Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis.

Background: Sleep apnea syndrome(SAS) and osteoarthritis (OA) are two prevalent diseases that often coexist, but the causal relationship between them remains unclear. In light of this, our team utilizes Mendelian Randomization and bioinformatics analysis methods to investigate the potential association between the two diseases. Methods: In this study, we utilized GWAS data pertaining to SAS and OA to assess the causal relationship between the two diseases through Mendelian randomization (MR) analysis. We then employed transcriptomic data to perform differential gene identification, WGCNA, shared gene determination, functional enrichment analysis, and colocalization analysis, all designed to further elucidate the mechanisms underlying the association between the two diseases. In the end, we utilized Mendelian randomization (MR) analysis again to delve deeper into the relationship between the two diseases and immune cells. Results: Our research findings indicate that SAS is a risk factor for OA (p = 0.000004), knee OA (p = 0.0000001) and hip OA(p = 0.001). Furthermore, OA (p = 0.000195), knee OA (p = 0.001) are significant risk factors for SAS. However, there is no clear evidence that hip OA (p = 0.892) is a risk factor for SAS. Interestingly, the genes shared between OA and SAS are significantly enriched in leukocyte migration, leukocyte chemotaxis. Moreover, colocalization analysis suggests that the genes JUNB, COL8A1, FOSB, and IER2 may be key genes associated with both diseases. Furthermore, 57 immune cell phenotypes are associated with SAS, 95 with OA, and 6 shared between both diseases. Conclusion: This research confirmed the bidirectional causal relationship between SAS and OA. Notably, the 4 genes (JUNB, COL8A1, FOSB, IER2) and 6 immune phenotypes are crucial for both diseases, these provide hopeful targets for future interventions against these two diseases.

CCDC28A deficiency causes sperm head defects, reduced sperm motility and male infertility in mice.

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.

Automatic Sleep Staging Based on Contextual Scalograms and Attention Convolution Neural Network Using Single-Channel EEG.

Single-channel EEG based sleep staging is of interest to researchers due to its broad application prospect in daily sleep monitoring recently. We proposed using contextual scalograms as input and developed a convolutional neural network with attention modules named Co-ScaleNet for sleep staging. The contextual scalograms were obtained by combining the same color channels of three original RGB scalograms from consecutive epochs, and a simple and efficient data augmentation was designed according to their various forms. The Co-ScaleNet consists of two main parts. Firstly, three parallel convolutional branches with attention modules correspondingly extract and fuse features from contextual scalograms at the top layers. The remaining part is a stack of lightweight blocks. We achieved an overall accuracy of 87.0% for healthy individuals, 84.7% for depressed patients. And we obtained comparable performance on the public Sleep-EDFx (82.8%), ISRUC (84.6%) and SHHS datasets (87.7%), including a high recall of N1. The contextual scalograms of R channel as input achieved the best performance, which conform to the features of interest in visual scoring. The attention modules improved the recall of N1 and N3. Overall, the contextual scalograms provided a novel scheme for both contextual information extraction and data augmentation. Our study successfully expanded its application to depression datasets, as well as patients with sleep apnea, demonstrating its wide applicability.

Oncostatin M/Oncostatin M Receptor Signal Induces Radiation-Induced Heart Fibrosis by Regulating SMAD4 in Fibroblast.

