Nimotuzumab plus concurrent chemo-radiotherapy in unresectable locally advanced oesophageal squamous cell carcinoma (ESCC): interim analysis from a Phase 3 clinical trial.

BACKGROUND: This prospectively randomised, double-blinded, placebo-controlled, multicenter Phase 3 clinical trial was conducted to assess the efficacy and safety profile of nimotuzumab (nimo) plus concurrent chemo-radiotherapy (CCRT) in patients with unresectable locally advanced ESCC. METHODS: Patients were randomly assigned (1:1) to receive CCRT plus nimotuzumab or placebo. The primary endpoint was overall survival (OS). In addition, interim analysis for short-term response rate was pre-defined. RESULTS: A total of 201 patients were randomised into two groups. Eighty patients in the nimo group and eighty-two in the placebo group were evaluable. Three to six months after treatment, 26 (32.5%) patients achieved complete response (CR) in the nimo group, and 10 (12.2%) in the placebo group (P = 0.002). The ORR of the nimo group was significantly higher than the placebo group (93.8% vs. 72.0%, P < 0.001). The two groups' grade 3-5 adverse drug reactions were 11.1% vs. 10.9% (P > 0.05). CONCLUSIONS: Nimotuzumab, in combination with chemo-radiotherapy, increased the CRR and ORR with a good safety profile. The OS is needed to be followed and finally analysed. CLINICAL TRIAL REGISTRATION: NCT02409186.

Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice.

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.

Retinal OCTA Image Segmentation Based on Global Contrastive Learning.

The automatic segmentation of retinal vessels is of great significance for the analysis and diagnosis of retinal related diseases. However, the imbalanced data in retinal vascular images remain a great challenge. Current image segmentation methods based on deep learning almost always focus on local information in a single image while ignoring the global information of the entire dataset. To solve the problem of data imbalance in optical coherence tomography angiography (OCTA) datasets, this paper proposes a medical image segmentation method (contrastive OCTA segmentation net, COSNet) based on global contrastive learning. First, the feature extraction module extracts the features of OCTA image input and maps them to the segment head and the multilayer perceptron (MLP) head, respectively. Second, a contrastive learning module saves the pixel queue and pixel embedding of each category in the feature map into the memory bank, generates sample pairs through a mixed sampling strategy to construct a new contrastive loss function, and forces the network to learn local information and global information simultaneously. Finally, the segmented image is fine tuned to restore positional information of deep vessels. The experimental results show the proposed method can improve the accuracy (ACC), the area under the curve (AUC), and other evaluation indexes of image segmentation compared with the existing methods. This method could accomplish segmentation tasks in imbalanced data and extend to other segmentation tasks.

Is hand grip strength a necessary supportive index in the phenotypic criteria of the GLIM-based diagnosis of malnutrition in patients with cancer?

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) has the potential to gain global acceptance for diagnosing malnutrition. Of which, calf circumference (CC) was proposed as an alternative to evaluate the reduced muscle mass (RMM). The present study aimed to evaluate whether including the hand grip strength (HGS) was helpful for diagnosing malnutrition under the GLIM framework. METHODS: We performed a multicenter, observational cohort study including 3998 patients with cancer at two teaching hospitals. The RMM criterion was separately assessed using the calf circumference (CC), or the CC and HGS combined. Accordingly, two methods of GLIM diagnosis were independently developed to determine the nutritional status of the patients. The diagnostic concordance, baseline characteristics, and outcomes of patients were compared across the malnourished-CC-HGS, malnourished-CC+HGS, and well-nourished groups. The Patient-Generated Subjective Global Assessment (PG-SGA) was used as a comparator to identify the optimal method. RESULTS: Malnutrition was identified in 1120 (28%) patients by the CC method and 1060 (26.5%) patients by the CC+HGS method. Compared to the well-nourished group, the malnourished-CC+HGS group (60 patients, 1.5%) had poorer nutritional characteristics, poorer Karnofsky Performance Status scores, poorer global quality of life scores, and higher Nutritional Risk Screening 2002 scores. The severity of malnutrition diagnosed using the CC method (Kappa = 0.136) showed higher agreement with the PG-SGA than the CC+HGS method (Kappa = 0.127). CONCLUSION: Compared to CC+HGS, the CC alone appears to be adequate to evaluate RMM under the GLIM framework. A simpler method might facilitate the application of these criteria in clinical settings by increasing efficacy and minimizing missed diagnoses.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

Mesenchymal stem cells increase heme oxygenase 1-activated autophagy in treatment of acute liver failure.

