bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and functional characteristics of OSA in children with comorbid asthma treated by leukotriene receptor antagonist: A descriptive study
Authors: Duong-Quy Sy , Nguyen-Hoang Yen , Nguyen-Ngoc-Quynh Le , Nguyen-Thi-Phuong Mai , Nguyen-Thi-Bich Hanh , Le-Thi-Minh Huong , Nguyen-Thi-Dieu Thuy
Published: January 2023

Background

Obstructive sleep apnea (OSA) is the most common form of respiratory disorders during sleep in children, especially those with severe asthma. However, optimal treatment of asthma might significantly improve OSA severity.

Methods

It was a cohort study including children aged >5 years old and diagnosed with asthma according to GINA (Global Initiative for Asthma). The data related to age, gender, height, weight, body mass index (BMI), clinical symptoms and medical history of asthma, spirometry (FEV1: forced expiratory in 1 s), and exhaled nitric oxide (FENO) were recorded for analysis. Respiratory polygraphy (RPG) was done for each study subject to diagnose OSA and its severity.

Results

Among 139 asthmatic children, 99 patients with OSA (71.2%) were included in the present study (9.3 ± 0.2 years): 58.6% with uncontrolled asthma and 32.3% with partial controlled asthma. The mean ACT (asthma control testing) score was 19.0 ± 3.4. The most frequent night-time symptoms were restless sleep (76.8%), snoring (61.6%), sweating (52.5%), and trouble breathing during sleep (48.5%). The common daytime symptoms were irritable status (46.5%) and abnormal behavior (30.3%). The mean AHI (apnea-hypopnea index) was 3.5 ± 4.0 events/h. There was a significant correlation between BMI and snoring index (R = 0.189 and P = 0.027), bronchial and nasal FENO with AHI (R = 0.046 and P < 0.001; R = 0.037 and P < 0.001; respectively). There was no significant correlation between asthma level, FEV1 and AHI. The severity of asthma and respiratory function were improved significantly after 3 months and 6 months of asthma treatment in combination with leukotriene receptor antagonist (LRA) treatment. The symptoms related to OSA were significantly improved after treatment with LRA. The severity of OSA was decreased significantly after 3 months and 6 months of treatment.

Conclusion

The treatment of asthmatic children with comorbid OSA by LRA in combination with standard therapy for asthma could improve the control of asthma and the symptoms and severity of OSA.
Inflammation and endothelial function relevant genetic polymorphisms in carotid stenosis in southwestern China
Authors: Liu Lin , Yi Xingyang , Luo Hua , Yu Ming
Published: January 2023

Aim

To evaluate the relationship between carotid stenosis with variants in genes referred to inflammation and endothelial function.

Methods

There was a multi-center, cross sectional survey in southwestern China. The eight communities were selected at random in southwestern China. The residents aged ≥40 years volunteered to participate in face-to-face survey. Subjects with at least three of the aforementioned eight stroke related risk factors or a history of stroke were classified as high-risk population for stroke. A total of 2,377 subjects were the high-risk population for stroke in the eight communities, and degree of carotid stenosis was assessed by carotid ultrasound. Genotypes of 6 variants in 3 genes related to inflammation and endothelial function were examined. Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction (GMDR).

Results

Carotid stenosis were found in 295 (12.41%) subjects, of whom 51 (17.29%) had moderate or severe stenosis. According to multivariate logistic regression analysis, we found that HABP2rs7923349TT was independent risk factor for carotid stenosis (OR, 1.96, 95% CI: 1.22–3.13, P = 0.005) and ITGA2rs1991013AG and HABP2rs7923349TT were independent risk factors for moderate to severe carotid stenosis (OR, 2.28, 95% CI: 1.28–4.07, P = 0.005; OR, 2.90, 95% CI: 1.19–7.08, P = 0.019). GMDR analysis showed that there was a significant gene-gene interaction between ITGA2 rs4865756 and HABP2 rs7923349, and the high-risk interactive genotype in the two variants was independently associated with a higher risk for carotid stenosis after adjusting the covariates (OR,1. 42, 95% CI 1.10–1.84, P = 0.008).

Conclusions

Prevalence of carotid stenosis was very high in the high-risk stroke population in southwestern China. Variants in genes referred in endothelial function were associated with the carotid stenosis. The high—risk interactive genotype in ITGA2 rs4865756 and HABP2 rs7923349 was independently associated with a higher risk for carotid stenosis.
Case report: A quantitative and qualitative diffusion tensor imaging (DTI) study in varicella zoster-related brachial plexopathy
Authors: Alberti Manfredi , Ginanneschi Federica , Rossi Alessandro , Monti Lucia
Published: January 2023

Diffusion tensor imaging (DTI) is considered feasible for the nerve plexuses' imaging and quantitative evaluation but its value in the clinical practice is still virtually unexplored. We present the DTI profile of a case of acute varicella-zoster virus (VZV)-related brachial plexopathy. A 72-year-old woman presented with left upper-limb segmental paresis involving the spinal metamers C6–C7, preceded by a painful dermatomal vesicular eruption in C5-T1 dermatomes. Clinical and electrophysiological findings and magnetic resonance imaging indicated a plexus involvement. DTI analysis showed decreased fractional anisotropy (FA) and an increase of all the other diffusivity indexes, i.e., mean, axial, and radial diffusivity. The mechanisms underlying DTI parameter differences between healthy and pathologic brachial plexus sides could be related to microstructural fiber damage. Water diffusion is affected within the nerve roots by increasing the diffusion distance, leading to increased diffusion perpendicular to the largest eigenvalue and therefore to decreased FA values The role of DTI in clinical practice has not been defined yet. Additional quantitative and qualitative DTI information could improve the assessment and follow-up of brachial plexopathy.
Temporal hyper-precision of brainstem neurons alters spatial sensitivity of binaural auditory processing with cochlear implants
Authors: Müller Michaela , Hu Hongmei , Dietz Mathias , Beiderbeck Barbara , Ferreiro Dardo N. , Pecka Michael
Published: January 2023

