A case of congenital bronchial atresia with tracheobronchial stenosis caused by emphysema: Successful management with thoracoscopic surgery.

Introduction: Congenital bronchial atresia (CBA), as a rare developmental abnormality of the lung, is usually asymptomatic and is accidently discovered in most cases. Currently, no standardized guidelines for the treatment or management of CBA have been established. Case presentation: A 22-year-old male soldier was referred to Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University due to chest tightness and shortness of breath after repeated strenuous activities. Contrast-enhanced computed tomography (CT) revealed an 18mm × 11mm solitary, well-circumscribed, and solid nodule with no enhancement in the right upper lobe (RUL), and emphysematous changes distributed throughout the RUL. A flexible bronchoscopic examination showed extrinsic compression stenosis in the bronchial opening of the right middle lobe (RML). After three-dimensional (3D) reconstruction CT and a multidisciplinary consultation, a diagnosis of CBA in the anterior segment (B3) of RUL was established. Subsequently, thoracoscopic right upper lobectomy was performed and resulted in an improved respiratory capacity 6 months after surgery. To date, the patient has good quality of life without any complication. Conclusion: This study underscores the role of bronchoscopy, 3D reconstruction CT, and a multidisciplinary consultation in the diagnosis of CBA, and highlights that a thoracoscopic intervention should be considered in such case.

Exosomal NAT10 from esophageal squamous cell carcinoma cells modulates macrophage lipid metabolism and polarization through ac4C modification of FASN.

N-acetyltransferase 10 (NAT10) is acknowledged as a tumor promoter in various cancers due to its role as a regulator of acetylation modification. Tumor-associated macrophages (TAMs) play a pivotal role in the tumor microenvironment (TME). However, the intercellular communication between esophageal squamous cell carcinoma (ESCC) cells and TAMs involving NAT10 remains poorly understood. This study aimed to elucidate the regulatory mechanism of NAT10 in modulating macrophage lipid metabolism and polarization. Experimental evidence was derived from in vitro and in vivo analyses. We explored the association between upregulated NAT10 in ESCC tissues, macrophage polarization, and the therapeutic efficacy of PD-1. Furthermore, we investigated the impact of methyltransferase 3 (METTL3)-induced m6A modification on the increased expression of NAT10 in ESCC cells. Additionally, we examined the role of exosomal NAT10 in stabilizing the expression of fatty acid synthase (FASN) and promoting macrophage M2 polarization through mediating the ac4C modification of FASN. Results indicated that NAT10, packaged by exosomes derived from ESCC cells, promotes macrophage M2 polarization by facilitating lipid metabolism. In vivo animal studies demonstrated that targeting NAT10 could enhance the therapeutic effect of PD-1 on ESCC by mediating macrophage reprogramming. Our findings offer novel insights into improving ESCC treatment through NAT10 targeting.

Microwave biosensor for the detection of growth inhibition of human liver cancer cells at different concentrations of chemotherapeutic drug.

Cytotoxicity assays are crucial for assessing the efficacy of drugs in killing cancer cells and determining their potential therapeutic value. Measurement of the effect of drug concentration, which is an influence factor on cytotoxicity, is of great importance. This paper proposes a cytotoxicity assay using microwave sensors in an end-point approach based on the detection of the number of live cells for the first time. In contrast to optical methods like fluorescent labeling, this research uses a resonator-type microwave biosensor to evaluate the effects of drug concentrations on cytotoxicity by monitoring electrical parameter changes due to varying cell densities. Initially, the feasibility of treating cells with ultrapure water for cell counting by a microwave biosensor is confirmed. Subsequently, inhibition curves generated by both the CCK-8 method and the new microwave biosensor for various drug concentrations were compared and found to be congruent. This agreement supports the potential of microwave-based methods to quantify cell growth inhibition by drug concentrations.

Hexaxial external fixator versus intramedullary nail in treating segmental tibial fractures: a retrospective study.

