Pharmacokinetic study of five ingredients from Chitong xiaoyanling granules in rats / 中国药房

OBJECTIVE To study the pharmacokinetics of paeoniflorin， hesperidin， naringenin， formononetin and enoxolone from Chitong xiaoyanling granules in rats. METHODS Six male SD rats fasted but not deprived of water for 12 h were given Chitong xiaoyanling granules （5.0 g/kg） intragastrically at one time. Blood was collected from inner canthus of rats at different time points after administration. Plasma samples were pretreated with acetonitrile precipitated protein （sulfamethoxazole as internal standard）， and the concentrations of 5 ingredients in plasma were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. The pharmacokinetic parameters of each ingredient were calculated using DAS 3.0 software. RESULTS After intragastric administration of Chitong xiaoyanling granules， tmax and t1/2 of formononetin were the shortest among 5 ingredients （0.25 h and 0.39 h， respectively）. For naringenin and enoxolone， the tmax was shorter， but t1/2 was longer， and there was an obvious double-peak phenomenon in the drug-time curve of naringenin. Compared with the other three components， cmax and AUC of paeoniflorin and hesperidin were not directly proportional to the content of in vitro components. CONCLUSIONS Formononetin， naringin and enoxolone in Chitong xiaoyanling granules were absorbed rapidly in rats， while paeoniflorin and hesperidin were absorbed slowly.

Research on KBP model refining method using multi-criterion optimization technology / 中华放射肿瘤学杂志

Objective:Utilizing multi-criterion optimization (MCO) technology to improve plan design quality based on knowledge-based planning (KBP) model.Methods:Fifty-five patients with nasopharyngeal carcinoma (NPC) who had completed radiotherapy were selected, and fixed-field intensity-modulated radiotherapy (IMRT) technology was used in each case. Among them, 40 cases were randomly selected as training set 1. Then, IMRT plans in training set 1 were preprocessed by MCO technology to construct a new training set 2. With the initial training set 1 and the processed training set 2 as training samples, the traditional KBP model and the MCO-KBP model refined by MCO technology were trained, respectively. Among the remaining 15 cases, 5 cases were randomly selected as the validation set, and the remaining 10 cases were used as the test set. After verification, the test set was used to statistically analyze the plan quality of the initial manual plan and the automatic plan generated by the traditional KBP model and the MCO-KBP model.Results:The target dose (D 95%) of plans generated by the traditional KBP model and the MCO-KBP model met the clinical requirements. Conformity index (CI) and homogeneity index (HI) were almost the same ( P>0.05), and the doses of organ at risk (OAR) of the automatic plans generated by the MCO-KBP model were lower than those of the traditional KBP model. For example, compared with the traditional KBP model, the average D max of the brainstem in the automatic plans generated by the MCO-KBP model was lower by 2.13 Gy, the average D mean of the left parotid gland was lower by 1.39 Gy, the average D mean of the right parotid gland was lower by 1.59 Gy, and the average D max of the left optic nerve was lower by 1.42 Gy, the average D max of the right optic nerve was lower by 1.16 Gy, and the average D max of the pituitary gland was lower by 1.88 Gy. All of the above-mentioned dosimetry indexes were statistically significant. Conclusion:Compared with the traditional KBP model, the IMRT plans designed by the refined MCO-KBP model have obvious advantages in the protection of OAR, which proves the feasibility of utilizing MCO technology to improve the plan design quality of the KBP model.

Fine-tuning cell organelle dynamics during mitosis by small GTPases / 医学前沿

During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer's disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.

