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Qi Huang,1– 3,* Xu-Yun Huang,1,2,* Yu-Ting Xue,1,2,* Xiao-Hui Wu,1,2,* Yu-Peng Wu,1,2,* Zhi-Bin Ke,1,2 Zhen Kang,1,2 Yi-Cheng Xu,1,2 Dong-Ning Chen,1,2 Yong Wei,1,2 Xue-Yi Xue,1,2 Zhi-Yang Huang,3 Ning Xu1,2,4 1Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 3Department of Urology, Quanzhou First Hospital, Fujian Medical University, Quanzhou, 362000, People’s Republic of China; 4Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xu, Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, 20 Chazhong Road, Fuzhou, 350005, People’s Republic of China, Tel +86-059187981687, Email drxun@fjmu.edu.cn Zhi-Yang Huang, Department of Urology, Quanzhou First Hospital, Fujian Medical University, No. 250, East Street, Licheng District, Quanzhou, Fujian, 362000, People’s Republic of China, Email hzy8902@126.comIntroduction: This study aims to explore the role of cuproptosis-related genes in ACC, utilizing data from TCGA and GEO repositories, and to develop a predictive model for patient stratification.Methods: A cohort of 123 ACC patients with survival data was analyzed. RNA-seq data of 17 CRGs were examined, and univariate Cox regression identified prognostic CRGs. A cuproptosis-related network was constructed to show interactions between CRGs. Consensus clustering classified ACC into three subtypes, with transcriptional and survival differences assessed by PCA and survival analysis. Gene set variation analysis (GSVA) and ssGSEA evaluated functional and immune infiltration characteristics across subtypes. Differentially expressed genes (DEGs) were identified, and gene clusters were established. A risk score (CRG_score) was generated using LASSO and multivariate Cox regression, validated across datasets. Tumor microenvironment, stem cell index, mutation status, drug sensitivity, and hormone synthesis were examined in relation to the CRG_score. Protein expression of key genes was validated, and functional studies on ASF1B and NDRG4 were performed.Results: Three ACC subtypes were identified with distinct survival outcomes. Subtype B showed the worst prognosis, while subtype C had the best. We identified 214 DEGs linked to cell proliferation and classified patients into three gene clusters, confirming their prognostic value. The CRG_score predicted patient outcomes, with high-risk patients demonstrating worse survival and possible resistance to immunotherapy. Drug sensitivity analysis suggested higher responsiveness to doxorubicin and etoposide in high-risk patients.Conclusion: This study suggests the potential prognostic value of CRGs in ACC. The CRG_score model provides a robust tool for risk stratification, with implications for treatment strategies.Keywords: cuproptosis, overall survival, immune microenvironment, molecular signature

Shao-Hao Chen,1,* Zhi-Bin Ke,1,* Yu-Peng Wu,1,* Dong-Ning Chen,1,* Xiang Yu,1 Yu Chen,2,3 Yong Wei,1 Qing-Shui Zheng,1 Xue-Yi Xue,1 Ning Xu1 1Department of Urology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 2Cancer Bio-Immunotherapy Center, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 3Department of Medical Oncology, Fujian Medical University Cancer Hospital and Fujian Cancer Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xu; Xue-Yi XueDepartment of Urology, The First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou 350005, People’s Republic of ChinaTel +86-59187981687Email drxun@fjmu.edu.cn; xuexueyi@fjmu.edu.cnPurpose: To identify the relevant factors, and create and validate a predictive scoring system for the duration of laparoscopic radical prostatectomy (LRP).Patients and Methods: We retrospectively analyzed clinicopathological data from 436 patients who underwent LRP between January 2014 and January 2019, of whom 304 cases were used as a model creation group and 132 were used as a validation group. Uni/multivariate linear regression analysis was performed to determine the predictors of the duration of the procedure and a novel scoring system was created using these predictors. External validation of the scoring system was performed. The Hosmer–Lemeshow test was used to determine the goodness-of-fit of the model and calibration plots were created for visual assessment.Results: “Prolonged duration” was defined as a duration of the procedure that was longer than the mean (> 150 min) duration. Multivariate analysis showed that body mass index (BMI), prostate volume, intravesicular protrusion of the prostate (IPP), the ratio of the cross-sectional areas of the prostate and the Retzius space (P/R), pelvic lymph node dissection, and neurovascular bundle (NVB) preservation were significant predictors of prolonged duration. A scoring system that included these six parameters was created and the area under the curve achieved during receiver operating characteristic analysis using this scoring system was 0.874 (95% confidence interval [CI]: 0.836– 0.913). The Hosmer–Lemeshow test showed that the scoring system was well calibrated (X2=5.339, P=0.376). The external validation showed that the model had high predictive accuracy (AUC=0.835, 95% CI: 0.764– 0.906) and goodness-of-fit (X2=4.401, P=0.493).Conclusion: The following factors were significantly associated with prolonged duration of laparoscopic radical prostatectomy: BMI, prostate volume, IPP, P/R, pelvic lymph node dissection, and NVB preservation. The novel scoring system created can be used to accurately predict the duration of the procedure, assess the difficulty of surgery, and improve perioperative efficiency.Keywords: prostate volume, intravesical protrusion of prostate, predictive factor, pelvic lymph node dissection, neurovascular bundle preservation, prostate cancer

Background: Disulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear., Methods: Firstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot., Results: Although SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients., Conclusion: This study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients., (© 2024. The Author(s).)

Objective: Polychlorinated biphenyls (PCBs) have caused great environmental concerns. The study aims to investigate underlying molecular mechanisms between PCBs exposure and prostate cancer (PCa)., Methods: To investigate the association between PCBs exposure and prostate cancer by using CTD, TCGA, and GEO datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to explore pathways associated with PCBs-related genes (PRGs). Using Lasso regression analysis, a novel PCBs-related prognostic model was developed. Both internal and external validations were conducted to assess the model's validity. Molecular docking was utilized to assess the binding capacity of PCBs to crucial genes. At last, preliminary experimental validations were conducted to confirm the biological roles of Aroclor 1254 in PCa cells., Results: The GO enrichment analysis of PRGs revealed that the biological processes were most enriched in the regulation of transcription from the RNA polymerase II promoter and signal transduction. The KEGG enrichment analysis showed that of the pathways in cancer is the most significantly enriched. Next, a PCBs-related model was constructed. In the training, test, GSE70770, and GSE116918 cohorts, the biochemical recurrences free survival of the patients with high-risk scores was considerably lower. The AUCs at 5 years were 0.691, 0.718, 0.714, and 0.672 in the four cohorts, demonstrating the modest predictive ability. A nomogram that incorporated clinical characteristics was constructed. The results of the anti-cancer drug sensitivity analysis show chemotherapy might be more beneficial for patients at low risk. The molecular docking analysis demonstrated PCBs' ability to bind to crucial genes. PCa cells exposed to Aroclor 1254 at a concentration of 1 μM showed increased proliferation and invasion capabilities., Conclusions: This study provides new insights into the function of PCBs in PCa and accentuates the need for deeper exploration into the mechanistic links between PCBs exposure and PCa progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited., Methods: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene., Results: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa., Conclusions: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Patient-clinician communication and shared decision-making face challenges in the perioperative period. Chatbots have emerged as valuable support tools in perioperative care. A simultaneous and complete comparison of overall benefits and harm of chatbot application is conducted., Materials: MEDLINE, EMBASE and the Cochrane Library were systematically searched for studies published before May 2023 on the benefits and harm of chatbots used in the perioperative period. The major outcomes assessed were patient satisfaction and knowledge acquisition. Untransformed proportion (PR) with a 95% CI was used for the analysis of continuous data. Risk of bias was assessed using the Cochrane Risk of Bias assessment tool version 2 and the Methodological Index for Non-Randomised Studies., Results: Eight trials comprising 1073 adults from four countries were included. Most interventions (n = 5, 62.5%) targeted perioperative care in orthopaedics. Most interventions use rule-based chatbots (n = 7, 87.5%). This meta-analysis found that the majority of the participants were satisfied with the use of chatbots (mean proportion=0.73; 95% CI: 0.62 to 0.85), and agreed that they gained knowledge in their perioperative period (mean proportion=0.80; 95% CI: 0.74 to 0.87)., Conclusion: This review demonstrates that perioperative chatbots are well received by the majority of patients with no reports of harm to-date. Chatbots may be considered as an aid in perioperative communication between patients and clinicians and shared decision-making. These findings may be used to guide the healthcare providers, policymakers and researchers for enhancing perioperative care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children's Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher's exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ 2 =12.948, P <0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ 2 =0.021, P =0.885). The positive rates of Mp increased with age ( χ 2 =1 722.21, P <0.001). The positive rates of Mp drug-resistant gene mutations also increased with age ( χ 2 =13.152, P <0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring ( χ 2 =1 085.149, P <0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

