Effects of Compound troxerutin and poreine cerebroside injection on cytochrome P450 enzyme in vivo and in vitro / 中国药房

OBJECTIVE To investigate the effects of Compound troxerutin and poreine cerebroside injection on the activity of cytochrome P450 （CYP450） enzyme in vivo and in vitro. METHODS Human liver microsomes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） and the specific probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 for 30 min. The production of corresponding metabolites was detected by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and the half inhibitory concentration （IC50） was calculated. The relative mRNA expression （i.e. induction multiple） of CYP450 enzyme was determined by real-time fluorescence quantitative PCR after human primary hepatocytes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） or 3 positive inducers of CYP1A2， CYP2B6， CYP3A4 for 48 hours. Male SD rats were randomly divided into control group （normal saline+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10， 10， 8 mg/kg） and experimental group （Compound troxerutin and poreine cerebroside injection 0.9 mL/kg+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10，10， 8 mg/kg）， with 6 rats in each group. The pharmacokinetic parameters of probe substrates were detected by UPLC-MS/MS and Cocktail probe drug method. RESULTS After the lzqpharm@126.com treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the activities of CYP2B6， CYP2C8 and CYP2C19 in human liver microsomes had no significant change， and IC50 could not be fitted； IC50 of CYP1A2， CYP2C9， CYP2D6 and CYP3A4 were 419.90%， 97.78%， 176.00%， 19.42%， respectively. After the treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the average induction multiple of CYP3A4 mRNA in human primary hepatocytes （No. MHK） was 4.88 （and the average induction multiples of 2 concentration points were higher than 2）. After the treatment of Compound troxerutin and poreine cerebroside injection， AUC0－t and AUC0－∞ of CYP2C8， CYP2C9 and CYP2C19 substrates were increased significantly， CL of CYP2C8 and CYP2C19 substrates were decreased significantly， while t1/2 of CYP2C9 substrate was prolonged significantly （P＜0.05）. CONCLUSIONS Compound troxerutin and poreine cerebroside injection has no obvious inhibitory effect on CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 in human liver microsomes in vitro， but can induce the mRNA expression of CYP3A4 in human primary hepatocytes in vitro， and can inhibit the activities of CYP2C8， CYP2C9 and CYP2C19 in rats in vivo.

Segmentation of core infarct in acute ischemic stroke in diffusion weighted imaging using cascaded VB-Net / 中华放射学杂志

Objective:To explore the detection and segmentation of ischemic core infarct volume of the acute stroke in diffusion weighted imaging (DWI) images using cascaded VB-Net.Methods:MRI data of 1 500 patients (2 456 lesions) with acute ischemic stroke in Henan Provincial People′s Hospital from December 2016 to December 2018 were retrospectively analyzed. Firstly, manual segmentation of ischemic core was performed on DWI images (b=1 000 s/mm 2), and then all data were divided into training set, validation set and independent test set by 8∶1∶1. Then, the cascaded VB-Net was constructed, and the core infarct was automatically detected and segmented in the test set. Interclass correlation coefficient (ICC) was used to evaluate the consistency of volume size measured by manual segmentation and cascaded VB-Net. The patients were divided into large ischemic core lesion group (ischemic core volume ≥10 ml) and small ischemic core lesion group (ischemic core volume<10 ml), and the Dice coefficient difference between the two groups was compared using Mann-Whitney U test. Results:In independent test set, cascaded model had the detection rate of 94.6% (243/257) with Dice coefficient of 0.76 (0.68, 0.84). The agreement of cacade VB-Net segmented [4.19(1.21,14.13)ml] and manual segmented ischemic core infarct volume [4.08(1.19,17.92)ml] was high (ICC=0.97, P<0.001). There was no significant difference in Dice coefficient between large and small lesion groups [0.76 (0.69, 0.85), 0.76 (0.67, 0.84), Z=-0.44, P=0.657]. Conclusions:The cascaded VB-Net model provided a tool to realize automatic detection, segmentation, and calculation of ischemic core infarct volume. It has good segmentation accuracy and high consistency with manual segmentation, which can provide an auxiliary decision-making tool for the selection of treatment plans.

