Aconitum, as a kind of common traditional Chinese medicine, contains multiple biological active substances, with a very high medicinal value but high toxicity. Its major toxic ingredients are aconitine, mesaconitine and hypaconitine, which are also efficient ingredients. Therefore, the safety of its clinical application has aroused wide attention. With the constant deepening of drug development studies, people want to learn about its toxic mechanism and the regularity of its emergence and development of its toxicology, so as to make a scientific and rational assessment for its safety. Therefore, toxicokinetics and metabonomics have gradually become important content in the new drug assessment. During the development of drug performance, it is crucial to establish a scientific, objective and standardized Aconitum safety evaluation system and correctly assess and utilize its toxicity. Having summarized studies on metabonomics and toxicokinetics of Aconitum drugs in recent years, authors proposed to strengthen the studies on Aconitum drug safety assessment and establish a scientific and standardized safety evaluation system as soon as possible, in order to make the national treasure more useful.
Aconitum ; chemistry ; toxicity ; Animals ; Drugs, Chinese Herbal ; pharmacokinetics ; toxicity ; Humans ; Metabolomics

Objective:To observe influence of alprostadil injection on contrast-induced nephropathy (CIN) in high risk patients after percutaneous coronary intervention (PCI).Methods: A total of 263 CIN high risk (CIN risk score ≥16 scores) patients were selected.According to random number table, patients were randomly divided into routine treatment group (n=121, received routine hydration therapy) and alprostadil group (n=142, received additional alprostadil injection based on routine treatment group).Serum creatinine (SCr), glomerular filtration rate(GFR), cystatin C (CysC) and β trace protein (β-TP) level before, 48h and 72h after PCI were measured and compared, and incidence rate of CIN, percentage of blood purification therapy and mortality were compared between two groups.Results: Compared with before PCI, there was significant rise in SCr level and significant reduction in GFR in both groups on 48h and 72h after PCI (P<0.01 all);Compared with routine treatment group, there were significant reductions in levels of SCr [72h: (190.04±28.92) μmol/L vs.(141.10±21.18) μmol/L], and significant rise in GFR [72h: (26.0±4.4) ml/min vs.(36.4±4.9) ml/min], and levels of CysC[72h: (1.75±0.74) mg/L vs.(1.47±0.55) mg/L] and β-TP [72h: (1.53±0.50) mg/L vs.(1.22±0.38) mg/L] significantly decreased in alprostadil group on 48h and 72h after PCI, P<0.05 or <0.01;there were significant reductions in incidence rate of CIN (30.6% vs.18.3%) and percentage of blood purification therapy (10.7% vs.3.5%) in alprostadil group, P=0.001, 0.045 respectively.There was no significant difference in mortality between two groups, P=0.728.Conclusion: Alprostadil injection can significantly improve kidney function, reduce incidence rate of CIN and percentage of blood purification therapy in CIN high risk patients after PCI, which is worth extending.

Objective The article described the design and building of a virtual reality technology-based rehabilitation system for patients with cognitive deficits, including overall idea, design and structure of the system, the key technology, such as formal description of the training data, man-machine interactive control, controlling simulation of the training process and virtual environment module development to achieve system implementation. The system is suitable for our country and military. It will create a new way for the cognitive rehabilitation and help to promote the application of virtual reality technology in rehabilitation

Objective To evaluate the effect of sedation with midazolam combined with propofol on delirium in mechanically ventilated patients in the intensive care unit (ICU).Methods Five hundred and twenty-two patients who required sedation and analgesia,endotracheal intubation and mechanical ventilation used to assist respiration,aged 28-64 yr,weighing 41-82 kg,were randomized into 2 groups according to the sedation protocols during therapy:sedation with midazolam group (group M,n =240) and sedation with midazolam + propofol group (group MP,n=232).In M and MP groups,sedation was induced with midazolam infusion 0.03-0.17 mg/min,and analgesia was induced with sufentanil infusion 0.07-0.14 μg/min.In group MP,when hemodynamics was stable,pressure support was 8-10 cmH2O,tidal volume＞400 ml,RR ＜25 bpm,and FiO2＜45％,sedation was induced with propofol infusion 0.8-2.0 mg/min instead,lasting for 12-24 h.Richmond Agitation Sedation Scale score was maintained at-1 to-2 during vcntilation.The development and duration of delirium were recorded.Delirium was divided into hyperactive delirium,hypoactive delirium and mixed delirium 3 subtypes,and the development and duration of the 3 subtypes of delirium were also recorded.Results There was no significant difference between the two groups in the incidence and duration of delirium.Compared to group M,the incidence of hyperactive delirium was significantly decreased,and no significant change was found in the incidence of hypoactive delirium and mixed delirium and the duration of the 3 subtypes of delirium in group MP.Conclusion Sedation with midazolam and propofol can decrease the development of hyperactive delirium,but can not shorten the duration of delirium in mechanically ventilated patients in the ICU.

