Animals ; Cochlea ; pathology ; Female ; Guinea Pigs ; Hyperlipidemias ; pathology ; physiopathology ; Male ; Otoacoustic Emissions, Spontaneous

Altitude ; Altitude Sickness ; Animals ; Hypoxia ; Iron ; Mice ; Spleen

Objective To study on the effectiveness of endoscopic ultrasonography(EUS)in detec- ting insulinoma preoperatively.Methods Fifteen patients with clinical and biochemical signs of insulinoma were examined by EUS using a radial-scanning ultrasound endoscope and abdominal ultrasonography,CT, DSA prior to surgery.The outcome was evaluated on the basis of surgery and examination of the resected specimens.Results Fifteen patients with 16 lesions of insulinoma were identified by surgery and pathology. The aceuraey of diagnosis with EUS was 13/15(86.7%),and that with B-US,CT,DSA was 3/15(20%), 5/15(33.3%),9/14(64.3%)respectively.In the 14 lesions identified by EUS,10 lesions were depicted to be hypoechogenic,1 lesion was isoechogenic and 3 lesions were hyperechogenie.All 14 lesions were well demarcated and surrounded by normal pancreatic tissue.The minimum size of the lesion visualized by EUS was 0.5cm.Ten lesions were correctly detected by EUS with size of 0.5～2.0cm.EUS missed diagnosis in 2 lesions not for their small size.EUS falsely indicated a 10mm lesion from two lesions inside the head of pancreas.One lesion outside the pancreatic tail and one lesion in the pancreatic head were missed by EUS in another case.Conclusion EUS is superior in assessing the location of pancreatic insulinoma than other ima- ging methods such as B-US,CT,DSA.

Objective:To evaluate the changes of left ventricular (LV) myocardial systolic strain and twist motion including global longitudinal strain(GLS), global circumferential strain(GCS), global radial strain(GRS), global area strain(GAS), LV basal segment rotation angle (Rotation-basal), LV apical segment rotation angle (Rotation-apical), LV twist angle (Twist), LV torsion(Torsion) by three-dimensional speckle tracking imaging(3D-STI) in adult patients with hypertrophic cardiomyopathy (HCM), and further to analyze the correlations between LV twist and its morphology and global systolic function.Methods:A total of 45 patients with HCM from the General Hospital of Ningxia Medical University from September 2017 to June 2019 were enrolled. In addition, 50 healthy subjects were recruited as a control group. Left atrial dimension(LAD), interventricular septal end-diastole dimension(IVSD), LV posterior wall end-diastole dimension (LVPWD), LV mass index(LVMI) and other parameters were respectively measured by conventional two-dimensional transthoracic echocardiography. LV end-diastole volume(EDV), LV end-systole volume(ESV), calculated stroke volume(SV) and LV ejection fraction (LVEF) were respectively measured by 3D transthoracic echocardiography. Full-volume 3D dynamic images were performed using matrix transducer X5-1. LV Rotation-basal, Rotation-apical, Twist and Torsion, GLS, GCS, GRS and GAS were respectively analyzed by off-line TomTec software. The differences of those parameters between the two groups were compared. The correlations between 3D-Torsion parameters and those parameters by two-dimensional echocardiography was further analyzed.Results:Compared with control group, LAD, IVSD, LVPWD and LVMI of HCM group were increased(all P<0.01), EDV, ESV, SV, LVEF and E/A were decreased(all P<0.01). Compared with control group, GLS, GCS and GRS of HCM group were decreased(all P<0.01). Rotation-basal, Rotation-apical, Twist and Torsion were increased(all P<0.01), and there was no significant difference of GAS between the two groups( P>0.05). In HCM group, IVSD was not correlated with Rotation-basal ( P>0.05), but negatively correlated with Rotation-apical, Twist and Torsion ( r=-0.327, -0.439, -0.374; all P<0.05); LVEF and LVMI were not correlated with Rotation-basal, Rotation-apical, Twist and Torsion (all P>0.05). Conclusions:①3D-STI can detect the earlier subtle changes of left ventricular three-dimensional systolic strain in HCM patients; ②LV three-dimensional Twist inereases considerably in HCM patients; ③LV Twist, Torsion and Rotation-apical are significantly decreased with the increase of IVSD in HCM patients; However, LVEF and LVMI are not significantly correlated with Rotation-basal, Rotation-apical, Twist and Torsion.

