The mechanical regulatory role of ATP13a3 in osteogenic differentiation of pre-osteoblasts.

PURPOSE: The process of osteogenic differentiation hinges upon the pivotal role of mechanical signals. Previous studies found that mechanical tensile strain of 2500 microstrain (µÎµ) at a frequency of 0.5 â€‹Hz promoted osteogenesis in vitro. However, the mechanism of the mechanical strain influencing osteogenesis at the cellular and molecular levels are not yet fully understood. This study aimed to explore the mechanism of mechanical strain on osteogenic differentiation of MC3T3-E1 cells. MATERIALS AND METHODS: Proteomics analysis was conducted to explore the mechanical strain that significantly impacted the protein expression. Bioinformatics identified important mechanosensitive proteins and the expression of genes was investigated using real-time PCR. The dual-luciferase assay revealed the relationship between the miRNA and its target gene. Overexpression and downexpression of the gene, to explore its role in mechanically induced osteogenic differentiation and transcriptomics, revealed further mechanisms in this process. RESULTS: Proteomics and bioinformatics identified an important mechanosensitive lowexpression protein ATP13A3, and the expression of Atp13a3 gene was also reduced. The dual-luciferase assay revealed that microRNA-3070-3p (miR-3070-3p) targeted the Atp13a3 gene. Furthermore, the downexpression of Atp13a3 promoted the expression levels of osteogenic differentiation-related genes and proteins, and this process was probably mediated by the tumor necrosis factor (TNF) signaling pathway. CONCLUSION: Atp13a3 responded to mechanical tensile strain to regulate osteogenic differentiation, and the TNF signaling pathway regulated by Atp13a3 was probably involved in this process. These novel insights suggested that Atp13a3 was probably a potential osteogenesis and bone formation regulator.

Anoikis-related gene signatures predict prognosis of lung adenocarcinoma patients and reveal immune infiltration.

Background: Lung adenocarcinoma (LUAD), a type of lung cancer, is one of the most aggressive and deadly malignancies worldwide. Malignant tumor cells exhibit strong anti-anoikis properties to achieve distant metastasis through the circulatory system. However, more research is needed to understand how anoikis is involved in the progression, metastasis and especially the prognosis of LUAD. Methods: We obtained anoikis-related genes (ARGs) from two websites, Harmonizome and Genecards, and integrated them to select and model the genes associated with LUAD prognosis. In addition, we investigated differences in the immune cell microenvironment and pathways of enrichment analysis between subtypes. We finally constructed a nomogram based on ARGs and used decision curve analysis (DCA) to demonstrate that this model could help clinicians make clinical decisions. Results: Sixty-four differentially expressed genes (DEGs) were found to be associated with survival, and of these, six were chosen to build a prognostic model. The time-dependent receiver operating characteristic (ROC) curves showed that the model had a satisfactory predictive ability. Enrichment analysis and immune microenvironment analysis revealed that the immune status and drug sensitivity of populations at high and low risk were different. We integrated the clinicopathological features of LUAD with the risk score to build the nomogram. The nomogram was shown to be a good predictor of short- and long-term survival in LUAD patients through DCA analysis. Conclusions: This new model based on six ARGs and nomograms in our study could help patients with LUAD develop personalized treatment plans.

Nomogram for predicting prognosis and identifying chemotherapy beneficiaries for completely resected stage I invasive mucinous lung adenocarcinoma.

