OBJECTIVE: To design and synthesize N-hydroxy-5-(3-substituted urea)-1H-indole-2-amide derivatives and investigate their anti-tumor activity in vitro. METHODS: A series of new N-hydroxy-5-(3-substituted ureido)-1H-indole-2-carboxamide derivatives (7a-7n)were designed and prepared from p-nitrophenylhydrazine and ethyl pyruvate. Their antitumor activities against Hela (breast cancer) lines, cervical cancer cell (MCF7) and human hepatoma cell lines (HepG2) were evaluated by methyl thiazolyl (MTT) method. RESULTS: Target compounds indicated certain antitumor activities, especially compound 7h showed the strongest cytotoxicity to Hela cells with a half inhibition concentration (IC50) of 7.31 μmol•L-1. CONCLUSION: The series of compounds show preferable antitumor activities, which are worthy of further study.

BACKGROUND:Herba epimedi, a traditional Chinese medicine, has a long time in dealing with various orthopedic disorders. Icarinwithmany biological activites is one of the most important compositions of Herba epimedi. OBJECTIVE:Toinvestigate the effects of icarin on osteogenic differentiation of mesenchymal stem cels and the underlying mechanisms. METHODS:Bone marrow mesenchymal stem cels were treated using icarin with or without osteogenic mediumin vitro. Osteogenic differentiation markers, including runt-related transcription factor 2, osteocalcin and osterix, were detected by real time-qPCR. Alizarin red staining was used to measure calcium nodes generated by osteoblasts induced frombonemarrow mesenchymal stem cels. The proximal tibia bone structure of rats fed with icarin (2 mgperday) for 5 weeks was detected and analyzed by MicroCT. RESULTS AND CONCLUSION:Icarin was able to promote the expression of genes related to osteogenic differentiation in the absence or presence of osteogenic induction. Icarin could obviously increase the quantity of calcium nodes whenmesenchymal stem celswere cultured in the osteogenic medium. The animal experiment showed that icarin improved formation of trabecular bone.

OBJECTIVES: Observational studies have suggested an association between preterm birth and stroke in late adulthood, but it remains unclear whether the association is causal. The purpose of this study was to evaluate the causal effects of gestational age on stroke and to determine the pathophysiological mechanisms underlying the causal associations. METHODS: Two-sample Mendelian randomization (MR) was performed to assess the causal effects of fetal gestational duration, early preterm birth (EPB), preterm birth, or postterm birth on stroke and its subtypes. Two-step Mendelian randomization (TSMR) and multivariable Mendelian randomization (MVMR) were additionally used to determine the role of common stroke risk factors, including cardiovascular diseases, hypertension, pulmonary impairment, inflammation, and metabolic diseases, in mediating the causal associations between gestational age and stroke and its subtypes. RESULTS: Genetically predicted EPB increased the risk of cardioembolic stroke (CES; odds ratio [OR], 1.115; 95% confidence interval [CI], 1.036 to 1.200; p=0.004) and large artery stroke (LAS; OR, 1.131; 95% CI, 1.031 to 1.241; p=0.009). The TSMR results showed that EPB was associated with a lower forced expiratory volume in the first second and forced vital capacity ratio (FEV1/FVC) (β=-0.020; 95% CI, -0.035 to -0.005; p=0.009), which increased the risk of CES and LAS. Further MVMR analysis showed that the associations between EPB and stroke disappeared after adjustment for FEV1/FVC. CONCLUSIONS Our data demonstrate that EPB is causally associated with an elevated risk of CES and LAS, and that pulmonary dysfunction mediates the causal impact of EPB on CES and LAS.

OBJECTIVETo analyze the relationship between the ictal onset zone and dominant interictal epileptiform foci in tuberous sclerosis complex (TSC) patients.

METHODClinical data of 20 patients with TSC which had epileptic seizures during Video-EEG monitoring was assessed. Consistency and dominance of focal interictal epileptiform activity and the ictal onset zone were identified. Concordance between interictal and ictal findings was analyzed.