PURPOSE: Radiation-induced heart fibrosis (RIHF) is a severe consequence of radiation-induced heart damage (RIHD) leading to impaired cardiac function. The involvement of oncostatin M (OSM) and its receptor (OSMR) in RIHD remains unclear. This study aimed to investigate the specific mechanism of OSM/OSMR in RIHF/RIHD. METHODS AND MATERIALS: RNA sequencing was performed on heart tissues from a RIHD mouse model. OSM levels were assessed in serum samples obtained from patients receiving thoracic radiation therapy (RT), as well as in RIHF mouse heart tissues and serum using enzyme-linked immunosorbent assay. Fiber activation was evaluated through costimulation of primary cardiac fibroblasts and NIH3T3 cells with RT and OSM, using Western blotting, immunofluorescence, and quantitative Polymerase Chain Reaction (qPCR). Adeno-associated virus serotype 9-mediated overexpression or silencing of OSM specifically in the heart was performed in vivo to assess cardiac fibrosis levels by transthoracic echocardiography and pathologic examination. The regulatory mechanism of OSM on the transcription level of SMAD4 was further explored in vitro using mass spectrometric analysis, chromatin immunoprecipitation-qPCR, and DNA pull-down. RESULTS: OSM levels were elevated in the serum of patients after thoracic RT as well as in RIHF mouse cardiac endothelial cells and mouse serum. The OSM rate (post-RT/pre-RT) and the heart exposure dose in RT patients showed a positive correlation. Silencing OSMR in RIHF mice reduced fibrosis, while OSMR overexpression increased fibrotic responses. Furthermore, increased OSM promoted histone acetylation (H3K27ac) in the SMAD4 promoter region, influencing SMAD4 transcription and subsequently enhancing fibrotic response. CONCLUSIONS: The findings demonstrated that OSM/OSMR signaling promotes SMAD4 transcription in cardiac fibroblasts through H3K27 hyperacetylation, thereby promoting radiation-induced cardiac fibrosis and manifestations of RIHD.

Non-small cell lung cancer cells with uncommon EGFR exon 19delins variants respond poorly to third-generation EGFR inhibitors.

BACKGROUND: This study compared the clinical efficacy of first-, second-, and third-generation tyrosine kinase inhibitors (TKIs) in previously untreated non-small cell lung cancer (NSCLC) patients harboring uncommon epidermal growth factor receptor (EGFR) exon 19delins variants. METHODS: We retrospectively analyzed the clinical outcomes of NSCLC patients with EGFR exon 19delins mutations who were treated with third- and first-generation EGFR TKIs. In vitro and in vivo studies were conducted to verify the sensitivity of these mutations to distinct generations of TKIs. Molecular simulation was used to investigate the structural characteristics of the EGFR mutant molecules. RESULTS: In a multicenter cohort of 1,526 patients, 37 (2.4 %) had uncommon EGFR 19delins mutations. Twenty-four patients were treated with first-generation EGFR TKIs, and third-generation TKIs were administered to ten patients as frontline therapy. Patients carrying EGFR exon 19delins mutations who were given third-generation TKIs exhibited comparatively shorter progression-free survival (PFS) and overall survival (OS) in relation to those who received first-generation EGFR inhibitors; median PFS: 6.9 months vs. 19.1 months (p < 0.001), Median OS: 19.1 months vs. 32.6 months (p < 0.001). In vivo and in vitro studies revealed that uncommon EGFR 19delins variants exhibit limited sensitivity to third-generation EGFR inhibitors in contrast to first- and second-generation EGFR inhibitors. The molecular binding affinity of third-generation EGFR TKIs toward uncommon EGFR 19delins mutations was less than that of first- and second-generation EGFR inhibitors. CONCLUSIONS: Uncommon EGFR 19delins variants respond poorly to third-generation EGFR inhibitors in NSCLC. Uncommon EGFR 19delins mutations may serve as an unfavorable predictive factor for the efficacy of third-generation EGFR TKI therapy, offering potential guidance for future clinical decision-making.

Effect of lumbosacral transitional vertebrae on sagittal balance of lumbo-pelvic complexity assessed by quantitative whole-body CT imaging.

