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1.
Chinese Journal of Urology ; (12): 752-756, 2020.
Artigo em Chinês | WPRIM | ID: wpr-869752

RESUMO

Objective:To evaluate the feasibility and efficacy of 68Ga-PSMA PET/CT-guided targeted prostate biopsy for the diagnosis of clinically significant prostate cancer(csPCa). Methods:This retrospective analysis allocated 89 patients with elevated PSA levels between 4.0-20.0 ng/ml to PET group(n=48) or TRUS group(n=41) between September 2017 and June 2019. Patients with PSMA-avid lesions (SUV max≥8.0) underwent PET-TB via a single-puncture percutaneous transgluteal approach (n=19), while patients with negative PSMA-PET underwent systematic TRUS-GB (n=29). Patients in the TRUS group who did not get 68Ga-PSMA PET/CT examination underwent TRUS-GB directly (n=41). The mean age, prostate volume, PSA value of PET group and TURS group were (71.2±9.1) years vs. (68.0±12.0) years, (62.9±29.1)ml vs. (65.4±38.9)ml , 8.8(6.6, 13.6) ng/ml vs. 9.8(7.1, 13.1)ng/ml, respectively (all P>0.05). The diagnostic efficacy and difference of PCa and csPCa between the two groups were compared. PET-TB adopts a new mode of percutaneous gluteus approach and carries out precise image fusion of PSMA-PET/CT and pelvic CT in the same machine and in the same position (prone position). Under the direct guidance of CT, the biopsy is performed with only one precise puncture. Results:PCa and csPCa were detected in 27/89(30.3%)and 20/89(22.5%)in all patients. PET group detected significantly more cases of PCa and csPCa than those of TRUS group [PCa: 41.7%(20/48) vs. 17.1%(7/41), χ2=6.328; csPCa: 33.3%(16/48) vs. 9.8%(4/41), χ2=7.055, P<0.01]. Of 19 patients with PSMA-PET positive, PET-TB detected 16 cases of PCa(84.2%) by a single needle puncture, and the proportions of cancer tissues were ≥80% in 2, 50%-79% in 8, and <50% in 6 cases. Among these, Gleason score was underestimated by biopsy histopathology in 2 patients. Of 3 patients with PET-TB negative, 1 case of low-risk PCa(Gleason 3+ 3) was detected by complementary TRUS-GB. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy of 68Ga-PSMA PET/CT(SUV max≥8.0) for the diagnosis of csPCa were 73.9%(14/19), 93.1%(27/29), 87.5%(14/16), 81.3%(26/32)and 85.4%(41/48), respectively. For PET-TB, only one patient had slight symptoms of haematuria after the puncture, no cases of hematochezia, hemospermia, urinary retention or pelvic infection were observed. Conclusions:68Ga-PSMA PET/CT is a feasible novel puncture technique that may serve as a triage tool for prostate biopsy, and PET-TB may improve the detection rate of csPCa compared with TURS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.

2.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 257-261, 2019.
Artigo em Chinês | WPRIM | ID: wpr-745452

RESUMO

Objective To evaluate the combined application of the maximum standardized uptake value (SUVmax) of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid (HBED-CC)-(Ahx) Lys-CO-Glu (PSMA-11) PET/CT imaging and the apparent diffusion coefficient (ADC) value of MRI in the differential diagnosis of prostate cancer (PCa).Methods Seventy untreated patients (age:(68.3± 12.1) years) with suspected PCa between December 2016 and April 2018 were prospectively studied.All patients underwent PET/CT and MRI examinations.The SUVmax and average ADC value were measured as diagnostic parameters,and the SUVmax/ADC ratio was calculated.The sensitivity and specificity of the 3 parameters were calculated by receiver operating characteristic (ROC) curve analysis.Results Of the 70 patients,31 were pathologically diagnosed as benign diseases and 39 were as PCa.The diagnostic sensitivity and specificity of average ADC value for PCa were 81% and 72%,respectively,with a threshold value of 1.08× 10-3 mm2/s (b=1 000 s/mm2).The diagnostic sensitivity and specificity of SUVmax were 82% and 71% for PCa with a critical value of 7.69,and those were 72% and 93% with SUVmax/ADC ratio of 11.87.Conclusion The combination of 68Ga-PSMA-11 PET/CT and MRI can improve the diagnostic specificity for PCa,and the SUVmax/ADC ratio is a valuable differential diagnostic index.

