slow until the year 2015. However, in the short term pancreatic cancer is still a major cancer.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; China ; epidemiology ; Cohort Studies ; Female ; Forecasting ; Humans ; Incidence ; Infant ; Male ; Middle Aged ; Pancreatic Neoplasms ; epidemiology ; Rural Population ; Sex Distribution ; Urban Population ; Young Adult

BACKGROUNDAlmost all reported fluorescence in situ hybridization (FISH) kits for prenatal diagnosis use probes from foreign (non-Chinese) countries. The aim of this study was to analyze the reliability of domestic (Chinese) FISH probe sets to detect aneuploidies of chromosomes 13, 18, 21, X, and Y related to prenatal diagnosis in 4210 cases.

METHODSCytogenetic karyotyping was carried out as a standard prenatal diagnostic test, and amniotic fluid cell interphase FISH analysis was performed using two sets of probes (centromeric probes for chromosomes 18, X, and Y, and locus-specific probes for chromosomes 13 and 21) provided by GP Medical Technologies, Beijing, China. Then we compared the two results and found the performance characteristics for informative FISH results of aneuploidies by the domestic kit probes.

RESULTSIn 4210 cases, 4126 cases generated karyotype results and 133 abnormal karyotypes (including 97 aneuploidies) were found. The FISH results of 98 cases (among them, 31 cases gave normal cytogenetic results) were uninformative. The rate of abnormal cases was 3.2% (133/4126). For the abnormal karyotypes, the rate of aneuploidy was 72.9% (97/133). Among the 97 aneuploidies, there were 58 cases of trisomy 21 (58/97, 59.8%), four cases of trisomy 13, 23 cases of trisomy 18, and 12 cases of sex chromosomal aneuploidies. The total concordance of the two methods was 97.9% (95/97; two cases were mosaics that had a low percentage of abnormal cells), and the concordance of trisomy 21, 13, and 18 by the two methods was 100%.

CONCLUSIONSThe two sets of the domestic FISH kit probes are reliable for prenatal diagnosis. The results demonstrate that FISH is a rapid and accurate clinical method for prenatal identification of chromosome aneuploidies.

Amniotic Fluid ; cytology ; Aneuploidy ; Chromosome Aberrations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Pregnancy

OBJECTIVEIn this study we investigated the functional restoration of nonsense mutations in the SCN5A gene.

METHODSThe readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel.

RESULTSIn transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins.

CONCLUSIONReadthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.

Codon, Nonsense ; HEK293 Cells ; Humans ; NAV1.5 Voltage-Gated Sodium Channel ; Patch-Clamp Techniques ; Plasmids ; RNA, Small Interfering ; Sodium Channels ; genetics ; metabolism ; Transfection