Influence of effects of transarterial chemoembolization before liver transplantation on the prognosis of hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the influence of effects of transarterial chemoembo-lization (TACE) before liver transplantation on the prognosis of hepatocellular carcinoma.Methods:The retrospective cohort study was conducted. The clinicopathological data of 311 hepatocellular carcinoma patients undergoing TACE before liver transplantation who were admitted to the Third Medical Center of Chinese PLA General Hospital from January 2005 to December 2012 were collec-ted. There were 276 males and 35 females, aged from 47 to 59 years, with a median age of 52 years. All the 311 patients underwent TACE before liver transplantation. Observation indicators: (1) effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors; (2) follow-up; (3) influencing factors for prognosis of hepatocellular carcinoma patients after liver transplantation. Follow-up was conducted using outpatient examination or telephone interview to detect recurrence and metastasis of tumor and survival and graft loss of patients up to December 2017. The patients were followed up every 2 to 4 weeks within 3 months after liver transplantation, and once every 1 to 3 months thereafter. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was analyzed using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the nonparametric rank sum test. The COX regression model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to draw survival curves and calculate survival rates, and the Log-rank test was used for survival analysis. Results:(1) Effects of hepatocellular carcinoma patients undergoing TACE and its relationship with clinicopathological factors. Of the 311 patients undergoing TACE, 57 cases had pathologic complete response (pCR) and 254 cases had pathologic partial response (pPR), respectively. Cases with alpha fetoprotein (AFP) <20 μg/L,20?400 μg/L, >400 μg/L, cases with microvascular invasion, cases with tumor number as single nodule, cases with tumor distribution at right lobe of liver, cases with tumor caliber of feeding artery (CFA) >1 mm were 26, 26, 5, 51, 6, 43, 46 in patients with pCR, versus 87, 64, 103, 158, 59, 125, 159 in patients with pPR, showing significant differences in the above indicators ( Z=3.35, χ2=4.54, 15.71, 12.89, 6.79, P<0.05). (2) Follow-up. All the 311 patients were followed up for 47.0 to 59.0 months, with a median follow-up time of 44.6 months. There were 11 cases undergoing tumor recurrence and 11 cases undergoing tumor metastasis in the 57 patients with pCR, and there were 96 cases undergoing tumor recurrence and 66 cases under-going tumor metastasis in the 254 patients with pPR. The 1-, 3-, 5-year tumor recurrence free rates were 98.2%, 91.1%, 80.3% in the 311 patients, respectively. The 1-, 3-, 5-year tumor recurrence free rates were 100.0%, 91.1%, 80.3% in the 57 patients with pCR, versus 82.0%, 68.4%, 59.4% in the 254 patients with pPR, showing significant differences in the above indicators ( χ2=13.47, P<0.05). Cases with graft loss were 11 and 96 in the 57 patients with pCR and the 254 patients with pPR, respectively, showing a significant difference ( χ2=7.06, P<0.05). (3) Influen-cing factors for prognosis of hepatocellular carci-noma patients after liver transplantation. Results of univariate analysis showed that gender, basic diseases as viral hepatitis C, AFP (20?400 μg/L, >400 μg/L), Milan criteria, microvascular invasion, tumor number, tumor distribution, tumor CFA, times of TACE, effects of TACE were related factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.49, 3.97, 1.78, 1.84, 2.41, 1.96, 3.00, 1.76, 0.19, 2.01, 3.07, 95% confidence interval as 0.30?0.81, 2.23?7.05, 1.03?3.06, 1.18?2.85, 1.63?3.56, 1.28?3.01, 2.04?4.40, 1.20?2.59, 0.13?0.28, 1.28?3.14, 1.63?5.76, P<0.05). Results of multi-variate analysis showed that AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR were independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=1.59, 2.06, 1.99, 2.05, 95% confidence interval as 1.22?2.07, 1.35?3.13, 1.29?3.07, 1.02?4.10, P<0.05) and tumor CFA >1 mm was an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation ( hazard ratio=0.10, 95% confidence interval as 0.05?0.19, P<0.05). Conclusions:The effects of TACE are related to AFP, microvascular invasion, tumor number, tumor distribution and tumor CFA. AFP >400 μg/L, exceeding Milan criteria, tumor number as multiple nodule,effects of TACE as pPR are independent risk factors influencing prognosis of hepatocellular carcinoma patients after liver transplantation and tumor CFA >1 mm is an independent protective factor influencing prognosis of hepatocellular carcinoma patients after liver transplantation.

Establishment and characterization of a rat model of hypertension with hyperlipidemia / 中国比较医学杂志

Objective To develop an ideal hypertension combined hyperlipidemia(HP/HL)rat model by feeding spontaneously hypertensive rats(SHRs)with high fat diet, and to evaluate the pathological changes in target organs including heart and kidney. Methods Twenty 3-week old male SHRs were randomly divided into two groups: normal fat control group(SHR-NC)and high fat group(SHR-HF). Moreover,ten 3-week old male Wistar-Kyoto rats(WKY)were taken as the model control group(WKY-NC). The rats in SHR-HF group were fed with high-fat diet to induce HP/HL, while rats of WKY-NC and SHR-NC groups were fed with normal diet. The systolic blood pressure(SBP)and body weight were measured every week. At the end of the experiment, the rats were sacrificed to take serum samples for blood lipid analysis including high density lipoprotein(HDL-C), low density lipoprotein(LDL-C), total cholesterol(TC)and triglyceride(TG). Heart and kidney tissue samples were collected to examine the pathological changes using HE and Masson staining. Results Compared with the SHR-NC group, the SHRs fed with high-fat diet for 23 weeks presented significant increase of blood pressure and TC, TG, LDL-C, and decrease of HDL-C. The HP/HL rat model showed pathological changes in the HP/HL target organs, heart and kidney. Renal tissues were severely damaged and showed a large area of fibrosis. Besides, left ventricular hypertrophy and myocardial fibrosis were also observed. Conclusions A HP/HL rat model is successfully constructed by feeding SHRs with high-fat diet for 23 weeks. Most importantly,this model exhibits progressive renal and cardiac alterations, similar to those of patients with HP/HL. This HP/HL rat model may become widely used for evaluation of HP/HL therapeutic drugs.

