Objective To diagnose 6 LQTS families by genetic analysis. Methods A total aof 6 LQTS pedigrees with 43 family members were brought together for genetic diagnosis by using short-sequence tandem-repeat (SIR) markers or sequencing. Genomic DNA was extracted from blood samples by standard procedure. STR markers or KCNQ1, KCNH2 and SCN5A were amplified. The haplotype analysis for LQTS was performed. If the family got the negative haplotype analysis, the sequencing was performed. Results LQTS patients were always linkaged with the SCNSA gene in family 1. KCNH2 was linkaged with the disease in family 2 to 5.21 gene carriers were identified from these 5 families. A mutation (A561V-KCNH2) was only found in the proband of family 6 and an SNP (G1691A) was found in all the members of the family. Conclusion Genetic diagnosis can not only improve presymptomatic diagnosis,bnt also provide the basis for personal therapy and research on disease-causing mutations.

OBJECTIVETo compare the clinical efficacy differences between acupoint catgut embedding and Kuntai capsule for perimenopausal syndrome, so as to provide an effective treatment method for perimenopausal syndrome.

METHODSThirty-three cases in the embedding group were treated with acupoint catgut embedding at back-shu points and front-mu points of liver, spleen and kidney combined with syndrome differentiation and disease differentiation, ten days per times; the Kuntai group was treated with oral administration of Kuntai capsule, 4 capsules each time, three times per day. The Kupperman index (KI) was observed in the two groups before treatment after 10 days, 30 days and 60 days of treatment, respectively; the efficacy was evaluated according to the ratio of KI.

RESULTSAfter the treatment, as treatment proceeded, the score of KI and ratio of KI were gradually reduced in two groups; the score of KI and ratio of KI in the embedding group after 10 days of treatment was lower than those in the Kuntai group (both P<0.05); after 10 days of treatment, the total effective rate was 36.4% (12/33) in the embedding group, which was superior to 3.0% (1/33) in the Kuntai group (P<0.05); however, after 30 days and 60 days of treatment, the differences of each index between two groups were not statistically significant (all P>0.05).

CONCLUSIONBoth the acupoint catgut embedding and Kuntai capsule could reduce the score of KI and improve clinical symptoms, and the acupoint catgut embedding has certain advantage on the early stage of treatment.

Acupuncture Points ; Acupuncture Therapy ; instrumentation ; Adult ; Catgut ; Female ; Humans ; Middle Aged ; Perimenopause ; physiology ; Treatment Outcome

OBJECTIVE: To research the value of polymorphism of salivary esterase(Set) in paternity and personal identification. METHODS: Phenotype and genotype of human salivary esterase were detected in 114 liquid saliva samples from the Chinese population by disc electrophoresis and fast blue RR staining assay. RESULTS: The frequency of Set type was F 22.81%, FS 50.88%, S2 6.31%. The estimated gene frequency of SetF was 0.4825 and SetS was 0.5175. The PE was 0.1875 and the DP was 0.6199. CONCLUSION Polymorphism of salivary esterase (Set) was practical in paternity and personal identification.
Esterases/genetics* ; Forensic Anthropology/methods* ; Gene Frequency ; Humans ; Paternity ; Polymorphism, Genetic ; Saliva/enzymology*

OBJECTIVETo prepare a new dosage formulation of activated carbon nanoparticles adsorbing mitomycin C (MMC-ACNP) and evaluate the beneficial effects of intraperitoneally applied MMC-ACNP as a drug delivery system for lymphatic targeting in preventing metastasis and recurrence of gastric cancer.

METHODSMMC-ACNP was prepared. Acute toxicity after its intraperitoneal administration was evaluated. An experiment on nude mice model with transplanted human gastric cancer in 6 groups was completed to assess the effects of drugs on intra-abdominal carcinomatosis.

RESULTSThe LD50 of MMC-ACNP was 46.80 mg/kg (in terms of MMC) while that of MMC aqueous solution was 9.33 mg/kg. The toxicity of MMC-ACNP was much less than that of the solution form. MMC-ACNP was superior to MMC aqueous solution in controlling carcinomatosis and tumor growth by intraperitoneal administration. Despite the high dose of MMC, leukopenia and thrombocytopenia were not observed in the MMC-ACNP treated group. Fine activated carbon particles adsorbing MMC entered the nuclei of tumor cells, so that the effects of the anticancer drug were reinforced.

CONCLUSIONMMC-ACNP gives a good promise of clinical use due to its advantages such as high selectivity and low toxicity.

