Comprehensive proteomic profiling of lung adenocarcinoma: development and validation of an innovative prognostic model.

Background: Lung adenocarcinoma (LUAD), a global leading cause of cancer deaths, remains inadequately addressed by current protein biomarkers. Our study focuses on developing a protein-based risk signature for improved prognosis of LUAD. Methods: We employed the least absolute shrinkage and selection operator (LASSO)-COX algorithm on The Cancer Genome Atlas database to construct a prognostic model incorporating six proteins (CD49B, UQCRC2, SMAD1, FOXM1, CD38, and KAP1). The model's performance was assessed using principal component, Kaplan-Meier (KM), and receiver operating characteristic (ROC) analysis, indicating strong predictive capability. The model stratifies LUAD patients into distinct risk groups, with further analysis revealing its potential as an independent prognostic factor. Additionally, we developed a predictive nomogram integrating clinicopathologic factors, aimed at assisting clinicians in survival prediction. Gene set enrichment analysis (GSEA) and examination of the tumor immune microenvironment were conducted, highlighting metabolic pathways in high-risk genes and immune-related pathways in low-risk genes, indicating varied immunotherapy sensitivity. Validation through immunohistochemistry from the Human Protein Atlas (HPA) database and immunofluorescence staining of clinical samples was performed, particularly focusing on CD38 expression. Results: Our six-protein model (CD49B, UQCRC2, SMAD1, FOXM1, CD38, KAP1) effectively categorized LUAD patients into high and low-risk groups, confirmed by principal component, KM, and ROC analyses. The model showed high predictive accuracy, with distinct survival differences between risk groups. Notably, CD38, traditionally seen as protective, was paradoxically associated with poor prognosis in LUAD, a finding supported by immunohistochemistry and immunofluorescence data. GSEA revealed that high-risk genes are enriched in metabolic pathways, while low-risk genes align with immune-related pathways, suggesting better immunotherapy response in the latter group. Conclusions: This study presented a novel prognostic protein model for LUAD, highlighting the CD38 expression paradox and enhancing our understanding of protein roles in lung cancer progression. It offered new clinical tools for prognosis prediction and provided assistance for future lung cancer pathogenesis research.

Therapeutic potential of ADSC-EV-derived lncRNA DLEU2: A novel molecular pathway in alleviating sepsis-induced lung injury via the miR-106a-5p/LXN axis.

This study investigates the molecular mechanisms by which extracellular vesicles (EVs) derived from adipose-derived mesenchymal stem cells (ADSCs) promote M2 polarization of macrophages and thus reduce lung injury caused by sepsis. High-throughput sequencing was used to identify differentially expressed genes related to long non-coding RNA (lncRNA) in ADSC-derived EVs (ADSC-EVs) in sepsis lung tissue. Weighted gene co-expression network analysis (WGCNA) was employed to predict the downstream target genes of the lncRNA DLEU2. The RNAInter database predicted miRNAs that interact with DLEU2 and LXN. Functional and pathway enrichment analyses were performed using GO and KEGG analysis. A mouse model of sepsis was established, and treatment with a placebo or ADSC-EVs was administered, followed by RT-qPCR analysis. ADSC-EVs were isolated and identified. In vitro cell experiments were conducted using the mouse lung epithelial cell line MLE-12, mouse macrophage cell line RAW264.7, and mouse lung epithelial cell line (LEPC). ADSC-EVs were co-cultured with RAW264.7 and MLE-12/LEPC cells to study the regulatory mechanism of the lncRNA DLEU2. Cell viability, proliferation, and apoptosis of lung injury cells were assessed using CCK-8, EdU, and flow cytometry. ELISA was used to measure the levels of inflammatory cytokines in the sepsis mouse model, flow cytometry was performed to determine the number of M1 and M2 macrophages, lung tissue pathology was evaluated by H&E staining, and immunohistochemistry was conducted to examine the expression of proliferation- and apoptosis-related proteins. High-throughput sequencing and bioinformatics analysis revealed enrichment of the lncRNA DLEU2 in ADSC-EVs in sepsis lung tissue. Animal and in vitro cell experiments showed increased expression of the lncRNA DLEU2 in sepsis lung tissue after treatment with ADSC-EVs. Furthermore, ADSC-EVs were found to transfer the lncRNA DLEU2 to macrophages, promoting M2 polarization, reducing inflammation response in lung injury cells, and enhancing their viability, proliferation, and apoptosis inhibition. Further functional experiments indicated that lncRNA DLEU2 promotes M2 polarization of macrophages by regulating miR-106a-5p/LXN, thereby enhancing the viability and proliferation of lung injury cells and inhibiting apoptosis. Overexpression of miR-106a-5p could reverse the biological effects of ADSC-EVs-DLEU2 on MLE-12 and LEPC in vitro cell models. Lastly, in vivo animal experiments confirmed that ADSC-EVs-DLEU2 promotes high expression of LXN by inhibiting the expression of miR-106a-5p, further facilitating M2 macrophage polarization and reducing lung edema, thus alleviating sepsis-induced lung injury. lncRNA DLEU2 in ADSC-EVs may promote M2 polarization of macrophages and enhance the viability and proliferation of lung injury cells while inhibiting inflammation and apoptosis reactions, thus ameliorating sepsis-induced lung injury in a mechanism involving the regulation of the miR-106a-5p/LXN axis.

Beyond ENO1, emerging roles and targeting strategies of other enolases in cancers.

