Alterations of the amplitude of low-frequency fluctuation induced by repetitive transcranial magnetic stimulation combined with antidepressants treatment for major depressive disorder.

We investigated the neuroimaging changes and clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants in major depressive disorder (MDD) patients. We scanned 35 patients with MDD and 27 healthy controls (HC) with resting-state functional magnetic resonance imaging (fMRI) before and after treatment. We analyzed amplitude of low-frequency fluctuation (ALFF) and the correlation with clinical variables. The rate of significant efficacy after treatment was higher in the combination treatment group than in the antidepressant group, although not statistically significant. At baseline, ALFF increased in the left middle temporal, brain stem, and left cerebellum and decreased in the right anterior cingulate (ACC), right orbital frontal cortex (OFC), and right caudate. ALFF increased in the left fusiform and decreased in the right lingual gyrus, left middle occipital gyrus, and left superior occipital gyrus after antidepressants. ALFF increased in the right ACC, right OFC, and right rectus after combination treatment. ALFF changes in the right ACC/OFC were negatively correlated with HAMD changes. After treatment, abnormal activity in some brain regions normalized, but these regions differed between the two treatment groups. rTMS combined with antidepressants therapy may improve MDD symptoms by improving neuronal activity levels in the right ACC and right OFC.

Novel Prognostic Model Construction of Tongue Squamous Cell Carcinoma Based on Apigenin-Associated Genes.

BACKGROUND: Clinical indexes are often selected as relevant factors for constructing prognostic models of tongue squamous cell carcinoma (TSCC) patients, while factors related to therapeutic targets are less frequently included. As Apigenin (API) shows anti-tumor properties in many tumors, in this study, we construct a novel prognostic model for TSCC patients based on Apigenin-associated genes through transcriptomic analysis. METHODS: The effect of Apigenin (API) on the cell characteristics of TSCC cells was measured by several phenotype experiments. RNA-seq was executed to ensure differentially expressed genes (DEGs) in squamous cell carcinoma-9 (SCC-9) cells after API treatment. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to verify the expression of API-related genes. Then, combined with the gene expression data and relevant individual information of TSCC samples acquired from The Cancer Genome Atlas (TCGA), an API-related model was built through Lasso regression and multivariate Cox regression. A receiver operating characteristic (ROC) curve and a nomogram and calibration curve were created to forecast patient outcomes to improve the clinical suitability of the API-related signature. The relationships between the two risk groups and function enrichment, immune infiltration characteristics, and drug susceptibility were analyzed. RESULTS: We demonstrated that API could inhibit the malignant behavior of TSCC cells. Among API-related genes, TSCC cells treated with API, compared to the control group, have higher levels of transmembrane protein 213 (TMEM213) and G protein-coupled receptor 158 (GPR158), and lower levels of caspase 14 (CASP14) and integrin subunit alpha 5 (ITGA5). An 7 API-associated gene model was built through Lasso regression and multivariate Cox regression that could direct TSCC prognostic status and tumor immune cell infiltration. In addition, we acquired 6 potential therapeutic agents for TSCC based on the prognostic model. CONCLUSIONS: Our research suggested the inhibition effect of API on TSCC cells and provided a novel prognostic model combined with therapeutic factors that can guide the prognosis of TSCC and clinical decision-making in TSCC.

Neuronatin Promotes the Progression of Non-Small Cell Lung Cancer by Activating the NF-κB Signaling.

