Down-regulation of KLRB1 is associated with increased cell growth, metastasis, poor prognosis, as well as a dysfunctional immune microenvironment in LUAD.

Killer cell lectin-like receptor B1 (KLRB1) is implicated in cancer progression and immunity. In this study, we aimed to evaluate the expression levels of KLRB1 in lung adenocarcinoma (LUAD) and analyze the relationship between KLRB1 expression levels, LUAD progression, and the tumor immune microenvironment. KLRB1 levels in LUAD were analyzed using data from the TCGA and XENA databases. Additionally, the diagnostic values of KLRB1 were analyzed in patients with LUAD. Survival and meta-analyses were employed to investigate the relationship between KLRB1 levels and other prognostic factors in patients with LUAD. Bioinformatics and cellular experiments were used to understand the functions and mechanisms of KLRB1. In addition, correlation analysis was used to investigate the relationship between KLRB1 levels and the immune microenvironment in LUAD. Reduced KLRB1 expression in LUAD was found to positively correlate with tumor size, distant metastasis, pathological stage, age, overall survival, diagnostic value, and disease-specific survival in patients with LUAD (P < 0.05). Conversely, increased KLRB1 expression was found to positively correlate with the overall survival and disease-specific survival in patients with LUAD (P < 0.05). We also found that the overexpression of KLRB1 can inhibit the proliferation, migration, and invasion of LUAD cells and promote apoptosis. KLRB1 was involved in immune cell differentiation, NF-kB, PD-L1, and PD-1 checkpoint pathways and others. Additionally, KLRB1 expression was linked to tumor purity, stromal, immune, and estimate scores, the levels of immune cells including B cells, CD8+ T cells, and CD4+ T cells, and immune cell markers in LUAD. Reduced KLRB1 expression has a significant positive correlation with diagnosis, poor prognosis, and immunity to cancer in patients with LUAD. KLRB1 inhibited cell proliferation and migration in patients with LUAD. These results suggest that KLRB1 may serve as a potential therapeutic target in patients with LUAD.

Repeatability assessment of anterior segment measurements in myopic patients using an anterior segment OCT with placido corneal topography and agreement with a swept-source OCT.

BACKGROUND: The precision of anterior segment biometric measurements in eyes has become increasingly important in refractive surgery. The purpose of this study is to assess the repeatability of the automatic measurements provided by a new spectral-domain optical coherence tomograph (SD-OCT)/Placido topographer (MS-39, CSO) and its agreement with a swept-source OCT (SS-OCT) biometer (CASIA SS-1000, Tomey) in patients with myopia. METHODS: The right eye of 235 subjects was scanned 3 times with both devices. The evaluated parameters included central corneal radius of the steep meridian, central corneal radius of the flat meridian, mean central corneal radius, thinnest corneal thickness, central corneal thickness, anterior chamber depth, corneal volume and diameter. The intraobserver repeatability of the MS-39 measurements was calculated using intraclass correlation coefficient (ICC), within subject standard deviation, coefficient of repeatability, coefficient of variation and repeated-measures analysis of variance of the 3 repeated measurements. The agreement between the two devices was evaluated by 95% limits of agreement (LoA). RESULTS: The majority of the parameters acquired from MS-39 showed high repeatability. The repeatability of corneal diameter was slightly lower than the other measurements, although the ICC remained high. Agreement with the CASIA SS-1000 was good, indicated by the Bland-Altman plots with narrow 95% LoA values for all parameters assessed. CONCLUSIONS: The high repeatability of automatic measurements by the new device supports its clinical application in eyes with myopia, and the good agreement between the two devices indicates they could be used interchangeably for the parameters evaluated.

SLC7A8 overexpression inhibits the growth and metastasis of lung adenocarcinoma and is correlated with a dismal prognosis.

