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BackgroundNeuroblastoma (NB) primarily arises in children who are

Mucormycosis is a rare opportunistic fungal infection associated with high mortality that typically occurs in immunocompromised patients. It is difficult to diagnose owing to non-specific clinical manifestations, the serologic index, imaging features, and the limitations of diagnostic methods. The incidence of invasive splenic mucormycosis is extremely rare, with only a few cases documented in the literature. We report a survival case of invasive splenic mucormycosis involving the liver caused by Rhizopus microsporus in a patient during consolidation therapy for acute monocytic leukemia (AML-M5). The patient initially presented with recurrent fever and splenomegaly accompanied by multiple focal hypodensities unresponsive to empiric anti-infective treatment. Splenic mucormycosis was diagnosed by Contrast-Enhanced Ultrasonography (CEUS) and metagenomic next-generation sequencing (mNGS). However, surgical intervention carries a high risk due to the progressive involvement of the liver in invasive splenic mucormycosis. Fortunately, monotherapy with amphotericin B was effective, and the patient underwent allo-HSCT. This case aims to emphasize the importance of utilizing mNGS and CEUS for the timely diagnosis of mucormycosis to help clinicians identify splenic mucormycosis and initiate appropriate therapy as soon as possible to improve therapeutic efficacy and prognosis.

BackgroundFluoropyrimidine is an important component of systemic chemotherapy for colorectal cancer (CRC). Fluoropyrimidine-induced cardiotoxicity (FIC) may result in delay and discontinuation of chemotherapy and, in severe cases, can even be life-threatening. To date, risk factors for FIC have not been well identified. This cohort study aimed to identify the predictors of FIC in CRC patients and develop a risk prediction nomogram model.MethodsBetween January 1, 2018 and December 31, 2020, colorectal cancer patients who received 5-fluoropyrimidine(5-Fu)/capecitabine-based chemotherapy in Affiliated Cancer Hospital of Guizhou Medical University were included. FIC was defined as an adverse cardiovascular event related to fluoropyrimidine that occurred during or within four weeks of completing chemotherapy. Risk factors were determined by LASSO algorithm and multivariate logistic regression analysis. Nomogram for predicting 5-Fu-induced cardiotoxicity was established and internally validated. The concordance index (C-index) and calibration curve were used to evaluate the nomogram’s discrimination and accuracy.ResultsA total of 916 patients were included for analysis, and 200 [21.8%,95% confidence interval (CI):19.12%-24.47%] experienced FIC. LASSO algorithm and multivariate logistic regression analysis determined that chemotherapy ≤3 cycles (OR=4.694, 95%CI=3.184-6.92), age≥ 60 (OR=1.678, 95%CI=1.143-2.464), BMI>22.97 (OR=1.77, 95%CI=1.202-2.606), and simultaneous use of bevacizumab (OR=2.922, 95%CI=1.835-4.653) were significant risk factors, and were included in the prediction model for 5-Fu induced cardiotoxicity. The C-index (95%CI) was 0.751 (0.706-0.795) by internal validation. For patients treated with capecitabine-based regimen, the incidence of FIC increased with the absolute value of neutrophils (OR=5.177, 95%CI=1.684-15.549) and eosinophils (OR=3.377,95% CI=1.237-9.22).ConclusionsOur study identified risk factors for FIC and established a prediction nomogram model based on chemotherapy cycle, age, BMI and use of target therapy for 5-FU induced Cardiotoxicity. The discriminative prediction model can be used for patient counselling and risk-stratification before undergoing chemotherapy in colorectal cancer.