Background: The variation at the lumbosacral junction certainly results in occult alignment changes in the lumbo-pelvic complexity (LPC). This retrospective case-control study aims to investigate the influences of lumbosacral transitional vertebrae (LSTV) on sagittal lumbo-pelvic balance assessment and provide some recommendations for preoperative imaging evaluation. Methods: Based on whole-body computed tomography (CT) images, a total of 210 individuals with complete segmentation anomalies of LSTV were included and divided into 23 presacral vertebrae (PSV) (sacralization, n=102), 25 PSV (lumbarization, n=108). The control group with 24 PSV (normal, n=100) was matched by age and gender. Sagittal lumbo-pelvic parameters including pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), sacral table angle (STA), sacral kyphosis (SK), and pelvic radius (PR) were measured at the ontogenetical S1 (Ontog S1) level and the morphological S1 (Morph S1), respectively. These parameters were compared using t-test, Kruskal-Wallis H test and post hoc test. Spearman's rank correlation coefficient and linear regression were used to investigate the association of lumbo-pelvic parameters with LSTV types and measurement levels. Results: All the parameters at the Ontog S1 differed significantly from those at the Morph S1 (all P<0.001). At the Ontog S1 level, PI, PT, SS, and LL were negatively correlated with vertebrae counts; SK and PR were positively correlated with vertebrae counts (all P<0.001). Instead, reverse results were obtained at the Morph S1 level. The measurement level and vertebrae counts were independent influence factors for the measurement of PI, PT, SS, SK, and PR (all P<0.05). Compared with the measured values of the matched controls, the variability of most lumbo-pelvic parameters (PI, SS, LL, STA, SK, PR values of 25 PSV subgroup, and PI, PT, SS, LL, STA values of 23 PSV subgroup) at the Morph S1 level were significantly smaller than that at the Ontog S1. The measurements of PT, SS, LL, and PR were less influenced by the measurement level and vertebrae counts than those of PI and SK. Conclusions: Morph S1 is more recommended for the measurements of most lumbo-pelvic parameters in patients with LSTV. The parameters (PT, SS, LL, STA, PR) are shown more stable and recommended to help reduce the effects caused by LSTV.

ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1.

Sperm with normal morphology and motility are essential for successful fertilization, and the strong attachment of the sperm head-tail coupling apparatus to the nuclear envelope during spermatogenesis is required to ensure the integrity of sperm for capacitation and fertilization. Here, we report that Arrdc5 is associated with spermatogenesis. The Arrdc5 knockout mouse model showed male infertility characterized by a high bent-head rate and reduced motility in sperm, which led to capacitation defects and subsequent fertilization failure. Through mass spectrometry, we found that ARRDC5 affects spermatogenesis by affecting NDC1 and SUN5. We further found that ARRDC5 might affect the vesicle-trafficking protein SEC22A-mediated transport and localization of NDC1, SUN5 and other head-tail coupling apparatus-related proteins that are responsible for initiating the attachment of the sperm head and tail. We finally performed intracytoplasmic sperm injection as a way to explore therapeutic strategies. Our findings demonstrate the essential role and the underlying molecular mechanism of ARRDC5 in anchoring the sperm head to the tail during spermatogenesis.

Reflecting on the cardiac toxicity in non-small cell lung cancer in the era of immune checkpoint inhibitors therapy combined with thoracic radiotherapy.

In recent years, immune checkpoint inhibitors (ICIs) have become a widely used treatment for non-small cell lung cancer (NSCLC), and the combination with traditional radiotherapy (RT) has shown significant potential in prolonging patient survival. However, both thoracic RT and ICIs can lead to cardiac toxicity, including radiation-induced heart damage (RIHD) and immunotherapy-related heart damage (IRHD). It still remains uncertain whether the combination of thoracic RT and immunotherapy will exacerbate acute or late cardiovascular (CV) toxicity and incidence. In this review, we summarize safety data from relevant clinical studies regarding CV toxicity for the combination therapy in NSCLC patients, explore the underlying synergetic mechanisms and common risk factors, and proposed treatment and management strategies. We hope to increase emphasis on the long-term assessment of CV toxicity risks associated with the combination therapy, and reduce the incidence of CV deaths resulting from such regimens.

Ectopic expression of human TUBB8 leads to increased aneuploidy in mouse oocytes.