Background: At present, there is a lack of studies in invasive mucinous adenocarcinoma (IMA) that combine clinicopathological and imaging features to stratify risk and select optimal treatment regimen. We aimed to develop and validate a nomogram for predicting recurrence-free survival (RFS) and identifying adjuvant chemotherapy (ACT) beneficiaries for completely resected stage I primary IMA. Methods: This retrospective study included 750 patients from three hospitals. Patients from two hospitals were divided into training (n=424) and validating cohort (n=185), and patients from the remaining other one hospital constituted external test cohort (n=141) and preoperative computed tomography (CT) image features of each patient were consecutively evaluated. The nomogram was developed by integrating significant prognostic factors of RFS identified in the multivariate analysis. The risk score (RS) based on nomogram was calculated in the entire cohort and the optimal cut-off point for risk stratification was obtained by X-tile software. The Kaplan-Meier method, log-rank test and interaction were used to evaluate the difference in RFS and overall survival (OS) between different risk and treatment groups. Results: Visceral pleural invasion (VPI, P<0.001), lymph-vascular invasion (LVI, P<0.001), tumor size (P<0.001), smoking history (P<0.001), lobulation (P<0.001) were identified as independent prognostic factors for RFS. The concordance index (C-index) of the nomogram was higher than that of tumor-node-metastasis (TNM) staging system (validation cohort: 0.73±0.09 vs. 0.62±0.08, P<0.001; external test cohort: 0.74±0.10 vs. 0.70±0.09, P=0.035). The patients with higher RS were associated with worse RFS [hazard ratios (HRs) ≥4.76] and OS (HRs ≥2.55) in all included cohorts. Chemotherapy benefits in terms of RFS and OS were observed for patients in higher RS group in both stage IB (interaction P=0.012 for RFS and P=0.037 for OS) and stage I IMA (interaction P<0.001 for both RFS and OS). Conclusions: The nomogram based on CT image and clinicopathologic features showed superior performance in predicting RFS for stage I IMA and might identify ACT candidates for personalized patient treatment.

Head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis staging in non-small cell lung cancer: a meta-analysis.

PURPOSE: The current meta-analysis aimed to compare the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) with 18F-FDG PET/magnetic resonance imaging (MRI) in non-small cell lung cancer (NSCLC) lymph node metastasis staging. METHODS: We searched the PubMed, Web of Science, and Embase databases for relevant articles between November 1992 and September 2022. Studies evaluating the head-to-head comparison of 18F-FDG PET/CT and 18F-FDG PET/MRI for lymph node metastasis in patients with NSCLC were included. The quality of each study was assessed using the Quality Assessment of Diagnostic Performance Studies-2 tool. RESULTS: The analysis includes six studies with a total of 434 patients. The pooled sensitivity of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.78 [95% confidence interval (CI): 0.59-0.90] and 0.84 (95% CI: 0.68-0.93), and the pooled specificity was 0.87 (95% CI: 0.72-0.94) and 0.87 (95% CI: 0.80-0.92), respectively. The accuracy of 18F-FDG PET/CT and 18F-FDG PET/MRI was 0.81 (95% CI: 0.71-0.90) and 0.84 (95% CI: 0.75-0.92), respectively. When the pre-test probability was set at 50%, the post-test probability for 18F-FDG PET/CT could increase to 85%, and the post-test probability for 18F-FDG PET/MRI could increase to 87%. CONCLUSION: 18F-FDG PET/CT and 18F-FDG PET/MRI have similar diagnostic performance in detecting lymph node metastasis in NSCLC. However, the results of this study were from a small sample study, and further studies with larger sample sizes are needed.

Diagnostic potential of [18F]FDG PET/MRI in non-small cell lung cancer lymph node metastasis: a meta-analysis.

PURPOSE: This meta-analysis evaluated the diagnostic accuracy and diagnostic value of [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC. METHODS: Relevant articles in PubMed, Embase, Web of Science, and the Cochrane Library were searched until January 2023. Research evaluating [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC was included. Pooled estimates of sensitivity, specificity, PLR, and NLR were calculated by the "Stata" software. RESULTS: Nine researches were included, containing 618 patients. The pooled sensitivity of [18F]FDG PET/MRI for detecting mediastinal lymph node staging of NSCLC was 0.82 (0.70-0.90), and the pooled specificity was 0.88 (0.82-0.93). PLR and NLR were 7.38 (4.73-11.52) and 0.20 (0.11-0.36), respectively. The AUC value of this imaging modality was 0.92 (0.90-0.94). The post-test probability for [18F]FDG PET/MRI might rise to 88% when the pre-test probability was set at 50%. CONCLUSIONS: We considered [18F]FDG PET/MRI as an effective imaging tool with relatively high specificity and sensitivity. It has great potential to be used in the clinical management of patients in NSCLC who are amenable to early surgery. More studies with large sample sizes in the same direction are needed in future to obtain more reliable evidence-based support.

Socioeconomic status, obesity, individual behaviors, diabetes, and risk for frozen shoulder: A Mendelian randomization study.