Adenocarcinoma, Mucinous ; pathology ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; adverse effects ; pharmacology ; Charcoal ; administration & dosage ; Drug Carriers ; Drug Delivery Systems ; Female ; Humans ; Injections, Intraperitoneal ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mitomycin ; administration & dosage ; adverse effects ; pharmacology ; Nanoparticles ; Neoplasm Transplantation ; Stomach Neoplasms ; pathology ; Thrombocytopenia ; chemically induced

BACKGROUNDNumerous studies have shown that reducing the level of tumor necrosis factor-alpha (TNFα) through the use of anti-TNF antibodies or soluble TNF receptor is a safe and efficacious treatment to inflammatory diseases such as rheumatoid arthritis. Therefore, novel approaches to achieve this outcome are desired. The aim of this study was to investigate the characterization of a small molecule inhibitor, Y316, which blocks TNF mRNA upregulation and TNF production by lipopolysaccharides (LPS) stimulated monocytes.

METHODSPeripheral blood mononuclear cells (PBMC) from healthy volunteers were plated in 24-well plates and stimulated with LPS (1 µg/ml), phorbol-12-myristate-13-acetate (PMA) (100 ng/ml), zymosan (10 µg/ml) and Tsst (100 ng/ml). Supernatants were collected after 4-hour culture at 37°C, and quantitative determination of TNFα, interleukin-1β (IL-1β), IL-6, IL-8, IL-10 and IL-2 production in the supernatants was performed by colorimetric enzyme-linked immunosorbent assay (ELISA). Total RNA of PBMC was isolated and cytokine mRNA quantitation was performed by using a RNA level measuring kit (R & D Systems). PBMC were pretreated with Y316 (10 µmol/L, 1 µmol/L, 0.1 µmol/L, 0.01 µol/L and 0.001 µmol/L) or dimethyl sulfoxide at 37°C for 10 minutes, and then stimulated with LPS or PMA, protein concentrations of p44.42, IKBα, P38 and Jun NH2-terminal kinase were determined by Western blotting. Cyclic adenosine-3',5'-monophosphate (cAMP) of PBMC was measured by enzyme immunoassay kit (Amersham Pharmacia Biotech).

RESULTSY316 blocked TNF production and inhibited the upregulation of TNF mRNA levels in response to LPS, and also prevented the production of IL-1 and IL-6. In contrast, Y316 augmented the production of IL-10 in LPS-stimulated monocytes. Y316 failed to prevent the production of IL-2 and TNF in antigen-stimulated T cells, suggesting that its effects may be cell-type specific. Y316 prevented the phosphorylation and activation of the MAPK, ERK, and therefore appeared to mediate its effects on TNF by acting at an early point in the signaling cascade induced in response to LPS. There was no effect of Y316 on cAMP levels either alone or in the presence of LPS.

CONCLUSIONSY316 appears to be a small molecule inhibiting TNF production, which may act via a novel mechanism. Identification of the target of Y316 may lead to the development of alternative strategies for achieving selective cytokine inhibition.

Anti-Inflammatory Agents ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Humans ; Interleukin-1 ; antagonists & inhibitors ; biosynthesis ; Interleukin-6 ; antagonists & inhibitors ; biosynthesis ; Lipopolysaccharides ; pharmacology ; Monocytes ; drug effects ; immunology ; Phosphorylation ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; biosynthesis

Objective To explore the establishment of a rat model of acute radiation-induced liver injury and sig-nificance of the dynamic changes of TGF-β1 expression.Methods Forty healthy 6-week old male SD rats were randomly divided into model group (n=30) and control group (n=10).The right liver of rats in the model group was given a single dose of 25 Gy 6 MV X-ray irradiation.Histopathological examination using HE staining and transmission electron microsco-py were conducted to observe the liver pathological changes in rats at 3, 5, and 10 days after irradiation, serum TGF-β1 was detected, and relevant indicators of liver function ( ALT, AST, ALP) were determined.Statistical analysis was per-formed using SPSS 17.0 software.Results At 3, 5 and 10 days after irradiation, early pathological changes in the liver cells were observed by electron microscopy, the expression of TGF-β1 was gradually increased with the time prolongation, and significant differences were found between the model group and the control group at different time points (P<0.05). The light microscopic observation of liver tissues did not show significant differences between the control group and model group.The liver ALT, AST, ALP at different time points did not show significant differences between the two groups ( P>0.05).Conclusion Electron microscopy can be used to evaluate the early changes of radiation-induced liver injury, pri-or to the alterations visible by routine light microscopy.TGF-β1 can be used to predict the degree of radiation-induced liver injury, and may be used as a sensitive serum cytokine in predicting the degree of radiation-induced acute liver injury.

OBJECTIVETo analyze the correlation between the phenotype and genotype of tooth agenesis using the tooth agenesis code (TAC) and the traditional descriptor for missing teeth.