Aneuploidy seriously compromises female fertility and increases incidence of birth defects. Rates of aneuploidy in human eggs from even young women are significantly higher than those in other mammals. However, intrinsic genetic factors underlying this high incidence of aneuploidy in human eggs remain largely unknown. Here, we found that ectopic expression of human TUBB8 in mouse oocytes increases rates of aneuploidy by causing kinetochore-microtubule (K-MT) attachment defects. Stretched bivalents in mouse oocytes expressing TUBB8 are under less tension, resulting in continuous phosphorylation status of HEC1 by AURKB/C at late metaphase I that impairs the established correct K-MT attachments. This reduced tension in stretched bivalents likely correlates with decreased recruitment of KIF11 on meiotic spindles. We also found that ectopic expression of TUBB8 without its C-terminal tail decreases aneuploidy rates by reducing erroneous K-MT attachments. Importantly, variants in the C-terminal tail of TUBB8 were identified in patients with recurrent miscarriages. Ectopic expression of an identified TUBB8 variant in mouse oocytes also compromises K-MT attachments and increases aneuploidy rates. In conclusion, our study provides novel understanding for physiological mechanisms of aneuploidy in human eggs as well as for pathophysiological mechanisms involved in recurrent miscarriages.

Optimal combination periprosthetic vasculature visualization and metal artifact reduction by spectral computed tomography using virtual monoenergetic images in total hip arthroplasty.

OBJECTIVES: To investigate the optimal parameters of spectral CT for preferably visualizing the periprosthetic vasculature and metal artifact reduction (MAR) in total hip arthroplasty (THA). METHODS: A total of 34 THA of 30 patients were retrospectively included. Image reconstructions included conventional image (CI), CI combined with MAR (CIMAR), and virtual monoenergetic images (VMI) combined with MAR (VMIMAR) at 50-120 keV. The attenuation and standard deviation of the vessel and artifact, and the width of artifact were measured. Qualitative scoring was evaluated including the vascular contour, the extent of artifact, and overall diagnostic evaluation. RESULTS: The attenuation, noise of the vessel and artifact, and the width of artifact decreased as the energy level increased (p < 0.001). The downtrend was relatively flat at 80-120 keV, and the vascular attenuation dropped to 200 HU at 90 keV. The qualitative rating of vascular contour was significantly higher at CIMAR (3.47) and VMIMAR 60-80 keV (2.82-3.65) compared with CI (2.03) (p ≤ 0.029), and the highest score occurred at 70 and 80 keV (3.65 and 3.56). The score of the extent of artifact was higher at VMIMAR 80 keV than CIMAR (3.53 VS 3.12, p = 0.003). The score of the overall diagnostic evaluation was higher at VMIMAR 70 and 80 keV (3.32 and 3.53, respectively) than CIMAR (3.12) (p ≤ 0.035). CONCLUSION: Eighty kiloelectron volts on VMIMAR, providing satisfactorily reduced metal artifacts and improved vascular visualization, can be an optimal recommended parameter of spectrum CT for the assessment of periprosthetic vasculature in THA patients. CRITICAL RELEVANCE STATEMENT: The metal artifact is gradually reducing with increasing energy level; however, the vascular visualization is worsening. The vascular visualization is terrible above 100 keV, while the vessel is disturbed by artifacts below 70 keV. The best performance is found at 80 keV. KEY POINTS: • VMIMAR can provide both reduced metal artifacts and improved vascular visualization. • Eighty kiloelectron volts on VMIMAR performs best in vascular visualization of total hip arthroplasty patients. • Energy spectrum CT is recommended for routine use in patients with total hip arthroplasty.

Non-coding RNAs and gastrointestinal cancers prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies.