BACKGROUND: Overexpression of solute carrier family 7 member 8 (SLC7A8) has been shown to relate to the survival time and tumor progression in cancer patients. However, the role of SLC7A8 in lung adenocarcinoma (LUAD) is still obscure. METHOD: The relationships between SLC7A8 expression in LUAD tissues and clinical values as well as immune infiltration were explored through bioinformatics. The functions and pathways of SLC7A8 in LUAD were investigated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Gene Set Enrichment Analysis, Western blotting, and other methods. RESULTS: We found that the expression of SLC7A8 was decreased significantly in LUAD tissues compared with normal tissues, which was related to the dismal survival time and disease progression. Moreover, it carried diagnostic value in LUAD and was a risk factor for dismal prognosis. Receiver operating characteristic curve analysis indicated that the expression level of SLC7A8 carried significant diagnostic value in LUAD. Overexpression of SLC7A8 inhibited the proliferation, invasion, and migration of LUAD cells, likely through a mechanism involving the cell cycle. SLC7A8 expression in LUAD was significantly correlated with the infiltration of immune cells, especially B cells, interstitial dendritic cells, mast cells, CD56 bright cells, natural killer cells, plasmacytoid dendritic cells, T follicular helper cells, T helper 2 and 17 cells, and immune factors. CONCLUSION: The downregulation of SLC7A8 was related to a dismal prognosis and immune cell infiltration in LUAD. Increasing the expression of SLC7A8 inhibited the growth and migration of LUAD cells, thereby improving the prognosis of patients.

Acupoint Stimulation for Pain Control in Enhanced Recovery After Surgery: Systematic Review and Meta-Analysis.

Introduction: Postoperative pain control is a challenge in enhanced recovery after surgery (ERAS). The current study reviewed the efficacy and safety of incorporating acupoint stimulation for postoperative pain control in ERAS. Methods: Ten databases for relevant randomized controlled trials (RCTs) published in English or Mandarin Chinese were searched from 1997 to 2022. The quality of each article was appraised using the Cochrane Collaboration Risk of Bias Criteria and the modified Jadad Scale. The primary outcome was pain control, measured using the visual analog scale 24 h after surgery. Results: Eleven trials met the eligibility criteria and were included in the study. Acupoint stimulation was found more effective than control treatments in terms of pain intensity (standardized mean difference [SMD] -0.94; 95% confidence interval [CI] -1.35 to -0.53), analgesic drug consumption (SMD -1.87; 95% CI -2.98 to -0.75), postoperative nausea (PON; SMD 0.31; 95% CI 0.13 to 0.73), postoperative vomiting (POV; SMD 0.57; 95% CI 0.11 to 2.92), and PON and POV (PONV; SMD 0.29; 95% CI 0.16 to 0.53). The Zusanli (ST36) and Neiguan (PC6) were the most-used acupoints in the included trials (8/11). The reported adverse reaction was only one case of bruising. Discussion: Acupoint stimulation improved pain control in patients undergoing ERAS more than control treatments. The findings provide an evidence-based premise for incorporating acupoint stimulation into ERAS strategies. More rigorous RCTs are needed in the future.

Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients.

BACKGROUND: The association between Killer cell lectin like receptor B1 (KLRB1) and cancer has been reported, but the roles of KLRB1 in breast invasive carcinoma (BRCA) has not been fully revealed. METHODS: Our study utilized the Cancer Genome Atlas (TCGA), Kaplan-Meier (K-M) Plotter, and TIMER databases to investigate the expression and clinical relevance of KLRB1 in BRCA and to explore its roles and mechanism in BRCA progression using gene set enrichment analysis, CCK-8, migration, apoptosis, and western blotting. We examined the relationship between KLRB1 expression and the BRCA immune microenvironment, using data from TCGA, and Gene Expression Profiling Interactive Analysis (GEPIA) databases and validated these findings in K-M Plotter databases. RESULTS: A significant decrease of KLRB1 expression was observed in BRCA patients. BRCA patients with low KLRB1 levels were associated with older age, advanced disease stage, HER2-positivity, poor prognosis, and a decreased survival probability compared to the high-expression group. Increased KLRB1 expression levels were correlated with inhibition of breast cancer cell proliferation, migration, and invasion, as well as promotion of cell apoptosis, possible through regulation of the NF-κB, PI3K/AKT, and TNF signaling pathways. Moreover, the study also indicated that decreased KLRB1 expression correlated with tumor purity, immune score, and immune cell infiltration (B cells, CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells, among others), cell markers, and immunotherapy. CONCLUSION: Decreased KLRB1 expression in BRCA is associated with poor prognosis and immune microenvironment. This study also highlights KLRB1 as a potential molecular marker for poor prognosis in BRCA patients, and therefore, it may provide clinical implications for the management of patients with BRCA.

