OBJECTIVEThe aim of this study is to determine whether the SUMO4 M55V polymorphism is associated with susceptibility to type 2 diabetes mellitus (T2DM).

METHODSA meta-analysis was performed to detect the potential association of the SUMO4 M55V polymorphism and susceptibility to T2DM under dominant, recessive, co-dominant (homogeneous and heterogeneous), and additive models.

RESULTSA total of eight articles including 10 case-control studies, with a total of 2932 cases and 2679 controls, were included in this meta-analysis. The significant association between the SUMO4 M55V polymorphism and susceptibility to T2DM was observed in the dominant model (GG + GA versus AA: OR = 1.21, 95% CI = 1.05-1.40, P = 0.009), recessive model (GG versus GA + AA: OR = 1.29, 95% CI = 1.07-1.356, P = 0.010), homozygous model (GG versus AA: OR = 1.41, 95% CI = 1.06-1.56, P = 0.001), and additive model (G versus A: OR = 1.18, 95% CI = 1.08-1.29, P = 0.001), and marginally significant in the heterozygous model (GA versus AA: OR = 1.16, 95% CI = 0.98-1.36, P = 0.080). In subgroup analyses, significant associations were observed in the Chinese population under four genetic models excluding the heterozygous model, whereas no statistically significant associations were observed in the Japanese population under each of the five genetic models.

CONCLUSIONThe meta-analysis demonstrated that the G allele of the SUMO4 M55V polymorphism could be a susceptible risk locus to T2DM, mainly in the Chinese population, while the association in other ethnic population needs to be further validated in studies with relatively large samples.

Diabetes Mellitus, Type 2 ; epidemiology ; genetics ; Genetic Predisposition to Disease ; epidemiology ; genetics ; Humans ; Small Ubiquitin-Related Modifier Proteins ; genetics ; metabolism

OBJECTIVETo compare the clinical effects of two methods of internal fixation in treating unstable femoral intertrochanteric fractures in elderly patients.

METHODSFrom August 2009 to August 2014, 68 elderly patients with unstable femoral intertrochanteric fracture treated with locking proximal femur plate and auxiliary short reconstructed plate (reconstructing calcar group) and proximal femoral nail antirotation (PFNA group) with clinical course from 1 to 3 days were retrospectively analyzed. In reconstructing calcar group, there were 30 patients including 8 males and 22 females, aged from 63 to 85 years old with an average of (73.41±5.12) years old, the fractures were classified to type AO 31-A2.2 in 12 cases, A2.3 in 11 cases, A3.3 in 7 cases according to AO/ASIF classification. In PFNA group, there were 38 patients including 10 males and 28 females, aged from 65 to 90 years old with an average of (74.26±4.53) years old, the fractures were classified to type AO 31-A2.2 in 15 cases, A2.3 in 13 cases, A3.3 in 10 cases. All fracture were caused by injury, leading pain and swelling. Femoral intertrochanteric fracture was confirmed by X ray films. The data of each group were collected for statistical analysis on the following aspects: the incision length, operation time, blood loss volume, postoperative partial weight bearing standing time, clinical healing time of fracture, postoperative complications, and hip functional score of Harris.

RESULTSAll incisions were healed at stage I. In the aspect of postoperative complications, there were 1 case of screw blade cutting and 1 case of deep venous thrombosis in PFNA group; there was 1 case of deep venous thrombosis in the reconstructing calcar group (²=0.000,=1.000). Patients were followed up from 20 to 24 months with an average of 22.5 months. There were no significant in postoperative partial weight bearing standing time, postoperative complications, hip functional score of Harris between two group. There were significant in the incision length, operation time, blood loss volume, clinical healing time of fracture. In the incision length, operation time, blood loss volume, clinical healing time of fracture, the PFNA group was significantly differently less than that of the reconstructing calcar group (<0.001). In the clinical healing time of fracture, the PFNA group was significantly differently less than that of the reconstructing calcar group (<0.05).

CONCLUSIONSFor the treatment of unstable femoral intertrochanteric fractures in elderly patients, reconstructing calcar and PFNA are both effective, and proximal femoral intramedullary nails may be the best choice, which can be simpler operation, smaller incision and less healing time.