The effect and mechanism of short-chain fatty acid regulate tacrolimus-related hyperglycemia in mice / 中华泌尿外科杂志

Objective:To investigate the effect and mechanism of short-chain fatty acids (SCFAs) on the side-effect of tacrolimus on blood glucose.Methods:The C57BL/6 mice were treated with tacrolimus orally (10 mg/kg, tacrolimus group), tacrolimus plus 150 mmol/L sodium butyrate and isovalerate mixed solution (SCFAs group), broad-spectrum antibiotics (antibiotic group), and tacrolimus plus broad-spectrum antibiotics (tac&abx group). After 8 weeks intervention, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), hemoglobin A1C (HbA1c) were tested as indicators of glucose metabolism, and the gut microbiota, SCFAs concentration in the ileocecal, serum glucagon-like peptide-1 (GLP-1), fasting serum insulin, and GLP-1 expression in intestinal mucosa were performed for intestinal-glucose metabolism mechanism.Results:The FBG and HbA1c were significantly increased in tacrolimus group[(7.31±0.97)mmol/L, (8.34±1.12)%] than control group [(5.23±0.30)mmol/L, (4.32±0.80)%, all P<0.05], which remained normal in antibiotic group [(4.92±0.31)mmol/L, (5.61±0.98)%)], tac&abx group[(5.95±0.37)mmol/L, (4.56±0.26)%] and SCFAs groups [(5.87±0.68)mmol/L, (5.07±1.79)%]. The OGTT in the tacrolimus group showed glucose tolerance impairment, while other groups remained normal. The ileocecal butyric acid and isovaleric acid concentrations in the tacrolimus group were (722.3±262.2) μg/g and (10.0±5.1)μg/g, lower than the control group[ (1 321.3±165.5) μg/g, (19.7±3.6)μg/g, P<0.05]. The above acids in the SCFAs group remained normal as in the control group [(1 375.7±451.6) μg/g, (24.5±11.5)μg/g)]. The fasting serum insulin in the tacrolimus group decreased significantly to (3.2 ± 0.6)mIU/L, compared with control[ (4.4±0.9) mIU/L]and SCFAs groups [(7.0±1.1) mIU/L]. The GLP-1 test indicated a significant decrease in the tacrolimus group[ (4.7±2.9)pg/ml, P<0.05] compared with the SCFAs group and control group [(42.5±19.9) pg/ml, (33.1±9.1) pg/ml]. Conclusions:Tacrolimus affects glucose metabolism through the SCFAs-associated GLP-1 pathway in the intestine, and oral supplementation with mixed SCFAs provides a new insight for the prevention and treatment of tacrolimus-induced hyperglycemia in transplant recipients.

Signal transducer and activator of transcription 3 promotes vascular endothelial cell proliferation and migration by fractalkine / 生物工程学报

Signal transducer and activator of transcription 3 (STAT3) and Chemokine CX3C ligand 1 (Fractalkine/CX3CL1) play important roles in vascular inflammation and injury. To study if STAT3 promotes vascular endothelial cell proliferation and migration through fractalkine, we overexpressed or knocked down STAT3 in vascular endothelial cells, and used quantitative real-time PCR and Western blotting to determine the effect of STAT3 on fractalkine expression. The wild type and STAT3 binding site mutant fractalkine promoter luciferase reporter plasmids were constructed, and luciferase activity assays were used to explore the effect of STAT3 on the transcriptional activity of the fractalkine promoter. MTT assays were used to detect the effect of overexpression or knockdown of STAT3 or fractalkine on the proliferation rate of vascular endothelial cells. Scratch assays were used to detect the effect of overexpression or knockdown of STAT3 or fractalkine on vascular endothelial cell migration. There results showed that overexpression of STAT3 could promote fractalkine expression, and knockdown of STAT3 could down-regulate fractalkine expression. STAT3 could directly bind to the promoter of fractalkine to promote its transcriptional activity via binding the GAS site of the fractalkine promoter. Knockdown of STAT3 could inhibit the migration of vascular endothelial cell, and overexpression of fractalkine antagonized this inhibition. Our data concluded that STAT3 promotes the proliferation and migration of vascular endothelial cell by binding the GAS site of the fractalkine promoter to promote fractalkine transcriptional activity and expression.