Effect of acupuncture inclusion in the enhanced recovery after surgery protocol on tumor patient gastrointestinal function: a systematic review and meta-analysis of randomized controlled studies.

Introduction: Acupuncture has been shown to be effective in restoring gastrointestinal function in tumor patients receiving the enhanced recovery after surgery (ERAS) protocol. The present systematic review and meta-analysis aimed to evaluate the rationality and efficacy of integrating acupuncture in the ERAS strategy to recuperate gastrointestinal function. Methods: We searched eleven databases for relevant randomized clinical trials (RCTs) of acupuncture for the treatment of gastrointestinal dysfunction in tumor patients treated with the ERAS protocol. The quality of each article was assessed using the Cochrane Collaboration risk of bias criteria and the modified Jadad Scale. As individual symptoms, the primary outcomes were time to postoperative oral food intake, time to first flatus, time to first distension and peristaltic sound recovery time (PSRT). Pain control, adverse events, and acupoint names reported in the included studies were also investigated. Results: Of the 211 reviewed abstracts, 9 studies (702 patients) met eligibility criteria and were included in the present systematic review and meta­analysis. Compared to control groups, acupuncture groups showed a significant reduction in time to postoperative oral food intake [standardized mean difference (SMD) = -0.77, 95% confidence interval (CI) -1.18 to -0.35], time to first flatus (SMD=-0.81, 95% CI -1.13 to -0.48), time to first defecation (SMD=-0.91, 95% CI -1.41 to -0.41, PSRT (SMD=-0.92, 95% CI -1.93 to 0.08), and pain intensity (SMD=-0.60, 95% CI -0.83 to -0.37).The Zusanli (ST36) and Shangjuxu (ST37) acupoints were used in eight of the nine included studies. Adverse events related to acupuncture were observed in two studies, and only one case of bruising was reported. Discussion: The present systematic review and meta­analysis suggested that acupuncture significantly improves recovery of gastrointestinal function and pain control in tumor patients receiving the ERAS protocol compared to the control group. Moreover, ST36 and ST37 were the most frequently used acupoints. Although the safety of acupuncture was poorly described in the included studies, the available data suggested that acupuncture is a safe treatment with only mild side effects. These findings provide evidence-based recommendations for the inclusion of acupuncture in the ERAS protocol for tumor patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42023430211.

Protective effect of water extracts of Veronicastrum latifolium (Hemsl.) Yamazaki on carbon tetrachloride-induced liver fibrosis in mice and its effect on intestinal flora.

Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl4-elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl4-induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl4-elicited liver fibrosis.

A neuromarker for deficit syndrome in schizophrenia from a combination of structural and functional magnetic resonance imaging.

AIM: Deficit schizophrenia (DS), defined by primary and enduring negative symptoms, has been proposed as a promising homogeneous subtype of schizophrenia. It has been demonstrated that unimodal neuroimaging characteristics of DS were different from non-deficit schizophrenia (NDS), however, whether multimodal-based neuroimaging features could identify deficit syndrome remains to be determined. METHODS: Functional and structural multimodal magnetic resonance imaging of DS, NDS and healthy controls were scanned. Voxel-based features of gray matter volume, fractional amplitude of low-frequency fluctuations, and regional homogeneity were extracted. The support vector machine classification models were constructed using these features separately and jointly. The most discriminative features were defined as the first 10% of features with the greatest weights. Moreover, relevance vector regression was applied to explore the predictive values of these top-weighted features in predicting negative symptoms. RESULTS: The multimodal classifier achieved a higher accuracy (75.48%) compared with the single modal model in distinguishing DS from NDS. The most predictive brain regions were mainly located in the default mode and visual networks, exhibiting differences between functional and structural features. Further, the identified discriminative features significantly predicted scores of diminished expressivity factor in DS but not NDS. CONCLUSIONS: The present study demonstrated that local properties of brain regions extracted from multimodal imaging data could distinguish DS from NDS with a machine learning-based approach and confirmed the relationship between distinctive features and the negative symptoms subdomain. These findings may improve the identification of potential neuroimaging signatures and improve the clinical assessment of the deficit syndrome.