BACKGROUND: It's difficult to treat segmental tibial fractures (STFs), which are intricate injuries associated with significant soft tissue damage. The aim of this study was to compare the clinical effect of hexaxial external fixator (HEF) and intramedullary nail (IMN) in treatment of STFs. METHODS: A total of 42 patients with STFs were finally recruited between January 2018 and June 2022. There were 25 males and 17 females with age range of 20 to 60 years. All fractures were classified as type 42C2 using the Arbeitsgemeinschaftfür Osteosythese/Orthopaedic Trauma Association (AO/OTA) classification. 22 patients were treated with HEF and 20 patients were treated with IMN. The condition of vascular and neural injuries, time of full weight bearing, bone union time and infection rate were documented and analyzed between the two groups. The mechanical medial proximal tibial angle (mMPTA), mechanical posterior proximal tibial angle (mPPTA), mechanical lateral distal tibial angle (mLDTA), mechanical anterior distal tibial angle (mADTA), hospital for special surgery (HSS) knee joint score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle joint score, range of motion (ROM) of flexion of keen joint and ROM of plantar flexion and dorsal flexion of ankle joint were compared between the two groups at the last clinical visit. RESULTS: There were no vascular and neural injuries or other severe complications in both groups. All 22 patients in HEF group underwent closed reduction but 3 patients in IMN group were treated by open reduction. The time of full weight bearing was (11.3 ± 3.2) days in HEF group and (67.8 ± 5.8) days in IMN group(P < 0.05), with bone union time for (6.9 ± 0.8) months and (7.7 ± 1.4) months, respectively(P < 0.05). There was no deep infection in both groups. In the HEF group and IMN group, mMPTA was (86.9 ± 1.5)° and (89.7 ± 1.8)°(P < 0.05), mPPTA was (80.8 ± 1.9)° and (78.6 ± 2.0)°(P < 0.05), mLDTA was (88.5 ± 1.7)° and (90.3 ± 1.7)°(P < 0.05), while mADTA was (80.8 ± 1.5)° and (78.4 ± 1.3)°(P < 0.05). No significant differences were found between the two groups at the last clinical visit concerning HSS knee joint score and AOFAS ankle joint score, ROM of flexion of keen joint and ROM of plantar flexion of ankle joint (P > 0.05). The ROM of dorsal flexion of ankle joint in IMN group was (30.4 ± 3.5)°, better than (21.6 ± 2.8)° in HEF group (P < 0.05). CONCLUSION: In terms of final clinical outcomes, the use of either HEF or IMN for STFs can achieve good therapeutic effects. While HEF is superior to IMN in terms of completely closed reduction, early full weight bearing, early bone union and alignment. Nevertheless, HEF has a greater impact on the ROM of dorsal flexion of the ankle joint, and much more care and adjustment are needed for the patients than IMN.

CREB3L4 promotes hepatocellular carcinoma progression and decreases sorafenib chemosensitivity by promoting RHEB-mTORC1 signaling pathway.

This study was designed to explore the roles of CREB3L4 in the pathogenesis and drug resistance of hepatocellular carcinoma (HCC). The proliferation of HCC lines was determined in the presence of CREB3L4 over-expression and silencing. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter assay were performed to screen the potential target of CREB3L4 on mTORC1. Xenografted tumor model was established to define the regulatory effects of CREB3L4 in the tumorigenesis. Then we evaluated the roles of CREB3L4 in chemosensitivity to sorafenib treatment. CREB3L4 significantly induced the HCC cell proliferation by modulating the activation of mTROC1-S6K1 signaling pathway via binding with RHEB promoter. Moreover, CREB3L4 dramatically inhibited the chemosensitivity to sorafenib treatment via up-regulating RHEB-mTORC1 signaling. CREB3L4 promoted HCC progression and decreased its chemosensitivity to sorafenib through up-regulating RHEB-mTORC1 signaling pathway, indicating a potential treatment strategy for HCC through targeting CREB3L4.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.

Genistein prevents the production of hypospadias induced by Di-(2-ethylhexyl) phthalate through androgen signaling and antioxidant response in rats.

Environmental estrogen exposure has increased dramatically over the past 50 years. In particular, prenatal exposure to estrogen causes many congenital diseases, among which reproductive system development disorders are extremely serious. In this study, the molecular mechanism of hypospadias and the therapeutic effect of genistein (GEN) were investigated through in vivo models prepared by Di-(2-ethylhexyl) phthalate (DEHP) exposure between 12 and 19 days of gestation. With increased DEHP concentrations, the incidence of hypospadias increased gradually. DEHP inhibited the key enzymes involved in steroid synthesis, resulting in decreasing testosterone synthesis. At the same time, DEHP increased reactive oxygen species (ROS) and produced inflammatory factors via NADPH oxidase-1 (NOX1) and NADPH oxidase-4 (NOX4) pathways. It also inhibited Steroid 5 α Reductase 2 (Srd5α2) and decreased dihydrotestosterone (DHT) synthesis. Additionally, DEHP inhibited the androgen receptor (AR), resulting in reduced DHT binding to the AR that ultimately retarded the development of the external reproductive system. GEN, a phytoestrogen, competes with DEHP for binding to estrogen receptor ß (ERß). This competition, along with GEN's antiestrogen and antioxidant properties, could potentially reverse impairments. The findings of this study provide valuable insights into the role of phytoestrogens in alleviating environmental estrogen-induced congenital diseases.