3.
Acta Pharmaceutica Sinica B ; (6): 937-951, 2019.
Artigo em Inglês | WPRIM | ID: wpr-774932

RESUMO

Artemisinin and its derivatives (ARTs) were reported to display heme-dependent antitumor activity. On the other hand, histone deacetylase inhibitors (HDACi) were known to be able to promote heme synthesis in erythroid cells. Nevertheless, the effect of HDACi on heme homeostasis in non-erythrocytes remains unknown. We envisioned that the combination of HDACi and artesunate (ARS) might have synergistic antitumor activity through modulating heme synthesis. studies revealed that combination of ARS and HDACi exerted synergistic tumor inhibition by inducing cell death. Moreover, this combination exhibited more effective antitumor activity than either ARS or HDACi monotherapy in xenograft models without apparent toxicity. Importantly, mechanistic studies revealed that HDACi coordinated with ARS to increase 5-aminolevulinate synthase (ALAS1) expression, and subsequent heme production, leading to enhanced cytotoxicity of ARS. Notably, knocking down significantly blunted the synergistic effect of ARS and HDACi on tumor inhibition, indicating a critical role of ALAS1 upregulation in mediating ARS cytotoxicity. Collectively, our study revealed the mechanism of synergistic antitumor action of ARS and HDACi. This finding indicates that modulation of heme synthesis pathway by the combination based on ARTs and other heme synthesis modulators represents a promising therapeutic approach to solid tumors.

4.
Journal of Jilin University(Medicine Edition) ; (6): 394-397,后插4, 2018.
Artigo em Chinês | WPRIM | ID: wpr-691584

RESUMO

Objective:To explore the key points of preoperative preparation,the experience of operation and attentions of postoperative treatment of surgical treatment in multiple tophi in the extremities.Methods:A total of 23 cases of multiple tophi in extremities were selected,all were male;aged from 31 to 65 years old,average 48.7 years old;the course of the disease ranged from 4 to 20 years,with an average of 9.13 years;the blood uric acid before operation ranged from 380 to 665 μmol·L-1,the level of uric acid was controlled by physicians before operation and the patients were not in the attack period.The patients underwent gout stone resection.Some of the patients underwent functional reconstruction and were treated with standardized gout medicine after operation. Results:Twenty-one cases of incision were grade A healing 2 weeks after operation,and 2 cases of incision still had uric acid salt exudation and healed after debridement suture.Among 23 cases,18 patients were followed for 4-12 months,an average of 8 months;5 patients were lost to follow-up.Compared with before operation,the joint function was improved,the degrees of joint activity were increased,and the discomfort was relieved in 16 patients after operation;there was no improvement in postoperative joint function in 2 patients,and the pain symptom in 1 patient with carpal tunnel syndrome was reduced.Conclusion:When properly indicated,the comprehensive therapy is the best treatment for the patients with multiple tophi in extremities.It is reliable and can improve the quality of life of the patients.

5.
Genomics, Proteomics & Bioinformatics ; (4): 99-107, 2018.
Artigo em Inglês | WPRIM | ID: wpr-772998

RESUMO

Like protein and DNA, different types of RNA molecules undergo various modifications. Accumulating evidence suggests that these RNA modifications serve as sophisticated codes to mediate RNA behaviors and many important biological functions. N-methyladenosine (mA) is the most abundant internal RNA modification found in a variety of eukaryotic RNAs, including but not limited to mRNAs, tRNAs, rRNAs, and long non-coding RNAs (lncRNAs). In mammalian cells, mA can be incorporated by a methyltransferase complex and removed by demethylases, which ensures that the mA modification is reversible and dynamic. Moreover, mA is recognized by the YT521-B homology (YTH) domain-containing proteins, which subsequently direct different complexes to regulate RNA signaling pathways, such as RNA metabolism, RNA splicing, RNA folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the mA recognition by YTH domain-containing proteins, which would shed new light on mA-specific recognition and provide clues to the future identification of reader proteins of many other RNA modifications.