Cholecystokinin neurons in mouse suprachiasmatic nucleus regulate the robustness of circadian clock.

The suprachiasmatic nucleus (SCN) can generate robust circadian behaviors in mammals under different environments, but the underlying neural mechanisms remained unclear. Here, we showed that the activities of cholecystokinin (CCK) neurons in the mouse SCN preceded the onset of behavioral activities under different photoperiods. CCK-neuron-deficient mice displayed shortened free-running periods, failed to compress their activities under a long photoperiod, and developed rapid splitting or became arrhythmic under constant light. Furthermore, unlike vasoactive intestinal polypeptide (VIP) neurons, CCK neurons are not directly light sensitive, but their activation can elicit phase advance and counter light-induced phase delay mediated by VIP neurons. Under long photoperiods, the impact of CCK neurons on SCN dominates over that of VIP neurons. Finally, we found that the slow-responding CCK neurons control the rate of recovery during jet lag. Together, our results demonstrated that SCN CCK neurons are crucial for the robustness and plasticity of the mammalian circadian clock.

Synergistic structural and functional alterations in the medial prefrontal cortex of patients with high-grade gliomas infiltrating the thalamus and the basal ganglia.

Background: High-grade gliomas (HGGs) are characterized by a high degree of tissue invasion and uncontrolled cell proliferation, inevitably damaging the thalamus and the basal ganglia. The thalamus exhibits a high level of structural and functional connectivity with the default mode network (DMN). The present study investigated the structural and functional compensation within the DMN in HGGs invading the thalamus along with the basal ganglia (HITBG). Methods: A total of 32 and 22 healthy controls were enrolled, and their demographics and neurocognition (digit span test, DST) were assessed. Of the 32 patients, 18 patients were involved only on the left side, while 15 of them were involved on the right side. This study assessed the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), gray matter (GM) volume, and functional connectivity (FC) within the DMN and compared these measures between patients with left and right HITBG and healthy controls (HCs). Result: The medial prefrontal cortex (mPFC) region existed in synchrony with the significant increase in ALFF and GM volume in patients with left and right HITBG compared with HCs. In addition, patients with left HITBG exhibited elevated ReHo and GM precuneus volumes, which did not overlap with the findings in patients with right HITBG. The patients with left and right HITBG showed decreased GM volume in the contralateral hippocampus without any functional variation. However, no significant difference in FC values was observed in the regions within the DMN. Additionally, the DST scores were significantly lower in patients with HITBG, but there was no significant correlation with functional or GM volume measurements. Conclusion: The observed pattern of synchrony between structure and function was present in the neuroplasticity of the mPFC and the precuneus. However, patients with HITBG may have a limited capacity to affect the connectivity within the regions of the DMN. Furthermore, the contralateral hippocampus in patients with HITBG exhibited atrophy. Thus, preventing damage to these regions may potentially delay the progression of neurological function impairment in patients with HGG.

Structural plasticity of the contralesional hippocampus and its subfields in patients with glioma.

