OBJECTIVETo investigate the frequency and type of PHEX gene mutations in children with X-linked hypophosphatemic rickets (XLH), the possible presence of mutational hot spots, and the relationship between genotype and clinical phenotype.

METHODSClinical data of 10 children with XLH was retrospectively reviewed. The relationship between gene mutation type and severity of XLH was evaluated.

RESULTSPHEX gene mutations were detected in all 10 children with XLH, including 6 cases of missense mutation, 2 cases of splice site mutation, 1 case of frameshift mutation, and 1 case of nonsense mutation. Two new mutations, c.2048T>C and IVS14+1delAG, were found. The type of PHEX gene mutation was not associated with the degree of short stature and leg deformity (P=0.571 and 0.467), and the mutation site was also not associated with the degree of short stature and leg deformity (P=0.400 and 1.000).

CONCLUSIONSMissense mutation is the most common type of PHEX gene mutation in children with XLH, and c.2048T>C and IVS14+1delAG are two new PHEX gene mutations. The type and site of PHEX gene mutation are not associated with the severity of XLH.

Adolescent ; Child ; Child, Preschool ; Familial Hypophosphatemic Rickets ; genetics ; Female ; Humans ; Infant ; Male ; Mutation ; PHEX Phosphate Regulating Neutral Endopeptidase ; genetics ; Retrospective Studies

OBJECTIVETo evaluate the oxidative stress in patients with colorectal cancer and to investigate the relationship between oxidative stress and colorectal cancer.

METHODSSeventy-six subjects were divided into two groups (36 colorectal cancer patients as the study group and 40 normal healthy individuals as the control group). Their protein oxidation, DNA damage, lipid peroxidation and antioxidants, vitamin C, vitamin E, glutathione (GSH), and antioxidative enzymes in serum were detected.

RESULTSThe levels of protein carbonyl and advanced oxidation protein products (AOPP) were significantly higher in the study group than in the control group (P<0.01). Serum 8-OHdG was significantly increased in the study group compared to the control group (P<0.01). However, the mean serum level of MDA and conjugated diene was lower in the study group than in the control group (P<0.01). The activity of antioxidative enzymes was significantly decreased in the study group compared to the control group (P<0.01). Serum vitamins C and E concentrations were significantly reduced in the study group compared to the control group (P<0.01).

CONCLUSIONColorectal cancer is associated with oxidative stress, and assessment of oxidative stress and given antioxidants is important for the treatment and prevention of colorectal cancer.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; metabolism ; DNA Damage ; Female ; Humans ; Lipid Peroxidation ; Male ; Middle Aged ; Oxidative Stress

To investigate a baculovirus insect cell system for expressing an interferon alpha 2b (IFNa2b)/immunoglobulin G-4 (IgG4) Fc fusion protein, which has long-acting antiviral effects. Human IFNa2b and IgG4 Fc cDNAs were generated by molecular cloning and inserted into a baculovirus shuttle vector, which was then transposed into the DH10 Bac strain to form recombinant Bacmid-IFN/Fc. The Bacmid-IFN/Fc was transfected into High five insect cells, and expression of the IFN/Fc fusion protein was detected by Western blotting and its biological activity was assessed by the cytopathic effect inhibition method. The IFNa2b and IgG4 Fc cDNA fragments were successfully amplified by RT-PCR using human peripheral lymphocytes. After cloning into the baculovirus shuttle vector, pFastBac1, and transforming into DH10 Bac competent cells, screening identified positive clones carrying the recombinant Bacmid-IFN/Fc. A Bacmid-IFN/Fc clone was successfully transfected into the High five insect cells and packaged into the baculovirus for expression of the IFN/Fc fusion protein. Western blotting revealed that the fusion protein expression was specific, and yielded a protein of 45 kD in size. The in vitro antiviral activity of the IFN/Fc fusion protein was 580 IU/mL. A novel IFN/Fc fusion protein was successfully generated using a baculovirus insect cell system, which may prove useful for providing future experimental data for development of a new long-acting interferon to treat chronic viral hepatitis.
Animals ; Antiviral Agents ; metabolism ; Baculoviridae ; genetics ; Cell Line ; Cloning, Molecular ; Gene Expression ; Gene Fusion ; Genetic Vectors ; Humans ; Immunoglobulin Fc Fragments ; biosynthesis ; genetics ; Immunoglobulin G ; biosynthesis ; genetics ; Insecta ; Interferon-alpha ; biosynthesis ; genetics ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, on impairment in a cortical impact model of traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms. Mice were injected (i.p.) with saline, 1 mg/kg (S)-4C3HPG, 5 mg/kg (S)-4C3HPG and 10 mg/kg (S)-4C3HPG (n=10 per group), respectively, at 30 min before moderate TBI. Neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA in injured cortex were also detected by real-time RT-PCR. The results showed that the neurological deficits and cerebral edema were significantly attenuated in mice pretreated with (S)-4C3HPG (5 and 10 mg/kg respectively) compared with those in mice pretreated with saline. Furthermore, (S)-4C3HPG treatment also decreased the glutamate concentration in CSF and the expressions of TNF-α and IL-1β mRNA remarkably in a dose-dependent manner. These results suggest that (S)-4C3HPG treatment attenuates cortical impact-induced brain injury possibly via suppression of glutamate release and inhibition of excessive inflammatory cytokine production. These findings highlight the potential benefit of glutamate metabotropic receptor ligand for preventing TBI.
Animals ; Brain Injuries ; drug therapy ; metabolism ; physiopathology ; Cytokines ; metabolism ; Glutamic Acid ; cerebrospinal fluid ; Glycine ; analogs & derivatives ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Metabotropic Glutamate ; agonists ; antagonists & inhibitors