BACKGROUNDThe interaction between activated microglia and T lymphocytes can yield abundant pro-inflammatory cytokines. Our previous study proved that thymus immune tolerance could alleviate the inflammatory response. This study aimed to investigate whether intrathymic injection of myelin basic protein (MBP) in mice could suppress the inflammatory response after co-culture of T lymphocytes and BV-2 microglia cells.

METHODSTotally, 72 male C57BL/6 mice were randomly assigned to three groups (n = 24 in each): Group A: intrathymic injection of 100 μl MBP (1 mg/ml); Group B: intrathymic injection of 100 μl phosphate-buffered saline (PBS); and Group C: sham operation group. Every eight mice in each group were sacrificed to obtain the spleen at postoperative days 3, 7, and 14, respectively. T lymphocytes those were extracted and purified from the spleens were then co-cultured with activated BV-2 microglia cells at a proportion of 1:2 in the medium containing MBP for 3 days. After identified the T lymphocytes by CD3, surface antigens of T lymphocytes (CD4, CD8, CD152, and CD154) and BV-2 microglia cells (CD45 and CD54) were detected by flow cytometry. The expressions of pro-inflammatory factors of BV-2 microglia cells (interleukin [IL]-1β, tumor necrosis factor-α [TNF-α], and inducible nitric oxide synthase [iNOS]) were detected by quantitative real-time polymerase chain reaction (PCR). One-way analysis of variance (ANOVA) and the least significant difference test were used for data analysis.

RESULTSThe levels of CD152 in Group A showed an upward trend from the 3rd to 7th day, with a downward trend from the 7th to 14th day (20.12 ± 0.71%, 30.71 ± 1.14%, 13.50 ± 0.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The levels of CD154 in Group A showed a downward trend from the 3rd to 7th day, with an upward trend from the 7th to 14th day (10.00 ± 0.23%, 5.28 ± 0.69%, 14.67 ± 2.71% at postoperative days 3, 7, and 14, respectively, P < 0.05). The ratio of CD4+/CD8 + T in Group A showed a downward trend from the 3rd to 7th day, with the minimum at postoperative day 7, then an upward trend from the 7th to 14th day (P < 0.05). Meanwhile, the levels of CD45 and CD54 in Group A were found as the same trend as the ratio of CD4+/CD8 + T (CD45: 83.39 ± 2.56%, 82.74 ± 2.09%, 87.56 ± 2.11%; CD54: 3.80 ± 0.24%, 0.94 ± 0.40%, 3.41 ± 0.33% at postoperative days 3, 7, and 14, respectively, P < 0.05). The expressions of TNF-α, IL-1β, and iNOS in Group A were significantly lower than those in Groups B and C, and the values at postoperative day 7 were the lowest compared with those at postoperative days 3 and 14 (P < 0.05). No significant difference was found between Groups B and C.

CONCLUSIONSIntrathymic injection of MBP could suppress the immune reaction that might reduce the secondary immune injury of brain tissue induced by an inflammatory response.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Antigens, Surface ; analysis ; Brain Injuries, Traumatic ; drug therapy ; CD4-CD8 Ratio ; Coculture Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Microglia ; immunology ; Myelin Basic Protein ; administration & dosage ; pharmacology ; T-Lymphocytes ; immunology

Bladder cancer remains a commonly diagnosed malignancy worldwide, bringing huge economic burden and high morbidity for patients. Assessment of prognostic significance of lymphovascular invasion (LVI) is a critical issue in the surgical management of bladder cancer after transurethral resection or radical cystectomy. A systematic search of PubMed, Embase and Cochrane Library was performed up to Oct 10, 2014 to identify eligible studies. Outcomes of interest were collected from studies comparing overall survival (OS), cancer specific survival (CSS) and recurrence free survival (RFS) in patients with the LVI. Results of studies were pooled, and combined hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for survival were used as the effect size estimation. Funnel plots were done to show the publication bias, while the forest plots and subgroup analyses were used to limit the heterogeneity. A total of 20 studies (10 663 patients) met the eligibility criteria and were included for this meta-analysis. Our pooled results showed that there were significant differences in OS (pooled HR, 1.71; 95%CI, 1.52-1.92; P<0.00001), CSS (pooled HR, 2.25; 95% CI, 1.80-2.81; P<0.00001) and RFS (pooled HR, 1.91; 95% CI, 1.57-2.32; P<0.00001) between the patients with LVI and the patients without LVI. There were significant heterogeneities observed in the studies concerning the relationship between LVI and CSS, RFS. There was no clear evidence of publication bias. When tumor stage was beyond T3, LVI lost its predictive value for CSS and RFS. For the patients who had negative lymph nodes, LVI was still an adverse predictor. Our pooled results demonstrate that LVI indicates poor prognosis of patients with bladder cancer after surgical procedures, and it can be of particular importance in clinical practice. However, these results need to be further confirmed by more adequately designed prospective studies.
Carcinoma, Squamous Cell ; diagnosis ; mortality ; pathology ; surgery ; Cystectomy ; mortality ; Female ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Male ; Neoplasm Invasiveness ; Neoplasm Staging ; Prognosis ; Survival Analysis ; Urinary Bladder Neoplasms ; diagnosis ; mortality ; pathology ; surgery ; Urothelium ; pathology ; surgery

