To investigate the metabolic rate and metabolites of 9-dehydro-17-dehydro-andrographolide, which is the main active ingredient in Xiyanping injection, by using the in vitro rat liver microsome incubation system. 9-dehydro-17-dehydro-andrographolide was incubated together with liver microsome mixed with NADPH. Its metabolic rate was studied by determining its residual concentrations with the UHPLC-MS/MS method; Its metabolites were identified by the UPLC-TOF-MS(E) method. The results showed that 9-dehydro-17-dehydro-andrographolide was metabolized faster than rat liver microsomes mixed with coenzymes, with t½ and CL of (19.7 ± 0.5) min and (35.1 ± 0.8) mL x min(-1) x g(-1) (protein), respectively. Based on the high resolution mass spectrum data and information from literatures, altogether nine metabolites of 9-dehydro-17-dehydro-andrographolide were identified in the incubation system, particularly hydroxylated and dehydrogenized products. The results of identification would provide a basis for screening out more active andrographolide derivatives.
Animals ; Chromatography, High Pressure Liquid ; Diterpenes ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Microsomes, Liver ; chemistry ; metabolism ; Molecular Structure ; Rats ; Tandem Mass Spectrometry

To investigate the application of a recently developed metallic oxide semiconductor field effect transistor(MOSFET)detector for use in vivo desimetry.Methods The MOSFET detector was calibrated for X-ray beams of 8 MV and 15 MV,as well as electron beams with energy of 6,8,12 and 18 MeV.The dose linearity of the MOSFET detector was investigated for the doses ranging from 0 up to 50 Gy using 8 MV X-ray beams.Angular effect was evaluated as well in a cylindrical PMMA phantom by changing the beam entrance angle every 15?clockwise.The MOSFET detector was then used for a breast cancer patient in vivo dose measurement, after the treatment plan was verified in a water phantom using a NE-2571 ion chamber,in vivo measurements were performed in the first and last treatment,and once per week during the whole treatment.The measured doses were then compared with planning dose to evaluate the accuracy of each treatment.Results The MOSFET detector represented a good energy response for X-ray beams of 8 MV and 15 MV,and for electron beams with energy of 6 MeV up to 18 MeV.With the 6 V bias,Dose linearity error of the MOSFET detector was within 3.0% up to approximately 50 Gy,which can be significantly reduced to 1% when the detector was calibrated before and after each measdurement.The MOSFET response varied within 1.5% for angles firm 270?to 90?.However,maximum error of 10.0% was recorded comparing MOSFET response between forward and backward direction.In vivo mea surement for a breast cancer patient using 3DCRT showed that,the average dose.deviation between measurement and calculation was 2.8%,and the maximum error was less then 5.0%.Conclusions The new MOSFET detector,with its advantages of being in size,easy use,good energy response and dose linearity,can be used for in vivo dose measurement.

OBJECTIVETo summarize the surgical outcome of patients with small cell esophageal carcinoma(SCEC).

METHODSClinical data of patients with esophageal carcinoma were retrospectively collected from March 2000 to March 2011 at the Thoracic Surgery Department of the Peking University Cancer Hospital. Data included tumor characteristics, staging, treatment, response, short-term outcome, and long-term survival.

RESULTSA total of 546 patients with esophageal carcinoma were identified, among whom there were 15 patients with SCEC(2.7%). Fourteen cases received multimodality treatment based on operation and one underwent operation alone. Four patients had preoperative chemotherapy and 10 had postoperative chemotherapy. Four patients had postoperative radiation. After excluding one case of postoperative death within 3 months, the median overall survival was 14.3 months(range, 4 to 99 months), significantly worse than those with non-SCEC(42.2 months, P<0.05).

CONCLUSIONSCEC is rare and the outcomes are poor. It should be considered as a systematic disease.

Adult ; Aged ; Carcinoma, Small Cell ; surgery ; therapy ; Combined Modality Therapy ; Esophageal Neoplasms ; surgery ; therapy ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

Rat aorta media, adventitia and cultured vascular smooth muscle cells (VSMCs) were used in this study to identify the source of nitric oxide (NO) generation from various cell types of vascular tissues and to elucidate the mechanisms involved in NO formation. Treatment of vascular media and VSMCs with lipopolysaccharide (LPS) or cytokines [tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta)] resulted in a dose-dependent increase of NO release. Inducible nitric oxide synthase (iNOS) in the stimulated VSMCs was significantly upregulated as shown by Western blot analysis. Protein kinase C (PKC) inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7) prevented LPS-, TNF-alpha- and IL-1beta-induced NO production, whereas N-(2-guanidinoethyl)-5-isoquinoline-sulfonamide (HA1004), an H7 analogue with little activity towards PKC, had no inhibition effect. The role of PKC in LPS- and cytokine-induced changes on NO formation was confirmed by using another structurally distinct PKC inhibitor chelerythrine. Treatment of VSMCs with protein tyrosine kinase (PTK) inhibitor genistein or tyrphostin AG18 also reduced the NO production evoked by LPS, TNF-alpha or IL-1beta, which was associated with inhibition of iNOS protein expression. In contrast, PKC inhibitor chelerythrine did not affect iNOS expression. These results suggest that PTK mediates LPS- and cytokine-induced NO formation by upregulation of iNOS expression. PKC may be involved in the post-translational modification of iNOS or the regulation of the availability of iNOS substrates and cofactors.
Animals ; Aorta, Thoracic ; cytology ; Cells, Cultured ; Cytokines ; pharmacology ; Interleukin-1beta ; pharmacology ; Lipopolysaccharides ; pharmacology ; Male ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Nitric Oxide ; biosynthesis ; Nitric Oxide Synthase Type II ; metabolism ; Protein Kinase C ; physiology ; Protein-Tyrosine Kinases ; physiology ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; pharmacology

