Search

Abstract Background Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real‐world study and a meta‐analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. Methods We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1‐, 2‐, and 3‐year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1‐year recurrence rate, R0 resection rate and adverse events. Moreover, a meta‐analysis of 27 published literatures was also conducted for comparison. Results In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1‐, 2‐, and 3‐year OS rates were 91.41% (95% CI: 85.15%–95.63%), 75.00% (95% CI: 66.58%–82.23%) and 64.84% (95% CI: 55.91%–73.07%).ORR and DCR were 31.2% (95% CI: 23.31–39.99) and 64.1% (95% CI: 55.15%–72.38%), and the 1‐year recurrence rate was 26.7% (95% CI: 22.5%–38.1%). Treatment‐related events occurred in 96.1% but were acceptable. In a meta‐analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1‐year recurrence rate of 12%. Conclusion NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.

Abstract Cancer stem cells (CSCs) represent both a key driving force and therapeutic target of tumoral carcinogenesis, tumor evolution, progression, and recurrence. CSC-guided tumor diagnosis, treatment, and surveillance are strategically significant in improving cancer patients’ overall survival. Due to the heterogeneity and plasticity of CSCs, high sensitivity, specificity, and outstanding targeting are demanded for CSC detection and targeting. Nanobiotechnologies, including biosensors, nano-probes, contrast enhancers, and drug delivery systems, share identical features required. Implementing these techniques may facilitate the overall performance of CSC detection and targeting. In this review, we focus on some of the most recent advances in how nanobiotechnologies leverage the characteristics of CSC to optimize cancer diagnosis and treatment in liquid biopsy, clinical imaging, and CSC-guided nano-treatment. Specifically, how nanobiotechnologies leverage the attributes of CSC to maximize the detection of circulating tumor DNA, circulating tumor cells, and exosomes, to improve positron emission computed tomography and magnetic resonance imaging, and to enhance the therapeutic effects of cytotoxic therapy, photodynamic therapy, immunotherapy therapy, and radioimmunotherapy are reviewed.

IntroductionThe introduction of Immune Checkpoint Inhibitors (ICIs) has marked a paradigm shift in treating Lung Squamous Cell Carcinoma (LUSC), emphasizing the urgent need for precise molecular biomarkers to reliably forecast therapeutic efficacy. This study aims to identify potential biomarkers for immunochemotherapy efficacy by focusing on plasma extracellular vesicle (EV)-derived long RNAs (exLRs).MethodsWe enrolled 78 advanced LUSC patients undergoing first-line immunochemotherapy. Plasma samples were collected, and exLR sequencing was conducted to establish baseline profiles. A retrospective analysis was performed on 42 patients to identify differentially expressed exLRs. Further validation of the top differentially expressed exLRs was conducted using quantitative reverse transcription PCR (qRT-PCR). Univariate Cox analysis was applied to determine the prognostic significance of these exLRs. Based on these findings, we developed a predictive signature (p-Signature).ResultsIn the retrospective analysis of 42 patients, we identified 460 differentially expressed exLRs, with pathways related to leukocyte migration notably enriched among non-responders. Univariate Cox analysis revealed 45 exLRs with prognostic significance. The top 6 protein-coding exLRs were validated using qRT-PCR, identifying CXCL8, SSH3, and SDHAF1 as differentially expressed between responders and non-responders. The p-Signature, comprising these three exLRs, demonstrated high accuracy in distinguishing responders from non-responders, with an Area Under the Curve (AUC) of 0.904 in the retrospective cohort and 0.812 in the prospective cohort.DiscussionThis study highlighted the potential of plasma exLR profiles in predicting LUSC treatment efficacy. Intriguingly, lower p-Signature scores were associated with increased abundance of activated CD4+ and CD8+ T cells, indicating a more robust immune environment. These findings suggest that the p-Signature could serve as a valuable tool in guiding personalized and effective therapeutic strategies for LUSC.

IntroductionPine wilt disease spreads rapidly, leading to the death of a large number of pine trees. Exploring the corresponding prevention and control measures for different stages of pine wilt disease is of great significance for its prevention and control.MethodsTo address the issue of rapid detection of pine wilt in a large field of view, we used a drone to collect multiple sets of diseased tree samples at different times of the year, which made the model trained by deep learning more generalizable. This research improved the YOLO v4(You Only Look Once version 4) network for detecting pine wilt disease, and the channel attention mechanism module was used to improve the learning ability of the neural network.ResultsThe ablation experiment found that adding the attention mechanism SENet module combined with the self-designed feature enhancement module based on the feature pyramid had the best improvement effect, and the mAP of the improved model was 79.91%.DiscussionComparing the improved YOLO v4 model with SSD, Faster RCNN, YOLO v3, and YOLO v5, it was found that the mAP of the improved YOLO v4 model was significantly higher than the other four models, which provided an efficient solution for intelligent diagnosis of pine wood nematode disease. The improved YOLO v4 model enables precise location and identification of pine wilt trees under changing light conditions. Deployment of the model on a UAV enables large-scale detection of pine wilt disease and helps to solve the challenges of rapid detection and prevention of pine wilt disease.

Acute kidney injury (AKI) is a life-threatening health condition associated with increasing morbidity and mortality. Despite extensive research on the mechanisms underlying AKI, effective clinical tools for prediction and treatment remain scarce. Oxidative stress and mitochondrial damage play a critical role in AKI and dopamine D4 receptor (DRD4) has been confirmed to be associated with oxidative stress. In this study, we hypothesized that DRD4 could attenuate AKI through its antioxidative and antiapoptotic effects. In vivo, DRD4 was remarkably decreased in the kidneys of mice subjected to ischemia/reperfusion injury (IRI) or cisplatin treatment. Notably, DRD4 significantly attenuated nephrotoxicity by suppressing oxidative stress and enhancing mitochondrial bioenergetics through the downregulation of reactive oxygen species (ROS) generation and NADPH oxidase 4 (NOX4) expression. In vitro, DRD4 demonstrated the ability to ameliorate oxidative stress-induced apoptosis in HK-2 cells subjected to hypoxia/reoxygenation- or cisplatin treatment. Transcriptome sequencing revealed that, mechanistically, DRD4 reduced the expression of its downstream target, interferon-stimulated gene 15 (ISG15), suppressing NOX4 ISGylation, enhancing the ubiquitination of NOX4, leading to its degradation, and ultimately counteracting oxidative stress-induced AKI. Altogether, these findings underscore the significance of DRD4 in AKI and elucidate DRD4 as a potential protectant against IRI or cisplatin-induced nephrotoxicity.