Purpose: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa)., Methods: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors., Results: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa., Conclusion: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: In the era of concurrent combination therapy in metastatic hormone sensitive prostate cancer, the impact of the testosterone level before initiating androgen deprivation therapy on treatment outcome is still uncertain. We aimed to investigate its effect on time-to-castration-resistance in a metastatic hormone sensitive prostate cancer cohort., Methods: This is a multi-center retrospective study of 5 databases from China, Japan, Austria and Spain including 258 metastatic hormone sensitive prostate cancer patients with androgen deprivation therapy initiated between 2002 and 2021. Baseline testosterone was divided into high and low groups using 12 nmol/L as cutoff level. Primary outcome was time-to-castration-resistance. Secondary outcomes were survival functions. Kaplan-Meier method was employed to evaluate the correlation between baseline testosterone and time-to-castration-resistance. Subgroup analysis was performed to elucidate the effect of upfront combination-therapy and metastatic volume., Results: Median age was 72 years. Median follow-up time was 31 months. Median pre-treatment prostate-specific-antigen level was 161 ng/mL. Majority of case were graded as International-Society-of-Urological-Pathology grade 5 (63.6%). 57.8% patients had high volume disease and 69.0% received upfront combination treatment. 44.6% of the cohort developed castration-resistance. The low testosterone group demonstrated shorter mean-time-to-castration-resistance (19.0 vs 22.4 months, p=0.031). The variance was more significant in patients without combination therapy (13.2 vs 26.3 months, p=0.015). Cancer-specific and overall survival were inferior in the low baseline testosterone level group without receiving combination therapy (p=0.001)., Conclusions: Lower pre-treatment testosterone level is correlated to shorter time-to-castration resistance and worse survival in metastatic prostate cancer patients without upfront combination therapy. Those with low baseline testosterone should be encouraged to adopt combination therapy to delay progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Wong, Chiu, Puche-Sanz, Xue, Chen, Gomez-Gomez, Heidegger, Kafka, Wei, Sakamoto and Ng.)

Background: The tumor microenvironment (TME) encompasses a variety of cells that influence immune responses and tumor growth, with tumor-associated macrophages (TAM) being a crucial component of the TME. TAM can guide prostate cancer in different directions in response to various external stimuli., Methods: First, we downloaded prostate cancer single-cell sequencing data and second-generation sequencing data from multiple public databases. From these data, we identified characteristic genes associated with TAM clusters. We then employed machine learning techniques to select the most accurate TAM gene set and developed a TAM-related risk label for prostate cancer. We analyzed the tumor-relatedness of the TAM-related risk label and different risk groups within the population. Finally, we validated the accuracy of the prognostic label using single-cell sequencing data, qPCR, and WB assays, among other methods., Results: In this study, the TAM&#95;2 cell cluster has been identified as promoting the progression of prostate cancer, possibly representing M2 macrophages. The 9 TAM feature genes selected through ten machine learning methods and demonstrated their effectiveness in predicting the progression of prostate cancer patients. Additionally, we have linked these TAM feature genes to clinical pathological characteristics, allowing us to construct a nomogram. This nomogram provides clinical practitioners with a quantitative tool for assessing the prognosis of prostate cancer patients., Conclusion: This study has analyzed the potential relationship between TAM and PCa and established a TAM-related prognostic model. It holds promise as a valuable tool for the management and treatment of PCa patients., (© 2024. The Author(s).)

Utilizing energy transfer catalysis, this research employed the bifunctional reagents benzotriazole carboxylic acid oxime esters to simultaneously generate benzotriazole and imine radicals. The synthesis of two distinct C-N bonds in a single conversion is showcased through radical addition and radical-radical cross-coupling processes between benzotriazole carboxylic acid oxime ester and olefins. This process facilitates the intermolecular two-component unsymmetrical diamination reaction of olefins. Using this approach, more than 40 benzotriazole-containing molecules were successfully synthesized using styrene, indole, and benzofuran as acceptors, with yields ranging from moderate to excellent.

Background: Many imaging scoring models have been developed for tumor surgery to provide critical guidance for the selection of surgical methods. However, little research has been aimed at developing scoring models for adrenal tumors and retroperitoneal laparoscopic adrenal surgery (RLAS), which has become the primary technique for treating adrenal tumors. The study set out to establish a computed tomography (CT)-based adrenal tumor scoring model for predicting perioperative outcomes in patients with adrenal tumors who have undergone RLAS., Methods: The retrospective analysis included 306 patients with adrenal tumors diagnosed by preoperative unenhanced or enhanced CT from January 2014 to August 2018 in the First Affiliated Hospital of Fujian Medical University. CT images were used to quantify the tumor location and size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the adhesion of periadrenal fat (PF); and the tumor CT enhancement value. We conducted multivariate ordinal logistic regression analysis to screen variables and performed principal component analysis to construct a novel scoring model for RLAS. The perioperative outcomes of RLAS were evaluated according to postoperative length of stay, operative time (OT), intraoperative blood loss (IBL), and postoperative complications., Results: The final scoring model included tumor size; the relationships of the tumors with the surrounding organs and tissues, the large abdominal blood vessels, and the upper poles of the kidneys and renal hila; the tumor CT enhancement value; the adhesion of the PF; and the functional status of adrenal tumors. The total score had positive correlations with the OT (r s =0.431), IBL (r s =0.446), and postoperative length (r s =0.180) (all P values <0.001). Compared to any single metric, the total score provided better prediction of OT and IBL. The grading system for RLAS based on the scoring model also performed well in predicting the complexity and difficulty of RLAS. The coincidence rate for these factors was good (all P values <0.001)., Conclusions: The developed model is feasible and repeatable in the prediction of the perioperative outcomes, complexity, and difficulty of RLAS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-764/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Objective: Genomic instability can drive clonal evolution, continuous modification of tumor genomes, and tumor genomic heterogeneity. The molecular mechanism of genomic instability still needs further investigation. This study aims to identify novel genome instabilityassociated lncRNAs (GI-lncRNAs) and investigate the role of genome instability in pan-Renal cell carcinoma (RCC)., Materials and Methods: A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation., Results: A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance., Conclusions: In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The aim of the study was to investigate associations between diabetic retinopathy (DR) and chronic kidney disease (CKD) in patients with type 2 diabetes (TD2)., Methods: The participants of the cross-sectional, community-based Tongren Health Care Study underwent a detailed medical and ophthalmological examination. We defined TD2 by a fasting plasma glucose concentration of ≥7.0 mmol/L or a medical history. CKD was classified as either reduced estimated glomerular filtration rate (eGFR) of &lt;60 mL/min/1.73 mm2 or presence of albuminuria. DR was assessed using color fundus photographs., Results: Out of 62,217 participants of the Tongren Health Care Study, 5,103 (8.2%) patients had TD2. The prevalence of DR was 12.8% (95% CI, 11.8%, 13.7%), CKD was 13.3% (95% CI, 12.4%, 14.3%), and the subtypes of CKD including reduced eGFR and albuminuria was 4.6% (95% CI, 4.2%, 5.1%) and 10.1% (95% CI, 9.3%, 10.9%), respectively. DR was detectable in 21.0% of the patients with CKD, while CKD was present in 20.9% of the DR patients. Higher DR prevalence was associated with higher prevalence of albuminuria and reduced eGFR (both p &lt; 0.05). Factors independently associated with the presence of CKD instead of DR were older age (p &lt; 0.001, OR = 1.05), a higher body mass index (p &lt; 0.001, OR = 1.14), a higher serum concentration of triglycerides (p &lt; 0.001, OR = 1.26), and a lower blood glucose (p &lt; 0.001, OR = 0.93). Having hypertension was additionally associated with the presence of reduced eGFR as compared with DR (p = 0.005, OR = 4.47)., Conclusions: TD2 patients of older age and with higher body mass index, hypertension, and dyslipidemia had a higher probability of being affected by CKD rather than DR, while those with a higher blood glucose level were more prone to DR than CKD., (© 2023 S. Karger AG, Basel.)

