AIMTo develop a new synthetic route for olmesartan medoxomil.

METHODSOlmesartan medoxomil was prepared from ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate via hydrolysis and lactonization to afford 4,4- dimethyl-2-propyl-4,6-dihydrofuro [3,4-d]-1H-imidazole-6-one which was condensed with 2-(triphenylmethyl)-5-[4'-(bromomethylbiphenyl)-2-yl] tetrazole, followed by esterification with 4-chloromethyl-5-methyl-1,3-dioxol-2-one, and deprotection. The chemical structure of the major impurity in condensation reaction is the regio-isomer in the imidazole moiety, and confirmed by single crystal X-ray diffraction. The corresponding regio-isomer of olmesartan medoxomil was synthesized from the impurity by similar method. Optimization of the condensation conditions reduced the impurity to a negligible quantity.

RESULTSSynthesis of olmesartan medoxomil by the new route gave a product of 60% yield and above 99.0% purity. The content of olmesartan medoxomil regio-isomer was effectively controlled to less than 0.1%.

CONCLUSIONA novel synthetic route for olmesartan medoxomil was developed successfully. The olmesartan medoxomil regio-isomer is reported for the first time.

Angiotensin II Type 1 Receptor Blockers ; chemical synthesis ; chemistry ; Animals ; Antihypertensive Agents ; chemical synthesis ; chemistry ; pharmacology ; Blood Pressure ; drug effects ; Imidazoles ; chemical synthesis ; chemistry ; pharmacology ; Molecular Structure ; Olmesartan Medoxomil ; Rats ; Stereoisomerism ; Tetrazoles ; chemical synthesis ; chemistry ; pharmacology

Hematopoietic progenitor kinase 1 ( HPK1 ) , also known as MAP4K1 , is a serine/threonine protein kinase and a member of the MAP4K family of mammalian Ste20-related pro¬tein kinases.Recent studies have found that HPK1 is assoeiated with the occurrence and progression of a variety of tumors, and may play an important role in some malignant tumors.This pa¬ per reviews the HPK1 signaling pathway, its relationship with tumor and drug development progress, so as to provide referenee for the research of HPK1 protein kinase.

OBJECTIVETo analyze the molecular characteristics of the newly isolated two Japanese encephalitis virus strains (JEV) in Wuhan.

METHODSThe mosquitoes were collected in Wuhan from April to October in 2009. The envelope (E) protein gene of JEV was detected using RT-PCR and sequenced. Sequence comparisons and phylogenetic analysis were conducted using DNAstar and MegAlign.

RESULTSTwo Japanese encephalitis virus (JEV) strains (WHJX09-9, WHJX09-10) were isolated from Culex tritaeniorhynchus among 16 mosquito pools and identified as genotype I. The result showed that the homology of the two strains was 98. 9% in nucleotides and 100% in deduced amines. The comparison between the new genotype 1 JEV strains and live attenuated vaccine strain SA14-14-2 in E gene showed that the homology of nucleotide sequence was 87.4% and 87.9%, the homology of amino acid was 96.9% (total 15 amino acid were different) in E gene. The mutation sites of amino acid distributed among three different coding domain, but no antigen binding site and neurotoxin-involved site of amino acid were changed.

CONCLUSIONWuhan had appeared a new genotype of JEV which was different from the former strain isolated in Wuhan, the new JEV strains still had neurotoxicity but had high homology with the vaccine strains adopted in Wuhan. The vaccine could still be adopted to prevent Japanese encephalitis if steps were take to eradicate mosquitos at the same time. laboratory surveillance were also an important task to build an early-warning mechanism against JEV.

Amino Acid Sequence ; Animals ; Cell Line ; China ; Culicidae ; virology ; Encephalitis Virus, Japanese ; chemistry ; classification ; genetics ; isolation & purification ; Genotype ; Insect Vectors ; virology ; Molecular Sequence Data ; Phylogeny ; Sequence Alignment ; Viral Envelope Proteins ; chemistry ; genetics

OBJECTIVETo compare the therapeutic effect and indication between standard large trauma craniotomy and routine craniotomy.

METHODSThere were 97 patients in the standard large trauma craniotomy group and 110 patients in the routine craniotomy group. The mortality, postoperative ICP (intracranial pressure), ratio of pupil rebound, complication and results of six month follow-up after operation were compared between the two groups.

RESULTSFifteen patients (15.6%) died in the standard large trauma craniotomy group and 30 (27.7%) in the routine craniotomy group. The postoperative mean ICP was 3.75 kPa+/-1.89 kPa in the standard large trauma craniotomy group and 5.11 kPa+/-1.57 kPa in the routine craniotomy group. The pupil rebound was found in 47 patients (61.0%) in the standard large trauma craniotomy group and in 41 patients (46.1%) in the routine craniotomy group (P<0.01). The rate of complication was lower in the standard large trauma craniotomy group, but no obvious difference in long-term therapeutic effect was found between the two groups.

CONCLUSIONSStandard large trauma craniotomy can attenuate brain hernia and the mortality of the patients with acute subdural hematoma. The incidence of complication can also be decreased. But the long term life quality of the patients can not be improved.

Acute Disease ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Chi-Square Distribution ; Craniotomy ; standards ; Female ; Follow-Up Studies ; Hematoma, Subdural ; mortality ; surgery ; Humans ; Intracranial Pressure ; Male ; Middle Aged ; Quality of Life ; Treatment Outcome

OBJECTIVETo present a new neurovascular island flap for fingertip reconstruction.