Abstract Objectives To investigate the association between grip strength (GS) and relative grip strength (rGS) with the prevalence and severity risk of SUI. Methods Female patients were retrieved from the NHANES 2011–2014. GS was measured using a digital hand dynamometer, rGS was defined as grip strength divided by BMI. Samples were classified into four groups based on quartiles of GS and rGS distribution (Q1-Q4)。Logistic regression models were established to detect the relationship between GS or rGS and SUI. The potential bias of baseline variables between SUI and non-SUI groups was controlled by performing the propensity score matching (PSM). Results A total of 4263 samples were included, with 3085 (85%) people in non-SUI group and 1178 (27.6%) people in SUI group. GS and rGS levels of people without SUI were higher than that of SUI patients. Monthly SUI patients’ GS and rGS levels were higher than weekly SUI patients’ level. Logistic regression analysis showed that risks of prevalence and severity of SUI decreased with increasing levels of GS and rGS. rGS was found to have a stronger association with SUI than GS [prevalence: GS: Q4 vs. Q1: aOR = 0.633, 95%CI = 0.508–0.789, p

BackgroundEffective self-management can enhance a patient’s quality of life and delay disease progression. However, motivating patients to adhere to self-management behavior following percutaneous coronary intervention (PCI) remains a challenge. With the robust development of positive psychology and interdisciplinary research, the role of psychology factors in patients’ health behavior has increasingly garnered attention. This study, focusing on positive psychological qualities, aims to investigate the relationship between inner strength, hope, and self-management in patients post-PCI, and to analyze the mediating role of hope between inner strength and self-management.MethodsA cross-sectional survey was conducted among 216 PCI patients from a tertiary hospital in Nanjing. Research instruments included a self-designed general information questionnaire, the Inner Strength Scale (ISS), the Herth Hope Index (HHI), and the Coronary Self-Management Scale (CSMS). T-test, analysis of variance, Pearson’s correlation analysis, and mediating effect test were utilized for statistical analysis.ResultsThe average scores of the ISS, HHI, and CSMS were 81.46 ± 12.00, 35.94 ± 5.38, and 86.79 ± 14.84, respectively. Inner strength was positively correlated with hope and self-management (r = 0.867, r = 0.630, respectively; all P < 0.05), and hope was positively correlated with self-management (r = 0.671, P < 0.05). Moreover, hope had a complete mediating effect between inner strength and self-management (β = 0.630, P < 0.01).ConclusionThe inner strength, hope, and self-management of patients with PCI are at a moderate level. Inner strength primarily influences patients’ self-management behavior through hope, suggesting that medical staff can target hope to help patients build confidence in life after illness, form and accumulate inner strength, thereby promoting their self-management and improving prognosis.

Abstract Background The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future.

The low thermal conductivity of phase change materials restricts their application fields such as thermal storage and electronic equipment cooling. In order to enhance the heat charging capacity of the phase change unit, fractal fins inspired by plant leaves were designed and manufactured. The changes in the solid–liquid interface, temperature distribution and liquid fraction in the phase change units with fractal fins during melting were investigated experimentally and compared units with the conventional rectangular fin. The results show that fractal fins have better heat transfer enhancement effects than rectangular fins because the enhancement of heat conduction exceeds the suppression of natural convection. Increasing the number of fins can also shorten the melting time and make the temperature distribution more uniform. Compared with the one rectangular fin unit, the full melting time of the unit with three fractal fins is reduced by 17.07%, and the bottom surface temperature is reduced by 27.47%. However, increasing the number of fins while using tree-like fractal fins may cause the fins to inhibit natural convection more than enhance heat conduction. The research in this paper will provide a better understanding of the melting process of phase change units with fins and provide data for future numerical simulations.

Abstract Polymerase I and transcript release factor (PTRF) plays a role in the regulation of gene expression and the release of RNA transcripts during transcription, which have been associated with various human diseases. However, the role of PTRF in glioma remains unclear. In this study, RNA sequencing (RNA-seq) data (n = 1022 cases) and whole-exome sequencing (WES) data (n = 286 cases) were used to characterize the PTRF expression features. Gene ontology (GO) functional enrichment analysis was used to assess the biological implication of changes in PTRF expression. As a result, the expression of PTRF was associated with malignant progression in gliomas. Meanwhile, somatic mutational profiles and copy number variations (CNV) revealed the glioma subtypes classified by PTRF expression showed distinct genomic alteration. Furthermore, GO functional enrichment analysis suggested that PTRF expression was associated with cell migration and angiogenesis, particularly during an immune response. Survival analysis confirmed that a high expression of PTRF is associated with a poor prognosis. In summary, PTRF may be a valuable factor for the diagnosis and treatment target of glioma.

Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibi-otics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users com-pared to non-users. Further experiments showed that macro-lides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibi-otic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.

Abstract Background Emerging evidence has highlighted the biological significance of pyroptosis in tumor tumorigenesis and progression. Nonetheless, the potential roles of pyroptosis in tumor immune microenvironment and target therapy of ovarian cancer (OC) remain unknown. Methods In this study, with a series of bioinformatic and machine learning approaches, we comprehensively evaluated genetic alterations and transcriptome profiles of pyroptosis-associated genes (PYAGs) with TCGA-OV datasets. Consensus molecular clustering was performed to determine pyroptosis-associated clusters (PACs) and gene clusters in OC. Subsequently, component analysis algorithm (PCA) was employed to construct Pyrsig score and a highly accurate nomogram was established to evaluate its efficacy. Meanwhile, we systematically performed association analysis for these groups with prognosis, clinical features, TME cell-infiltrating characteristics, drug response and immunotherapeutic efficacy. Immunohistochemistry was conducted to verify molecular expression with clinical samples. Results The somatic mutations and copy number variation (CNV) of 51 PYRGs in OC samples were clarified. Two distinct PACs (PAC1/2) and three gene clusters (A/B/C) were identified based on 1332 OC samples, PAC1 and gene cluster A were significantly associated with favorable overall survival (OS), clinicopathological features and TME cell-infiltrating characteristics. Subsequently, Pyrsig score was successfully established to demonstrate the prognostic value and immune characteristics of pyroptosis in OC, low Pyrsig score, characterized by activated immune cell infiltration, indicated prolonged OS, increased sensitivity of some chemotherapeutic drugs and enhanced efficacy of anti-PD-L1 immunotherapy, Consequently, a nomogram was successfully established to improve the clinical applicability and stability of Pyrsig score. With clinical OC samples, GSDMD and GZMB proteins were validated highly expressed in OC and associated with immune infiltration and Pyrsig score, GZMB and CD8 proteins were regarded as independent prognostic factors of OC. Conclusion This work revealed pyroptosis played a non-negligible role in prognosis value, clinicopathological characteristics and tumor immune infiltration microenvironment in OC, which provided novel insights into identifying and characterizing landscape of tumor immune microenvironment, thereby guiding more effective prognostic evaluation and tailored immunotherapy strategies of OC.