BACKGROUND AND OBJECTIVE: Understanding the regulatory mechanisms involving neuronatin (NNAT) in non-small cell lung cancer (NSCLC) is an ongoing challenge. This study aimed to elucidate the impact of NNAT knockdown on NSCLC by employing both in vitro and in vivo approaches. METHODS: To investigate the role of NNAT, its expression was silenced in NSCLC cell lines A549 and H226. Subsequently, various parameters, including cell proliferation, invasion, migration, and apoptosis, were assessed. Additionally, cell-derived xenograft models were established to evaluate the effect of NNAT knockdown on tumor growth. The expression of key molecules, including cyclin D1, B-cell leukemia/lymphoma 2 (Bcl-2), p65, matrix metalloproteinase (MMP) 2, and nerve growth factor (NGF) were examined both in vitro and in vivo. Nerve fiber density within tumor tissues was analyzed using silver staining. RESULTS: Upon NNAT knockdown, a remarkable reduction in NSCLC cell proliferation, invasion, and migration was observed, accompanied by elevated levels of apoptosis. Furthermore, the expression of cyclin D1, Bcl-2, MMP2, and phosphorylated p65 (p-p65) showed significant downregulation. In vivo, NNAT knockdown led to substantial inhibition of tumor growth and a concurrent decrease in cyclinD1, Bcl-2, MMP2, and p-p65 expression within tumor tissues. Importantly, NNAT knockdown also led to a decrease in nerve fiber density and downregulation of NGF expression within the xenograft tumor tissues. CONCLUSION: Collectively, these findings suggest that neuronatin plays a pivotal role in driving NSCLC progression, potentially through the activation of the nuclear factor-kappa B signaling cascade. Additionally, neuronatin may contribute to the modulation of tumor microenvironment innervation in NSCLC. Targeting neuronatin inhibition emerges as a promising strategy for potential anti-NSCLC therapeutic intervention.

Improved Gaussian plume model for atmospheric dispersion considering buoyancy and gravitational deposition: The case of multi-form tritium.

Various types of radionuclides have different atmospheric dispersion characteristics, such as buoyancy and gravitational deposition phenomenon of light gas and heavy particles, respectively. Gaussian plume model was widely used to describe atmospheric dispersion behaviors of radioactive effluents, particularly for the purpose of engineering environmental impact assessment or nuclear emergency support. Nonetheless, buoyancy and gravitational deposition were rarely reported in previous work for tritium in particular, which might cause a deviation in evaluating near-surface concentration distribution and radiation dose to the public. Based on the multi-form tritium case, we made a quantitative description for the buoyancy and gravitational deposition phenomenon and discussed the feasibility of developing an improved Gaussian plume model to predict near-surface concentration distribution. Firstly, tritium concentration distribution near to the surface was predicted by using computational fluid dynamics method (CFD) and standard Gaussian plume model to reach consistency without consideration of buoyancy and gravitational deposition effects. Secondly, effects of buoyancy and gravitational deposition were identified by species transport model for gaseous tritium and discrete phase model for droplet tritium with integrating the buoyancy force caused by density variation of gaseous tritium and gravitational force of droplet tritium with enough size. Thirdly, buoyancy and gravitational deposition correction factors were obtained to modify the standard Gaussian plume model. Lastly, predictive results by improved Gaussian plume model were compared with CFD method. It was proved the improved correction method enables higher accuracy in predicting the atmospheric concentration distribution of gaseous pollutants with density variation or particles with gravitational deposition properties.

Insights into near-surface distribution characteristics of multi-form tritium with consideration of atmospheric buoyancy and gravitational deposition.

Tritium contributes majority to the total airborne radioactive effluents from the nuclear facility because of its considerable production and difficulty in separation. Tritium inventory in the fusion reactor would reach an unprecedented magnitude which brings new safety concern. After being released into the atmosphere, inconsistent atmospheric dispersion behaviors might appear regarding different physicochemical forms such as gaseous state HT, gaseous-aerosol-droplet state HTO. In this study, atmospheric dispersion characteristics of multi-form tritium were investigated based on the computational fluid dynamics method validated by multi-fan type wind tunnel experiments. Species transport model and discrete phase model were used to describe atmospheric dispersion of gaseous and aerosol-droplet state tritium, respectively. Deposition velocity was predicted for gaseous and aerosol-droplet state tritium with different particle sizes. Conditions for describing the changes of particle diameter and its influencing on near-surface tritium distribution due to condensation were provided. The results show that buoyancy effect would strengthen along with the increasing gaseous tritium mass fraction in the airborne effluents. We also indicated that obvious gravitational deposition would appear once gaseous HTO was transformed into droplet state HTO with the particle diameter larger than 20 µm. Both the atmospheric buoyancy and deposition phenomenon would result in a quite different near-surface tritium distribution.

The prognosis of TP53 and EGFR co-mutation in patients with advanced lung adenocarcinoma and intracranial metastasis treated with EGFR-TKIs.