The ability to localize a sound source in complex environments is essential for communication and navigation. Spatial hearing relies predominantly on the comparison of differences in the arrival time of sound between the two ears, the interaural time differences (ITDs). Hearing impairments are highly detrimental to sound localization. While cochlear implants (CIs) have been successful in restoring many crucial hearing capabilities, sound localization via ITD detection with bilateral CIs remains poor. The underlying reasons are not well understood. Neuronally, ITD sensitivity is generated by coincidence detection between excitatory and inhibitory inputs from the two ears performed by specialized brainstem neurons. Due to the lack of electrophysiological brainstem recordings during CI stimulation, it is unclear to what extent the apparent deficits are caused by the binaural comparator neurons or arise already on the input level. Here, we use a bottom-up approach to compare response features between electric and acoustic stimulation in an animal model of CI hearing. Conducting extracellular single neuron recordings in gerbils, we find severe hyper-precision and moderate hyper-entrainment of both the excitatory and inhibitory brainstem inputs to the binaural comparator neurons during electrical pulse-train stimulation. This finding establishes conclusively that the binaural processing stage must cope with highly altered input statistics during CI stimulation. To estimate the consequences of these effects on ITD sensitivity, we used a computational model of the auditory brainstem. After tuning the model parameters to match its response properties to our physiological data during either stimulation type, the model predicted that ITD sensitivity to electrical pulses is maintained even for the hyper-precise inputs. However, the model exhibits severely altered spatial sensitivity during electrical stimulation compared to acoustic: while resolution of ITDs near midline was increased, more lateralized adjacent source locations became inseparable. These results directly resemble recent findings in rodent and human CI listeners. Notably, decreasing the phase-locking precision of inputs during electrical stimulation recovered a wider range of separable ITDs. Together, our findings suggest that a central problem underlying the diminished ITD sensitivity in CI users might be the temporal hyper-precision of inputs to the binaural comparator stage induced by electrical stimulation.
Targeting the pathological network: Feasibility of network-based optimization of transcranial magnetic stimulation coil placement for treatment of psychiatric disorders
Authors: Cao Zhengcao , Xiao Xiang , Zhao Yang , Jiang Yihan , Xie Cong , Paillère-Martinot Marie-Laure , Artiges Eric , Li Zheng , Daskalakis Zafiris J. , Yang Yihong , Zhu Chaozhe
Published: January 2023

It has been recognized that the efficacy of TMS-based modulation may depend on the network profile of the stimulated regions throughout the brain. However, what profile of this stimulation network optimally benefits treatment outcomes is yet to be addressed. The answer to the question is crucial for informing network-based optimization of stimulation parameters, such as coil placement, in TMS treatments. In this study, we aimed to investigate the feasibility of taking a disease-specific network as the target of stimulation network for guiding individualized coil placement in TMS treatments. We present here a novel network-based model for TMS targeting of the pathological network. First, combining E-field modeling and resting-state functional connectivity, stimulation networks were modeled from locations and orientations of the TMS coil. Second, the spatial anti-correlation between the stimulation network and the pathological network of a given disease was hypothesized to predict the treatment outcome. The proposed model was validated to predict treatment efficacy from the position and orientation of TMS coils in two depression cohorts and one schizophrenia cohort with auditory verbal hallucinations. We further demonstrate the utility of the proposed model in guiding individualized TMS treatment for psychiatric disorders. In this proof-of-concept study, we demonstrated the feasibility of the novel network-based targeting strategy that uses the whole-brain, system-level abnormity of a specific psychiatric disease as a target. Results based on empirical data suggest that the strategy may potentially be utilized to identify individualized coil parameters for maximal therapeutic effects.
Rat model of asphyxia-induced cardiac arrest and resuscitation
Authors: Yu Shuhang , Wu Chenghao , Zhu Ying , Diao Mengyuan , Hu Wei
Published: January 2023

Neurologic injury after cardiopulmonary resuscitation is the main cause of the low survival rate and poor quality of life among patients who have experienced cardiac arrest. In the United States, as the American Heart Association reported, emergency medical services respond to more than 347,000 adults and more than 7,000 children with out-of-hospital cardiac arrest each year. In-hospital cardiac arrest is estimated to occur in 9.7 per 1,000 adult cardiac arrests and 2.7 pediatric events per 1,000 hospitalizations. Yet the pathophysiological mechanisms of this injury remain unclear. Experimental animal models are valuable for exploring the etiologies and mechanisms of diseases and their interventions. In this review, we summarize how to establish a standardized rat model of asphyxia-induced cardiac arrest. There are four key focal areas: (1) selection of animal species; (2) factors to consider during modeling; (3) intervention management after return of spontaneous circulation; and (4) evaluation of neurologic function. The aim was to simplify a complex animal model, toward clarifying cardiac arrest pathophysiological processes. It also aimed to help standardize model establishment, toward facilitating experiment homogenization, convenient interexperimental comparisons, and translation of experimental results to clinical application.
The cellular model for Alzheimer's disease research: PC12 cells
Authors: Xie Danni , Deng Ting , Zhai Zhenwei , Sun Tao , Xu Ying
Published: January 2023

