Difference in liver injury induced by dictamnine between males and females: based on untargeted metabolomics / 中国中药杂志

In recent years, reports of adverse reactions related to traditional Chinese medicine(TCM) have been on the rise, especially some traditionally considered "non-toxic" TCM(such as Dictamni Cortex). This has aroused the concern of scholars. This study aims to explore the metabolomic mechanism underlying the difference in liver injury induced by dictamnine between males and females through the experiment on 4-week-old mice. The results showed that the serum biochemical indexes of liver function and organ coefficients were significantly increased by dictamnine(P<0.05), and hepatic alveolar steatosis was mainly observed in female mice. However, no histopathological changes were observed in the male mice. Furthermore, a total of 48 differential metabolites(such as tryptophan, corticosterone, and indole) related to the difference in liver injury between males and females were screened out by untargeted metabolomics and multivariate statistical analysis. According to the receiver operating characteristic(ROC) curve, 14 metabolites were highly correlated with the difference. Finally, pathway enrichment analysis indicated that disorders of metabolic pathways, such as tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis(linoleic acid metabolism and arachidonic acid metabolism), may be the potential mechanism of the difference. Liver injury induced by dictamnine is significantly different between males and females, which may be caused by the disorders of tryptophan metabolism, steroid hormone biosynthesis, and ferroptosis pathways.

Species Differences of Bakuchiol-induced Liver Injury in Mice Based on Transcriptomics / 中国实验方剂学杂志

ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

Metabolomic screening for diagnostic biomarkers of drug-induced chronic liver injury related cirrhosis / 药学学报

About 15%-20% of drug-induced liver injury (DILI) will progress to chronic manifestation (CH-DILI), which sometimes advances rapidly to liver cirrhosis (LC-DILI) within 0.5-1 year with deteriorative clinical prognosis. Therefore, it is important to find a non-invasive diagnosis for early detection of liver cirrhosis. In this study, the metabolomic profiles revealed significant differences in the metabolites from the plasma of LC-DILI versus CH-DILI. We found 35 differential metabolites through principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Through pathway enrichment analysis, some up-regulated metabolic pathways reflected impaired liver functions such as bile acid, lipid synthesis and decomposition during cirrhosis. Five biomarkers were found to exhibit effective diagnosis value (AUC > 0.6), including phosphatidylcholine, lysoPC (18:1 (9Z)), creatine, taurochenodeoxycholic acid and taurocholic acid. Furthermore, we found that the relative content ratio between phosphatidylcholine and lysoPC (18:1 (9Z)) had a better distinguishing ability (AUC = 0.867). The relative content ratio also had the feature to reduce systematic errors of sample processing and instrument detection, therefore having a greater value for clinical application.

Metabolomic study on the hepatotoxic or hepatoprotective effects of rhubarb to normal or hepatic fibrosis rats / 药学学报

Focusing on the TCM-related adverse drug reactions, especially those conventionally non-toxic TCM induced hepatotoxicity, this paper has proposed and established the disease-syndrome-based toxicology evaluation pattern and approach for TCM, not only the normal rats, but the hepatic fibrosis model rat were studied hepatotoxic or hepatoprotective effects of rhubarb, meanwhile liver histopathology changes by histological tests such as HE and TUNEL staining. The metabolomics analysis method will be employed to screen the key metabolites and possible metabolic pathway of the dual effects of rhubarb in rats. The results showed that rhubarb could result in significant liver injury in normal rats, indicated by the elevation of plasma serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities (P L-arginine, creatine, L-valine, retinyl ester, and prostaglandin F2α were confirmed by multivariate statistical analysis and metabolic pathways enrichment analysis linked to six metabolic pathways, including taurine and hypotaurine metabolism, primary bile acid biosynthesis, arginine and proline metabolism, arachidonic acid metabolism, retinol metabolism and valine, leucine and isoleucine biosynthesis. In summary, the results suggested the dual effects of rhubarb screened by taurine and hypotaurine metabolism, primary bile acid biosynthesis and arginine and proline metabolism may be the key metabolic pathway related to You Gu Wu Yun phenomenon of rhubarb. This study will provide new vision and illustration of scientific evidences for the hepatotoxicity assessment and rational use of those drugs containing anthraquinones.

