Trophinin-associated protein expression correlates with shorter survival of patients with glioma: a study based on multiple data fusion analysis.

BACKGROUND: Trophinin-associated protein (TROAP) mediates embryonic transfer, regulates microtubules, and is associated with the biological behavior of various cancers. However, there is limited information on the role of TROAP in glioma. METHODS AND RESULTS: We obtained clinical information on 1948 patients with glioma from The Cancer Genome Atlas, Gene Expression Omnibus and the Chinese Glioma Genome Atlas. Basal assays were used to measure changes in TROAP expression levels in high-grade glioma cell lines and in normal human astrocytes. Quantitative reverse transcription polymerase chain reaction assays showed that TROAP expression was higher in glioma cell lines than in normal astrocytes. The expression level of TROAP in 749 glioma was significantly higher than that in 228 normal brain tissues using Student's t test. The expression of TROAP has a positive relationship with the clinical characteristics of poor prognosis, such as WHO grade, age and has negatively correlated with the indicators of beneficial prognosis, such as IDH mutation and 1p19q co-deletion. Kaplan-Meier survival curves, single multifactor analysis were used to analyze correlations between TROAP and clinical features and prognosis of gliomas. In addition, TROAP overexpression was an independent risk factor for glioma and was associated with reduced overall survival of patients with glioma particularly in patients with WHO grade III and grade IV glioma. Gene set enrichment analysis showed that homologous recombination, cell cycle, and p53 signaling pathways were enriched in samples overexpressing TROAP. CONCLUSION: TROAP is a potential risk factor associated with poor prognosis in patients with glioma and may act as a highly specific biomarker, offering the possibility of individualized glioma treatment.

Impact of thymosin α1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection: a propensity score-matched analysis.

BACKGROUND: There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients. METHODS: A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients. RESULTS: After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy. CONCLUSION: Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

Is It Necessary to Perform the Pharmacological Interventions for Intrahepatic Cholestasis of Pregnancy? A Bayesian Network Meta-Analysis.

BACKGROUND AND OBJECTIVE: Although many meta-analyses have evaluated the pharmacotherapy of intrahepatic cholestasis of pregnancy (ICP) and recommended ursodeoxycholic acid (UDCA) as an effective treatment, the defect of the pair-wise analyses and the mixture of the control group made the outcome uncertain and unclear. We aimed to employ Bayesian network meta-analysis (NMA) to compare the maternal and fetal outcomes after UDCA, S-adenosylmethionine (SAMe) mono-therapy or the combination treatment of these two drugs for ICP patients. METHODS: Multiple electronic database searches were conducted for articles published up to 1 September 2018. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk-of-bias tool. Poisson Bayesian network meta-analysis was employed to identify the synthesized evidence from the relevant trials, with reporting hazard risks (HRs) and 95% credible intervals (CrIs). RESULTS: The pooled outcomes of the 13 randomized controlled trials (RCTs) with 625 participants indicated that none of the three regimens can significantly improve maternal and fetal outcomes. CONCLUSION: This NMA of the RCTs clarified that the current intervention has no favorable effect on pruritus and other symptoms in ICP patients.

Combination of mild therapeutic hypothermia and adipose-derived stem cells for ischemic brain injury.

Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia (33°C) was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the mRNA expression of the proinflammatory cytokines interleukin-1ß, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.

[Effect of pamidronate on cementoclast and osteoclast differentiation factor expression during orthodontic tooth movement in rats].

PURPOSE: To investigate the influence of pamidronate on cementoclast and osteoclast differentiation factor(ODF) expression during orthodontic tooth movement in rats. METHODS: 24 female, 6-week-old SPF Wistar rats were selected and the animal models for orthodontic tooth movement were established. Each rat's maxillary was divided into experimental side and control side. Pamidronate(50 µL) was injected into the sub-periosteum area adjacent to the left upper first molar(experimental side) every 3 days during the experiment, while 0.9%NS(50 µL) was injected into the corresponding area of the control side. The rats were executed in batch on the 3rd, 7th and 14th day respectively during the orthodontic treatment for detecting the amount of cementoclast and the expression of ODF in the periodontal tissues. All statistical analysis was performed using PASW Statistics 18 software package. RESULTS: The amount of cementoclasts was significantly less in the experimental side than that in the control side on the 7th and 14th days(P<0.05). The expression of ODF was significantly less in the experimental side than that in the control side on the 7th and 14th days(P<0.05). CONCLUSIONS: Local injection of pamidronate can reduce the number of cementoclast and the expression of ODF.

Synthesis and antityrosinase mechanism of benzaldehyde thiosemicarbazones: novel tyrosinase inhibitors.

p-Hydroxybenzaldehyde thiosemicarbazone (HBT) and p-methoxybenzaldehyde thiosemicarbazone (MBT) were synthesized and established by (1)H NMR and mass spectra. Both compounds were evaluated for their inhibition activities on mushroom tyrosinase and free-cell tyrosinase and melanoma production from B(16) mouse melanoma cells. Results showed that both compounds exhibited significant inhibitory effects on the enzyme activities. HBT and MBT decreased the steady state of the monophenolase activity sharply, and the IC(50) values were estimated as 0.76 and 7.0 µM, respectively. MBT lengthened the lag time, but HBT could not. HBT and MBT inhibited diphenolase activity dose-dependently, and their IC(50) values were estimated as 3.80 and 2.62 µM, respectively. Kinetic analyses showed that inhibition type by both compounds was reversible and their mechanisms were mixed-type. Their inhibition constants were also determined and compared. The research may supply the basis for the development of new food preservatives and cosmetic additives.

[Comparative study of mesh-plug and polypropylene hernia system tension-free hernioplasty for inguinal hernia].

OBJECTIVE: To compare the effects of mesh-plug and polypropylene hernia system (PHS) tension-free hernioplasty so as to explore the strategy of treatment for different patients. METHODS: Eighty patients with inguinal hernia were assigned into 3 equal groups according to the randomization schedule: PHS group and mesh-plug group. The operating time and the outcomes were recorded. RESULTS: The operating times of the mesh-plug group was 73.8 minutes significantly longer than that of the PHS group (56.5 minutes, P < 0.05). There was no significant difference in the recovery progress between these 2 groups. The numbers of patients who had sense of foreign body and numbness in the mesh-plug group were significantly greater than those in the PHS group (both P < 0.05). CONCLUSIONS: Mesh-plug tension-free hernioplasty is indicated for most inguinal hernia patients owing to the simple operation. More rational in design and more effective in reduction of recurrence, PHS is suitable for thin patients or patients with week or large transversalis fascia defection. And PHS is able to reduce the postoperative discomfort.