Alzheimer's disease (AD) is a common age-related neurodegenerative disease characterized by progressive cognitive decline and irreversible memory impairment. Currently, several studies have failed to fully elucidate AD's cellular and molecular mechanisms. For this purpose, research on related cellular models may propose potential predictive models for the drug development of AD. Therefore, many cells characterized by neuronal properties are widely used to mimic the pathological process of AD, such as PC12, SH-SY5Y, and N2a, especially the PC12 pheochromocytoma cell line. Thus, this review covers the most systematic essay that used PC12 cells to study AD. We depict the cellular source, culture condition, differentiation methods, transfection methods, drugs inducing AD, general approaches (evaluation methods and metrics), and in vitro cellular models used in parallel with PC12 cells.
The different manifestations of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT in evaluation of the steroid therapy response for IgG4-related disease: A case report
Authors: Jia Guorong , Bian Dejian , Cheng Chao , Wang Meitang , Zuo Changjing
Published: January 2023

IgG4-related disease is a fibrous-inflammatory process belonging to immunomodulation disorders. We report a case of a 57-year-old man with the IgG4-related disease (RD). 68Ga-FAPI-04 PET/CT showed more significant uptake in most lesions than in 18F-FDG PET/CT except for the cervical and mediastinal lymph nodes. Besides, uptake in the submandibular glands were only detected in 68Ga-FAPI-04 PET/CT. The biopsy result of the cervical lymph nodes confirmed the diagnosis of IgG4-related disease. After treatment, only slight FDG-avid cervical lymph nodes were observed in the 18F-FDG PET/CT, while the raised uptake of 68Ga-FAPI-04 could be observed in the pancreas and submandibular glands. 68Ga-FAPI-04 PET-CT might have promising applications in evaluating IgG4-RD, whether in initial or follow-up imaging during steroid therapy.
Impacts of hesperidin on whey protein functionality: Interacting mechanism, antioxidant capacity, and emulsion stabilizing effects
Authors: Wang Yin , Guo Yangkai , Zhang Longtao , Yuan Meilan , Zhao Li , Bai Chunqing , McClements David Julian
Published: January 2023

The objective of this work was to explore the possibility of improving the antioxidant capacity and application of whey protein (WP) through non-covalent interactions with hesperidin (HES), a citrus polyphenol with nutraceutical activity. The interaction mechanism was elucidated using several spectroscopic methods and molecular docking analysis. The antioxidant capacity of the WP-HES complexes was analyzed and compared to that of the proteins alone. Moreover, the resistance of oil-in-water emulsions formulated using the WP-HES complexes as antioxidant emulsifiers to changes in environmental conditions (pH, ion strength, and oxidant) was evaluated. Our results showed that HES was incorporated into a single hydrophobic cavity in the WP molecule, where it was mainly held by hydrophobic attractive forces. As a result, the microenvironments of the non-polar tyrosine and tryptophan residues in the protein molecules were altered after complexation. Moreover, the α-helix and β-sheet regions in the protein decreased after complexation, while the β-turn and random regions increased. The antioxidant capacity of the WP-HES complexes was greater than that of the proteins alone. Non-radiative energy transfer from WP to HES was detected during complex formation. Compared to WP alone, the WP-HES complexes produced emulsions with smaller mean droplet diameters, exhibited higher pH and salt stability, and had better oxidative stability. The magnitude of these effects increased as the HES concentration was increased. This research would supply valuable information on the nature of the interactions between WP and HES. Moreover, it may lead to the creation of dual-function antioxidant emulsifiers for application in emulsified food products.
Effects of resveratrol on renal ischemia-reperfusion injury: A systematic review and meta-analysis
Authors: Lan Tian-ying , Dun Rong-liang , Yao Dong-sheng , Wu Feng , Qian Yi-ling , Zhou Yuan , Zhan Tian-tian , Shao Ming-hai , Gao Jian-dong , Wang Chen
Published: January 2023

Renal ischemia-reperfusion (I/R) injury may lead to acute kidney injury, which is characterized by high morbidity and mortality rates. Resveratrol (RSV) can be extracted from Chinese herbs, and multiple animal experiments have demonstrated its potential for renal protection. This systematic review evaluates the protective effect of RSV against renal I/R injury in animal models. The PubMed, Embase, Web of Science, and Science Direct databases were searched for animal experiments related to RSV in renal I/R injury from their establishment to June 2022. In total, 19 studies were included with 249 animals (129 treated with RSV and 120 as controls). The pooled analysis revealed that RSV administration significantly decreased serum creatinine (SCr) levels (16 studies, n = 243, WMD = −58.13, 95% CI = −79.26 to −37.00, p < 0.00001) and blood urea nitrogen (BUN) levels (12 studies, n = 163, WMD = −34.37, 95% CI = −46.70 to −22.03, p < 0.00001) in the renal I/R injury model. The level of malondialdehyde (MDA), an oxidative stress index, was alleviated [7 studies, n = 106, standardized mean difference (SMD) = −6.05, 95% CI = −8.90 to −3.21, p < 0.0001] and antioxidant enzymes such as glutathione (GSH) (7 studies, n = 115, SMD = 9.25, 95% CI = 5.51–13.00, p < 0.00001) and catalase (CAT) (4 studies, n = 59, SMD = 8.69, 95% CI = 4.35–13.03, p < 0.0001) were increased after treatment of RSV. The subgroup analysis suggested that 5–10 mg/kg of RSV optimally protects against renal I/R injury as both the BUN and SCr levels were significantly decreased at this dosage. The protective effects of RSV against renal I/R injury might be attributed to multiple mechanisms, such as inhibiting oxidative stress, apoptosis, inflammation, fibrillation, and promoting autophagy. For a deeper understanding of the protective effects of RSV, experimental studies on animal models and large randomized controlled trials in humans are needed.
The influence of KCl concentration on the gelation of myofibrillar protein giant squid (Dosidicus gigas) due to molecular conformation change
Authors: Niu Fuge , Ma Shuang , Zhang Xiuzhen , Ritzoulis Christos , Chen Yueyue , Pan Weichun
Published: January 2023