Metabolomic study on immunological stress-mediated hepatotoxicity of Polygonum multiflorum and its processed products of nine times steaming and nine times sunning / 药学学报

It is investigated that the hepatotoxicity of Polygonum multiflorum (PM)was attenuated by its processed products of nine times steaming and nine times sunning(RPM)based on immunological stress-mediated animal model by using metabolomics method. Sprague-Dawley(SD)rats were intragastrically administered with(5.4 g crude drug per kg body weight)of 50% alcohol extracts of PM and its processed products of nine times steaming and nine times sunning respectively or co-treated with non-toxic dose of lipopolysaccharide(LPS, 2.8 mg·kg-1)via tail vein injection. The plasma alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were assayed and the isolated livers were evaluated for histopathological changes. Global metabolomics profiling, multivariate analysis and data base searching were performed to discover common differential metabolites for idiosyncratic liver injury. The results showed that co-treatment with non-toxic dose of LPS and PM could result in significant liver injury, indicated by the elevation of plasma ALT and AST activities, as well as obvious liver histologic damage; whereas RPM failed to induce detectable liver injury. Furthermore, 10 potential metabolomics biomarkers that differentially expressed in LPS/PM group compared with LPS/RPM without liver injury were identified by untargeted metabolomics, mainly involved ten pathways: sphingolipid metabolism, linoleic acid metabolism, taurine and hypotaurine metabolism, steroid hormone biosynthesis, galactose metabolism, steroid biosynthesis, metabolism of xenobiotics by cytochrome P450, pyrimidine metabolism, biosynthesis of unsaturated fatty acids, primary bile acid biosynthesis. This work illustrated the idiosyncratic hepatotoxicity of heshouwu and provided a metabolomic insight into diosyncratic liver injury of PM and RPM.

Influence of drug metabolizing enzyme inhibitors on liver injury susceptibility to trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside / 药学学报

By using the drug metabolizing enzyme inhibitors, the effects of metabolic factors on potential liver injury induced by the main component, trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside(trans-SG), in Polygonum multiflorum was investigated. The main metabolic enzyme isoforms involved in trans-SG metabolism were also screened. The results showed that trans-SG at the dosage 31 mg·kg-1 did not cause liver injury; and the combination of trans-SG with the phase I metabolic enzyme inhibitor, 1-benzylimidazole (10 mg·kg-1), did not change the degree of liver injury(compared with LPS + trans-SG group, P > 0.05). However, the combination of trans-SG with phase II metabolic enzyme inhibitor, ketoconazole(35 mg·kg-1), significantly increased the degree of liver injury(compared with LPS + trans-SG group, P < 0.05). The phase I metabolites of trans-SG were not detected in human liver microsomes phase I metabolism system, while the phase II trans-SG metabolites were detected in recombinant human UGT isozymes phase II metabolism system. Six isoforms of uridine diphosphate glucuronate transferase(UGT)exhibited abilities to metabolize trans-SG and the order of metabolic ability was: UGT1A1 > UGT1A9 > UGT1A7 > UGT1A10 > UGT2B7 > UGT1A8. The results showed that trans-SG was mainly metabolized by UGT in phase II metabolism. The inhibition of drug metabolizing enzymes of phase II can increase the liver injury susceptibility of trans-SG, which provides a reference to the evaluation of susceptible factors and drug incompatibility research of Polygonum multiflorum.