Assuntos
Animais , Humanos , Adenosina , Química , Metabolismo , Ligação Proteica , Domínios Proteicos , RNA , Química , Metabolismo , Proteínas de Ligação a RNA , Química , Metabolismo
6.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 142-146, 2017.
Artigo em Chinês | WPRIM | ID: wpr-708792

RESUMO

Objective To assess the role of 68Ga-N,N'-bis (2-hydroxy-5-(carboxyethyl) benzyl) ethylenediamine-N,N'-diacetic acid(HBED-CC)-(Ahx) Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L,Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesionbased analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging,MRI).x2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine,with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients,liver metastasis in 2 patients (5 lesions),and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver,lymph node and bone metastases were 15.06±2.77,7.54±5.20,19.01± 16.96,respectively.The diagnostic sensitivity,specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54),3/3 vs 1/3,96.49% (55/57) vs 59.65% (34/57).The sensitivities and accuracies of the two modalities were significantly different(x2=19.943,22.593,both P<0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC,suggesting that it is of great value for the clinical management and treatment.

7.
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 142-146, 2017.
Artigo em Chinês | WPRIM | ID: wpr-513682

RESUMO

Objective To assess the role of 68Ga-N,N′-bis(2-hydroxy-5-(carboxyethyl)benzyl) ethylenediamine-N,N′-diacetic acid(HBED-CC)-(Ahx)Lys-CO-Glu(PSMA-11) PET/CT on the detection of metastatic lesions from castration-resistant prostate cancer (CRPC).Methods Sixteen patients with CRPC who underwent 68Ga-PSMA-11 PET/CT between January 2015 and November 2015 were recruited in this study.Mean age of patients was (72±9) years.The PSA levels were 4-12 356 μg/L, Gleason score was 7-10.PET/CT was performed at 1 h postinjection of 68Ga-PSMA-11.Patient-based analysis and lesion-based analysis were performed.ROI analysis was used to calculate the tumor uptake (SUVmax).Final diagnosis was based on histopathology and results of other imaging examinations(99Tcm-MDP imaging, MRI).χ2 test was used to compare the diagnostic efficiencies of PET and CT.Results No adverse effects were observed in patients.68Ga-PSMA-11 PET/CT showed moderate physiologic uptake in salivary glands and proximal small intestine, with predominant tracer clearance by the kidneys.All patients were positive on 68Ga-PSMA-11 PET/CT.Bone metastasis was found in 16 patients, liver metastasis in 2 patients (5 lesions), and lymph node metastasis in 4 patients (26 lesions).The SUVmax of liver, lymph node and bone metastases were 15.06±2.77, 7.54±5.20, 19.01±16.96, respectively.The diagnostic sensitivity, specificity and accuracy on bone metastasis with 68Ga-PSMA-11 PET and CT were 96.30%(52/54) vs 61.11%(33/54), 3/3 vs 1/3, 96.49%(55/57) vs 59.65%(34/57).The sensitivities and accuracies of the two modalities were significantly different(χ2=19.943, 22.593, both P<0.01).Conclusions 68Ga-PSMA-11 PET/CT could precisely detect both primary and metastatic lesions of CRPC, suggesting that it is of great value for the clinical management and treatment.

8.
Pakistan Journal of Medical Sciences. 2016; 32 (1): 176-180
em Inglês | IMEMR | ID: emr-178600

RESUMO

Objective: To compare the effects of thoracotomy and total thoracoscopic surgery on coronary artery fistulae complicated with ectasia


Methods: Forty-six patients with coronary artery fistulae complicated with ectasia were randomly divided into a treatment group and a control group [n=23] which were given totally thoracoscopic surgery and thoracotomy respectively. Both groups were followed up


