A bibliometric analysis of the application of the PI3K-AKT-mTOR signaling pathway in cancer.

PI3K-AKT-mTOR plays as important role in the growth, metabolism, proliferation, and migration of cancer cells, and in apoptosis, autophagy, inflammation, and angiogenesis in cancer. In this study, the aim was to comprehensively review the current research landscape regarding the PI3K-AKT-mTOR pathway in cancer, using bibliometrics to analyze research hotspots, and provide ideas for future research directions. Literature published on the topic between January 2006 and May 2023 was retrieved from the Web of Science core database, and key information and a visualization map were analyzed using CiteSpace and VOSviewer. A total of 5800 articles from 95 countries/regions were collected, including from China and the USA. The number of publications on the topic increased year on year. The major research institution was the University of Texas MD Anderson Cancer Center. Oncotarget and Clinical Cancer Research were the most prevalent journals in the field. Of 26,621 authors, R Kurzrock published the most articles, and J Engelman was cited most frequently. "A549 cell," "first line treatment," "first in human phase I," and "inhibitor" were the keywords of emerging research hotspots. Inhibitors of the PI3K-AKT-mTOR pathway and their use in clinical therapeutic strategies for cancer were the main topics in the field, and future research should also focus on PI3K-AKT-mTOR pathway inhibitors. This study is the first to comprehensively summarize trends and development s in research into the PI3K-AKT-mTOR pathway in cancer. The information that was obtained clarified recent research frontiers and directions, providing references for scholars of cancer management.

Astragaloside IV protects LO2 cells from oxidative damage caused by radiation-induced bystander effect through Akt/Nrf2 pathway.

Background: The protective effects of astragaloside IV (ASIV) on various diseases are well known, but its potential impact on radiation-induced bystander effect (RIBE) has remained unclear. Objective: This study aimed to explore the protective mechanism of ASIV against oxidative damage caused by RIBE in LO2 cells. Methods: To construct the RIBE model, the conditioned medium from HepG2 cells irradiated with radiation was transferred to nonirradiated LO2 cells. LY294002, a commonly used phosphatidylinositol 3-kinase/Akt pathway inhibitor, was added to LO2 cells 1 h before exposing HepG2 cells to radiation. LO2 cells were then collected for analyses after RIBE exposure. Results: The study found that ASIV significantly improved cell proliferation and promoted the recovery of mitochondrial membrane potential while reducing the rate of apoptosis. Western blot analyses demonstrated that ASIV upregulated B-cell lymphoma 2 and downregulated B-cell lymphoma 2-related X protein and cleaved-caspase 3. Measurement of reactive oxygen species, superoxide dismutase, glutathione peroxidase, and malondialdehyde levels showed that ASIV effectively restored the oxidative stress state induced by RIBE. Additionally, immunofluorescence and western blots analyses confirmed that ASIV enhanced the translocation of Nrf2 to the nucleus and activated downstream nicotinamide adenine dinucleotide phosphate: quinine oxidoreductase 1 and heme oxygenase 1. Importantly, Akt pathway inhibitor repressed ASIV-induced activation of Nrf2 and its protective effect against RIBE. Conclusion: This study demonstrates that ASIV protects LO2 cells against oxidative damage caused by RIBE through activation of the Akt/Nrf2 pathway.

Individualized psychiatric imaging based on inter-subject neural synchronization in movie watching.

The individual heterogeneity is a challenge to the prosperous promises of cutting-edge neuroimaging techniques for better diagnosis and early detection of psychiatric disorders. Individuals with similar clinical manifestations may result from very different pathophysiology. Conventional approaches based on comparing group-averages provide insufficient information to support the individualized diagnosis. Here we present an individualized imaging methodology that combines naturalistic imaging and the normative model. This paradigm adopts video clips with rich cognitive, social, and emotional contents to evoke synchronized brain dynamics of healthy participants and builds a spatiotemporal response norm. By comparing individual brain responses with the response norm, we could recognize patients using machine learning techniques. We applied this methodology to recognize first-episode drug-naïve schizophrenia patients in a dataset containing 72 patients and 54 healthy controls. Some segments of the video evoked more synchronized brain activity in the healthy controls than in the schizophrenia patients. We built a spatiotemporal response norm by averaging the brain responses of the healthy controls in a training set, and trained a classifier to recognize patients based on the differences between individual brain responses and the norm. The performance of the classifier was then evaluated using an independent test set. The mean accuracies from a 5-fold cross-validation were 0.71-0.78 depending on the parameters such as the number of features and the width of the sliding windows. These findings reflected the potential of this methodology towards a clinical tool for individualized diagnosis.

Segregated precuneus network and default mode network in naturalistic imaging.