RESULTOf the 20 patients, 7 were female, and 13 were male. The age of epilepsy onset was from 15 d to 6 years. The Video-EEG monitoring age was from 6 months to 11 years. Family history was found in three cases. Abnormality in neuroimaging existed in 17 of 18 patients who were examined. Interictal EEG showed hypsarrhythmia in 3 patients, multifocal epileptiform activity with a dominant focus in 12 patients, both focal and generalized discharges in 2 patients, and only focal discharges in 3 patients. The seizures types during EEG monitoring included epileptic spasms, partial seizure, atypical absence, and generalized or focal myoclonic seizure. The most common seizure type was partial seizure and then epileptic spasms. EEG in 4 patients with epileptic spasms showed ictal generalized discharges and interictal hypsarrhythmia or generalized discharges. Clinical manifestation of epileptic spasms was asymmetric in 3 patients. Lateralization and location of interictal and ictal discharges were consistent in 2 of the 3 patients, while only lateralization consistency in 1 of the 3 patients. Partial seizures as the only seizure type were monitored in 13 patients. Of the 13 patients, lateralization and location of interictal and ictal discharges were inconsistent in 2 patients (15%), consistent in 8 patients (62%), lateralization or location consistent in 2 patients (15%). One case could not be analyzed because of uncertainty of lateralization and location of seizure onset.

CONCLUSIONIn the majority of patients with TSC, multifocal interictal epileptiform activity is present, in which a most dominance of focal epileptiform activity could be found. For some epileptic seizures or the majority of partial seizures, the ictal onset zone is concordant with the dominance of focal interictal epileptiform foci. The concordance might have positioning reference significance for preoperative evaluation of epilepsy surgery.

Brain ; pathology ; physiopathology ; Brain Mapping ; methods ; Cerebral Cortex ; pathology ; physiopathology ; Child ; Child, Preschool ; Electroencephalography ; statistics & numerical data ; Epilepsies, Partial ; diagnosis ; etiology ; physiopathology ; Female ; Humans ; Infant ; Infant, Newborn ; Magnetic Resonance Imaging ; Male ; Predictive Value of Tests ; Retrospective Studies ; Seizures ; diagnosis ; etiology ; physiopathology ; Tuberous Sclerosis ; complications ; diagnosis ; physiopathology

OBJECTIVETo investigate the therapeutic effect of drug treatment for patients with sudden sensorineural hearing loss (SSNHL) accompanied with feeling of ear fullness (FEF).

METHODSA prospective clinical multicenter research was carried out from August 2007 to October 2011. SSNHL patients aged between 18 to 65 years old and accepted no medication were recruited, with a duration less than two weeks. The patients were divided into four types according to the hearing curve: type A was acute SSNHL in low tone frequencies, type B was acute SSNHL in high tone frequencies, type C was acute SSNHL in all frequencies, and type D was total deafness. Each type was subdivided into two groups by the accompaniment of SEF or not. And each type had four different treatment programs, based on the unified designed randomized table. All patients were followed up for four weeks from the initial examination.

RESULTSA total of 1 024 cases with single side SSNHL were recruited in the study from 33 hospitals in China, including 565 cases accompanied with FEF (55.18%), and 459 cases without FEF (44.82%). By classification of audiogram, 205 cases were type A (20.20%), of whom 122 were accompanied with FEF (59.51%); 141 cases belonged to type B (13.77%), of whom 74 were accompanied with FEF (52.48%); 402 cases were type C (39.25%), of whom 229 were accompanied with FEF (56.97%); and 276 cases were classified as type D (26.95%), of whom 140 were accompanied with FEF (50.72%). No significant difference was observed in total effective rate between the SSNHL patients accompanied with FEF or not in four acoustic types (P > 0.05). Among four acoustic types, the clinical cure rate of patients accompanied with FEF in type A was 93.44%, ranking the first; followed by 84.28% for type C; 75.71% for type D; and 70.27% for type B, respectively.

CONCLUSIONSThe therapeutic effect for patients accompanied with FEF in type A is satisfactory. The presence of FEF do not impact the therapeutic effect for SSNHL patients.

Adolescent ; Adult ; Aged ; China ; Hearing Loss, Sensorineural ; therapy ; Hearing Loss, Sudden ; therapy ; Hearing Tests ; Humans ; Middle Aged ; Prospective Studies ; Young Adult