There are few studies on risk factors for frozen shoulder, and even fewer Mendelian randomization (MR) studies on frozen shoulder. Therefore, we conducted a two-sample MR study to explore whether socioeconomic status (years of schooling, average total household income before tax), obesity (body mass index and waist circumference), individual behaviors (smoking initiation, alcohol intake frequency, coffee intake, nonoily fish intake, tea intake, beef intake, bread intake, cheese intake, oily fish intake, and fresh fruit intake), and diabetes (type 1 and type 2 diabetes) are associated with frozen shoulder. The exposure datasets and the outcome dataset were extracted from the MRC Integrative Epidemiology Unit at the University of Bristol Open genome-wide association studies project (https://gwas.mrcieu.ac.uk/). We conducted MR analyses using the inverse variance weighted (primary method), MR-Egger, and weighted median methods and conducted heterogeneity and pleiotropy analyses. Type 1 diabetes (OR: 1.103; 95% CI: 1.053-1.156; P = .0000410) was associated with an increased risk of frozen shoulder. Cheese intake (OR: 0.490; 95% CI: 0.267-0.899; P = .0213), non-oily fish intake (OR: 0.0993; 95% CI: 0.0220-0.448; P = .00267), years of schooling (OR: 0.453; 95% CI: 0.349-0.588; P = .00000000277), and average total household income before tax (OR: 0.434; 95% CI: 0.253-0.743; P = .00236) were discovered as protective factors. No horizontal pleiotropy was found in all analyzes we performed (P > .05). Our study indicated that type 1 diabetes was a risk factor for frozen shoulder while cheese intake, non-oily fish intake, years of schooling, and average total household income before tax were considered as protective factors for frozen shoulder.

Esophageal cancer stem cells reduce hypoxia-induced apoptosis by inhibiting the GRP78-perk-eIF2α-ATF4-CHOP pathway in vitro.

Background: Due to the abnormal angiogenesis, cancer stem cells (CSCs) in esophageal cancer (EC) have the characteristics of a hypoxic microenvironment. However, they can resist hypoxia-induced apoptosis. the molecular mechanism underlying the resistance of esophageal CSCs to hypoxia-induced apoptosis is currently unclear. Therefore, this study will investigate the molecular mechanism based on CHOP-mediated endoplasmic reticulum stress. Methods: CD44+CD24- cells in EC9706 cells were screened by fluorescence-activated cell sorting (FACS). To clarify which apoptosis pathway esophageal CSCs resist hypoxia-induced cell apoptosis through, the effects of hypoxia on apoptosis were detected by nuclear staining, flow cytometry, and JC-1 reagent, the effects of hypoxia on the expression of apoptosis-related proteins were detected by western blotting (WB) assay and quantitative polymerase chain reaction (qPCR) assay. To clarify the mechanisms of CD44+CD24- cells resistance to hypoxia-induced apoptosis is achieved by inhibiting the activation of endoplasmic reticulum stress (ERS) pathway, silenced CHOP and PERK cell lines of EC9706 cells and overexpressed CHOP and PERK cell lines of CD44+CD24- cells were constructed, the effects of hypoxia on apoptosis, cell cycle, and mitochondrial membrane potential were detected by flow cytometry and JC-1 reagent. WB assay and qPCR assay were used to detect the expressions of apoptosis-related proteins and ERS-related proteins. Results: Hypoxia significantly induce apoptosis and cycle arrest of EC9706 cells (P<0.05), but did not affect apoptosis and cycle of CD44+CD24- cells (P>0.05). Hypoxia considerably induced the activation of mitochondrial and ERS apoptosis pathways in EC9706 cells (P<0.05), but did not affect Fas receptor apoptosis pathways (P>0.05). The three apoptosis pathways were not affected by hypoxia in CD44+CD24- cells (P>0.05). Silencing the CHOP and PERK gene inhibited hypoxia-induced apoptosis of EC9706 cells (P<0.05). CHOP and PERK overexpression promoted hypoxia-induced apoptosis of CD44+CD24- cells (P<0.05), whereas mitochondrial membrane permeability inhibitors inhibited hypoxia-induced apoptosis of CD44+CD24- cells overexpressed CHOP gene. Conclusions: CD44+CD24- tumor stem cells in EC resist to hypoxia-induced apoptosis by the inhibition of ERS-mediated mitochondrial apoptosis pathway, which suggested that ERS pathway can serve as a potential target for reducing EC treatment resistance in clinical treatment.