ObjectiveThis study aims to compare the characteristics of early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) and non-ETP ALL patients and the outcomes of these patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodA total of 57 patients with T-cell acute lymphoblastic leukemia/lymphoma receiving allo-HSCT at our center between January 2016 and March 2022 were enrolled in the study. Twenty-eight patients were diagnosed as ETP-ALL/LBL (28/57, 49.12%) in the cohort.ResultsThe baseline characteristic was not significantly different between the two groups. The median time for myeloid engraftment was 14 days (ranged from 11 to 21) versus 14 days (ranged from 10 to 20) (P = 0.067) and 18 days (ranged from 12 to 27) versus 15.5 days (ranged from 12 to 72) (P = 0.183) for platelet engraftment in the ETP-ALL/LBL and non-ETP ALL groups, respectively. There was no significant difference in 5-year overall survival (54.74% ± 10.33% vs. 64.20% ± 10.30%, P = 0.786), relapse-free survival (56.22% ± 10.11% vs. 57.17% ± 12.71%, P = 0.841), cumulative incidence of relapse (30.14% ± 9.85% vs. 22.79% ± 8.24%, P = 0.774), and non-relapse mortality (19.52% ± 8.99% vs. 25.95% ± 14.44%, P = 0.967) between the two groups. The incidence of acute graft versus host disease (aGVHD) (P = 0.922), II–IV aGVHD (P = 0.940), III–IV aGVHD (P = 0.664), cytomegalovirus infection (P = 0.862), Epstein–Barr virus infection (P = 0.610), and severe bacterial infection (P = 0.145) was also similar.ConclusionThe prognosis of patients with ETP-ALL/LBL was similar to non-ETP ALL patients when they received allo-HSCT.

ObjectiveTo investigate the role of pre-treatment magnetic resonance imaging (MRI) radiomics for the preoperative prediction of lymph node (LN) metastasis in patients with hypopharyngeal squamous cell carcinoma (HPSCC).MethodsA total of 155 patients with HPSCC were eligibly enrolled from single institution. Radiomics features were extracted from contrast-enhanced axial T-1 weighted (CE-T1WI) sequence. The most relevant features of LN metastasis were selected by the least absolute shrinkage and selection operator (LASSO) method. Univariate and multivariate logistic regression analysis was adopted to determine the independent clinical risk factors. Three models were constructed to predict the LN metastasis status: one using radiomics only, one using clinical factors only, and the other one combined radiomics and clinical factors. Receiver operating characteristic (ROC) curves and calibration curve were used to evaluate the discrimination and the accuracy of the models, respectively. The performances were tested by an internal validation cohort (n=47). The clinical utility of the models was assessed by decision curve analysis.ResultsThe nomogram consisted of radiomics scores and the MRI-reported LN status showed satisfactory discrimination in the training and validation cohorts with AUCs of 0.906 (95% CI, 0.840 to 0.972) and 0.853 (95% CI, 0.739 to 0.966), respectively. The nomogram, i.e., the combined model, outperformed the radiomics and MRI-reported LN status in both discrimination and clinical usefulness.ConclusionsThe MRI-based radiomics nomogram holds promise for individual and non-invasive prediction of LN metastasis in patients with HPSCC.