Aim: Provide an overview and a systematic evaluation of the evidence quality on the association between non-coding RNAs (ncRNAs) and prognosis value for gastrointestinal cancers (GICs). Methods: We searched the literature from three electronic databases: Pubmed, Embase, and Web of science, then carefully screened and extracted the primary information and results from the included articles. We use A measurable systematic review and meta-analysis evaluation tool (AMSTAR2) to evaluate the quality of methodology and then use the Grading of Recommendations Assessment 2, Development and Evaluation guideline (GRADE) make sure the reliability of the meta-analysis. Results: Overall, 182 meta-analyses from 58 studies were included in this study. Most of these studies are of low or very low quality. Using the scoring tool, we found that only two meta-analyses were rated as high reliability, and 17 meta-analyses were rated as medium reliability. Conclusions: Although ncRNA has good prognostic value in some studies, only a tiny amount of evidence is highly credible at present. More research is needed in the future. PROSPERO registration number: CRD42022382296.

Investigating the influence of an adjustable zoned air mattress on sleep: a multinight polysomnography study.

Introduction: A comfortable mattress should improve sleep quality. In this study, we sought to investigate the specific sleep parameters that could be affected by a mattress and explore any potential differences between the effects felt by each sex. Methods: A total of 20 healthy young adults (10 females and 20 males; 22.10 ± 1.25 years) participated in the experiments. A smart adjustable zoned air mattress was designed to maintain comfortable support, and an ordinary mattress was used for comparison. The participants individually spent four nights on these two mattresses in four orders for polysomnography (PSG) scoring. Sleep architecture, electroencephalogram (EEG) spectrum, and heart rate variability (HRV), which reflect the central and autonomic nervous activities, were used to compare the difference between the two mattresses. Results: An individual difference exited in sleep performance. The modes of influence of the mattresses were different between the sexes. The adjustable air mattress and the increase in experimental nights improved female participants' sleep efficiency, while male participants exhibited a smaller response to different mattresses. With an increasing number of experiment nights, both sexes showed increased REM and decreased N2 proportions; the N3 sleep proportion decreased in the male participants, and the heart rate decreased in both sexes. The performance of the EEG spectrum supports the above results. In addition, the adjustable air mattress weakened automatic nerve activity during N3 sleep in most participants. The female participants appeared to be more sensitive to mattresses. Experiment night was associated with psychological factors. There were differences in the results for this influence between the sexes. Conclusion: This study may shed some light on the differences between the ideal sleep environment of each sex.

Bi-allelic variants in ASTL cause abnormal fertilization or oocyte maturation defects.

Fertilization is a fundamental process of development, and the blocking mechanisms act at the zona pellucida (ZP) and plasma membrane of the egg to prevent any additional sperm from binding, permeating and fusing after fertilization. In clinical practice, some couples undergoing recurrent IVF failures that mature oocytes had abnormal fertilization for unknown reason. Ovastacin encoded by ASTL cleave the ZP protein ZP2 and play a key role in preventing polyspermy. Here, we identified bi-allelic variants in ASTL that are mainly characterized by fertilization problems in humans. All four independent affected individuals had bi-allelic frameshift variants or predicted damaging missense variants, which follow a Mendelian recessive inheritance pattern. The frameshift variants significantly decreased the quantity of ASTL protein in vitro. And all missense variants affected the enzymatic activity that cleaves ZP2 in mouse egg in vitro. Three knock-in female mice (corresponding to three missense variants in patients) all show subfertility due to low embryo developmental potential. This work presents strong evidence that pathogenic variants in ASTL cause female infertility and provides a new genetic marker for the diagnosis of fertilization problems.

The Effect of Farmland Transfer on Agricultural Green Total Factor Productivity: Evidence from Rural China.

