ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan. ProTides are aryloxyphosphoramidates (or aryloxyphosphonamidates) which contain a phosphorus atom combined with an amino acid ester and an aryloxy group. These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation, which afford effective solutions to the drawbacks of current nucleoside analogues. At present, ProTide technology has been extensively applied in the field of antiviral research. It has been successful in providing a number of approved drugs and clinical candidates, such as sofosbuvir and so much more, highlighting the promising future in drug discovery. This review summarizes the brief history and characteristics of ProTide technology, as well as its application in the exploration of antiviral drugs.

Child, Preschool ; Humans ; Male ; Tricuspid Valve Insufficiency ; etiology ; Tricuspid Valve Prolapse ; congenital

Objective To analyze the prevalence of the various hematological malignancies (HM) in Harbin.Methods Study data was collected from January 2010 to December 2011.All cases were diagnosed and classified on the basis of blood test,bone marrow puncture,histochemical staining and typing and classified by the French American British classification.The age and sex distribution of HM and its subtypes were analyzed.Results Of 2214 Chinese people diagnosed with HM,acute myeloid leukaemia (AML) (33.5 ％) and myelodysplastic syndromes (MDS) (29.9 ％) were the most prevalent and of 742 AML,the most frequent subtypes were M3.With the growth of age,the rates of chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) were increased,but in acute lymphocytic leukemia (ALL),this trend was reversed.The distribution of HM increased with age between 0-60 years old,in above 60 years old,the frequency of some chronic HM including CLL,chronic myelomonocytic leukemia (CMML),chronic neutrophilic leukemia (CNL) and MM were continued to rise,but other HM subtypes were decrease,lower than in 41-60 years old groups.This study also revealed that M0 and MPAL were more common in 0-20 years as well as ALL.For patients never drinking alcohol and drinking for at least 10 years maybe associated with acute leukemia [OR =1.53 (95 ％ CI 1.05-2.23)],while smoking wasn' t a substantial risk factor for acute and chronic leukemia (P =0.20,0.48).Conclusions The epidemiology of HM in Harbin indicates that AML is the most prevalent,followed by MDS.Prevalence of CLL and MM increases with the age in patients above 60 years old.Drinking for at least 10 years maybe associated with acute leukemia.

Objective:To evaluate the in vitro release behavior of doxorubicin(Dox)-loaded microspheres and the stability of Dox during encapsulation process and in vitro release.Methods: Dox-loaded microspheres were prepared by double emulsion(W/O/W) method with poly(lactic-co-glycolic acid)(PLGA) as the carrier material.The physical and chemical characteristics of microspheres,including the mean diameter,morphology,drug entrapment efficiency and loading rate,were evaluated.The in vitro release behavior and its influencing factors were determined by ultraviolet spectrophotometry.Dox stability was evaluated by HPLC method during the encapsulation process and in vitro release.Results: The prepared microspheres had a complete spheric shape and dispersive quality.The mean diameter of the microspheres was 85 ?m;the drug entrapment efficiency was 95.1%;and the loading rate was 14.8%.Releasing rate of the microspheres slowed down with the increase of PLGA concentration and the decrease of W/O value.The encapsulation process had no obvious effect on the stability of Dox,while Dox degraded during in vitro release as the prolongation of time.On day 10,the peak area of degraded material accounted for 2.46%.Conclusion: Dox can be encapsulated in the microspheres by double emulsion method and different release rates of Dox can be achieved by adjusting PLGA concentration and W/O volume ratio.

Oncogene c-jun is a member of jun family,the immediately early genes(IEGs),and belongs to one of the nuclear transcription factors of basic leucine zipper(bZIP)family.Combined with many gene promotors,c-jun is involved in the regulation of gene transcription.Its products play important roles in regulating gene expression,cell proliferation,differentiation and apoptosis.The structure,biological funetion,regulation of c-jun and its roles contributing to tissue damage are reviewed in this article,which may provide understanding for severity of tissue injury and wound age estimation in the field of forensic pathology.

Objective:To explore the clinical effect of Pingchuan Decoction combined with routine western medicine therapy in the treatment of acute attack of bronchial asthma in children. Methods:From January 2017 to June 2019, 118 children with acute attack of bronchial asthma were selected from the Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and they were randomly divided into control group (59 cases) and observation group (59 cases) according to the random number table. The control group was treated with routine western medicine therapy, and the observation group was treated with Pingchuan Decoction on the base of control group, and both groups were treated for 14 days. The main symptom scores before and after treatment were evaluated. The percentage of forced vital capacity expressed as percent predicted (FVC% pred) and the forced expiratory volume in 1 second expressed as percent predicted (FEV1% pred) were measured by pulmonary function meter. The levels of CD3 +, CD4 + and CD4 +/CD8 + in peripheral blood were detected by flow cytometry. The adverse reactions during the treatment were recorded and the clinical efficacy was evaluated. Results:The total clinical effective rate was 93.2% (55/59) in the observation group and 71.2% (42/59) in the control group, where the difference between the two groups was statistically significant ( χ2=9.790, P=0.002). After treatment, the scores of cough, wheezing and wheezing rale in the observation group were significantly lower than those in the control group ( t=27.695, 17.573, 32.827, P<0.001). After treatment, FVC% pred [(80.21 ± 4.06)% vs. (71.71 ± 3.95)%, t=11.526], FEV1% pred [(78.84±3.92)% vs. (72.26 ± 3.59)%, t=9.508] in the observation group were significantly higher than those in the control group ( P<0.01). The levels of CD3 + [(74.05 ± 5.13)% vs. (67.44 ± 4.98)%, t=7.101], CD4 + [(48.43 ± 4.31)% vs. (42.20 ± 4.06)%, t=8.082] and the ratio of CD4 +/CD8 + (1.67 ± 0.29 vs. 1.34 ± 0.25, t=6.620) in the observation group were significantly higher than those in the control group ( P<0.01). During the treatment, the incidence of adverse reactions was 10.2% (6/59) in the observation group and 6.8% (4/59) in the control group, and there was no significant difference between the two groups ( χ2=0.437, P=0.509). Conclusion:The Pingchuan Decoction combined with routine western medicine therapy can reduce the clinical symptoms of children with acute attack of bronchial asthma, improve lung function, improve organism immunity and clinical effect with safety.