Results: All patients survived the surgeries and were discharged from the hospital. The treatment group had significantly less intraoperative blood loss, earlier postoperative ambulation and shorter postoperative hospitalization stay more than those of the control group [P<0.05]. The two groups had similar plasm cortisol and adrenocorticotropic hormone levels one day before and after surgery. These levels peaked on the postoperative 3rd day, but those of the treatment group were significantly lower [P<0.05]. The two groups had similar left and right atrial diameters as well as left ventricular ejection fractions [LVEFs] before surgery, but the treatment group had significantly higher postoperative LVEF [P<0.05] as well as significantly smaller left and right atrial diameters in the postoperative 1[st] and 3rd months [P<0.05]. The treatment group was significantly less prone to postoperative complications such as chest pain, atelectasis and pulmonary infection than the control group [P<0.05]


Conclusion: Total thoracoscopic surgery promoted the recovery of coronary artery fistulae complicated with ectasia, improved cardiac remodeling and cardiac function, and alleviated stress reaction, with wellproved safety

9.
Journal of China Pharmaceutical University ; (6): 1-15, 2015.
Artigo em Chinês | WPRIM | ID: wpr-811896

RESUMO

@#The protein p53 plays an important role in the regulation of DNA repair, cell cycle arrest, apoptosis, senescence, autophagy and metabolism. MDM2 and MDM4 are the key negative regulatory proteins of p53. Inhibition of MDM2 and MDM4 has become a research hotspot in cancer therapy. Currently, seven MDM2 inhibitors(RG7112, MI-77301, RG7388, AMG232, CGM097, MK-8242, DS-3032b)and one MDM2/MDM4 dual inhibitor(ALRN-6924)have entered clinical trials. This paper highlights small molecule discovery, pharmacological activities and clinical research advances of MDM2 inhibitors in clinical trials, in addition, this review introduces research advances of MDM2/MDM4 dual inhibitors.

10.
Journal of Biomedical Engineering ; (6): 465-469, 2015.
Artigo em Chinês | WPRIM | ID: wpr-359625

RESUMO

Currently, all the conventional antibiotics have developed corresponding drug-resistant pathogenic strains, which have increasingly become a serious threat to people's health. Development of completely new types of antibiotics is one of effective ways to solve the drug resistance issue. Antimicrobial peptides with broad-spectrum antibacterial and antimicrobial activity and wild variety become the ideal alternative to traditional antibiotics. Antimicrobial peptides are derived from wide range of sources, such as plants, animals, and microorganisms. Mechanism of function of the antimicrobial peptides and the investigation approaches of different antimicrobial peptides also vary dramatically. In this paper, we give an overview of preparation, antibacterial mechanisms, and research methodology of antimicrobial peptides.


Assuntos
Animais , Humanos , Antibacterianos , Anti-Infecciosos , Peptídeos Catiônicos Antimicrobianos , Farmacologia
11.
Journal of Biomedical Engineering ; (6): 910-913, 2015.
Artigo em Chinês | WPRIM | ID: wpr-359548

RESUMO

Lipopolysaccharide (LPS), the important component of the outer membrane of Gram-negative bacteria, contributes to the integrity of the outer membrane, and protects the cell against bactericidal agents. LPS, also called endotoxin synonymously, is well known as a potent inducer of the innate immune system that often causes septic shock in the intensive cares. Chemically, the amphiphilic LPS is made up of three parts, i.e., hydrophobic lipid A, hydrophilic core oligosaccharide chain, and hydrophilic O-antigenic polysaccharide side chain. Specially, the lipid A is known to be responsible for a variety of biological effects during Gram-negative sepsis. LPS can elicit a strong response from innate immune system and result in local or systemic adverse reactions. LPS can trigger massive inflammatory responses and may result in immunopathology, for which the molecular basis is mediated by the signal path- way of LPS. In recent years, a tremendous progress has been made in determining the associated proteins and receptors in the LPS signaling that leads to the disease. This review gives a summary of recent progresses of research on LPS and LPS receptors.