BACKGROUND: Intravenous transplantation has been regarded as a most safe method in stem cell therapies. There is evidence showing the homing of bone marrow stem cells (BMSCs) into the injured sites, and thus these cells can be used in the treatment of acute myocardial infarction (MI). This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model. METHODS: A total of 60 New Zealand rabbits were randomly divided into three groups: control group, epicardium group (group I) and ear vein group (group II). The BMSCs were collected from the tibial plateau in group I and group II, cultured and labeled. In the three groups, rabbits underwent thoracotomy and ligation of the middle left anterior descending artery. The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead II and III of electrocardiogram suggested successful introduction of myocardial infarction. Two weeks after myocardial infarction, rabbits in group I were treated with autogenous BMSCs at the infarct region and those in group II received intravenous transplantation of BMSCs. In the control group, rabbits were treated with PBS following thoracotomy. Four weeks after myocardial infarction, the heart was collected from all rabbits and the infarct size was calculated. The heart was cut into sections followed by HE staining and calculation of infarct size with an image system. RESULTS: In groups I and II, the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group (P<0.05). However, there was no significant difference in the infarct size between groups I and II (P>0.05). CONCLUSION: Transplantation of BMSCs has therapeutic effect on MI. Moreover, epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.

AIM: To assess the differentiation of rat mesenchymal stem cell (MSC) in the microenvironment of retinitis pigmentosa(RP) induced by the administration of sodium iodate. METHODS: In vitro cultured Lewis rat MSC were injected into the subretinal space of NaIO3 induced RP rat eyes (30g/L NaIO3 100mg/kg). To observe the trace and differentiation of MSC by immuno-fluorescent method successively in 5 weeks after the surgery.RESULTS: The majority of the transplanted cells stay in retinal pigment epithelium(RPE) layer and cones and rods layer. From the 2nd week after transplantation, the engrafted MSC expressed PCK and rhodopsin under fluorescent microscope.CONCLUSION: MSC can survive mainly in the outer layer of retina in the microenvironment of RP and differentiate forward the RPE cell and photoreceptor.

Objective To investigate the regularity of intrapulnonary lobar and segmental lymph nodes metastasis in patients with cT1N0M0 stage lung adenocarcinoma.To provide a basis for more accurate determination of N stage and indication for pulmonary segmental resection.Methods A prospective study was performed from March 2014 to December 2015.103 cases of cT1 N0M0 stage lung adenocarcinoma received lobectomy and mediastinal lymph node dissection in the thoracic surgery department of China-Japan Friendship Hospital.Intrapulmonary lobar and segmental lymph nodes were dissected and sorted carefully then sent to the pathological department with the corresponding lung specimen and other lymph nodes.Statistical analysis was carried out considering size of the lesion,imaging features,serum CEA levels,pathological subtypes and so on.Results In total 103 cases,pN0 was confirmed in 82 cases,pN1 in 15 cases,pN1 + N2 in 5 cases,and skipping-pN2 in 1 case.14 cases(93.3％) in pN1 group were detected with station 12-14 lymph node metastasis,while only 5 cases (33.3％) were detected with station 12-14 LSNs metastasis.4 cases(66.7％) in pN2 group were detected with station 12-14 lymph node metastasis,while only 1 case(16.7％) with station 13 and station 7 lymph node metastasis.If LSNs were not detected,the false negative rate of N staging could be as high as 6.1％ (5/82),The rate of missed diagnosis of lymph node metastasis might be 30％ (6/20) to N1 stations alone.41.2％ (7/17)cases with metastasis to the adjacent LSNs had been proved with metastasis to the isolated LSNs.The metastasis rate of the isolated LSNs was significantly lower(P =0.049) in pure GGNs compared with those part-solid/solid nodules.Invasive adenocarcinoma had higher metastasis rate of isolated LSNs,compared with preinvasive lesions or minimally invasive adenocarcinomas,with no statistical difference between groups (P =0.055).No significant difference in isolated LSNs metastasis rate was found between groups with different serum CEA levels(P =0.251) or tumor size(P =0.197).Conclusion Dissection of intrapulmonary lobar and segmental lymph nodes might facilitate a more accurate N stage,reduce the false negative rate of lymph node metastasis,and provide basis for more accurate assessment of prognosis and postoperative adjuvant treatment.The sampling area of lymph nodes during segmental resection should include the adjacent LSNs of the target segment.The isolated LSNs metastasis rate of cT1N0M0 stage lung adenocarcinoma with pureGGN as imaging feature is relative low,which might be suitable for segmentectomy when meeting other criteria.