ß-Glucans in particulate and solubilized forms elicit varied immunomodulatory and apoptosis effects in teleost macrophages in a dosedependent manner.

ß-Glucans are a group of heterogeneous glucose polymers that possess immunomodulatory activities. The complex nature of their structures, uncertainty regarding the doses, and variable immune effects pose a challenge to comprehensive understanding. In this study, we investigated the immune responses and apoptosis effects in Nile tilapia (Oreochromis niloticus) head kidney macrophages (MФ) upon exposure to two ß-Glucans (Paramylon and Laminarin) at low and high doses. Our results demonstrate that Paramylon elicits more robust immune responses than Laminarin, albeit with a dose-limiting effect. We also observed that the high-dose Paramylon induces apoptosis, whereas no such effect was detected in Laminarin treatment. Mechanistically, high-dose Paramylon activates the intrinsic apoptosis pathway, with significantly up-regulation of intrinsic apoptosis-related genes and impaired mitochondrial function. On the other hand, Laminarin triggers metabolic reprogramming in MФ, resulting in the enrichment of the metabolite α-Ketoglutarate, which protects the MФ from apoptosis. Overall, our findings highlight the importance of identifying the optimal dose range for ß-Glucans, based on sources or structures, to achieve maximal immunomodulatory effects. These results have important implications for the design and optimization of ß-Glucans-based drugs or adjuvants in immunotherapies.

Obesity and risk for respiratory diseases: a Mendelian randomization study.

Background: No existing comprehensive Mendelian randomization studies have focused on how obesity affects respiratory diseases. Methods: BMI and waist circumference, mainly from the UK Biobank, and 35 respiratory diseases from the FinnGen Biobank were subjected to Mendelian randomization analyses. In this study, the inverse variance weighting method was used as the predominant analysis method and was complemented by MR-Egger and weighted median methods. Horizontal pleiotropy and potential outliers were detected by employing the MR-PRESSO method. Results: This study indicated that obesity rises the possibility of acute upper respiratory infections (BMI: OR=1.131, p<0.0001; WC: OR=1.097, p=0.00406), acute sinusitis (BMI: OR=1.161, p=0.000262; WC: OR=1.209, p=0.000263), acute pharyngitis (WC: OR=1.238, p=0.0258), acute laryngitis and tracheitis (BMI: OR=1.202, p=0.0288; WC: OR=1.381, p=0.00192), all influenza (BMI: OR=1.243, p=0.000235; WC: OR=1.206, p=0.0119), viral pneumonia (WC: OR=1.446, p=0.000870), all pneumoniae (BMI: OR=1.174, p <0.0001; WC: OR=1.272, p <0.0001), bacterial pneumoniae (BMI: OR=1.183, p=0.000290; WC: OR=1.274, p<0.0001), acute bronchitis (BMI: OR=1.252, p <0.0001; WC: OR=1.237, p=0.000268), acute unspecified lower respiratory infection (BMI: OR=1.303, p=0.000403), chronic tonsils and adenoids diseases (BMI: OR=1.236, p <0.0001; WC: OR=1.178, p=0.000157), chronic laryngotracheitis and laryngitis (WC: OR=1.300, p=0.00785), COPD (BMI: OR=1.429, p <0.0001; WC: OR=1.591, p <0.0001), asthma (BMI: OR=1.358, p <0.0001; WC: OR=1.515, p <0.0001), necrotic and suppurative conditions of lower respiratory tract (WC: OR=1.405, p=0.0427), pleural effusion (BMI: OR=1.277, p=0.00225; WC: OR=1.561, p<0.0001), pleural plaque (BMI: OR=1.245, p=0.0312), other diseases of the respiratory system (BMI: OR=1.448, p <0.0001; WC: OR=1.590, p <0.0001), and non-small cell lung cancer (BMI: OR=1.262, p=0.00576; WC: OR=1.398, p=0.00181). This study also indicated that obesity decreases the possibility of bronchiectasis (BMI: OR=0.705; p=0.00200). Conclusion: This study revealed that obesity increases the risk of the majority of respiratory diseases (including 20 of all 35 respiratory diseases) and that obesity decreases the risk of bronchiectasis.

