The pharmacokinetic research of traditional Chinese medicines (TMC) is an inalienable part of the chain of TCM modernization and plays an important role in the TCM novel drug development. However, the researching method and system that is consistent with the specific characteristics of TCM, i.e., multiple-components and targets, is still lacking. Furthermore, the current understanding of the critical scientific questions of TCM pharmacokinetics remains still unclear. This review makes a brief summary of our recent developments on the pharmacokinetic exploration of TCMs, mainly including integral pharmacokinetic study of multiple components, herbalome analysis both in vitro and in vivo, mechanism based compatibility study for herbal components interactions, and the representative pharmacokinetic study for single herbal compound. Furthermore, the critical scientific questions of TCM pharmacokinetics are discussed based on understanding the requirements of novel drug developments from TCM.
Animals ; Drug Combinations ; Drug Interactions ; Drug Synergism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Humans ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry ; Principal Component Analysis ; Quantitative Structure-Activity Relationship

Objective This study is to analyse the clinical feature and risk factors of morbidity after pulmonary resection for lung cancer in patients older than 70 years. Methods The clinical records of 222 patients older than 70 years who had undergone pulmonary resection for their lung cancer was reviewed. The patients were divided into 3 groups: group Ⅰ including the patients who had severe postoperative complications, group Ⅱ including the patients who had mild complications and group Ⅲ including the patients who had no complications. Moreover, the definitions were made that group A1 = group Ⅰ+ Ⅱ , group B1 = group Ⅲ, group A2 = group Ⅰ and group B2 = group Ⅱ + Ⅲ. Univariate analyses and multivariate binary logistic regressions relating postoperative morbidity to risk factors were performed between the group Al and Bl, A2 and B2, resulting in the identification of the independent risk factors for overall morbidity and major morbidity. Results Preoperative comorbidity was recorded in 161 patients (72.5%). Lobectomy (64.9% ) was the predominant surgical procedure. The median number of dissected LN was 14, with the range of 0 to 57. The overall morbidity was 63.5% , including major morbidity of 13.5%. Perioperative mortality was 1.8% (4 cases). The results of binary logistic regression analyses indicated that the independent risk factors for overall morbidity were preoperative weight loss (P =0.020), ASA score (P＜0.001), MVV (% predicted) (P=0. 020 ) and the number of dissected LN ( P = 0.004 ). The independent risk factors for major morbidity were ASA score ( P =0.003), MVV (% predicted) (P= 0.018) and the location of tumor (P=0.007). Conclusion Preoperative weight loss and numbers of dissected mediastinal lymph nodes were risk factor for lung cancer patients older than 70 years, Proper perioperative management for the elderly patients with high ASA score, low MVV (% predicted) or central tumor, could reduce the major postoperative morbidity.

Objective Surgical approech differs between China and western countries in the treatment of middle/lower aegment thoracic esophageal cancer. This study was designed to compare the effects of different surgical modalities on traumatic reaction, heal-ing process and lymph node dissection.Methods Fifty-nine petients,diagnosed with middle/lower segment of thoracic esophageal cancer, were enlisted and had undergone curative RO esophagectomy.The patients were categorized based on different approaches as the following three groups:group of Ivor-Lewis operation,group of McKeown operation and group of esophagectomy through left tran-sthoracic approach.Clinical data was summarized and malyzed.Results (1)No surgical death was reported in this study.(2)There were no statistical difference among the three groups in tenms of postoperative hospital stay,diration of systemic inflammatory re-sponse syndrome and total body fluid loes (P=0.287,0.641,0.355).(3) The number of total lymph nodes harvested from the above three groups was 22.5(11-39),26(14-56).and 17(7-44)(P=0.005),respectively.The number of abdominal lymph nodes harvested from the above three groups was 10(5-26),12(4-32),and 8(3-19)(P=0.021),respectively.No statistical difference was found to the number of thoracic lymph nodes among three groups.(4)Lymph node metastasis occurred most frequently in the station of pericardial lymph nodes,followed by middle thoracic paraesophageal nodes along the left gastric ar-tery.The range of metastasized lymph nodes dissected through left transthoracic approach was much limited compated with right tran-sthoracic approach.Conchuslon The was no difference between left and right transthoracic approach in terms of surgical trauma and overall rehabilitation.The number of lymph nodes harvested from right transthoracic approach surpassed that from the left approach, which might be due to the extent of abdoominal lymphadenectomy.Considering wide range of lymph node metastasis,We recommedn a more extended lymph node dissection for middle/lower segment of thoracic esophageal cancer for the purpose of better local control control and survival benefit.

