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 investigate the predictive value of preoperative serum human epididymis protein 4 (HE4) and CA125 in patients with high risk of stage Ⅰ endometrial cancer (EC)and to identify the optimal cutoff values. Methods Clinical and pathological data of 231 patients with stage Ⅰ EC were included in this study. Patients were divided into high risk group (n=96) and low risk group (n=135). The preoperative serum levels of HE4 and CA125 were measured, and their correlations with clinical pathological features were analyzed. The ROC curves were generated to determine optimal cutoff values of HE4 and CA125 levels with the maximum Youden index for prediction of high risk EC. Results There were significant differences in serum levels of HE4 and CA125 between patients with different depths of myometrial invasion, with or without vascular invasion, with or without lower uterine segment involvement, with different diameters of tumor and different risk classifications of stage ⅠEC (P<0.05). There were significant differences in serum levels of HE4 between patients with different menopausal status, hypertension, pathological types, histological grading and the involvement of cervical endometrial glands (P<0.05). The preoperative serum levels of HE4 and CA125 were positive correlated (r=0.262, P<0.05). The AUC value of HE4 for diagnosing stageⅠEC was 0.794(95%CI:0.734-0.854),the cutoff value was 74 pmol/L, the sensitivity was 75.0%, specificity was 83.0%, positive predictive value was 75.8%, negative predictive value was 82.4% and the accuracy rate was 79.7%. The AUC value of CA125 for diagnosing stage Ⅰ EC was 0.696 (95%CI: 0.624-0.767), the cutoff value was 17 kU/L, the sensitivity was 56.3%, specificity was 85.9%, positive predictive value was 74.0%, negative predictive value was 73.4%and the accuracy rate was 73.6%, respectively. The AUC value of combination of both markers was 0.847 (95%CI: 0.796-0.899), the corresponding values were 95.8%, 77.0%, 74.8%, 96.3%and 84.8%, respectively. Conclusion The best cutoff values of HE4 and CA125 are 74 pmol/L and 17 kU/L for detecting high risk stageⅠEC. The combined detection is better than that of the single detection in sensitivity, negative predictive value and accuracy rate.

OBJECTIVETo explore the efficacy of homemade hemostatics of injected gelatin matrix (HIGM) for immediately treating blunt hepatic trauma in canine model without additional pressure.

METHODSA total of 27 commercial hybrid dogs underwent celiotomy to establish hepatic trauma model after general anesthesia. The dogs were prospectively randomized into 3 groups: the treatment group (n=9, with the direct application of homemade hemostat), the positive control group (n=9, with thrombin solution), and the negative control group (n=9, with 0.9% normal saline). Time to hemostasis and intra-abdominal blood loss were recorded, and heart rate (HR), mean arterial pressure (MAP), and hematological parameters were compared among these three groups. Gross examinations were performed 30 minutes after surgery.

RESULTSSignificantly shorter time to hemostasis [(1.20±0.33) min] and less blood loss [(47.22±8.61) ml] were observed in the treatment group than in control groups (P 0.05). No cases of bleeding occurred in any animals in the treatment group, and no signs of infection and adhesion formation were evident due to exposure to HIGM. Two cases in the positive control group (22.22%) were found to have rebleeding. All animals in the negative control group experienced visible bleeding.

CONCLUSIONHIGM is effective for controlling bleeding after hepatic trauma without the additional compression, and therefore may be valuable in field surgery.

Animals ; Disease Models, Animal ; Dogs ; Gelatin ; administration & dosage ; Hemostatics ; administration & dosage ; Injections ; Liver ; injuries

OBJECTIVETo study the hypoglycemic effect of the extract of B. polyandra (SHG).

METHODThe diabetic mice were induced by alloxan in ICR mice. The blood glucose concentration was measured by glucose oxidase method. The serum insulin level was determined by 125I-insulin radioimmunoassay kit. The hypoglycemic effect was evaluated by the levels of both fasting and no-fasting blood glucose. The effect on serum insulin level was estimated by the values of the blood insulin and the changes of the blood glucose induced by the glucose intraperitoneal injection. The effect on the glucose absorption was investigated by the oral sucrose or starch tolerance test.

