A novel nomogram based on inflammation biomarkers for predicting radiation cystitis in patients with local advanced cervical cancer.

BACKGROUNDS: Platelet-to-albumin ratio (PAR) is a new systemic inflammatory prognostic indicator associated with many inflammatory diseases. However, its role in radiation cystitis (RC) is obscure. This study aimed to explore whether PAR could be used as an effective parameter for predicting the RC risk in local advanced cervical cancer (CC) treated with radiotherapy. METHODS: A total of 319 local advanced CC patients who received radical radiotherapy at Fujian Cancer Hospital were enrolled between December 2018 and January 2021. Demographics and clinical parameters were retrospectively analyzed. Univariate and multivariate analyses were used to identify the risk factors for RC. Backward and stepwise regression was applied to construct two monograms-one with primary significant factors and the other with extra inflammatory biomarkers. A DeLong test was applied to compare the prediction abilities of two nomograms. Calibration curves and decision curve analysis (DCA) evaluated its prediction consistency, discrimination ability, and clinical net benefit. RESULTS: Univariate analysis showed that age, tumor size, stage, total radiation dose, pelvic radiation dose, Systemic Immune-Inflammation Index (SII), platelet-to-lymphocyte ratio (PLR), and PAR were significantly associated with RC occurrence (all p < 0.05). Multivariate analyses indicated that age, tumor size, stage, total radiation dose, and PAR were independent factors (all p < 0.05). Then, the area under curve (AUC) value of the nomogramSII+PAR was higher (AUC = 0.774) compared to that of the baseline nomogram (AUC = 0.726) (pDelong = 0.02). Also, the five-cross validation confirmed the stability of the nomogramSII+PAR. Moreover, the calibration curve and DCA exhibited the nomograms' good prediction consistency and clinical practicability. CONCLUSIONS: PAR and SII could be valued for CC patients who are treated with radiation therapy. The nomogram based on PAR and SII could stratify patients who need extra intervention and nursing care to prevent bladder radiation damage and improve patients' quality of life.

The management of uterine tumor resembling an ovarian sex cord tumor (UTROSCT): case series and literature review.

AIMS: To present a case series of 11 rare uterine tumors resembling ovarian sex cord tumors (UTROSCTs), and review the literature on this topic to offer up-to-date treatment management for UTROSCTs. METHOD: Eight cases from Fujian Cancer Hospital between January 2017 and May 2023 and three patients from Fujian Union Hospital between October 2012 and October 2020 were retrospectively reviewed. All cases were pathologically confirmed as UTROSCTs by two senior and experienced pathologists. Clinical behaviors, medical data, histopathological features, therapy approaches, and survival outcomes were discussed. RESULTS: The median age at initial diagnosis was 53 years (29-70 years). 3 (27.3%) patients were under 40. Seven cases presented with abnormal vaginal bleeding, one with menstrual disorder, one with abnormal vaginal secretion, and two patients were accidentally found by physical examination without any symptoms. Three patients were initially misdiagnosed with endometrial cancer by MRI. Curettage was performed in all cases. Nine of them were well diagnosed by routine curettage, except for two samples, which were identified after surgery. Immunohistochemical biomarkers, such as CD99, Desmin, WT-1, CK, Vimentin, SMA, α-Inhibin, Ki67, CD56, ER, PR, and CR, tend to be positive in UTRO SCs patients. Six patients underwent hysterectomy with bilateral salpingo-oophorectomy. Two cases received a radical hysterectomy with bilateral salpingo-oophorectomy, retroperitoneal lymph node dissection, and omentum dissection. Three UTROSCTs were under observation after mass resection. The median PFS was 24 months (range 1-125 months). CONCLUSION: UTROSCT is a rare mesenchymal tumor with low malignant potential. Treatment modalities should be carefully considered to balance the therapy outcomes and patient needs. Surgery conservative management might be suitable for young women with fertility desires.

A novel nomogram and risk stratification for early metastasis in cervical cancer after radical radiotherapy.