ObjectiveTo describe the modified (narrowed) gastric tube and two methods on the establishmentof enteral feeding pathway in esophagectomy.MethodsFrom July 2003 to April 2006,we made traditional gastric tube for patients underwent esophagectomy to substitute the dissected esophagus while from May 2006 to November 2009,we made modified gastric tube for the same purpose.From July 2003 to November 2009,enteral nutrition tubes for all these patients are placed intraoperatively by two different ways,which made early post-operative nutrition support possible for these patients.ResultsNo perioperative death occurred among the patients.The length of the modified gastric tube ensured the anastomosis by circular stapler at the apex thorax or in the bases of cervical region.No statistical differences were found between the two group in terms of survival rate.The intraoperative establishment of enteral nutrition pathway ensured the early enteral nutrition support after the operation.ConclusionThe utility of the modified gastric tube extends the length of gastric tube to make mechanical anastomose easier and safer; meanwhile,the intraoperative establishment of enteral nutrition pathway ensures the early enteral nutrition support after the operation.

OBJECTIVETo investigate the effect of Compound Qingqin Liquid (CQL) on the expression level of angiotensin II (Ang II) and COX-2 mRNA transcription and protein expression in the renal tissue of rats with uric acid nephropathy.

METHODSSD rats were randomly divided into the blank control group, the model group, the positive drug group, the high, moderate, and low dose CQL group according to number randomization principle. The model was established by gastrogavage of adenine, accompanied with yeast feeding. Distilled water was given by gastrogavage to rats in the blank control group and the model group. Allopurinol at the daily dose of 9.33 mg/kg was given by gastrogavage to rats of the positive control group. CQL at the daily dose of 3.77 g/kg, 1.89 g/kg, and 0.09 g/kg was respectively given by gastrogavage to rats in the high, moderate, and low dose CQL groups. All treatment lasted for 6 weeks. Rats were randomly divided at week 4 (3 in the blank control group, and 6 in the rest groups), and the rest rats were killed at week 6. The renal tissue was extracted. The expression level of Ang II and COX-2 mRNA transcription were detected by RT-PCR. The expression level of Ang II was detected by ELISA. The expression level of COX-2 protein was detected by Western blot and immunohistochemical assay.

RESULTSCompared with the blank control group, except the mRNA expression of Ang II at week 4, the mRNA and protein expression of Ang II and COX-2 obviously increased at week 4 and 6 in the model group (P < 0.01, P < 0.05). The COX-2 protein expression at week 4 was obviously lower in the high and moderate dose CQL groups than in the model group and the low dose CQL group (P < 0.05); the average integral of optical density value was obviously lower in the positive control group than in the model group. Except the mRNA expression of Ang II in the high dose CQL group at week 6, the mRNA and protein expression of Ang II obviously decreased in the positive control group and each dose CQL group (P < 0.01, P < 0.05). Of them, the effects were better in the high and moderate dose CQL groups than in the positive control group and the low dose CQL group (P < 0.05, P < 0.01). Besides, the mRNA expression of COX-2, the average integral of optical density value were obviously lower in the positive control group and each dose CQL group than in the model group (P < 0.05). The protein expression of COX-2 was obviously lower in the high and moderate dose CQL groups than in the model group (P < 0.05). Of them, the mRNA expression of COX-2 was better in the moderate dose CQL group than in the positive control group (P < 0.05); the protein expression of COX-2 was better in the high dose CQL group than in the low dose CQL group (P < 0.05).