The preliminary study on clinical application of CRT+ARC technique in patients with locally advanced lung cancer / 实用肿瘤学杂志

Objective This paper investigated the clinical application of CRT+ARC technique in locally advanced lung cancer. Methods A total of 100 patients with locally advanced lung cancer who underwent radiotherapy in our hospital from March 1,2016 to March 1,2017 were randomly assigned to the experimental and control groups. Each group consisted of 50 patients. The CRT+ARC plans were made for the experimental group,and the CRT + intensity-modulated radiotherapy(IMRT)(CRT+IMRT) plans for the control group. According to the World Health Organization( WHO) criteria,the short-term efficacy of patients was as-sessed. According to the imaging examination and the Radiation Therapy Organization Group(RTOG)standard,the occurrence of major side effects of radiation pneumonia was identified. Results The effective rate of treatment was 82% in the experimental group and 76% in the control group. There was no difference in the effective rate between the two groups(χ2 =0. 542,P=0. 461). The incidence of pneumonia in the experimental group was 22% ,and 18% in the control group. There was also no difference in the incidence of pneumonia between the two groups(χ2 =0. 250,P=0. 617). Conclusion In the clinical application of locally advanced lung cancer, CRT+ARC technique has no difference in the short-term efficacy and the main side effects of radiation pneumonitis compared with CRT+IMRT.

Research progress in endoscopic retrograde cholangiopancreatography-mediated photodynamic therapy for cholangiocarcinoma / 中南大学学报(医学版)

The malignant degree of cholangiocarcinoma is high, and the early diagnosis is difficult. The vast majority of patients are unresectable when they are diagnosed. The patients have low quality of life and short survival cycle. Traditional radiotherapy and chemotherapy have poor efficacy and lead to side effects, and thus lack effective control measures for cholangiocarcinoma. Endoscopic retrograde cholangiopancreatography (ERCP) is an important method for diagnosing and treating biliary tract diseases. Photodynamic therapy (PDT) is a new local treatment for cholangiocarcinoma. In recent years, ERCP-mediated PDT treatment of cholangiocarcinoma has gradually emerged. ERCP-mediated PDT can effectively relieve the symptoms of patients with cholangiocarcinoma, improve the patients' quality of life, prolong the survival cycle, and is expected to become a new treatment for cholangiocarcinoma.

Establishment of orthotopic colorectal cancer model by colonoscopy with submucosal injection in living mice / 国际生物医学工程杂志

Objective To set up a living mice colonoscopy platform to establish an orthotopic model of colorectal cancer in mice under direct vision,and to observe its biological behavior such as metastasis.Methods Eighteen-week-old male C57/BL mice were anesthetized,and the intestinal lumen of the mice was examined by a self-developed living mice colonoscopy and Olympus URF-P5 ureteroscopy,respectively.The imaging effects of the two methods were compared.Human colon cancer HT-29 cells were injected into the colonic mucosa of BALB/c-nu mice under direct vision.The colonoscopy was performed on the 3rd,7th and 15th day after the injection to observe the tumor formation in the intestinal lumen.The mice were sacrificed when the body weight decreased significantly or cachexia appeared,and then the abdominal cavity was examined including the tumor formation and metastasis.Results The self-developed living mice colonoscopy platform can provide clear vision of enteric cavity,and no mice died in the colonoscopy examination.In vivo subcutaneous injection of HT-29 cells in mice was performed with a perforation rate of 15％,a mortality rate of 33.3％,a tumor formation rate of 62.5％,an abdominal metastasis rate of 60％,a liver metastasis rate of 25％,and an abdominal wall transfer rate of 25％.Conclusion The self-developed mice colonoscopy platform can be used for the study of colorectum in living mice.The imaging effect is no less than that of Olympus URF-P5 ureteroscopy.In addition,an orthotopic colorectal cancer model can be established by this platform combing with submucosal injection technology.