The 1,2-iminylalkylation of diazenes using alkyl iodides in combination with an O -benzoyl oxime is reported. In this transformation, O -benzoyl oxime acted as a radical precursor and XAT mediator. In addition to common alkyl iodides, other alkyl iodides such as iodomethane, iodomethane- d 3 , trifluoroiodomethane, ethyl difluoroiodoacetate, and iodoalkanes containing unprotected hydroxyl and amide groups can also serve as C-radical precursors in the 1,2-iminylalkylation with electrophilic diazenes as radical acceptors.

In this study, a metal-free difunctionalization strategy for diazenes was developed using a range of bifunctionalization reagents. This strategy involves a unique N(sp 3 )-N(sp 2 ) radical coupling between the hydrazine radical and the imine radical. More than 30 triazane core motifs were constructed by installing imines and various functional groups, including alkyl, phenyl, cyanoalkyl, and sulfonyl groups, on both ends of the nitrogen-nitrogen bond of diazenes in an efficient manner.

Objective: To identify tumor-associated macrophages (TAMs) related molecular subtypes and develop a TAMs related prognostic model for prostate cancer (PCa)., Methods: Consensus clustering analysis was used to identify TAMs related molecular clusters. A TAMs related prognostic model was developed using univariate and multivariate Cox analysis., Results: Three TAMs related molecular clusters were identified and were confirmed to be associated with prognosis, clinicopathological characteristics, PD-L1 expression levels and tumor microenvironment. A TAMs related prognostic model was constructed. Patients in low-risk group all showed a more appreciable biochemical recurrence-free survival (BCRFS) than patients in high-risk group in train cohort, test cohort, entire TCGA cohort and validation cohort. SLC26A3 attenuated progression of PCa and prevented macrophage polarizing to TAMs phenotype, which was initially verified., Conclusions: We successfully identified molecular clusters related to TAMs. Additionally, we developed a prognostic model involving TAMs that exhibits excellent predictive performance for biochemical recurrence-free survival in PCa., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Carbohydrate antigen 15-3 (CA15-3) is an important biomarker for early diagnosis of breast cancer. Herein, a label-free electrochemical immunosensor was built based on three-dimensional (3D) urchin-like core-shell Au@PdCu nanocrystals (labeled Au@PdCu NCs) for highly sensitive detection of CA15-3, where K 3 [Fe(CN) 6 ] behaved as an electroactive probe. The Au@PdCu NCs were synthesized by a simple one-pot wet-chemical approach and the morphology, structures, and electrocatalytic property were investigated by several techniques. The Au@PdCu NCs prepared worked as electrode material to anchor more antibodies and as signal magnification material by virtue of its exceptional catalytic property. The developed biosensor exhibited a wide linear detection range from 0.1 to 300 U mL -1 and a low limit of detection (0.011 U mL -1 , S/N = 3) for determination of CA15-3 under the optimal conditions. The established biosensing platform exhibits some insights for detecting other tumor biomarkers in clinical assays and early diagnosis., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objective: To analyze the prevalence, genotype distribution and hematological characteristics of α,β-thalassaemia carriers in Huizhou area of Guangdong Province., Methods: 10 809 carriers of simple β-thalassaemia and 1 757 carriers of α,β-thalassaemia were enrolled as our study cohort. The hematological parameters were detected by automated blood cell counters and automatic capillary electrophoresis. Suspension array technology, gap-polymerase chain reaction (gap-PCR) and PCR-reverse dot blot were used for the genotyping of thalassaemia carriers., Results: The prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province was 1.99%. A total of 62 genotypes were detected, and the most prevalent genotype was -- SEA / αα , β CD41-42 / β N (19.29%), the next was -- SEA / αα , β IVS-II-654 / β N (16.73%). Significant differences in mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were found between different genotype groups for simple β-thalassaemia and α,β-thalassaemia. Violin plots showed that carriers with co-inheritance of β-thalassaemia and mild α-thalassaemia expressed the lightest anemia, and carriers with co-inheritance of β-thalassaemia and hemoglobin H (Hb H) disease expressed the most severe anemia., Conclusion: There is a high prevalence of α,β-thalassaemia in Huizhou area of Guangdong Province. Because of the lack of specific hematological makers for diagnosis of α,β-thalassaemia, it is necessary to distinguish it from simple β-thalassaemia by genotyping of α- and β-thalassaemia in order to correctly guide genetic counseling and prenatal disgnosis.

Objective: To explore whether 68 Ga-PSMA-11 PET/CT-derived parameters could predict biochemical response to abiraterone acetate (AA) treatment and prognosis in metastatic prostate cancer patients developing castration resistance after chemohormonal therapy at hormone-sensitive stage., Methods: The clinicopathologic data of 106 mCRPC cases receiving AA treatment were retrospectively analyzed. Logistic regression analysis was used to determine the independent predictors of biochemical response to AA treatment. Cox analyses were applied to investigate the independent prognostic factors for time to biochemical progression (TTBP) and radiological progression-free survival (rPFS). Survival analysis and ROC curve were also used., Results: Multivariable Logistic analysis demonstrated that prior ADT duration ≥ 12 months, low prostate specific membrane antigen receptor-expressing tumor volume (PSMA-TV), low tumor to liver ratio (TLR) were independent predictors of biochemical response to AA treatment. Multivariate Cox analysis demonstrated that low PSMA-TV and low TLR were independent prognostic factors of longer TTBP and rPFS. The TTBP and rPFS of patients with higher PSMA-TV or TLR were significantly decreased compared with that of patients with lower PSMA-TV and TLR. The area under ROC curve (AUC) of combining ADT duration, PSMA-TV and TLR was 0.82 for predicting biochemical response to AA, which was significantly increased compared with that of other 68 Ga-PSMA-11 PET/CT-derived parameters alone., Conclusions: Low PSMA-TV, low TLR were vital independent predictors of biochemical response to AA treatment and were associated with preferable prognosis in mCRPC patients. Combining ADT duration, PSMA-TV and TLR performed well in distinguishing AA responders from non-responders in mCRPC patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Immunogenic cell death (ICD) plays a vital role in tumor progression and immune response. However, the integrative role of ICD-related genes and subtypes in the tumor microenvironment (TME) in prostate cancer (PCa) remains unknown., Materials and Methods: The sample data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer-related databases. We first divided the subtypes based on ICD genes from 901 PCa patients and then identified the prognosis- related genes (PRGs) between different ICD subtypes. Subsequently, all the patients were randomly split into the training and test groups. We developed a risk signature in the training set by least absolute shrinkage and selection operator (LASSO)-Cox regression. Following this, we verified this prognostic signature in both the training test and external test sets. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, the artificial neural network (ANN) and fundamental experiment study were constructed to verify the accuracy of the prognostic signature., Results: We identified two ICD clusters with immunological features and three gene clusters composed of PRGs. Additionally, we demonstrated that the risk signature can be used to evaluate tumor immune cell infiltration, prognostic status, and an immune checkpoint inhibitor. The low-risk group, which has a high overlap with group C of the gene cluster, is characterized by high ICD levels, immunocompetence, and favorable survival probability. Furthermore, the tumor progression genes selected by the ANN also exhibit potential associations with risk signature genes., Conclusion: This study identified individuals with high ICD levels in prostate cancer who may have more abundant immune infiltration and revealed the potential effects of risk signature on the TME, immune checkpoint inhibitor, and prognosis of PCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kang, Sun, Lin, Huang, Huang, Chen, Zheng, Xue, Xu and Wei.)

