Genetic variant near TERC influencing the risk of gliomas with older age at diagnosis in a Chinese population.

A recent genome-wide association study has identified an association between rs1920116 near TERC and high-grade glioma in populations of European ancestry. In order to evaluate the effect of the SNP rs1920116 near TERC in the Chinese population, we examined associations of this candidate SNP with glioma in a sample of 1970 Chinese Han individuals. SNP genotype data were available for 980 Chinese glioma patients and 990 healthy controls. Logistic regression analyses were performed to evaluate the association between rs1920116 and glioma risk adjusted for age, gender and stratified by tumor grade where appropriate. The allele G at TERC rs1920116 are risk factors for gliomas, and its association with glioma risk was consistent across tumor subgroups in the Chinese Han population (OR = 1.18-1.21). In order to assess variation in SNP effect size at different patient ages, glioma cases and controls were divided into 3 age strata, in years: <50, 50-59, and 60+. The results of multiple logistic regression analyses indicate that the SNP has age-specific effects on the risk of developing glioma. Our report confirmed the effects of rs1920116 near TERC on glioma occurring in older peoples in the Chinese Han population for the first time. As TERC is a candidate for inter-individual variation in telomere length, our study supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life.

Human amniotic epithelial stem cells inhibit microglia activation through downregulation of tumor necrosis factor-α, interleukin-1ß and matrix metalloproteinase-12 in vitro and in a rat model of intracerebral hemorrhage.

BACKGROUND AIMS: The molecular mechanisms by which stem cell transplantation improves functional recovery after intracerebral hemorrhage (ICH) are not well understood. Accumulating evidence suggests that microglia cells are activated shortly after ICH and that this activation contributes to secondary ICH-induced brain injury. We studied the effect of human amniotic epithelial stem cells (HAESCs) on microglia activation. METHODS: To study the effect of HAESCs in vitro, we used thrombin to activate the microglia cells. Twenty-four hours after thrombin treatment, the levels of tumor necrosis factor-α and interleukin-1ß were measured by enzyme-linked immunosorbent assay. In vivo, the HAESCs were transplanted into the rat striatum 1 day after collagenase-induced ICH. The expression levels of matrix metalloproteinase (MMP)-12 and microglia infiltration in the peri-hematoma tissues were determined 7 days after ICH through the use of reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively. RESULTS: Thrombin-activated microglia expression of tumor necrosis factor-α, interleukin-1ß and MMP-12 was significantly reduced through contact-dependent and paracrine mechanisms when the HAESCs were co-cultured with microglia cells. After transplantation of HAESCs in rat brains, the expression levels of MMP-12 and microglia infiltration in the peri-hematoma tissues were significantly reduced. CONCLUSIONS: Our observations suggest that microglia activation could be inhibited by HAESCs both in vitro and in vivo, which may be an important mechanism by which the transplantation of HAESCs reduces brain edema and ameliorates the neurologic deficits after ICH. Therefore, we hypothesize that methods for suppressing the activation of microglia and reducing the inflammatory response can be used for designing effective treatment strategies for ICH.

Clinical Diagnostic Value of circ-ARHGER28 for Breast Cancer and its Effect on MCF 7 Cell Proliferation and Apoptosis.

