This paper studied the relationship between apolipoprotein E isoforms and hyperlipidemia among 92 cases of diabetes mellitus, 174 cases with impaired glucose tolerance and 124 sex-age-matched controls. The results demonstrated that the patients with abnormal glucose tolerance had higher frequency of E2/3 isoforms and lower frequency of E, / , in com parison with controls. Hyperlipoproteinemia were mainly related to hyperglycemia but the Apo E isoforms which ex pressed different alleles also associated with hyperlipoproteinemia.

Objective To investigate the gene mutation in a pedigree with pachyonychia congenita typeⅡ(PC-Ⅱ)and to explore the relationship between the mutation and clinical manifestations.Methods The exon1of K17gene of genomic DNA from peripheral blood was amplified by PCR,and the PCR products were sequenced by automated sequencing system.Results In all the3patients of the pedigree with PC-Ⅱ(2patients presented as delayed-onset PC at4and15-16years of age respectively),the codon92(AAT)of K17gene was mutated as AGT,which caused missense mutation(N92S)in the1A domain of keratin17,but the2unaffected members of the pedigree and50unrelated controls had no such mutation.Conclusions Mutation of N92S in the1A domain of keratin17exists in this pedigree with PC-Ⅱ.Our results indicate that mutation in the1A domain of keratin17can present as delayed-onset pachyonychia congenita.Therefore,the site and type of keratin mutation are not the sole determinant of the age of onset for PC-Ⅱ,there may be other genetic and/or environmental factors that determine the age of onset of PC-Ⅱ.

Objective To explore the induced effects of colchicine in different concentration and times on Foeniculum vulgare polyploidy.Methods Seed germination rate and mutation rate,morphology of radicle induced mutants,chromosome number,tissue structure,and content and component of essential oil,which induced by colchicine in different concentiation and times were investigaled using the method of soaking seeds.Results The results showed that 0.13% of colchicine concentration and 24 h inducing time had the best induction on F.vulgare polyploidy.Compared to the control,the radicle of mutant was thicker,the chromosome number increased clearly,and the cell number in radicle manifolded distinctly.Among the four main components of essential oil,the contents of Dill apiol in anamorphosis radicle was a little lower than that of the control,but the contents of limonene,(E)-anethole,and camphene in anamorphosis radicle were all remarkably higher than that of the control after induced by colchicine.ConclusionThe content of main essential oil components in fennel mutant induced by colchicine is remarkably enhanced.The study provides the theoretical basis for the breeding of F.vulgare new varieties of high oil content.

Aged ; Drug-Related Side Effects and Adverse Reactions ; blood ; therapy ; Emergency Treatment ; Female ; Hemoperfusion ; Humans ; Hypnotics and Sedatives ; poisoning ; Male ; Middle Aged ; Serum ; chemistry

In recent years, artificial intelligence (AI) has developed rapidly, with improved computing power and algorithms, which has greatly facilitated the collection and processing of biological, chemical information and clinical data, injecting new vitality into the research and development of new drugs.In this review, we began with a brief overview of the development and the main algorithms of AI in drug discovery.Then we elaborated through several specific cases on the various scenarios of AI application, including target identification, protein structure prediction, hit generation and optimization etc.Finally, we focused on a recent example to discuss the high efficiency of "end-to-end" application of AI.

OBJECTIVETo investigate the expression and mutation of Mad1, Mxi1 and Rox genes in leukemia cells.

METHODSExpression and mutation of Mad1, Mxi1 and Rox genes in bone marrow mononuclear cells (BMMNC) from 26 de novo acute leukemia (AL) patients, and in peripheral blood mononuclear cells (PBMNC) from 30 healthy volunteers, as well as in 7 human leukemic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), single strand conformational polymorphism (SSCP) and DNA sequencing.

RESULTSRT-PCR showed that all the above cells expressed Mad1, Mxi1 and Rox mRNA. SSCP revealed four polymorphisms: two in Mad1, one each in Mxi1 and Rox. DNA sequencing detected nine missense mutations: two in Mad1 in AL patients, four in Mxi1 (three in AL patients and one in KG-1 cell line), and three in Rox in AL patients. The mutations of Mad1, Mxi1 and Rox mRNA were detected in 2, 3 and 3 patients, respectively.

CONCLUSIONIt is for the first time to demonstrate the mutations of Mad1, Mxi1 and Rox genes in AL patients suggesting these mutated genes involve in the pathogenesis of leukemia.

Adolescent ; Adult ; Aged ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; metabolism ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Female ; Humans ; Leukemia ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; metabolism ; Polymorphism, Single-Stranded Conformational ; Repressor Proteins ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