OBJECTIVEThis paper aims to assess the interaction between common variations in catalase (CAT) polymorphic gene and environmental factors for antioxidant defense enzyme in modulating individual susceptibility to colorectal cancer (CRC).

METHODSA case-control study with 880 colorectal cancer cases and 848 controls was conducted to investigate whether variations in the catalase (CAT) gene, one of the genes involved in scavenging oxidative stress, influenced susceptibility to CRC.

RESULTSThe interaction between life style and genotypes as well as with their effects on colorectal cancer was deduced from the present study. Significant difference (P = 0.01) was identified in the distribution of CAT genotype between the colorectal cancer cases and the controls. The CRC cases had significantly lower mean activity than the controls (P < 0.01). Correlation analyses revealed statistically significant correlations between CAT activity and CAT genotype (P < 0.01).

CONCLUSIONThe risk of CRC was associated with smoking, low vegetable consumption, high pork and poultry consumptions, and low or high BMI. This is the first study reporting an association of polymorphism CAT-21A > T with colorectal cancer. Low CAT activity was associated with an increased risk of CRC; however, no evidence was found to support an association between CAT-21A > T polymorphism and CRC risk.

Adult ; Aged ; Case-Control Studies ; Catalase ; genetics ; Colorectal Neoplasms ; enzymology ; epidemiology ; metabolism ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Oxidative Stress ; Polymerase Chain Reaction

OBJECTIVETo explore the awareness on sever acute respiratory syndrome (SARS) and public health emergencies among general publics.

METHODSA cluster sampling method was implemented in Harbin and Jiagedaqi district of Daxinanling of Heilongjiang province. Research subjects were divided into three groups as city, township and rural areas and were given questionnaires to fill in. Data was analyzed with Epi-data and SPSS.

RESULTS2003 available questionnaires were collected. The general publics well understood the knowledge on public health emergencies and the SARS with the whole recognition rate more than 60 percent. During the epidemics, people in city, town and countryside were calm (71.7%). The rates of attitude towards the government were significantly different among the subjects living with the city, town or rural areas. The city group expressed the highest favor to the government and media, 71.8% of them gave the credit on the control of SARS to the effective method taken by the government and 65.0% of them showed that they had enough confidence on the governmental ability of dealing with crises while the countryside group trusted the hospitals and relative specialists the most.

CONCLUSIONIt is essential for the government to interact and communicate with the publics through media, medical and related institutions when confronting with the public health emergencies. Publicity on health knowledge and coping system on emergency should play key roles in the development of an effective public health system while the government should lead the battle.

China ; Data Collection ; Emergencies ; Health Knowledge, Attitudes, Practice ; Humans ; Public Health ; Rural Population ; Severe Acute Respiratory Syndrome ; Urban Population

Objective To analyze and summarize the clinical characteristics and risk factors for patients with hemorrhagic transformation (HT) after cerebral infarction to provide guidance for its clinical treatment and prevention.Methods In this study,data from 49 hospitalized patients with HT in the First Department of Neurology,China-Japan Union Hospital of Jilin University from October 2009 to March 2012,were reviewed retrospectively and 106 cases with acute cerebral infarction only during the same period,were chosen randomly as controls.Gender and age of the patients were comparable.Relevant information was collected.SPSS 17.0 statistical package was applied for data processing.Qualitative data were processed with x2 test,and measurable data was processed with t-test.Each index was analyzed with uni-variate analysis while statistically significant risk factors were included in the logistic review model to conduct the multivariate regression analysis.Results (1) Clinical symptoms deteriorating after hemorrhage in 21 cases accounted for 42.9％ of the HT group,among which the cases on degree of disturbance to consciousness had an aggravation in 8 cases and hemiplegia increase in another 7 cases.Headaches and dizziness were found in 5 cases.(2)Number of infarction within 15 days after the occurrence of HT accounted for 87.0％.(3)HT-related factors increased the risk of HT in cerebral infarction such as cortical infarction,large area of infarction,atrial fibrillation,cerebral embolism,diabetes and high level of low-density lipoprotein cholesterol (P＜0.05).The most important factors were atrial fibrillation and cerebral embolism.(4)PH-2 seemed more unlikely to link with clinical symptoms than other subtypes of HT.Conclusion Cerebral infarction after occlusion of the main artery trunk was prone to HT,especially when it appeared within 15 days.Short-term prognosis seemed to be related to the subtypes of HT,with risk factors as cortical infarct,massive cerebral infarction,atrial fibrillation,cerebral embolism,diabetes,high low-density lipoprotein cholesterol etc.on HT.

