The over-expression of Polo-like kinase 1(Plk1)is critical in the producing and progressing of multi-ple human tumors and is recognized as an effective target for the development of novel anti-cancer drugs.Currently a variety of small molecules targeting ATP or substrates binding sites have entered different stages of clinical trials.Polo-box domain(PBD)is a unique domain of Plks which plays an important role in the sub-cellular location of Plks and also in the recognition of their substrates,therefore it has become an attractive target for the development of novel target-directed Plk1 inhibitors.In this paper,PBD function of Plk1 was intro-duced,the progress of small molecule and phosphoserine /phosphothreonine contained short peptide Plk1 inhibi-tors targeting PBD was summarized.Further development of this kind of inhibitors was also proposed.

Objective To investigate the perihematomal changes of hyperacute parenchymal hematomas and the clinical value by MRI. Methods Multi-sequence MRI was performed on 4 hematomas in vitro and on 15 pigs with lobar intracerebral hemorrhage (ICH) for about 30～60 min and 3 h respectively. The integrity of blood-brain barrier (BBB) in ICH pigs was assessed by electron microscopy and Evan's blue dye technique. MR scanning was performed on 2 ICH patients proved by CT for 4 and 9 h after onsets. Results FLAIR and T 2-weighted images showed hyperintensity signal around the hematomas in vitro and in pigs with ICH within 1 h, and more obviously at 3 h. When the gelose cavity was cut, plasma was seen around the clot. The perihematomal ADC values of the pigs increased both within 1 and at 3 h after ICH. However, the BBB was intact at 3 h, which was proved by electron microscopy and Evan's blue dye technique. Water-like intensity signal was observed around the hematomas in two patients with acute ICH. Conclusion The perihematomal changes of hyperacute ICH observed on MRI are resulted from the blood clot contraction and the serum formation and extravasation, but not real cerebral edema.

Objective To explore the risk and treatment of laparoscopic cholecystectomy(LC) in patients with liver cirrhosis and cholelithiasis.Methods To summarize the clinical data of 28 patients with liver cirrhosis and cholelithiasis.The patients were repeated right upper quadrant pain,including 4 cases of gallbladder neck stones incarcerated,gallbladder effusion.Among them,there were 20 cases of hepatitis B cirrhosis,5 cases of schistosomiasis cirrhosis,3 cases of alcohol.Results There were 6 patients with hemorrhage during operation.Among them,5 patients were treated with gelatin sponge,hemostatic gauze and bio-glue spray to stop bleeding,1 case was transferred to open surgery because of bleeding.The remaining 27 cases of LC were successful.Complications occurred in 8 patients,3 cases of increased liver function abnormalities,1 case of upper gastrointestinal bleeding,1 case of mild hepatic encephalopathy,2 cases of significant ascites formation,1 patient underwent subtotal resection of the gallbladder with Hartmanns bag,and bile was found in the ascites after surgery,but the bile disappeared after five days.All patients with complications after symptomatic treatment were cured,no death,no major bleeding and liver failure,bile duct injury,severe biliary fistula and other serious complications.Conclusion Although the risk of LC in patients with liver cirrhosis is higher than that in the general population,with the help of current high-tech surgical instruments,we can safely accomplish this with an improved surgical procedure.As these patients require high technical requirements of surgery,surgeons must have a wealth of experience and familiar laparoscopic liver and gallbladder anatomy.

To explore the dynamic expression and role of Aquaporin5 (AQP5) in lung development and hyperoxia lung injury, gestation 21-day Sprague-Dawley (SD) rats (term=22 days) were randomly assigned to air group and hyperoxia group within 12-24 h after birth. The rats in hyperoxia group were continuously exposed to about 85% oxygen and those in air group to room air. After 1 to 14 days of exposure, total lung RNA was extracted and the expression of AQP5 mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemistry and western-blot were used to detect the expression of AQP5 protein. The results showed that the expression of AQP5 in premature rats lung could be detected at various time points after birth, and the positive staining was restricted to the type I alveolar epithelial cells. In air group, the AQP5 expression was detected in a very low level at day 1, but exhibited a persistent increase after birth. Compared with the air group, the expression of AQP5 in hyperoxia group was increased at day 1, and had significant difference in mRNA level (P<0.05), but decreased significantly in mRNA and protein levels after 4 to 14 days (P<0.01 or P<0.05 respectively). It was concluded that AQP5 might play a key role in the alveolar period of premature rats by regulating the lung water balance. Hyperoxia exposure leads to a down-regulation of the AQP5 expression, which may be an important factor for the development of hyperoxia lung injury.