Background: Androgen deprivation therapy (ADT) use in prostate cancer (PCa) has seen a rising trend. We investigated the relationship between ADT and adverse changes in metabolic parameters in an Asian population., Methods: This is an international prospective multicenter single-arm cohort yielded from the real-life experience of ADT in Asia (READT) registry. Consecutive ADT-naïve patients diagnosed of PCa and started on ADT were prospectively recruited from 2016 and analyzed. Baseline patient characteristics, PCa disease status, and metabolic parameters were documented. Patients were followed up at 6-month interval for up to 5 years. Metabolic parameters including body weight, lipid profiles, and glycemic profiles were recorded and analyzed., Results: 589 patients were eligible for analysis. ADT was associated with adverse glycemic profiles, being notable at 6 months upon ADT initiation and persisted beyond 1 year. Comparing to baseline, fasting glucose level and hemoglobin A1c level increased by 4.8% (p < 0.001) and 2.7% (p < 0.001), respectively. Triglycerides level was also elevated by 16.1% at 6th month and by 20.6% at 12th month compared to baseline (p < 0.001). Mean body weight was 1.09 kg above baseline at 18th month (p < 0.001)., Conclusion: ADT was associated with adverse metabolic parameters in terms of glycemic profiles, lipid profiles, and body weight in the Asian population. These changes developed early in the treatment and can persist beyond the first year. Regular monitoring of the biochemical profiles during treatment is paramount in safeguarding the patients' metabolic health., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Organophosphorus pesticides (OP) have extensive applications in agriculture, while their overuse causes inevitable residues in food, soil, and water, ultimately being harmful to human health and even causing diverse dysfunctions. Herein, a novel colorimetric platform was established for quantitative determination of malathion based on peroxidase mimic AuPt alloy decorated on CeO 2 nanorods (CeO 2 @AuPt NRs). The synthesized nanozyme oxidized colorless 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H 2 O 2 . Besides, the oxidized TMB was inversely reduced by ascorbic acid (AA), which were originated from hydrolysis of L-ascorbic acid-2-phosphate (AA2P) with the assistance of acid phosphatase (ACP). Based upon this observation ACP analysis was explored by colorimetry, showing a wid linear range of 0.2 ~ 3.5 U L -1 and a low limit of detection (LOD = 0.085 U L -1 , S/N = 3). Furthermore, malathion present in the colorimetric system inhibited the activity of ACP and simultaneously affected the generation of AA, in turn promoting the recovery of the chromogenic reaction. Based on this, the LOD was decreased to 1.5 nM (S/N = 3) for the assay of malathion with a wide linear range of 6 ~ 100 nM. This simple colorimetric platform provides some informative guidelines for determination of other pesticides and disease markers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: With arterial hypertension as a global risk factor for cerebrovascular and cardiovascular diseases, we examined whether retinal blood vessel caliber and tortuosity assessed by a vessel-constraint network model can predict the incidence of hypertension., Methods: The community-based prospective study included 9230 individuals who were followed for 5 years. Ocular fundus photographs taken at baseline were analyzed by a vessel-constraint network model., Results: Within the 5-year follow-up, 1279 (18.8%) and 474 (7.0%) participants out of 6813 individuals free of hypertension at baseline developed hypertension and severe hypertension, respectively. In multivariable analysis, a higher incidence of hypertension was related to a narrower retinal arteriolar diameter ( P  < 0.001), wider venular diameter ( P  = 0.005), and a smaller arteriole-to-venule diameter ratio ( P  < 0.001) at baseline. Individuals with the 5% narrowest arteriole or the 5% widest venule diameter had a 17.1-fold [95% confidence interval (CI):7.9, 37.2] or 2.3-fold (95% CI: 1.4, 3.7) increased risk for developing hypertension, as compared with those with the 5% widest arteriole or the 5% narrowest venule. The area under the receiver operator characteristic curve for predicting the 5-year incidence of hypertension and severe hypertension was 0.791 (95% CI: 0.778, 0.804) and 0.839 (95% CI: 0.821, 0.856), respectively. Although the venular tortuosity was positively associated with the presence of hypertension at baseline ( P  = 0.01), neither arteriolar tortuosity nor venular tortuosity was associated with incident hypertension (both P  ≥ 0.10)., Conclusion and Relevance: Narrower retinal arterioles and wider venules indicate an increased risk for incident hypertension within 5 years, while tortuous retinal venules are associated with the presence rather than the incidence of hypertension. The automatic assessment of retinal vessel features performed well in identifying individuals at risk of developing hypertension., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). ., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS , which was the potential biomarker related to PCa liquid-liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

As one of the most toxic chemical substances, aflatoxin B1 (AFB1) has a strong carcinogenic effect even at a trace level in human and animal, which severely threatens human health and even causes cancers. Therefore, ultrasensitive detection of AFB1 is of significant importance. For such analysis, dual II-scheme sheet-like Bi 2 S 3 /Bi 2 O 3 /Ag 2 S heterostructures were prepared by the in-situ growth method, which exhibited high separation efficiency for the electron-hole (e - -h + ) pairs, prominent stability, and high photoactivity. Moreover, the dendritic nanorod-like Au@Pd@Pt (Au@Pd@Pt DNRs) nanozyme was homely synthesized, whose peroxidase-like activity was scrupulously investigated by catalytical oxidation of diaminobenzidine (DAB) in the presence of H 2 O 2 . Integration by the aptasensing strategy, a photoelectrochemical (PEC) "signal-on" aptasensor was prepared, which exhibited a broader linear range of 0.5 pg mL -1 -100 ng mL -1 with a lower limit of detection (LOD = 0.09 pg mL -1 , S/N = 3). This work provides a feasible strategy to develop advanced PEC biosensors for actual analysis of environmental pollutants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

N-terminal pro-B-type natriuretic peptide is a major cardiac biomarker for early diagnosis and prognosis of heart failure. Herein, a novel label-free electrochemical immunosensor was developed based on home-made branched AuPd nanocrystals/N-doped porous carbon (AuPd NCS/NPC) for ultrasensitive and high-selective detection of N-terminal pro-B-type natriuretic peptide. Specifically, the AuPd NCS/NPC was prepared by a one-pot wet-chemical strategy by using thymine as a green structural directing agent, whose morphology, structures, and properties were strictly examined, showing high-efficiency catalysis towards electro-reduction of hydrogen peroxide. Under the optimized conditions, the fabricated sensor exhibited a dynamic linear range of 0.001 ∼ 10 ng mL -1 and a low limit of detection (0.34 pg mL -1 , S/N = 3) for immunoassay of N-terminal pro-B-type natriuretic peptide. Furthermore, this platform was explored for detection of the biomarker in human serum sample with satisfactory results. Thus, the built biosensor can render valuable guidance for prospective clinical diagnostic applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Human epididymis protein 4 (HE4) is a vital biomarker for early diagnosis of epithelial ovarian cancer (EOC). Herein, a new label-free biosensor was developed using K 3 [Fe(CN) 6 ] as the electrochemical probe for ultrasensitive immunoassay of HE4 based on PtNi nanocubes assemblies (NCAs) as efficient biosensing interfaces. The PtNi NCAs were synthesized by a simple solvothermal approach, where N-hexadecyltrimethylammonium chloride (HTAC) and 2,2'-bis(4,5-dimethylimidazole) (BDMM) behaved as co-structuring directors. Under the optimal conditions, the obtained HE4 immunosensor displayed a wide detection range from 0.001 to 100 ng mL -1 and a low detection limit (0.11 pg mL -1 , S/N = 3). As a result, the current sensing platform would serve as a useful reference for detecting cancer biomarkers in the clinical assay and diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Indoleamine 2,3-dioxygenase 1 (IDO1), the enzyme that catabolizes tryptophan (Trp) metabolism to promote regulatory T cells (Tregs) and suppress CD8 + T cells, is regulated by several intrinsic signaling pathways. Here, we found that tobacco smoke, a major public health concern that kills 8 million people each year worldwide, induced IDO1 in normal and malignant lung epithelial cells in vitro and in vivo. The carcinogen nicotine-derived nitrosaminoketone (NNK) was the tobacco compound that upregulated IDO1 via activation of the transcription factor c-Jun, which has a binding site for the IDO1 promoter. The NNK receptor α7 nicotinic acetylcholine receptor (α7nAChR) was required for NNK-induced c-Jun activation and IDO1 upregulation. In A/J mice, NNK reduced CD8 + T cells and increased Tregs. Clinically, smoker patients with non-small-cell lung cancer (NSCLC) exhibited high IDO1 levels and low Trp/kynurenine (Kyn) ratios. In NSCLC patients, smokers with lower IDO1 responded better to anti-PD1 antibody treatment than those with higher IDO1. These data indicate that tobacco smoke induces IDO1 to catabolize Trp metabolism and immune suppression to promote carcinogenesis, and lower IDO1 might be a potential biomarker for anti-PD1 antibodies in smoker patients, whereas IDO1-high smoker patients might benefit from IDO1 inhibitors in combination with anti-PD1 antibodies., (© 2022. The Author(s).)