OBJECT: This study aimed to establish an effective risk nomogram to predict the early distant metastasis (EDM) probability of cervical cancer (CC) patients treated with radical radiotherapy to aid individualized clinical decision-making. METHODS: A total of 489 patients with biopsy-confirmed CC between December 2018 and January 2021 were enrolled. Logistic regression with the stepwise backward method was used to identify independent risk factors. The nomogram efficacy was evaluated by using the area under the receiver operating characteristic curve (AUC), C-index by 1000 bootstrap replications, etc. Finally, patients were divided into high- and low-risk groups of EDM based on the cut-off value of nomogram points. RESULTS: 36 (7.36%) CC patients had EDM, and 20 (55.6%) EDM had more than one metastatic site involved. Age below 51 (OR = 2.298, p < 0.001), tumor size larger than 4.5 cm (OR = 3.817, p < 0.001) and radiotherapy (OR = 3.319, p < 0.001) were independent risk factors of EDM. For the nomogram model, C-index was 0.701 (95% CI = 0.604-0.798), and 0.675 (95% CI = 0.578-0.760) after 1000 bootstrap resampling validations. The Hosmer-Lemeshow test demonstrated no overfitting (p = 0.924). According to the Kaplan-Meier curve of risk score, patients with high risk were more prone to get EDM (p < 0.001). CONCLUSION: This is the first research to focus on EDM in CC patients. We have developed a robust scoring system to predict the risk of EDM in CC patients to screen out appropriate cases for consolidation therapy and more intensive follow-up.

Nomograms constructed for predicting diagnosis and prognosis in cervical cancer patients with second primary malignancies: a SEER database analysis.

PURPOSE: Cervical cancer (CC) patients are more likely to develop second primary malignancies (SPMs) than general population. With the advancement in cancer therapy, CC patients are achieving long-term survival, leading SPMs to our attention. Our study aims to establish diagnostic and prognostic nomograms for CC patients with second primary malignancies (CCSPMs) to help make personalized follow-up plans and treatments. METHODS: Data of CCSPMs between 2000 and 2019 was extracted from SEER. The proportions and the median interval time of CCSPM onset were calculated. 11 related clinical characteristics, including age, race, marital status, grade, FIGO stage, radiotherapy, chemotherapy, and surgery, were further explore. Logistic and Cox regressions were employed to predict risk factors for CCSPMs diagnosis. Finally, two nomograms were developed to predict the probability occurrence and prognosis of CCSPMs, respectively. RESULTS: For diagnostic nomogram construction, 59,178 CC patients were randomly divided into training (n = 41,426) and validation cohorts (n = 17,752). For prognostic nomogram construction, 3527 CCSPMs patients were randomly divided into training (n = 2469) and validation cohorts (n = 1058). The diagnostic nomogram consisting of above 11 independent risk factors (all P < 0.05), had high accuracy (AUCtraining = 0.851 and AUCvalidating = 0.845). The prognostic nomogram integrated with eight independent prognostic factors such as treatments, FIGO stage and TNM stage performed well in predicting 5-year OS (AUCtraining = 0.835 and AUCvalidating = 0.837). CONCLUSION: Our diagnostic and prognostic nomograms could facilitate clinicians to quantify individual SPMs risk and survival probabilities and optimize the surveillance recommendations and personalized clinical decision-making.

Significance of Immunogenic Cell Death-Related Prognostic Gene Signature in Cervical Cancer Prognosis and Anti-Tumor Immunity.