Background: TP53 mutation is a poor factor for non-small cell lung cancer (NSCLC), while the effect of TP53 on prognosis in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (LUAD) with brain metastasis remains elusive and needs further exploration. Methods: We retrospectively analyzed 236 patients and tested for TP53- and EGFR-mutant status in metastasis LUAD patients who had received first-line EGFR-tyrosine kinase inhibitor (TKI) treatment. Survival rates were calculated by the Kaplan-Meier method. Furthermore, univariate and multivariate Cox analyses were performed to identify the independent prognostic factors. Results: There were 114 patients with confirmed non-brain metastasis (NBM), 74 patients with preliminary diagnosis early brain metastasis (EBM), and 48 patients with late brain metastasis (LBM). TP53 and EGFR co-mutations were found in 35/236 patients (14.8%). The median progression-free survival (PFS) and overall survival (OS) in the EGFR mutation and TP53 wild-type group were significantly longer than those in the EGFR and TP53 co-mutation group in all advanced LUAD or NBM. Concurrently, PFS and OS were found to be not significant in EBM and LBM patients. Subgroup analysis revealed longer median PFS and OS in the TP53 wild-type group compared to the TP53 mutant group in L858R patients and not significant in EGFR Exon 19 deletion patients. In LBM patients, the time to brain metastasis in the EGFR mutation and TP53 wild-type group was longer than that in the EGFR and TP53 co-mutation group, and TP53 mutant status was an independent prognostic factor for brain metastasis. The TP53 wild-type group exhibited a higher objective remission rate (ORR) and disease control rate (DCR) than the TP53 mutant group in NBM, EBM, and LBM patients, irrespective of primary lung and brain metastatic lesions. Conclusion: TP53/EGFR co-mutation patients receiving first-line EGFR-TKI treatment had poor prognoses in advanced LUAD, especially with L858R mutation. Moreover, TP53/EGFR co-mutation patients treated with EGFR-TKIs may more easy developed intracranial metastasis.

Based on clinical Ki-67 expression and serum infiltrating lymphocytes related nomogram for predicting the diagnosis of glioma-grading.

Background: Compelling evidence indicates that elevated peripheral serum lymphocytes are associated with a favorable prognosis in various cancers. However, the association between serum lymphocytes and glioma is contradictory. In this study, a nomogram was established to predict the diagnosis of glioma-grading through Ki-67 expression and serum lymphocytes. Methods: We performed a retrospective analysis of 239 patients diagnosed with LGG and 178 patients with HGG. Immunohistochemistry was used to determine the Ki-67 expression. Following multivariate logistic regression analysis, a nomogram was established and used to identify the most related factors associated with HGG. The consistency index (C-index), decision curve analysis (DCA), and a calibration curve were used to validate the model. Results: The number of LGG patients with more IDH1/2 mutations and 1p19q co-deletion was greater than that of HGG patients. The multivariate logistic analysis identified Ki-67 expression, serum lymphocyte count, and serum albumin (ALU) as independent risk factors associated with HGG, and these factors were included in a nomogram in the training cohort. In the validation cohort, the nomogram demonstrated good calibration and high consistency (C-index = 0.794). The Spearman correlation analysis revealed a significant association between HGG and serum lymphocyte count (r = -0.238, P <0.001), ALU (r = -0.232, P <0.001), and Ki-67 expression (r = 0.457, P <0.001). Furthermore, the Ki-67 expression was negatively correlated with the serum lymphocyte count (r = -0.244, P <0.05). LGG patients had lower Ki-67 expression and higher serum lymphocytes compared with HGG patients, and a combination of these two variables was significantly higher in HGG patients. Conclusion: The constructed nomogram is capable of predicting the diagnosis of glioma-grade. A decrease in the level of serum lymphocyte count and increased Ki-67 expression in HGG patients indicate that their immunological function is diminished and the tumor is more aggressive.

Optimal design of transcranial magnetic stimulation coil with iron core.