Abstract Obesity is one of the most serious global health problems, with an incidence that increases yearly and coincides with the development of cancer. Adipose tissue macrophages (ATMs) are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression. However, the functions of ATMs on the progression of obesity-associated cancer remain unclear. In this review, we describe the origins, phenotypes, and functions of ATMs. Subsequently, we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment, including the direct exchange of dysfunctional metabolites, inordinate cytokines and other signaling mediators, transfer of extracellular vesicle cargo, and variations in the gut microbiota and its metabolites. A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.

Twisted artificial muscles based on natural fibers are of special interest in diverse fields. However, current research is limited either by the material itself, or by the preparation methods requiring complex processing or specialized equipment. In this study, a facile and green method is introduced to prepare hair artificial muscles with extremely large tensile stroke and fast recovery. The maximum tensile stroke for the hair artificial muscles upon water actuation is as large as 10 000% and the large‐stroke muscles can recover fast in ethanol. In addition, these hair artificial muscles maintain their excellent performance after either 100 water–ethanol stimulation cycles or staying in open air for 5 months. Moreover, the hair artificial muscle is able to contract by 59% when lifting 10 times its own weight, pull a wheel model or climb a long distance under water, and work as a smart water‐sensitive switch. This work provides new insights into the development of simpler and more environmentally friendly methods for preparing advanced natural fiber‐based artificial muscles that have broad applications in soft robotics and biomedical engineering. An interactive preprint version of the article can be found here: https://doi.org/10.22541/au.167385630.01748766/v1.

Abstract Background With the extensive use of aspirin in obstetrics and reproductive medicine, concerns of potentially related congenital anomalies have been raised in previous studies. However, there is a lack of evidence concerning the safety of application of aspirin during pregnancy in Chinese population, especially during the first trimester. Patients and methods We retrospectively included a total of 2,763 patients with 2,856 fetuses (2670 singleton births and 93 pairs of twins), among whom 1,684 took low dose aspirin (LDA) during pregnancy (the LDA group) and the other 1,079 were not exposed to LDA (the control group). The primary outcome was the rate of fetal congenital anomalies, and was compared between the LDA group and the control group. We also conducted logistic regression to examine the potential risk factors of congenital abnormalities. Results The average daily dose of LDA taken was 67.6 mg. The rate of congenital anomalies was comparable between the two groups, suggesting low teratogenicity of LDA application during pregnancy (3.3% vs. 2.8%; P = 0.421). The duration of LDA exposure and the time of LDA exposure showed no association with congenital anomalies. A previous history of fetal congenital anomalies was associated with an increased risk of the recurrence of congenital anomalies in the siblings (adjusted OR = 3.00, 95% CI: 1.00–8.60; P = 0.041). Conclusion Exposure to LDA during pregnancy did not increase the risk of congenital anomalies in the fetus, suggesting that it was safe to apply LDA during pregnancy. A history of previous fetal abnormalities was found to be an independent risk factor of congenital anomalies. Our study suggests that LDA can be safely applied during pregnancy without increasing risks of congenital anomalies.

The catalytic activity of regenerable nanozymes is currently the bottle neck for their wider employment. Here, the authors report on single-atom nanozymes of RhN4, VN4, and Fe-Cu-N6 with higher catalytic activities than natural enzymes, and demonstrate the Rh/VN4 recyclability and scalp healing properties in bioactive sutures.

Abstract Background To investigate whether carboplatin-liposomal paclitaxel neoadjuvant chemotherapy (NACT) benefits patients with locally advanced cervical cancer (LACC) through avoiding or delaying postoperative radiation. Methods A total of 414 patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO 2009) stages IB2–IIA2 were included in the retrospective cohort study, who had received carboplatin-liposomal paclitaxel chemotherapy followed by radical surgery (NACT group) or primary radical surgery (PRS group) between 2007 and 2017 at our hospital. The baseline clinicopathological characteristics at diagnosis, postoperative pathological risk factors, and oncological outcomes after surgery, including postoperative radiation (as adjuvant treatment or treatment of recurrent diseases), progression-free survival (PFS), and overall survival (OS), were compared between the groups. Before treatment, the patients in the NACT group had significantly more advanced tumor stages and larger tumor sizes than those in the PRS group. Results The NACT reduced the tumor volumes remarkedly with a response rate of 62.4%, and the tumors in the NACT group were smaller than those in the PRS group when the patients were subjected to radical surgery. Furthermore, postoperative pathology examination revealed less frequent deep stromal invasion in the NACT group than in the PRS group. According to the presence of pathological risk factors for recurrence, 54.82% of women in the NACT group needed adjuvant radiotherapy, while 60.87% in the PRS group, and in fact, 33.00% of NACT patients and 40.09% of PRS patients received adjuvant radiation. In addition, 8.12% of NACT patients and 9.68% of PRS patients underwent radiotherapy after relapse. The cumulative postoperative radiation rate was significantly lower in the NACT group (P = 0.041), while the differences in 5-year OS and PFS were not statistically significant between the groups. Conclusions NACT reduces the pathological risk factors and the use of radiation without compromising survival in patients with LACC, which may protect younger patients from radiation-related side effects and subsequently improve the quality of life. Trial registration ISRCTN Registry, ISRCTN24104022

PurposeTo investigate the attitudes among cardiac surgery ICU patients and their families regarding life-sustaining treatment.MethodsA total of 172 pairs of patients in the cardiac surgery ICU of Nanjing First Hospital and their family members were enrolled in this study that examined their attitudes toward life-sustaining treatment using a willingness to care for life-sustaining treatment questionnaire. The consistency of the attitudes of patients and family members toward life-sustaining treatment was analyzed by the chi-square test with a paired design.ResultsThe most popular life-sustaining treatment for cardiac ICU patients was noninvasive mechanical ventilation (79.1%); the most unpopular was intra-aortic balloon counterpulsation (48.3%). Most patients and their families had not considered electric defibrillation (65.7%), but most understood and were willing to permit cardiopulmonary resuscitation (76.2%). Few family members agreed that patients should receive a pacemaker (25.0%). The consistency of life support attitudes of patients and their families ranged from 12.8% to 60.5% for procedures both would agree to, 1.2% to 19.8% for procedures they were unwilling to permit, and 0.6% to 39.0% for procedures they had not considered. Kappa values ranged from 0.218 to 0.597 (P

Abstract The molecular underpinnings of acquired resistance to carboplatin are poorly understood and often inconsistent between in vitro modeling studies. After sequential treatment cycles, multiple isogenic clones reached similar levels of resistance, but significant transcriptional heterogeneity. Gene-expression based virtual synchronization of 26,772 single cells from 2 treatment steps and 4 resistant clones was used to evaluate the activity of Hallmark gene sets in proliferative (P) and quiescent (Q) phases. Two behaviors were associated with resistance: (1) broad repression in the P phase observed in all clones in early resistant steps and (2) prevalent induction in Q phase observed in the late treatment step of one clone. Furthermore, the induction of IFNα response in P phase or Wnt-signaling in Q phase were observed in distinct resistant clones. These observations suggest a model of resistance hysteresis, where functional alterations of the P and Q phase states affect the dynamics of the successive transitions between drug exposure and recovery, and prompts for a precise monitoring of single-cell states to develop more effective schedules for, or combination of, chemotherapy treatments.