METHODSPatients with isolated hypodontia caused by PAX9 or MSX1 mutation reported before May 2007 were enrolled. The teeth missing rate and TAC code were recorded. The missing teeth patterns caused by the two mutations were compared.

RESULTSThe teeth missing rates in each teeth positions were significantly different between maxillary and mandibular except maxillary central incisor, lateral incisor and mandibular canine, first molar (P<0.05, P<0.001). MSX1 gene mutation often led to the loss of maxillary first premolar, maxillary second premolar, and mandibular second premolar, while PAX9 gene mutation often led to the loss of the first, second, and third molars. The results were similar when analyzed either by TAC code analysis or by traditional descriptor.

CONCLUSIONSPAX9 and MSX1 gene mutation can cause different phenotypes of tooth agenesis. The TAC code can be used in the analysis of the correlation between phenotype and genotype of the missing teeth patients.

Anodontia ; genetics ; Genotype ; Humans ; MSX1 Transcription Factor ; genetics ; Mutation ; PAX9 Transcription Factor ; genetics ; Phenotype

OBJECTIVETo investigate the relationship between the length of telomere DNA and age at different altitude areas.

METHODSAll 172 peripheral blood samples were randomly selected from healthy individuals of different ages from 25 to 65 years old. High altitude group (47 males, 48 females) living at an altitude of 4380 m (HA group), sea level group (39 males, 38 females) living at an altitude of 43 m (SL group). The terminal restriction fragment (TRF) length of telomere DNA was measured by Southern blotting analysis. The plasma levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were assayed.

RESULTSAverage TRF lengths of males and females in HA groups were 10.45 +/- 1.35 and 10.50 +/- 1.45. Average TRF lengths of males and females in SL groups were 11.29 +/- 1.10 and 11.31 +/- 1.13. A negative correlation was shown between the average TRF length and age of males in two groups (P < 0.01). This was also the case for females. ANOVA test was used to analyze the difference between TRF length and gender at different ages (P < 0.001). It was shown that there was significant difference in TRF length between the male (25 years old and 55 years old) and female (25 years old and 55 years old) in two groups at different ages (P < 0.05). The plasma levels of SOD and MDA were significant different between HA groups and SL groups (25-44 years old groups/45-65 years old groups) (P < 0.05).

CONCLUSIONObviously shortening of telomere was observed by increasing of ages in high altitude groups. There was a negative correlation between the length of telomere DNA and ages. Telomere shortening became more obviously in high altitude group than in sea level group in keeping with the age increases.

Adult ; Age Factors ; Aged ; Altitude ; Blood Cells ; DNA ; genetics ; Female ; Humans ; Leukocytes ; Male ; Malondialdehyde ; Middle Aged ; Repetitive Sequences, Nucleic Acid ; Superoxide Dismutase ; Telomere ; genetics

Adult ; Aged ; Carcinoma, Hepatocellular ; genetics ; pathology ; Female ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; Liver Neoplasms ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; RNA, Messenger ; genetics ; Young Adult

[Objective]To explore the effect of alpha2-macroglobulin(α2M)on superoxide anion(.O2-)content, superoxide dismutase(SOD)activity and the process of cell-to-myofibroblast transformation in human skin fibroblasts (HSF)after X-ray irradiation.[Methods]HSF cells were irradiated with 0,5,10,15 and 20 Gy X-ray.The change of. O2- content and SOD activity in the supernatant of cell culture medium were measured on the first day after irradiation. The protein expression of alpha-smooth muscle actin(α-SMA)was detected by Western blot on the fifth day after irradia-tion.The most sensitive radiation dose is selected.HSF cells were irradiated with the above sensitive dose.Respectively, 1h before irradiation,1 h after irradiation,the experimental group cell culture medium was added to a final concentration of 0.25 mg/mL,0.5 mg/mL of α2M.The change of.O2-content,SOD activity and the protein expression of α-SMA were detected.[Results]HSF cells were irradiated with 5~20 Gy doses of X-ray..O2- content increased,SOD activity de-creased and α-SMA protein expression increased gradually(P<0.05).The addition of α2M at 1 h after 10Gy X-ray irradi-ation reduced the.O2- content,increased the SOD activity and downregulated the protein expression of α-SMA in HSF cells(P<0.05). There was no significant change in the administration at 1 h before irradiation.[Conclusion]HSF cells increased.O2-content significantly,while SOD activity decreased,and the tendency to transform myofibroblasts after X-ray irradiation.α2M can reduce the.O2-content,increase the SOD activity in HSF cells and inhibit the transformation of fibroblasts into myofibroblasts after irradiation.Indicating that α2M can play a role in radiation protection by anti-oxida-tion and anti-fibrosis.