Objective. Iron core coils offer a passive way to increase the induced electric field intensity during transcranial magnetic stimulation (TMS), but the influences of core position and dimensions on coil performance have not been elaborately discussed before.Approach.In this study, with the basic figure-of-eight (Fo8) and slinky coil structures, iron core coil optimization is performed with the finite element method considering core position and dimensions. A performance factor combining performance parameters, including the maximum induced electric field, stimulation depth, focus, and heat loss, is utilized to evaluate the comprehensive coil performance.Main results.According to the performance factor, both iron core coils obtain the best overall performance with a fill factor 0.4 and the two legs of the iron core close to the inner sides of the coil. Finally, three prototypes are constructed-the basic, optimized, and full-size slinky iron core coil-and magnetic field detection demonstrates a good agreement with the simulation results.Significance.The proposed systematic optimization approach for iron core coil based on Fo8 and slinky basic structure can be applied to improve TMS coil performance, reduce power requirements, and guide the design of other iron core TMS coils.

Clinical Analysis of 50 Cases of Primary Pulmonary Lymphoma: A Retrospective Study and Literature Review.

Objective: This study aimed at to raise the awareness understanding of primary pulmonary lymphoma (PPL) by analyzing the clinical manifestation, imaging, pathology, diagnosis, treatment, and prognostic features of 50 cases of PPL. Methods: The study of 50 individuals with PPL diagnosed at the First affiliated hospital of Nanchang university between January 2009 and December 2019 was performed. Results: Overall, 27 males and 23 females were enrolled, with an average age of 57.6 ± 15.6 years. The primary symptoms included, cough (n = 37), expectoration (n = 25), sputum with blood (n = 12), and chest pain (n = 12). Two individuals had Hodgkin's lymphoma and 48 patients had non-Hodgkin's lymphoma (NHL). We divided the NHL cases into mucosa-associated lymphoid tissue lymphoma (MALT) (n = 21), diffuse large B-cell lymphoma (n = 12), small lymphocytic lymphoma (n = 2), mantle B-cell lymphoma (n = 2), follicular lymphoma (n = 1), B-cell lymphoma without further classification (n = 8), and T-cell lymphoma (n = 2). The imaging findings revealed that unilateral lung involvement was more common among the patients. The longest follow-up duration up to December 2019 was 123 months with 40 surviving patients. The 5-year overall survival and progression-free survival were 46.7% and 44.4%, respectively. Age was an independent predictive factor for the 5-year survival (hazard ratio, 8.900; P = .038), (P < .05). Conclusion: PPL is a uncommon disease with atypical clinical manifestations and is often misdiagnosed. Immunohistochemistry is currently the standard used in pathologic evaluation of PPL. MALT prognosis is better in contrast with other kinds of PPL. Surgery or radiotherapy can be considered in patients with limited lesions, and chemotherapy is the first treatment option for diffuse lesions. Age of ≥ 60 years was reported as an independent adverse predictive factor.

Transmission reconstruction algorithm by combining maximum-likelihood expectation maximization and a convolutional neural network for radioactive drum characterization.

One of the most critical factors that affect reconstructions of the activity of a radioactive drum is the accuracy of tomographic gamma scanning transmission reconstruction. The traditional algorithms applied for reconstructing the density map, such as maximum-likelihood expectation maximization (MLEM), algebraic reconstruction technique, or filtered back-projection, produce a grid distribution with severe grid artifacts and a high level of noise, which significantly degrade the detail of the transmission image, thereby increasing the reconstruction error for both the density map and the activity. Thus, we propose a novel algorithm for transmission reconstruction by combining MLEM and a deep convolutional neural network (CNN). The CNN is trained using a supervised learning approach with image pairs obtained from the drum's ground truth (target) and the result constructed using MLEM (input). Our experimental results indicate that the proposed reconstruction algorithm can significantly improve the spatial resolution while also removing grid artifacts. In addition, the algorithm is sufficiently robust when dealing with a noisy input image. When the input image contained 20% noise, the mean squared error of the output image decreased by 78.51% compared with the conventional reconstruction method, and the peak signal-to-noise ratio and structural similarity index measure for the output image improved by 81.19% and 71.74%, respectively. The new algorithm improves the accuracy of the radioactive drum density map reconstruction as well as decreasing the measurement time required. We consider that the proposed algorithm is an effective new method for use in the field of radioactive waste drum transmission image reconstruction.