Abstract Background The aim of this prospective, pilot, single‐arm phase II trial was to evaluate the safety and efficacy of anlotinib combined with etoposide and platinum‐based regimens in the first‐line treatment of extensive‐stage small cell lung cancer (ES‐SCLC). Methods This phase II study was conducted at Fudan University Shanghai Cancer Center between December 2018 and December 2020. All patients received standard chemotherapy (etoposide plus cisplatin/carboplatin) consisting of four courses and anlotinib at 12 mg once per day for 2 weeks followed by a one‐week rest. Anlotinib administration was continued until disease progression, intolerable adverse events (AEs) or patient withdrawal from the study. The primary outcome measure was progression‐free survival (PFS). The secondary outcome measures were overall survival (OS), objective control rate (ORR), disease control rate (DCR) and AEs. Results Thirty‐seven patients were included in this study, and 30 patients were eligible for efficacy analysis. ORR and DCR were 90.0% and 96.7%, respectively. The estimated PFS and OS were 6.0 months (95% CI: 1.1–11.9 months) and 14.0 months (95% CI: 8.6–19.4 months), respectively. No unexpected adverse effects were reported. Hypertension (20/37, 54.1%), anemia (16/37, 43.2%), alopecia (15/37, 40.5%), elevated transaminases (9/37, 24.3%) and alkaline phosphatase (9/37, 24.3%) were the most commonly reported AEs. Thirteen patients (35.1%) reported grade 3–5 AEs. No treatment‐related deaths occurred during this study. Conclusion The addition of anlotinib to standard etoposide/platinum chemotherapy achieved encouraging PFS and OS in previously untreated ES‐SCLC patients, with an acceptable tolerability profile and no new safety signals observed.

Introduction. Sepsis is a common syndrome in critically ill patients. Fibrinogen was reported to be associated with the prognosis of sepsis patients. Materials and Methods. Data was acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression was utilized to estimate the relationship between fibrinogen and inhospital mortality. The cumulative incidence of mortality by fibrinogen level was estimated through the Kaplan-Meier curve. Restricted cubic spline (RCS) was used to assess nonlinear relationship. Subgroup analysis was also conducted to evaluate the robustness of the association between fibrinogen and inhospital mortality. Propensity score matching (PSM) was applied to adjust for confounding factors. Results. A total of 3365 patients, including 2031 survivors and 1334 nonsurvivors, were enrolled in our study. The survivors had a significantly elevated levels of fibrinogen compared with the deceased. The elevated level of fibrinogen was significantly associated with a decrease in mortality in multivariate Cox regression before and after PSM (HR 0.66, P

Abstract The heterogeneity and the complex cellular architecture have a crucial effect on breast cancer progression and response to treatment. However, deciphering the neoplastic subtypes and their spatial organization is still challenging. Here, we combine single-nucleus RNA sequencing (snRNA-seq) with a microarray-based spatial transcriptomics (ST) to identify cell populations and their spatial distribution in breast cancer tissues. Malignant cells are clustered into distinct subpopulations. These cell clusters not only have diverse features, origins and functions, but also emerge to the crosstalk within subtypes. Furthermore, we find that these subclusters are mapped in distinct tissue regions, where discrepant enrichment of stromal cell types are observed. We also inferred the abundance of these tumorous subpopulations by deconvolution of large breast cancer RNA-seq cohorts, revealing differential association with patient survival and therapeutic response. Our study provides a novel insight for the cellular architecture of breast cancer and potential therapeutic strategies.

Abstract Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.

Abstract Tumor progression requires bidirectional cell-to-cell communication within a complex tumor microenvironment (TME). Extracellular vesicles (EVs) as carriers have the capacity to shuttle regulatory molecules, including nucleic acids, proteins, and lipids, between cancer cells and multiple stromal cells, inducing remarkable phenotypic alterations in the TME. Recently proposed the concept “immunogenic stress”, which means in some stressed microenvironment, cancer cells can release EVs containing specific immunoregulatory mediators, depending on the initiating stress-associated pathway, thereby provoking the changes of immune status in the TME. Considerable evidence has revealed that the intracellular mechanisms underlying the response to diverse stresses are mainly autophagy, endoplasmic reticulum (ER) stress reactions and the DNA damage response (DDR). In addition, the activation of immunogenic stress responses endows hosts with immune surveillance capacity; in contrast, several cargoes in EVs under immunogenic stress trigger a passive immune response by mediating the function of immune cells. This review discusses the current understanding of the immunogenic stress pathways in cancer and describes the interrelation between EVs and immunogenic stress to propose potential treatment strategies and biomarkers.

Abstract Objective To compare three commonly used low-molecular-weight heparins (LWMHs) in the treatment of recurrent spontaneous abortion (RSA) by evaluating the anti-Xa peak levels and adverse reactions. Methods In this single-center, observational study, we enrolled 310 patients with RSA in whom anti-Xa levels were measured during pregnancy. Patients were divided into three groups according to the LMWH they used: the nadroparin group, enoxaparin group and dalteparin group. We compared the peak anti-Xa levels and the coagulation status of each group, and analyzed the incidence of adverse reactions, including local allergy, liver and renal dysfunction, and the impact on platelet. Results Patients in the enoxaparin group had a higher anti-Xa peak level than those in the nadroparin group (0.80 ± 0.22 IU/ml vs. 0.61 ± 0.24 IU/ml; P

Abstract Background Neurotrauma is a worldwide public health problem which can be divided into primary and secondary damge. The primary damge is caused by external forces and triggers the overproduction of peroxides and superoxides, leading to long-lasting secondary damage including oxidative stress, wound infection and immunological reactions. The emerging catalysts have shown great potential in the treatment of brain injury and neurogenic inflammation, but are limited to biosafety issues and delivery efficiency. Results Herein, we proposed the noninvasive delivery route to brain trauma by employing highly active gold clusters with enzyme-like activity to achieve the early intervention. The decomposition rate to H2O2 of the ultrasmall gold clusters is 10 times that of glassy carbon (GC) electrodes, indicating excellent catalytic activity. The gold clusters can relieve the oxidative stress and decrease the excessive O2 ·− and H2O2 both in vitro and in vivo. Besides, gold clusters can accelerate the wound healing of brain trauma and alleviate inflammation via inhibiting the activation of astrocytes and microglia through noninvasive adminstration. decrease the peroxide and superoxide of brain tissue. Conclusions Present work shows noninvasive treatment is a promising route for early intervention of brain trauma.