The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer.

Background: Germline HLA class I molecule supertypes are shown to correlate with response to anti-PD-1 therapy. Here, we investigate the significance of germline HLA-A and HLA-B supertypes in tumour microenvironment of non-small-cell lung cancer. Methods: Totally 278 NSCLC patients were collected retrospectively. HLA genotyping was conducted using next-generation sequencing. The evaluation of tumour-infiltrating lymphocytes was performed by multiplex immunohistochemistry assay. Correlations among HLA supertypes, tumour infiltrating lymphocytes, and clinicopathological characteristics were assessed. Results: HLA-A03 and HLA-B62 were the supertypes with the highest proportions, at 69.1% and 52.2%, respectively. HLA-A02 or HLA-B62, but not HLA-A03, associated with higher PD-L1+ tumour and stromal cells levels, CD68+ cells, and CD68+PD-L1+ cells. Patients with both HLA-A02 and HLA-B62 supertypes displayed significantly higher PD-L1+ cells, CD68+ cells, and CD8+ cells levels than patients with other supertypes (P = 0.0301, P = 0.0479, P = 0.0192). These cells collectively constitute a hot but immunosuppressive tumour microenvironment. Accordingly, patients with both HLA-A02 and HLA-B62 supertypes had short progression-free survival after surgery (HR = 2.27, P = 0.0373). Conclusions: The HLA-A02B62 supertype could serve as a possible indicator of poor prognosis in early-stage lung cancer. However, it may also act as a favorable prognostic factor for immunotherapy, given its association with a PD-L1-positive tumour microenvironment.

Nomogram for predicting survival after lymphatic metastasis in esophageal cancer: A SEER analysis.

Lymphatic metastasis (LM) is a significant mechanism for the spread of esophageal cancer (EC) and predicts the poor prognosis of EC patients. This research aimed to assess the survival of patients with LM from EC by developing a nomogram. In this retrospective study, EC patients with LM from 2004 to 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were divided by year of diagnosis into a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were employed to determine the prognostic factors of LM, and a nomogram was constructed. The discrimination and calibration of the nomogram were compared by the C-index, area under the curve value, and calibration plots. The survival time difference was compared using Kaplan-Meier curves. A total of 11,695 patients with EC were included in this analysis. LM occurred in 56.5% (n = 6614) of EC patients. In the post-propensity score matching (PSM) cohort, patients with LM had significantly lower median overall survival (OS) than those without LM. Multivariate Cox regression was used to identify the eleven independent prognostic factors. The C-index was 0.709 in both the training and test sets, revealing the good predictive performance of the nomogram. Based on the results of calibration plots and the receiver operating characteristic (ROC) curve, we demonstrate the great performance of the prognostic model. The survival time of EC patients with LM was remarkably lower than that of EC patients without LM. The nomogram model established in this study can precisely predict the survival of EC patients with LM.

Nomogram for predicting the likelihood of liver metastases at initial diagnosis in patients with Siewert type II gastroesophageal junction adenocarcinoma.

The liver is one of the most ordinary metastatic sites of gastroesophageal junction adenocarcinoma and significantly affects its prognosis. Therefore, this study tried to construct a nomogram that can be applied to predict the likelihood of liver metastases from gastroesophageal junction adenocarcinoma. 3001 eligible patients diagnosed with gastroesophageal junction adenocarcinoma between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were involved in the analysis. Patients were randomly divided into a training cohort and an internal validation cohort using R software, with an allocation ratio of 7:3. According to the consequences of univariate and multivariate logistic regression, we constructed a nomogram for predicting the risk of liver metastases. The discrimination and calibration ability of the nomogram was appraised by the C-index, ROC curve, calibration plots, and decision curve analysis (DCA). We also used Kaplan-Meier survival curves to compare differences in overall survival in patients with gastroesophageal junction adenocarcinoma with and without liver metastases. Liver metastases developed in 281 of 3001 eligible patients. The overall survival of patients with gastroesophageal junction adenocarcinoma with liver metastases before and after propensity score matching (PSM) was obviously lower than that of patients without liver metastases. Six risk factors were finally recognized by multivariate logistic regression, and a nomogram was constructed. The C-index was 0.816 in the training cohort and 0.771 in the validation cohort, demonstrating the good predictive capacity of the nomogram. The ROC curve, calibration curve, and decision curve analysis further demonstrated the good performance of the predictive model. The nomogram can accurately predict the likelihood of liver metastases in gastroesophageal junction adenocarcinoma patients.