Antiplatelet aggregation bioactivity of Polygoni Multiflori Radix with chemical fingerprints and spectrum-effect correlation analysis / 中国中药杂志

To explore the active substance of antiplatelet aggregation of Polygoni Multiflori Radix by using chemical fingerprints and antiplatelet aggregation bioactivity test for spectrum-effect correlation analysis. The Polygoni Multiflori Radix was tested by antiplatelet aggregation in vitro, and the results showed that 50% aqueous ethanol extract of Polygoni Multiflori Radix had more potent antiplatelet aggregation effect than 10% or 90% aqueous ethanol extract, and ultrasonic extraction was superior to refluxing extraction in the aspect of antiplatelet aggregation. The antiplatelet aggregation bioactivity of the different Polygoni Multiflori Radix extracts was evaluated and the results showed that the inhibition rate was 32.03%-74.56%. Spectrum-effect correlation analysis indicated that trans-stilbene glucoside, cis-stilbene glucoside and catechinic acid had higher correlation coefficient and they were 0.963 (P<0.01), 0.902 (P<0.01) and 0.656 (P<0.05) respectively; furthermore, all of the above three compounds demonstrated significant antiplatelet aggregation bioactivities. Considering their content difference in Polygoni Multiflori Radix, we calculated the relative active contributions, and the results suggested that trans-stilbene glucoside was the main active substance of Polygoni Multiflori Radix in the aspect of antiplatelet aggregation in vitro.

The value of diffusion tensor imaging and fiber tractography in cervical spondylotic myelopathy / 中国骨伤

<p><b>OBJECTIVE</b>To study the diagnostic value of diffusion tensor imaging (DTI) in cervical spondylotic myelopathy.</p><p><b>METHODS</b>Twenty healthy volunteers and fifty patients with cervical spondylotic myelopathy underwent DTI in the Affiliated Hospital of Medical College of Ningbo University from January 2014 to April 2015. Healthy volunteers served as controls. Fifty patients were divided into three groups (group A , B, C) according to cervical MRI scan standard. Group A (17 cases) had only the dura mater spinalis compressed; Group B (23 cases) showed the cervical spinal cord compressed, but no high signal in it; Group C (10 cases) had the cervical spinal cord compressed with high signal in the same level. The average apparent diffusion coefficients(ADC) and fractional anisotropy (FA)values in these examinee were analyzed and all subjects were performed fiber tracking.</p><p><b>RESULTS</b>There was no statistically significant differences in ADC and FA values in C2/C3, C3/C4, C4/C5, C5/C6, C6/C7 of control group (P>0.05). The average ADC and FA values in control group were (0.875 +/- 0.096) x10(3) mm2/s and 0.720 +/- 0.051, respectively; compared with group A,there was no statistically significant difference; compared with group B and C, there was significant difference; comparison among group A, B, C, there was significant differences.</p><p><b>CONCLUSION</b>DTI can early and accurately quantify the changes of microstructure in cervical spondylotic myelopathy. Fiber tracking can show the damage range of spinal cord lesions.</p>

CT and MRI manifestations of the axial area primary peripheral primitive neuroectodermal tumors / 中国骨伤