ObjectivesTo investigate the prevalence of adverse pregnancy outcomes (APOs) in women and the impact of pre-pregnancy couples' genital Chlamydia Trachomatis (GCT) infection and other infections on APOs.Study designData on genital infections were collected from the Free Pre-pregnancy Health Check (FPHC) in Shenzhen, China. Data on APOs were collected from a 1-year telephone follow-up of pregnancy status and subsequent pregnancy outcomes.MethodsAPO data were used to count adverse outcomes, and logistic regression was conducted to determine the association between APOs and GCT infection.ResultsFrom December 2018 to December 2019, among 4,429 couples who underwent FPHC; 1,925 were pregnant, and 1,816 couples were tracked for pregnancy outcomes, including 1,471 normal pregnancies and 345 (19.00%) APOs. The rest of 109 pregnant couples did not answer the phone or refused to answer the pregnancy outcome during the follow-up. Among APOs, the number of spontaneous abortions was 122 (35.36%), the number of macrosomia was 85 (24.64%), the number of low birth weight (LBW) & preterm births (PTB) was 39 (11.30%), the number of LBW was 34 (9.86%), and the number of PTB was 31 (8.99%). The prevalence of GCT infection in females and males was 4.24% [95% Confidence Interval, (CI): 3.41–5.27%] and 3.58% (95% CI: 2.79–4.57%), respectively. More than half (52.69%, 49/93) of the couples were GCT-concordant. The prevalence of APOs in couples without GCT infection was 18.74% (332/1,772). The prevalence of APOs in female GCT-discordant was 32.14% (9/28), and the prevalence of APOs in male GCT-discordant was 25% (4/16). The prevalence of APOs in GCT-concordant was 12.24% (6/49). Multivariable analysis indicated that females 30–35 years old [adjusted Odds Ratio (aOR) = 1.08, 95% CI: 1.01–1.17] and over 35 years old (aOR = 1.16, 95% CI: 1.03–1.32) were more likely to experiencing APOs.ConclusionAlthough only women's age was found to be associated with APOs, the prevalence of APOs with GCT-discordant in couples, especially female GCT-discordant, was higher than in those without infection or who were GCT-concordant, suggesting that these groups, especially in older women, should be paid more attention to in follow-ups to improve reproductive health.

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that is characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are the most abundant immune cell type within TAME, although their diversity in the TAME is not clear. We first reveal that infiltration of M2-like macrophages in the TAME is associated with poor survival in breast cancer. To explore lipid-associated alterations in the TAME, we also detected the levels of FFAs transporters including fatty acid binding proteins (FABPs) and fatty acid transport protein 1 (FATP1). The results indicated that expression of fatty acid transporters in the TAME is tightly linked to the function of macrophages and predicts survival in breast cancer. To explore the impact of FFAs transporters on the function of macrophages, we performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Consequently, we identified a special subpopulation of macrophages defined as lipid-associated macrophages (LAMs), highly expressed macrophage markers (CD163, SPP1 and C1QC), genes involved in lipid metabolism (FABP3, FABP4, FABP5, LPL and LIPA) and some lipid receptors (LGALS3 and TREM2). Functionally, LAMs were characterized by a canonical functional signature of M2-like macrophages, lipid accumulation and enhancing phagocytosis, and they were mostly distributed in tumor-adipose junctional regions. Finally, the allograft cancer mouse models confirmed that LAMs depletion in the TAME synergizes the antitumorigenic effects of anti-PD1 therapy. In summary, we defined a novel subtype of macrophages in the TAME, that has unique features and clinical outcomes.

BackgroundMany studies have focused on the distribution and specific clinical symptoms caused by Chlamydia trachomatis. Still, relatively few studies have focused on the associations between Chlamydia trachomatis genotypes and cervical intraepithelial lesions.ObjectivesThis study was conducted to determine the distribution of Chlamydia trachomatis genotypes and its associations with cervical intraepithelial lesions among women of reproductive age. The presence of other STIs coinfection was also evaluated.Method375 Chlamydia trachomatis positive cervical swabs collected from women of reproductive age were analyzed though molecular assay. Multivariate logistic regression analyses (covariates include contraception, gravidity (≥1), abnormal vaginal discharge, adverse pregnancy outcomes, reproductive tract symptoms and abnormal cervical cytology) were performed to evaluate the associations between Chlamydia trachomatis genotypes and cervical intraepithelial lesions and genital clinical symptoms.ResultsAmong 375 Chlamydia trachomatis positive cervical swabs, the prevalence of coinfection with Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginitis, Vulvovaginal candidiasis, and HPV were 0.8%, 2.7%, 2.4%, 10.1% and 15.5%, respectively. 306 were genotyped successfully, and nine genotypes were identified. The most common genovar was E (25.16%, 77/306), followed by J (22.55%, 69/306), F (17%, 52/306), D (14.4%, 44/306), K (7.2%, 22/306), G (6.9%, 21/306), H (5.2%, 16/306), B (1.0%, 3/306), Ia (0.7%, 2/306). Genotype H was associated with abnormal cervical cytology [p = 0.006, aOR = 8.16 (1.86–36.6)]. However, this study observed no association between Chlamydia trachomatis genotypes and any genital clinical symptoms.ConclusionsChlamydia trachomatis genotype H may be a high risk factor for cervical intraepithelial lesions, which is useful for treatment and management measures for patients with cervical intraepithelial lesions.

BackgroundThe association between hematologic parameters and anti-programmed death-1 (PD-1) inhibitors was generally examined without considering therapy lines and medicine types. The study was aimed to identify potential hematologic biomarkers associated with clinical outcome in patients with non-small cell lung cancer (NSCLC) treated with first-line pembrolizumab and subsequent-line nivolumab.Materials and methods161 NSCLC patients were categorized into first-line pembrolizumab group (pembrolizumab group) and subsequent-line nivolumab group (nivolumab group). Univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of hematologic parameters for clinical outcomes.ResultsThe median progression-free survival (mPFS) was 9.6 months in the pembrolizumab group and 4.1 months in the nivolumab group (HR =1.61; P = 0.012); the median overall survival (mOS) was not reached in the pembrolizumab group and 17.7 months in the nivolumab group (HR =1.37; P = 0.23). Of the 79 patients in the pembrolizumab group, baseline PD-L1 tumor proportion score (TPS)≥1% was an independent factor of longer PFS and OS. Age≥60 years, absolute platelet count (APC)≥220×109/L and platelet-to-lymphocyte ratio (PLR)≥120 were associated with inferior PFS. Of the 82 patients in the nivolumab group, absolute neutrophil count (ANC)≥3×109/L was associated with longer PFS, while LDH (lactate dehydrogenase)≥160 U/L was associated with inferior PFS and derived neutrophil-to-lymphocyte ratio (dNLR)≥1.2 was associated with longer OS.ConclusionOur study identified multiple clinically accessible prognostic biomarkers in the peripheral blood in both the pembrolizumab and nivolumab subgroups.