In recent years, transplantation of mesenchymal stem cells (MSCs) has attracted much attention as a potential cell-based therapy for acute liver failure (ALF). As an inducible enzyme, heme oxygenase 1 (HO-1) has been reported to have cytoprotective, anti-apoptotic and immunoregulatory effects. Autophagy, a conserved catabolic process in cells, may be an important pathway for MSCs to treat ALF. In this study, we aimed to explore whether MSCs treat ALF by regulating autophagy and whether HO-1 was involved in the same pathway. Bone marrow-derived MSCs were isolated from Sprague-Dawley rats and cultured according to an established protocol. Co-culture systems of MSCs and hepatocytes were used to assess autophagy in the treatment of ALF. Meanwhile, MSCs were transplanted into rats with d-galactosamine (Gal)-induced ALF. Autophagy inhibitor (3-methyladenine, 3-MA), HO-1 inhibitor (zinc protoporphyrin, ZnPP) and PI3K specific inhibitor (LY294002) were employed in the study. Blood samples and liver tissues were collected before euthanasia. Survival rate, liver function, inflammatory factors, histology, Ki67 and TUNEL staining were determined. MSCs transplantation alleviated ALF both in vivo and in vitro. Autophagy and autophagy-related proteins were significantly up-regulated during MSCs treatment. 3-MA attenuated the therapeutic effect of MSCs. Administration of LY294002 before ALF induction inhibited hepatocyte autophagy. During the MSCs treatment, the HO-1 expression was increased, while inhibiting HO-1 attenuated the therapeutic effect of MSCs as well as hepatocyte autophagy. These findings suggested MSCs could alleviate ALF by increasing the HO-1 expression, which played an important role in activating autophagy through PI3K/AKT signaling pathway.

Identification of a RNA-seq-based signature to improve prognostics for uterine sarcoma.

OBJECTIVE: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality. This study focused on the identification of a RNA-Seq expression signature for prognosis prediction in uterine sarcoma. METHODS: We obtained RNA-Seq expression profiles from The Cancer Genome Atlas database, and differentially expressed genes were identified between US tissues and normal tissues. Univariate Cox proportional hazards regression analysis and LASSO Cox model were performed to identify and construct the prognostic gene signature. Time-dependent receiver operating characteristic, Kaplan-Meier curve and multivariate Cox regression analysis were used to assess the prognostic capacity of the six-gene signature. The nomogram was developed including prognostic signature and independent clinical factors to predict the overall survival (OS) of US patients. The functional enrichment and somatic mutation analysis were also analyzed by bioinformatics to understand the molecular mechanisms. RESULTS: This study identified a prognostic signature based on 6 genes: FGF23, TLX2, TIFAB, RNF223, HIST1H3A and AADACL4. In the training group, the median OS in the high- and low-risk groups was 19.6 vs 88.1 months (HR, 0.1412, 95% CI: 0.03295 - 0.6054; P = 0.002), respectively. In the testing group, the median OS in the high- and low-risk groups were 30 vs NR (not reach) months (HR, <0.0001, 95% CI: 0 - inf; P = 0.03). In all of patients, the low-risk group showed significant better survival compared with the high-risk group in OS, PFI, DSS and DFI. The nomogram based on the gene signature and radiation therapy was developed and successfully predicted the OS of US patients. The patients in the high-risk group displayed distinct mutation signatures comparing to patients in the low-risk group. Functional enrichment analysis indicated that the signature can play a vital role in cancer-related biological processes. CONCLUSION: Our study established a novel 6-gene signature and nomogram which could improve prognosis prediction in patients with US.

Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

[Study on regulation mechanism of Toutongning capsule through TNF signaling pathway in treatment of migraine based on systems pharmacology method].