ObjectiveThe study was designed to explore the evolution of non-small cell lung cancer (NSCLC) management in the last 20 years.MethodsThe top 100 most-cited papers on NSCLC treatment were retrieved from the Web of Science Core Collection database. R and VOSviewer were used to extract bibliographic information, including the year of publication, countries/regions, institutions, authors, journals, keywords, impact factor, and total citations. The topic and type of papers were checked independently by authors. Bibliometric analysis was conducted and visualized with R, CiteSpace, Excel and VOSviewer to identify output dynamics, research forces, topics, hotspots, and frontiers in the field.ResultsThe average citation of each retrieved top 100 most-cited NSCLC management papers was 1,725 (range: 615-7,340). Fifty-seven corresponding authors were from the United States. This country contributed the most papers (n=76), followed by Germany (n=34), France (n=33), and South Korea (n=32). The top contributors were Paz-Ares L. (n=12) and Reck M. (n=12). The Memorial Sloan Kettering Cancer Center published the largest number of papers (n=20). There were two significant citation paths, indicating publications in medicine/medical/clinical journals primarily cited journals in molecular/biology/genetics fields, partly cited health/nursing/medicine fields. Top-cited papers mainly came from the New England Journal of Medicine (n=33, citations=80,427), followed closely by the Journal of Clinical Oncology (n=28, citations=32,408). “Chemotherapy” (n=36) was the keyword with the greatest frequency of co-occurrence. “Open-label” was the keyword with the strongest burst strength (=4.01), followed by “nivolumab” (=3.85), “blockade” (=2.86), and “efficacy” (=2.85).ConclusionsThe United States as a nation and the Memorial Sloan Kettering Cancer Center as an institute contributed the most to this field. The New England Journal of Medicine is the most eye-catching journal. Hotspots of NSCLC management have almost undergone an evolution from chemotherapy and radiotherapy to targeted therapy to immunotherapy. Molecular/biological/genetic fields become the main research base for NSCLC treatment. Immunotherapy and combination therapy are research frontiers.

Breast cancer is one of the leading causes of mortality in females. Over the past decades, intensive efforts have been made to uncover the pathogenesis of breast cancer. Interleukin-6 (IL-6) is a pleiotropic factor which has a vital role in host defense immunity and acute stress. Moreover, a wide range of studies have identified the physiological and pathological roles of IL-6 in inflammation, immune and cancer. Recently, several IL-6 signaling pathway-targeted monoclonal antibodies have been developed for cancer and immune therapy. Combination of IL-6 inhibitory antibody with other pathways blockage drugs have demonstrated promising outcome in both preclinical and clinical trials. This review focuses on emerging studies on the strong linkages of IL-6/IL-6R mediated regulation of inflammation and immunity in cancer, especially in breast cancer.

ObjectiveThis study aims to investigate the effect of polymorphisms of programmed cell death-ligand 1 (PD-L1) on the risk and patient’s outcomes of epithelial ovarian cancer (EOC).MethodsTotally, 568 patients and 532 healthy women were included. Three polymorphisms in the PD-L1 gene, rs2297136, rs4143815 and rs4742098, were genotyped by the polymerase chain reaction/ligase detection reaction (PCR-LDR). Survival analysis was performed in 234 patients (received primary debulking surgery followed by platinum-based chemotherapy).ResultsPatients with the rs2297136 AG + GG genotypes had shorter progression-free survival (PFS) (hazard ratio (HR)=1.44, 95% CI=1.03-2.01) and overall survival (OS) (HR=1.55, 95% CI=1.06-2.27) than those with the AA genotype. Moreover, the mRNA and protein expression levels of PD-L1 in EOC tissues with the rs2297136 AG + GG genotypes were remarkably higher than those with the AA genotype (P=0.032 and P=0.047, respectively). Survival analysis showed that high expression of PD-L1 mRNA was remarkably associated with worse 10-year PFS (HR=1.55, 95% CI=1.28-1.88) and OS (HR=1.51, 95% CI=1.00-2.28) in EOC patients.ConclusionsThe rs2297136 may not only effectively influence the expression of PD-L1, but also is significantly associated with EOC patients’ outcomes.

