Objective　To explore the reasons for differences in the clinical manifestations of Wallenberg syndrome，and provid valuable information for clinical work. Methods　A retrospective analysis of 41 cases of Wallenberg syndrome clinical and imaging data. Our patients were grouped according to age，risk factors and vascular lesions. The clinical differences were studied in each group of patients. Results　The most common clinical symptoms and signs of Wallenberg syndrome was vertigo and dizziness，followed dysarthria，ataxia，sensory disturbances，gag reflex diminished or disappeared，difficulty swallowing，nausea or vomiting，Horner syndrome，nystagmus. Age and clinical symptom scores were negatively correlated （P=0.002）. Hypertension，diabetes，hyperlipidemia，and smoking in patients with clinical manifestations were no significant correlation. The vertebral artery and vertebral artery combined cerebellar artery disease patients were statistically significant different with pure posterior inferior cerebellar artery disease patients in the emergence of dysarthria （P=0.029），nausea/vomiting（P=0.033） and dysphagia（P=0.002）. Conclusion　Clinical manifestations of Wallenberg syndrome are varied. Age and clinical symptom scores were negatively correlated. Vertebral artery and vertebral artery joint cerebellar artery disease more easily lead to dysarthria，dysphagia，and nausea/vomiting.

To discover novel fluoroquinolone lead compounds as possible anti-infective or/and antitumor chemotherapies, combination principle of pharmacophore-based drug design, a series of novel tricyclic fluoroquinolone title compounds, [1,2,4]triazino[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives ( 5a-5p), were designed and synthesized with a fused [1,2,4]-triazine ring unit. Their structures were characterized by spectral data and elemental analysis and the in vitro antibacterial and anti-cell proliferation activities were also evaluated. The results showed that the titled compounds exhibited more significant inhibitory activities against drug-resistant bacteria (Methicillin-resistant Staphylococcus aureus and multi drug-resistant Escherichia coli strains) and three tested cancer cell lines (human hepatoma SMMC-7721, murine leukemia L1210 and human murine leukemia HL60 cells). Interestingly, SAR showed that compounds with electron-donating groups attached to benzene ring had stronger antibacterial activity than antitumor activity, but electron-withdrawing compounds displayed more potential antitumor activity than antibacterial activity, especially antitumor activity of nitro compounds was comparable to comparison doxorubicin. Thus, novel triazine-fused tricyclic fluoroquinolones as potent anti-infective or/and antitumor lead compounds are valuable to pay attention and for further development.

To explore an efficient strategy for the conversion of antibacterial fluoroquinolones into antitumor fluoroquinolones, an azole heterocyclic ring of oxadiazole instead of the C-3 carboxylic acid group with a functionalized hydrazone group as a modified side-chain, fifteen novel 2-(fluoroquinolon-3-yl)-oxadiazole-5- sulfanylacetylhydrazone derivatives 7a-7o were designed and synthesized on the basis of the pharmacophore hybridization principle from pefloxacin, separately. The structures for fifteen title compounds were characterized by elemental analysis, 1H NMR and MS, and their in vitro antitumor activity against Hep-3B cell line was evaluated by a MTT assay. The results showed that the title compounds exhibited more significantly inhibitory activity than that of the parent pefloxacin, in which compounds with electron-withdrawing group attached on aryl ring had more potency than that of compounds with electron donating group, especially compounds with a carboxylic substituent were comparable to comparison doxorubicin. It suggests that it is favorable for an improvement of antitumor activity to remain a carboxylic acid unit at the aromatic ring.

To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan-1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron-drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan-1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation.

To discover novel antitumor rhodanine unsaturated ketones, a series of fluoroquinolone (rhodanine α, β-unsaturated ketone) amine derivatives (5a-5r) were designed and synthesized with fluoroquinolone amide scaffold as a carrier. The structures of eighteen title compounds were characterized by elemental analysis, 1H NMR and MS. The in vitro anti-proliferative activity against Hep-3B, Capan-1 and HL60 cells was evaluated by MTT assay. The results showed that the title compounds not only had more significant anti-proliferative activity against three tested cancer cell lines than that of the parent ciprofloxacin 1, but also exhibited the highest activity against Capan-1 cells. The SAR revealed that some compounds carrying aromatic heterocyclic rings or phenyl attached to an electron-withdrawing carboxyl or sulfonamide substituent were comparable to or better than comparison doxorubicin against Capan-1 cells. As such, it suggests that fluoroquinolone (rhodanine α, β-unsaturated ketone) amines are promising leads for the development of novel antitumor fluoroquinolones or rhodanine analogues.