Objective: To analyze the clinical phenotype and detect the pathogenic gene in a Chinese pedigree with autosomal dominant polycystic kidney disease(ADPKD). Methods: The proband of this study was hospitalized in Dongguan City People's Hospital on October 10, 2017, due to "left maxillary apical cyst". Clinical phenotypes were noted, imaging examinations and determination of biochemical indicators were carried out for the clinical diagnosis of the proband. Genomic DNA was extracted from peripheral venous blood. Whole-exome genotyping of the proband was performed with the next generation sequencing technology, and the candidate mutation site of the patient and his family members was verified by PCR and Sanger sequencing technology. The mutation site was further screened in 150 unrelated healthy Chinese controls. Mutation frequency within human populations and bioinformatics analysis were predicted with softwares including ExAC, dbSNP, HGMD, 1000 genomes, ClinVar, PKDB, Mutation Taster and PhyloP. Results: The proband, a 46-year-old male, was diagnosed with hypertension, positive urine occult blood and elevated blood creatinine. B-ultrasound and CT examinations showed that he had bilateral polycystic kidney with left kidney stones and polycystic liver. The gene analysis showed that the c.11017-10C>A heterozygous splice mutation in PKD1 gene was identified in the proband, his second younger brother, younger sister, daughter and niece, but absent in 150 healthy controls. Bioinformatics analysis showed it has been reported in the dbSNP, ClinVar, HGMD, PKDB and Mutation Taster databases. Some databases predicted it has a harmful function for probably leading to production of a truncated polycystin1(PC1) protein. Conclusion: c.11017-10C>A underlies the Chinese ADPKD pedigree and expands mutation spectrum of PKD1.

Objective: To investigate the clinicopathological, immunophenotypic and molecular features of colorectal amphicrine carcinoma (AC). Methods: Eight cases of colorectal AC were collected at the Nanjing Drum Tower Hospital and Nanjing First Hospital, Nanjing, China from 2013 to 2020. The histopathological, immunohistochemical and molecular features were analyzed. The relevant literature was reviewed. Results: There were 6 males and 2 females, with an average age of 56 years (range 28-80 years). The tumor sites were as follows: 4 cases in sigmoid colon, 3 cases in rectum, and 1 case in transverse colon. Microscopically, there were three different patterns in the tumors, including nests with collagen hyperplasia, sheets of cells with scant stroma, and glandular or cribriform growth of goblet- or signet ring-like cells. The tumor cells generally had abundant cytoplasm with abundant mucin or eosinophilic granules. The nuclei were oval or irregular with fine chromatin and inconspicuous nucleoli. Mitotic figures were common. Neuroendocrine granules and mucin granules could be identified clearly under electron microscope. All cases showed frequent perineural and lymphovascular invasions, lymphatic metastasis, and advanced stage. Regarding immunohistochemical and specific stains, the tumor cells expressed more than two neuroendocrine markers, particularly CD56 and synaptophysin which were diffusely positive in 7 of the 8 cases. They also showed intracellular mucin in the amphicrine components which was positive for D-PAS. KRAS G12C or NRAS Q61 gene mutations were found in 2 patients. Among the six cases with complete follow-up, four of them died of the disease within three years of the diagnoses, while two were alive without known disease progression. Conclusions: Colorectal AC is a rare, distinct entity with both epithelial and neuroendocrine differentiation. It mainly occurs in the sigmoid colon and rectum. It typically has aggressive clinical courses, dismal prognosis and characteristic histological features and immunophenotype, which highlight the importance of recognizing this entity for clinicians and pathologists.

A signal-on sandwich-like electrochemical immunosensor was built for determination of cytokeratin 19 fragments 21-1 (CYFRA 21-1) in non-small cell lung cancer (NSCLC) by confining electroactive dye (e.g., methylene blue, MB) as a probe for amplifying signals. Specifically, core-shell gold@rhodium dendritic nanocrystals (Au@Rh DNCs) behaved as a substrate for primary antibody and accelerate interfacial electron transfer. Besides, hollow carbon spheres (HCSs) were subsequently modified with polydopamine (PDA) and PtPd nanoparticles for sequential integration of the secondary antibody and confinement of MB as a label, termed as MB/PtPd/PDA/HCSs for clarity. The built sensors showed a broad linear range (100 fg mL -1  ~ 100 ng mL -1 ) for detection of CYFRA 21-1 with an ultra-low detection limit (31.72 fg mL -1 , S/N = 3), coupled with satisfactory performance in human serum samples. This work can be explored for assays of other proteins and provides some constructive insights for early and accurate diagnosis of NSCLC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: To investigate the prevalence of Gunn's dots (GDs) and associated systemic factors in adult Chinese., Methods: A cross-sectional study enrolling participants older than 45 years from a community-based study. Gunn's dots were evaluated using fundus photography, and associated systemic factors were analyzed. Patients with any retinal or optic neuropathy were excluded., Results: The study included 4,118 participants (mean age: 58.3 ± 9.9 years; male: 1,699/41.3%). Gunn's dots were found in 931 participants, with a prevalence of 22.6 ± 0.8% (95% confidence interval [CI]: 21.3-23.9). Systemic factors associated with a higher GD prevalence were younger age (odds ratio [OR]: 0.92; 95% CI: 0.91-0.93; P < 0.001), higher estimated glomerular filtration rate (eGFR) (OR: 1.01; 95% CI: 1.001-1.02; P = 0.022), and higher serum concentration of triglycerides (OR: 1.08; 95% CI: 1.004-1.16; P = 0.040). The GD prevalence was 3.5 (OR = 3.46; 95% CI: 1.06-11.35) and 4.4 (OR = 4.37; 95% CI: 1.27-15.09) times greater for participants with an eGFR of ≥90 mL/minute/1.73 m2 and an eGFR of ≥100 mL/minute/1.73 m2, respectively, as compared with participants with an eGFR of <60 mL/minute/1.73 m2., Conclusion: The GD prevalence (mean: 22.6%) was associated with younger age, higher eGFR, and higher serum triglyceride concentrations. The presence of GDs may serve as indicators of healthy renal function.