OBJECTIVES: To characterize the structural plasticity of the contralesional hippocampus and its subfields in patients with unilateral glioma. METHODS: 3D T1-weighted MRI images were collected from 55 patients with tumors infiltrating the left (HipL, n = 27) or right (HipR, n = 28) hippocampus, along with 30 age- and sex-matched healthy controls (HC). Gray matter volume differences of the contralesional hippocampal regions and three control regions (superior frontal gyrus, caudate nucleus, and superior occipital gyrus) were evaluated using voxel-based morphometry (VBM) analyses. Volumetric differences in the hippocampus and its subregional volume were measured using the FreeSurfer software. RESULTS: Compared with HC, patients with unilateral hippocampal glioma exhibited significantly larger gray matter volume in the contralesional hippocampus and parahippocampal regions (cluster = 571 voxels for HipL; cluster 1 = 538 voxels and cluster 2 = 88 voxels for HipR; family-wise error corrected p < 0.05). No significant alterations were found in control regions. Volumetric analyses showed the same trend in the contralesional hippocampal subregions for both patient groups, including the CA1 head, CA3 head, hippocampus amygdala transition area (HATA), fimbria, and the granule cell molecular layer of the dentate gyrus head (GC-ML-DG head). Notably, the differences of the contralesional HATA (HipL: η2 = 0.418, corrected p = 0.002; HipR: η2 = 0.313, corrected p = 0.052) and fimbria (HipL: η2 = 0.450, corrected p < 0.001; HipR: η2 = 0.358, corrected p = 0.012) still held after the Bonferroni correction. CONCLUSIONS: Our findings provide evidence for macrostructural plasticity of the contralateral hippocampus in patients with unilateral hippocampal glioma. Specifically, HATA and fimbria exhibit great potential in this process. KEY POINTS: • Glioma infiltration of the hippocampal regions induces a significant increase in gray matter volume on the contralateral side. • Specifically, the HATA and fimbria regions exhibit favorable plastic potential in the process of lesion-induced structural remolding.

The role of extreme heat exposure on premature rupture of membranes in Southern California: A study from a large pregnancy cohort.

BACKGROUND: Significant mortality and morbidity in pregnant women and their offspring are linked to premature rupture of membranes (PROM). Epidemiological evidence for heat-related PROM risk is extremely limited. We investigated associations between acute heatwave exposure and spontaneous PROM. METHODS: We conducted this retrospective cohort study among mothers in Kaiser Permanente Southern California who experienced membrane ruptures during the warm season (May-September) from 2008 to 2018. Twelve definitions of heatwaves with different cut-off percentiles (75th, 90th, 95th, and 98th) and durations (≥ 2, 3, and 4 consecutive days) were developed using the daily maximum heat index, which incorporates both daily maximum temperature and minimum relative humidity in the last gestational week. Cox proportional hazards models were fitted separately for spontaneous PROM, term PROM (TPROM), and preterm PROM (PPROM) with zip codes as the random effect and gestational week as the temporal unit. Effect modification by air pollution (i.e., PM2.5 and NO2), climate adaptation measures (i.e., green space and air conditioning [AC] penetration), sociodemographic factors, and smoking behavior was examined. RESULTS: In total, we included 190,767 subjects with 16,490 (8.6%) spontaneous PROMs. We identified a 9-14% increase in PROM risks associated with less intense heatwaves. Similar patterns as PROM were found for TPROM and PPROM. The heat-related PROM risks were greater among mothers exposed to a higher level of PM2.5 during pregnancy, under 25 years old, with lower education and household income level, and who smoked. Even though climate adaptation factors were not statistically significant effect modifiers, mothers living with lower green space or lower AC penetration were at consistently higher heat-related PROM risks compared to their counterparts. CONCLUSION: Using a rich and high-quality clinical database, we detected harmful heat exposure for spontaneous PROM in preterm and term deliveries. Some subgroups with specific characteristics were more susceptible to heat-related PROM risk.

Radiogenomics to characterize the immune-related prognostic signature associated with biological functions in glioblastoma.