<p><b>OBJECTIVE</b>To explore CT and MRI manifestations of the axial area peripheral primitive neuroectodermal tumors (pPNETs) in order to improve the knowledge of this disease.</p><p><b>METHODS</b>The clinical data of 10 patients with pPNETs underwent pathologically confirmed were retrospectively analyzed from October 2008 to May 2014. There were 7 males and 3 females, aged from 8 to 49 years old with median of 23.6 years. The preoperative multi-slice spiral CT scan was completed in 3 cases, plain CT scan and enhancement in 4 cases; MRI and enhancement scanning in 5 cases; and among them, 2 cases underwent both MRI and CT scan.</p><p><b>RESULTS</b>In-bone type was found 6 cases and out-bone type was found 4 cases. Three cases occurred in sacral vertebrae, 2 cases in lumbar vertebrae, 1 case in cervical vertebrae, 1 case in cervical spinal canal, 1 case in coccyx, 1 case in the right iliac bone, 1 case in presacral space. Cross sectional the smallest tumor maximum level was 1.1 cmx 1.2 cm in size, the biggest tumor was 8.0 cm x 9.2 cm, the median size was 4.4 cm x 5.7 cm, of them, the tumor of maximal diameter larger than 5 cm had 6 cases. Except 2 cases-without destruction of bone, the other 5 cases with osteolytic destruction, 2 cases with calcification, 1 case with mixed. Equidensite was main in CT scan, 1 case with uniform density, other 6 cases with uneven density,in which 3 cases with "floating ice" change; 1 case with moderate strengthening, other 3 cases with obviously strengthening, 2 cases with multiple small blood vessels in enhancement scanning. MRI of 5 cases showed the signal of isointensity on T1WI, the slightly high signal on T2WI and the signal was not uniform; after enhancement scan, the signal of 5 cases obviously enhanced. Two patients complicated with vertebral compression fractures, no periosteal reaction was found in all patients, and no the destruction of intervertebral disk was found in 5 patients of MRI scan.</p><p><b>CONCLUSION</b>The axial area pPNETs is common among children and the youth, and the mass often is huge. The mass of in-bone type often envelopes the vertebral body, and main located on prevertebral space, all associated with bone destruction, osteolytic destruction is common, and primary vertebral bodies also is common, attachment primary or involvement is few found, it can involve the spinal canal and anterior wall of spinal canal is common, some cases complicate with multiple newly born small vessels. The mass of out-hone type in deep soft tissue is common, minority primary spinal canal, many complicated with vertebral bone destruction, osteolytic destruction was main. The intervertebral disk was not invaded and intervertebral space has not stenosis. CT scan offer complicate with "floating ice" sign, and in-bone type is common. Isointensity is main on MRI TlWI and slightly longer signal is main on MRI T2WI, strengthening signal is obvious.</p>

Imaging features of anatomical variations of the dorsal pancreas / 中华普通外科杂志

Objective To evaluate imaging features and clinical significance of anatomical variations of the dorsal pancreas.Methods CT and MR imaging data of 47 cases with variations of the dorsal pancreas were collected.Imaging characteristics of the dorsal pancreas were analysed.Results (1) Narrow dorsal pancreas:the agenesis of dorsal pancreas (7 cases) appeared as short pancreas,their length was (91.59 ± 22.39) mm.4 cases of pancreatic head volume increased,with tadpole-like retention of the pancreas,including 3 cases of annular pancreas.2 cases with polysplenia syndrome and congenital abscence of the hepatic segment of inferior vena cava.(2) Abnormaly enlarged dorsal pancreas:①the broadening of the pancreatic tail (n =18):the maximum diameter of pancreatic tail was (36.12 ± 6.59) mm,the pancreas was similar to the dumbbell-shaped.②Processes locally of pancreatic contour (n =13),which were local process at the ventral aspect of pancreas,the height was (15.72 ±2.65) mm,the width was (18.59 ± 3.64) mm,most often seen on the neck of the pancreas.(3) Dorsal pancreas related divisium:①Pancreas separated by fat spatium (n =7),the width was (3.51 ± 2.42),the deepness was (19.45 ± 5.84),it showed the crack-like fat density (signal) shadow,5 cases (5/7) located in the pancreatic body and tail,2 cases (2/7) located at the junction of ventral pancreas and dorsal pancreas.②The bifurcation of the pancereatic tail (n =3),limitations forked tail of the pancreas was dovetail-like performance.The maximum width diameter was (26.63 ± 1.75) mm,the bifurcation angle was (99.27 ± 30.73) degrees.Conclusions The developmental anomalies of dorsal pancreas can lead to a number of variations of pancreas,some of which can induce corresponding disease and be mistaken for neoplasm.