Introduction

Protein gelation process is of importance in food industry. The objective of this study is to investigate the influence of salt concentration variation, which induced protein conformation change, on protein’s intermolecular interactions and its gelation process.

Methods

Paramyosin has been separated and purified from myofibrillar protein extracted from giant squid. Then Giant squid’s paramyosin molecular mass and intermolecular interactions were quantified by means of light scattering techniques. Finally, the micro-rheology study via diffusing wave spectroscopy (DWS) technique revealed that this conformation change dramatically affected myofibrillar protein gelation process.

Results

The obtained apparent molecular weight (ca 2 × 105 g/mol) suggested that protein molecules existed as dimers, while the second virial coefficient A2 significantly reduced from −3.98456 × 10−5 to −5.07575 × 10−4 ml mol/g2 when KCl concentrated from 0.15 to 1 mol/L. Light scattering data also suggest that paramyosin dimers are stiff, with a persistence length of 120 nm, almost the length of a molecule and independent of salt concentration. Mean-square displacement (MSD) of tracer particles at 5 temperatures with 4 salt concentrations displayed that this conformation change had dramatic effect. Therefore, G’ and G” were remarkably altered with at least one order of magnitude difference owing to this event occurrence.

Conclusions

Paramyosin conformation change due to KCl concentrated enhances attractive interactions with apparent molecular mass increase, which resulted in majority paramyosin molecules (> 99%) in dimeric form and promoted aggregates formation. DWS technique revealed that the conformation change dramatic affected this process characterized by the correlation functions, MSD, and G’ and G”. This study brings forward data on understanding the effect of a major salt supplement, KCl, on the chemical physics of a major muscle protein.
Comparative assessment of Cucurbita moschata seed polypeptides toward the protection of human skin cells against oxidative stress-induced aging
Authors: Liu Chunhuan , Wang Peiyu , Yang Cheng , Zhao Bingtian , Sun Peidong
Published: January 2023

Skin aging has attracted much attention among the current aging population of society. The seeds of Cucurbita moschata possess a variety of potential biological activities as a healthy diet. However, limited information is available on the skin-antiaging properties of C. moschata seed protein and its hydrolysate. Herein, we developed a novel strategy for protecting human skin cells against oxidative stress-induced aging by C. moschata seed polypeptides. C. moschata seed polypeptides (CSPs) with different molecular weight distributions were successfully prepared by controlling the protease hydrolysis time. The proportions of < 1,000 Da polypeptides of P-1, P-2, and P-3 were 0.11, 20.26, and 92.72%, respectively. P-3 contained the highest proportion of polypeptides of size < 1,000 Da, which was observed to promote human skin fibroblast (HSF) growth by MTT assay, cell cycle, and morphology. P-3 has an efficient repair effect on the H2O2-induced aging of HSF cells. To explain this phenomenon, cell lifespan, intracellular ROS level, superoxide dismutase (SOD) activity, and glutathione (GSH) content were investigated to reveal the interactions between P-3 and antiaging. With the increase in P-3 concentration, the ROS level significantly decreased, and the SOD activity and GSH content significantly increased in H2O2-induced HSF cells. These findings indicated that CSPs have the potential to inhibit skin aging, which could be advantageous in the health industry for providing personal care.
Evaluation of the synergistic effects of epigallocatechin-3-gallate-loaded PEGylated-PLGA nanoparticles with nimodipine against neuronal injury after subarachnoid hemorrhage
Authors: Yang Xianguang , Han Mengguo , Wang Xue , Wang Jian , Sun Xiaoxue , Zhang Chunyan , Yan Shuaiguo , Huang Liyong , Chen Ying
Published: January 2023