BACKGROUND: Paraquat (PQ) is a world-wide used herbicide and also a type of common poison for suicide and accidental poisoning. Numerous studies have proved that the concentration of serum PQ plays an important role in prognosis. Spectrophotometry, including common spectrophotometry and second-derivative spectrophotometry, is commonly used for PQ detection in primary hospitals. So far, lack of systematic research on the reliability of the method and the correlation between clinical features of patients with PQ poisoning and the test results has restricted the clinical use of spectrophotometry. This study aimed to evaluate the reliability and value of spectrophotometry in detecting the concentration of serum PQ. METHODS: The wavelengths for detecting the concentration of serum PQ by common and second-derivative spectrophotometry were determined. Second-derivative spectrophotometry was applied to detect the concentration of serum PQ. The linear range and precision for detection of PQ concentration by this method were confirmed. The concentration of serum PQ shown by second-derivative spectrophotometry and HPLC were compared in 8 patients with PQ poisoning. Altogether 21 patients with acute poisoning 4 hours after PQ ingestion treated in the period of October 2008 to September 2010 were retrospectively reviewed. The patients were divided into higher and lower than 1.8 μg/mL groups based on their concentrations of serum PQ measured by second-derivative spectrophotometry on admission. The severity of clinical manifestations between the two groups were analyzed with Student's t test or Fisher's exact test. RESULTS: The absorption peak of 257 nm could not be found when common spectrophotometry was used to detect the PQ concentration in serum. The calibration curve in the 0.4–8.0 μg/mL range for PQ concentration shown by second-derivative spectrophotometry obeyed Beer's law with r=0.996. The average recovery rates of PQ were within a range of 95.0％ to 99.5％, relative standard deviation (RSD) was within 1.35％ to 5.41％ (n=6), and the lower detection limit was 0.05 μg/mL. The PQ concentrations in serum of 8 patients with PQ poisoning shown by second-derivative spectrophotometry were consistent with the quantitative determinations by HPLC (r=0.995, P<0.0001). The survival rate was 22.2％ in patients whose PQ concentration in serum was more than 1.8 μg/mL, and the incidences of acidosis, oliguria and pneumomediastinum in these patients were 55.6％, 55.6％and 77.8％, respectively. These clinical manifestations were different significantly from those of the patients whose PQ concentration in serum was less than 1.8 μg/mL (P<0.05). CONCLUSIONS: For common spectrophotometry, the wavelength at 257 nm was not suitable for detecting serum PQ as no absorbance was shown. Second-derivative spectrophotometry was reliable for detecting serum paraquat concentration. Serum PQ concentration detected by second-derivative spectrophotometry could be used to predict the severity of clinical manifestations of patients with PQ poisoning, and PQ content higher than 1.8 μg/mL 4 hours after ingestion could be an important predictive factor for poor prognosis.

Objective To explore the utility of different body composition for the prediction of myocardial ischemia in exercise in type 2 diabetes mellitus (T2DM) patients. Methods T2DM outpatients were selected from Jul. 2013 to Nov. 2014 (male 83, female 57) to measure body composition and clinical biochemical parameters, and divided them into two groups according to treadmill exercise testing results. Group A cases were positive (27 patients) and Group B cases were negative (113 patients). SPSS19.0 was used to make statistical analysis. Results (1) The age, gender, diabetes mellitus (DM) duration, medical history of hypertension and dyslipidemia, body mass index (BMI), waist circumference, the waist-hip fat ratio of the two groups had no significant difference (P>0.05). (2) The fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) between the two groups had no significant difference. Compared with group B, the low density lipoprotein cholesterol (LDL-C) of group A [(2.48 ± 0.75) mmol/L vs. (2.81 ± 0.77) mmol/L, t=2.009, P<0.05] decreased significantly. (3) Overall body fat percentage, skeletal muscle weight of the two groups had no significant difference. Compared with group B, the waist-hip fat ratio (0.93±0.06 vs. 0.88±0.08, t=-2.790, P<0.01) andvisceral fat area [(99.47 ± 32.84) cm2 vs. (81.10 ± 25.47) cm2, t=-2.822, P<0.01] of group A increased significantly, while this difference mainly existed in male patients visceral fat area [(100.99±39.33) cm2 vs. (79.91 ± 27.09) cm2, t=-2.231, P<0.05], and waist-hip fat ratio was different in female patients of the two groups (0.91±0.06 vs. 0.85±0.09, t=-2.043, P<0.05) . Conclusion Abdominal obesity, especially visceral fat accumulation had close correlation with myocardial ischemia in exercise in T2DM patients. Waist-hip fat ratio and visceral fat area may be more effective indicators of myocardial ischemia in exercise in T 2DM patients than BMI.