BACKGROUND/AIM: Clinical diagnostic value of circ-ARHGER28 in breast cancer (BC), and the biological functions of circ-ARHGER28 on the proliferation and apoptosis of MCF-7 cells were investigated. MATERIALS AND METHODS: Human circRNA microarray was performed to analyze the expression of circRNAs in BC patients. RT-qPCR combined with bioinformatics analysis was applied to verify the candidate circRNAs in BC tissues and peripheral blood samples. Circ-ARHGER28 was chosen as the candidate gene for further research. The clinical diagnostic value and biological functions of circ-ARHGER28 were analyzed. The overexpression and negative control vector of circ-ARHGER28 were constructed and transfected to MCF-7 cells. The CCK 8 assay and clone formation experiments were applied to detect the cell proliferative and migratory abilities. Flow cytometry was used to analyze cell apoptosis and cell cycle distribution. RT-qPCR and Western blot were performed to detect apoptosis and expression of PI3K/AKT/mTOR-associated genes and proteins. RESULTS: Overexpression of circ-ARHGER28 inhibited the proliferation, colony formation and migration of MCF-7 cells, while increasing the population of the cells in the G2/M phase and the apoptotic rate. Apoptosis associated genes and proteins were significantly increased, whereas gene and protein expression of PI3K, AKT and mTOR were decreased in the cells. CONCLUSION: Circular RNA ARHGER28 exhibits promising diagnostic value for BC. Circ-ARHGER28 inhibited MCF-7 cell proliferation and increased the apoptotic rate. The function of circ-ARHGER28 was associated with the PI3K/AKT/mTOR signaling pathway. Circ-ARHGER28 could be an ideal biomarker for BC diagnosis and a novel target for BC therapy.

Reference intervals of complete blood count parameters for individuals aged 80 to 89 years in Guizhou, China: A STROBE-compliant retrospective study.

The reference intervals of complete blood count (CBC) parameters were commonly based on healthy individuals aged 20 to 79 years. However, these values are not optimal for correct clinical diagnosis in older individuals (e.g., 80-89 years). Although the reference intervals for this age group have been reported in China, there is no population-based report in Guizhou province. A total of 481 healthy adults (238 males and 243 females) aged 80 to 89 years were recruited from Affiliated Hospital of Zunyi Medical University in Guizhou. The CBC parameters were detected by Sysmex XN-9000 automatic hematology analyzer. The reference intervals of the components were analyzed according to the guidelines of International Federation of Clinical Chemistry. This study reported the reference intervals of CBC parameters. There were significant differences were examined in some reference intervals between the different gender groups, especially for RBC-related parameters. Compared with national standards, the most of all conventional reference intervals for CBC parameters were decreased. The present study provided the local reference intervals of CBC parameters for individuals aged 80 to 89 years in Guizhou, China. Some of our results were sex-specific, and most of our results show lower values while comparing with commonly used reference intervals in China. Therefore, more attentions should be paid to these differences, and accurate reference intervals will facilitate clinical diagnosis and decision-making in these populations.

Safety Analysis of Simultaneous Cranioplasty and Ventriculoperitoneal Shunt Placement.

AIM: To investigate the safety of combined cranioplasty (CP) and ventriculoperitoneal shunt (VPS) placement. Furthermore, we investigated whether the sequence of these procedures affects the postoperative complication rates associated with staged CP and VPS placement. MATERIAL AND METHODS: We retrospectively investigated patients who developed communicating hydrocephalus after decompressive craniectomy and subsequently underwent VPS placement and CP at the hospital at which this study was performed between January 2009 and December 2019. Patients were categorized into group 1 (simultaneous CP and VPS placement) and group 2 (CP and VPS placement performed separately). Group 2 was subcategorized into subgroup 2a (CP performed before VPS placement) and subgroup 2b (VPS placement performed before CP). The Student?s t and Chi square tests were used to analyze intergroup differences. RESULTS: This study included 86 patients; 22 in group 1 and 64 in group 2 (24 patients in subgroup 2a and 40 patients in subgroup 2b). No statistically significant difference was observed in the overall complication rates between groups 1 and 2 (36.4% vs. 28.1%, P=0.591). However, the incidence of infections was significantly higher in group 1 than in group 2 (22.7% vs. 4.7%, P=0.024). Subgroup analysis showed that the overall complication rate was signi?cantly lower in subgroup 2a than in subgroup 2b (12.5% vs. 37.5%, P=0.031). CONCLUSION: Simultaneous CP and VPS placement is associated with a high incidence of infections. Moreover, compared with initial CP, initial VPS placement is associated with a significantly higher risk of overall complications in patients who undergo a staged procedure.

Four common polymorphisms in microRNAs and the risk of adult glioma in a Chinese case-control study.