Subarachnoid hemorrhage (SAH) is a devastating subtype of stroke with high mortality and morbidity. Although serious side effects might occur, nimodipine, a second-generation 1,4-dihydropyridine calcium channel blocker, is clinically used to improve neurological outcomes after SAH. Recently, (-)-epigallocatechin-3-gallate (EGCG) has been reported to inhibit Ca2+ overloading-induced mitochondrial dysfunction, oxidative stress, and neuronal cell death after SAH; however, low bioavailability, instability, and cytotoxicity at a high dose limited the clinical application of EGCG. To overcome these limitations, PEGylated-PLGA EGCG nanoparticles (EGCG-NPs) were constructed to enhance the bioavailability by using the double-emulsion method. Antioxidative activity, cytotoxicity, behavioral, and immunohistochemistry studies were carried out to determine the neuroprotective effectiveness after cotreatment with EGCG-NPs (75 mg/kg/d preconditioning for 7 days before SAH) and nimodipine (10 mg/kg/d after 30 min of SAH) by using in vivo SAH models. The optimized EGCG-NPs with a Box–Behnken design showed a small particle size of 167 nm, a zeta potential value of −22.6 mV, an encapsulation efficiency of 86%, and a sustained-release profile up to 8 days in vitro. Furthermore, EGCG-NPs (75 mg/kg/d) had superior antioxidative activity to free EGCG (100 mg/kg/d). EGCG-NPs combined with nimodipine exhibited significant synergistic effects against neuronal cell death by suppressing oxidative stress, Ca2+ overloading, mitochondrial dysfunction, and autophagy after SAH. These results suggest that cotreatment with EGCG-NPs and nimodipine may serve as a promising novel strategy for the treatment of SAH.
The value of metabolic LncRNAs in predicting prognosis and immunotherapy efficacy of gastric cancer
Authors: Du Peizhun , Liu Pengcheng , Patel Rajan , Chen Shiyu , Hu Cheng’en , Huang Guangjian , Liu Yi
Published: January 2023

Introduction

As a unique feature of malignant tumors, abnormal metabolism can regulate the immune microenvironment of tumors. However, the role of metabolic lncRNAs in predicting the prognosis and immunotherapy of gastric cancer (GC) has not been explored.

Methods

We downloaded the metabolism-related genes from the GSEA website and identified the metabolic lncRNAs. Co-expression analysis and Lasso Cox regression analysis were utilized to construct the risk model. To value the reliability and sensitivity of the model, Kaplan–Meier analysis and receiver operating characteristic curves were applied. The immune checkpoints, immune cell infiltration and tumor mutation burden of low- and high-risk groups were compared. Tumor Immune Dysfunction and Exclusion (TIDE) score was conducted to evaluate the response of GC patients to immunotherapy.

Results

Twenty-three metabolic lncRNAs related to the prognosis of GC were obtained. Three cluster patterns based on metabolic lncRNAs could distinguish GC patients with different overall survival time (OS) effectively (p<0.05). The risk score model established by seven metabolic lncRNAs was verified as an independent prognostic indicator for predicting the OS of GC. The AUC value of the risk model was higher than TNM staging. The high-risk patients were accompanied by significantly increased expression of immune checkpoint molecules (including PD-1, PD-L1 and CTLA4) and increased tumor tolerant immune cells, but significantly decreased tumor mutation burden (TMB). Consistently, TIDE values of low-risk patients were significantly lower than that of high-risk patients.

Discussion

The metabolic lncRNAs risk model can reliably and independently predict the prognosis of GC. The feature that simultaneously map the immune status of tumor microenvironment and TMB gives risk model great potential to serve as an indicator of immunotherapy.
Crosstalk between protein kinases AKT and ERK1/2 in human lung tumor-derived cell models
Authors: Stulpinas Aurimas , Sereika Matas , Vitkeviciene Aida , Imbrasaite Ausra , Krestnikova Natalija , Kalvelyte Audrone V.
Published: January 2023

There is no doubt that cell signaling manipulation is a key strategy for anticancer therapy. Furthermore, cell state determines drug response. Thus, establishing the relationship between cell state and therapeutic sensitivity is essential for the development of cancer therapies. In the era of personalized medicine, the use of patient-derived ex vivo cell models is a promising approach in the translation of key research findings into clinics. Here, we were focused on the non-oncogene dependencies of cell resistance to anticancer treatments. Signaling-related mechanisms of response to inhibitors of MEK/ERK and PI3K/AKT pathways (regulators of key cellular functions) were investigated using a panel of patients’ lung tumor-derived cell lines with various stemness- and EMT-related markers, varying degrees of ERK1/2 and AKT phosphorylation, and response to anticancer treatment. The study of interactions between kinases was the goal of our research. Although MEK/ERK and PI3K/AKT interactions are thought to be cell line-specific, where oncogenic mutations have a decisive role, we demonstrated negative feedback loops between MEK/ERK and PI3K/AKT signaling pathways in all cell lines studied, regardless of genotype and phenotype differences. Our work showed that various and distinct inhibitors of ERK signaling – selumetinib, trametinib, and SCH772984 – increased AKT phosphorylation, and conversely, inhibitors of AKT – capivasertib, idelalisib, and AKT inhibitor VIII – increased ERK phosphorylation in both control and cisplatin-treated cells. Interaction between kinases, however, was dependent on cellular state. The feedback between ERK and AKT was attenuated by the focal adhesion kinase inhibitor PF573228, and in cells grown in suspension, showing the possible role of extracellular contacts in the regulation of crosstalk between kinases. Moreover, studies have shown that the interplay between MEK/ERK and PI3K/AKT signaling pathways may be dependent on the strength of the chemotherapeutic stimulus. The study highlights the importance of spatial location of the cells and the strength of the treatment during anticancer therapy.
Influencing factors of LDCT recommendation by physicians in Sichuan Province, China
Authors: Li Ruicen , Chai Qi , Chen Feng , Liu Qing , Zhang Hong
Published: January 2023