CONCLUSIONCQL was capable of lowering the expression level of Ang II, COX-2 mRNA transcription and protein expression, thus suppressing the inflammatory pathological injury of the renal tissue.

Angiotensin II ; metabolism ; Animals ; Cyclooxygenase 2 ; genetics ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Kidney ; metabolism ; Kidney Diseases ; drug therapy ; metabolism ; Male ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uric Acid

A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells. Malic enzyme 1(ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool. ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis. In the present study, we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma(NPC) cells. High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells. However, there were no obvious changes in the other two pathways for glucose metabolism: glycolysis and oxidative phosphorylation. Interestingly, NADPH was decreased under low-glucose condition in ME1-repressed cells relative to wild-type cells, whereas no significant difference was observed under high-glucose condition. ME1-repressed cells had significantly decreased tolerance to low-glucose condition. Moreover, NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress. Furthermore, diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein. Collectively, these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.
Carcinoma ; Cell Line, Tumor ; Cell Movement ; Cell Survival ; Glucose ; metabolism ; Glycolysis ; Humans ; Malate Dehydrogenase ; metabolism ; NADP ; metabolism ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Oxidation-Reduction ; Oxidative Phosphorylation ; Pentose Phosphate Pathway ; Proto-Oncogene Proteins c-akt ; metabolism

Objective To summarize the diagnosis and treatment experience of patients with middle cerebral artery aneurysms (MCAAs) associated with intra-Sylvian hematomas. Methods The clinical data of 21 patients with ruptured MCAAs associated with intra-Sylvian hematomas (haemorrhage ≥20mL), admitted to our hospital from November 2006 to May 2011, were analyzed retrospectively. Treatment experiences of MCAAs associated with intra-Sylvian hematomas with microsurgery were concluded. Results Among them,12 patients were performed clipping and 8 were performed resection and clipping. Bypass of superficial temporal artery to middle cerebral artery was performed before occlusion of the afferent artery in 1 patient.When the patients discharged from hospital,their Glasgow outcome scale (GOS) were 4-5 scores in 16 patients,3 scores in 3,2 scores in 1 and 1 score in 1; excellent outcomes were achieved in 15 patients, no marked changes in 4 patients, and post-operative complications were observed in 1 patient; 1 perioperative death occurred. Conclusion Ruptured MCAAs combined with intra-Sylvian hematomas should be differed from hypertension hemorrhage of basal ganglia areas; intraoperative Doppler sonography,introperative indocyanine green angiography and neurophysiological monitoring are helpful during the surgical treatment.

Objective To evaluate the feasibility and safety of using pediatric donation after brain death donors during split liver transplantation .Methods The clinical data were retrospectively reviewed for 8 pediatric recipients undergoing split liver transplantation with a donor age of 2 .7-7 years .The clinical characteristics of donors/recipients ,perioperative course ,postoperative recovery and complications along with graft and recipient survival rate were analyzed .Results The split procedure was performed ex situ (n=3) and in situ (n=1) ,all liver grafts were split into left lateral lobes and extended right lobes . The recipients were children aged 4 .7-105 .5 months . The mean follow-up period was (8 .1 ± 0 .6) months and the graft/recipient survival rates approached 100％ . Graft functions remained normal in all recipients at the end of follow-ups .Two recipients undergoing liver grafting with long cold ischemia time exhibited slower recovery of graft function .Pathological examination of graft biopsy indicated ischemic and hypoxic changes .Portal vein stenosis occurred in one recipient .Percutaneous transhepatic portal vein balloon dilatation was performed and the recipient recovered well .Cytomegalovirus infection occurred in 5/8 recipients and serum virological marker returned to normal after ganciclovir therapy . The youngest donor age was 2 .7 years and both recipients of donor liver recovered well .Conclusions Split liver transplantation with a donor age of 2 .7-7 .0 years may achieve ideal clinical outcomes in well-matched donors and recipients .