Background: Immunogenic cell death (ICD) can reshape the immune microenvironment of tumors. Driven by stressful pressure, by directly destroying tumor cells and activating the body's adaptive immunity, ICD acts as a modulator of cell death, enabling the body to generate an anti-tumor immune response that produces a more effective therapeutic effect, while tumor cells are driven to kill. Hence, this research aimed to find and evaluate ICD-related genetic signatures as cervical cancer (CC) prognostic factors. Methods: Data of CC patients from the Tumor Genome Atlas (TCGA) were used as the basis to obtain immunogenic cell-death-related prognostic genes (IPGs) in patients with CC, using the least absolute shrinkage and selection operator and Cox regression screening, and the IPGs scoring system was constructed to classify patients into high- and low-risk groups, with the Gene Expression Omnibus (GEO) dataset as the validation group. Finally, the difference analysis of single-sample gene set enrichment analysis, tumor microenvironment (TME), immune cells, tumor mutational burden, and chemotherapeutic drug sensitivity between the high-risk and low-risk groups was investigated. Results: A prognostic model with four IPGs (PDIA3, CASP8, IL1, and LY96) was developed, and it was found that the group of CC patients with a higher risk score of IPGs expression had a lower survival rate. Single and multifactor Cox regression analysis also showed that this risk score was a reliable predictor of overall survival. In comparison to the low-risk group, the high-risk group had lower TME scores and immune cell infiltration, and gene set variation analysis showed that immune-related pathways were more enriched in the high-risk group. Conclusion: A risk model constructed from four IPGs can independently predict the prognosis of CC patients and recommend more appropriate immunotherapy strategies for patients.

Design of coherent wideband radiation process in a Nd3+-doped high entropy glass system.

We discover that the spatially coherent radiation within a certain frequency range can be obtained without a common nonlinear optical process. Conventionally, the emission spectra were obtained by de-exciting excited centers from real excited energy levels to the ground state. Our findings are achieved by deploying a high-entropy glass system (HEGS) doped with neodymium ions. The HEGS exhibits a much broader infrared absorption than common glass systems, which can be attributed to be high-frequency optical branch phonons or allowable multi-phonon processes caused by phonon broadening in the system. A broadened phonon-assisted wideband radiation (BPAWR) is induced if the pump laser is absorbed by the system. The subsequent low-threshold self-absorption coherence modulation (SACM) can be controlled by changing excitation wavelengths, sample size, and doping concentrations. The SACM can be red-shifted through the emission of phonons of the excited species and be blue-shifted by absorbing phonons before they are de-excited. There is a time delay up to 1.66 ns between the pump pulse and the BPAWR when measured after traveling through a 35 mm long sample, which is much longer than the Raman process. The BPAWR-SACM can amplify the centered non-absorption band with a gain up to 26.02 dB. These results reveal that the shift of the novel radiation is determined by the frequency of the non-absorption band near the absorption region, and therefore the emission shifts can be modulated by changing the absorption spectrum. When used in fiber lasers, the BPAWR-SACM process may help to achieve tunability.

Interleukin-17 promotes the development of cisplatin resistance in colorectal cancer.

Cisplatin (DDP)-based anticancer therapy is an important chemotherapeutic strategy for the treatment of colorectal cancer. However, its beneficial effect is largely compromised by adverse reactions, and more importantly, by the development of drug resistance. Therefore, it is crucial to determine the potential mechanism underlying the development of DDP resistance in colorectal cancer. Interleukin-17 (IL-17) is a proinflammatory cytokine that has been found to serve an important role in the host defense during cancer development. It has been suggested that IL-17 is key to promoting the development of resistance to DDP in several major types of cancer. However, the role of IL-17 in DDP resistance in colorectal cancer has not been extensively investigated. In the present study, it was observed that IL-17 was significantly upregulated in colorectal tumor samples, compared with the adjacent tissues. Furthermore, IL-17 was found to promote the viability of HCT116 colorectal cells treated with DDP, whilst blocking IL-17 signaling leading to HCT116 cell apoptosis. IL-17 was also shown to regulate the expression of several apoptosis-related proteins, including phosphorylated-protein kinase B (p-Akt), apoptosis regulator BAX (Bax), apoptosis regulator Bcl-2 (Bcl-2) and serine/threonine-protein kinase mTOR (mTOR). These findings indicated that IL-17 facilitates the development of DDP resistance in colorectal cancer by inhibiting cancer cell apoptosis through targeting p-Akt, Bax, Bcl-2 and mTOR. Overall, the findings of the present study suggest that a combination of DDP and an IL-17 inhibitor may prove to be a highly efficient strategy for colorectal cancer treatment.