A resting-state network centered at the precuneus has been recently proposed as a precuneus network (PCUN) or "parietal memory network". Due to its spatial adjacency and overlapping with the default mode network (DMN), it is still not consensus to consider PCUN and DMN separately. Whether considering PCUN and DMN as different networks is a critical question that influences our understanding of brain functions and impairments. Previous resting-state studies using multiple methodologies have demonstrated a robust separation of the two networks. However, since there is no gold standard in justifying the functional difference between the networks in resting-state, we still lack of biological evidence to directly support the separation of the two networks. This study compared the responses and functional couplings of PCUN and DMN when participants were watching a movie and examined how the continuity of the movie context modulated the response of the networks. We identified PCUN and DMN in resting-state fMRI of 48 healthy subjects. The networks' response to a context-rich video and its context-shuffled version was characterized using the variance of temporal fluctuations and functional connectivity metrics. The results showed that (1) scrambling the contextual information altered the fluctuation level of DMN and PCUN in reversed ways; (2) compared to DMN, the FC within PCUN showed significantly higher sensitivity to the contextual continuity; (3) PCUN exhibited a significantly stronger functional network connectivity with the primary visual regions than DMN. These findings provide evidence for the distinct functional roles of PCUN and DMN in processing context-rich information and call for separately considering the functions and impairments of these networks in resting-state studies.

Homotopic Connectivity in Early Pontine Infarction Predicts Late Motor Recovery.

Connectivity-based methods are essential to explore brain reorganization after a stroke and to provide meaningful predictors for late motor recovery. We aim to investigate the homotopic connectivity alterations during a 180-day follow-up of patients with pontine infarction to find an early biomarker for late motor recovery prediction. In our study, resting-state functional MRI was performed in 15 patients (11 males, 4 females, age: 57.87 ± 6.50) with unilateral pontine infarction and impaired motor function during a period of 6 months (7, 14, 30, 90, and 180 days after stroke onset). Clinical neurological assessments were performed using the Fugl-Meyer scale (FM).15 matched healthy volunteers were also recruited. Whole-brain functional homotopy in each individual scan was measured by voxel-mirrored homotopic connectivity (VMHC) values. Group-level analysis was performed between stroke patients and normal controls. A Pearson correlation was performed to evaluate correlations between early VMHC and the subsequent 4 visits for behavioral measures during day 14 to day 180. We found in early stroke (within 7 days after onset), decreased VMHC was detected in the bilateral precentral and postcentral gyrus and precuneus/posterior cingulate cortex (PCC), while increased VMHC was found in the hippocampus/amygdala and frontal pole (P < 0.01). During follow-up, VMHC in the precentral and postcentral gyrus increased to the normal level from day 90, while VMHC in the precuneus/PCC presented decreased intensity during all time points (P < 0.05). The hippocampus/amygdala and frontal pole presented a higher level of VMHC during all time points (P < 0.05). Negative correlation was found between early VMHC in the hippocampus/amygdala with FM on day 14 (r = -0.59, p = 0.021), day 30 (r = -0.643, p = 0.01), day 90 (r = -0.693, p = 0.004), and day 180 (r = -0.668, p = 0.007). Furthermore, early VMHC in the frontal pole was negatively correlated with FM scores on day 30 (r = -0.662, p = 0.013), day 90 (r = -0.606, p = 0.017), and day 180 (r = -0.552, p = 0.033). Our study demonstrated the potential utility of early homotopic connectivity for prediction of late motor recovery in pontine infarction.

Effect of femtosecond and microkeratome flaps creation on the cornea biomechanics during laser in situ keratomileusis: one year follow-up.

AIM: To compare the corneal biomechanical outcomes at one year after laser in situ keratomileusis (LASIK) with the flaps created by Ziemer and Moria M2 microkeratome with 110 head and -20 blade. METHODS: Totally 100 eyes of 50 consecutive patients were enrolled in this prospective study and divided into two groups for corneal flaps created by ZiemerFemto LDV and Moria M2 microkeratome with 110 head and -20 blade. Corneal biomechanical properties including cornea resistance factor (CRF) and cornea hysteresis (CH) were measured before and 1, 3, 6, 12mo after surgery by ocular response analyzer. Central cornea thickness and corneal flap thickness were measured by optical coherence tomography. RESULTS: The ablation depth (P=0.693), residual corneal thickness (P=0.453), and postoperative corneal curvature (P=0.264) were not significant different between Ziemer group and Moria 110-20 group after surgery. The residual stromal bed thickness, corneal flap thickness, CH and CRF at 12mo after surgery were significant different between Ziemer group and Moria 110-20 group (P<0.01);Ziemer group gained better corneal biomechanical results. The CRF and CH increased gradually from 1 to 12mo after surgery in Ziemer group, increased from 1 to 6mo but decreased from 6 to 12mo in Moria 110-20 group. Both CRF and CH at one year after surgery increased with the increasing of residual cornea thickness; pre-LASIK CRF, CRF also increased with residual stromal bed thickness, while CH decreased with the increasing of pre-LASIK intraocular pressure and cornea flap thickness (P<0.01). CONCLUSION: In one year follow-up, femtosecond laser can provide better cornea flaps with stable cornea biomechanics than mechanical microkeratome.