The Role of Iron Metabolism in Sepsis-associated Encephalopathy: a Potential Target.

Sepsis-associated encephalopathy (SAE) is an acute cerebral dysfunction secondary to infection, and the severity can range from mild delirium to deep coma. Disorders of iron metabolism have been proven to play an important role in a variety of neurodegenerative diseases by inducing cell damage through iron accumulation in glial cells and neurons. Recent studies have found that iron accumulation is also a potential mechanism of SAE. Systemic inflammation can induce changes in the expression of transporters and receptors on cells, especially high expression of divalent metal transporter1 (DMT1) and low expression of ferroportin (Fpn) 1, which leads to iron accumulation in cells. Excessive free Fe2+ can participate in the Fenton reaction to produce reactive oxygen species (ROS) to directly damage cells or induce ferroptosis. As a result, it may be of great help to improve SAE by treatment of targeting disorders of iron metabolism. Therefore, it is important to review the current research progress on the mechanism of SAE based on iron metabolism disorders. In addition, we also briefly describe the current status of SAE and iron metabolism disorders and emphasize the therapeutic prospect of targeting iron accumulation as a treatment for SAE, especially iron chelator. Moreover, drug delivery and side effects can be improved with the development of nanotechnology. This work suggests that treating SAE based on disorders of iron metabolism will be a thriving field.

Unveiling the role of hypoxic macrophage-derived exosomes in driving colorectal cancer progression.

The crosstalk between tumor cells and macrophages under hypoxic conditions has been acknowledged as a pivotal determinant in the progression of colorectal cancer (CRC). Previous research has underscored the significance of exosomes derived from hypoxic tumor cells in facilitating tumor progression through inducing the polarization of macrophages towards the M2-like phenotype. The precise influence of hypoxic macrophage-derived exosomes (HMDEs) on the progression of CRC has not yet been fully elucidated. The objective of this study was to investigate the role of HMDEs in the progression of CRC. We discovered that there was an elevated release of exosomes derived from macrophages in hypoxic conditions. Additionally, the hypoxia-induced macrophage-derived exosomes played a crucial role in promoting the progression of CRC. We have also demonstrated that HMDEs have the ability to induce cell cycle transition and inhibit cell apoptosis, thereby promoting the growth of CRC cells. Furthermore, the underlying molecular mechanisms of these effects have been identified. The overexpression of Hif-1α results in its direct interaction with distinct regions (-521- -516 bp and -401- -391 bp) of the Hsp90 promoter during hypoxic circumstances. This binding event led to the overexpression of Hsp90 and the subsequent elevation of Hsp90 protein levels within HMDEs. Importantly, the crucial interaction between Hsp90 and Lats1 resulted in the deactivation of Lats1 and the inhibition of Yap phosphorylation. Ultimately, this series of events lead to the deactivation of the Hippo signaling pathway. Our in vivo and in vitro studies presented compelling evidence for the crucial role of hypoxic macrophage-derived exosomal Hsp90 in promoting CRC progression through the inhibition of the Hippo signaling pathway. These findings represented a significant advancement in our comprehension of the complex interplay between macrophages and CRC cells under hypoxic conditions.

Evaluating the Role of Morphological Parameters in the Prostate Transition Zone in PHI-Based Predictive Models for Detecting Gray Zone Prostate Cancer.

Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P < .05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. Conclusion: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZ-adjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions.

The potential effects and mechanism of echinacoside powder in the treatment of Hirschsprung's Disease.