Assuntos
Antibacterianos , Química , Desenho de Fármacos , Bactérias Gram-Negativas , Lipopolissacarídeos , Química
12.
Acta Pharmaceutica Sinica B ; (6): 300-309, 2015.
Artigo em Inglês | WPRIM | ID: wpr-310023

RESUMO

Chronic constipation is a common gastrointestinal disease severely affecting the patient׳s quality of life. The traditional treatment of constipation is the use of laxatives. Recently, several new drugs including lubiprostone, linaclotide and prucalopride have been approved for treatment of chronic constipation. However, a significant unmet medical need still remains, particularly among those patients achieving poor results by current therapies. The 5-HT4 receptor modulators velusetrag and naronapride, the guanylate cyclase C agonist plecanatide and the ileal bile acid transporter inhibitor elobixibat are recognized as the most promising drugs under investigation. Herein, we give a comprehensive review on the pharmacological therapeutics for the treatment of chronic constipation, with the purpose of reflecting the drug development trends in this field.

13.
Chinese Journal of Biochemical Pharmaceutics ; (6): 181-185, 2015.
Artigo em Chinês | WPRIM | ID: wpr-463358

RESUMO

Antimicrobial peptides ( AMPs) are critical component of the innate immune system of organisms, and have been demonstrated with the activity against a variety of microorganisms including bacteria, yeast, fungi, viruses and even tumor cells.Broad-spectrum activity and low propensity for resistance development make the AMPs as a kind of great potential for development of new anti-infective agents.In this paper, the origins, the action, the mechanism, the application prospects are reviewed.

14.
Chinese Journal of Medical Imaging ; (12): 481-485, 2015.
Artigo em Chinês | WPRIM | ID: wpr-468460

RESUMO

PurposeTo evaluate the feasibility of a low-dose contrast medium protocol for 64-slice spiral CT angiography (CTA) of cerebral and carotid using a low-tube-voltage setting, and to compare the display effect of cerebral and carotid arteries by low-tube-voltage low-dose contrast medium and routine-tube-voltage routine-dose contrast medium scanning, and to assess the effect on radiation dose.Materials and MethodsEighty consecutive patients were prospectively selected to perform cerebral and carotid CTA inspection. The patients were randomly divided into control group and low dose group with 40 people in each group. The voltage in control group was 120 kV and the contrast agent was 80 ml; those in low dose group were 80 kV and 50 ml, respectively. The artery image quality was evaluated and venous interference was scored. The CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and radiation dose in both groups were statistically analyzed.Results The consistency of uniform in artery image quality score and venous interference score was rather high according to the assessment of two physicians (Kappa=0.782 and 0.867). There was no statistical difference in artery image quality score, venous interference score, SNR and CNR between the two groups (Z=-0.864--0.032,P>0.05). The CT value in low dose group was higher than that in control group (differences with statistical significance,t=-8.789-1.715,P<0.05). The CT dose index of volume, dose-length product and effective dose in low dose group were all signiifcantly lower than those in control group (Z=-8.888,t=78.092 and 78.350, respectively,P<0.05).Conclusion The use of low tube voltage and low contrast dose in cerebral and carotid CTA examination can result in high quality images which meets the diagnostic needs and obviously reduce radiation dosage.

15.
Chinese Journal of Primary Medicine and Pharmacy ; (12): 2283-2284, 2014.
Artigo em Chinês | WPRIM | ID: wpr-451709

RESUMO

Objective To investigate the effects of ziprasidone and chlorpromazine on the ECG and cognitive function of patients with first episode of schizophrenia .Methods According to the digital table ,90 patients with first-episode schizophrenia were divided into two groups ,45 cases in each group .The control group was given chlorproma-zine,while the observation group received oral ziprasidone .Clinical efficacy,cognitive function and ECG results were compared before and after treatment .Results The PANSS scores of the study group and the control group were (57.78 ±4.16) points and (58.43 ±4.33) points after treatment,which were significantly lower than (72.62 ± 4.66)points and (72.39 ±4.87)points before treatment (t=7.15,7.46,all P0.05).The total number of tests of WCST ,continuous errors and CT error rate in study group after treatment were (73.32 ±5.08),(40.35 ±4.15) and (12.72 ±2.00)%,which were signif-icantly lower than (86.43 ±5.58),(67.72 ±4.26) and (21.02 ±2.33)%before treatmemt and (84.32 ±5.16), (65.82 ±4.25) and (20.05 ±2.20)%in the control group(t=6.84,7.21,7.85,7.52,8.21,8.12,all P<0.05). WCST categories completed and the number of CT net scores were (5.32 ±0.40) and (125.83 ±11.65) points, which were significantly higher than (3.41 ±0.38) and (102.82 ±10.72) points before treatment and (3.52 ± 0.39) and (108.37 ±10.24)points in the control group,the differences were statistically significant (t=6.72,7.11, 7.01,7.53,all P<0.05).The incidence rate of abnormal ECG in study group was 22.22% after treatment,which was significantly lower than 55.56% in the control group(χ2 =11.02,P<0.05).Conclusion Ziprasidone and chlorpromazine have a equivalent efficacy in the treatment of first-episode schizophrenia ,but ziprasidone can signifi-cantly improve cognitive function and has little effect on ECG ,it is safe.