METHODSBased on the transverse palmar branch of the digital artery, this flap was designed on the volar side of a digit and reversed to repair the fingertip defects.

RESULTS12 fingers in 11 patients were reconstructed using this flap. Of them, 11 flaps survived and one necrosed. The contour of the reconstructed fingers looked well.

CONCLUSIONThis new neurovascular island flap provides excellent padding and sensation for fingertip reconstruction. The technique is simple.

Adolescent ; Adult ; Female ; Finger Injuries ; surgery ; Fingers ; blood supply ; surgery ; Humans ; Male ; Middle Aged ; Reconstructive Surgical Procedures ; methods ; Skin Transplantation ; Surgical Flaps ; blood supply ; Young Adult

To investigate the influence of Anxin granules combined with tirofiban on acute myocardial infarction (AMI) Patients after elective percutaneous coronary intervention (PCI). One hundred and twenty AMI patients were randomly divided into treatment group and control group. The patients in the two groups were all given Tirofiban 30mins before PCI . The treatment group was added Anxin granules 30 mins before and after PCI. Tissue factor (TF) and von willebrand factor (vWF) were tested at 6 hours after operation. Syndromatology alteration of traditional Chinese medicine (TCM) and bleeding complications were observed at 4 weeks after operation. Both TF and vWF at 6 hours after operation of the treatment group was lower than the control group significantly (P < 0.01), while the condition of myocardial ischemia at 90 mins after operation of the treatment group was better than control group with significance. The syndromatology alteration of TCM especially spontaneous perspiration and hypodynamia of the treatment group were improved significantly compared to control group 4 weeks after operation. All patients in both groups had no bleeding complications and thrombopenia. The study suggests that Anxin granules combined with tirofiba can improve the clinical efficacy and the endothelial function of AMI patients after PCI with no increase in bleeding events.
Aged ; Angioplasty, Balloon, Coronary ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Middle Aged ; Myocardial Infarction ; complications ; metabolism ; surgery ; Postoperative Hemorrhage ; drug therapy ; etiology ; metabolism ; prevention & control ; Thromboplastin ; metabolism ; von Willebrand Factor ; metabolism

OBJECTIVETo study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China.

METHODSThe mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members.

RESULTSThirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents.

CONCLUSIONThe mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

Asian Continental Ancestry Group ; genetics ; China ; epidemiology ; DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Diabetes Mellitus ; genetics ; Genetic Testing ; Hearing Loss, Sensorineural ; genetics ; Humans ; Insulin Resistance ; genetics ; Molecular Sequence Data ; Mutation ; Prevalence ; RNA, Transfer, Amino Acyl ; genetics

Adolescent ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged

OBJECTIVETo evaluate the occurrence and management of complications following minimally invasive percutaneous nephrolithotomy (MPCNL).

METHODSThe data of 4326 cases of MPCNL from January 2001 to February 2006 were reviewed, including 2451 male cases and 1875 female cases. Their age ranged from 4 to 82 years with a mean of 42 years. Of 4326 cases, 1221 cases had simple nephrolithiasis, 1735 staghorn nephrolithiasis, 386 upper ureterolithiasis, 90 serious stone street after extracorporeal shock wave lithotripsy, and 894 residual calculi after open surgery.

RESULTSAmong the 4326 cases of MPCNL, complications occurred in 445 cases (10.3%). Of the 445 cases, 20 had massive hemorrhage, 13 pleural injuries, 1 colonic perforation, 343 fever attacks (T > 38 degrees C), 13 septic shocks, 16 perinephric urinoma, 9 perinephric abscess, 26 renal perforating injuries, 1 guide wire misled into inferior vena cava, 3 died.

CONCLUSIONSMPCNL is a minimally invasive operation. However, serious complications would occur if the procedure were ignored. The improvement in the prevention and management of complications can promote the application of this procedure.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Kidney Calculi ; surgery ; Male ; Middle Aged ; Nephrostomy, Percutaneous ; adverse effects ; methods ; Postoperative Complications ; prevention & control ; therapy ; Ureteral Calculi ; surgery

OBJECTIVETo investigate the genetic and clinical features of mutations and sequence variations of the transcription factor 1 gene (TCF1, HNF-1A) in Chinese with familial early-onset and/or multiplex diabetes mellitus.

METHODSAll ten exons of the TCF1 gene were screened, including exon and intron junctions, by direct sequencing method in 341 unrelated Chinese subjects, including 80 healthy controls and 261 probands of early-onset and/or multiplex diabetes pedigrees.

RESULTSFive mutations were found in all. Four of the 5 different TCF1 mutations were newly identified novel mutations(T82M, Q130H, G253G, P353fsdelACGGGCCTGGAGC), mean body mass index of mutation carriers was 21.9 kg/m (2), and insulin secretion was impaired in the mutation carriers. In this study, the maturity-onset diabetes of the young type III (MODY3) only accounted for 3% of Chinese early-onset diabetes. Moreover, eleven substitutions were identified in 261 probands. Of them, three variants IVS1-8 (G-->A), IVS1 -128 (T-->G ) and IVS2+21 (G-->A) were not observed in 80 healthy controls and one of them IVS1-8 (G-->A) was not reported previously and the two promoter variants co-segregated with diabetes.

CONCLUSIONTCF1 gene is not a common cause of early-onset and/or multiplex diabetes among Chinese patients.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Diabetes Mellitus ; ethnology ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Hepatocyte Nuclear Factor 1-alpha ; genetics ; Humans ; Male ; Mutation ; Polymerase Chain Reaction