Comparison of Visual Outcomes After Femtosecond LASIK, Wave Front-Guided Femtosecond LASIK, and Femtosecond Lenticule Extraction.

PURPOSE: To compare the mesopic contrast sensitivity (CS) and higher order aberrations (HOAs) at 3 months after femtosecond-laser in situ keratomileusis (LASIK) (FS-LASIK), wave front-guided femtosecond LASIK (WF-LASIK), and femtosecond lenticule extraction (FLEx) for the correction of myopia and myopic astigmatism. METHODS: In this prospective nonrandomized study, 332 right eyes of 332 patients were treated with FS-LASIK, WF-LASIK, or FLEx. The HOAs and mesopic CS were evaluated preoperatively and at 3 months postoperatively. RESULTS: At 3 months of follow-up, 98 eyes (96.1%) of the FS-LASIK group, 92 eyes (98.9%) of the WF-LASIK group, and 133 eyes (96.4%) of the FLEx group had an uncorrected distance visual acuity of 20/20 or better. The HOAs improved from 0.34 µm during preoperative examination to 0.56 µm of the end of the follow-up in the FS-LASIK group, from 0.31 to 0.41 µm in the WF-LASIK group, and from 0.32 to 0.54 µm in the FLEx group (all P < 0.01). At a spatial frequency of 12 cycles per degree, a better mesopic CS was observed in the WF-LASIK group (1.47) than in the FS-LASIK (1.36) and FLEx (1.33) groups (P < 0.01); a better mesopic CS with glare was also noted in the WF-LASIK group (1.37) than in the FS-LASIK (1.25) and FLEx (1.29) groups (P < 0.01). CONCLUSIONS: The FS-LASIK, WF-LASIK, and FLEx procedures result in comparable refractive results at 3 months postoperatively. However, there is improvement in the mesopic CS and HOAs after WF-LASIK.

[Treatment of vocal cord submucosal bleeding with pricking therapy].

OBJECTIVE: To observe the clinical efficacy of pricking bleeding of 3 points of the thumb tip, and 3 points of the auricular helix for treatment of vocal cord submucosal bleeding (VCSB), so as to provide a better therapy for it. METHODS: Sixty VCSB patients were equally randomized into pricking bleeding group and ultrasonic atomizing inhalation (UAI) group. Pricking bleeding was applied to Shaoshang (LU 11, 0. 1 cun to the nail on the radial side), Zhongshang (the center of the thumb back, 0. 1 cun to the nail), Laoshang (0. 1 cun to the nail on the ulnar side), Lun 1, 3 and 5 (MA-H) of the helix, once daily for 7 days. Ultrasonic atomizing inhalation treatment was given to patients of the UAI group for 15 min every time, once daily for 7 days. The scores of symptoms and signs and their difference values were calculated before and after the treatment. The acoustical parameters maximum phonation time (MPT), frequency perturbation quotient (FPQ), amplitude perturbation quotient (APQ), ratio of harmonic to noise (H/N) were detected by using a USSA Computer Language Phonetic Spectrum Analysis System. RESULTS: Of the two 30 cases of VCSB patients in the pricking bleeding and UAI groups, 20 (66.67%) and 12(40.00%)were cured, 7 (23.33%) and 6 (20.00%) were improved remarkably, 3 (10.00%) and 8 (26.67%) improved, and 0 and 4 (13.33%) failed, with the cure plus markedly effective rates being 90% and 60%, respectively. The cure plus markedly effective rate of the pricking bleeding group was significantly superior to that of the UAI group (P<0. 01). The difference values between pre-treatment and post-treatment in hoarseness, laryngalgia, throat dryness, throat burning sensation, throat clearing, vocal bleeding, glottis dysraphism, and total score were significantly higher in the pricking bleeding group than those in the UAI group (P<0.05). In comparison with the pre-treatment, MPT and H/N values were increased obviously (P<0. 05), and FPQ and APQ decreased clearly in the two groups after the treatment (P<0.05), suggesting an improvement of the acoustical parameters after the treatment. But, no significant differences were found between the two groups (P>0. 05). CONCLUSION: Pricking bleeding therapy is effective in relieving submucosal bleeding of the vocal cord and can improve its clinical symptoms and signs.