BACKGROUNDSingle nucleotide polymorphisms (SNPs) in the deoxycytidine kinase (dCK) gene are associated with chemosensitivity to nucleoside analogs. 2',2'-Difluoro 2'-deoxycytidine (gemcitabine) is a first-line nucleoside analog drug in the treatment of pancreatic cancer. However, the association between SNPs in the dCK gene and chemosensitivity to gemcitabine has not been fully established. Therefore, the present study aimed to investigate the relationship between SNPs in the dCK gene and chemosensitivity to gemcitabine in human pancreatic cancer cell lines.

METHODSSeven SNPs in the dCK gene were sequenced in six human pancreatic cancer cell lines. The chemosensitivity of these six cell lines to gemcitabine were evaluated in vitro with a Cell Counting Kit-8 (CCK-8) test. Inhibition rates were used to express the chemosensitivity of pancreatic cancer cell lines to gemcitabine.

RESULTSThe genotype of the A9846G SNP in the dCK gene was determined in six human pancreatic cancer cell lines. The cell lines BxPC-3 and T3M4 carried the A9846G SNP genotype AG, whereas cell lines AsPC-1, Mia PaCa2, SW1990 and SU86.86 carried the GG genotype. Cell lines with the AG genotype (BxPC-3 and T3M4) were more sensitive to gemcitabine compared with cell lines with the GG genotype (AsPC-1, Mia PaCa2, SW1990 and SU86.86) and significantly different inhibition rates were observed between cell lines carrying the AG and GG genotypes (P < 0.01).

CONCLUSIONSVariants in the A9846G SNP of the dCK gene were associated with sensitivity to gemcitabine in pancreatic cancer cell lines. The dCK A9846G SNP may act as a genetic marker to predict chemotherapy efficacy of gemcitabine in pancreatic cancer.

Antimetabolites, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Cell Survival ; drug effects ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Deoxycytidine Kinase ; genetics ; Genotype ; Humans ; Pancreatic Neoplasms ; enzymology ; genetics ; Polymorphism, Single Nucleotide ; genetics

Objective To study the application effect and significance of clinical nursing pathway (CNP)on patients with gastrointestinal polypus.Methods A total of 100 patients with gastrointestinal polypus were randomly divided into tow groups,observation group and control group,each group has 50 patients.Control group were treated with routine care and observation group were treated with clinical nursing pathway table by nurse-in-charge and the nurse on duty.To analyze the the days the patients stayed and the hospital expenses,evaluate the patients'master level of health knowledge,and investigate patient satisfaction.Results The days that the patients stayed and the hospital expenses of observation group was much lower than control group,but the master level of health knowledge and patient satisfaction was higher than control,and the differences were statistically significant(P<0.05).Conclusions CNP can shorten the days that the patients stayed,reduce hospital expenses,standardize medical care conduct,enhance communications between nurse and patient,improve patient satisfaction and healthy education effect and avoid medical tangle,all of the above has very strong clinical practicability.

Allogeneic stem cell transplantation (allo-SCT) is currently the only curative option for patients with X-linked agammaglobulinemia (XLA). In this study, patient 1 aged 4 years who underwent allogeneic peripheral blood stem cell transplantation (allo-PBSCT) from HLA-mismatched unrelated donor; patient 2 aged 24 years (childhood onset) with primary cutaneous acral CD8 T cell lymphoma who underwent allo-PBSCT from haploidentical relative donor. Both were treated by reduced toxicity myeloablative conditioning with post-transplantation cyclophosphamide (PTCy), anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA) for graft-versus-host-disease (GVHD) prophylaxis. In patient 1, neutrophil and platelet engraftment were observed on day 11 post-transplantation; the donor chimerism dropped on day 90 post-transplantation, and recovered on day 150 with donor lymphocyte infusion (DLI). In patient 2, neutrophil and platelet engraftment were observed on days 20 and 87 post-transplantation respectively, with complete donor chimerism on day 30 post-transplantation. The serum levels of IgG, IgM and IgA and the percentage of CD19 B cells in peripheral blood of patients 1 and 2 returned to normal within 2 months and more than 1 year after transplantation respectively. There was no evidence of acute GVHD for the two patients. Patient 1 developed a limited type of skin chronic GVHD after DLI, which disappeared after anti-GVHD treatment. This is the first report of successful treatment for two XLA patients using PTCy with allo-PBSCT from HLA-mismatched unrelated donor or haploidentical donor, combining with improved conditioning, which expands the pool of eligible donors for patients with XLA.
Agammaglobulinemia ; therapy ; Genetic Diseases, X-Linked ; therapy ; Graft vs Host Disease ; HLA Antigens ; Hematopoietic Stem Cell Transplantation ; Humans ; Peripheral Blood Stem Cell Transplantation ; Treatment Outcome ; Unrelated Donors ; Young Adult