Safety and efficacy of postoperative adjuvant therapy with atezolizumab and bevacizumab after radical resection of hepatocellular carcinoma.

BACKGROUND: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors. METHODS: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed. RESULTS: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy. CONCLUSION: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications.

Clinical analysis of tubular stapler-assisted nested anastomosis in the prevention of postoperative esophageal cancer complications.

Background: Esophageal cancer (EC) is one of the most common malignant tumor types. Surgery is considered the treatment of choice for patients with early- and mid-stage EC. However, because of the traumatic nature of EC surgery and the need for gastrointestinal reconstruction, high rates of postoperative complications such as anastomotic leakage or stenosis, esophageal reflux, and pulmonary infection exist. Its time to explore a novel esophagogastric anastomosis method for McKeown EC surgery to reduce the postoperative complication. Methods: This study recruited a total of 544 patients who underwent McKeown resection for EC between January 2017 and August 2020. The tubular stapler-assisted nested anastomosis was taken as the time node, including 212 patients in the traditional tubular mechanical anastomosis group and 332 patients in the tubular stapler-assisted nested anastomosis group. The 6-month postoperative incidence of anastomotic fistula and anastomotic stenosis was recorded. Anastomosis in McKeown operation for EC and the influence of different anastomosis methods on clinical efficacy were investigated. Results: Compared with traditional mechanical anastomosis, tubular stapler-assisted nested anastomosis had a lower incidence of anastomotic fistula (0% vs. 5.2%), lung infection (3.3% vs. 11.8%), gastroesophageal reflux (6.9% vs. 16.0%), anastomotic stenosis (3.0% vs. 10.4%), neck incision infection (0.9% vs. 7.1%), anastomositis (16.6% vs. 23.6%), and a shorter surgical duration (11.02±1.54 vs. 18.53±3.20 min). Statistical significance was indicated at P<0.05. No significant difference was detected in the incidence of arrhythmia, recurrent laryngeal nerve injury, or chylothorax between the 2 groups. Due to its good effect in McKeown surgery for EC, stapler-assisted nested anastomosis has been widely used in McKeown surgery for EC, and has become a common anastomosis method in our department for McKeown surgery for EC. However, large sample-sized studies and long-term efficacy observation are still needed. Conclusions: The use of tubular stapler-assisted nested anastomosis can significantly reduce the incidence of complications such as anastomotic fistula, anastomotic stricture, gastroesophageal reflux, and pulmonary infection; therefore, it constitutes the preferred technique for cervical anastomosis in McKeown esophagogastrectomy.

Development and validation of a nomogram model for lung cancer based on radiomics artificial intelligence score and clinical blood test data.

Background: Artificial intelligence (AI) discrimination models using single radioactive variables in recognition algorithms of lung nodules cannot predict lung cancer accurately. Hence, we developed a clinical model that combines AI with blood test variables to predict lung cancer. Methods: Between 2018 and 2021, 584 individuals (358 patients with lung cancer and 226 individuals with lung nodules other than cancer as control) were enrolled prospectively. Machine learning algorithms including lasso regression and random forest (RF) were used to select variables from blood test data, Logistic regression analysis was used to reconfirm the features to build the nomogram model. The predictive performance was assessed by performing the receiver operating characteristic (ROC) curve analysis as well as calibration, clinical decision and impact curves. A cohort of 48 patients was used to independently validate the model. The subgroup application was analyzed by pathological diagnosis. Findings: A total of 584 patients were enrolled (358 lung cancers, 61.30%,226 patients for the control group) to establish the model. The integrated model identified eight potential factors including carcinoembryonic antigen (CEA), AI score, Pro-Gastrin Releasing Peptide (ProGRP), cytokeratin 19 fragment antigen21-1(CYFRA211), squamous cell carcinoma antigen(SCC), indirect bilirubin(IBIL), activated partial thromboplastin time(APTT) and age. The area under the curve (AUC) of the nomogram was 0.907 (95% CI, 0.881-0.929). The decision and clinical impact curves showed good predictive accuracy of the model. An AUC of 0.844 (95% CI, 0.710 - 0.932) was obtained for the external validation group. Conclusion: The nomogram model integrating AI and clinical data can accurately predict lung cancer, especially for the squamous cell carcinoma subtype.