Toutongning capsule (TTNC) is a traditional Chinese medicine(TCM) with good effect for treating migraine in clinical application. In this paper, a systems pharmacology method was carried out to study the TNF mechanism of the TTNC on the migraine. First, the ingredients for TTNC were collected from TCM databases, and ADME properties prediction was firstly applied to screen out the active compounds of TTNC. Then, the target searching and identification was performed by using CSDT model, and the targets were mapped to the migraine disease to determine the active targets through some common databases like TTD. To obtain the targets related with TNF signaling pathway, KEGG pathway analysis was performed by DAVID online analysis tool. Finally, the "herbs-compounds-targets" network was built by Cytoscape software. According to the results of degree and betweenness in the network, the key active compounds and targets were determined to explore the TNF mechanism for TTNC. Results showed that 19 active compounds and 8 targets played a crucial role in the treatment of migraine by TNF pathway for TTNC. This work provided a new perspective to deepen the understanding of the TNF signaling pathway mechanism in migraine treatment by TTNC, and may provide a necessary theoretical basis for the determination of effective markers and the clinical research of this medicine.

Green tea, black tea consumption and risk of endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: Several studies have assessed the association between green and black tea consumption and the risk of endometrial cancer (EC) and have yielded inconsistent results. OBJECTIVE: The purpose of this meta-analysis is to systematically analyze the effect of green tea and black tea on EC risk. METHODS: PubMed, Embase, Cochrane Library and China Biological Medicine Database were searched through February 2, 2015 to identify studies that met pre-stated inclusion criteria. Overall relative risk (RR) was estimated based on the highest and lowest levels of green/black tea consumption. Dose-response relationships were evaluated with the data from categories of green/black tea intake in each study. RESULTS: For green tea, the summary RR indicated that the highest green tea consumption was associated with a reduced risk of EC (RR 0.78, 95 % CI 0.66-0.92). Furthermore, an increase in green tea consumption of one cup per day was associated with an 11 % decreased risk of developing EC. (RR 0.89, 95 % CI 0.84-0.94). For black tea, no statistically significant association was observed in the meta-analysis (highest versus non/lowest, RR 0.99, 95 % CI 0.79-1.23; increment of one cup/day, RR 0.99, 95 % CI 0.94-1.03). The power of the estimate of green tea and black tea with risk of EC was 84.33 and 5.07 %, respectively. The quality of evidence for the association between green and black tea with EC risk was moderate and very low, respectively. CONCLUSIONS: The results from this meta-analysis indicate that green tea, but not black tea, may be related to a reduction of EC risk. Large population-based randomized controlled trials and large prospective cohort studies are required to obtain a definitive conclusion and determine the mechanisms underlying this association.

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

[Anti-hypertensive Effect of Total Flavonoids of Cydonia oblonga Leaves and Its Mechanism Based on Anti-inflammatory Function].

OBJECTIVE: To study the anti-hypertensive effect of total flavonoids of Cydonia oblonga leaves in spontaneously hypertensive rats, then to preliminarily investigate the mechanism of action based on anti-inflammatory function. METHODS: Spontaneously hypertensive rats were divided into six groups as spontaneously hypertensive control group (SHR), captopril group (25 mg/kg), Eucommia ulmoides group (30 mg/kg), total flavonoids of Cydonia oblonga leaves low (40 mg/kg), middle (80 mg/kg) and high dose (160 mg/kg) groups. Eight Wistar-Kyoto (WKY) rats were given distilled water as the control. The drugs were given by intragastric administration for 16 weeks, then the contents of IL-1ß, IL-6, IL-10, TNF-α and CRP in rats serum were detected. The weight and the blood pressure of rats were measured at 0 min and 2, 4, 6, 8, 10, 12, 14, 16 weeks after drug administrated. RESULTS: Compared with control group, the contents of IL-1ß, IL-6, TNF-α and CRP were increased and IL-10 was decreased; Compared with SHR group, the contents of IL-1ß,IL-6, TNF-α and CRP were decreased in total flavonoids of Cydonia oblonga leaves groups. CONCLUSION: Total flavonoids of Cydonia oblonga leaves show an anti-hypertensive activity in spontaneously hypertensive rats and the mechanism is related to the function of anti-inflammatory.

Cancer biotherapy: review and prospect.