Quantitative prediction of dynamic HTO migration behavior in the soil and non-negligible evapotranspiration effect.

Tritium is mainly produced from nuclear facilities apart from nuclear tests. After being released to the environment, tritium would cause water & food contamination due to its radioactivity and mobility. This study investigated dynamic characteristics of tritiated water (HTO) migration in the soil and evapotranspiration effect based on realistic environmental conditions. The influences of soil types and time-varying environmental factors such as precipitation and evapotranspiration on tritium migration behaviors were specially discussed under normal continuous and accidental short-term release conditions. Radiation dose caused by dynamic tritium evapotranspiration was evaluated. The results show that tritium migration velocity in the soil is much higher than other particles such as cesium due to negligible adsorption of tritium by the soil. Tritium migration in the soil from up to down is attributed to precipitation. On the contrary, evapotranspiration factor would carry tritium movement along the opposite direction. A considerable fraction approximately 55% of tritium deposited in the soil would be reemitted into the air from bare soil and plant leaves due to evapotranspiration effect. Subsequently, the radiation dose caused by second plume due to evapotranspiration effect might be higher than the first plume due to direct release from the nuclear facility under routine discharge.

Nomogram Predicting Cancer-Specific Death in Parotid Carcinoma: a Competing Risk Analysis.

PURPOSE: Multiple factors have been shown to be tied to the prognosis of individuals with parotid cancer (PC); however, there are limited numbers of reliable as well as straightforward tools available for clinical estimation of individualized mortality. Here, a competing risk nomogram was established to assess the risk of cancer-specific deaths (CSD) in individuals with PC. METHODS: Data of PC patients analyzed in this work were retrieved from the Surveillance, Epidemiology, and End Results (SEER) data repository and the First Affiliated Hospital of Nanchang University (China). Univariate Lasso regression coupled with multivariate Cox assessments were adopted to explore the predictive factors influencing CSD. The cumulative incidence function (CIF) coupled with the Fine-Gray proportional hazards model was employed to determine the risk indicators tied to CSD as per the univariate, as well as multivariate analyses conducted in the R software. Finally, we created and validated a nomogram to forecast the 3- and 5-year CSD likelihood. RESULTS: Overall, 1,467 PC patients were identified from the SEER data repository, with the 3- and 5-year CSD CIF after diagnosis being 21.4% and 24.1%, respectively. The univariate along with the Lasso regression data revealed that nine independent risk factors were tied to CSD in the test dataset (n = 1,035) retrieved from the SEER data repository. Additionally, multivariate data of Fine-Gray proportional subdistribution hazards model illustrated that N stage, Age, T stage, Histologic, M stage, grade, surgery, and radiation were independent risk factors influencing CSD in an individual with PC in the test dataset (p < 0.05). Based on optimization performed using the Bayesian information criterion (BIC), six variables were incorporated in the prognostic nomogram. In the internal SEER data repository verification dataset (n = 432) and the external medical center verification dataset (n = 473), our nomogram was well calibrated and exhibited considerable estimation efficiency. CONCLUSION: The competing risk nomogram presented here can be used for assessing cancer-specific mortality in PC patients.

The Ki-67 Proliferation Index-Related Nomogram to Predict the Response of First-Line Tyrosine Kinase Inhibitors or Chemotherapy in Non-small Cell Lung Cancer Patients With Epidermal Growth Factor Receptor-Mutant Status.