16.
Chinese Journal of Microsurgery ; (6): 289-293, 2012.
Artigo em Chinês | WPRIM | ID: wpr-429129

RESUMO

Objective To examine the effect of valproic acid (VPA) on concentration of Intracellular Ca2+ and on cell apoptosis in spinal cord motor neurons after brachial plexus injury in rats. Methods Totally 210 adult male Wistar rats were randomly divided into Sham operation group (disposed the brachial plexus nerve root, but not cutted it off), control group (rats with brachial plexus nerve root amputating wound)and VPA group(rats with brachial plexus nerve root amputating wound and fed by VPA water),with 70 rats in each group.The specimens were taken at 12,24,48,72 h,1,2 and 4 weeks after operation.Whole-cell patch-clamp recording techniques were used to assayed the L-type calcium channel of motoneuron and monitored the changes in intracellular concentration of Ca2+ with spectrofluorometer. The motoneruron apoptosis was detected by TUNEL. Results The set of indicators did not change in the sham group.From 12h to 1 weeks after the operation, the electrical current of L-type calcium channel and the intra-cellular Ca2+ concentration of the neuron were obviously more in control group than in sham operation group (P <0.05). From 12 h to 4 weeks after the injury, there were more apoptosis neurons in control group than in sham operation group (P < 0.05). There was no obviously difference in electrical current of L-type calcium channel between the VPA group and the control group at each time point(P > 0.05).Compared to the control group,the intra-cellular Ca2+ concentration was lower in VPA group from 48 h to 1 week after nerve injury (P < 0.05) ; the number of apoptosis neurons were less in VPA group from 24 h to 2 weeks after the injury (P < 0.05). Conclusions Brachial plexus nerve root amputating wound in rats can increase the intra-cellular Ca2+ concentration and apoptosis of the motor neuron.VPA can reduce the intra-cellular Ca2+ concentration and apoptosis,but has no effect on the L-type calcium channel of the motor neuron.

17.
Journal of China Pharmaceutical University ; (6): 112-117, 2010.
Artigo em Chinês | WPRIM | ID: wpr-480434

RESUMO

In this study,a series of new sildenafil analogues 11-27 possessing a guanidine group were synthesized to investigate their PDE5 inhibitory activity and selectivity using[~3H]cGMP SPA kit in vitro and efficacy in the rat model of erection.Most of the compounds showed potent activity against PDE5,and more importantly,several compounds exhibited higher PDE5 selectivity over PDE6 than that of sildenafil.Structure-activity relationship of these sildenafil analogues was also discussed.Within this series of compounds,compound 15(IC_(50) =1.7 nmol/L)not only exhibited more potent PDE5 inhibitory activity than that of sildenafil (IC_(50) = 6.5 nmol/L),but also showed functional efficacy in the rat model of erection.

18.
Journal of China Pharmaceutical University ; (6): 493-498, 2010.
Artigo em Chinês | WPRIM | ID: wpr-480417

RESUMO

Soladulcidine is a steroidal alkaloid abundant in Solanum dulcamara L. with antitumor and other biological activities. In this study, ten soladulcidine derivatives were synthesized through esterification at C-3-hydroxy group, modification at NH group of F ring of esterification of E ring-opening products. The in vitro antiproliferative activity of these synthesized derivatives against prostate cancer (PC-3) cell line was assessed. Within this series of compounds, compound 19 exhibited the most potent inhibitory effect against the proliferation of PC-3 cell line (IC50=4.80±.9μmol/L).