Possible complications, such as intestinal obstruction and inflammation of the intestinal tract, can have a detrimental effect on the prognosis after surgery for Hirschsprung disease. The aim of this study was to investigate the potential targets and mechanisms of action of echinacoside to improve the prognosis of Hirschsprung disease. Genes related to the disease were obtained through analysis of the GSE96854 dataset and four databases: OMIM, DisGeNET, Genecard and NCBI. The targets of echinacoside were obtained from three databases: PharmMapper, Drugbank and TargetNet. The intersection of disease genes and drug targets was validated by molecular docking. The valid docked targets were further explored for their expression by using immunohistochemistry. In this study, enrichment analysis was used to explore the mechanistic pathways involved in the genes. Finally, we identified CA1, CA2, CA9, CA12, DNMT1, RIMS2, RPGRIP1L and ZEB2 as the core targets. Except for ZEB2, which is predominantly expressed in brain tissue, the remaining seven genes show tissue specificity and high expression in the gastrointestinal tract. RIMS2 possesses a high mutation phenomenon in pan-cancer, while a validated ceRNA network of eight genes was constructed. The core genes are involved in several signaling pathways, including the one-carbon metabolic process, carbonate dehydratase activity and others. This study may help us to further understand the pharmacological mechanisms of echinacoside and provide new guidance and ideas to guide the treatment of Hirschsprung disease.

Long-term, real-time and label-free live cell image processing and analysis based on a combined algorithm of CellPose and watershed segmentation.

Developing a rapid and quantitative method to accurately evaluate the physiological abilities of living cells is critical for tumor control. Many experiments have been conducted in the field of biology in an attempt to measure the proliferation and movement abilities of cells, but existing methods cannot provide real-time and objective data for label-free cells. The quantitative imaging technique, including an automatic segmentation algorithm for individual label-free cells, has been a breakthrough in this regard. In this study, we develop a combined automatic image processing algorithm of CellPose and watershed segmentation for the long-term and real-time imaging of label-free cells. This method shows strong reliability in cell identification regardless of cell densities, allowing us to obtain accurate information about the number and proliferation ability of the target cells. Additionally, our results also suggest that this method is a reliable way to assess real-time data on drug cytotoxicity, cell morphology, and cell movement ability.

Identification of the molecular subtypes and construction of risk models in neuroblastoma.

The heterogeneity of neuroblastoma directly affects the prognosis of patients. Individualization of patient treatment to improve prognosis is a clinical challenge at this stage and the aim of this study is to characterize different patient populations. To achieve this, immune-related cell cycle genes, identified in the GSE45547 dataset using WGCNA, were used to classify cases from multiple datasets (GSE45547, GSE49710, GSE73517, GES120559, E-MTAB-8248, and TARGET) into subgroups by consensus clustering. ESTIMATES, CIBERSORT and ssGSEA were used to assess the immune status of the patients. And a 7-gene risk model was constructed based on differentially expressed genes between subtypes using randomForestSRC and LASSO. Enrichment analysis was used to demonstrate the biological characteristics between different groups. Key genes were screened using randomForest to construct neural network and validated. Finally, drug sensitivity was assessed in the GSCA and CellMiner databases. We classified the 1811 patients into two subtypes based on immune-related cell cycle genes. The two subtypes (Cluster1 and Cluster2) exhibited distinct clinical features, immune levels, chromosomal instability and prognosis. The same significant differences were demonstrated between the high-risk and low-risk groups. Through our analysis, we identified neuroblastoma subtypes with unique characteristics and established risk models which will improve our understanding of neuroblastoma heterogeneity.

Construction a new nomogram prognostic model for predicting overall survival after radical resection of esophageal squamous cancer.

Background: Esophageal cancer is one of the deadliest malignancies in the world, and 5-year overall survival (OS) of esophageal cancer ranges from 12% to 20%. Surgical resection remains the principal treatment. The American Joint Commission on Cancer (AJCC) TNM (tumor, node, and metastasis) staging system is a key guideline for prognosis and treatment decisions, but it cannot fully predict outcomes. Therefore, targeting the molecular and biological features of each patient's tumor, and identifying key prognostic biomarkers as effective survival predictors and therapeutic targets are highly important to clinicians and patients. Methods: In this study, three different methods, including Univariate Cox regression, Lasso regression, and Randomforest regression were used to screen the independent factors affecting the prognosis of esophageal squamous cell carcinoma and construct a nomogram prognostic model. The accuracy of the model was verified by comparing with TNM staging system and the reliability of the model was verified by internal cross validation. Results: Preoperative neutrophil lymphocyte ratio(preNLR), N-stage, p53 level and tumor diameter were selected to construct the new prognostic model. Patients with higher preNLR level, higher N-stage, lower p53 level and larger tumor diameter had worse OS. The results of C-index, Decision Curve Analysis (DCA), and integrated discrimination improvement (IDI) showed that the new prognostic model has a better prediction than the TNM staging system. Conclusion: The accuracy and reliability of the nomogram prognostic model were higher than that of TNM staging system. It can effectively predict individual OS and provide theoretical basis for clinical decision making.