Exploring the effect and mechanism of farmland transfer on agricultural green total factor productivity (AGTFP) in China is of great significance for exerting the effectiveness of China's farmland transfer policy and promoting green agricultural development. Based on panel data from 30 provinces from 2005 to 2020, this paper applies a two-way fixed effects model to analyze the impact of farmland transfer on AGTFP, and the mechanism of farmland transfer on AGTFP is also investigated. We find that farmland transfer has a significant and sound promoting effect on AGTFP, with respect to multiple robustness checks; there is heterogeneity regarding the impact of farmland transfer on AGTFP in terms of food functions, and farmland transfer can promote regional AGTFP through nonagricultural labor transfer and agricultural technology utilization. When considering the fact that farmland transfer has increased China's AGTFP, the Chinese government should continue to adhere to the farmland transfer policy, accelerate nonagricultural labor transfer, improve the level of agricultural technology utilization, and ultimately promote green agricultural development.

Changes in the cortical network during sleep stage transitions.

Sleep state transitions are closely related to insomnia, drowsiness, and sleep maintenance. However, how the cortical network varies during such a transition process remains unclear. Changes in the cortical interaction during the short-term process of sleep stage transitions were investigated. In all, 40 healthy young participants underwent overnight polysomnography. The phase transfer entropy of six frequency bands was obtained from 16 electroencephalography channels to assess the strength and direction of information flow between the cortical regions. Differences in the cortical network between the first and the last 10 s in a 40-s transition period across wakefulness, N1, N2, N3, and rapid eye movement were, respectively, studied. Various frequency bands exhibited different patterns during the sleep stage transitions. It was found that the mutual transitions between the sleep stages were not necessarily the opposite. More significant changes were observed in the sleep deepening process than in the process of sleep awakening. During sleep stage transitions, changes in the inflow and outflow strength of various cortical regions led to regional differences, but for the entire sleep progress, such an imbalance did not intensify, and a dynamic balance was instead observed. The detailed findings of variations in cortical interactions during sleep stage transition promote understanding of sleep mechanism, sleep process, and sleep function. Additionally, it is expected to provide helpful clues for sleep improvement, like reducing the time required to fall asleep and maintaining sleep depth.

Pulmonary decellularized extracellular matrix (dECM) modified polyethylene terephthalate three-dimensional cell carriers regulate the proliferation and paracrine activity of mesenchymal stem cells.

Introduction: Mesenchymal stem cells (MSCs) possess a high degree of self-renewal capacity and in vitro multi-lineage differentiation potential. Decellularized materials have garnered considerable attention due to their elevated biocompatibility, reduced immunogenicity, excellent biodegradability, and the ability to partially mimic the in vivo microenvironment conducive to cell growth. To address the issue of mesenchymal stem cells losing their stem cell characteristics during two-dimensional (2D) cultivation, this study established three-dimensional cell carriers modified with lung decellularized extracellular matrix and assessed its impact on the life activities of mesenchymal stem cells. Methods: This study employed PET as a substrate material, grafting with polydopamine (PDA), and constructing a decellularized extracellular matrix (dECM) coating on its surface, thus creating the PET/PDA/dECM three-dimensional (3D) composite carrier. Subsequently, material characterization of the cellular carriers was conducted, followed by co-culturing with human umbilical cord mesenchymal stem cells in vitro, aiming to investigate the material's impact on the proliferation and paracrine activity of mesenchymal stem cells. Results and Discussion: Material characterization demonstrated successful grafting of PDA and dECM materials, and it had complete hydrophilicity, high porosity, and excellent mechanical properties. The material was rich in various ECM proteins (collagen I, collagen IV , laminin, fibronectin, elastin), indicating good biocompatibility. In long-term in vitro cultivation (14 days) experiments, the PET/PDA/dECM three-dimensional composite carrier significantly enhanced adhesion and proliferation of human umbilical cord-derived mesenchymal stem cells (HUCMSCs), with a proliferation rate 1.9 times higher than that of cells cultured on tissue culture polystyrene (TCPS) at day 14. Furthermore, it effectively maintained the stem cell characteristics, expressing specific antigens for HUCMSCs. Through qPCR, Western blot, and ELISA experiments, the composite carrier markedly promoted the expression and secretion of key cell factors in HUCMSCs. These results demonstrate that the PET/PDA/dECM composite carrier holds great potential for scaling up MSCs' long-term in vitro cultivation and the production of paracrine factors.