Background: The correlation between Ki-67 and epidermal growth factor receptor (EGFR)- or Kristen rat sarcoma viral oncogene homolog (KRAS)-mutant status in advanced or postoperative-recurrent non-small cell lung cancer (NSCLC) has fewer studies reported, and the prognostic role of Ki-67 with first-line EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy remains controversial. Methods: A total of 295 patients were tested for EGFR-mutant status in advanced or postoperative-recurrent NSCLC and received first-line EGFR-TKIs or chemotherapy for treatment. Ki-67 expression was retrospectively analyzed by immunohistochemistry. The Kaplan-Meier method was used to calculate survival rates. The multivariate Cox proportional hazards model was used to generate a nomogram. The established nomogram was validated using the calibration plots. Results: The expression levels of Ki-67 were divided into low (<60%, n = 186) and high (≥60%, n = 109) groups, based on the receiver operating characteristic curve. The expression levels of Ki-67 were found to be higher in patients with KRAS mutations when compared to KRAS wildtype, and EGFR wildtype was higher than EGFR mutations. The median overall survival (OS) of the low Ki-67 expression group was significantly longer than that of the high Ki-67 group, no matter in all NSCLC, EGFR mutations, EGFR wildtype, KRAS-mutant status, EGFR-TKIs, or chemotherapy of patients (P < 0.05). Subgroup analysis showed that the KRAS wildtype or EGFR mutations combine with low Ki-67 expression group had the longest median OS than KRAS mutations or EGFR wildtype combine with Ki-67 high expression group (P < 0.05). In the training cohort, the multivariate Cox analysis identified age, serum lactate dehydrogenase (LDH), serum Cyfra211, EGFR mutations, and Ki-67 as independent prognostic factors, and a nomogram was developed based on these covariates. The calibration curve for predicting the 12-, 24-, and 30-month OS showed an optimal agreement between the predicted and actual observed outcomes. Conclusions: The Ki-67 expression-based nomogram can well predict the efficacy of first-line therapy in NSCLC patients with EGFR- or KRAS-mutant status, high expression levels of Ki-67 correlated with a poor prognosis.

A Competing Risk Nomogram for Predicting Cancer-Specific Death of Patients With Maxillary Sinus Carcinoma.

OBJECTIVES: Herein, we purposed to establish and verify a competing risk nomogram for estimating the risk of cancer-specific death (CSD) in Maxillary Sinus Carcinoma (MSC) patients. METHODS: The data of individuals with MSC used in this study was abstracted from the (SEER) Surveillance, Epidemiology, and End Results data resource as well as from the First Affiliated Hospital of Nanchang University (China). The risk predictors linked to CSD were identified using the CIF (cumulative incidence function) along with the Fine-Gray proportional hazards model on the basis of univariate analysis coupled with multivariate analysis implemented in the R-software. After that, a nomogram was created and verified to estimate the three- and five-year CSD probability. RESULTS: Overall, 478 individuals with MSC were enrolled from the SEER data resource, with a 3- and 5-year cumulative incidence of CSD after diagnosis of 42.1% and 44.3%, respectively. The Fine-Gray analysis illustrated that age, histological type, N stage, grade, surgery, and T stage were independent predictors linked to CSD in the SEER-training data set (n = 343). These variables were incorporated in the prediction nomogram. The nomogram was well calibrated and it demonstrated a remarkable estimation accuracy in the internal validation data set (n = 135) abstracted from the SEER data resource and the external validation data set (n = 200). The nomograms were well-calibrated and had a good discriminative ability with concordance indexes (c-indexes) of 0.810, 0.761, and 0.755 for the 3- and 5-year prognosis prediction of MSC-specific mortality in the training cohort, internal validation, and external validation cohort, respectively. CONCLUSIONS: The competing risk nomogram constructed herein proved to be an optimal assistant tool for estimating CSD in individuals with MSC.

Sex-related differences in the efficacy of immune checkpoint inhibitors in malignancy: a systematic review and meta-analysis.

Although disease susceptibility is known to differ between men and women, it is controversial whether the efficacy of immune checkpoint inhibitors for malignancies also differs between the sexes. We conducted a meta-analysis to explore the impact of sex on immune checkpoint inhibitor treatment outcomes. We searched PubMed, Embase and the Cochrane Library databases from inception to October 1, 2020 for randomized controlled trials of immune checkpoint inhibitors with hazard ratios (HRs) stratified by sex. We calculated the pooled HRs for men and women using the ln(HR), and assessed the heterogeneity between the two estimates through an interaction test. In total, 22,268 patients from 39 randomized controlled trials were included. Immune checkpoint inhibitors yielded better overall survival than conventional agents in both men (HR: 0.75, 95% confidence interval [CI]: 0.71-0.80) and women (HR: 0.77, 95% CI: 0.70-0.85). Progression-free survival benefits were also observed in both men (HR: 0.64, 95% CI: 0.58-0.70) and women (HR: 0.67, 95% CI: 0.58-0.77) treated with immune checkpoint inhibitors. No sex differences in the response to immune checkpoint inhibitors were found when overall survival and progression-free survival were used as the endpoints.