The role and mechanism of SDF-1/CXCR4 signaling pathway in rat model of chronic renal allograft rejection / 中华器官移植杂志

Objective To investigate the role and mechanism of SDF-1/CXCR4 in the development of chronic rejection (CR) in rat models.Methods CR rat models were established using Fisher 344 to Lewis rats.In the blank control group (n=10),Lewis rats getting isotransplantation were treated with Cyclosporine A.CR rat models were established in positive group (n=10) and the rats were treated with Cyclosporine A.CR rat models were also established in CXCR4 antagonism group (n=10) and the rats were treated with both Cyclosporine A and AMD3100 (1 mg/kg).The serum creatinine levels were monitored every week.Kidney grafts were harvested 12 weeks after transplantation for histological analysis.We evaluated graft injuries using chronic allograft damage index (CADI) scores.Q-PCR and Western blotting were used to measure CXCR4,TGF-β1/Smad3 signaling pathway and α-smooth muscle actin (α-SMA) expression in renal allograft tissues.Results The serum creatinine levels in blank control group and CXCR4 antagonism group were significantly lower than those in positive control group (P<0.05).The blank control group and CXCR4 antagonism group presented milder pathological manifestations of CR.The CADI score in CXCR4 antagonism group was 3.54,which was lower than that of positive control group (P<0.05).The expression of biological markers in TGF-β1/Smad3 signaling pathway and SDF-1/CXCR4 signaling pathway was significantly lower in blank control group and CXCR4 antagonism group than in positive control group (P<0.05).Conclusion SDF-1/CXCR4 signaling pathway may play a crucial role in the development of CR.The usage of SDF-1/CXCR4 antagonist can protect renal allograft by inhibiting the TGF-β1/Smad3 pathway.Therefore,antagonism of CXCR4 may provide a novel way to prevent the development of CR.

Clinical Observation of Xingnaojing Injection Combined with Butylphthalide in the Treatment of Middle Cerebral Artery Infarction / 中国药房

OBJECTIVE:To investigate the effects and safety of Xingnaojing injection combined with butylphthalide on neuro-logical function,cognitive function,coagulation function and living activity. METHODS:A total of 106 patients with middle cere-bral artery infarction in Wuhan University People's Hospital during Jun. 2014-Dec. 2015 were divided into control group and obser-vation group according to random number table,with 53 cases in each group. Besides routine symptomatic treatment,control group was given Butylphthalide soft capsules 0.2 g,po,tid. Observation group was additionally given Xingnaojing injection 20 mL added into 0.9% Sodium chloride injection 250 mL,ivgtt,qd. Both groups were treated for 14 d. The neurological function score (NI-HSS,NFDS),cognitive function score (MoCA,MMSE),coagulation function indexes (PT,APTT,FIB),BI score were ob-served in 2 groups before and after treatment. The occurrence of secondary remote damage and ADR were recorded. RESULTS:Eight patients withdrew from the study,including 3 patients of control group and 5 of observation group. Before treatment,there was no statistical significance in neurological function scores(NIHSS,NFDS),cognitive function scores(MoCA,MMSE),coag-ulation function indexes or BI scores between 2 groups (P>0.05). After treatment,NIHSS,NFDS scores and FIB of 2 groups were decreased significantly compared to before treatment,and the observation group was significantly lower than the control group,with statistical significance (P0.05). CONCLUSIONS:For middle cerebral artery infarction,the application of Xingnaojing injection combined with butylphthalide can reduce the risk of remote damage,promote the recovery of neurological function and cognitive func-tion,and improve coagulation function and living activity with good safety.