Effect of EGFR amplification on the prognosis of EGFR-mutated advanced non-small-cell lung cancer patients: a prospective observational study.

BACKGROUND: Epidermal growth factor receptor (EGFR) amplification refers to the copy number increase of EGFR gene, and is often identified as a "bypass" way of Epidermal growth factor receptor Tyrosine kinase inhibitors (EGFR-TKI) resistance. We aimed to explore the effect of EGFR amplification on EGFR mutation treatment-naive advanced non-squamous non-small cell lung cancer (NSCLC) patients. METHODS: We conducted a prospective observational study in single center, enrolling advanced non-squamous NSCLC patients receiving Tyrosine kinase inhibitors (TKIs) between March 3, 2019, and February 1, 2022. Next-generation sequencing (NGS) was used to detect genetic alterations in tumor tissue samples. Progression-free survival (PFS) curves were performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate factors affecting the efficacy of TKIs. RESULTS: A total of 117 treatment-naive advanced NSCLC patients were identified in this study. EGFR amplification was found in 22 of 117 (18.8%) patients with EGFR mutations. Of 22 patients with EGFR amplification, 10 patients harbored EGFR 19 del, 11 patients with 21-L858R. The median follow-up time was 22.47 months. The median PFS of the patients with or without EGFR amplification was 8.25 months and 10.67 months, respectively (log-rank test, P = 0.63). In multivariate analysis, EGFR amplification was not an independent prognosis factor for the patients receiving first-line TKIs [HR = 1.38, 95%CI (0.73-2.58), P = 0.321]. Subgroup analysis revealed that EGFR amplification is a risk factor for progression in the brain metastasis population. [HR = 2.28, 95%CI (1.01, 5.14), P = 0.047]. CONCLUSION: EGFR amplification is not an independent prognosis factor for PFS in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.

The mechanism of acentrosomal spindle assembly in human oocytes.

Meiotic spindle assembly ensures proper chromosome segregation in oocytes. However, the mechanisms behind spindle assembly in human oocytes remain largely unknown. We used three-dimensional high-resolution imaging of more than 2000 human oocytes to identify a structure that we named the human oocyte microtubule organizing center (huoMTOC). The proteins TACC3, CCP110, CKAP5, and DISC1 were found to be essential components of the huoMTOC. The huoMTOC arises beneath the oocyte cortex and migrates adjacent to the nuclear envelope before nuclear envelope breakdown (NEBD). After NEBD, the huoMTOC fragments and relocates on the kinetochores to initiate microtubule nucleation and spindle assembly. Disrupting the huoMTOC led to spindle assembly defects and oocyte maturation arrest. These results reveal a physiological mechanism of huoMTOC-regulated spindle assembly in human oocytes.

Unraveling the Role of Objective Food Environment in Chinese Elderly's Diet-Related Diseases Epidemic: Considering Both Healthy Food Accessibility and Diversity.

The essential role of the objective food environment in achieving healthy aging has been widely recognized worldwide. However, the existing empirical evidence is mostly based on Western cases, and how the objective food environment associates with health outcomes among Chinese elderly remains poorly understood. By merging nationally representative micro survey data with Baidu-based spatial data on the location of food outlets, this study develops accessibility and diversity indicators to explore the relationship between food environment and diet-related diseases among Chinese elderly and investigates how healthy lifestyles moderate this relationship. The results show that improvement in healthy food accessibility and diversity decreases both the probability and the number of diet-related diseases that the elderly suffer. Having more healthy lifestyle factors is associated with a lower risk of suffering from diet-related diseases and strengthens the negative effect of healthy food environment on suffered diet-related diseases. Heterogeneity effect analysis suggests that the relationship between objective food environment and diet-related diseases differs by city scale and income level. The findings of this study shed light on designing tailor-made policies for non-Western countries to promote healthy aging.