BackgroundWe aimed to assess clinical factors associated with tumor recurrence and build a nomogram based on identified risk factors to predict postoperative recurrence in patients with pituitary adenomas (PAs) who underwent gross-total resection (GTR).MethodsA total of 829 patients with PAs who achieved GTR at Tongji Hospital between January 2013 and December 2018 were included in this retrospective study. The median follow-up time was 66.7 months (range: 15.6–106.3 months). Patients were randomly divided into training (n = 553) or validation (n = 276) cohorts. A range of clinical characteristics, radiological findings, and laboratory data were collected. Uni- and multivariate Cox regression analyses were applied to determine the potential risk factors for PA recurrence. A nomogram model was built from the identified factors to predict recurrence. Concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) were used to determine the predictive accuracy of the nomogram. Decision curve analysis (DCA) was performed to evaluate the clinical efficacy of the nomogram.ResultsPseudocapsule-based extracapsular resection (ER), cavernous sinus invasion (CSI), and tumor size were included in the nomogram. C-indices of the nomogram were 0.776 (95% confidence interval [CI]: 0.747–0.806) and 0.714 (95% CI: 0.681–0.747) for the training and validation cohorts, respectively. The area under the curve (AUC) of the nomogram was 0.770, 0.774, and 0.818 for 4-, 6-, 8-year progression-free survival (PFS) probabilities in the training cohort, respectively, and 0.739, 0.715 and 0.740 for 4-, 6-, 8-year PFS probabilities in the validation cohort, respectively. Calibration curves were well-fitted in both training and validation cohorts. DCA revealed that the nomogram model improved the prediction of PFS in both cohorts.ConclusionsPseudocapsule-based ER, CSI, and tumor size were identified as independent predictors of PA recurrence. In the present study, we developed a novel and valid nomogram with potential utility as a tool for predicting postoperative PA recurrence. The use of the nonogram model can facilitate the tailoring of counseling to meet the individual needs of patients.

ObjectiveTo evaluate the efficacy and safety of thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MVA), and laser ablation (LA), for treating lymph node metastasis (LNM) from papillary thyroid carcinoma (PTC).Design and MethodsPubMed and EMBASE were searched for studies reporting the efficacy and safety of thermal ablation for treating LNM in PTC. After selecting the relevant literature (including 11 papers, 208 patients, 412 lymph nodes), the QUADAS-2 tool was used to evaluate its quality. Then, both the fixed-effects and random-effects models combined with subgroup analysis were used to calculate data on volume changes in metastatic lymph nodes and changes in serum thyroglobulin (Tg) levels. We pooled the proportion of major and overall complication rates and complete disappearance rates and used subgroup forest plots and funnel plots for visual representation. Because of publication bias, we also performed a trim-and-filled model for correction. The rate of recurrence and distant metastasis with ablated details were pooled.ResultsIn the 11 articles (208 patients and 412 diseased lymph nodes), all thermal ablation methods showed effectiveness in reducing lymph node volume (P = 0.02) and serum Tg levels (P < 0.01) which showed no between-group difference. The pooled proportion of major complications was 0%(95% CI: -0.14; 0.15, P = 1) and the overall complication rate was 5% (95% CI: -0.09; 0.20, P = 1), which revealed no significant difference among modalities. The pooled proportion of the complete disappearance rate was 82% (95% CI: 0.43; 0.96, P < 0.01) and the data with statistical significance which contains RFA and LA showed complete disappearance rate was 59% and 81% respectively.ConclusionAll thermal ablation methods, including RFA, MWA, and LA, were effective and safe for treating LNM in PTC and were especially suitable for nonsurgical patients. Besides, subgroup analysis showed no significant difference, except for LA is better than RFA in complete disappearance rate.

BackgroundTo effectively reduce the irradiated bowel volume so as to reduce intestinal toxicity from pelvic radiotherapy, treatment in the prone position with a full bladder on a belly board is widely used in pelvic radiotherapy for rectal cancer patients. However, the clinical applicable condition of this radiotherapy mode is unclear. The aim of this study was to preliminarily identify patients who were not eligible for this radiotherapy mode by analyzing the effect of abdominal circumference on the irradiated bowel volume.MethodsFrom May 2014 to September 2019, 179 patients with locally advanced rectal cancer were retrospectively reviewed in our center. All patients received pelvic radiotherapy. Weight, height, AC, and body mass index (BMI) were used as the research objects, and the irradiated bowel volume at different dose levels (V10, V20, V30, V40, V50) was selected as the outcome variable. Multivariate linear regression and sensitivity analyses were used to evaluate the correlation between AC and irradiated bowel volume. Generalized additive model (GAM) and piecewise linear regression were used to further analyze the possible nonlinear relationship between them.ResultsAmong the four body size indicators, AC showed a negative linear correlation with the irradiated bowel volume, which was the most significant and stable. In adjuvant radiotherapy patients, we further discovered the threshold effect between AC and irradiated bowel volume, as AC was greater than the inflection point (about 71 cm), irradiated bowel volume decreased rapidly with the increase in AC. t-test showed that in patients with small AC (