19.
Chinese Journal of Medical Imaging Technology ; (12): 282-284, 2010.
Artigo em Chinês | WPRIM | ID: wpr-472260

RESUMO

Objective To observe the effect of the average heart rate (HR) and the variability of HR on image quality of 3D free-breathing whole-heart coronary MR angiography (MRCA). Methods A total of 65 healthy volunteers underwent retrospectively electrocardiography-gated 3D free-breathing whole-heart coronary MRA with ECG-gated 3D segmented-k-space gradient echo sequence. Two observers evaluated image quality of each coronary segment. Visualization of the proximal coronary arteries (CA) with coronary MRA was qualitatively evaluated using a four point grading scale (1: excellent; 2: good; 3: moderate; 4: non-diagnostic). Pearson correlation analysis was performed to analyze the correlation between image quality of each coronary artery and the average HR and heart rate variability. Results Average HR was 64.5±13.3 beats per minute (bpm) (range 40-86 bpm) with a variability of (6.1%±2.6)%. No significant correlation presented between mean HR and image quality of all segments of the left circumflex and left anterior descending artery except the right coronary artery (P<0.05). heart rate variability significantly correlated with overall image quality (P<0.001) and image quality of each coronary artery. Conclusion heart rate variability influences the image quality of 3D free-breathing coronary MRA more obvious than HR does.

20.
Chinese Journal of Anesthesiology ; (12): 743-746, 2010.
Artigo em Chinês | WPRIM | ID: wpr-387019

RESUMO

Objective To investigate the effect of oleanolic acid pretreatment on hepatic ischemiareperfusion (I/R) injury in rats. Methods One hundred and twenty-eight male SD rats weighing 230-250 g were randomly divided into 4 groups (n = 32 each): sham operation group (group S), I/R group, 0.5% sodium carboxymethyl cellulose group (group CMC) and oleanolic acid preconditioning (group OA). Partial liver ischemia was produced by clamping hepatic portal vein and hepatic arteries for 60 min with atraumatic mini-clamp, followed by 12 h of reperfusion in group I/R, CMC and OA. Oleanolic acid suspension 100 mg/kg was infused intragastrically in group OA, while the equal volume of 0.5% CMC-Na (in group CMC) and drinking water (in group S and I/R) was infused intragastrically instead once a day for 7 days, and then hepatic I/R was performed at day 8. The left liver was removed and blood sample was taken from inferior vena cava at 0, 3, 6 and 12 h ofreperfusion for determination of serum alanine amino transferase (ALT) activity, superoxide dismutase (SOD)activity, malondialdehyde (MDA) and glutathione (GSH) content, and expression of phospho-phosphatidylinositol3-kinase (p-PI3K), Akt, p-Akt, Bcl-2, Bax, p-Bad and Bad in the liver, and microscopic examination. Results Serum ALT activity and MDA content in the liver were significantly increased, SOD activity and GSH content in the liver were significantly decreased, expression of p-PI3K, p-Akt, Bax, Bad and p-Bad was up-regulated, and Bcl-2 expression was down-regulated during reperfusion in group I/R, CMC and OA as compared with group S (P <0.05). Compared with group I/R, serum ALT activity and MDA content in the liver were significantly decreased, SOD activity and GSH content in the liver were significantly increased, expression of p-PI3K, p-Akt,Bcl-2 and p-Bad was up-regulated, and expression of Bad and Bax was down-regulated during reperfusion in group OA (P < 0.05), but no significant change was found in the indexes mentioned above in group CMC (P > 0.05).Serum ALT activity and MDA content in the liver were significantly lower, SOD activity and GSH content in the liver were significantly higher, expression of p-PI3K, p-Akt, Bcl-2 and p-Bad was significantly higher, and expression of Bad and Bax was significantly lower during reperfusion in group OA than in group CMC (P < 0.05).The pathological changes in the liver were milder in group OA than in group I/R. Conclusion Oleanolic acid pretreatment can alleviate hepatic I/R injury by activating PI3K/Akt signaling pathway and inhibiting apoptosis.

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