Objective To solve the danger and difficulty in transferring seriously injured victims. Methods The operating principle, construction design, electronic control system and software program flowchart of a robot transfer arm for victim-transfer were introduced.Results and Conclusion The victim didn not have to change their body posture during transfer. The procedure is very simple.A push at only one key is enough,without secondary injury.

[ ABSTRACT] AIM: To investigate the protective effect of autophagy on oxidized low density lipoprotein ( ox-LDL)-induced macrophage apoptosis and the underlying molecular mechanisms .METHODS:The RAW264.7 macropha-ges were pretreated with 3 mmol/L 3-methyladenine (3-MA), 1 μmol/L rapamycin (Rap) or 4 mmol/L 4-phenylbutyric acid ( PBA) respectively for 1 h and then treated with ox-LDL (100 mg/L) for 12 h.The cell viability and apoptosis were determined by MTT assay and flow cytometry with Annexin V-FITC/PI staining, respectively.The activities of lactate de-hydrogenase ( LDH) in the medium and caspase-3 in the cells were determined by detection kits .The protein levels of bec-lin-1 (a molecular marker of autophagy ), glucose-regulated protein 78 (GRP78, an endoplasmic reticulum stress marker) and C/EBP homologous protein ( CHOP, a key-signaling component of endoplasmic reticulum stress-induced apoptosis ) were examined by Western blot .Microtubule-associated protein 1 light chain 3 (LC3, another molecular marker of autoph-agy) was observed under laser scanning confocal microscope .RESULTS: Treatment of the RAW264.7 macrophages with ox-LDL at 100 mg/L for 12 h resulted in significant decrease in cell viability , and dramatic elevation in LDH leakage , cell apoptosis and caspase-3 activity, which were promoted by 3-MA (an autophagy inhibitor) and inhibited by Rap (an autoph-agy inducer ) .ox-LDL induced autophagy in the macrophages as assessed by beclin-1 upregulation and frequent granulation of LC3, which were inhibited by 3-MA and promoted by Rap.Interestingly, 3-MA enhanced, while Rap blocked, the CHOP upregulation induced by ox-LDL.Moreover , PBA ( endoplasmic reticulum stress inhibitor ) significantly inhibited ox-LDL-induced GRP78 upregulation and autophagy as determined by the attenuation of beclin-1 upregulation and frequent granula-tion of LC3.CONCLUSION: Endoplasmic reticulum stress mediates ox-LDL-induced autophagy in macrophages , and moderates activation of autophagy may protect macrophages from ox-LDL-induced apoptosis by inhibiting CHOP expression .

Objective: To evaluate the efficacy of Tuina (Chinese therapeutic massage) manipulation plus horse-riding squat exercise in treating knee osteoarthritis (KOA) and optimize the combining protocol. Methods: Based on a 2×2 factorial design, 120 eligible KOA patients were randomized into a manipulation group (group A1B2), a manipulation plus horse-riding squat group (group A1B1), a sitting knee-adjustment group (group A2B2 group), and a sitting knee-adjustment plus horse-riding squat group (group A2B1), with 30 cases in each group. The intervention was conducted three times a week, lasting for four weeks. The Western Ontario and McMaster Universities osteoarthritis index (WOMAC) was taken as the major measure for efficacy evaluation (including three component scores, pain, stiffness, and daily function, and total score). Results: The three component scores (pain, stiffness, and daily function) and the total score of WOMAC showed significant differences after the intervention in the four groups (P<0.05). There were significant inter-group differences in the WOMAC stiffness score amongst the four groups after the intervention (P<0.05). In group A1B1, the step length, stride, walking speed, and knee joint flexion angle changed significantly after treatment (P<0.05). After the intervention, the step length changed significantly in group A1B2 (P<0.05), and the walking speed changed significantly in group A2B1 (P<0.05). There were no significant differences in the step length, stride, walking speed, or knee joint flexion angle among the four groups (P>0.05). The extensor peak torque at 180 °/s changed significantly in group A1B2 after treatment (P<0.05). Neither the intra-group nor the inter-group comparisons of the four groups revealed significant differences in the other isokinetic muscle strength parameters (P>0.05). The main effect of manipulation showed significant in affecting the WOMAC pain and total scores (P<0.05). The main effect of horse-riding squat exercise showed significant in affecting the WOMAC pain and stiffness scores (P<0.05). Conclusion: The four treatment protocols all can improve the symptoms of KOA, for instance, relieving pain and stiffness, and enhancing daily function. Group A2B1 produces the most eminent effect in relieving joint stiffness. The main effects of both manipulation and horse-riding squat exercise are significant in reducing pain. Besides, the main effect of horse-riding squat exercise is significant in relieving joint stiffness.