OBJECTIVETo investigate the therapeutic effects of the conditioning regimen with busulfan plus cyclophosphamide (BU+CY) or total body irradiation plus cyclophosphamide (TBI+CY) on haploidentical stem cell transplantation (HSCT) in hematologic malignancy.

METHODSThe clinical outcomes of 77 HSCT recipients with hematologic malignancy from January 2001 to December 2010, including 21 AML, 33 ALL, 19 CML and 4 MDS were retrospectively evaluated. Among them, 65 patients obtained complete remission (CR) and 12 non-remission (NR) before transplantation; 39 patients received conditioning regimen with BU+CY, and 38 with TBI+CY.

RESULTSThere were no statistically significant differences in hematopoietic reconstitution, disease free survival (DFS), and transplant- related mortality (TRM) between two groups. The estimated 3- years overall survival (OS) was 56.4% for BU+CY and 31.6% for TBI + CY (P=0.0283). The overall relapse rate was similar between two groups (15.4% vs 34.2%; P=0.1538). However, the accumulative probability of relapse at 1-year was significantly lower in BU+CY than that in TBI+CY group (2.56% vs 26.67%; P=0.0116). The incidence of grade II-IV graft-versus-host disease (GVHD) was similar between two regimens (20.5% in BU+CY group and 18.4% in TBI+CY group; P=0.8168). The incidence of chronic GVHD (cGVHD) was higher in the TBI+CY group than that of BU+CY group (84.6% vs 41.1%; P=0.0007). The extensive GVHD obtained the similar outcome (30.8% vs 10.5%; P=0.0416).

CONCLUSIONPatients using BU+CY as conditioning regimen before transplant could obtain a better 3 year OS and lower short-term relapse rate. The TBI+CY conditioning regimen could significantly increase the incidence of cGVHD without increasing the acute GVHD. BU+CY conditioning regimen could be used for HSCT, but the attention should be paid to prevent the related hemorrhagic cystitis.

Adolescent ; Adult ; Busulfan ; administration & dosage ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Transplantation Conditioning ; methods ; Whole-Body Irradiation ; Young Adult

OBJECTIVETo investigate the epidemiological characteristics of human infections with avian influenza A (H7N9) in China and to provide scientific evidence for the adjustment of preventive strategy and control measures.

METHODSDemographic and epidemiologic information on human cases were collected from both reported data of field epidemiological investigation and the reporting system for infectious diseases.

RESULTSA total of 433 cases including 163 deaths were reported in mainland China before June 4, 2014. Two obvious epidemic peaks were noticed, in March to April, 2013 and January to February, 2014. Confirmed cases emerged in 14 areas of China. Five provinces, including Zhejiang, Guangdong, Jiangsu, Shanghai, and Hunan, reported about 85% of the total cases. Median age of the confirmed cases was 58 years (range, 1-91), with 70% as males. Of the 418 cases with available data, 87% had ever exposed to live poultry or contaminated environments. 14 clusters were identified but human to human transmission could not be ruled out in 9 clusters.

CONCLUSIONHuman infections with avian influenza A (H7N9) virus showed the characteristics of obvious seasonal distribution, with certain regional clusters. The majority of confirmed cases were among the elderly, with more males seen than the females. Data showed that main source of infection was live poultry and the live poultry market had played a significant role in the transmission of the virus.