Malignant tumors pose a grave threat to the quality of human life. The prevalence of malignant tumors in China is steadily rising. Presently, clinical interventions encompass surgery, radiotherapy, and pharmaceutical therapy in isolation or combination. Nonetheless, these modalities fail to completely eradicate malignant tumor cells, frequently leading to metastasis and recurrence. Conversely, tumor biotherapy has emerged as an encouraging fourth approach in preventing and managing malignant tumors owing to its safety, efficacy, and minimal adverse effects. Currently, a range of tumor biotherapy techniques are employed, including gene therapy, tumor vaccines, monoclonal antibody therapy, cancer stem cell therapy, cytokine therapy, and adoptive cellular immunotherapy. This study aims to comprehensively review the latest developments in biological treatments for malignant tumors.

Fibroblast Growth Factor 23 is a Potential Prognostic Biomarker in Uterine Sarcoma.

BACKGROUND: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics. METHODS: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus and a Suining cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients. RESULTS: Compared with uterine normal smooth muscle and uterine leiomyoma, FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma exhibited the highest expression of FGF23 among the subtypes. Survival analysis revealed no correlation between FGF23 expression and either overall survival or progression-free survival in US (P > 0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125, and tumor recurrence were independent prognostic factors for survival of US patients. CONCLUSION: FGF23 was highly expressed in US and was promising as a novel potential biomarker for the diagnosis and prognosis of US.

A Single-Arm Multi-Center Phase II Clinical Trial of Cadonilimab (anti-PD-1/CTLA-4) in Combination with or without Conventional Second-Line Treatment for Patients with Extensive Stage Small Cell Lung Cancer.

BACKGROUND: Cadonilimab (AK104) is a bispecific IgG-single-chain Fv fragment (ScFv) antibody that binds to PD-1 and CTLA-4. Cadonilimab has shown encouraging anti-tumour activity and a favourable safety profile in several tumour types. In second-line treatment, there is no defined standard of care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Cadonilimab is expected to show substantial clinical efficacy. OBJECTIVE: To assess the antitumor activity and safety of cadonilimab monotherapy or combination with conventional therapy in ES-SCLC patients who failed first-line treatment. METHODS: In this multicenter, open-label, phase II study, ES-SCLC patients who had failed first-line treatment, also aged 18 years to 70 years with histologically or cytologically confirmed ES-SCLC, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2 were eligible. Patients will receive cadonilimab 10 mg/kg every three weeks (Q3 W) among 24 months until progressive disease (PD) or adverse events (AE) discovery. The primary endpoint is progression-free survival (PFS). TRIAL REGISTRATION: NCT05901584.

TCCIA: a comprehensive resource for exploring CircRNA in cancer immunotherapy.

BACKGROUND: Immunotherapies targeting immune checkpoints have gained increasing attention in cancer treatment, emphasizing the need for predictive biomarkers. Circular RNAs (circRNAs) have emerged as critical regulators of tumor immunity, particularly in the PD-1/PD-L1 pathway, and have shown potential in predicting immunotherapy efficacy. Yet, the detailed roles of circRNAs in cancer immunotherapy are not fully understood. While existing databases focus on either circRNA profiles or immunotherapy cohorts, there is currently no platform that enables the exploration of the intricate interplay between circRNAs and anti-tumor immunotherapy. A comprehensive resource combining circRNA profiles, immunotherapy responses, and clinical outcomes is essential to advance our understanding of circRNA-mediated tumor-immune interactions and to develop effective biomarkers. METHODS: To address these gaps, we constructed The Cancer CircRNA Immunome Atlas (TCCIA), the first database that combines circRNA profiles, immunotherapy response data, and clinical outcomes across multicancer types. The construction of TCCIA involved applying standardized preprocessing to the raw sequencing FASTQ files, characterizing circRNA profiles using an ensemble approach based on four established circRNA detection tools, analyzing tumor immunophenotypes, and compiling immunotherapy response data from diverse cohorts treated with immune checkpoint blockades (ICBs). RESULTS: TCCIA encompasses over 4,000 clinical samples obtained from 25 cohorts treated with ICBs along with other treatment modalities. The database provides researchers and clinicians with a cloud-based platform that enables interactive exploration of circRNA data in the context of ICB. The platform offers a range of analytical tools, including browse of identified circRNAs, visualization of circRNA abundance and correlation, association analysis between circRNAs and clinical variables, assessment of the tumor immune microenvironment, exploration of tumor molecular signatures, evaluation of treatment response or prognosis, and identification of altered circRNAs in immunotherapy-sensitive and resistant tumors. To illustrate the utility of TCCIA, we showcase two examples, including circTMTC3 and circMGA, by employing analysis of large-scale melanoma and bladder cancer cohorts, which unveil distinct impacts and clinical implications of different circRNA expression in cancer immunotherapy. CONCLUSIONS: TCCIA represents a significant advancement over existing resources, providing a comprehensive platform to investigate the role of circRNAs in immuno-oncology.