Targeting islet cell using 18F-Fallypride: in vitro and histoautoradiography study / 中华核医学与分子影像杂志

Objective To evaluate the feasibility of dopamine D2 receptor imaging agent (s)-(-)-N-(1-allylpyrrolidine-2-N-methyl)-5-(3-18F)-2,3-dimethoxy Benzamide (18F-Fallypride) for targeting islet cell imaging.Methods (1) Cytology experiment:Islet cells of 15×103 cells/well were incubated with 3.70 kBq/well 18F-Fallypride for 1 h and the uptake rate of cells was calculated (cell counts/(supernatant counts + cell counts)× 100％).Under the same experiment conditions,6 inhibiting groups were administrated with different concentration of dopamine inhibitors droperidol (1.0× 10-6,4.0× 10-6,2.0× 10-5,1.0× 10-4,5.0× 10-4 and 1.0× 10-3 mol/L,respectively).After 30 min,3.70 kBq of 18F-Fallypride was added to each inhibiting group,and the inhibiting rate was calculated.(2) Autoradiography:18 normal ICR mice were divided into 6 groups.For group A,ICR mice were injected with 18F-Fallypride (55 ± 5) MBq/mice through tail vein.For the other 5 inhibiting groups (group B-F),ICR mice were injected with different doses of droperidol (0.2,0.4,0.6,0.8 and 1.0 mg/kg,respectively),and after 30 min 18F-Fallypride were injected through tail vein.Ten minutes later,pancreas of ICR mice was taken for preparation of tissue section autoradiography.The data were analyzed by one-way analysis of variance and the least significant difference t test.Results (1) The 18F-Fallypride uptake rate of control group was (18.40± 1.21) ％.The uptake rates of inhibiting groups were (16.11±1.37)％,(15.76±0.99)％,(13.90±1.02)％,(8.86±0.73)％,(7.26±0.62)％ and (6.92±0.58)％,respectively,which decreased with the decreasing concentration of droperidol (F=50.01,P＜0.01).When the concentration of droperidol was 1.0× 10-4 mol/L,the uptake rate reached the lowest with inhibiting rate of 51.85％.(2) The autoradiography showed that the pancreas gray scale value of group A was 1.21×106 digital light units (DLU)/mm2.The pancreas gray scale value of groups B to F decreased with increasing concentration of inhibitor:0.93× 106,0.77× 106,0.59× 106,0.32× 106 and 0.25×106 DLU/mm2,respectively.Conclusions 18F-Fallypride may specifically and efficiently bind to dopamine receptors of islet cells.It may be a potential tracer for islet cells imaging.

The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory / 药学学报

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

Effect of ultrasound-and nerve stimulator-guided femoral nerve and lateral femoral cutaneous nerve block versus general anesthesia on knee joint surgery in elderly patients / 中华老年医学杂志

Objective To investigate the effect of ultrasound-and nerve stimulator-guided femoral nerve and lateral femoral cutaneous nerve block versus general anesthesia on knee joint surgery in elderly patients.Methods The 110 elderly patients with spinal anesthetic contraindication and undergoing lower extremity surgery from June 2014 to June 2015 were randomly divided into observation group (n =55) and control group (n =55).The observation group received both ultrasound-and nerve stimulator-guided femoral nerve and lateral femoral cutaneous nerve block,and the control group was given general anesthesia.Anesthesia procedure,sensory block onset time,changes in heart rate and mean artery pressure (MAP) after anesthesia,the total quantity of fluids infusion,dosage of vasopressor and hypotensor,adverse anesthetic reactions,anesthetic fees,anesthetic effect were recorded.Results Anesthetic preparation and practicing time had no difference between the two groups [(8.3 ± 1.7) min vs.(7.7 ± 1.2) min,(t =1.661,P=0.139)].The block onset time was longer in observation group than in control group [(10.3 ± 1.4) min vs.(3.2±0.6) min,t=50.180,P＜0.01].The changes in MAP had significant difference between the two groups [5 min after anesthesia:(89.24 ± 8.30) mmHg and (77.90 ± 8.05) mmHg;after operation:(96.60±8.03) mmHg and (106.22±8.88) mmHg;P＜0.05].There were significant differences in the fluid infusion quantity,dosage of vasopressor and hypotensor,adverse reactions during or after anesthesia,and anesthetic fees between the two groups [(1150.9± 231.6) ml vs.(1400.0±256.5) ml,(3.91±1.21) mg vs.(10.83±2.19)mg,(1.80±0.37) mg vs.(8.27±1.25)mg,3.6％ vs.18.2％,(1239.1±202.9) Yuan vs.(2307.2±205.6) Yuan,all P＜0.05].No significant difference was found in anesthesia effect between the two groups (P =0.198).Conclusions The ultrasound-and nerve stimulator-guided femoral nerve and lateral femoral cutaneous nerve block versus general anesthesia is more simple and safe for the knee joint surgery in elderly patients,with less complications,lower cost and higher satisfaction of patients.