Exploration of Prognostic Biomarkers among Replication Factor C Family in the Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the common cancers with a high incidence and mortality. The human replication factor C (RFC) family contains 5 subunits that play an important role in DNA replication and DNA damage repair. RFCs are abnormally expressed in a variety of cancers; some of them are differentially expressed in HCC tissues and related to tumor growth. However, the expression, prognostic value, and effect targets of the whole RFC family in HCC are still unclear. To address these issues, we performed a multidimensional analysis of RFCs in HCC patients by Oncomine, UALCAN, GEPIA, Human protein atlas, Kaplan-Meier plotter, cBioPortal, GeneMANIA, String, and LinkedOmics. mRNA expression of RFCs was significantly increased in HCC tissues. There was a significant correlation between the expression of RFC2/3/4/5 and tumor stage of HCC patients. Besides, high mRNA expression of RFC2/4 was associated with worse overall survival (OS). Moreover, genetic alterations of RFCs were associated with worse OS in HCC patients. We found that genes co-expressed with RFC2/4 were mainly involved in biological processes, such as chromosome segregation, mitotic cell cycle phase transition, and telomere organization and they activated the cell cycle and spliceosome pathways. The gene set is mainly enriched in cancer-related kinases AURKA, ATR, CDK1, PLK1, and CHEK1. E2F family members were the key transcription factors for RFCs. Our results suggest that differentially expressed RFC2 and RFC4 are potential prognostic biomarkers in HCC and may act on E2F transcription factors and some kinase targets to dysregulate the cell cycle pathway. These efforts may provide new research directions for prognostic biomarkers and therapeutic targets in HCC.

Development and Validation of a Novel Nomogram for Predicting Tumor-Distant-Metastasis in Patients with Early T1-2 Stage Lung Adenocarcinoma.

BACKGROUND: Distant metastasis in early T1-2 (diameter≤5 cm) stage lung adenocarcinoma (ET-LUAD) patients largely affect treatment strategies in clinical practice. However, the associated mechanism remains unclear and related studies is less. This study aimed to establish and validate a novel nomogram to predict the risk of distant metastasis in ET-LUAD. METHODS: A total of 258 patients diagnosed with ET-LUAD and not receiving any treatment were recruited into this study. The patients were randomly divided into a training cohort and validation cohort in a ratio of 1:2. Univariate and multivariate logistic regression analysis was used to select the most significant predictive risk factors associated with distant metastasis in the training cohort. The established nomogram was validated by the consistency index (C-index), calibration curve, and decision curve analysis (DCA). RESULTS: There were 124 patients with confirmed distant metastasis and 134 patients with non-distant metastases ET-LUAD were enrolled in the study. Multivariate logistic hazards regression analysis identified independent risk factors associated with distant metastasis to include platelet-to-lymphocyte ratios (PLR), lactate dehydrogenase (LDH), neural-specific enolase (NSE), carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (Cyfra211), which were included in the establishment of the nomogram. The nomogram achieved a high consistency (C-index=0.792), good calibration, and high clinical application value in the validation cohort. CONCLUSION: The established nomogram can be used to predict distant metastasis in high-risk ET-LUAD nonmetastasis patients and can also be used by doctors to guide preventive and individualized treatment for ET-LUAD patients.

The use of clozapine is protective for low bone mineral density induced by prolactin-raising antipsychotics in inpatients with schizophrenia.