RESULTBoth of the fasting and no-fasting blood glucose levels were decreased significantly by the treatment of 20 or 30 g raw materials crude drug x kg (-1) SHG orally for 7-10 d in ICR mice or in alloxan diabetic mice. In the oral sucrose tolerance test or oral starch tolerance test, the administration of SHG reduced significantly the peak value of the blood glucose and the area under the blood glucose-time curve (AUC) in normal or alloxan diabetic mice, respectively. These effects of SHG were similar to those of acarbose, a kind of alpha-glucosidase inhibitors. In the oral glucose tolerance test in normal and alloxan diabetic mice, SHG decreased both the blood glucose peak and the AUC induced by the glucose loading. But in the intraperitoneal injection glucose tolerance test the levels of insulin in both SHG and control mice were similar, however, the changes of the blood glucose level after the glucose-loading for 30 min in SHG mice was much lower than that in control mice.

CONCLUSIONWith the treatment of SHG, the fasting and no-fasting blood glucose concentrations were decreased and the glucose tolerance improved significantly in both normal and alloxan diabetic mice, and the inhibition of a-glucosidase might be one of its major mechanisms.

Administration, Oral ; Alloxan ; Animals ; Area Under Curve ; Blood Glucose ; analysis ; Diabetes Mellitus, Experimental ; blood ; chemically induced ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Glucose ; administration & dosage ; pharmacokinetics ; Glucose Tolerance Test ; Hypoglycemic Agents ; administration & dosage ; isolation & purification ; pharmacology ; Injections, Intraperitoneal ; Insulin ; blood ; Male ; Mice ; Mice, Inbred ICR ; Phytotherapy ; Plants, Medicinal ; chemistry ; Random Allocation ; alpha-Glucosidases ; metabolism

Liver damage often leads to apoptosis of liver cells and the mechanism of apoptosis is very extensive.The article reviewed several as-pects including death receptor -mediated apoptosis, mitochondrial da-mage mediated apoptotic pathway and Bcl-2 family-mediated apoptosis.

Purpose::Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in underfoot impact loading environments.Methods::The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures.Results::The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model.Conclusion::Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.

Objective:To investigate the molecular testing of liquid-based cytology (LBC) specimens from advanced non-small cell lung cancer (NSCLC) patients and the reliability of guiding targeted therapy.Methods:The LBC specimens and clinical data of 412 advanced NSCLC patients from March 2015 to April 2017 in the Cancer Hospital, Chinese Academy of Medical Sciences were collected, of which 32 patients had postoperative or biopsy specimens. The real-time quantitative polymerase chain reaction was used to detect mutations of EGFR, KRAS and BRAF, and analyze the correlation between gene mutations and clinicopathological characteristics. The results of genetic testing of LBC specimens and histology specimens were examined for concordance. Clinical efficacy was evaluated in 142 patients treated with EGFR-tyrosine kinase inhibitor (TKI) drugs, and survival analysis was performed using the Kaplan-Meier method.Results:Of the 412 LBC specimens, 216 (52.4%) had EGFR mutations, 36 (8.7%) had KRAS gene mutations, and 3 (0.7%) had BRAF gene mutations. EGFR mutation was associated with gender, pathology type, and specimen source, with a higher EGFR mutation rate in female patients (63.0%) than in male patients (40.8%, P<0.001) and a higher EGFR mutation rate in adenocarcinoma (54.3%) than in non-adenocarcinoma (0.0%, P<0.001). KRAS mutation was related to gender, with a higher EGFR mutation rate in male patients (12.2%) than in female patients (5.6%, P=0.016). The three cases with multiple co-mutations were all stage Ⅳ male adenocarcinoma patients. Thirty-two patients with both LBC specimens and histology specimens had concordant genetic results between LBC specimens and histology specimens in 30 patients ( Kappa=0.91). Twelve patients with both histology and LBC specimens from metastases had identical genetic results ( Kappa=1.00). Nineteen patients with histology specimens from primary foci in lungs and LBC specimens from metastases had concordant genetic results between two specimens in 18 patients ( Kappa=0.92). The disease control rate (DCR) for EGFR mutation-positive patients treated with EGFR-TKI was 89.0% (89/100) and the progression-free survival time (PFS) was 13.8 months, both higher than those of EGFR mutation-negative patients [DCR of 30.8% (4/13) and median PFS of 1.4 months, P<0.01]. Conclusions:The results of molecular testing of LBC specimens and histological specimens are highly consistent, which demonstrates LBC specimens can be a crucial source of gene testing for advanced NSCLC. Molecular typing of advanced NSCLC based on the results of genetic testing of LBC specimens and guiding EGFR-TKI drug-targeted therapy can achieve high DCR and PFS, which has important clinical value.

