Clinical Efficacy of Temozolomide and Its Predictors in Aggressive Pituitary Tumors and Pituitary Carcinomas: A Systematic Review and Meta-Analysis

Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable.Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment.Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007).Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy

TiO2 Nanoparticles Anchoring on Two-Dimensional Bi2Se3 Nanosheet As An Enhanced Visible Light Catalyst

Abstract Titanium dioxide (TiO2) has been widely studied in the field of photocatalysis. However, the development of TiO2 was limited by the photoresponse only in the ultraviolet region and the rapid recombination of photogenerated electron-hole pairs. In this work, TiO2 and two-dimensional (2D) bismuth selenide (Bi2Se3) hybrid nanosheets (TiO2/Bi2Se3 HNs) have been prepared via a simple ultrasonic route. X-ray diffraction pattern and Raman spectra were carried out to confirm that as-prepared samples were pure and well crystalized. Besides, the microstructure characterization proves that 2D Bi2Se3 nanosheets have high specific surface area and can serve as a stable platform to construct the intimate interaction with TiO2. Furthermore, photoelectrochemical (PEC) measurements demonstrate that the TiO2/Bi2Se3 HNs exhibit excellent photocatalytic performance under visible light, which were much better than pure TiO2 and Bi2Se3. More importantly, the photocurrent density was quite stable and only dropped by 10% after 125 cycles. In summary, the improved photocatalytic activity is due to the unique characteristic of 2D Bi2Se3 nanosheets, such as maximized reaction sites and good electrical conductivity, and the positive coupling effect of the TiO2/Bi2Se3 heterojunction. This study indicates that TiO2/Bi2Se3 HNs photocatalysts have excellent potential for photocatalytic application.</jats:p

Plasma Metabolomic Profiling of Individuals Susceptible to High Altitude through Gas Chromatograph- mass Spectrometry

Abstract Objective We aimed to characterize metabolic alterations of people ascending to high altitude and susceptible to acute mountain sickness (AMS). Methods Peripheral blood samples were collected from 36 healthy volunteers on the 3rd day ascending to high altitude (4300m). AMS status was assessed using the Lake Louise Questionnaire. Plasma samples were characterized by gas chromatography-mass spectrometry (GC-MS) and principal component analysis (PCA) was used to discriminate the metabolite changes between sea level and high altitude status and between AMS group and non-AMS group. Results High altitude hypobaric hypoxia caused significant and comprehensive metabolic changes in plasma, including 18 metabolites between sea level and high altitude, 6 metabolites between AMS group and non-AMS group. By using MetaboAnalyst 3.0, several key metabolic pathways were found to be involved, including cysteine and methionine metabolism, alanine, aspartate and glutamate metabolism. Conclusion The GC-MS profiling was a useful approach to analyze metabolites variances and provides potential targets for further investigation to understand the pathophysiological mechanism of hypobaric hypoxia and susceptibility to high altitude.</jats:p

Puerarin Attenuates Ovalbumin-Induced Lung Inflammation and Hemostatic Unbalance in Rat Asthma Model

Aim. We aimed to investigate and evaluate the preventive activity of puerarin on the ovalbumin-induced asthma rat model. Materials and Methods. Male Wistar rats were sensitized intraperitoneally on days 0, 7, and 14 and challenged to ovalbumin intratracheally on day 21. Groups of sensitized rats were treated randomly either with placebo, puerarin, dexamethasone, or puerarin combined with dexamethasone, from days 15 to 20. Inflammatory markers, including cell counts in bronchoalveolar lavage fluid (BALF), inflammatory cytokines, histopathology, and coagulation parameters, such as coagulation tests and the activity of coagulation factors, were analyzed. Results. Puerarin significantly inhibited the recruitment of inflammatory cells in BALF and lung tissue. At the same time, the release of IL-4, IL-10, and IFN-γ in serum and the expression of mRNAs in lung tissue homogenate were changed by puerarin. Administration of puerarin also effectively rectified the coagulation disorder in asthmatic rats, such as prothrombin time (PT) (P<0.01), thrombin time (TT) (P<0.05), fibrinogen (FIB) (P<0.01),the activity of factor II (FII) (P<0.01), the activity of factor V (FV) (P<0.05), the activity of factor VII (FVII) (P<0.05), the activity of factor X (FX) (P<0.05), the activity of factor VIII (FVIII) (P<0.01), the activity of factor IX (FIX) (P<0.05), and the activity of factor XII (FXII) (P<0.05). Conclusions. Our results provide a clue that puerarin was useful for the preventive of allergic airway disease in rodents

Impact of growth hormone-secreting pituitary adenoma on limbic system and its correlation with cognitive impairment

Purpose: To assess the quantitative gray matter volume of the limbic system in growth hormone-secreting pituitary adenoma (GHPAs) patients and its correlation to cognitive function. Method: 91 right-handed patients with pituitary adenomas were retrospectively included from the First Affiliated Hospital of Sun Yat-sen University −48 with GHPAs and 43 with non-functioning pituitary adenomas (NFPAs). Participants underwent serum hormone assessment, regular sellar MRI scanning with T1WI-MPRAGE. Cognitive function was gauged using MoCA and MMSE. Brain region auto-segmentation and gray matter volume calculation were conducted on the Brainsite platform. Results: Compared to NFPAs patients, GHPAs patients had higher gray matter volume (758,285 vs 674,610 mm³, p < 0.001). No significant volumetric differences in both sides of limbic system gray matter while there were evident differences in the relative volumes of limbic system gray matter between groups. GHPAs patients scored lower on MOCA (24.0 (2.18) vs 25.1 (2.28), p < 0.031), with no difference in MMSE. We observed a significant correlation between the relative limbic volume and MOCA scales, while no evident correlation was found between relative limbic volume and serum hormone or tumor aggressiveness. Univariate and multivariate Logistic regression showed that hippocampus and limbic cortex (parahippocampal gyrus and internal olfactory area) of advantageous hemisphere correlated significantly with occurrence of mild cognitive impairment with the C-statistic reaching 0.90. Conclusion: Patients with GHPAs show a relative decrease in limbic gray matter volume, especially in the hippocampus and limbic cortex of the dominant hemisphere, which is associated with mild cognitive impairment