Background: The jejunal mesentery supplied by the superior mesenteric vascular tree has emerged as a viable site for vascularized lymph node transplantation. Among other benefits, it has the advantage of avoidance of the risk of donor-site lymphedema. This article reports the technique and outcomes of a novel approach to jejunal mesenteric vascularized lymph node transplantation with flap harvest from the mesenteric root to reduce the risk of small bowel ischemic complications., Methods: A consecutive series of patients that underwent jejunal mesenteric vascularized lymph node transplantation to treat upper extremity lymphedema were included. Preoperative and postoperative measurements were taken at fixed intervals using standardized techniques including Perometer volumetry, LDex bioimpedance spectroscopy, the Lymphedema Life Impact Scale, and the Quick Disabilities of the Arm, Shoulder and Hand tool. Demographic, treatment, and outcomes data were collected, and descriptive statistics were used., Results: There were 25 patients included, all of whom had maximized their conservative therapy before undergoing surgery. At 12 months postoperatively reduction in limb volume difference was 36.7 percent (p < 0.001), reduction in LDex score was 41.4 percent (p = 0.0015), and reductions in the Lymphedema Life Impact Scale and Quick Disabilities of the Arm, Shoulder and Hand scores were 55.7 percent (p = 0.0019) and 47.5 percent (p = 0.027), respectively. In 11 patients, there was a history of cellulitis (multiple episodes in eight), and at up to 24 months' follow-up postoperatively there were no episodes reported (p < 0.001)., Conclusion: Upper extremity lymphedema can be effectively treated surgically using the jejunal mesenteric vascularized lymph node transplantation, resulting in reduced limb volume and extracellular fluid, and improved patient-reported limb function and outcomes measures compared with optimized conservative therapy alone., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

The importance of anti-androgen therapy for prostate cancer (PC) has been well recognized. However, the mechanisms underlying prostate cancer resistance to anti-androgens are not completely understood. Therefore, identifying pharmacological targets in driving the development of castration-resistant PC is necessary. In the present study, we sought to identify core genes in regulating steroid hormone pathways and associating them with the disease progression of PC. The selection of steroid hormone-associated genes was identified from functional databases, including gene ontology, KEGG, and Reactome. The gene expression profiles and relevant clinical information of patients with PC were obtained from TCGA and used to examine the genes associated with steroid hormone. The machine-learning algorithm was performed for key feature selection and signature construction. With the integrative bioinformatics analysis, an eight-gene signature, including CA2 , CYP2E1 , HSD17B , SSTR3 , SULT1E1 , TUBB3 , UCN , and UGT2B7 was established. Patients with higher expression of this gene signature had worse progression-free interval in both univariate and multivariate cox models adjusted for clinical variables. The expression of the gene signatures also showed the aggressiveness consistently in two external cohorts, PCS and PAM50. Our findings demonstrated a validated eight-gene signature could successfully predict PC prognosis and regulate the steroid hormone pathway.

Background and Objectives: This study evaluates clinical outcomes of vascularized lymph node transplantation (VLNT) from the lateral thoracic region and technical modifications., Methods: Consecutive patients that underwent lateral thoracic VLNT to treat extremity lymphedema were included. Demographic and treatment data were recorded, and outcomes data including limb volume, LDex score, and Lymphedema Life Impact Scale (LLIS), QuickDASH, and LEFS questionnaires, were collected prospectively. Consecutive patients that underwent single-photon emission computed tomography (SPECT/CT) lymphoscintigraphy axillary reverse lymphatic mapping (RLM) were analyzed to characterize the physiological drainage of the normal upper extremity., Results: A consecutive series of 32 flaps were included. At 24 months postoperatively mean reduction in limb volume excess was 47.2% (±11.6; p = 0.0085), LDex score was 63.1% (±8.5; p < 0.001), and LLIS score was 65.1% (±7.4; p < 0.001). Preoperatively 14/31 patients (45.2%) reported cellulitis, and postoperatively there were no episodes at up to 24 months (p < 0.001). No patient developed donor extremity lymphedema at mean 18.6 (±8.3) months follow-up. SPECT/CT-RLM of 182 normal axillae demonstrated that the sentinel lymph node(s) of the upper extremity was consistently anatomically located in the upper outer quadrant of the axilla (97%)., Conclusions: VLNT from the lateral thoracic region is effective and versatile for the treatment of lymphedema with a low donor site complication rate., (© 2022 Wiley Periodicals LLC.)

Objective: To identify ferroptosis-related molecular clusters, and to develop and validate a ferroptosis-based molecular signature for predicting biochemical recurrence-free survival (BCRFS) and tumor immune microenvironment of prostate cancer (PCa). Materials and Methods: The clinical data and transcriptome data of PCa were downloaded from TCGA and GEO database. Ferroptosis-related genes (FRGs) were obtained from FerrDb database. We performed consensus clustering analysis to identify ferroptosis-related molecular subtypes for PCa. Univariate and multivariate Cox regression analysis were used to establish a ferroptosis-based signature for predicting BCRFS. Internal verification, external verification and subgroup survival analysis were then successfully performed. Results: There was a total of 40 differentially expressed FRGs in PCa. We then identified three ferroptosis-related molecular clusters of PCa, which have significantly different immune infiltrating cells, tumor immune microenvironment and PD-L1 expression level. More importantly, a novel ferroptosis-based signature for predicting BCRFS of PCa based on four FRGs (including ASNS, GPT2, NFE2L2, RRM2) was developed. Internal and external verifications were then successfully performed. Patients with high-risk score were associated with significant poor BCRFS compared with those with low-risk score in training cohort, testing cohort and validating cohort, respectively. The area under time-dependent Receiver Operating Characteristic (ROC) curve were 0.755, 0.705 and 0.726 in training cohort, testing cohort and validating cohort, respectively, indicating the great performance of this signature. Independent prognostic analysis indicated that this signature was an independent predictor for BCRFS of PCa. Subgroup analysis revealed that this signature was particularly suitable for younger or stage T III-IV or stage N0 or cluster 1-2 PCa patients. Patients with high-risk score have significantly different tumor immune microenvironment in comparison with those with low-risk score. The results of qRT-PCR successfully verified the mRNA expression levels of ASNS, GPT2, RRM2 and NFE2L2 in DU-145 and RWPE-1 cells while the results of IHC staining exactly verified the relative protein expression levels of ASNS, GPT2, RRM2 and NFE2L2 between PCa and BPH tissues. Conclusions: This study successfully identified three ferroptosis-related molecular clusters. Besides, we developed and validated a novel ferroptosis-based molecular signature, which performed well in predicting BCRFS and tumor immune microenvironment of PCa., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ke, You, Sun, Zhu, Li, Chen, Su, Zheng, Wei, Xue and Xu.)

Introduction: Idiopathic hypogonadotropic hypogonadism (IHH) is a rare reproductive disorder resulting from gonadotropin-releasing hormone (GnRH) deficiency. However, in only approximately half of patients with IHH is it possible to identify a likely molecular diagnosis. Mice lacking Slit2 have a reduced number or altered patterning of GnRH neurons in the brain. In order to assess the contribution of SLIT2 to IHH, we carried out a candidate gene burden test analysis., Methods: A total of 196 IHH probands and 2,362 ethic-matched controls were recruited for this study. The IHH probands and controls were subjected to whole-exome sequencing. In the IHH patients with SLIT2 variants and their available family members, detailed phenotyping and segregation analysis were performed., Results: Nine heterozygous SLIT2 rare sequencing variants (RSVs) were identified in 13 probands, with a prevalence of 6.6%. Furthermore, we identified an increased mutational burden for SLIT2 in this cohort (odds ratio = 2.2, p = 0.021). The segregation analysis of available IHH families revealed that the majority of SLIT2 RSVs were inherited from unaffected or partially affected parents., Conclusion: Our study suggests SLIT2 as a new IHH-associated gene and expands the clinical and genetic spectrum of IHH. Furthermore, SLIT2 alone does not appear to be sufficient to cause the disorder, and it may interact with other IHH-associated genes to induce a clinical phenotype., (© 2022 S. Karger AG, Basel.)