The idiosyncratic hepatotoxicity of Polygonum multiflorum based on endotoxin model / 药学学报

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.

Comparison of processed and crude Polygoni Multiflori Radix induced rat liver injury and screening for sensitive indicators / 中国中药杂志

To investigate the difference of liver injury in rats gavaged with crude and processed Polygoni Multiflori Radix. The 75% ethanol extract of crude and processed Polygoni Multiflori Radix (50 g · kg(-1) crude medicine weight/body weight) were continuous oral administered to rats for 6 weeks. Serum biochemical indicators were dynamically detected, the change of liver histopathology was assessed 6 weeks later. Principal component analysis (PCA) was adopted to screen sensitive indicator of the liver damage induced by polygoni multiflori radix. Biochemical tests showed that the crude Polygoni Multiflori Radix group had significant increase of serum ALT, AST, ALP, DBIL and TBIL (P < 0.01 or P < 0.05) and significant decreases of serum IBIL and TBA (P < 0.01 or P < 0.05), while the processed Polygoni Multiflori Radix group showed no obvious changes, compared to the untreated normal group. Histopathologic analysis revealed that crude Polygoni Multiflori Radix group exhibited significant inflammatory cells infiltration in portal area around the blood vessels, tissue destruction and local necrosis of liver cells. There were not obvious pathological changes in processed Polygoni Multiflori Radix group. The results demonstrated that the injury effect of processed Polygoni Multiflori Radix on liver injury of rats was significantly lower than that of unprocessed, and that processing can effectively reduce the hepatotoxicity of Polygoni Multiflori Radix. Traditional transaminase liver function indicators were not sensitive for crude Polygoni Multiflori Radix induced liver damage. The serum content of DBIL and TBIL can reflect the liver damage induced by crude Polygoni Multiflori Radix early and can be sensitive indicators for clinical monitoring the usage of it.

The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory / 药学学报

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

The idiosyncratic hepatotoxicity of Polygonum multiflorum based on endotoxin model / 药学学报

The liver injury induced by Polygonum multiflorum Thunb. (PM) was investigated based on idiosyncratic hepatotoxicity model co-treated with lipopolysaccharide (LPS) at a non-hepatotoxic dose. Sprague-Dawley (SD) rats were intragastrically administered with three doses (18.9, 37.8, 75.6 g crude drug per kg body weight) of 50% alcohol extracts of PM alone or co-treated with non-toxic dose of LPS (2.8 mg·kg(-1)) via tail vein injection. The plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were assayed and the isolated livers were evaluated for histopathological changes. The dose-toxicity relationships of single treatment of PM or co-treatment of LPS were investigated comparatively to elucidate the idiosyncratic hepatotoxicity of PM. The results showed that no significant alterations of plasma ALT and AST activities were observed in the groups of solo-administration of LPS (2.8 mg·kg(-1), i.v.) or different dosage (18.9, 37.8 and 75.6 g·kg(-1), i.g.) of PM, compared to normal control group (P > 0.05); while significant elevations were observed in the co-administration groups of PM and LPS. Treatment with LPS alone caused slight infiltration of inflammatory cells in portal area but no evident hepatocytes injury. Co-treatment with LPS and PM (75.6 g·kg(-1), i.g.) caused hepatocyte focal necrosis, loss of central vein intima and a large number of inflammatory cell infiltration in portal areas. When further reduce the dosage of PM, significant increases of plasma ALT and AST activities (P < 0.05) were still observed in co-administration groups of LPS and PM (1.08 or 2.16 g·kg(-1)), but not in LPS or PM solo-administration groups. Nevertheless, the co-treatment of low dosage of PM (0.54 g·kg(-1)) with LPS did not induce any alteration of plasma ALT and AST. In conclusion, intragastric administration with 75.6 g·kg(-1) of PM did not induce liver injury in normal rats model; while the 2 folds of clinical equivalent dose of PM (1.08 g·kg(-1)) could result in liver injury in the LPS-based idiosyncratic hepatotoxicity model, which could be used to evaluate the idiosyncratic hepatotoxicity of PM.