Grading of clear cell renal cell carcinoma using diffusion MRI with a fractional order calculus model.

BACKGROUND: The fractional order calculus (FROC) model has been developed to describe restrained motion of water molecules as well as microstructural heterogeneity, providing a novel tool for non-invasive tumor grading. PURPOSE: To evaluate the role of the FROC model in characterizing clear cell renal cell carcinoma (ccRCC) grades. MATERIAL AND METHODS: A total of 59 patients diagnosed with ccRCC were included in this prospective study. The diffusion metrics derived from the mono-exponential model (apparent diffusion coefficient [ADC]), intra-voxel incoherent motion [IVIM] model [D, D*, f], and FROC model [Dfroc, ß, µ]) were calculated and compared between low- and high-grade ccRCCs. Binary logistic regression analysis was performed to establish the diagnostic models. Receiver operating characteristic (ROC) analysis and DeLong test were performed to evaluate and compare the diagnostic performance of metrics in grading ccRCC. RESULTS: All the metrics except D* and f exhibited statistical differences between low- and high-grade ccRCCs. ROC analysis showed individual FROC parameters, µ, Dfroc, and ß, outperformed ADC and IVIM parameters in grading ccRCC. For single parameter, µ demonstrated the highest AUC value, sensitivity, and diagnostic accuracy in discriminating the two ccRCC groups while ß exhibited the optimal specificity. Importantly, the combination of Dfroc, µ, and ß could further improve the diagnostic performance. CONCLUSION: The FROC parameters were superior to ADC and IVIM parameters in grading ccRCC, indicating the great potential of the FROC model in distinguishing low- and high-grade ccRCCs.

Euclidean distance-based Raman spectroscopy (EDRS) for the prognosis analysis of gastric cancer: A solution to tumor heterogeneity.

The prognosis analysis of gastric cancer is critical for selection of treatments and development of advanced therapeutic methods. A prognosis approach that is accurate, fast, convenient, and of low cost for gastric cancers is in high demand. Raman spectroscopy is a label-free and non-destructive technique to provide molecular fingerprints of biological samples, holding promises for cancer prognosis. However, the major challenge of gastric cancer prognosis lies in the widely existing tumor heterogeneity, which leads to unexpected spectral variations within one type of samples. In this work, we have developed the Euclidean distance (ED)-based Raman spectroscopy (EDRS) method for the prognosis analysis of gastric cancer to eliminate the influence of tumor heterogeneity. Raman spectra were first collected on the slices of paraffin-preserved tumor tissues from gastric cancer patients. A standard spectrum to represent the 'worst prognostic tumor cells' was then established. The similarity between each spectrum of tissues and the standard spectrum was assessed by ED, to provide a direct assessment on the prognosis status. We have successfully classified the patients into poor and favorable prognosis groups, either based on the averaged regional ED values (sensitivity of 75 %, specificity of 96.8 %), or based on the minimal ED values at the patient level (sensitivity of 90 %, specificity of 100 %). EDRS was also investigated for survival analysis (AUC = 0.955), much better than the commonly applied post-neoadjuvant therapy (ypTNM) category (AUC = 0.718). Our work highlights EDRS as a rapid, accurate, low-cost and robust tool for heterogeneous cancer-related prognosis assessment and survival prediction, providing new insights for spectroscopic tumor analysis.

TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3ß/ß-catenin pathway.

Ten-eleven translocation 3 (TET3) participates in tumorigenesis and malignant transformation by mediating DNA demethylation and specific gene activation in malignances. This study aims to elucidate its molecular function and regulatory mechanism in esophageal squamous cell carcinoma (ESCC). Stable ESCC cells that infected with TET3 overexpression (OE) and knockdown lentiviral vector had been established. The biological behaviors and molecular mechanism of TET3 were demonstrated by cell biology experiments in vitro and in vivo. Tissues from patients with ESCC were used to demonstrate the clinical value of TET3. Our findings revealed that TET3 is highly expressed in ESCC tissues and related to poor prognosis of patients with ESCC. OE of TET3 presented a significant effect on proliferation, metastatic potential, and spheroid formation of ESCC cells by activating the PI3K/AKT/GSK3ß/ß-catenin axis. Knockdown of TET3 could remarkably reverse these malignant phenotypes. Patients with ESCC with high TET3 expression resulted in a shorter overall survival (OS) and disease-free survival. Based on the multivariate analysis, TET3 could be an independent favorable factor for predicting OS and recurrence. The high expression of TET3 not only aggravates malignant behaviors in vitro and in vivo but also becomes a novel biomarker for clinical monitoring and individualized precision treatment for patients with ESCC.