BackgroundRenal sarcoma (RS) is rarely seen in clinical practice. The purpose of this study was to develop a prognostic nomogram model, which could predict the probability of overall survival (OS) and cancer-specific survival (CSS) in adult patients with RS.MethodsPatients diagnosed with RS were recruited from the SEER database between 2004 and 2015, and randomized to two cohorts: the training cohort and the validation cohort. Uni- and multivariate Cox regression analyses in the training cohort were used to screen independent prognostic factors for OS and CSS. Prognostic nomograms for OS and CSS were created separately for adult RS patients based on independent risk factors. The area under the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomograms.ResultsA total of 232 eligible patients were recruited, including 162 in the training cohort and 70 in the validation cohort. Sex, histological type, SEER stage, and surgery were independent prognostic factors for OS, while histological type, SEER stage, surgery, chemotherapy were independent prognostic factors for CSS. Based on the above independent prognostic factors, prognostic nomograms for OS and CSS were created respectively. In the training cohort, the AUCs of the nomograms for OS and CSS were 0.742 and 0.733, respectively. In the validation cohort, the AUCs of the nomograms for OS and CSS were 0.837 and 0.758, respectively. The calibration curves of the nomograms showed high consistencies between the predicted and actual survival rates. Finally, the DCA demonstrated that the nomograms in the wide high-risk threshold had a higher net benefit than the SEER stage.ConclusionA prognostic nomogram for renal sarcoma was created and validated for reliability and usefulness in our study, which assisted urologists in accurately assessing the prognosis of adult RS patients.

Immune responses in nonlymphoid tissues play a vital role in the maintenance of homeostasis. Lots of evidence supports that tissue-specific immune cells provide defense against tumor through the localization in different tissue throughout the body, and can be regulated by diverse factors. Accordingly, the distribution of nervous tissue is also tissue-specific which is essential in the growth of corresponding organs, and the occurrence and development of tumor. Although there have been many mature perspectives on the neuroendocrine regulation in tumor microenvironment, the neuroendocrine regulation of tissue-specific immune cells has not yet been summarized. In this review, we focus on how tissue immune responses are influenced by autonomic nervous system, sensory nerves, and various neuroendocrine factors and reversely how tissue-specific immune cells communicate with neuroendocrine system through releasing different factors. Furthermore, we pay attention to the potential mechanisms of neuroendocrine-tissue specific immunity axis involved in tumors. This may provide new insights for the immunotherapy of tumors in the future.

BackgroundBody mass index (BMI) is a vital risk factor for kidney stones, but physical activity may reduce the incidence of kidney stones. However, it remains unknown whether physical activity reduces the effect of high BMI on kidney stones in diabetes participants.MethodsWe included clinical information from 4,008 adult participants with diabetes from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2018. Univariate and multivariate logistic regression analyses were used to analyze the relationship between BMI and kidney stones, as well as the risk of BMI and kidney stones in different physical activity subgroups.ResultsA total of 4,008 diabetic participants were included in this study, of whom 652 (16.3%) self-reported a history of kidney stones. Logistic regression analysis showed a positive association between BMI and kidney stones. After adjusting for other confounders, the adjusted ORs for the risk of kidney stones was 1.514 (95% CI, 1.134–2.022, p = 0.005) for participants with BMI ≥30 kg/m2 among all participants; the risk of kidney stones was elevated (OR = 1.572, 95% CI, 1.134–2.022, p = 0.005) in group without physical activity, and a reduced risk (OR = 1.421, 95% CI, 0.847–2.382, p = 0.183) in the group with physical activity. Furthermore, similar results were found in most subgroups.ConclusionOur study suggests that high BMI is a risk factor for diabetes kidney stone participants and that physical activity may moderate this relationship to some extent.

Evaluation of the deviation zone based on discrete measured points is crucial for quality control in manufacturing and metrology. However, deviation-zone evaluation is a highly nonlinear problem that is difficult to solve using traditional numerical optimization methods. Swarm intelligence has many advantages in solving this problem: it produces gradient-free, high-quality solutions and is characterized by its ease of implementation. Therefore, this study applies an improved Harris hawks algorithm (HHO) to tackle the problem. The average fitness is applied to replace the random operator in the exploration phase to solve the problem of conflicting exploration strategies due to randomness. In addition, the salp swarm algorithm (SSA) with a nonlinear inertia weight is embedded into the HHO, such that the superior explorative ability of SSA can fill the gap in the exploration of HHO. Finally, the optimal solution is greedily selected between SSA-based individuals and HHO-based individuals. The effectiveness of the proposed improved HHO optimizer is checked through a comparison with other swarm intelligence methods in typical benchmark problems. Moreover, the experimental results of form deviation-zone evaluation on primitive geometries show that the improved method can accurately solve various form deviations, providing an effective general solution for primitive geometries in the manufacturing and metrology fields.

BackgroundOrthotopic neobladder reconstruction has become the preferred method of urinary diversion after radical cystectomy in major medical centers. We performed modified Y-shaped ileal orthotopic neobladder reconstruction and presented the functional results and postoperative complications of the modified surgery.MethodsWe included 21 patients with bladder cancer who underwent radical cystectomy at our center between February 2019 and December 2019. All patients underwent robotic-assisted laparoscopic radical cystectomy and lymph node dissection plus modified Y-shaped ileal orthotopic neobladder reconstruction. We collected the demographic and pathological history of the patients, and perioperative and postoperative functional outcomes and postoperative complications were recorded.ResultsAll surgeries were successful and no serious postoperative complications occurred. The mean operative time was 321.43 ± 54.75 min, including 101.67 ± 10.88 min required for neobladder reconstruction. Liquid intake was encouraged about 5 days after surgery, stent and catheter were removed after 13.52 ± 3.28 days, and the patients were discharged 1–2 days after removing the catheter. No ureteral anastomotic and neobladder urethral anastomotic strictures occurred. The volume of the neobladder at 1-year post-surgery was 195.24 ± 16.07 mL and the maximum urinary flow rate was 20.64 ± 2.22 mL/s.ConclusionWe describe the robotic-assisted modified Y-shaped ileal orthotopic neobladder reconstruction performed at our center, which requires a simple suture and short neobladder construction time, minimizes the occurrence of anastomotic stenosis, facilitates smooth patient emptying, and is clinically scalable and applicable.