The study aimed to investigate the influencing factors of physicians in recommending low-dose computed tomography (LDCT) for lung cancer screening to high-risk groups. A total of 1767 participants with good knowledge of LDCT were included in a cross-sectional study. Data about physicians’ demographics, perception of barriers on LDCT screening, medical conditions for practicing medicine and the behavior of recommending LDCT were collected by a questionnaire. Physicians who care about the transportation convenience of patients were less likely to recommend LDCT (OR 0.568, 95% CI (0.423 to 0.763), p < 0.05). The physicians who considered LDCT expensive, recommended LDCT less than others (OR 0.308, 95% CI (0.186 to 0.510), p < 0.05). The false positive rate of LDCT can decrease the possibility of physicians’ recommending (OR 0.542, 95% CI (0.387 to 0.758), p < 0.05). The physicians in oncology department and health management center were more likely to recommend LDCT (OR 2.282, 95% CI (1.557 to 3.345); OR 2.476, 95% CI (1.618 to 3.791)). The convenience of transportation, the price, and the\ false positive rate may be the main concerns among physicians on recommending LDCT to high-risk groups. The influencing factors of physicians’ recommending on LDCT was various. Information technology, government support in price and self-improvement of LDCT should be gathered together to break the barriers on physicians’ recommending on LDCT.
Up-regulated GRB7 protein in gastric cancer cells correlates with clinical properties and increases proliferation and stem cell properties
Authors: Pei Yuan-yuan , Ran Jian , Wen Lijuan , Liu Xiaoyi , Xiang Li , Liu Weiqiang , Wei Fengxiang
Published: January 2023

Introduction

It has been reported that GRB7 is closely related to a variety of human solid tumors, but its role in gastric cancer has not been reported yet. The purpose of this study was to investigate the expression level and intracellular effects of GRB7 in human gastric cancer.

Methods

Real-time fluorescent quantitative PCR and Western blot were used to detect the expression of GRB7 in gastric cancer cell lines. The immunohistochemical staining and SPSS analysis verified the GRB7 protein expression. Stable gastric cancer cell lines, MTT experiments, clone formation experiments, cell cycle flow cytometry experiments, sphere formation experiments and lateral subpopulation cell sorting experiments were conducted to investigate the role of GRB7 in gastric cancer cells.

Results

We found that the expression of GRB7 in gastric cancer cell lines was higher than that of the corresponding normal gastric epithelial cells, and correspondingly higher in gastric cancer tissues than its paired adjacent tissues. GRB7 protein was expressed more highly in cancer tissues than in adjacent tissues. GRB7 protein expression levels were positively correlated with the clinical stage of gastric cancer patients, and negatively correlated with the survival prognosis of patients. GSEA analysis of GRB7 mRNA levels in gastric cancer tissues and normal gastric epithelial tissues from public databases showed that GRB7 may affect cell proliferation and related processes of intracellular stem cells. GRB7 can promote the proliferation of gastric cancer cells and is positively related to the self-renewal ability of gastric cancer stem cells.

Discussion

This study shows that GRB7 molecules highly expressed in gastric cancer tissues can promote the proliferation of gastric cancer cells and increase the proportion of gastric cancer stem cells, so it is expected to become a diagnostic molecule or potential therapeutic target for gastric cancer.
Correlation between lung cancer probability and number of pulmonary nodules in baseline computed tomography lung cancer screening: A retrospective study based on the Chinese population
Authors: Wu Quanyang , Zhao Shijun , Huang Yao , Wang Jianwei , Tang Wei , Zhou Lina , Qi Linlin , Zhang Zewei , Xie Yuting , Zhang Jiaxing , Li Hongjia , Wu Ning
Published: January 2023

Background

Screening for lung cancer with LDCT detects a large number of nodules. However, it is unclear whether nodule number influences lung cancer probability. This study aimed to acquire deeply insight into the distribution characteristics of nodule number in the Chinese population and to reveal the association between the nodule number and the probability of lung cancer (LC).

Methods

10,167 asymptomatic participants who underwent LDCT LC screening were collected. Noncalcified nodules larger than 4 mm were included. The nodule number per participant was determined. We defined five categories according to the number of nodules (based on nodule type and size): one, two, three, four, and more than four nodules. We stratified the nodules as groups A, B, and C and participants as Amax, Bmax, and Cmax groups, and explored the association between nodule number and the probability of LC on nodule and participant levels.

Results

97 participants were confirmed to have LC. The probabilities of LC were 49/1719, 22/689, 11/327, 6/166, and 9/175 in participants with one, two, three, four, and more than four nodules (p>0.05), respectively. In the Bmax group, the probability of LC was significantly higher in participants with one nodule than those with >4 nodules (p<0.05), and the probability of LC showed a negative linear trend with increasing nodule numbers (p<0.05). Based on the nodule-level analyses, in Group B, LC probability was significantly higher when participants had a solitary nodule than when they had >4 nodules (p<0.05).