Adaptation, Psychological ; Aged ; Animals ; China ; epidemiology ; Demography ; Environmental Pollution ; Female ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; epidemiology ; prevention & control ; transmission ; Male ; Meat ; Poultry ; Research Design

OBJECTIVETo investigate the function of abnormal fibrinogen in two inherited dysfibrinogenemia pedigrees.

METHODSRoutine coagulation tests were conducted in the probands and related family members. The antigen and activity levels of fibrinogen were detected by immunoturbidimetry assay and clauss assay, respectively. All the exons and exon-intron boundaries of the three fibrinogen genes and antithrombin gene（AT3）were analyzed by PCR amplification and direct sequencing. Routine thrombelastography (TEG) test and functional fibrinogen TEG test were both used to make a comprehensive evaluation of coagulation status and functional fibrinogen level in patients. The molecular weights of the three peptides from fibrinogen were measured by Western blot. The function of abnormal fibrinogen was assessed by fibrinogen dynamic polymerization and fibrinolysis velocity.

RESULTSThe coagulation routine tests were normal in two probands except for prolonged thrombin time (TT) and reptilase time (RT), as well as reduced activity levels of 0.5 g/L and 0.6 g/L fibrinogen, respectively. The antigen levels of fibrinogen were 2.32 g/L and 2.66 g/L in two probands, which were in the normal reference range. The genotype analysis showed that Arg275His in fibrinogen γ chain (γ Arg275His) existed in both probands and patients in these two pedigrees. Meanwhile, proband B's grandfather and aunt also carried heterozygote g.5876T>C (Ser116Pro) mutation in AT3. The results of routine TEG test demonstrated that the α values of proband B and his father were close to and lower than the lower limit of reference range, respectively, while the MA values were normal in both of them. However, functional fibrinogen TEG test revealed obviously reduced MA value. All the probands and patients demonstrated prolonged lag-off time and reduced peak value in fibrinogen dynamic polymerization tests. Meanwhile, most of fibrin formed from the patients' plasma could not be dissolved completely by plasminogen (PLG) and urokinase-typeplasminogenactivator (u-PA) at a certain time.

CONCLUSIONWe first reported cases of inherited dysgibrinogenemia associated with inherited AT deficiency. γArg275His mutation caused the abnormal fibrinogen in terms of fibrin mono polymerization and possibly in fibrinolysis. Combined use of routine TEG test and functional fibrinogen TEG test with comprehensive analyses of the parameters in both tests could better evaluate the level of functional fibrinogen and predict the risk of hemorrhage and thrombosis in patients with inherited dysfibrinogenemia.

Adult ; Afibrinogenemia ; genetics ; Child ; Female ; Fibrinogen ; genetics ; Fibrinogens, Abnormal ; genetics ; physiology ; Genotype ; Humans ; Male ; Mutation ; Pedigree ; Phenotype

OBJECTIVETo explore the influence of water fluoride exposure on reproductive hormones in female.

METHODSCross-sectional study was conducted in seven villages of a county in Henan province by using simple random sampling including high fluoride area, defluoridation project area and control area on April, 2011 based on the preliminary study results of fluoride concentration in drinking water. Women who were born and growth or lived in the village at least 5 years and aged 18-48 years old were recruited using cluster sampling. They were divided into high fluoride group (HFG, 116 subjects), defluoridation project group (DFPG, 132 subjects) and control group (CG, 227 subjects) in accordance with the above areas. All subjects accepted questionnaire and physical checkup. Fasting blood and morning urine samples were collected. The concentration of fluoride in urine was determined by fluoride ion selective electrode method. The serum level of GnRH was detected using enzyme linked immunosorbent assay (ELISA). The serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) were determined by chemiluminesence immunoassay (CLIA).