Clinical effect of different treatment protocols for osteoporotic hip fractures in senile patients / 中华老年医学杂志

Objective To investigate the clinical effect of different treatment protocols for osteoporotic hip fracture in senile patients.Methods Clinical data of 156 senile patients with osteoporosis hip fracture admitted to our hospital from Jan.2012 to Jan.2015 were retrospectively analyzed.The clinical effects of different treatment protocols for osteoporosis hip fracture were compared and analyzed.Results 32 cases were treated with conservative treatment,15 cases with total hip replacement,45 cases with artificial femoral head replacement,16 cases with intramedullary fixation,10 cases with extramedullary fixation,38 cases with skeletal traction,and the excellent rate was 56.2％,93.3％,91.1％,62.5％,60.0％ and 63.2％,respectively.Conclusions An appropriate surgical treatment should be selected based on patient's self-conditions and fracture characteristics,while combining with drugs treatment and functional exercise so as to increase the clinical effect in senile patients with osteoporotic hip fracture.

Locking compression plate for treatment in the osteoporotic of unstable distal radius fractures / 中国基层医药

Objective To evaluate the effect of locking compression plate for treatment in the osteoporotic of unstable distal radius fractures.Methods 48 cases of osteoporotic of unstable distal radius fractures were treated with open reduction and LCP fixation through volar approach.They were 8 men and 40 women aged from 58 to 77 years (range,63.7 years).They were all diagnosed by dual energy X ray absorptiometry before operation.According to AO/OTA criterion,there were 12 patients with type B2 fractures,10 cases with type B3,8 cases with type C1,13 cases with type C2,5 cases with type C3.All patients were performed locking plate fixations through volar approach and no bone graf.All patients were assessed from time of fracture healing,palmar tilt,radiographic measurements of ulnar inclination,radial height,and range of motion after 18 months,to evaluate the effect of clinical results and postopera-tive functional recovery.Results The patients were followed up for average 17.8 months (range,12 -24 months). All fratures united within 6 months (3 to 7 months),no infection in all patients,reduction loss in 2 cases after operation,traumatic arthritis in three.According to the Cooney criterion,the result was excellent in 35 pateints,good in 9 cases,fair in 3 cases and poor in 1 case,and the excellence rate was 92%.Conclusion The valor approach with locking compression plate can provide firm fixation and allow early functional exercise and so is suitable for unstable distal radius fracture especially in the osteoporotic of unstable distal radius fractures.

Hepatitis B vaccination: a new strategy to prevent hepatitis B recurrence after liver transplantation for hepatitis B virus-related recipients / 中华肝胆外科杂志

Objective To investigate the efficacy of hepatitis B vaccination in preventing hepatitis B (HBV) recurrence after liver transplantation for hepatitis B virus-related (HBV-related) recipients.Methods 30 healthy recipients who survived for more than 2 years after liver transplantation received vaccination using hepatitis B surface antigen (HBsAg)-containing vaccine.There were a total of 5 injections at 0 month, 1 month, 2 months, 3 months and 6 months respectively, and each dose was 40 μg.Thirty healthy adults who received hepatitis B vaccination during the same period were selected into the control group.The antibody of hepatitis B surface (Anti-HBs) titer was tested at 1 month, 2 months, 3 months, 6 months, 9 months and 12 months after the first vaccination.Results 6.7％ (2/30) of the liver transplantation recipients had good response (defined as a rise of Anti-HBs titer of more than 100 IU/L at 12 months after the primary vaccination), and 16.7％ of recipients (5/30) had partial response (Anti-HBs titer in 3 patients at less than 100 IU/L, Anti-HBs titer in 2 patients at more than 100 IU/L at first, then less than 100 IU/L after 12 months).For the 9 patients who received liver transplantation for acute liver failure, 2 had good response (22.2％) and another 2 patients (22.2％) had partial response.For the liver transplant recipients who survived for more than 5 years, 2 had good response (22.2％) and another patient (11.1％) had partial response.In the healthy control group, the good response rate was 73.3％ (22/30), and the partial response rate was 10％ (3/30).Conclusions Some HBV-related liver transplant recipients could acquire Anti-HBs by vaccination.Good response rate was lower in the HBV-related group of liver transplant recipients than in the healthy control group of people.Recipients for liver transplantation carried out for acute liver failure and recipients who survived for more than 5 years had higher response rates to HBV vaccination.HBV vaccination can be a way to prevent HBV recurrence in some liver transplant recipients.