OBJECTIVETo assess the early curative effect of epidural or intravenous administration of steroids during a percutaneous endoscopic lumbar discectomy (PELD).

METHODS28 consecutive patients who underwent PELD due to large lumbar disc herniation between November 2014 and January 2016 were followed up for 6 months. These patients were divided into two groups according to the treatment they received after PELD. 14 patients (Group A) were treated by PELD and epidural steroids, while the other 14 patients (Group B) were treated by PELD and intravenous steroids. We evaluated the effectiveness by the preoperative and postoperative visual analogue scale (VAS) scores for back and leg pain, and the postoperative Oswestry disability index (ODI) at 3 weeks after surgery via the clinical charts and telephone interview. Postoperative hospital stay and time return to work were investigated as well.

RESULTSThere is a significant decrease in VAS (back, leg), ODI, and time return to work (p < 0.05). For VAS (back), Group A showed a significant decrease compared with Group B at 1 day and 1 week after surgery (p = 0.011, p = 0.017). As for VAS (leg), Group A showed a significant decrease compared with Group B at 1 day, 1 week, 3 weeks, and 3 months follow-up examinations (p = 0.002, p = 0.006, p < 0.001, p < 0.001). For ODI, Group A showed a notable decrease compared with Group B (p < 0.001). The postoperative hospital stay in two groups was not statistically different (p = 0.636). But the time return to work in Group A was significantly shorter than that in Group B (p = 0.023).

CONCLUSIONPatients who underwent PELD with epidural steroid administration for large lumbar disc herniation showed favorable curative effect compared with those who underwent PELD with intravenous steroid administration.

Adult ; Betamethasone ; administration & dosage ; Diskectomy, Percutaneous ; methods ; Endoscopy ; Female ; Glucocorticoids ; administration & dosage ; Humans ; Injections, Epidural ; Injections, Intravenous ; Intervertebral Disc Displacement ; surgery ; Length of Stay ; Lumbar Vertebrae ; surgery ; Male ; Pain Measurement ; Retrospective Studies

Objective: To investigate the expressions of migration and invasion inhibitory protein (MIIP) and p21-activated kinase 1 (PAK1) in endometrial carcinoma (EC) and their correlation with clinicopathological features. Methods: The protein levels of MIIP and PAK1 in 135 paraffin-embedded EC tissues, 55 atypical hyperplasia of endometrium (AHE) and 88 normal endometrium (NE) tissues were quantified by immunohistochemistry, the clincial significance and the relationship of these two proteins were also analyzed. Results: The positive rates of MIIP expression in NE, AHE and EC tissues were 52.3%(46/88), 41.8% (23/55) and 34.8% (47/135), respectively. The expression of MIIP in EC was significantly lower than that of MIIP in NE (P<0.05). The positive rates of PAK1 expression in NE, AHE and EC tissues were 45.5% (40/88), 50.9% (28/55) and 62.2% (84/135), respectively. The expression of PAK1 in EC tissues was significantly higher than that of PAK1 in NE tissues (P<0.05). The expression of MIIP in EC tissues was significantly associated with myometrial invasion, International Federation of Gynaecology and Obstetrics (FIGO) stage and lymph node metastasis (P<0.05). The expression of PAK1 in EC tissues was significantly related with differentiation, myometrial invasion, FIGO stage and lymph node metastasis (P<0.05). The expressions of MIIP and PAK1 in EC tissues were marginally related with the overall survival of patients (P=0.092, P=0.052). The expression of MIIP in EC was negatively correlated with PAK1 (r=-0.329, P<0.001). Conclusions The down-regulation of MIIP and up-regualtion of PAK1 paticipate in the initiation and development of EC, which are correlated with the poor prognosis of EC. The protein expression of MIIP is inversely related with PAK1 in EC.