Aims: To examine the prevalence of primary epiretinal membranes (ERMs) and associated systemic factors. Methods: The cross-sectional, community-based Tongren Health Care Study enrolled participants who received regular health examinations in the Beijing Tongren Hospital from 2017 to 2019. Using fundus photographs, retinal specialists assessed the presence of ERMs and their systemic associations. Results: Primary ERMs were detected in 841/22820 individuals, with a prevalence of 3.7% [95% confidence intervals (CI): 3.4-3.9%] in the total study population (mean age: 44.5 ± 13.8 years) and 6.5% (95% CI: 6.1-7.0%) in individuals aged 40+ years. In multivariable analysis, a higher ERMs prevalence was associated with older age [odds ratio (OR): 1.10; P < 0.001], higher serum cholesterol concentration (OR: 1.14; P = 0.003) and higher serum sodium concentration (SSC) (OR: 1.12; P < 0.001). In women, a higher SSC, even within the normal range, was associated with an increased risk of ERMs (OR: 1.19; P < 0.001). Female participants with an SSC of 144-145mmol/L as compared with those with an SSC of 135-137 mmol/L had a 5-fold increased odds of having ERMs (All women: OR: 5.33; P < 0.001; Women aged 40+years: OR: 4.63; P < 0.001). Conclusion: Besides older age and higher serum cholesterol concentration, a higher SSC, even if within the normal range, was independently associated with a higher ERM prevalence in women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xue, Cui, Zhu, Xu, Zhang, Chen, Wang and Jonas.)

Background: Isolated hypogonadotropic hypogonadism (IHH) is a clinical syndrome described by failure of gonadal function secondary to defects on the synthesis, secretion, or action of the gonadotropin-releasing hormone (GnRH). The secreted glycoprotein SEMA3A binds its receptors NRP1 or NRP2 and PLXNA to participate in axonal projection, dendritic branching, synaptic formation, and neuronal migration. Deficiency in SEMA3A, NRP1, NRP2, and PLXNA1 have been related to abnormal GnRH neuron development in mice and IHH in humans., Methods: The aim of this study was to examine the genotypic and phenotypic spectra of the NRP1, NRP2, and PLXNA1 genes in a large cohort of IHH probands from China. We screened NRP1, NRP2, and PLXNA1 variants in Chinese IHH patients by whole exome sequencing and pedigree analysis., Results: We identified 10 heterozygous missense variants in PLXNA1, five heterozygous missense variants in NRP1, and two heterozygous missense variants in NRP2. NRP1 variants were found only in IHH patients with defective olfaction (i.e., Kallmann syndrome, KS). In addition, 85% (17/20) of patients harbored variants in other IHH-associated genes., Conclusion: Our study greatly enriched the genotypic and phenotypic spectra of PLXNA1, NRP1, and NRP2 in IHH. It may be conducive to the genetic counseling, diagnosis, and treatment of IHH with mutations in the PLXNA1, NRP1, and NRP2 genes. Furthermore, our results indicated that NRP1 were strongly linked to hearing loss., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

In the recent decade, the importance of DNA damage repair (DDR) and its clinical application have been firmly recognized in prostate cancer (PC). For example, olaparib was just approved in May 2020 to treat metastatic castration-resistant PC with homologous recombination repair-mutated genes; however, not all patients can benefit from olaparib, and the treatment response depends on patient-specific mutations. This highlights the need to understand the detailed DDR biology further and develop DDR-based biomarkers. In this study, we establish a four-gene panel of which the expression is significantly associated with overall survival (OS) and progression-free survival (PFS) in PC patients from the TCGA-PRAD database. This panel includes DNTT , EXO1 , NEIL3 , and EME2 genes. Patients with higher expression of the four identified genes have significantly worse OS and PFS. This significance also exists in a multivariate Cox regression model adjusting for age, PSA, TNM stages, and Gleason scores. Moreover, the expression of the four-gene panel is highly correlated with aggressiveness based on well-known PAM50 and PCS subtyping classifiers. Using publicly available databases, we successfully validate the four-gene panel as having the potential to serve as a prognostic and predictive biomarker for PC specifically based on DDR biology.

Objective: To investigate the influence of prostatic calculi on the results of prostate biopsy in patients with a PSA level of 4－10 μg/L., Methods: We reviewed the clinical data on 317 patients with a PSA level of 4－10 μg/L on prostate biopsy performed in The First Affiliated Hospital of Fujian Medical University between May 2012 and May 2019, concerning age, body mass index (BMI), prostate volume, PSA level, FPSA/TPSA ratio, PSA density (PSAD), scores on Prostate Imaging Reporting and Data System version 2 (PI-RADS), prostatic calculi and pathological findings. Using logistic regression analysis and ROC curves, we evaluated the influence of prostatic calculi on the results of prostate biopsy., Results: Multivariate analysis showed that age and the PI-RADS score were independent risk factors of positive prostate biopsy, while the prostate volume, FPSA/TPSA ratio and calculus burden were independent protective factors, and that the PI-RADS score was an independent risk factor of clinically significant PCa, while calculus burden and FPSA/TPSA ratio were independent protective factors. Subgroup analysis of the prostatic calculi revealed that the rates of positive prostate biopsy and clinically significant PCa were higher in the patients with calculi in the peripheral zone than in the other groups, but lower in those with calculi in the central or transitional zone than in the peripheral zone and non-calculus groups., Conclusions: The rates of positive prostate biopsy and clinically significant PCa are low in prostatic calculus patients with a PSA level of 4－10 μg/L, especially in those with calculi in the central or transitional zone.