Forensic Medicine ; Humans ; Kidney Transplantation ; Polycystic Kidney Diseases

OBJECTIVETo test whether postconditioning could inhibit the expression of phospho-JNK (P-JNK) mitogen activated protein kinase (MAPK) and study its relation to apoptosis of cardiocyte.

METHODSSixty rats were randomly divided into six groups: sham, reperfusion injury (R/I), postconditioning (Post), SP600125 (I_JNK), anisomycin and postconditioning (Ani+Post) and anisomycin (Ani) groups. After acute myocardial infarction was induced in rats, placebo solution (DMSO), SP600125 (6 mg/kg) or anisomycin (2 mg/kg) was injected through jugular vein 5 min before reperfusion; 6 h later 3 rats of each group were executed and the hearts were separated to measure the signaling molecules (phospho-JNK, TNF alpha, Caspase-8, Bcl-2/Bax, cytochrome-c). Twenty-two hours later hemodynamic data were measured in the left rats, and then blood samples were taken to determine serum markers of cardiac damage, and hearts were separated to measure the infarction area and cardiocyte apoptosis.

RESULTPostconditioning improved +/-DP/DTmax of left ventricle, limited infarct area, relieved apoptosis and necrosis of cardiocytes, and inhibited the expression of P-JNK (1.12 +/-0.21 Compared with 1.90 +/-0.32, P<0.05). At the same time the levels of TNFalpha Caspase-8, Bax and Cyt-c were lower in Post group than those in R/I group, but Bcl-2 expression levels were higher. I_JNK group presented the similar protection effect of postconditioning [TUNEL index: (6.23 +/-2.43)% Compared with (18.22 +/-5.10)%, P<0.05; Infarct area: (23.44 +/-6.34)% Compared with (42.31 +/-8.21)%, P<0.05]. On the other hand, Ani+Post group partially lost cardioprotection effect [TUNEL index: (14.12 +/-2.00)% Compared with (18.22 +/-5.10)%,P>0.05; Infarct area: (35.27 +/-5.28)% Compared with (42.31+/-8.21)%,P>0.05], because of the activation of JNK MAPK.

CONCLUSIONPostconditioning can inhibit phosphorylation of JNK MAPK, which attenuates cardiocyte apoptosis by both extrinsic and mitochondria pathway.

Animals ; Apoptosis ; drug effects ; Ischemic Preconditioning, Myocardial ; JNK Mitogen-Activated Protein Kinases ; metabolism ; pharmacology ; Male ; Myocardial Infarction ; enzymology ; pathology ; therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; enzymology ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the differences between clinicopathological features and prognosis of alpha-fetoprotein (AFP) negative (AFP < 20 ng/ml) and positive (AFP ≥ 20 ng/ml) hepatocellular carcinoma (HCC) patients.

METHODSClinicopathological data of 142 AFP-negative and 109 AFP-positive HCC patients who underwent RO radical hepatectomy in the Cancer Hospital of Chinese Academy of Medical Sciences between January 2006 and December 2011 were retrospectively reviewed and analyzed in this study.

RESULTSCompared with the AFP-negative patients, a higher female to male sex ratio, the later Barcelona Clinic Liver Cancer ( BCLC) stage, more liver capsule invasion and poorer Edmondson-Steiner grade were in the AFP-positive cases (P < 0.05 for all). Furthermore, the 1-, 3-, and 5- year overall survival rates were 94.4%, 82.4% and 61.0% in the AFP-negative group and 87.2%, 61.1% and 40.2%, respectively, in the AFP-positive group (P < 0.001). The multivariate analysis with Cox's proportional hazards model showed that AFP status, tumor size and Edmondson-Steiner grade are independent risk factors for survival of all the patients (P < 0.05) , and large tumor and Edmondson-Steiner grades III/IV are independent risk factors for worse survival in AFP-negative patients (P < 0.05). However, large tumor diameter was proved to be an independent risk factor leading to poor prognosis of AFP-positive cases (P < 0.05).

CONCLUSIONHigh levels of AFP indicate that the tumors are more malignant and with unfavorable prognosis.

Asian Continental Ancestry Group ; Carcinoma, Hepatocellular ; chemistry ; mortality ; pathology ; surgery ; Female ; Hepatectomy ; Humans ; Liver Neoplasms ; chemistry ; mortality ; pathology ; surgery ; Male ; Multivariate Analysis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Survival Rate ; alpha-Fetoproteins ; analysis