Recently traditional Chinese medicine (TCM)-induced liver injury has been an unresolved critical issue which impacts TCM clinical safety. The premise and key step to reduce or avoid drug-induced liver injury (DILI) is to identify the drug source of liver injury in early stage. Then the timely withdrawal of drug and treatment can be done. However, the current diagnosis of DILI is primarily governed by exclusive method relying on administering history supplied by patients and experience judgment from doctors, which lacks objective and reliable diagnostic indices. It is obvious that diagnosis of TCM-induced liver injury is especially difficult due to the complicated composition of TCM medication, as well the frequent combination of Chinese and Western drugs in clinic. In this paper, we proposed construction of research pattern and method for objective identification of TCM-related DILI based on translational toxicology, which utilizes clinical specimen to find specific biomarkers and characteristic blood-entering constituents, as well the clinical biochemistry and liver biopsy. With integration of diagnosis marker database, bibliographic database, medical record database and clinical specimen database, an integrative diagnosis database for TCM-related DILI can be established, which would make a transformation of clinical identification pattern for TCM-induced liver injury from subjective and exclusive to objective and index-supporting mode. This would be helpful to improve rational uses of TCM and promote sustainable development of TCM industry.
Animals ; Biomarkers, Pharmacological ; metabolism ; Biopsy ; methods ; Chemical and Drug Induced Liver Injury ; diagnosis ; metabolism ; pathology ; Early Diagnosis ; Humans ; Liver ; drug effects ; pathology ; Medicine, Chinese Traditional ; adverse effects ; Rats

The aim of this Post-Marketing Surveillance study was to assess efficacy,safety and acceptance of acarbose treatment in Chinese type 2 diabetic patients under day-to-day practice conditions.A total of 2 480 patients were enrolled by 231 physicians throughout China into an open,prospective,uncontrolled,non- randomised,multi-centre study.Main efficacy parameters were the changes in fasting and postprandial blood glucose concentrations as well as in HbA-(1C) levels after acarbose treatment.The majority of patients had been previously treated with other oral anti-diabetic medication or insulin and received concomitant anti-diabetics during the mean observation period of 13.5 weeks.Most patients started on a daily acarbose dose of 50 mg t.i.d. Acarbose treatment reduced fasting blood glucose concentrations by 56.1 mg/dl ( 18 mg/dl glucose = 1 mmol/L glucose) and 2h-postprandial values by 111.3 mg/dl over the study period.HbA-(1C) decreased by 1.9% and body weight by 0.9 kg.76 acarbose-relatod adverse events occurred;two patients experienced serious adverse events. The attending physicians assessed treatment efficacy as“very good”or“good”for 90.1% of the patients, tolcrability for 89.1% and acarbose acceptance for 87.1% of the patients.Acarbose is efficacious,safe and well accepted by Chinese type 2 diabetic patients under day-to-day routine conditions,both as anti-diabetic mono- therapy and in combination with other anti-dlabetic drugs.

OBJECTIVE: To observe the effect of intrathecal injection of ketamine and clonidine for chronic constriction injury (CCI) in rats. METHODS: Thirty-two SD male rats weighing 220-280 g were anesthetized with intraperitoneal chloral hydrate 300 mg/kg. A catheter was implanted in the subarachnoid space at the lumbal region and CCI rat models were made successfully. On the 4th day after the surgery, the rats were randomly divided into 4 group: a control group,injecting 0.9%NS 20 microL intrathecally; a ketamine group, injecting ketamine 1 mg/kg(20 microL) intrathecally; a clonidine group (CL), injecting clonidine 20 microg/kg (20 microL) intrathecally; a combined ketamine and clonidine group, injecting ketamine 0.5mg/kg and clonidine 10 g/kg (20 microL) intrathecally, once a day for 1 week. BME-410A Plantar Analgesia Tester was used to measured pain threshold before the administration and 30 min after the administration. The rats were killed after the test was finished. And then we detected the nitric oxide synthase (NOS) activity and the NO production in the spinal cord. RESULTS: The combined injection of ketamine (0.5mg/kg)and clonidine(10 g/kg) produced significantly more potent analgesia than the injection of ketamine (1 mg/ kg) or clonidine (20 microg/ kg)alone. The NOS activity and the production of NO in the combined injection group were significantly lower than those of the single injection group (P<0.05). The weight of rats post-administration increased obviously in the 4 groups (P<0.05). CONCLUSION The combined injection of ketamine and clonidine can produce synergistic ab-irritation without obvious side effects.
Analgesics ; administration & dosage ; adverse effects ; therapeutic use ; Animals ; Clonidine ; administration & dosage ; adverse effects ; therapeutic use ; Drug Combinations ; Injections, Spinal ; Ketamine ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Neuralgia ; drug therapy ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism

Objective To investigate the differences in the clinical symptoms and magnetic resonance imaging (MPd) findings of the spinal cord lesions between patients with neuromyelitis optica (NMO) and multiple sclerosis (MS) and explore the mechanisms that result in these differences. Methods The clinical symptoms and MRI findings of the spinal cord were retrospectively analyzed in 21 MS patients and 23 NMO patients admitted in the Third Affiliated Hospital of Sun Yat-Sen University from January, 2004 to January, 2007. Results Female patients were more frequently affected by NMO, and the NMO patients had a older mean age at onset with higher Expanded Disability Status Scale (EDSS) score than the MS patients. Chi-square test showed significant differences in the rotes of bilateral deep sensory dysfunction, zonesthesia, and sphincter disturbance between the NMO and MS patients (P<0.05). The majority of these clinical symptoms were found to result form corresponding spinal cord lesions defined by MRI. Conclusion NMO is a demyelinating disease that represents an independent clinical entity from MS, and has special mechanisms responsible for its characteristic clinical symptoms and MRI findings of the spinal cord.

AIMTo investigate the chemical constituents from Picria fel-terrae Lour.

METHODSColumn chromatography techniques were used to isolate the chemical constituents, physico-chemical constants and spectroscopic analysis were employed for structural elucidation. Results Two triterpenoids named picfeltarraenone I (1) and picfeltarraenin XI (2) were isolated, and their structures were established to be 3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5,23-diene (1) and 3,11,22-trioxo-16alpha-hydroxy-(20S,24)-epoxy-cucurbit-5, 23-diene-2beta-O-beta-D-glucopyranoside (2), respectively.

CONCLUSIONCompound 2 is a new compound, the 13CNMR data of compound 1 is reported for the first

Glucosides ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plants, Medicinal ; chemistry ; Scrophulariaceae ; chemistry ; Triterpenes ; chemistry ; isolation & purification

OBJECTIVETo investigate the relation of the viral markers in serum and those expressed by hepatocytes to pathological lesions of hepatic tissue in patients with chronic hepatitis B.

METHODSThe relation of viral markers including HBsAg, HBsAb, HBeAg, HBeAb, HBcAb and HBV DNA in serum of 647 patients with chronic hepatitis B and HBsAg, HBcAg expressed by hepatocytes in 418 of these patients to pathological lesions of hepatic tissue was determined.

RESULTSViral markers in serum and those expressed by hepatocytes in patients with chronic hepatitis B were closely correlated with pathological lesions of hepatic tissue.

CONCLUSIONThe degree of inflammation and fibrosis in hepatic tissue is milder in serum HBsAg, HBeAb, HBcAb positive and HBV DNA negative patients but more serious in those with negative hepatocytic expression of HBsAg and HBcAg. HBV DNA is not significantly associated with pathological lesions of hepatic tissue.

Adolescent ; Adult ; Child ; Child, Preschool ; DNA, Viral ; blood ; genetics ; Female ; Hepatitis B Core Antigens ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; immunology ; physiology ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Infant ; Infant, Newborn ; Liver ; pathology ; virology ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study the clinicopathologic features and biologic behavior of pediatric immature teratoma.

METHODSThe clinical data, pathologic features, immunohistochemical findings (for cyclin D1, P27 and Ki-67) and follow-up information of 39 cases of pediatric immature teratoma were analyzed.

RESULTSAmongst the 39 cases studied, 12 arose in the sacrococcygeal region, 12 in testis, 5 in retroperitoneum, 4 in ovary, 4 in abdomen and 2 in mediastinum. Histologically, 16 cases were of grade 1, 8 cases of grade 2 and 15 cases of grade 3. Seven of the cases contained foci of yolk sac tumor. Immature neuroepithelial features used in histologic grading included the presence of primitive neural tubules, immature rosettes, undifferentiated neuroblastoma cells and primitive neuroectodermal structures. Immunohistochemical study showed that cyclin D1 was positive in 3 cases of grade 1 tumors, 4 cases of grade 2 tumors and 9 cases of grade 3 tumors. The positivity rates for p27 were 8, 3 and 6 cases respectively, while those for Ki-67 were 3, 4 and 13 cases respectively. Follow-up data were available in 30 cases. Three of them, including 2 cases with histologic grade 3 (with or without yolk sac tumor component), recurred after operation.

CONCLUSIONSThe expression of cyclin D1 and Ki-67 is a useful adjunct in histologic grading. On the other hand, p27 overexpression shows little correlation with tumor grade. The prognosis of immature teratoma in children is different from that in adults. Sacrococcygeal immature teratoma occurring in patients younger than 1 year old and with low histologic grade do not require postoperative chemotherapy if the tumor is completely excised. Similarly, for testicular immature teratoma occurring in patients below 1 year of age, regardless of tumor grading, need no adjunctive therapy. On the other hand, ovarian immature teratoma with high histologic grade requires postoperative chemotherapy, regardless of age of the patients. The presence of microscopic foci of yolk sac tumor is a useful predictor of recurrence in pediatric immature teratoma.

Adolescent ; Cyclin D1 ; metabolism ; Endodermal Sinus Tumor ; drug therapy ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; Ki-67 Antigen ; metabolism ; Male ; Mediastinal Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Ovarian Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Proliferating Cell Nuclear Antigen ; metabolism ; Retroperitoneal Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Sacrococcygeal Region ; Survival Rate ; Teratoma ; drug therapy ; metabolism ; pathology ; surgery ; Testicular Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; alpha-Fetoproteins ; metabolism

AIMTo separate and identify the chemical constituents of the aril of Torreya grandis cv. Merrilli.

METHODSThree lignins were isolated by chromatography and their chemical structures were elucidated by IR, EI-MS, 1HNMR, 13CNMR, DEPT and 2D-NMR spectral methods.

RESULTSThree lignins were identified as pinonesinol, dihydrodehydrodiconiferylalcohol and (7,8-cis-8,8'-trans)-2',4'dihydroxyl-3, 5-dimethoxy-lariciresinol.

CONCLUSIONThese compounds were isolated from this plant for the first time, and compound III is a new compound.

Fruit ; chemistry ; Furans ; chemistry ; isolation & purification ; Lignin ; analogs & derivatives ; chemistry ; isolation & purification ; Molecular Conformation ; Molecular Structure ; Plants, Medicinal ; chemistry ; Taxaceae ; chemistry

BACKGROUNDThe failure of hormone treatment for advanced prostate cancer might be related to aberrant activation of the androgen receptor. We have shown that (125)I labeled triple-helix forming oligonucleotide (TFO) against the androgen receptor gene inhibits androgen receptor expression and cell proliferation of LNCaP prostate cancer cells in vitro. This study aimed at exploring the effects of the (125)I-TFO on prostate tumor growth in vivo using a nude mouse xenograft model.

METHODSTFO was labeled with (125)I by the iodogen method. Thirty-two nude mice bearing LNCaP xenograft tumors were randomized into 4 groups and were intratumorally injected with (125)I-TFO, unlabeled TFO, Na(125)I and normal saline. Tumor size was measured weekly. The tumor growth inhibition rate (RI) was calculated by measurement of tumor weight. The expression of the androgen receptor gene was performed by RT-PCR and immunohistochemical study. The prostate specific antigen (PSA) serum levels were measured by enzyme linked immunosorbent assay. The tumor cell apoptosis index (AI) was detected by TUNEL assay.

RESULTSTumor measurements showed that tumor development was significantly inhibited by either (125)I-TFO or TFO, with tumor RIs of 50.79% and 32.80% respectively. (125)I-TFO caused greater inhibition of androgen receptor expression and higher AIs in tumor tissue than TFO. Both the tumor weight and the PSA serum levels in (125)I-TFO treated mice ((0.93 +/- 0.15) g and (17.43 +/- 1.85) ng/ml, respectively) were significantly lower than those ((1.27 +/- 0.21) g and (28.25 +/- 3.41) ng/ml, respectively) in TFO treated mice (all P < 0.05). Na(125)I did not significantly affect tumor growth and androgen receptor expression in tumor tissue.

CONCLUSIONSThe (125)I-TFO can effectively inhibit androgen receptor expression and tumor growth of human prostate cancer xenografts in vivo. The inhibitory efficacy of (125)I-TFO is more potent than that of TFO, providing a reference for future studies of antigen radiotherapy.

Androgen Receptor Antagonists ; Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunohistochemistry ; Iodine Radioisotopes ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oligonucleotides ; chemistry ; pharmacology ; therapeutic use ; Prostate-Specific Antigen ; blood ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology ; Receptors, Androgen ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays ; methods

OBJECTIVETo study the clinical significance of abnormal protein bands (APB) in multiple myeloma (MM) patients treated with bortezomib-based induction regimen and autologous stem cell transplantation (ASCT).

METHODSSixty-eight MM patients submitted to bortezomib-based induction therapy and ASCT from January 2007 to July 2012 were retrospectively studied. Monoclonal protein was detected by immunofixation electrophoresis (IFE).

RESULTSOf all 68 patients, 33 (48.5%) patients had APB. At the first emergence of an APB, two patients with light chain type achieved CR and before transplantation, and thirty-one patients were after transplantation with median time of 104 (ranged 33-404) days. The median duration of APB appearance was 105 (ranged 35-801) days. Patients who developed APB compared with those without APB, had a significantly higher CR plus very good partial response (VGPR) rates (100.0% vs 85.7%%, P=0.017) and CR rates (87.9% vs 62.9%) (P=0.03). There were no significant differences in gender, age, HGB, ALB, β2-microglobulin, M protein type, Durie-Salmon and ISS stages, the case number of first line or second line treatment, induction courses of bortezomib-based regimen, and the mode of ASCT. With a median follow-up of 33.4 (ranged 7.0-71.7) months, patients with APB tended to have a longer overall survival (OS) versus non-APB patients, although no significant difference obtained (P＞0.05). Among APB patients, OS was longer in patients whose appearance of APB occurred ＜6 months after transplantation than those ≥ 6 months, but the significant difference was not obtained yet (P＞0.05).

CONCLUSIONSPatients who developed APB had a significantly better response to bortezomib-based induction regimen followed ASCT. APB emergence has a good prognostic significance.

Adult ; Aged ; Boronic Acids ; therapeutic use ; Bortezomib ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; metabolism ; therapy ; Myeloma Proteins ; metabolism ; Prognosis ; Pyrazines ; therapeutic use ; Retrospective Studies ; Transplantation, Autologous