This study aimed to assess the effects of the antidiabetic drug Exendin-4 (Exe-4), a GLP-1 receptor agonist, on the response of human endometrial cancer cells to chemotherapy under high glucose (HG) conditions. Cell viability was detected using a cell counting kit (CCK)-8. Cell apoptosis and reactive oxygen species (ROS) levels were measured by flow cytometry. Gene expression was evaluated by real-time PCR and immunoblotting. The chemotherapeutic drug cisplatin (DDP) dose-dependently inhibited both human endometrial adenocarcinoma Ishikawa and HEC1B cells, a response reversed by HG. Meanwhile, Exe-4 attenuated hyperglycemia’s effect by elevating intracellular lactate dehydrogenase (LDH) and ROS production. Similarly, DDP-induced elevation of intracellular rhodamine123 was attenuated by HG, and Exe-4 reversed HG’s impact. The chemoresistance genes multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein (Pgp) were upregulated. At the same time, topoisomerase II (TOPO II) was downregulated under HG conditions, suggesting HG-induced chemoresistance. Exe-4 did not significantly influence the above genes. DDP downregulated Bcl-2 and Bcl-XL and upregulated Bax, cytosolic cytochrome c, and PARP under normal glucose (NG) versus HG conditions, and Exe-4 attenuated these effects. Upstream of Bax/Bcl, acetylated P53 was upregulated by DDP and downregulated by HG, whose effect was reversed by Exe-4. DPP treatment significantly induced apoptosis and cell cycle arrest in the S phase under NG, and HG reduced these effects. Prolonged exposure to HG induces DDP chemoresistance in human endometrial cancer cells but is alleviated by Exe-4.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. Tumor metastasis is one of the major causes of high mortality of HCC. Identifying underlying key factors contributing to invasion and metastasis is critical to understand the molecular mechanisms of HCC metastasis. Here, we identified RNA binding protein L23 (RPL23) as a tumor metastasis driver in HCC. RPL23 was significantly upregulated in HCC tissues compared to adjacent normal tissues, and closely related to poor clinical outcomes in HCC patients. RPL23 depletion inhibited HCC cell proliferation, migration and invasion, and distant metastasis. Mechanistically, RPL23 directly associated with 3’UTR of MMP9, therefore positively regulated MMP9 expression. In conclusion, we identified that RPL23 might play an important role in HCC metastasis in an MMP9-dependent manner and be a potential therapeutic target for HCC tumorigenesis and metastasis.

RNA editing is a widespread post-transcriptional mechanism to introduce single nucleotide changes to RNA in human cancers. Here, we characterized the global RNA editing profiles of 373 hepatocellular carcinoma (HCC) and 50 adjacent normal liver samples from The Cancer Genome Atlas (TCGA) and revealed that most editing events tend to occur in minor percentage of samples with moderate editing degrees (20–30%). Moreover, these RNA editing prefer to be A-to-I RNA editing in protein coding genes, especially in 3′UTR regions. Considering the association between DNA mutation and RNA editing, our analysis found that RNA editing maybe a complementary event for DNA mutation of HCC risk genes in HCC patients. We next identified 454 HCC-related editing sites, and many locate on the same genes with the same editing patterns. The functional consequences of editing revealed 2,086 functional editing sites and demonstrated that most editing in coding regions are non-synonymous variations. Furthermore, our results showed that editing in the 3′UTR regions tend to influence miRNA–target binding, and the editing degree seems to be negatively correlated with gene expression. Finally, we found that 46 HCC-related editing sites with consequence are able to distinguish the prognosis differences of HCC patients, suggesting their clinical relevance. Together, our results highlight RNA editing as a valuable molecular resource for investigating HCC mechanisms and clinical treatments.