Neospora caninum is the etiologic agent of bovine neosporosis, which affects the reproductive performance of cattle worldwide. The transmembrane protein, NcSRS2, and dense-granule protein, NcGRA7, were identified as protective antigens based on their ability to induce significant protective immune responses in murine neosporosis models. In the current study, NcSRS2 and NcGRA7 genes were spliced by overlap-extension PCR in a recombinant adenovirus termed Ad5-NcSRS2-NcGRA 7, expressing the NcSRS2-NcGRA7 gene, and the efficacy was evaluated in mice. The results showed that the titer of the recombinant adenovirus was 10(9)TCID50/ml. Three weeks post-boost immunization (w.p.b.i.), the IgG antibody titer in sera was as high as 1:4,096. IFN-gamma and IL-4 levels were significantly different from the control group (P<0.01). This research established a solid foundation for the development of a recombinant adenovirus vaccine against bovine N. caninum.
Adenoviridae/*genetics ; Animals ; Antibodies, Fungal/blood ; Antigens, Fungal/genetics/*immunology ; *Drug Carriers ; Fungal Proteins/genetics/*immunology ; Fungal Vaccines/administration & dosage/genetics/*immunology ; Immunoglobulin G/blood ; Interferon-gamma/blood ; Interleukin-4/blood ; Mice ; Mice, Inbred BALB C ; Neospora/genetics/*immunology ; Recombinant Fusion Proteins/genetics/immunology ; Vaccines, Synthetic/administration & dosage/genetics/immunology

BACKGROUNDVascular hyporeactivity, which occurs in the terminal stage of hemorrhagic shock, is believed to be critical for treating hemorrhagic shock. The present study was designed to examine whether the CB1 cannabinoid receptor (CB1R) was involved in the development of vascular hyporeactivity in rats suffering from hemorrhagic shock.

METHODSSixteen animals were randomly divided into two groups (n = 8 in each group): sham-operated (Sham) and hemorrhagic shock (HS) groups. Hemorrhagic shock was induced by bleeding. The mean arterial pressure (MAP) was reduced to and stabilized at (25 +/- 5) mmHg for 2 hours. The vascular reactivity was determined by the response of MAP to norepinephrine (NE). In later experiments another twelve animals were used in which the changes of CB1R mRNA and protein in aorta and superior mesenteric artery (SMA) were analyzed by RT-PCR and Western blotting. In addition, we investigated the effects of a CB1R antagonist on the vascular hyporeactivity and survival rates in rats with hemorrhagic shock. Survival rates were analyzed by the Fisher's exact probability test. The MAP response was analyzed by one-way analysis of variance (ANOVA).

RESULTSVascular hyporeactivity developed in all animals suffering from hemorrhagic shock. The expression of CB1R mRNA and protein in aorta and 2 - 3 branches of the SMA were significantly increased in the HS group after the development of vascular hyporeactivity when compared to those in Sham group. When SR141716A or AM251 was administered, the MAP response to NE was (41.75 +/- 4.08) mmHg or (44.78 +/- 1.80) mmHg respectively, which was higher than that in saline groups with (4.31 +/- 0.36) mmHg (P < 0.01). We also showed an increased 4-hour survival rate in the SR141716A or AM251-treated group with 20% or 30%, but with a statistically significant difference present between the AM251-treated and saline groups (P < 0.05).

CONCLUSIONSCB1R is involved in vascular hyporeactivity resulting from hemorrhagic shock in rats, and CB1R antagonist may be useful in treating patients with traumatic, hemorrhagic shock who need field-rescue or initial treatment.

Animals ; Blotting, Western ; Gene Expression Regulation ; drug effects ; Hypotension ; metabolism ; Male ; Piperidines ; pharmacology ; Pyrazoles ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1 ; antagonists & inhibitors ; genetics ; metabolism ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Shock, Hemorrhagic ; metabolism ; mortality ; Survival Rate