Objective: To observe the efficacy of stereotactic radiotherapy combined with gemzar for treatment of unresectable pancreatic cancer.Methods: Gemzar at dose of 1000mg/m 2,28 days per cycle,drug was given at 1,8,15 days,for two cycles.After 24 hours all patients were treated with stereotactic radiotherapy.Per fraction was 5～7G Y,three times per week.The total dose was 40～48G Y.Results: 13 patients were followed up for one year,symptoms were reduced and median survival was 12 months.Conclusion: Stereotactic radiotherapy combined with gemzar has important valves for unresectabal pancreatic cancer.

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

Adrenalectomy ; Adult ; Angiomyolipoma ; pathology ; surgery ; Follow-Up Studies ; Humans ; Kidney ; pathology ; Kidney Neoplasms ; pathology ; surgery ; Lymph Node Excision ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Nephrectomy ; Ureter ; surgery

OBJECTIVETo investigate the potential protective effect of the mitochondria-targeted antioxidant Mitoquinone (MitoQ) on post-thaw human sperm.

METHODSSemen samples were collected from 60 normal fertile men, each divided into six parts of equal volume to be incubated at 37 °C in normal saline (G0, control) or in the extender with 2 nmol/L (G1), 20 nmol/L (G2), 200 nmol/L (G3), 2 µmol/L (G4), and 20 µmol/L of MitoQ (G5). After one hour of incubation, the samples were subjected to computer-assisted semen analysis (CASA) for sperm motility, flow cytometry for reactive oxygen species (ROS), thiobarbituric acid assay for the concentration of malondialdehyde (MDA), and MitoTracker fluorescent staining and flow cytometry for the sperm mitochondrial membrane potential (MMP). Then, the semen were cryopreserved with none (B0), 200 nmol/L (B1), and 2 µmol/L of MitoQ (B2), followed by detection of the changes in the ROS, MDA, and MMP of the post-thaw sperm.

RESULTSThe percentage of progressively motile sperm and total rate of sperm motility were significantly higher in G3 ([30.8 ± 10.2]% and [70.6 ± 9.0]%) and G4 ([32.7 ± 13.5]% and [70.3 ± 11.9]%) than in G0 ([17.6 ± 5.0]% and [54.9 ± 11.5]%) (P < 0.05). The level of ROS dropped markedly with the increased concentration of MitoQ, 86.5 ± 31.6 in G3, 93.6 ± 42.0 in G4, and 45.1 ± 15.0 in G5, as compared with 160.8 ± 39.7 in G0 (P < 0.05). The content of MDA was remarkably lower in G3 ([0.9 ± 0.5] µmol/mg) and G4 ([0.9 ± 0.5] µmol/mg) than in G0 ([1.9 ± 1.1] µmol/mg) (P < 0.05), but not in G5 ([1.7 ± 0.7] µmol/mg), which was even higher than in G3 and G4 (P < 0.05). The MMP showed a significant reduction in G5 (1156 ± 216) in comparison with G0 (1701 ± 251) (P < 0.05) but exhibited no remarkable difference between G0 and G1 (1810 ± 298), G2 (1995 ± 437), G3 (1950 ± 334), or G4 (1582 ± 314). The percentage of progressively motile sperm and total rate of sperm motility after freezing-thawing were significantly decreased as compared with those of the fresh semen (P < 0.01), but both were remarkably higher in B1 ([3.2 ± 2.3]% and [ 43.0 ± 9.5]%) than in B0 ([0.8 ± 0.6]% and [26.5 ± 11.4]%) (P < 0.05). The ROS level was significantly lower in B1 and B2 than in B0 (34.6 ± 12. 3 and 37.0 ± 10.5 vs 56.9 ± 14.3, P < 0.05), and so was the MDA content ([1.4 ± 0.5] and [1.4 ± 0.6] µmol/mg vs [2.6 ± 1.0] µmol/mg, P < 0.05), but the MMP was markedly higher in B1 and B2 than in B0 (1010.0 ± 130.5 and 880.6 ± 128.6 vs 721.1 ± 24.8, P < 0.05).

CONCLUSIONAddition of MitoQ to the freezing extender at 200 nmol/L may effectively improve the quality of human sperm and MitoQ is a good protective addictive for human sperm cryopreservation.

Antioxidants ; Cryopreservation ; Humans ; Male ; Malondialdehyde ; analysis ; Membrane Potential, Mitochondrial ; Mitochondria ; Organophosphorus Compounds ; pharmacology ; Oxidative Stress ; drug effects ; Reactive Oxygen Species ; Semen ; Semen Analysis ; Semen Preservation ; Sperm Motility ; Spermatozoa ; drug effects ; Ubiquinone ; analogs & derivatives ; pharmacology