Emerging evidence has shown that microRNAs (miRNAs) participate in human carcinogenesis as tumor suppressors or oncogenes. It has been suggested that four common single nucleotide polymorphisms (SNPs; miR-146aG > C, 149C > T, 196a2C > T, and 499A > G) are associated with susceptibility to numerous malignancies. However, published results are inconsistent and inclusive. To further investigate the role of these loci, we examined the association of the miRNA polymorphisms with the risk of gliomas in a Han population in northeastern China. Both miR-146aG > C and 196a2C > T showed allelic differences between glioma patients and healthy controls in the studied population, with an OR of 1.30 (P = 0.0006) and an odds ratio (OR) of 1.25 (P = 0.003), respectively. Logistic regression analysis also revealed that the 146aG > C and 196a2C > T wild-type homozygous carriers had an increased glioma risk compared to the variant carriers. Besides, in pairwise comparisons two SNP combinations were associated with the risk of glioma. Among others, carriers of both homozygous risk genotypes, i.e., 146aGG and 196a2CC were associated with a nearly 4-fold increased risk of glioma (OR = 3.77, P = 1.3 × 10(-4)). Overall, glioma risk increased with increasing numbers of risk variant alleles. These results suggest that the miR-146aG > C and 196a2C > T might influence the risk of developing glioma in a northeastern Han Chinese population.

Intensive insulin therapy on infection rate, days in NICU, in-hospital mortality and neurological outcome in severe traumatic brain injury patients: a randomized controlled trial.

OBJECTIVES: Evaluate the impact of an intensive insulin therapy and conventional glucose control protocol during staying in neurological intensive care unit (NICU) on infection rate, days in NICU, in-hospital mortality and long-term neurological outcome in severe traumatic brain injury (TBI) patients. METHODS: A total of 240 patients with severe TBI (GCS score 3-8) admitted to NICU were prospectively enrolled and randomly assigned either to conventional insulin therapy or to intensive insulin therapy. Patients in intensive glucose control group (n=121) received continuous insulin infusion to maintain glucose levels between 4.4 m mol/l (80 mg/dl) and 6.1 m mol/l (110 mg/dl). Patients in the conventional treatment group (n=119) were not given insulin unless glucose levels were greater than 11.1 m mol/l (200mg/dl). Both groups were treated with insulin infusion to maintain normoglycemia after leaving NICU. Comparison was made against conventional insulin therapy using a randomized trial design. The primary outcomes is the mortality rate at 6 months follow-up. The second outcomes including ICU infection rate, duration of ICU stay, in-hospital mortality rate and neurologic outcome at 6 months follow-up. RESULTS: There was no significant difference in gender (66% vs. 67% male), age (46+/-11 years vs. 45+/-10 years), APACHE II score (30 vs. 29), TISS-28 score (47 vs. 46), and Glasgow Coma Score (GCS, 5.3 vs. 5.3) between the two groups. Overall mortality rates at 6 months follow-up were similar in the 2 groups (61 of 117, 52.1% vs. 62 of 116, 53.4%; P=0.8). The infection rate during the study was significantly higher in patients who received conventional insulin therapy than that in patients who received intensive insulin therapy (46.2% vs. 31.4%; P<0.05). The days stay in NICU was shorter in intensive insulin control group than that in conventional therapy group [4.2 days vs. 5.6 days (medians) P<0.05]. The in-hospital mortality during the study was similar in conventional and intensive therapy groups (34 of 119, 28.6% vs. 35 of 121, 28.9% in the conventional and intensive insulin therapy groups; P=0.85). The neurologic outcome according to Glasgow Outcome Score (GOS) at 6 months (GOS 5 and 4) was better in the intensive insulin therapy group (34 of 117, 29.1%) than that in the conventional therapy group (26 of 116, 22.4%, P<0.05). CONCLUSIONS: Mortality rates at 6 months follow-up are not affected by intensive glucose control in patients with severe TBI. Intensive insulin therapy decreases infection rate and days in NICU and improves the neurological outcome at 6 months follow-up, while has no obvious influence on in-hospital mortality of severe TBI patients.