Integrated neutrophil-to-lymphocyte ratio and handgrip strength better predict survival in patients with cancer cachexia.

OBJECTIVES: Systemic inflammation and skeletal muscle strength play crucial roles in the development and progression of cancer cachexia. In this study we aimed to evaluate the combined prognostic value of neutrophil-to-lymphocyte ratio (NLR) and handgrip strength (HGS) for survival in patients with cancer cachexia. METHODS: This multicenter cohort study involved 1826 patients with cancer cachexia. The NLR-HGS (NH) index was defined as the ratio of neutrophil-to-lymphocyte ratio to handgrip strength. Harrell's C index and receiver operating characteristic (ROC) curve analysis were used to assess the prognosis of NH. Kaplan-Meier analysis and Cox regression models were used to evaluate the association of NH with all-cause mortality. RESULTS: Based on the optimal stratification, 380 women (NH > 0.14) and 249 men (NH > 0.19) were classified as having high NH. NH has shown greater predictive value compared to other indicators in predicting the survival of patients with cancer cachexia according to the 1-, 3-, and 5-y ROC analysis and Harrell's C index calculation. Multivariate survival analysis showed that higher NH was independently associated with an increased risk of death (hazard ratio = 1.654, 95% confidence interval = 1.389-1.969). CONCLUSION: This study demonstrates that the NH index, in combination with NLR and HGS, is an effective predictor of the prognosis of patients with cancer cachexia. It can offer effective prognosis stratification and guidance for their treatment.

Exploring the optimal indicator of short-term peridiagnosis weight dynamics to predict cancer survival: A multicentre cohort study.

BACKGROUND: Body weight and its changes have been associated with cancer outcomes. However, the associations of short-term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short-term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. METHODS: This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height-adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight-related indicators and compared their prognostic performance using Harrell's C-index, integrated discrimination improvement, continuous net reclassification improvement and time-dependent C-index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan-Meier analysis and multivariable-adjusted Cox regression models. RESULTS: The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow-up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C-index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P < 0.05). Time-dependent C-index analysis also indicated that peridiagnosis RWC was optimal for predicting OS. The multivariable-adjusted RCS analysis revealed an N-shaped non-linear association between peridiagnosis RWC and OS (PRWC < 0.001, Pnon-linear < 0.001). Univariate survival analysis showed that the peridiagnosis RWC groups could represent distinct mortality risk stratifications (P < 0.001). Multivariable survival analysis showed that, compared with the maintenance group (weight change < 5%), the significant (gain >10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5-10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5-10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. CONCLUSIONS: The prognostic performance of peridiagnosis RWC is superior to other weight-related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change-related premature deaths.

Alternative splicing of PSMD13 mediated by genetic variants is significantly associated with endometrial cancer risk.

OBJECTIVE: Accumulating evidence has shown that aberrant alternative splicing events are closely associated with the onset and development of cancer. However, whether genetic variants-associated alternative splicing is linked to risk of endometrial cancer remains largely uncertain. METHODS: We identified single nucleotide polymorphisms (SNPs) locates in the splicing number trait locus (sQTL) of endometrial cancer using the CancerSplicing QTL database. In parallel with bioinformatics analysis, we conducted a case-control study comprising 2,000 cases and 2,013 controls to assess the association between identified SNP which possesses mRNA splicing function and endometrial cancer susceptibility. Furthermore, we used the Kaplan-Meier Plotter, The Human Protein Atlas, SPNR, and Spliceman2 databases for sQTL and differential gene expression analyses to identify the genetic variant which most potentially influence the risk of endometrial cancer through alternative splicing to reveal the potential mechanism by which candidate SNPs regulate the risk of endometrial cancer. RESULTS: The results indicated that SNP rs7128029 A