Conclusion

LC probability does not significantly change with the number of nodules. However, when stratified by the nodule size, the effect of nodule number on LC probability was nodule-size dependent, and greater attention and active follow-up are required for solitary nodules especially SNs/solid component of PSNs measuring 6-15 mm or NSNs measuring 8-15 mm. Assessing the nodule number in conjunction with nodule size in baseline LDCT LC screening is considered beneficial.
Uterine cervical Müllerian adenosarcoma possibly arising from ovarian cystadenofibroma: A case report and review of the literature
Authors: Zhu Xinxin , Peng Chao , Huang Yan , Zhou Yingfang
Published: January 2023

Uterine cervical Müllerian adenosarcoma (MA), a rare malignant tumor of the female reproductive organs, is composed of a benign epithelium and a low-grade malignant stromal component. Because few studies have investigated the clinical management of MA, misdiagnosis often occur. Therefore, we proposed an optimal course of clinical management for patients with MA. MA is possibly a malignant transformation of the cystadenofibroma. In this study, we present a case of a 46-year-old woman who presented with symptoms of MA of the uterine cervix, such as metrorrhagia and a cyst in the cervical canals, after transvaginal excision of the left ovarian mucinous cystadenofibroma.
Artificial intelligence applicated in gastric cancer: A bibliometric and visual analysis via CiteSpace
Authors: Zhang Guoyang , Song Jingjing , Feng Zongfeng , Zhao Wentao , Huang Pan , Liu Li , Zhang Yang , Su Xufeng , Wu Yukang , Cao Yi , Li Zhengrong , Jie Zhigang
Published: January 2023

Objective

This study aimed to analyze and visualize the current research focus, research frontiers, evolutionary processes, and trends of artificial intelligence (AI) in the field of gastric cancer using a bibliometric analysis.

Methods

The Web of Science Core Collection database was selected as the data source for this study to retrieve and obtain articles and reviews related to AI in gastric cancer. All the information extracted from the articles was imported to CiteSpace to conduct the bibliometric and knowledge map analysis, allowing us to clearly visualize the research hotspots and trends in this field.

Results

A total of 183 articles published between 2017 and 2022 were included, contributed by 201 authors from 33 countries/regions. Among them, China (47.54%), Japan (21.86%), and the USA (13.11%) have made outstanding contributions in this field, accounting fsor 82.51% of the total publications. The primary research institutions were Wuhan University, Tokyo University, and Tada Tomohiro Inst Gastroenterol and Proctol. Tada (n = 12) and Hirasawa (n = 90) were ranked first in the top 10 authors and co-cited authors, respectively. Gastrointestinal Endoscopy (21 publications; IF 2022, 9.189; Q1) was the most published journal, while Gastric Cancer (133 citations; IF 2022, 8.171; Q1) was the most co-cited journal. Nevertheless, the cooperation between different countries and institutions should be further strengthened. The most common keywords were AI, gastric cancer, and convolutional neural network. The “deep-learning algorithm” started to burst in 2020 and continues till now, which indicated that this research topic has attracted continuous attention in recent years and would be the trend of research on AI application in GC.

Conclusions

Research related to AI in gastric cancer is increasing exponentially. Current research hotspots focus on the application of AI in gastric cancer, represented by convolutional neural networks and deep learning, in diagnosis and differential diagnosis and staging. Considering the great potential and clinical application prospects, the related area of AI applications in gastric cancer will remain a research hotspot in the future.
Current state of NK cell-mediated immunotherapy in chronic lymphocytic leukemia
Authors: Wang Zong-Han , Li Wei , Dong Hao , Han Fujun
Published: January 2023

Chronic lymphocytic leukemia (CLL) has become one of the most common hematological diseases in western countries, with an annual incidence of 42/100,000. Conventional chemotherapy and targeted therapeutic drugs showed limitations in prognosis or in efficiency in high-risk patients. Immunotherapy represented is one of the most effective therapeutic approaches with the potential of better effect and prognosis. Natural killer (NK) cells are good options for immunotherapy as they can effectively mediate anti-tumor activity of immune system by expressing activating and inhibiting receptors and recognizing specific ligands on various tumor cells. NK cells are critical in the immunotherapy of CLL by enhancing self-mediated antibody-dependent cytotoxicity (ADCC), allogeneic NK cell therapy and chimeric antigen receptor-natural killer (CAR-NK) cell therapy. In this article, we reviewed the features, working mechanisms, and receptors of NK cells, and the available evidence of the advantages and disadvantages of NK cell-based immunotherapies, and put forward future study directions in this field.
Prognostic relevance of rib invasion and modification of T description for resected NSCLC patients: A propensity score matching analysis of the SEER database
Authors: Chen Yiyong , Zhang Juan , Chen Jing , Yang Zijie , Ding Yun , Chen Wenshu , Guo Tianxing , Zhao Lilan , Pan Xiaojie
Published: January 2023

Introduction

The impact of rib invasion on the non-small cell lung cancer (NSCLC) T classifications remains unclear. Our study aims to verify the impact of rib invasion on survival in patients with NSCLC through multicenter data from the Surveillance, Epidemiology, and End Results (SEER) database, and proposed a more appropriate pT for the forthcoming 9th tumor-node-metastasis (TNM) classifications.

Method

The SEER database was used to collect T2b-4N0-2M0 NSCLC cases from the period of 2010-2015 according to the 7th TNM classification system. Subsequently, the T classification was restaged according to the 8th TNM classification system based on the following codes: tumor size and tumor extension. Cases with T1-2 disease and incomplete clinicopathological information were excluded. Finally, 6479 T3 and T4 NSCLC patients were included in the present study and divided into a rib invasion group (n = 131), other pT3 group (n = 3835), and pT4 group (n = 2513). Propensity-score matching (PSM) balanced the known confounders of the prognosis, resulting in two sets (rib invasion group vs. other pT3 and pT4 group). Overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier survival curves, and predictive factors of OS and CSS were assessed by Cox regression.