Purpose: To assess potential associations between the prevalence of age-related macular degeneration (AMD) and systemic parameters in a Chinese population., Design: Cross-sectional study., Methods: The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital from 2017 to 2019. Detailed medical examinations and ophthalmic examinations were applied, including fundus photography. AMD was evaluated according to the Beckman Initiative guidelines., Results: The study included 7,719 participants (mean age: 60.5 ± 8.1 years; range: 50-97 years). The prevalence of any, early, intermediate, and late AMD was 1,607 of 7,719 (20.8%; 95% confidence interval [CI]: 20.1%, 21.9%), 832 of 7,719 (10.8%; 95% CI: 10.1%, 11.5%), 733 of 7,719 (9.5%; 95% CI: 8.9%, 10.2%), and 42 of 7,719 (0.50%; 95% CI: 0.40%, 0.70%), respectively. In multivariate analysis, the prevalence of any AMD increased with higher blood monocyte count (odds ratio [OR]:3.49; 95% CI: 2.26, 5.38; P < .001), after adjusting for older age (OR: 1.06; 95% CI: 1.05, 1.07; P < .001), higher serum concentration of calcium (OR: 2.52; 95% CI: 1.32, 4.84; P = .005), high-density lipoproteins (OR: 1.39; 95% CI: 1.19, 1.61; P < .001), and lower lipoprotein a (OR: 0.99; 95% CI: 0.98, 0.99; P = .02). Similar findings were obtained for the prevalence of intermediate and late AMD combined. The association between higher monocyte count and higher AMD prevalence showed the highest odds ratio for the age group of 50-59 years (any AMD: OR: 4.35, P < .001; intermediate and late AMD: OR: 6.14, P < .001). Individuals with a monocyte count of ≥0.5 × 10 9 /L as compared to participants with a monocyte of 0.1-0.4 × 10 9 /L had a 1.45-fold increased risk for any AMD (OR: 1.45; 95% CI: 1.27, 1.64; P < .001) and 1.58 fold increase risk for intermediate/late AMD (OR: 1.58; 95% CI: 1.33, 1.87; P < .001)., Conclusion: A higher prevalence of early AMD, intermediate AMD, late AMD, and any AMD was associated with a higher peripheral monocyte count. In agreement with previous studies, the observation suggests monocytes playing a role in the pathogenesis of AMD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: A growing body of evidence supports the efficacy of surgical treatments for lymphedema. This study reports the outcomes of vascularized lymph node transplantation (VLNT) for the treatment of patients with lymphedema compared with maximal conservative treatment alone., Study Design: Consecutive patients undergoing VLNT to treat primary and secondary lymphedema affecting the upper or lower extremities were included. All patients were optimized preoperatively with conservative therapy. Demographic and treatment information was collected, and outcomes data were electronically captured prospectively; descriptive statistics were performed., Results: There were 134 patients included that had achieved maximal reductions by conservative therapy preoperatively. This series included jejunal mesenteric (n = 25), groin (n = 43), lateral thoracic (n = 31), omental or right gastroepiploic (n = 21), and submental (n = 14) VLN flaps. At 24 months postoperatively, there were significant reductions in limb volume change (mean [SD] 45.7% [8.7%]; p = 0.002) LDex score (mean [SD] 59.8% [8.7%]; p < 0.001), Lymphedema Life Impact Scale score (mean [SD] 61.6% [5.9]; p < 0.001), and cellulitis episodes (97.9%; p < 0.001). At 3 and 6 months postoperatively, limb volume change was significantly greater for the upper than the lower extremity, otherwise outcomes were similar. There were no flap losses and overall outcomes were similar between the different VLN flap types., Conclusions: Treatment of lymphedema using VLNT resulted in progressive, significant reductions in limb volume, bioimpedance spectroscopy measurements of extracellular fluid, and episodes of cellulitis, with improved patient-reported outcomes and limb function measures compared with maximal conservative therapy alone. The complication rate was low and there were no significant outcomes differences between the VLNT types., (Copyright © 2021 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Acute kidney injury (AKI) is a common organ dysfunction in ICU and up to now there is no good way to predict the AKI progression and patient prognosis. Blood electrolyte tests are common in ICU, but there are few studies on early blood electrolytes and the AKI progression and patient prognosis. Therefore, we concentrated on the serum sodium and potassium levels before AKI diagnosis and evaluated the relationship between serum sodium and potassium levels and the severity and prognosis of AKI., Methods: This study included data of all patients from the MIMIC-III. We used the urine output criteria in the KDIGO as diagnostic criteria for oliguric AKI. Patients admitted to the ICU several times only included their initial ICU admission results. Patients younger than 18 years old, diagnosed with AKI stage 3, ICU stays less than 24 h or without corresponding laboratory results or data were excluded. The included patients were divided into four groups based on the interquartile range of serum sodium and potassium. We evaluated the serum sodium and potassium levels before AKI diagnosis and AKI severity and prognosis through retrospective analysis., Results: Patients with serum potassium > 4.6 mmol/L were more likely to progress to AKI stage 3 or death than patients with serum potassium ≤ 4.6 mmol/L (overall p < 0.0001). Patients with sodium < 137 mmol/L or > 141 mmol/L had a higher risk of progressing to AKI stage 3 (overall p = 0.00023) and risk of death (overall p < 0.0001) than other patients. In the Cox regression model, after adjusting for age, sex, and BMI, serum sodium or potassium were associated with AKI progression and prognosis (p < 0.01). After continuing to adjust for comorbidities, serum potassium was still associated with AKI progression and prognosis (p < 0.01), but serum sodium was only associated with prognosis (p = 0.027). After adjusting for other indicators, there was no statistically significant correlation between serum sodium or potassium and AKI progression and prognosis. After adjusting for serum sodium or potassium, the corresponding results were not significantly different from those before adjustment., Conclusion: This study found that abnormal serum sodium or potassium levels before AKI diagnosis were more likely to lead to AKI progression and poor prognosis, of which lower serum sodium and higher serum potassium were more likely to progress to AKI stage 3 or death.

Spermatogenesis is a highly sophisticated process that comprises of mitosis, meiosis, and spermiogenesis. RNF216 (ring finger protein 216), an E3 ubiquitin ligase, has been reported to be essential for spermatogenesis and male fertility in mice. However, the stages affected by Rnf216 deficiency and its underlying molecular pathological mechanisms are still unknown. In this study, we generated Rnf216-deficient mice (Rnf216 -/- ) using CRISPR-Cas9 technology. Knockout of Rnf216 led to infertility in male but not female mice. Rnf216 knockout affected the prophase of meiosis I, as no genotypic difference was observed until 12 dpp (days postpartum). Rnf216 -/- spermatocytes were incompletely arrested at the zygotene stage and underwent apoptosis at approximately the pachytene stage. The proportion of zygotene spermatocytes was significantly increased, whereas the proportion of pachytene spermatocytes was significantly decreased in Rnf216 -/- testes. Nevertheless, there was no significantly genotypic difference in the number of diplotene spermatocytes. We further revealed that the PKA catalytic subunit β (PRKACB) was significantly increased, which subsequently resulted in elevated PKA activity in testes from adult as well as 9 dpp Rnf216 -/- mice. RNF216 interacts with PRKACB and promotes its degradation through the ubiquitin-lysosome pathway. Collectively, our results revealed an important role for RNF216 in regulation of meiosis and PKA stability in the testes., (© 2021 Federation of American Societies for Experimental Biology.)

Pheochromocytoma and paraganglioma (PCPG) is a rare neuroendocrine tumor. This study aims to identify vital prognostic genes which were associated with PCPG tumor microenvironment (TME). We downloaded transcriptome data of PCPG from TCGA database and calculated the immune scores and stromal scores by using the ESTIMATE algorithm. DEGs related to TMB were then identified. We conducted WGCNA to further extract the TME-related modules. GO, KEGG pathway analysis, and PPI network were performed. Survival analysis was conducted to identify the hub genes associated with the prognosis of PCPG. A total of 150 PCPG samples were included in this study. We obtained 1507 and 2067 DEGs based on immune scores and stromal scores, respectively. WGCNA analysis identified the red module and brown module were correlated with immune sores while the turquoise module and red module were significantly associated with stromal scores. Functional enrichments analysis revealed that 307 TME-related genes were correlated with the inflammation or immune response. Survival analysis showed that three TME-relate genes (ADGRE1, CCL18, and LILRA6) were associated with PCPG prognosis. These three hub genes including ADGRE1, CCL18, and LILRA6 might be involved in the progression of PCPG and could serve as potential biomarkers and novel therapeutic targets.

Objective To describe the inpatient care expenditure of the terminally ill patients in the geriatric ward of Peking Union Medical College Hospital and facilitate future research on the economic outcomes of hospice and palliative care.Methods The histories of patients admitted to the Department of Geriatrics of Peking Union Medical College Hospital during 2018 were reviewed by trained doctors.According to the diagnosis and overall health state,terminally ill patients were selected and enrolled in the study.Demographics,health and disease information,prescriptions,and expenditure details were retrieved from the HIS system.Results In 2018,35 patients were terminally ill and eligible for hospice care,including 20 males and 15 females,with the average age of(78±8)years(59-91 years),the average age-adjusted Charlson Comorbidity Index of 10±3,and the median Barthel index of 40(10,70).These patients had malignant tumor(23 cases),heart failure(4 cases),end-stage renal disease(1 case),end-stage liver disease(2 cases),dementia(4 cases)and other severe diseases(3 cases).The patients received standard care within the scope of internal medicine and geriatrics.Finally,8 patients died during hospitalization,and 27 were discharged alive.The 35 patients had the median length of stay of 15(12,23)days,the median inpatient expenditure of CNY 21 500(13 800,37 600),and the median daily expenditure of CNY 1425(970,2503).The percentage of expenditure was(28.5±12.3)% for medication,(33.2±18.0)% for tests and examinations,and 11.5%(6.4%,15.8%)for accommodation and medical services.The medications for symptom control costed CNY(77±58)per day on average,accounting for(5.2±3.5)% of the total expenditure.Conclusions The inpatient expenditure for terminally ill patients in the tertiary grade A hospital was higher than that reported in community hospitals providing hospice care.In terms of expenditure constitution,the money spent on medications and tests/examinations were similar,and the percentage of expenditure on medications for symptom control was low.There is a need for further research on the economic impact of hospice and palliative care among terminally ill patients in China.