Decidual polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are essential to immune tolerance during pregnancy. A reduction in the number of these cells is associated with unexplained recurrent pregnancy loss (URPL). In our previous study, we reported that PMN-MDSCs are a group of mature neutrophils that are activated by the decidua microenvironment. In the present study, we show that the decidua microenvironment induces substantial lipid accumulation in neutrophils during their differentiation to PMN-MDSCs. Lower levels of lipid accumulation are detected in PMN-MDSCs from URPL patients, and the amount of lipid in the PMN-MDSCs is positively correlated with the proportion of PMN-MDSCs. Next, we demonstrate that decidua-derived IL6 with the presence of arachidonic acid upregulates fatty acid-binding protein 5 (FABP5) via the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Fy -60ABP5 then continuously stimulates intracellular lipid accumulation. Increased intracellular lipid accumulation mediates arachidonic acid metabolism, a pathway that is significantly activated by the induction of the decidua microenvironment, to stimulate the synthesis of prostaglandin E2 (PGE2) and finally induce the differentiation of PMN-MDSCs. To summarize, decidua-derived IL6 facilitates the differentiation of PMN-MDSCs from neutrophils via the pSTAT3/FABP5/PGE2 pathway. Defects in the process may result in impaired differentiation and dysfunction of PMN-MDSCs in URPL. These findings enhance our understanding of the physiological mechanisms of immune tolerance in pregnancy and provide therapeutic options for URPL.

BackgroundThe aim of this study was to investigate the prognostic role of the dynamics of sarcopenia in the pre- to postoperative for patients with renal cell carcinoma (RCC) undergoing laparoscopic nephrectomy.MethodsThis study included 261 patients who underwent laparoscopic nephrectomy between 2014 and 2019. The skeletal muscle index (SMI) of the L3 lumbar region was used to assess sarcopenia. The overall population was divided into four groups according to the dynamics of sarcopenia from pre- to postoperative: group 1 (both pre- and postoperative sarcopenia), group 2 (preoperative non-sarcopenia to postoperative sarcopenia), group 3 (preoperative sarcopenia to postoperative non-sarcopenia), and group 4 (both pre- and postoperative non-sarcopenia). The endpoints of the study were overall survival (OS) and cancer-specific survival (CSS).ResultsOf the 261 patients who underwent laparoscopic nephrectomy, 103 (39.5%) had preoperative sarcopenia and 183 (70.1%) had postoperative sarcopenia. Patients with pre- or postoperative sarcopenia had poor survival outcomes. Sarcopenia dynamic was a better predictor of OS (AUC = 0.737) and CSS (AUC = 0.696) in patients with RCC than pre- and postoperative sarcopenia, and patients in group 4 of sarcopenia dynamic had the best OS and CSS. In addition, sarcopenia dynamics was an independent risk factor for OS and CSS, with a 94.5% reduction in OS risk (HR = 0.055, 95% CI 0.007–0.407, p = 0.003) and a 91.9% reduction in CSS risk (HR = 0.081, 95% CI 0.011–0.616, p = 0.015) in the group 4 compared with the group 1.ConclusionOur study is the first to assess the prognostic value of pre- and postoperative sarcopenia dynamics in patients with RCC.

Abstract Autophagy is a prominent mechanism to preserve homeostasis and the response to intracellular or extracellular stress. Autophagic degradation can be selectively targeted to dysfunctional subcellular compartments. Centrosome homeostasis is pivotal for healthy proliferating cells, but centrosome aberration is a hallmark of diverse human disorders. Recently, a process called centrosome-phagy has been identified. The process involves a panel of centrosomal proteins and centrosome-related pathways that mediate the specific degradation of centrosomal components via the autophagic machinery. Although autophagy normally mediates centrosome homeostasis, autophagy defects facilitate ageing and multiple human diseases, such as ciliopathies and cancer, which benefit from centrosome aberration. Here, we discuss the molecular systems that trigger centrosome-phagy and its role in human disorders.

Abstract Cancer-associated adipocytes (CAAs), as a main component of the tumor-adipose microenvironment (TAME), have various functions, including remodeling the extracellular matrix and interacting with tumor cells or infiltrated leukocytes through a variety of mutual signals. Here, we summarize the primary interplay among CAAs, the immune response and cancer with a focus on the mechanistic aspects of these relationships. Finally, unifying our understanding of CAAs with the immune cell function may be an effective method to enhance the efficacy of immunotherapeutic and conventional treatments.

Abstract Breast cancer (BC) is the most common malignancy among women. Mesenteric estrogen-dependent adipogenesis gene (MEDAG) was first reported as a novel adipogenic gene, and its involvement and mechanism in visceral adiposity were analyzed. However, the role of MEDAG in BC is unclear. The biological roles and corresponding mechanisms were investigated in vitro and in vivo. We found that MEDAG was highly expressed in BC samples and that a high MEDAG expression was correlated with clinicopathological characteristics and poor survival in BC patients. MEDAG knockdown inhibited cell proliferation, invasion, and migration; triggered epithelial-to-mesenchymal transition (EMT); and enhanced epirubicin sensitivity in vitro. The opposite results were observed in MEDAG-overexpressing cells. The inhibition of MEDAG suppressed tumor growth and metastasis in vivo. Mechanistically, MEDAG knockdown led to decreased phosphorylation levels of AKT, increased levels of p-AMPK, and reduced levels of p-mTOR, while the overexpression of MEDAG had the opposite effects. Moreover, the activation of p-AKT and inhibition of p-AMPK restored the effect of MEDAG on EMT and chemosensitivity in BC cell lines, indicating that MEDAG functions as an oncogene by regulating the AKT/AMPK/mTOR pathway. MEDAG regulates BC progression and EMT via the AKT/AMPK/mTOR pathway and reduces chemosensitivity in BC cells. Therefore, MEDAG is a promising target for BC.

Artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have emerged to tackle limitations of noble metals or transition metal oxides. Here, the authors report Au25 clusterzymes which are endowed with high catalytic activity and selectivity in a range of enzyme-mimicking reactions.

This paper introduces a robust normal estimation method for point cloud data that can handle both smooth and sharp features. Our method is based on the inclusion of neighborhood recognition into the normal mollification process in the neighborhood of the current point: First, the point cloud surfaces are assigned normals via a normal estimator of robust location (NERL), which guarantees the reliability of the smooth region normals, and then a robust feature point recognition method is proposed to identify points around sharp features accurately. Furthermore, Gaussian maps and clustering are adopted for feature points to seek a rough isotropic neighborhood for the first-stage normal mollification. In order to further deal with non-uniform sampling or various complex scenes efficiently, the second-stage normal mollification based on residual is proposed. The proposed method was experimentally validated on synthetic and real-world datasets and compared to state-of-the-art methods.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12943-018-0899-5.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-019-1210-3.