Objective To discuss how to protect the intracranial vertebral artery and posterior inferior cerebellar artery by observing and measuring the intracranial vertebral artery in the surgery adopt far lateral approach. Methods Mimicking far lateral approach, 20 adult cadaveric heads connected to neck fixed with 10% formalin were dissected. Intracranial segment of the vertebral arteries and their main branches were exposed and measured under operating microscope. Results The intracranial vertebral artery joined with the contralateral one into the basilar artery after traveling through the atlanto-occipital sulcus. The relationship between the vertebral artery and the hypoglossal nerve is close. Thirty sides (75%) of the vertebral arteries traveled to pons medulla sulcus in front of the hypoglossal nerve roots and 2 sides (5%) behind the hypoglossal nerve roots, while 8 sides (20%) traveled among the hypoglossal nerve roots; 70% of the vertebral arteries were contacted to the hypoglossal nerve roots, 30% of which compressed the hypoglossal nerve. The main branches of intracranial segment of the vertebral arteries were the posterior inferior cerebellar arteries, the anterior spinal arteries, the posterior meningeal arteries,and some perforating arteries. Posterior inferior cerebellar arteries all originated from the intracranial vertebral artery were the largest vertebral artery's branches; their trip was mostly loop-shaped and they had close relationship with Ⅸ, Ⅹ, Ⅺ cranial nerves. The starting points of the posterior inferior cerebellar arteries were different, even in the same specimen, but most of them originated from the upper 1/3intracranial vertebral artery. No anterior inferior cerebellar artery was noted originated from the vertebral artery in our specimen. Anterior spinal arteries originated from the vertebral arteries joined with the branches of the bilateral vertebral arteries and traveled down through the tortuous anterior median fissure to supply the spinal cord. Conclusion Being familiar with the characteristics and anatomic vertebral arteries variations of the intracranial vertebral artery and its branches can contribute to identify and protect the intracranial segment of the vertebral artery and its main branches in the surgery adopt far-lateral approach.

OBJECTIVETo assess the impact of early enteral nutrition (EN) on the intestinal motility of patients after esophagectomy.

METHODSThirty-five consecutive patients undergoing esophagectomy for esophageal cancer by a single surgical team from the Peking University Cancer Hospital from June 2011 to July 2011 were enrolled. Patients were randomly divided into EN group (n=20) and parenteral nutrition group (control group, n=15) within 24 h after esophagectomy procedure. Bowel sound recovery time was monitored by auscultation, and the gastrointestinal tract symptoms were recorded.

RESULTSBowel sound recovery time was (45.1±20.3) h in the EN group, and was (56.7±17.0) h in the control group (P=0.082). Gastrointestinal symptoms such as nausea, abdominal distension, diarrhea occurred in 4 patients in EN group and 3 patients in control group and were alleviated by lowering infusion speed and more off-bed ambulation, and no significant difference was seen between the two groups (P=1.000).

CONCLUSIONSEarly enteral nutrition in the patients after esophagectomy is safe and feasible. Early enteral nutrition does not delayed bowel function recovery or increase gastrointestinal symptoms.

Aged ; Enteral Nutrition ; Esophageal Neoplasms ; physiopathology ; therapy ; Female ; Gastrointestinal Motility ; physiology ; Humans ; Male ; Middle Aged ; Postoperative Care ; Prospective Studies

OBJECTIVETo explore the early rehabilitation effect of acupuncture on brain arousal in severe craniocerebral injury.

METHODSOne hundred and two cases of severe craniocerebral injury were randomly divided into an observation group and a control group, 51 cases in each one. Based on the conventional nursing care in neurological external medicine, in observation group, acupuncture was applied at Shuigou (GV 26), Neiguan (PC 6) and Sanyinjiao (SP 6) mainly. In control group, functional electric stimulation was applied at stimulate the affected muscles of the upper limbs. Thirty days later, the lucid rate from coma, lucid interval and clinical efficacy were compared between two groups. RESULTS; The lucid rate from coma was 82.4% (42/51) in observation group, which was higher than 56.9% (29/51) in control group (P < 0.01). The lucid interval in observation group was shortened remarkably as compared with control group (P < 0.01), and the clinical efficacy was superior apparently to that in control group (P < 0.01).

CONCLUSIONOn the basis of conventional treatment, acupuncture intervention at early stage can accelerate the recovery of brain arousal function in patients with severe craniocerebral injury.

Acupuncture Therapy ; Adolescent ; Adult ; Aged ; Arousal ; Brain ; physiopathology ; Child ; Craniocerebral Trauma ; physiopathology ; rehabilitation ; therapy ; Humans ; Male ; Middle Aged ; Young Adult