Pathogenic spectrum and bacterial resistance of severe community-acquired pneumonia / 中国小儿急救医学

Objective To study the distribution of pathogenic spectrum in children with severe community-acquired pneumonia(CAP) and bacteria antibiotic resistance.Methods One hundred and ninety-three children with severe CAP were enrolled from Mar 2011 to Feb 2012.Sputum specimens were collected for bacterial culture and drug sensitive test.Meanwhile mycoplasma pneumonia and chlamydia trachomatis were detected by fluorescent quantitative polymerase enzyme technology.Antigen of virus were detected by immunofluorescence assay.Results A total of 96 cases (49.7％) were bacteria positive in 193 children with severe CAP.The top four bacteria strains were klebsiella pneumoniae,staphylococcus aureus,escherichia coli and streptococcus pneumoniae.Most of gram-negative bacteria were resistant to ampicillin,cefazolin,ceftriaxone,ceftazidime,and compound sulfamethoxazole,but were sensitive to piperacillin/tazobactam,imipenem,ciprofloxacin,levofloxacin,amikacin.Gram-positive bacteria were resistant to penicillin and erythromycin,but sensitive to vancomycin.Fifty-three cases (27.5 ％,53/193) were virus Positive,81.1％ of which were less than 1 year old.Respiratory syncytial virus accounted for the most prevalent pathogen,followed by adenovirus,influenza virus A.Mycoplasma pneumoniae were positive in 4 patients (2.1％,4/193),chlamydia trachomatis were positive in 3 patients (1.6％,3/193).Mixed infection was found in 23 cases (11.9％,23/193).There were 14 cases (7.2％,14/193) with undetected pathogens.Conclusion Bacterium is the major pathogen in children with severe CAP and the virus is the second.The initial antibiotics administration of piperacillin/tazobactam or carbapenem and vancomycin should be chosen for severe bacteria pneumonia.

Therapeutic Effect of Anisodamine on Experimental Pulmonary Edema After Sea-water Drowning / 中国医师杂志

Objective To study the therapeutic effect of anisodamine on pulmonary edema after sea-water drowning(PE-SWD). Methods Rat models of PE-SWD were set up by infusing sea-water into rats lungs,and then were randomly divided into PE-SWD model group(M group) and therapeutic group with anisodamine(T group). Blood-gas indexes of arterial blood were measured at 0.5, 1, 2, 4 and 6 hours after infusion. TNF-? levels in the plasma,bronchoalveolar lavage fluid (BALF) and lung tissues were detected by ELISA. At the same time,the dry/wet weight of lung was also measured. Results The levels of blood PaO_2,SO_2 and pH in T group were obviously higher than those in M group 2h after infusion. The dry/wet weight of lung in T group was lower than that in M group. The concentration of TNF-? in plasma, BALF and lung tissues in the both M and T groups significantly higher than that in control group, and reached maximum 1h after infusion. After infusion,the TNF-? contentration in all tested specimens in T group was obviously lower than that in M group. Conclusion There was the therapeutic effect of anisodamine on the pulmonary edema after sea-water drowning possibly by decreasing TNF-? level.

Chemical constituents of Taxodium ascendens / 中草药

Objective To investigate the chemical constituents of Taxodium ascendens collected in Yunnan Province of China.Methods Column chromatography techniques were used for separation and purification of the compounds and extensive spectral analyses including 2D NMR spectrum were employed for structural elucidation.Results Fourteen compounds were isolated from the branches and leaves of T.ascendens.Structures of six compounds were identified by 13C-NMR,1H-NMR,and MS as following: tetrahydro-2,4-bis(4-hydroxyphenyl)-2H-pyran-3,5-diol(Ⅰ),3,5-bis(4-hydroxyphenyl)-4-pentene-1,2-diol(Ⅱ),3,5,7,3′,5′-pentahydroxyflavan(Ⅲ),4-(2,3-dihydro-3-hydroxymethyl-5-(3-hydroxypropyl)-7-methoxybenzofuran-2-yl)-2-methoxyphenol(Ⅳ),2-(3,4-dimethoxyphenoxy)-tetrahydro-6-(hydroxymethyl)2H-pyran-3,4,5-triol(Ⅴ),2,5-dihydro-3,5-bis(4-hydroxyphenyl)-2furanmethanol(Ⅵ).Conclusion Compound Ⅰ is a new compound named as ascenden pyrandiol and other compounds are isolated from T.ascendens for the first time.