The uhrastructure and atrial natriuretic peptide(ANP)mRNA in myocardium of streptozotocin-induced diabetic rats were studied along with the effect of rosiglitazone.It was found that the myocardial ultrastructure was demaged in diabetic rats.Rosiglitazone may ameliorate the lesion in myocardium,and lower the ANP mRNA in diabetic rats(1.14?0.05 at 6 weeks and 1.12?0.09 at 10 weeks vs 0.97?0.14,both P

The expression of the vgb gene in vivo could improve the fermentation density and then contribute the extracellular secretion of the product of bxn gene. Constructed the recombination plasmid pPIC9K-vgbbxn and transformed into Pichia pastoris GS115. The results of PCR and SDS-PAGE indicate that the vgb gene and bxn gene had integrated into the genome of Pichia pastoris GS115 and expressed in efficient level. Also, the protein activity of their products had been verified respectively. Shake flask fermentation experiments showed that the presence of VHb in yeast Pichia pastoris efficiently enhanced cell growth and secretive expression of bxn gene under hypoxic habitats.
Aminohydrolases ; genetics ; metabolism ; Bacterial Proteins ; genetics ; physiology ; Electrophoresis, Polyacrylamide Gel ; Pichia ; genetics ; Plasmids ; Polymerase Chain Reaction ; Recombinant Proteins ; biosynthesis ; Truncated Hemoglobins ; genetics ; physiology

To study the pharmacokinetic process of Danshensu in cerebal ischemia injury model rats and the correlation with its anti-cerebral ischemia effect. In this study, the middle cerebral artery occlusion (MCAO) model was established, in which all of the rats were intravenously injected of Danshensu at a single dose of 40 mg x kg(-1). The HPLC-DAD method was applied to determine the plasma concentration of Danshensu at different time points and draw the drug-time curve. Meanwhile, the superoxide dismutase (SOD) and the lactate dehydrogenase (LDH) activity were determined to draw the time-effect curve. The DAS 3.2. 6 software was used to process the data, analyze their correlation, compare the pharmacokinetic difference between model and normal rats after the administration of the same doses of Danshensu and the changes in pharmacodynamic indicators of model rats after the administration, and evaluate the effect of Danshensu in treating the cerebral ischemia disease. According to the results, the pharmacokinetic processes of Danshensu in the cerebral ischemia-reperfusion and normal rats were consistent to the two-compartment model. The main pharmacokinetic parameters were: t1/2alpha were (0.267 +/- 0.026), (0.148 +/- 0.020) h;t1/2beta were (1.226 +/- 0.032), (1.182 +/- 0.082) h; AUC0-infinity were (42.168 +/- 4.007), (26.881 +/- 1.625) mg x L(-1) x h. After the cerebral ischemia-reperfusion, the activity of SOD decreased and the activity of LDH increased. Danshensu could inhibit the decrease in the SOD activity and the increase in the LDH activity within a certain period of time. This indicated that Danshensu could stay longer in cerebral ischemia-reperfusion rats than in normal rats and eliminated more slowly, which reflected the rationality of Danshensu in the clinical treatment of cerebral ischemia diseases. Danshensu's effect against the cerebral ischemic injury may be related with its level in vivo. Its plasma concentration is positively related to the SOD activity and negatively related to the LDH activity.
Animals ; Brain Ischemia ; drug therapy ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; therapeutic use ; Male ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry

BACKGROUNDThis study transferred a recombinant gene encoding human insulin like growth factor-1 (hIGF-1) into modified primary skeletal myoblasts with a retroviral vector (pLgXSN) and determined whether the hIGF-1 promoted growth of skeletal muscle in rat.

METHODShIGF-1cDNA was amplified in vitro from normal human liver cells by using RT-PCR and cloned into plasmid vector pLgXSN. The recombinant vector pLghIGF-1SN and control vector pLgGFPSN were transfected into packaging cell PT67 and G418 was used to select positive colony. Myoblasts were infected with a high titre viral supernatant and transduction efficiency was evaluated as GFP expression. The expression of hIGF-1 mRNA in myoblasts was investigated by immunocytochemistry and RT-PCR. MTT assays detected the growth of myoblasts in vitro. Myoblasts transduced with pLghIGF-1SN were injected into hind limb muscles of 10 - 12 week male SD rats. Formed tissues were harvested 4 weeks later. Myocyte diameter, mean weight of hind limb and body were measured to evaluate the skeletal muscle growth.