Objective To investigate the induction of microRNA (microRNA-106a,miR-106a)on the peritoneal metastasis of human gastric cancer cell BGC-823 by regulating matrix metalloproteinase inhibitor 2 (tissue inhibitor of metalloproteinases 2,TIMP2).Methods Human gastric cancer cell line BGC-823 was cultured to the logarithmic growth phase. The cells were divided into three groups: BGC-823, BGC-823/anti-miR-106a (antagomir)and BGC-823/negative control.Real-time PCR was used to identify the effect of antagomir.Transwell assay was used to detect the cell migratory and invasive abilities of these three groups in vitro .With small incision, the cells were injected into the abdominal cavity of nude mice to prepare a xenograft model.The animals were divided into two groups:miR-antagomir and miR-NC.The tumor growth in the nude mice was generally observed and estimated.Immunohistochemistry and Western blot methods were used to detect the expression of metastasis-associated protein TIMP2 on the several abdominal organs.Results The expression level of miR-106a was down- regulated in BGC-823/anti-miR-106a group,with the fold change of 0.05±0.01,which was significantly different from that in NC group (t=-18.001,P＜0.001).In vitro exogenously silencing of miR-106a gene,the numbers of invasive and migratory cells in BGC-823/anti-miR-106a group were both significantly lower than those in BGC-823 and BGC-823/negative control groups (P＜0.001).In vivo xenograft model showed that the down-regulation of miR-106a weakened the peritoneal metastasis ability of BGC-823 cells in nude mice abdominal cavity,which was reflected by the decrease of tumor number and tumor size.With the inhibition of miR-106a,the expression of TIMP2 in miR-antagomir group was significantly higher than that in miR-NC group (P＜0.05).Conclusion BGC-823 cell has the tumorigenicity in nude mice.Silencing of miR-106a inhibits gastric cancer cell metastasis, which suggests that it has the oncogenic function.MiR-106a may induce the strengthened peritoneal metastasis ability of BGC-823 cell through acting on TIMP2.

Objective To explore the relationship between size,shape and function of the left atrium appendage (LAA) and its thrombosis in patients with atrial fibrillation (AF) by transesophageal echocardiography (TEE) to provide evidence for clinical risk assessment,prognosis evaluation and treatment guidance.Method Length,diameter,end-diastolic volume (EDV) and ejection velocity (PEV) of LAA were measured in 41 patients with AF,and thrombus in LAA was detected by TEE.Results Thrombus in LAA was detected in seven of 41 patients of AF (17%).No significant difference in size and EDV was found between the patients with and without thrombus,but there was significant difference in PEV between them (P

OBJECTIVETo evaluate the feasibility of using multi-slice helical computed tomography (MS-CT) to accurately distinguish serous cystadenomas from mucinous cystadenomas or cystadenocarcinomas of the pancreas and to determine their radiographic appearances that can be applied for differentiative diagnosis.

METHODSWe performed a single-blind retrospective analysis of CT images of 30 patients with pathologically proven primary cystic pancreatic neoplasms (12 cases of serous cystadenomas, 14 cases of mucinous cystadenomas, and 4 cases of mucinous cystadenocarcinomas) to reach a diagnosis of either serous cystadenoma or mucinous cystic tumor. CT features such as tumor location, septations, presence of calcification, features of cystic wall, papillary excrescences, and size of the largest cyst were recorded. Statistical analysis was performed to evaluate the efficacy of certain CT findings in the differentiation of serous cystadenomas and mucinous neoplasms.

RESULTSTotally 9 (75.0%) serous cystadenomas and 16 (88.9%) mucinous tumors were correctly diagnosed. Three serous cystadenomas were misdiagnosed as mucinous cystadenomas, while 2 mucinous neoplasms were misdiagnosed as serous cystadenomas. And 9 (75.0%) serous cystadenomas were located at the pancreatic head and neck areas, while 12 (66.7%) mucinous neoplasms were located at the pancreatic body and tail areas (P < 0.05). The presence of calcification, especially central calcification, had statistical significance in differentiating serous cystadenoma from mucinous neoplasms (P < 0.05). The size of the largest cyst over 2 cm was positive associated with mucinous neoplasms (P < 0.05).

CONCLUSIONCT characteristics between serous cystadenomas and mucinous neoplasms of the pancreas have distinct difference, which validates the values of CT in differentiating these tumors. However, atypical CT appearances may compromise its diagnostic accuracy.

Cystadenocarcinoma, Mucinous ; diagnostic imaging ; pathology ; Cystadenoma, Mucinous ; diagnostic imaging ; pathology ; Cystadenoma, Serous ; diagnostic imaging ; pathology ; Diagnosis, Differential ; Diagnostic Errors ; Humans ; Pancreatic Neoplasms ; diagnostic imaging ; pathology ; Retrospective Studies ; Single-Blind Method ; Tomography, Spiral Computed

AIMTo study the effects of protease inhibitors on the large and small intestinal absorption of insulin in rats and to explore the mechanism of various protease inhibitors in different intestinal regions.

METHODSThe intestinal absorption of insulin was evaluated by its hypoglycemic effect and serum insulin level using an in situ loop method with the washing treatment.

RESULTSAdministration of insulin alone did not decrease the glucose level at either intestinal region with or without the washing treatment. With the unwashing treatment, there were no hypoglycemic effects in small intestinal loop when coadministration of insulin with protease inhibitors. With the washing treatment, the biological effects of insulin were amplified a little in small intestinal loop; obvious hypoglycemic effects were found in large intestinal loop with or without the washing treatment. The effectiveness of protease inhibitors was susceptible to their categories, concentrations and activities of proteolytic enzymes in different regions. The efficacy order of various protease inhibitors for enhancing hypoglycemic response of insulin was: leupeptin > sodium glycocholate > bacitracin > bestatin > cystatin; the percutaneous enhancement effects were observed in the presence of either sodium glycocholate or bacitracin.

CONCLUSIONCoadministration of protease inhibitors could increase the insulin efficacy more effectively in the large intestine than in the small intestine.

Animals ; Bacitracin ; pharmacology ; Biological Availability ; Blood Glucose ; metabolism ; Colon ; metabolism ; Glycocholic Acid ; pharmacology ; Insulin ; pharmacokinetics ; Intestinal Absorption ; drug effects ; Intestine, Small ; metabolism ; Leupeptins ; pharmacology ; Male ; Protease Inhibitors ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar