OBJECTIVETo study the constituents with the pain-relieving activity from the stem rind of Daphne giraldii.

METHODThe partition of the ethanol extract and chromatographic separation of the fractions were carried out by the monitoring of anelgesic pharmacological activity. The structures of the isolated compounds were determined by MS and NMR.

RESULTFour compounds were isolated from the pain-relieving fraction. Three of them were identified as diterpenes, gniditrin (1), gnidicin (2) and daphnetoxin (3). Compound 4 was determined as Z-octadecyl caffeate.

CONCLUSIONCompounds 1, 2 and 4 were isolated from the plant for the first time.

Analgesics ; chemistry ; isolation & purification ; pharmacology ; Caffeic Acids ; chemistry ; isolation & purification ; pharmacology ; Daphne ; chemistry ; Diterpenes ; chemistry ; isolation & purification ; pharmacology ; Heterocyclic Compounds, 4 or More Rings ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

Aim To study the effect of the total flavonoids of turpinia arguta seen (TFS) on immune function of rats with adjuvant arthritis. Methods Adjuvant arthritis (AA) was induced on d0 by intradermal injection of Complete Freund′s Adjuvant (FCA), containing 10 mg heat-inactive BCG in 1ml paraffin oil. On d 28 after immunization, AA rats were killed by cervical decollation. Immune cells (splenocytes and peritoneal macrophages) were obtained, then cultured in vitro with TFS. Some immune indexes were detected respectively such as the splenocytes proliferation and the productions of IL-1 and IL-2 were measured by the method of cell proliferation, the production of prostaglandin E2 was determined by radioimmunoassay. Results Compared with normal groups, the response of splenocytes to ConA and LPS was lowered, IL-2 syn-thesis was decreased, and IL-1 and PGE_2 released from PM? were elevated. TFS (10~ -8 ~10~ -4 mg?L~ -1 ) not only increased splenocytes proliferation, which induced by ConA and LPS, and IL-2 production of splenocytes, but also reduced the elevated productions of IL-1 and PGE_2 released from peritoned macrophate in AA rats in vitro. Conculsion TFS could adjust abnormal immune function in AA rats.

OBJECTIVEX-linked adrenoleukodystrophy (ALD) is a genetically determined disorder that involves the nervous system white matter, axons, adrenal cortex and testes. The typical clinical manifestations are progressive psychomotor regression, vision and/or auditory impairment and adrenal insufficiency. The clinical manifestation, biochemical change and genetic counseling work of X-linked ALD were analyzed.

METHODSThe clinical features of 29 cases with ALD were summarized and analyzed, including symptoms and signs, measurement of blood very long chain fatty acids (VLCFA), adrenal function, cranial magnetic resonance imaging (MRI) and pedigree investigation.

RESULTSAmong these 29 cases, the clinical phenotype could be classified into childhood cerebral (22 cases), adolescent cerebral (4 cases), adrenomyeloneuropathic (1 case), Addison's disease (1 case) and asymptomatic or presymptomatic (1 case) types. Nine of them had positive family history. Pedigree investigation was consistent with typical sex-linked recessive inheritance. There were 45 ALD patients in these 29 pedigrees. The neurological manifestations varied among members of the same family. Nine cases died during follow up. The causes of death were central respiratory failure or other complications of ALD and so on. Laboratory tests demonstrated abnormally high plasma levels of VLCFA in ALD patients; MRI demonstrated symmetric butterfly-like low T(1) and high T(2) signals in the parieto-occipital white matter. The impairment in the splenium of corpus callosum made the bilateral lesion region converge into one. It could progress anteriorly and injure the bilateral posterior limb of internal capsule and the temporal lobe, and could injure the brainstem inferiorly. Following intravenous injection of contrast material, thin stripe of lacelike enhancement could be observed.

CONCLUSIONSThe atypical initial symptom of ALD was seizures. The MRI showed abnormal signal in the cerebellar white matter. This disease can influence the normal development of children, this was more pronounced in the childhood cerebral ALD type. It tended to progress rapidly with dementia, vegetative state or death. Since antenatal diagnostic method is available now, emphasis should be made on the antenatal examination in order to make an early diagnosis and abort pregnancy if necessary.

Adolescent ; Adrenoleukodystrophy ; blood ; diagnosis ; therapy ; Child ; Child, Preschool ; China ; Fatty Acids ; blood ; Female ; Follow-Up Studies ; Humans ; Male ; Pedigree ; Treatment Outcome

OBJECTIVETo investigate clinicopathological and immunohistochemical features of 31 cases of oral teratoid cyst.

METHODSThirty-one cases of oral teratoid cyst according with Meyer's diagnosis criteria were retrospectively studied and their histochemistry and immunohistochemistry were performed from the files of Department of Pathology, School of Stomatology, Wuhan University between 1963 and 2003.

RESULTSTwenty-seven cases (87.10%) were children, and twenty-four cases were congenital. The ratio of male-to-female was 1:0.55, and the affected sites were floor of mouth (22 cases) and tongue (8 cases). Clinical findings were nonspecific, and prognosis was good following complete excision. Histology indicated that squamous, respiratory and/or gastrointestinal epithelium consistiuted basic structure of teratoid cyst in addition to simple cuboidal epithelium in 8 cases. Antibody against AE1/AE3 was strongly expressed and CK16 was weak in four types of epithelial lining of oral teratoid cyst. Expression of AE1, CK7, 8/18, 19 varied in superficial, suprabasal and basal cells of squamous epithelium but were strong in respiratory, gastrointestinal and simple columnar epithelium; only gastrointestinal epithelium expressed CK20 heterogeneously.

CONCLUSIONSOral teratoid cyst showed the highest incidence in children, and floor of mouth and tongue were mostly affected sites. Features of histology were complex, and immunohistochemistry indicated that epithelium of oral teratoid cyst shared similar patterns of cytokeratin with counterpart of normal tissues, showing different origin and differentiation of epithelial lining of the present cyst.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry ; Infant ; Keratins ; metabolism ; Male ; Mouth Neoplasms ; metabolism ; pathology ; Retrospective Studies ; Teratoma ; metabolism ; pathology ; Young Adult

Objective To study the mechanism of organic anion trans-porting polypeptide1B1 (OATP1B1) and cytochrome P2C9 (CYP2C9 ) genetic polymorphism effect on the metabolism and transport of fluvasta-tin.Methods Build OATP1B1*1a,*5and*15 recombinant plasmid model and CYP2C9*1,*3 recombinant enzyme model to compare up-take and enzymatic kinetic parameters of fluvastatin in different models.Results The fluvastatin intake of OATP1B1*5 gene, OATP1B1*15 gene, OATP1B1*1a gene are ( 3.27 ±0.53 ), ( 6.88 ±2.01 ), (6.32 ±1.23 ) pmol· min-1· mg-1 protein.Compared with OATP1B1*1a, OATP1 B1*5 reduces the transport capacity of fluvastatin ( P <0.05 ) and OATP1B1*15 gene increases (P<0.05).The CLintof CYP2C9*3 and CYP2 C9*1 metabolizing fluvastatin are 0.42 , 1.25 ( P<0.05 ).The activities of CYP2C9*3 are lower than CYP2C9*1.Conclusion The OATP1B1 521 site and the CYP2C9 359 site might be the molecular action site of transport fluvastatin.Therefore , more attention should be payed in clinical applications to prevent damage caused by OATP 1B1 and CYP3A4 genetic polymorphism.

Objective: The current study was designed to observe the clinical results of late course accelerated hyperfractionation(LCAH) radiotherapy in Stage I- II nasopharyngeal carcinoma(NPC) patients. Methods: A total of 108 patients with Stage I- II NPC were divided at random into two groups: conventional fractionation(CF) and LCAH, The patients in CF group received a fraction of 2 Gy daily, 5 days per week, to total dose of 70 Gy/7weeks. The patients in LCAH group were treated with the same fractionation as CF group to dose of 36- 40 Gy, and followed by late course accelerated hyperfractionation radiotherapy: 1.5 Gy, twice daily, with the interval of 6 hours between fractions, to total dose of 69 Gy/6weeks. Results: The complete response rate in the nasopharynx was 89.47％ in the LCAHR and 70.97％ in the CFR at the end of the course (P=0.05). Disappeared rate of cervical lesion was not significant different between two groups (P >0.05). The survival rates of 1, 2, and 3-year were 98.13％ ,93.95％ ,90.87％ in the LCAH and 96.12％ ,80.97％ ,78.55％ in the CF, respectively (P=0.06). There was no significant difference in radiation reaction and sequela between two groups( P >0.05) . Conclusion: The clinical results of LCAH radiotherapy in Stage I- II NPC may be better than conventional fractionation radiotherapy, is worth further study.

OBJECTIVETo investigate the resection range of mesorectum and rectum below the inferior margin of tumor for the total mesorectum excision (TME) in middle-low rectal cancer.

METHODSSixty patients were enrolled in the study. After TME operation, serial 5 mm interval sections were made in specimens of middle-low rectal cancer. The retrograde metastasis of rectal cancer was observed by routine HE staining.

RESULTSThe phenomena of retrograde metastasis in mesorectum were found in 15 cases, and the distance of retrograde metastasis was 0.5-4.0(2.47+/-1.06) cm, which was correlated with Dukes stage, lymph node metastasis and histological differentiation. The retrograde metastases in bowel were found in 11 cases, and the distance of retrograde metastasis was 0.5-4.0 (1.64+/-1.16) cm, which was correlated with histological differentiation.

CONCLUSIONSThe distal mesorectum should be resected at least 4 cm when TME is carried out, and the distal bowel at least 2.5 cm. More than 5 cm mesorectum and bowel should be resected when advanced Dukes stage, extensive lymph node metastasis and poor histological differentiation occurred.

Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Rectal Neoplasms ; pathology ; Rectum ; pathology

Atropa belladonna L. is the officially medicinal plant species and the main commercial source of scopolamine and hyoscyamine in China. In this study, we reported the simultaneous overexpression of two functional genes involved in biosynthesis of scopolamine, which respectively encoded the upstream key enzyme putrescine N-methyltransferase (PMT; EC 2.1.1.53) and the downstream key enzyme hyoscyamine 6beta-hydroxylase (H6H; EC 1.14.11.11) in transgenic hair root cultures of Atropa belladonna L. HPLC results suggested that four transgenic hair root lines produced higher content of scopolamine at different levels compared with nontransgenic hair root cultures. And scopolamine content increased to 8.2 fold in transgenic line PH2 compared with that of control line; and the other four transgenic lines showed an increase of scopolamine compared with the control. Two of the transgenic hair root lines produced higher levels of tropane alkaloids, and the content increased to 2.7 fold in transgenic line PH2 compared with the control. The gene expression profile indicated that both PMT and H6H expressed at a different levels in different transgenic hair root lines, which would be helpful for biosynthesis of scopolamine. Our studies suggested that overexpression of A. belladonna endogenous genes PMT and H6H could enhance tropane alkaloid biosynthesis.
Atropa belladonna ; enzymology ; genetics ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; Hyoscyamine ; metabolism ; Methyltransferases ; genetics ; metabolism ; Mixed Function Oxygenases ; genetics ; metabolism ; Plant Roots ; enzymology ; genetics ; Plants, Genetically Modified ; enzymology ; genetics ; Plants, Medicinal ; enzymology ; genetics ; Scopolamine Hydrobromide ; metabolism ; Synthetic Biology ; Tropanes ; metabolism

OBJECTIVETo study the clinicopathologic and immunohistochemical features, biological behavior, diagnosis and treatment of solid pseudopapillary tumor of the pancreas (SPTP).

METHODSA retrospective clinical and clinicopathologic analysis was made on 33 cases of SPTP admitted from May 2001 to 2010 July. There were 7 male and 26 female patients, aging from 13 to 66 years with a mean of 34.3 years.

RESULTSThe tumor was located in pancreatic head of 10 patients, in pancreatic neck of 5 patients, in pancreatic body and tail of 18 patients. Of the 33 patients treated with surgery, 8 underwent simple resection of pancreatic tumor, 6 underwent pancreaticoduodenectomy, 3 underwent tumor resection plus pancreaticojejunostomy, 1 underwent tumor resection plus pancreaticogastrostomy, 11 underwent distal pancreatectomy, 4 underwent distal pancreatectomy plus spleen resection (1 underwent mesohepatectomy for hepatic metastasis). Sixteen of the 33 operations were completed by laparoscopy. Histologically, tumors were composed of papillary and microcystic solid structures, with uniformed population of cells. The pancreas and blood vessels invasion were identified in 3 cases, one of them was combined with liver metastasis, and they are male. Immunohistologically, the tumors were positive for α1-antitrypsin, α1-antichymotrypsin, β-catenin, CD10, CD56 and vimentin (all cases), neuron-specific enolase (3 cases), synaptophysin (6 cases), chromogranin A (4 cases), progesterone receptor (28 cases), estrogen receptor (3 cases), S-100 (6 cases). Totally 33 cases were followed up with a median period of 49 months without tumor recurrence.

CONCLUSIONSSPTP is of low graded malignancy. It primarily affects young women. It may be located in any part of pancreas. Immunohistochemistry is very important for the diagnosis and differential diagnosis of SPTP. Surgical resection is recommended as the treatment of choice. Laparoscopic distal pancreatectomy or tumor resection is feasible and safe for some selected patients, and the prognosis is good.

Adolescent ; Adult ; Aged ; Carcinoma, Papillary ; diagnosis ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; diagnosis ; pathology ; surgery ; Retrospective Studies ; Young Adult

As an extension of the structure-based drug discovery, fragment-based drug discovery is matured increasingly, and plays an important role in drug development. Fragments in a small library, with lower molecular mass and high "ligand efficiency", are detected by SPR, MS, NMR, X-ray crystallography technologies and other biophysical methods. Then they are considered as starting points for chemical optimization with the guidance of structural biology methods to get good "drug-like" lead and candidate compounds. In this article, we reviewed the current progress of fragment-based drug discovery and detailed a number of examples to illustrate the novel strategies.
Computer-Aided Design ; Crystallography, X-Ray ; Drug Discovery ; methods ; Ligands ; Magnetic Resonance Spectroscopy ; Peptide Fragments ; chemical synthesis ; chemistry ; Protein Conformation ; Small Molecule Libraries ; Surface Plasmon Resonance