Surgery and postoperative radiotherapy affect the prognosis of esophageal cancer: A SEER analysis.

The principal treatment modalities for esophageal cancer are radiation, chemotherapy and surgery or a combination of them. In some sense, technological advances have tremendously heightened patients' survival rates. Nevertheless, the debate on the prognostic value of postoperative radiotherapy (PORT) has never ceased. On that account, this study made an effort to probe deep into the effects of PORT and surgery on the prognosis of stage III esophageal cancer. Our study included patients diagnosed with stage III esophageal cancer between 2004 and 2015 through the Surveillance, Epidemiology, and End Results (SEER) program. We performed propensity score matching (PSM) on the basis of whether surgery was carried out and whether PORT conducted. We identified the independent risk factors by multivariate Cox regression and constructed a nomogram model. In this research, we included 3940 patients, and the median follow-up is 14 months: 1932 cases without surgery; 2008 cases with surgery, and 322 cases of them underwent PORT. In the postPSM patient cohort, patients who underwent surgery had a median overall survival rate (OS) of 19.0 (95% confidence interval [CI] 17.2-20.8) and a median cancer-specific survival rate (CSS) of 23.0 (95% CI 20.6-25.3) months, which were remarkably higher than those without surgery (P < .001). The OS（P < .05）and CSS（P < .05）of the patients who underwent PORT were lower than those who did not. Similar results were obtained in the groups of N0 and N1. This study revealed surgery can heighten patients' survival rate, while PORT could not elevate patients' survival rate in stage III esophageal cancer patients.

Conditioned medium of PC­3 prostate cancer cells affects microRNA and mRNA profiles in mechanically strained osteoblasts.

Bone is the main site of metastasis from prostate cancer; therefore, it is important to investigate the microRNAs (miRNAs) and mRNA associated with bone metastases from prostate cancer. Since an appropriate mechanical environment is important in the growth of bone, in the present study, the miRNA, mRNA, and long non-coding RNA (lncRNA) profiles of mechanically strained osteoblasts treated with conditioned medium (CM) from PC-3 prostate cancer cells were studied. MC3T3-E1 osteoblastic cells were treated with the CM of PC-3 prostate cancer cells and were simultaneously stimulated with a mechanical tensile strain of 2,500 µÎµ at 0.5 Hz; the osteoblastic differentiation of the MC3T3-E1 cells was then assessed. In addition, the differential expression levels of mRNA, miRNA and lncRNA in MC3T3-E1 cells treated with the CM of PC-3 cells were screened, and some of the miRNAs and mRNAs were verified by reverse transcription-quantitative PCR (RT-qPCR). The signal molecules and signaling pathways associated with osteogenic differentiation were predicted by bioinformatics analysis. The CM of PC-3 prostate cancer cells suppressed osteoblastic differentiation of MC3T3-E1 cells. A total of seven upregulated miRNAs and 12 downregulated miRNAs were selected by sequencing and further verified using RT-qPCR, and related differentially expressed genes (11 upregulated and 12 downregulated genes) were also selected by sequencing and further verified using RT-qPCR; subsequently, according to the enrichment of differentially expressed genes in signaling pathways, nine signaling pathways involved in osteogenic differentiation were screened out. Furthermore, a functional mRNA-miRNA-lncRNA regulatory network was constructed. The differentially expressed miRNAs, mRNAs and lncRNAs may provide a novel signature in bone metastases of prostate cancer. Notably, some of the signaling pathways and related genes may be associated with pathological osteogenic differentiation caused by bone metastasis of prostate cancer.