RESULTSThe average age was (39.44 ± 7.34), (38.84 ± 8.03), (37.45 ± 7.70) years old in female from DFPG, HFG and CG respectively, there were no significant differences among the three groups (F = 3.02, P = 0.05). The urine fluoride levels were (1.34 ± 1.07), (2.59 ± 1.57), (0.92 ± 0.46) mg/ml in female from DFPG, HFG and CG respectively, there was a significant difference among three groups (F = 105.38, P < 0.01). No significant differences were observed of serum GnRH, LH, T, FSH and E2 among three groups in follicular phase (P > 0.05). The serum levels of E2 in Ovulatory period were 67.73, 58.09, 84.96 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in CG (H = 4.00, P < 0.05). The serum levels of T in Ovulatory period were 0.55, 0.45, 0.55 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 6.47, P < 0.05), but no significant difference was observed between HFG and CG (H = 2.41, P > 0.05). The serum levels of GnRH in Luteal phase were 24.09, 20.16, 23.50 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 14.14, P < 0.05) and CG (H = 12.53, P < 0.05). The serum level of E2 in luteal phase were 81.47, 64.60, 74.55 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 5.69, P < 0.05). As for LH, FSH and T, no significant differences were observed among the three groups (P > 0.05 respectively). The abnormal rates of E2 level were 22.73 (30/102), 37.93 (44/72), 20.26 (46/181) in female from DFPG, HFG and CG respectively. The E2 abnormal rate in female from HFG was higher that from DFPG (χ(2) = 6.82, P < 0.05) and CG (χ(2) = 12.38, P < 0.05).

CONCLUSIONFluoride exposure may influence reproductive hormones in female, especially in ovulatory and luteal phase of menstrual cycle.

Adult ; Cross-Sectional Studies ; Drinking Water ; chemistry ; Environmental Exposure ; adverse effects ; Estradiol ; blood ; Female ; Fluorides ; adverse effects ; urine ; Follicle Stimulating Hormone ; blood ; Gonadotropin-Releasing Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Menstrual Cycle ; drug effects ; Middle Aged ; Progesterone ; blood ; Testosterone ; blood

BACKGROUNDThe prevalence of chronic kidney disease (CKD) and prediabetes has increased in China, and at different rates in different locations. Therefore a community-based screening research was conducted in order to determine the prevalence of CKD and prediabetes, and to analyze associated risk factors of CKD and prediabetes in a city of Southern China.

METHODSA total of 7801 community residents aged 18 year and older from 6 communities were screened by a stratified random cluster sampling method. An estimated glomerular filtration rate (eGFR), albuminuria, fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) were measured. Age-standardized prevalence was calculated by the direct method with the use of data on the population distribution in China in 2006. Multivariate logistic analysis was used to analyze the risk factors of CKD and prediabetes, and association of insulin resistance (IR) with CKD and prediabetes was analyzed.

RESULTSThe age-standardized prevalence of CKD was 12.5%, eGFR < 60 ml×min(-1)×1.73 m(-2) was 2.7% and ACR (albumin to creatinine ratio) > 30 mg/g was 10.3%. The age-standardized prevalence of prediabetes was 12.1%. Logistic regression suggests that IR was a common independent risk factor of CKD and prediabetes. Further analysis show that HOMA-IR was increased with the aggravation of kidney injury and FPG.

CONCLUSIONCKD and prediabetes have become a major public health problem in Zhuhai, Southern China; insulin resistance may be an important risk factor.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State ; epidemiology ; Prevalence ; Renal Insufficiency, Chronic ; epidemiology ; Risk Factors ; Surveys and Questionnaires

The purpose of this study was to investigate the impact of leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3) on the biological features of bladder cancer cell lines. The plasmids of over-expressed LRIG3 and the blank plasmid serving as control were transfected into the bladder cancer cell lines, T24, EJ and BIU-87, and the expression levels of LRIG3 mRNA and protein were detected by using real-time PCR and Western blotting. The changes in the cell cycle and apoptosis were examined by using flow cytometry. The invasive ability was measured by Transwell assay, and CCK-8 assays were used to measure the proliferation of cells. As compared with the control group, the LRIG3 mRNA and protein expression levels in LRIG3 cDNA-transfected group were raised significantly (P<0.05). The average number of cells with up-regulated LRIG3 passing through the inserted filter was decreased significantly as compared with the control group (P<0.05). Up-regulation of LRIG3 also could inhibit proliferation and induce apoptosis of T24, EJ and BIU-87 cells. Except BIU-87, the T24 and EJ cells transfected with LIRG3 cDNA were arrested in G(0)/G(1) phase compared to the control group (P<0.05). In conclusion, the over-expression of LRIG3 could influence the cell cycle and invasion, inhibit proliferation and induce apoptosis in the three bladder cancer cell lines.
Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Membrane Proteins ; genetics ; metabolism ; Neoplasm Invasiveness ; Up-Regulation ; Urinary Bladder Neoplasms ; metabolism ; pathology