Objective To establish a new method for rapid detection of β-thalassemia by investigating six clinical common mutation types.Methods Fifty cases of clinical wild-type samples and 42 cases ofβ-thalassemia samples were collected, and β-globin gene was amplified by PCR.Uniform ligation probe ( ULP) specific probes were designed for hybridization reaction to increase the reaction specificity and real-time PCR was performed to increase the sensitivity.After that, PCR products were verified by agarose electrophoresis.After examining the specificity and sensitivity, Kappa test between LDR-ULP method and reverse dot blot( RDB) method was conducted.Results Hybridization efficiency was improved 2.53 times by LDR-ULP hybridization.Each mutant type showed a significant amplification curve, whereas the wild-type had no significant curve within 40 cycles.The limit of determination of this method was 5 pg.The results of 92 cases of peripheral blood samples detected by the method of LDR-ULP and RDB were completely consistent.Conclusion In this study, a simple, inexpensive, rapid new method to detect β-thalassemia were established.

OBJECTIVETo investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people.

METHODSTotally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing.

RESULTSFourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing.

CONCLUSIONThese results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.

Aged ; Aged, 80 and over ; Apolipoproteins B ; genetics ; Base Sequence ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Longevity ; genetics ; Male ; Middle Aged ; Minisatellite Repeats ; genetics ; Molecular Sequence Data ; Polymerase Chain Reaction ; Polymorphism, Genetic ; genetics

Objective To establish a homothermal and fast detecting method on pathogenic bacteria by combining recombinase-aid amplification (RAA) with molecular beacon.Methods The establishment of the methodology.Staphylococcus aureus specific primers were designed from the relative region of the staphylococcal protein A (SPA).Asymmetry amplification was optimized by adjusting the primer concentration ratios.The results of amplification and hybridization were visualized and analyzed by agarose gel electrophoresis and fluorescence detection.The sensitivity was identified by detecting dilute positive plasmids.And the specificity was determined using RAA method by detecting 72 pathogenic bacteria,including Staphylococcus aureus and other Staphylococcus spp.from the Department of Clinical Laboratory of Daping Hospital in December 2016.Besides,the Kappa analysis and the clinical diagnosis efficiency were investigated by analyzing 39 extra strains in the laboratory in December 2016.Results When the concentration ratio of restrictive and non-restrictive primer was 1:20,the yield efficiency of single-stranded DNA (ssDNA) reached the peak.And as for the hybridization efficiency,the asymmetry amplification was higher than symmetry amplification.Twenty copies/μl was proposed as the limits of detection by testing dilute plasmids.And the RAA hybridization method could distinguish Staphylococcus aureus with other Staphylococcus spp.Comparing with traditional detection methods with a Kappa index of 0.860,this method shows a good consistency.By analyzing the 111 bacteria,the sensitivity of the method is 92.5％ (37/40),the specificity is 97.2％ (69/71),the positive predictive value is 94.9％ (37/39),the negative predictive value is 95.8％ (69/72),the positive likelihood radio is 33.04,the negative likelihood radio is 0.077,the Youden index is 0.897 and the Kappa index is 0.902.Conclusion Through the combination of asymmetry recombinase-aid amplification optimization and molecular beacon probe,a new method of detecting bacteria DNA with RAA hybridization technique is established,providing the foundation for its clinical application.

Objectives To investigate the relationship between single nucleotide polymorphism (SNP)H558R in SCN5A gene and chronic Keshan disease (KSD) complicated with hypertension,and the relationship between H558R and occurrence of arrythmia in chronic KSD complicated with hypertension.MethodsThirty nine patients with chronic KSD complicated with hypertension and 63 geographical region matched hypertension control subjects were recruited in our study in Fuyu county,Qiqihaer city,Heilongjiang province between 2006 and 2010.H558R polymorphism in case and control groups was genotyped using the polymerase chain reaction single-strand conformation polymorphism(PCR-SSCP) and sequenced,and electrocardiography(ECG) characteristics were examined in the two groups.Case-control study analytical methods were applied to analyze the relationship between H558R and chronic KSD complicated with hypertension,and the relationship between H558R and occurrence of arrythmia in chronic KSD patients complicated with hypertension.Results Subjects of genotype 558 TC in the case group had a decreased risk of chronic KSD complicated with hypertension with odds ratio of 0.288[95％ confidence interval (CI):0.104 - 0.794],and subjects of genotype TC in chronic KSD complicated hypertension patients had a decreased risk of QRS prolongation with odds ratio of 0.061 (95％CI:0.006 - 0.612).Conclusions Polymorphism H558R in SCN5A gene may be a predisposition factor of chronic KSD complicated with hypertension and occurrence of arrythmia in chronic KSD complicated with hypertension.