OBJECTIVES: The tumor microenvironment and immune cell infiltration (ICI) associated with glioblastoma (GBM) play a vital role in cancer development, progression, and prognosis. This study aimed to establish an ICI-related prognostic biomarker and explore the associations between ICI signatures and radiomic features in patients with GBM. METHODS: The gene expression and survival data of patients with GBM were obtained from three databases. Based on the ICI pattern, an individualized ICI score for each GBM patient was developed in the discovery set (n = 400) and independently verified in the validation set (n = 374). A total of 5915 radiomic features were extracted from the intratumoral and peritumoral regions. Recursive feature elimination and support vector machine methods were performed to select the key features and generate a model predictive of low- or high- ICI scores. The prognostic value of the identified radio genomic model was examined in an independent dataset (n = 149) using imaging and survival data. RESULTS: We found that higher ICI scores often indicated worse patient prognosis (multivariable hazard ratio: 0.48 and 0.63 in discovery and validation set, respectively) and higher expression levels of immune checkpoint-related genes. A model that combined 11 radiomic features could well distinguish tumors with different ICI scores (AUC = 0.96, accuracy = 94%). This model was proven to be helpful for noninvasive prognostic stratification in an independent validation cohort. CONCLUSIONS: ICI scores may serve as an effective prognostic biomarker to characterize potential biological processes in patients with GBM. This ICI signature can be evaluated noninvasively through radiogenomic analysis. KEY POINTS: • Immune cell infiltration (ICI) scores can serve as an effective prognostic biomarker in patients with glioblastoma. • The ICI signature can be evaluated noninvasively through radiomic features derived from the intratumoral and peritumoral regions. • The prognostic value of the radiogenomic model can be verified by independent survival and MRI data.

Radiomics-Based Machine Learning to Predict Recurrence in Glioma Patients Using Magnetic Resonance Imaging.

OBJECTIVE: Recurrence is a major factor in the poor prognosis of patients with glioma. The aim of this study was to predict glioma recurrence using machine learning based on radiomic features. METHODS: We recruited 77 glioma patients, consisting of 57 newly diagnosed patients and 20 patients with recurrence. After extracting the radiomic features from T2-weighted images, the data set was randomly divided into training (58 patients) and testing (19 patients) cohorts. An automated machine learning method (the Tree-based Pipeline Optimization Tool) was applied to generate 10 independent recurrence prediction models. The final model was determined based on the area under the curve (AUC) and average specificity. Moreover, an independent validation set of 20 patients with glioma was used to verify the model performance. RESULTS: Recurrence in glioma patients was successfully predicting by machine learning using radiomic features. Among the 10 recurrence prediction models, the best model achieved an accuracy of 0.81, an AUC value of 0.85, and a specificity of 0.69 in the testing cohort, but an accuracy of 0.75 and an AUC value of 0.87 in the independent validation set. CONCLUSIONS: Our algorithm that is generated by machine learning exhibits promising power and may predict recurrence noninvasively, thereby offering potential value for the early development of interventions to delay or prevent recurrence in glioma patients.

Endometrial transcriptome profiling of patients with recurrent implantation failure during hormone replacement therapy cycles.

Background: The molecular mechanisms underlying window of implantation (WOI) displacement in patients with recurrent implantation failure (RIF) remain unclear. This study aims to explore the transcriptomic signatures of endometrium with normal and displaced WOIs and to identify the causes of endometrial receptivity (ER) abnormalities and WOI displacement in RIF patients. Methods: In this study, 40 RIF patients were recruited and underwent personalized embryo transfer (pET) guided by the predicted results of endometrial receptivity diagnosis (ERD) model. Transcriptome analysis of endometrium from patients with clinical pregnancies after pET was performed to identify differentially expressed genes (DEGs) associated with WOI displacement. Gene expression data from HRT and natural cycle endometrium were compared to identify specific gene expression patterns of ER-related genes during WOI. Results: The ERD results indicated that 67.5% of RIF patients (27/40) were non-receptive in the conventional WOI (P+5) of the HRT cycle. The clinical pregnancy rate in RIF patients improved to 65% (26/40) after ERD-guided pET, indicating the effectiveness of transcriptome-based WOI prediction. Among the 26 patients with clinical pregnancy, the gene expression profiles of P+5 endometrium from advanced (n=6), normal (n=10) and delayed (n=10) WOI groups were significantly different from each other. Furthermore, 10 DEGs identified among P+5 endometrium of 3 groups were involved in immunomodulation, transmembrane transport and tissue regeneration, which could accurately classify the endometrium with different WOIs. Additionally, a large number of ER-related genes showed significant correlation and similar gene expression patterns in P+3, P+5, and P+7 endometrium from HRT cycles and LH+5, LH+7, and LH+9 endometrium from natural cycles. Conclusion: Our study shows that ER-related genes share similar gene expression patterns during WOI in both natural and HRT cycles, and their aberrant expression is associated with WOI displacements. The improvement of pregnancy outcomes in RIF patients by adjusting ET timing according to ERD results demonstrates the importance of transcriptome-based endometrial receptivity assessment and the clinical efficiency of ERD model.