RESULTSRecombinant retroviral plasmid vector pLghIGF-1SN was constructed successfully. The titre of the packaged recombinant retrovirus was 1 x 10(6) cfu/ml. The transfection rate of PT67 cells reached 100% after G418 screening. hIGF-1 expression was positive in myoblast-IGF-1. The proliferation rate of myoblast-IGF-1 in vitro was higher than GFP-myoblast or myoblast (P < 0.05). The mean weights of hind limb and body of rats injected myoblast-IGF-1 were higher than those of the rats injected with myoblast-GFP or myoblast (P < 0.05). Myocyte diameter had a significant increase in IGF-1 group compared to GFP group and myoblast group (P < 0.05).

CONCLUSIONSThe transfection of the human IGF-1 gene mediated by a retroviral vector can promote the growth of skeletal muscle in rats. Genetically modified primary skeletal myoblasts provide a possibly effective approach to treat some skeletal muscle diseases.

Animals ; Cells, Cultured ; DNA, Recombinant ; genetics ; Genetic Vectors ; Insulin-Like Growth Factor I ; genetics ; physiology ; Muscle, Skeletal ; growth & development ; Myoblasts ; physiology ; Rats ; Rats, Sprague-Dawley ; Retroviridae ; genetics ; Transfection

OBJECTIVETo study the effects of sodium on rat osteoblast function and explore the role of epithelial sodium channel (ENaC) in such effects.

METHODSThe proliferation and differentiation of rat osteoblasts were evaluated following treatment with 1×10(-4) mol/L to 1 mol/L Na(+). The mRNA expressions of the osteogenic genes and ENaC-α gene in the treated cells were assessed using RT-PCR.

RESULTSWithin the concentration of 1×10(-4) mol/L to 1 mol/L, Na(+) showed a two-way effect on the osteoblasts: low-concentration Na(+) (1×10(-4) mol/L) significantly promoted osteoblast differen- tiation, while at higher concentrations (0.5 and 1 mol/L), Na(+) produced an opposite effect. Sodium did not significantly affect osteoblast proliferation. Low-concentration Na(+) significantly increased the transcription of Cbfa1, OPN and OC, while high concentrations of Na(+) decreased their transcription. Low-concentration Na(+) also enhanced the mRNA expression of ENaC-α, but high-concentration Na(+) treatment lowered ENaC-α mRNA expression.

CONCLUSIONNa(+) displays a direct dose-related effect on osteoblasts by affecting its differentiation, osteogenic gene expression profile, and ENaC-α gene expression, suggesting the involvement of ENaC in Na(+)-mediated functional modulation of rat osteoblasts.

Animals ; Animals, Newborn ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Epithelial Sodium Channels ; metabolism ; Osteoblasts ; cytology ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium Chloride ; pharmacology ; Transcriptome

Objective To summarize the preliminary clinical outcomes of combination therapy with molecular targeted agents/immunological agents and to explore the potential value of multidisciplinary therapy in the treatment of postoperative refractory recurrent hepatobiliary tumor.Methods 52 cases of postoperative refractory recurrent hepatobiliary tumor during June 2016 to January 2019 from outpatient and inpatient departments at the First Medical Center of PLA General Hospital were prospectively collected,including 37 males and 15 females,with a mean age of (56.2 ± 8.5) years.Referring to the results of next-generation sequencing (NGS) and other-omics,we designed individualized therapy options for each patient.Follow-ups were done regularly and tumor responses were assessed by modified response evaluation criteria in solid tumors (mRECIST).Results Of 52 patients,median follow-up was 10 months (range 3-31 months).14 (26.9％) patients achieved a complete response (CR).8 (15.3％) patients achieved a partial response (PR).14 (26.9％) patients had stable disease (SD).16 (30.8％,including 4 deaths) had progressive disease (PD).Objective response rate and disease control rate were 42.3％ (22/52) and 69.2％ (36/52),respectively.The median progression-free survival (PFS) was 7 months.6-and 12-month overall survival rates were 100％ (48/48),87.5％ (21/24),respectively.Conclusions Precision medicine has good guidance on the treatment of refractory recurrence of hepatobiliary tumors.The combination therapy of multi-target tyrosine kinase inhibitors and immune checkpoint inhibitors may achieve better disease control and deserve further promotion in clinical application.