Objective To investigate the efficacy and safety of cranio ⁃ orbital approach for the removal of cavernous sinus ⁃ orbital communication trigeminal schwannomas. Methods and Results A total of 23 patients with cavernous sinus⁃orbital communication trigeminal schwannoma were included from January 2013 to January 2019, the combined cranio⁃orbital approach (modified Dolenc approach combined with supraorbital approach) was used for surgical resection of tumors. Total tumor resection was performed in 20 cases and nearly total resection in 3 cases. Thirteen patients with preoperative visual loss, 7 of them further decreased visual acuity; 5 cases with preoperative eye movement disorder and/or ptosis, 3 cases with residual eye movement disorder, and 11 cases appeared new eye movement disorders after surgery. None of the 23 cases occurred cerebrospinal fluid leakage, intracranial hematoma or intracranial infection occurred, no death and no tumor recurrence case. Conclusions Cavernous sinus⁃orbital communication trigeminal schwannoma, due to the special tumor occurrence site and surrounding anatomical structure, was easy to cause complications such as visual loss and eye movement disorder during operation. The combined cranio⁃ orbital approach was used, it may increase the total resection rate, and also show relatively low surgical complications rate. DOI：10.3969/j.issn.1672⁃6731.2020.12.011

Abstract Background Ultrasound (US) imaging is known to underestimate tumor size in clinical. This study is aimed to compare the size measurements of hepatocellular carcinoma (HCC) in three US imaging modalities, i.e. two-dimensional (2D) imaging, the arterial phase (AP) and the late phase (LP) imaging of contrast-enhanced US (CEUS). Methods Fifty-eight clinically proved HCC patients were included. The 2D and CEUS imaging were performed with Siemens S2000, Philips iu22 and BioSound Twice. 2.5 mL of SonoVue® was injected for every CEUS performance. Two physicians measured the maximal longitudinal and the transverse diameters of the tumors in 2D, the AP and the LP of CEUS from one image section. The three measurements were compared by paired t test. Results The mean longitudinal diameter of HCC appeared to be maximal in the AP (4.73 ± 2.04 cm) of CEUS and minimal in the LP (3.98 ± 1.99 cm) of CEUS. The 2D diameter (4.26 ± 2.07 cm) was in the middle between two CEUS measurements. There were significant differences between any two measurements. Conclusion There is size difference between the three kinds of HCC measurement. It appeared to be maximal in the AP of CEUS and minimal in the LP. The 2D diameter was in the middle.

AimTo assess the effect of preoperative blood glucose (POBG) levels on the length of stay (LOS) in patients with kidney stones undergoing percutaneous nephrolithotomy (PCNL).MethodsWe conducted a retrospective study of patients who underwent PCNL at the Zhongda Hospital of Southeast University from 2013 to 2019. The relationship between POBG level and LOS was investigated by dose-response analysis curves of restricted cubic spline function.ResultsWe included 310 patients and divided them into three groups ( 2 weeks than patients with POBG levels 2 weeks. Similar results were observed in the subgroups analysis.ConclusionWe demonstrated that higher POBG levels were significantly associated with longer LOS in patients with kidney stones undergoing PCNL.

Background: In renal clear cell carcinoma, a common cancer of the urinary system, 25–30% patients are metastatic at initial diagnosis and 20–30% patients have a tendency of recurrence and metastasis after local surgery. With the rapid development of tumor immunology, immune agents have brought new directions to tumor therapy. However, no relevant studies have explored the role of immune-related genes in kidney cancer metastasis.Methods: Co-expressed metastatic immune-related differentially expressed genes (mIR-DEGs) were screened by GSE12606, GSE47352, and immunorelated genes. Then, differential expression analysis, prognostic analysis, and univariate and multivariate Cox regression analysis in KIRC were performed to determine independent prognostic factors associated, and the risk prognostic model was established. The correlation of hub mIR-DEGs with clinicopathological factors, immune invasion, and immune checkpoints was analyzed, and the expression of hub mIR-DEGs and their effect on tumor were re-evaluated by OCLR scores in KIRC.Results: By comprehensive bioassay, we found that FGF17, PRKCG, SSTR1, and SCTR were mIR-DEGs with independent prognostic values, which were significantly associated with clinicopathological factors and immune checkpoint–related genes. The risk prognostics model built on this basis had good predictive potential. In addition, targeted small molecule drugs, including calmidazolium and sulfasalazine, were predicted for mIR-DEGs. Further experimental results were consistent with the bioinformatics analysis.Conclusion: This study preliminarily confirmed that FGF17, PRKCG, SSTR1, and SCTR were targeted genes affecting renal cancer metastasis and related immune responses and can be used as potential therapeutic targets and prognostic biomarkers for renal cancer. Preliminary validation found that PRKCG and SSTR1 were consistent with predictions.

BNIP3 is a proapoptotic protein that mediates apoptosis, necrosis and autophagy. However, the involvement of BNIP3 in cisplatin‐induced apoptosis in ovarian cancer is not clear. In this study, we examined the role of BNIP3 in ovarian cancer during cisplatin treatment and its correlation with clinical outcomes. We first measured cisplatin cytotoxicity and BNIP3 levels before and after cisplatin exposure for ovarian cancer cell lines A2780, SKOV3, OVCAR4, OV2008, ES2 and HO8910. BNIP3 was observed to be differentially expressed in these cell lines, and cisplatin induced a significant increase in BNIP3 levels in A2780 and OVCAR4. BNIP3 knockdown with siRNA in A2780 and OVCAR4 significantly reduced cisplatin cytotoxicity in these two cell lines and alleviated cisplatin‐induced apoptosis. We searched the online databases Gene Expression Omnibus and The Cancer Genome Atlas to analyze the correlation between BNIP3 level and overall survival and progression‐free survival in patients with ovarian cancer. Pooled analyses showed that higher BNIP3 level was correlated with poorer overall survival (95% confidence intervals; hazard ratio = 1.18, 1.04–1.34; P = 0.013) and progression‐free survival (95% confidence intervals; hazard ratio = 1.26, 1.10–1.43; P = 0.00049). However, the results of individual datasets and stratification analyses of histology, FIGO (Federation Internationale de Gynecolgie et d’Obstetrique) stage, chemotherapy regimen and P53 mutation status varied. These findings indicate that cisplatin‐induced apoptosis is dependent on BNIP3 level in ovarian cancer cell lines. Targeting BNIP3 may therefore be a potential way of restoring cisplatin sensitivity.