The abnormality of ubiquitin proteasome pathway is an important factor leading to the imbalance of protein homeostasis. In this process, the deubiquitinase responsible for removing the ubiquitin chain of protein substrate is very important. Its abnormal activity or expression can cause the functional changes of key oncogenic/tumor suppressor proteins, which directly or indirectly lead to the occurrence, development and malignant evolution of tumors. Based on this, the discovery and research of small molecule inhibitors targeting deubiquitinases have become a hot field of anti-tumor candidate drugs. This review will focus on the regulatory effect and mechanism of ubiquitin proteasome pathway, especially deubiquitinase on tumor, introduce the application of deubiquitinase small molecule inhibitors in tumor treatment, and discuss the research status and latest progress of small molecule inhibitors, so as to provide ideas for the research of new anti-tumor strategies based on deubiquitinase.

OBJECTIVETo investigate the effects of combined use of low-dose hydroxyurea (HU) and sodium butyrate (NaB) on the expression of 7 globin genes (zeta, alpha, epsilon, Ggamma, Agamma, delta, and beta) in human erythroid progenitor cells.

METHODSHuman erythroid progenitor cells were cultured using a two-step liquid culture system and treated with HU and NaB either alone or in combination. The inhibitory effects of the agents on the cell growth were monitored with trypan blue exclusion assay, and the changes in the mRNA of the 7 globin genes were detected using RT-PCR.

RESULTSLow-dose HU combined with NaB resulted in significantly lower inhibition rate of the erythroid progenitor cells than routine dose HU and NaB used alone (28.56% and 38.80%, respectively, P<0.05). Compared with untreated cells (0.653-/+0.092 and 0.515-/+0.048), HU combined with NaB significantly increased the expression of Ggamma-and Agamma- mRNA (1.203-/+0.018 and 0.915-/+0.088, respectively, P<0.05), and HU and NaB used alone produced similar effects (1.305-/+0.016 and 0.956-/+0.029 for HU, and 1.193-/+0.070 and 0.883-/+0.012 for NaB, P>0.05). HU and NaB, either used alone or in combination or at different doses, caused no significant changes in the other globin genes (zeta, alpha, epsilon, delta and beta) (P>0.05).

CONCLUSIONLow-dose HU combined with NaB can up-regulate gamma globin gene expression, especially Ggamma-mRNA expression, to decrease the growth inhibition on human erythroid progenitor cells in vitro, but produces no significant effect on the expressions of zeta, alpha, epsilon, delta and beta genes.

Anemia, Sickle Cell ; genetics ; Butyrates ; administration & dosage ; pharmacology ; therapeutic use ; Cells, Cultured ; Drug Therapy, Combination ; Erythroid Precursor Cells ; cytology ; drug effects ; physiology ; Erythropoiesis ; drug effects ; Humans ; Hydroxyurea ; administration & dosage ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; gamma-Globins ; genetics ; metabolism

Objective To investigate the prevalence of mutation in the locus 306 of embB gene in multi-drug resistant (MDR) Mycobacterium tuberculosis (TB) and evaluate the prospects for using it as a molecular marker to detect MDR-TB.Methods The 291 strains enrolled in this study were from the reference laboratory of Shanghai municipal centers for disease control and prevention, all of which had been tested for drug susceptibility.Mutation in embB 306 was screened both by amplification refractory mutation system (ARMS) and DNA sequencing.The mutation frequencies of embB 306 in the sample groups varied in drug resistance were statistically analyzed.Results 38(51.4% ) of the 74 MDR-TB were embB 306-mutant (X2 =93.8,P＜0.01).Of the 24 TB resistant to at least two drugs but not MDR, 9(37.5% ) were embB 306 mutant (X2 =60.1 ,P＜0.01 ).But only two(4.9% ) embB 306-mutant strains were found in 41 strains resistant to only one drug (X2 =6.8,P=0.0093).None embB 306-mutant strains were found in 152 pansensitive strains.The specificity of using embB 306 as a molecular marker for detecting multi-drug resistant TB was 94.9% (206/217).Conclusions As a molecular marker for screening drug resistant TB,especially MDR-TB, the gene locus embB 306 shows a relatively high sensitivity and specificity, promising a sound future for its application in clinics to realize fast screening of patients infected with MDR-TB and to provide evidence for appropriate medication.