Patients with advanced thyroid carcinoma have poor prognosis with low overall survival. Unfortunately, the underlying mechanisms of thyroid carcinoma progression remain unclear. The elevated expression of thymidine kinase 1 (TK1) has been implicated in the progression of thyroid carcinoma, while the role of TK1 in thyroid carcinoma progression has not been explored. The present study aimed to determine the role TK1 in the progression of thyroid cancer and to explore the underlying molecular mechanisms. In this study, it was found that serum TK1 levels were markedly increased in the patients with thyroid nodules. Further online data mining showed that TK1 expression was upregulated in thyroid carcinoma tissues, and higher expression of TK1 was correlated with shorter disease-free survival of patients with thyroid carcinoma. Silencing of TK1 suppressed cell proliferation, invasion, migration, and epithelial–mesenchymal transition, and also induced cell apoptosis in the thyroid carcinoma cell lines. Animal studies showed that TK1 knockdown inhibited in vivo tumor growth of thyroid carcinoma cells. Importantly, miR-34a-5p was found to be downregulated in the thyroid carcinoma cells. Furthermore, miR-34a-5p targeted the 3′ untranslated region of TK1 and suppressed the expression of TK1 in thyroid carcinoma cell lines. In summary, first, these results demonstrated the upregulation of TK1 in thyroid nodules and thyroid carcinoma tissues; second, TK1 promoted thyroid carcinoma cell proliferation, invasion, and migration; lastly, TK1 was negatively regulated by miR-34a-5p. Our study may provide novel insights into the role of TK1 in regulating thyroid carcinoma progression.

Breast cancer is the leading cause of cancer-related deaths in women; however, its underlying etiology remains largely unknown. In this study, we systematically analyzed breast cancer tissues using comprehensive iTRAQ labeled quantitative proteomics, identifying 841 differentially expressed proteins (474 and 367 significantly over- and under-expressed, respectively), which were annotated by protein domain analysis. All the heat shock proteins identified were upregulated in breast cancer tissues; Hsp90 upregulation was also validated by RT-qPCR and immunohistochemistry, and high Hsp90 protein levels correlated with poorer survival. Hsp90AA1 overexpression promoted MDA-MB-231 cell proliferation, whilst BJ-B11, an Hsp90 inhibitor, hampered their invasion, migration, and proliferation in a time and dose-dependent manner and induced cell cycle arrest and apoptosis. BJ-B11 inhibited the expression of epithelial-mesenchymal transition (EMT) marker in MDA-MB-231 cells, whereas Hsp90AA1 promoted its expression. Moreover, BJ-B11 inhibited tumor growth in xenograft model. Altogether, Hsp90 activation is a risk factor in breast cancer patients, and BJ-B11 could be used to treat breast cancer.

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare and fatal disease with no special clinical manifestations. Here, we report the dynamic brain magnetic resonance imaging (MRI) changes in a 30-year-old female PDLG patient over a 10-month period. MRI showed aggressive dilation of the subarachnoid space and the ventricular system, numerous encapsulated cysts in the subarachnoid space and the dilated cerebral sulci, diffuse reticulated or focal nodular enhancement in the subarachnoid space, as well as overall enhancement in the cystic walls. In addition to the aforementioned PDLG pathological findings, MRI also revealed non-contrasted solid lesions and a contrasted cyst-like lesion in the paraventricular areas. The dynamic and multiform neuroradiological changes help us to understand the pathological process of PDLG. Of particular interest is the discovery that parenchymal infiltration can occur in PDLG.