Role of up-regulated microRNA145 in viability, apoptosis, invasion and metastasis of hepatoma cells / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effects of microRNA145 ( miRNA145 ) on the viability, apoptosis, inva-sion and metastasis of hepatoma HepG2 cells.METHODS: HepG2 cells were randomly allocated into 3 groups: blank control group, empty mimic transfected group and miRNA145 mimic transfected group.Under the induction of Lipofectami-neTM 2000, the recombinant was transfected into HepG2 cells.After transfection, the expression level of miRNA145 was detected by real-time PCR.The protein level of N-cadherin and the mRNA expression levels of miRNA145 and N-cadherin were detected by Western blot and real-time PCR.The cell viability was detected by MTS assay.The cell cycle and apopto-sis were analyzed by flow cytometry.Invasion and metastasis were detected by Transwell assay.RESULTS:Compared with negative control, miRNA145 expression was up-regulated significantly, while the expression of N-cadherin was down-regu-lated significantly.Meanwhile, the cell viability, cell cycle, apoptosis, invasion and metastasis of hepatoma HepG2 cells were all significantly inhibited (P<0.05).CONCLUSION:miRNA145 dramatically inhibits viability, apoptosis, inva-sion and metastasis of hepatoma cells.

Dosimetric comparison of intensity-modulated arc radiotherapy and fixed beam dynamic intensity-modulated radiation therapy in nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVE@#To compare the dosimetric differences of dosiology between intensity-modulated arc radiotherapy (IMAT) and dynamic intensity-modulated radiation therapy (dIMRT) in nasopharyngeal carcinoma.@*METHODS@#CT data from 25 patients treated in our radiotherapy center were selected randomly for this study. For each patient, the IMAT technique and the fixed beam dIMRT technique were accomplished by the simultaneously integrated boost. Dose volume histogram (DVH) data, isodose distribution, monitor units (MUs) and treatment time were compared in the two techniques.@*RESULTS@#There was no significant difference between the IMAT and the dIMRT in dose received by 95% of target volumes (D(95)) (P>0.05). Overall, the mean dose (D(mean)), maximal dose (D(max)) and volume percentage receiving at least of 107% of the prescribed dose (V(107%)) of planning target volume (PTV) for the IMAT were increased slightly ,compared with the dlMRT (P0.05). Compared with the dlMRI, the D(max) of brain stem for the IMAT was increased slightly (P<0.05). Similar trends was observed for the D(mean) and dose received by 50% of volume (D(50)) of the left and right parotid glands (P<0.05). Healthy tissue (defined as the volume of the body minus PTV,B-P) irradiated from 800 cGy in the IMAT was higher, and that from 1200-4500 cGy was lower compared with the dlMRI (P<0.05).The average number of MUs was reduced by 62.7% per fraction, and the treatment time was on average reduced by 60.1% per fraction in the IMAT compared with the dlMRI.@*CONCLUSION@#There is a slight difference in dosiology between the two radiotherapy techniques investigated, but they both meet the clinical requirement. Compared with the dIMRT, the IMAT delivers less irradiation to healthy tissue, uses fewer MUs and takes less time during radiotherapy for nasopharyngeal carcinoma.

In situ absorption and metabolism of stilbene glycoside in rat / 药物分析学报

Stilbene glycoside (TSG) has been shown to have many beneficial properties. It is therefore essential to understand the absorption and metabolism of TSG in detail. We determined the recovery of TSG and its metabolites (TSG sulfate/glucuronides) in rat gastric contents, gastric mucosa, portal vein plasma, celiac arterial plasma, bile, and urine after administration of 15mg of TSG in 0.5mL physiological saline or incubation for 20min in situ in the stomach of rats. Within 20min, (64.0±9.8)% of the administered TSG disappeared from the stomach; later, TSG was recovered in both free and conjugated forms in plasma and bile, but not in urine. On the other hand, only free TSG was detected in the gastric contents and mucosa; it was also detected in the portal vein plasma as (48.1±3.5)% of the total TSG (all forms of TSG). However, the proportion of free TSG in the celiac arterial plasma and bile decreased to 4%-10%. In addition, the proportion of free TSG to total TSG in the liver microsome incubation mixture after TSG was incubated in liver microsome at 37℃ for 30min was very low [(10.6 ± 2.6)%]. These results indicate that TSG could be quickly absorbed from the rat stomach, conjugated in liver and excreted in bile. Such novel information would be helpful for the use of TSG as a beneficial natural product which may improve its proposed efficacy in preventing chronic diseases.