BACKGROUND: Elastic intramedullary nail is commonly used in the treatment of fractures of children, but few studies concern the elastic intramedullary nail for treating fractures in adults. OBJECTIVE: To investigate the repair effect of elastic intramedullary nail in the treatment of 22-A fracture in forearm of adults. METHODS: From January 2015 to April 2016, a total of 21 adult patients with the 22-A fracture (35 fractures) were treated with manipulative reduction and elastic intramedullary nail fixation in the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The follow-up time was 12-18 months. Radiographs were taken and the guidance of the limb function training was given at regular intervals. The Andserson scoring system was used to evaluate the patients' forearm limb function. Fracture healing, elbow, wrist joint activity and forearm rotation were recorded. The satisfactory questionnaires were recorded. The patients were divided into three grades as satisfaction, general satisfaction and dissatisfaction; simultaneously, reasons were recorded. RESULTS AND CONCLUSION: (1) The Andserson scoring was satisfactory in 16 cases accounted for 76%, general satisfaction in 3 cases accounted for 14%, dissatisfaction in 2 cases accounted for 10%. (2) Wrist joint activity increased from (172±4)° before the operation to (181±3)° at the end of the follow-up. Elbow joint activity increased from (102±18)° before the operation to (124±13)° at the end of the follow-up. Forearm rotation activity increased from (84±11)° before the operation to (155±13)° at the end of the follow-up (P < 0.05). (3) In the follow-up of the 21 patients, 13 patients were satisfied with the result of surgery; 5 patients were generally satisfied; 2 patients were dissatisfied because the limited limb functions; and 1 patient was dissatisfied because of the nail irritability; the dissatisfaction rate accounted for 14%. (4) Elastic intramedullary nail can obtain affirmative effect in the treatment of adult 22-A fracture of the forearm; and clinical application should be based on the type of fracture.

OBJECTIVETo evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring.

METHODSIn a multicenter, randomized, double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP) remained ≥ 90 mm Hg (1 mm Hg = 0.133 kPa) were randomly divided into benazepril 10 mg/amlodipine 5 mg (BZ10/AML5) fixed-dose combination therapy group (once a day, n = 113), and benazepril monotherapy group (daily 20 mg, n = 107). In the two groups the patients with SeDBP ≥ 90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks, and the patients with SeDBP < 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients (the combination therapy group n = 38, monotherapy therapy group n = 36) completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis.

RESULTSThe randomized, double-blind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment (a SeDBP < 90 mm Hg or a decrease of 10 mm Hg or more from baseline) were (11.7 ± 6.8) mm Hg, 65.7% and 88.5% in the combination therapy group, respectively, and were (7.7 ± 6.9) mm Hg, 35.5% and 65.5% in the monotherapy group, respectively. There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs (P < 0.001). The fixed combination significantly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine (10 mg/5 mg) and benazepril (20 mg) alone were 83.1%/76.0% and 85.8%/79.5%, respectively. Adverse events rates were 16.8% in the combination therapy group and 35.5% in the monotherapy group (P < 0.001).

CONCLUSIONSThe combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.

Adult ; Amlodipine ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Antihypertensive Agents ; administration & dosage ; therapeutic use ; Benzazepines ; administration & dosage ; therapeutic use ; Calcium Channel Blockers ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Combinations ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged

Adolescent ; Adult ; Aged ; Child ; Endoscopy, Gastrointestinal ; methods ; Female ; Gastrointestinal Hemorrhage ; diagnosis ; pathology ; Humans ; Male ; Middle Aged