Result

Survival outcomes of the rib invasion group were worse than the other pT3 group (OS: 40.5% vs. 46.5%, p = 0.035; CSS: 49.2% vs. 55.5%, p = 0.047), but comparable to the pT4 group (OS: 40.5% vs. 39.9%, p = 0.876; CSS: 49.2% vs. 46.3%, p = 0.659). Similar results were obtained after PSM. Multivariate analyses for all patients revealed that age at diagnosis, gender, N stage, T stage, surgical modalities, and adjuvant therapy had a predictive value for the prognosis.

Conclusion

The rib invasion group had a worse prognosis than the other pT3 groups, but was similar to the pT4 group. Our recommendation is to change the classification of rib invasion to pT4 disease and further validate this in the forthcoming 9th TNM classification.
Assessment of the prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in perihilar cholangiocarcinoma patients following curative resection: A multicenter study of 333 patients
Authors: Ge Ming-Yang , Liu Zhi-Peng , Pan Yu , Wang Jiao-Yang , Wang Xiang , Dai Hai-Su , Gao Shu-Yang , Zhong Shi-Yun , Che Xiao-Yu , Zuo Jing-Hua , Liu Yun-Hua , Liu Xing-Chao , Fan Hai-Ning , Chen Wei-Yue , Wang Zi-Ran , Yin Xian-Yu , Bai Jie , Zhang Yan-Qi , Jiang Yan , Gong Yi , Chen Zhi-Yu
Published: January 2023

Background & Aims

Tumor-associated chronic inflammation has been determined to play a crucial role in tumor progression, angiogenesis and immunosuppression. The objective of this study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in perihilar cholangiocarcinoma (pCCA) patients following curative resection.

Methods

Consecutive pCCA patients following curative resection at 3 Chinese hospitals between 2014 and 2018 were included. The NLR was defined as the ratio of neutrophil count to lymphocyte count. PLR was defined as the ratio of platelet count to lymphocyte count. The optimal cutoff values of preoperative NLR and PLR were determined according to receiver operating characteristic (ROC) curves for the prediction of 1-year overall survival (OS), and all patients were divided into high- and low-risk groups. Kaplan-Meier curves and Cox regression models were used to investigate the relationship between values of NLR and PLR and values of OS and recurrence-free survival (RFS) in pCCA patients. The usefulness of NLR and PLR in predicting OS and RFS was evaluated by time-dependent ROC curves.

Results

A total of 333 patients were included. According to the ROC curve for the prediction of 1-year OS, the optimal cutoff values of preoperative NLR and PLR were 1.68 and 113.1, respectively, and all patients were divided into high- and low-risk groups. The 5-year survival rates in the low-NLR (<1.68) and low-PLR groups (<113.1) were 30.1% and 29.4%, respectively, which were significantly higher than the rates of 14.9% and 3.3% in the high-NLR group (≥1.68) and high-PLR group (≥113.1), respectively. In multivariate analysis, high NLR and high PLR were independently associated with poor OS and RFS for pCCA patients. The time-dependent ROC curve revealed that both NLR and PLR were ideally useful in predicting OS and RFS for pCCA patients.

Conclusions

This study found that both NLR and PLR could be used to effectively predict long-term survival in patients with pCCA who underwent curative resection.
Recent advances in the molecular prognostication of meningiomas
Authors: Wang Elaina J. , Haddad Alexander F. , Young Jacob S. , Morshed Ramin A. , Wu Joshua P. H. , Salha Diana M. , Butowski Nicholas , Aghi Manish K.
Published: January 2023

Meningiomas are the most common primary intracranial neoplasm. While traditionally viewed as benign, meningiomas are associated with significant patient morbidity, and certain meningioma subgroups display more aggressive and malignant behavior with higher rates of recurrence. Historically, the risk stratification of meningioma recurrence has been primarily associated with the World Health Organization histopathological grade and surgical extent of resection. However, a growing body of literature has highlighted the value of utilizing molecular characteristics to assess meningioma aggressiveness and recurrence risk. In this review, we discuss preclinical and clinical evidence surrounding the use of molecular classification schemes for meningioma prognostication. We also highlight how molecular data may inform meningioma treatment strategies and future directions.
Case report: Primary intracranial mucosa-associated lymphoid tissue lymphoma presenting as two primary tumors involving the cavernous sinus and extra-axial dura, respectively
Authors: Tian Shiyun , Pan Tao , Gao Bingbing , Li Wanyao , Liu Jiashen , Zou Kun , Miao Yanwei
Published: January 2023

Primary intracranial mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of brain tumor, with only a few reported cases worldwide that mostly have only one lesion with conventional magnetic resonance imaging (MRI) findings. Here, we present a special case of intracranial MALT lymphoma with two mass lesions radiographically consistent with meningiomas on MRI before the operation. A 66-year-old woman was admitted to the hospital with intermittent right facial pain for 1 year, aggravated for the last month. Brain MRI showed two extracerebral solid masses with similar MR signal intensity. One mass was crescent-shaped beneath the skull, and the other was in the cavernous sinus area. Lesions showed isointensity on T1WI and T2WI and an intense homogeneous enhancement after contrast agent injection. Both lesions showed hyperintensity in amide proton transfer–weighted images. The two masses were all surgically resected. The postoperative pathology indicated extranodal marginal zone B-cell lymphoma of MALT. To improve awareness of intracranial MALT lymphoma in the differential diagnosis of extra-axial lesions among clinicians, we present this report and briefly summarize previously reported cases to describe the clinical, pathological, radiological, and treatment features.