Low bone mineral density (BMD) is common among patients with schizophrenia; however, the pathogenesis is still unclear. Different types of antipsychotics may have different effects on BMD in inpatients with schizophrenia. INTRODUCTION: This retrospective study aimed to evaluate the effects of prolactin-raising (PR) antipsychotics vs. clozapine combined with PR antipsychotics on BMD of patients with schizophrenia and analyzed clinically related factors that may affect BMD. METHODS: A total of 125 participants (males/females = 62/63) were included. Patients were treated with PR antipsychotics vs. clozapine combined with PR antipsychotics. They were similar in demographic and clinical characteristics. BMD was examined in their lumbar spine and proximal femur by a dual-energy X-ray (DEXA) absorption measurement device. Laboratory variables (including blood levels of prolactin, estradiol, testosterone, and cortisol) were collected. RESULTS: Among 125 inpatients with schizophrenia, the prevalence of osteoporosis and low BMD (including osteoporosis and osteopenia) was 26.4% and 64%. The average BMD T value in patients receiving clozapine combined with PR antipsychotics was significantly higher than in patients receiving PR antipsychotics (p < 0.05). Patients in the clozapine combined with PR antipsychotic group had higher testosterone levels than the PR antipsychotic group (Z = - 2.77, p = 0.006). Linear logistic regression analysis indicated that clozapine combined with PR antipsychotic treatment (p < 0.05) and higher estradiol level (p < 0.05) may be significantly associated with higher BMD. CONCLUSIONS: Our results suggest that the use of clozapine may be a protective factor for low BMD induced by PR antipsychotics in inpatients with schizophrenia. The possible mechanism is that clozapine may protect BMD by regulating estrogen and testosterone levels, but the mechanism by which clozapine regulates these two sex hormones needs further investigation.

Outcomes of Treatment for Elderly Patients With Trigeminal Neuralgia: Percutaneous Balloon Compression Versus Microvascular Decompression.

OBJECTIVE: The study aimed to evaluate the surgical outcomes of percutaneous balloon compression (PBC) and microvascular decompression (MVD) in the treatment of elderly patients with trigeminal neuralgia (TN). METHODS: A total of 30 patients who underwent PBC surgery (PBC group) and 30 patients who received MVD surgery (MVD group) were included. The treatment efficacy, Barrow Neurological Institute (BNI) pain intensity score, inflammatory response, the rates of complication and recurrence were analyzed respectively. RESULTS: The total efficacy was 93.33% in the PBC group and 90.00% in the MVD group (P > 0.05), respectively. The pain relief rate was 90.00% and 86.67% after PBC and MVD surgery, respectively (P > 0.05). The levels of IL-1ß, TNF-α, and IL-6 were significantly decreased at post-operative 3 days and 5 days compared with pre-operation in the 2 groups (P < 0.05). The post-operative complication rates regarding masticatory muscle weakness and facial numbness in the PBC group were higher than MVD group (P < 0.05). Nevertheless, the incidences of herpes simplex and keratohelcosis were similar between the 2 groups (P > 0.05). The recurrence rates were also similar between the 3 groups (P > 0.05). CONCLUSION: Percutaneous balloon compression and MVD are effective in the treatment for elderly TN, which can effectively improve the post-operative cure rate of pain prognosis and reduce the inflammatory response. However, PBC is a minimally invasive, safe and effective method for patients in poor general condition and refused treatment with craniotomy.

A meta-analysis on XRCC1 R399Q and R194W polymorphisms, smoking and bladder cancer risk.

To elucidate the role of X-ray repair cross-complementing group 1 (XRCC1) R399Q and R194W genotypes in bladder cancer risk, all available studies were considered in the present meta-analysis, with 4152 patients and 5372 controls for R399Q and 3215 patients and 4313 controls for R194W. Studies were identified in PubMed up to June 2008. Overall, the 399Q allele showed no significant effect on bladder cancer compared to 399R allele in all subjects. Insignificant association between R399Q and bladder cancer was observed under other genetic contrasts in worldwide population, Caucasians and never-smokers. Among ever-smokers, protective effects of 399QQ genotype were observed under recessive model [P = 0.004, fixed-effects (FEs) model odds ratio (OR) = 0.65; 95% confidence interval (CI) (0.49, 0.86), I(2) = 0% P(heterogeneity) = 0.57] and homozygote contrast (P = 0.01, FE OR = 0.66; 95% CI (0.49, 0.90), I(2) = 0%, P(heterogeneity) = 0.76). No apparent effect of 194W allele compared to 194R on bladder cancer risk was found in all subjects and Caucasians. It indicated that XRCC1 R399Q and R194W might not be risk factors to bladder cancer, but the 399QQ genotype decreased susceptibility of bladder cancer under recessive model and homozygote contrast among ever-smokers. Further studies based on larger, stratified population were required to explore the role of XRCC1 polymorphisms in bladder cancer risk.