Kallistatin (Kal) is a negative acute phase endogenous protein which can inhibit tumor angiogenesis, growth and metastasis effectively. To express and purify recombinant human kallistatin (rHKal), and characterize its biological activity, P. pastoris was transformed with pPIC9-Kal/GS115 (His4) to express rHKal. The fermentation was carried out in a 7.5 L bioreactor with high density cell culture. 1%-2% methanol was added to the medium to induce the expression of rHKal. The secretion was purified with phenyl sepharose, G-25 sepharose, heparin sepharose and Sephacryl S-100 chromatography. The biological activity of purified bulk rHKal on HUVEC was evaluated with MTT and tube formation assays. The final expression of rHKal in the supernatant reached 50 mg x L(-1), the purity of bulk rHKal after purification was above 98%. A dose-dependent inhibition of rHKal on HUVEC proliferation was observed, however, a U-shaped dose-response curve of rHKal on capillary formation of HUVEC was revealed. The described protocol provides an effective means for preparing rHKal that could be used for anti-angiogenesis therapy in the future.
Bioreactors ; Capillaries ; drug effects ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Fermentation ; Human Umbilical Vein Endothelial Cells ; Humans ; Pichia ; genetics ; metabolism ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology ; Serpins ; biosynthesis ; genetics ; pharmacology

To investigate the cardioprotective effect of formononetin (FMN) on no-reflow (NR) after myocardial ischemia-reperfusion and its molecular mechanism based on integrated pharmacology and experimental verification, firstly, human breast cancer MCF-7 cells and myocardial NR rats were used to confirm the estrogenic activity and the effect of alleviating NR of FMN, respectively. Male SD rats were divided into Sham, NR, FMN (20 mg·kg^-1) and sodium nitroprusside (SNP, 5.0 mg·kg^-1) groups, which were administered once a day for one week, the experiment was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019095). The pharmacological analysis and in vivo study of NR rats were integrated to reveal the mechanism of FMN improving NR. The results showed that FMN had estrogenic effect and reduced NR by improving cardiac structure and function, reducing NR, ischemic myocardial area and pathological injury of cardiomyocytes. Integrated pharmacology predicts that the mechanism of FMN improving NR is mainly related to phosphatidyinositol-3-kinase-protein kinase B (PI3K-Akt) signal pathway. Phytoestrogens play a role in cardiovascular protection mainly by activating G protein-coupled estrogen receptor (GPER). GPER is also an important regulator in the upstream of PI3K-Akt signaling pathway. This study found that FMN can significantly activate GPER, p-PI3K, p-Akt and phospho-endothelial nitric oxide synthase (p-eNOS). It has good binding ability with GPER and eNOS protein. In this study, through the integration of pharmacology and experimental evaluation, it is revealed that FMN activates PI3K/Akt/eNOS signal pathway by activating GPER, thus significantly improving NR.

OBJECTIVETo identify the etiological agent of acute gastroenteritis outbreaks occurred in 6 hospitals in Beijing from November to the end of 2006 and to characterize the virus on molecular biology.

METHODSRota-strip was used to detect rotavirus antigen and PAGE for rotavirus RNA in stool specimens collected from patients with gastroenteritis at the first stage. Reverse transcription-polymerase chain reaction(RT-PCR) was performed to detect Norovirus in stool specimens. Full length of Norovirus VP1 genes were amplified from Norovirus positive samples by RT-PCR and sequenced after the gene was cloned into vector pUCm-T. The sequences of partial VP1 gene at the 5' end of full-length gene were obtained from 2 of the Norovirus positive samples to analyze the relationship of these viruses at molecular level.

RESULTSNorovirus was detected in 17 of the 30 stool specimens with an overall positive rate of 56.7%. Positive rates were all above 42.9% in specimens collected from each of the hospital. Sequence analysis on one of the full-length of VP1 amplified by RT-PCR from one of the positive specimens NV8-Beijing indicated that it belonged to G II-4 genotype. This strain shared 94.8% and 95.2% identities over the complete major capsid gene to Lanzhou strain form Lanzhou China and Farmington Hill strain from USA which belonged to G II-4 genotype, but only 91.1% identity to the CR2905 from Beijing China identified from specimen collected in late 2004. The sequences of 5' end of VP1 genes amplified from other two samples collected from different hospitals showed only one nucleotide mutation compared to NV8-Beijing in the correspondence part, indicating that these two strains also belonged to G II-4 genotype.

CONCLUSIONNorovirus was the etiological agent causing outbreaks of acute gastroenteritis in hospitals in Beijing and the strain with G II-4 genotype which was closer to the Lanzhou and Farmington strains than Beijing strains identified in 2004.

Acute Disease ; Antigens, Viral ; analysis ; Caliciviridae Infections ; epidemiology ; virology ; China ; epidemiology ; Disease Outbreaks ; Feces ; virology ; Gastroenteritis ; epidemiology ; virology ; Hospitals ; Humans ; Norovirus ; genetics ; isolation & purification ; Reverse Transcriptase Polymerase Chain Reaction