Synergetic reorganization of the contralateral structure and function in patients with unilateral frontal glioma.

Objective: This study aimed to investigate the contralateral structural and functional plasticity induced by frontal gliomas. Methods: Patients with left (n = 49) or right (n = 52) frontal diffuse glioma were enrolled along with 35 age- matched healthy controls (HCs). The gray-matter volumes (GMVs) of the contralesional region were measured using the voxel-based morphometry (VBM) analysis. Additionally, the amplitude of low-frequency fluctuation (ALFF) of the contralesional region was calculated via resting state functional magnetic resonance imaging (MRI) to assess functional alterations. Result: The GMV of the contralateral orbitofrontal cortex of the right or left frontal gliomas was significantly larger than the corresponding GMV in the controls. In the patients with right frontal glioma, the GMV and ALFF in the left inferior frontal gyrus were significantly increased compared with those in the controls. Conclusion: Glioma invasion of the frontal lobe can induce contralateral structural compensation and functional compensation, which show synergy in the left inferior frontal gyrus. Our findings explain why patients with unilateral frontal glioma can have functional balance, and offer the possibility of preserving the brain function while maximizing tumor removal.

TRAT1 overexpression delays cancer progression and is associated with immune infiltration in lung adenocarcinoma.

The roles and mechanisms of T-cell receptor (TCR)-associated transmembrane adaptor 1 (TRAT1) in lung adenocarcinoma (LAC) have not yet been reported in the relevant literature. Therefore, this study aimed to understand the roles and mechanisms of TRAT1 in LAC using bioinformatics and in vitro experiments. TRAT1 expression levels in LAC samples were analysed using various databases. TRAT1 co-expressed genes were acquired by the correlation analysis of LAC tissues. The functional mechanisms and protein network of TRAT1 co-expressed genes were analysed using bioinformatics analysis. The expression of TRAT1 was activated in LAC cells, and the roles of TRAT1 overexpression in the growth and migration of cancer cells was investigated using flow cytometry, Cell Counting Kit-8 (CCK-8), and migration and invasion assays. The relationship between TRAT1 overexpression, the immune microenvironment, and RNA modification was evaluated using correlation analysis. TRAT1 expression levels were significantly abnormal at multiple mutation sites and were related to the prognosis of LAC. TRAT1 co-expressed genes were involved in cell proliferation, adhesion, and differentiation, and TRAT1 overexpression significantly inhibited cell viability, migration, and invasion and promoted apoptosis of A549 and H1299 cells, which might be related to the TCR, B cell receptor (BCR), MAPK, and other pathways. TRAT1 expression levels were significantly correlated with the ESTIMATE, immune, and stromal scores in the LAC microenvironment. Additionally, TRAT1 expression levels were significantly correlated with the populations of B cells, CD8 T cells, cytotoxic cells, and other immune cells. TRAT1 overexpression was significantly correlated with the expression of immune cell markers (such as PDCD1, CD2, CD3E) and genes involved in RNA modification (such as ALKBH1, ALKBH3, ALKBH5). In conclusions, TRAT1 overexpression inhibited the growth and migration of LAC cells, thereby delaying cancer progression, and was correlated with the LAC microenvironment and RNA modifications.