To search for fluoroquinolones(FQs)with antitumor activity;the C-3 carboxylic acid group of peflox-acin (1)was replaced by fused heterocyclic core;and twelve novel thiazolo[3;2-b][1;2;4]triazole heterocycles(6a-6l)were designed and synthesized.The structures of target compounds were characterized by elemental anal-ysis and spectral data.The results of the in vitro antiproliferative effect on SMMC-7721;L1210 and HL60 cell lines showed that the title compounds exhibited more significant antitumor activity than both of the pefloxacin and the corresponding opening-ring intermediates(5 a-5 l).Among them;the target compounds which possess a ben-zene ring bearing a hydroxyl group (6e)or a fluorine atom (6j)exhibited more potent antiproliferative effect on SMMC-7721 cells than other compounds.Therefore;the antitumor fluoroquinolones can be designed by replacing the C-3 carboxylic acid group of fluoroquinolones with the thiazolo[3;2-b][1;2;4]triazole moiety.

OBJECTIVE To study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide （H2O2）， and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4（NFATc4）. METHODS H9c2 myocardial cells were cultured in vitro and divided into blank group， H2O2 group， and 50， 100， 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h， and then were subjected to H2O2 （200 μmol/L） stimulation for 12 hours together with the H2O2 group； relative survival rate was detected in each group， and the levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in cell supernatant and reactive oxygen species （ROS） in H9c2 cells were measured. Meanwhile， the expressions of apoptosis-related proteins [B cell lymphoma 2 （Bcl- 2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore， the NFATc4 interference sequence was transfected， and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2- induced myocardial cells were investigated. RESULTS Compared with blank group， relative cell viability， the levels of SOD and CAT， relative expression of Bcl-2 were decreased significantly， while the levels of MDA and ROS， relative expressions of Bax， cleaved caspase-3 and nuclear protein NFATc4 were increased significantly （P＜0.05 or P＜0.01）. Compared with the H2O2 group， the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly （P＜0.05）. After the transfection of the NFATc4 interference sequence， the expression of nuclear protein NFATc4 was down-regulated significantly； the levels of MDA and SOD， the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly， while the levels of SOD and CAT， and the protein expression of Bcl-2 were all increased/up-regulated significantly， compared with H2O2 group （P＜ 0.05）. CONCLUSIONS Mangiferin can relieve H2O2-induced oxidative stress of H9c2 cells， reduce the apoptosis and inhibit the nuclear translocation of NFATc4， thereby alleviating myocardial cell damage； reducing the nuclear level of NFATc4 protein is related to reducing H2O2-induced oxidative stress and cell apoptosis.

OBJECTIVETo observe the effects of Shenqi Compound (SQC) on the mRNA expression of angiotensin II type 1 receptor (AT1R) in the aorta of Goto-Kakizaki (GK) rats.

METHODSTotally 67 GK rats were randomly divided into 5 groups, i.e., the GK group (n =18), the model group (n =16), the atorvastatin group (n =17), and the SQC group (n =16). Another a normal control group was set up (n =18). The diabetic macrovascular disease model was prepared by adding L-NAME (at the daily dose of 0.10 mg/mL) in drinking water for GK rats. GK rats, except those in the normal control group were fed with high fat diet. Atorvastatin (at the daily dose of 1.60 mg/kg) and SQC (at the daily dose of 1.44 g/kg) were respectively administered by gastrogavage, once daily for 35 successive days. The blood glucose was determined by glucose oxidase method once per week. After 5-week medication, the contents of triglyceride (TG) and total cholesterol (TC) were determined by ELISA. The serum concentrations of angiotensin I (Ang II) were determined by RIA. The mRNA expression of AT1R in the aorta was determined by real-time quantitative reverse transcriptase PCR (RT-PCR).