Serum multi-cytokines screening identifies TRAIL and IL-10 as probable new biomarkers for prostate health index diagnostic utility adjustment in grey zone aggressive prostate cancer detection: A single-center data in China.

Objective: To identify less invasive and easily applicable serum cytokine-derived biomarkers which contribute to the diagnostic utility and risk assessment ability of the prostate health index (PHI) based multivariable model in grey zone aggressive prostate cancer (AG PCa) early detection. Methods: Serum 45 cytokines screening was performed in a small training cohort consisting of 10 sera by Luminex liquid array-based multiplexed immunoassays and identified TRAIL and IL-10 as new biomarkers for PHI diagnostic utility adjustment for further validation with a multivariable predictive model in a cohort including 79 aggressive prostate cancer patients and 209 benign prostatic hyperplasia or indolent PCa patients within the PSA grey zone. Results: TRAIL and IL-10 were identified as potential serum biomarkers for AG PCa detection by the result of multi-cytokines screening in the univariate analysis, while multivariable logistic regression confirmed the AUC of the full risk predictive model (0.915) including tPSA, fPSA, PHI, TRAIL, and IL-10 was higher than various diagnostic strategies. DCA suggested a superior net benefit and indicated a good discriminative ability of the full risk model consistently with the result of the nomogram. Conclusion: We suggest a significant advantage for the PHI-based multivariate combinations of serum TRAIL and IL-10 comparing to PHI or other serum-derived biomarkers alone in the detection and risk stratification of grey zone AG PCa.

Preoperative Neutrophil to Lymphocyte Ratio Predicts Complications After Esophageal Resection That can be Used as Inclusion Criteria for Enhanced Recovery After Surgery.

Background: The neutrophil to lymphocyte ratio (NLR) has been reported as an indicator for poor prognosis in many cancers including esophageal cancer. However, the relationship between the NLR and postoperative complications after esophageal cancer resection remains unclear. At present, enhanced recovery after surgery (ERAS) lacks inclusion criteria. The aim of this study is to determine whether the preoperative NLR (preNLR) can predict complications after esophageal cancer resection, which could represent the criteria for ERAS. Methods: This was a retrospective study on 171 patients who underwent esophagectomy at Hospital between November 2020 and November 2021(68 patients from Changhai Hospital, 65 patients from Shanghai General Hospital and 38 patients from Affiliated Hospital of Qingdao University). Univariate and multivariate logistic regression analyses were performed to demonstrate that the preNLR could predict complications after esophagectomy. Results: A preNLR cutoff value of 2.30 was identified as having the greatest ability to predict complications with a sensitivity of 76% and specificity of 65%. Moreover, the Chi-squared test results showed that the preNLR was significantly associated with complications (x2 = 13.641, p < 0.001), and multivariate logistic regression analysis showed that body mass index (BMI), p stage and preNLR were independent variables associated with the development of postoperative complications (p < 0.05). Conclusion: The preNLR can predict complications after esophagectomy, and these predicted complications can represent the criteria for recruiting patients for ERAS.

CD147 Mediates 5-Fluorouracil Resistance in Colorectal Cancer by Reprogramming Glycolipid Metabolism.

Chemoresistance against 5-fluorouracil (5-FU) is a major issue for colorectal cancer (CRC) patients. Increasing evidence for the roles of CD147 in glycolipid metabolic reprogramming and chemoresistance of tumor cells has emerged in recent years. However, whether CD147 contributes to 5-FU resistance in CRC and the role of abnormal glycolipid metabolism in this process remain poorly understood. We analyzed CD147 expression in primary tumor samples of CRC patients and found that upregulated CD147 correlated with decreased 5-FU chemosensitivity and an unfavorable prognosis of CRC patients. Moreover, in vivo and in vitro experiments confirmed that CD147 regulates glycolipid metabolism through two separate pathways. Mechanistically, CD147 upregulates HIF-1α-mediated glycolysis by activating the PI3K/AKT/mTOR pathway and CD147 also attenuates PPARα-mediated fatty acid oxidation by activation of the MAPK pathway. Most importantly, we found that CD147 confers 5-FU resistance in CRC via these glycolipid metabolic signatures. Our results demonstrated that CD147 is a potential 5-FU resistance biomarker for CRC patients and a candidate therapeutic target to restore 5-FU sensitivity of 5-FU-resistant CRC by remodeling glycolipid metabolism.