The imaging findings of unexpected splenic autotransplantation after splenectomy / 中华肝胆外科杂志

Objective To study the imaging findings of unexpected splenic autotransplantation after splenectomy and to improve diagnostic accuracy of splenic autotransplantation.Methods The findings of 10 patients with splenic autotransplantation confirmed by histology in our hospital were retrospectively reviewed.In 7 patients CT and plain and dynamic enhanced MRI scanning were carried out,and in 2 of them 99mTc-DRBC scanning were also done.In 3 patients,plain and dynamic enhanced CT scannings were done.Results (1) Multiple lesions were detected in 7 patients and a single lesion in 3 patients.The masses were round and oval.The nodules were in the splenic fossa in 9 patients,in the pancreatic tail in 4 patients,in the right liver in 2 patients and in other of parts of the abdominal cavity in 2 patients.These nodules varied in size and 94.6％ showed a maximum diameter of less than 3 cm; (2) The findings on CT and MR:all the nodules were homogeneous with soft tissue density.There was no cystic degeneration,necrosis and calcification.In one patient with a nodule in the pancreatic tail,there was a slightly short T1 and short T2 signals.Other nodules showed long T1 and long T2 signals.All the signals from the nodules were homogeneous and their outlines were clear.In a patient with a nodule in the right liver,the blood supply came from the abdominal aorta.There was a surrounding thin layer of low-density ring which showed long T1 and long T2 signals.The enhanced features on CT and MR were similar.The nodules showed homogeneous or inhomogeneous enhancement in the arterial phase,with continuous homogeneous enhancement in the portal venous phase,with an obvious decline in the delayed phase;(3) The findings of 18 F-FDG PET:The nodules had obvious increase in FDG uptake.Conclusions In patients with a history of splenic trauma or splenectomy,abdominal nodules with multiple,homogeneous density or signal,clear outline,enhanced features similar to spleen,splenic autotransplantation should be considered.99mTc-DRBC scanning is helpful in the diagnosis of splenic autotransplantation.

CT-guided radiofrequency ablation for the treatment of osteoid osteoma in femoral neck：preliminary experience in 6 cases / 介入放射学杂志

Objective To evaluate the feasibility, safety and efficacy of CT-guided radiofrequency ablation in treating osteoid osteoma located at femoral neck. Methods Six patients with osteoid osteomas in the femoral neck received CT-guided percutaneous radiofrequency ablation. In all patients the main complaint was pain at the hip, and the course of disease varied from one month to 2 years, with an average of 8 months. Under spinal anesthesia the surgery was performed. With the help of CT guidance , a 3.5 to 4.0 mm coaxial drill system was inserted into the nidus, and an osseous access was established, then the bone biopsy needle was used to obtain specimens for pathological examination. Subsequently, a 1.5 to 2.0 cm active tip was introduced through a non-cooled radiofrequency needle into the nidus. Radiofrequency ablation was performed with the therapeutic temperature of 90℃, lasting for 6 minutes. The pain visual analogue scale (VAS) was used to evaluate the clinical effectiveness. The postoperative MRI findings were compared with the preoperative ones. Results Three days after the treatment, different degrees of pain relief was obtained in all patients, and all patients could get out of bed and walked around in one week. Postoperative VSA was significantly decreased (P<0.01). No severe complications occurred during and after the procedure. And no recurrence was seen during the follow-up period. Conclusion For the treatment of osteoid osteoma located at femoral neck, CT-guided radiofrequency ablation is a safe and effective minimally invasive treatment with fewer complications and satisfactory clinical results.