Comprehensive Analysis of the Cadmium Tolerance of Abscisic Acid-, Stress- and Ripening-Induced Proteins (ASRs) in Maize.

In plants, abscisic acid-, stress-, and ripening-induced (ASR) proteins have been shown to impart tolerance to multiple abiotic stresses such as drought and salinity. However, their roles in metal stress tolerance are poorly understood. To screen plant Cd-tolerance genes, the yeast-based gene hunting method which aimed to screen Cd-tolerance colonies from maize leaf cDNA library hosted in yeast was carried out. Here, maize ZmASR1 was identified to be putative Cd-tolerant through this survival screening strategy. In silico analysis of the functional domain organization, phylogenetic classification and tissue-specific expression patterns revealed that maize ASR1 to ASR5 are typical ASRs with considerable expression in leaves. Further, four of them were cloned for testifying Cd tolerance using yeast complementation assay. The results indicated that they all confer Cd tolerance in Cd-sensitive yeast. Then they were transiently expressed in tobacco leaves for subcellular localization analysis and for Cd-challenged lesion assay, continuously. The results demonstrated that all 4 maize ASRs tested are localized to the cell nucleus and cytoplasm in tobacco leaves. Moreover, they were confirmed to be Cd-tolerance genes in planta through lesion analysis in Cd-infiltrated leaves transiently expressing them. Taken together, our results demonstrate that maize ASRs play important roles in Cd tolerance, and they could be used as promising candidate genes for further functional studies toward improving the Cd tolerance in plants.

Comparative analysis of Cd-responsive maize and rice transcriptomes highlights Cd co-modulated orthologs.

BACKGROUND: Metal tolerance is often an integrative result of metal uptake and distribution, which are fine-tuned by a network of signaling cascades and metal transporters. Thus, with the goal of advancing the molecular understanding of such metal homeostatic mechanisms, comparative RNAseq-based transcriptome analysis was conducted to dissect differentially expressed genes (DEGs) in maize roots exposed to cadmium (Cd) stress. RESULTS: To unveil conserved Cd-responsive genes in cereal plants, the obtained 5166 maize DEGs were compared with 2567 Cd-regulated orthologs in rice roots, and this comparison generated 880 universal Cd-responsive orthologs groups composed of 1074 maize DEGs and 981 rice counterparts. More importantly, most of the orthologous DEGs showed coordinated expression pattern between Cd-treated maize and rice, and these include one large orthologs group of pleiotropic drug resistance (PDR)-type ABC transporters, two clusters of amino acid transporters, and 3 blocks of multidrug and toxic compound extrusion (MATE) efflux family transporters, and 3 clusters of heavy metal-associated domain (HMAD) isoprenylated plant proteins (HIPPs), as well as all 4 groups of zinc/iron regulated transporter protein (ZIPs). Additionally, several blocks of tandem maize paralogs, such as germin-like proteins (GLPs), phenylalanine ammonia-lyases (PALs) and several enzymes involved in JA biosynthesis, displayed consistent co-expression pattern under Cd stress. Out of the 1074 maize DEGs, approximately 30 maize Cd-responsive genes such as ZmHIPP27, stress-responsive NAC transcription factor (ZmSNAC1) and 9-cis-epoxycarotenoid dioxygenase (NCED, vp14) were also common stress-responsive genes reported to be uniformly regulated by multiple abiotic stresses. Moreover, the aforementioned three promising Cd-upregulated genes with rice counterparts were identified to be novel Cd-responsive genes in maize. Meanwhile, one maize glutamate decarboxylase (ZmGAD1) with Cd co-modulated rice ortholog was selected for further analysis of Cd tolerance via heterologous expression, and the results suggest that ZmGAD1 can confer Cd tolerance in yeast and tobacco leaves. CONCLUSIONS: These novel findings revealed the conserved function of Cd-responsive orthologs and paralogs, which would be valuable for elucidating the genetic basis of the plant response to Cd stress and unraveling Cd tolerance genes.