RESULTSThe blood glucose level was obviously lower in both the atorvastatin group and the SQC group after 4 weeks of medication (P <0.05). Besides, it was significantly lower in the SQC group than in the model group by the end of the 4th week (P <0.05). The concentrations of TG, TC and serum Ang II , and the mRNA expression of AT1R in the aorta were significantly higher in the model group than in the normal control group (P <0.01). After 5-week medication, the concentrations of TG, TC and serum Ang I , and the mRNA expression of AT1 R in the aorta were significantly lower in the atorvastatin group and the SQC group than in the model group (P <0.01, P <0.05). The mRNA expression of AT1R was significantly higher in the SQC group than in the atorvastatin group (P <0.05).

CONCLUSIONSSQC could significantly reduce the levels of blood glucose, TG, TC, down-regulate the mRNA expression of AT1R in the aorta, and decrease the expressions of serum Ang II of GK rats with diabetic macrovascular disease. AT1 R might be one of effective targets of SQC in treating diabetic macrovascular diseases.

Angiotensin II ; blood ; Animals ; Aorta ; drug effects ; metabolism ; Blood Glucose ; analysis ; Cholesterol ; blood ; Diabetes Mellitus, Experimental ; drug therapy ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Male ; RNA, Messenger ; genetics ; Rats ; Receptor, Angiotensin, Type 1 ; genetics ; metabolism ; Triglycerides ; blood

This study aimed to identify the type of carnitine palmitoyltransferase 2 (CPT2) gene mutation in the child with carnitine palmitoyltransferase II (CPT II) deficiency and her parents and to provide the genetic counseling and prenatal diagnosis for the family members. As the proband, a 3-month-old female baby was admitted to the hospital due to fever which had lasted for 8 hours. Tandem mass spectrometric analysis for blood showed an elevated plasma level of acylcarnitine, which suggested CPT II deficiency. The genomic DNA was extracted from peripheral blood of the patient and her parents. Five exon coding regions and some intron regions at the exon/intron boundaries of the CPT2 gene were analyzed by PCR and Sanger sequencing. Amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of CPT2 gene mutation. Sanger sequencing results showed that two mutations were identified in the CPT2 gene of the proband: c.886C>T (p.R296X) and c.1148T>A (p.F383Y), which were inherited from the parents; the second child of the mother inherited the mutation of c.886C>T (p.R296X) and showed normal acylcarnitine spectrum and normal development after birth. It is concluded that the analysis of CPT2 gene mutations in the family suggested that the proband died of CPT II deficiency and that the identification of the mutations was helpful in prenatal diagnosis in the second pregnancy.
Carnitine O-Palmitoyltransferase ; deficiency ; genetics ; Female ; Humans ; Infant ; Metabolism, Inborn Errors ; diagnosis ; genetics ; Mutation ; Prenatal Diagnosis

X-linked ichthyosis (XLI) is a metabolic disease with steroid sulfatase deficiency and often occurs at birth or shortly after birth. The encoding gene of steroid sulfatase, STS, is located on the short arm of the X chromosome, and STS deletion or mutation can lead to the development of this disease. This study collected the data on the clinical phenotype from a family, and the proband, a boy aged 11 years with full-term vaginal delivery, had dry and rough skin and black-brown scaly patches, mainly in the abdomen and extensor aspect of extremities. Peripheral blood samples were collected from each family member and DNA was extracted. Multiplex ligation-dependent probe amplification (MLPA) was used to measure the copy number of STS on the X chromosome. Whole-genome microarray was used to determine the size of the segment with microdeletion in the X chromosome. MLPA was then used for prenatal diagnosis for the mother of the proband. The results revealed that the proband and another two male patients had hemizygotes in STS deletion. Gene microarray identified a rare deletion with a size of 1.6 Mb at Xp22.31 (chrX: 6,516,735-8,131,442). Two female family members were found to be carriers. Prenatal diagnosis showed that the fetus carried by the proband's mother was a carrier of this microdeletion. This study showed STS gene deletion in this family of XLI, which causes the unique skin lesions of XLI. MLPA is a convenient and reliable technique for the molecular and prenatal diagnosis of XLI.
Child ; Humans ; Ichthyosis, X-Linked ; diagnosis ; genetics ; Male ; Mutation ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis ; Steryl-Sulfatase ; genetics