Aerobic glycolysis is a hallmark property of cancer metabolism. Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate into phosphoenolpyruvate. In mammals, enolases exist in three isoforms, encoded by the genes ENO1, ENO2, and ENO3. The altered expression of enolases is a common occurrence in various types of cancer. Although most published studies on enolases have predominantly focused on the role of ENO1 in cancer, ENO2 and ENO3 have recently emerged as crucial regulatory molecules in cancer development. Significant progress has been made in understanding their multifaceted roles in oncogenesis. In this comprehensive review, we provide an overview of the structure, subcellular localization, diagnostic and prognostic significance, biological functions, and molecular mechanisms of ENO2 and ENO3 in cancer progression. The importance of enolase in cancer development makes it a novel therapeutic target for clinical applications. Furthermore, we discuss anticancer agents designed to target enolases and summarize their anticancer efficacy in both in vitro and in vivo studies.

miR-214 could promote myocardial fibrosis and cardiac mesenchymal transition in VMC mice through regulation of the p53 or PTEN-PI3K-Akt signali pathway, promoting CF proliferation and inhibiting its ng pathway.

INTRODUCTION: This study aimed to investigate the role of miR-214 in the bidirectional regulation of p53 and PTEN and its influence on myocardial fibrosis and cardiac mesenchymal transformation in mice with viral myocarditis (VMC). METHODS: The study established a VMC model in BALB/c mice by injecting them with the CVB3 virus intraperitoneally. Techniques such as ELISA, H&E staining, Masson staining, immunohistochemical staining, RT-qPCR, western blot, and dual-luciferase reporter gene assay were used to detect the expression levels of relevant factors in tissues and cells. Isolation and culture of cardiac fibroblasts (CFs) were also conducted. RESULTS: The study found that miR-214 bidirectional regulation of p53 and PTEN promotes myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. The expression levels of collagen-related peptides, inflammatory-related factors, miR-214, mesenchymal transformation-related factors, and fibrosis-related factors were significantly increased, while the expression levels of p53, PTEN, and epithelial/endothelial cell phenotype marker factors were significantly decreased. Downregulation of miR-214 or upregulation of p53 and PTEN expression inhibited inflammatory cell and fibroblast infiltration in VMC mouse myocardial tissue. It reduced the proliferation ability while increasing the apoptosis of cardiac fibroblasts. CONCLUSION: miR-214 plays a significant role in the bidirectional inhibition of p53 and PTEN, which leads to myocardial fibrosis and cardiac mesenchymal transformation in mice with VMC. Downregulation of miR-214 or upregulation of p53 and PTEN expression may provide potential therapeutic targets for treating VMC-induced cardiac fibrosis and mesenchymal transformation.

Ginsenoside Rg3 alleviates the migration, invasion, and angiogenesis of lung cancer cells by inhibiting the expressions of cyclooxygenase-2 and vascular endothelial growth factor.

Lung cancer (LC) is a common cancer with high incidence and mortality rates. In recent years, ginsenoside Rg3 (Rg3), a traditional medicine, is widely used for the treatment of LC. Herein, we concentrate on assessing the effect of Rg3 on LC cell migration and invasion. The effects of Rg3 (0, 25, 50, and 100 µg/ml) on the viability, migration, invasion, angiogenesis, and expressions of epithelial-mesenchymal transition (EMT)-related proteins, cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) of LC cell lines were evaluated by cell counting kit-8 (CCK-8), scratch, transwell, tube formation, and western blot assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess transfection efficiency. COX2 overexpression plasmid and short hairpin RNA for VEGF (shVEGF) were applied to evaluate whether the effect of Rg3 is related to COX2 and VEGF through rescue assay. In this study, Rg3 significantly dose-dependently suppressed the viability, migration, invasion, angiogenesis, and protein expressions of N-cadherin, vimentin, COX2, and VEGF in H1299 and A549 cells, while promoting the expression of E-cadherin protein. COX2 overexpression markedly reversed the effects of Rg3 on the viability, migration, invasion, angiogenesis, and EMT-related protein expression levels in LC cells; however, such effects of COX2 overexpression were offset by VEGF knockdown. In sum, Rg3 alleviates the migration, invasion, and angiogenesis of LC cells by inhibiting the expressions of COX2 and VEGF.

Results of the performance test for quality assessment of personal radiation dosimetry services including the influence of the dosimeter readout frequency.

This study was to determine the significance of factors considered for the measurement accuracy of personal dosimeter in dosimetry services such as dosimetry service, irradiation category, years of use and readout frequency. The investigation included management information questionnaire, on-site visit and blind test. The blind test with random selected personal badge was used in inter-comparison of eight dosimetry services, and the test results followed ANSI/HPS N13.11 criteria. This study also analyzed the measurement deviations if they felt in the criteria of ICRP 75 or not. One-way ANOVA tests were used to analyze the significant difference of the measurement deviations in different dosimetry services, irradiation categories, and years of use. Simple linear-regression test was performed for the significance of the prediction model between measurement deviations and readout frequencies. All visited dosimetry services followed the proper statue of basic management and passed the performance check of the tolerance level. The average deviations corresponding to category I, category II deep dose, and category II shallow dose were 6.08%, 9.49%, and 10.41% respectively. There had significant differences of measurement deviation in different dosimetry services (p < 0.0001) and irradiation categories (p = 0.016) but no significant difference in years of use (p = 0.498). There was no significance in the linear-regression model between measurement deviation and badge readout frequencies. Based on the regular calibration of the personal dosimeter, the deviation of the measured value is mainly affected by different dosimetry services and irradiation categories; and there shows no significant influence by years of use and readout frequency.

Involvement of the TNF-α/SATB2 axis in the induced apoptosis and inhibited autophagy of osteoblasts by the antipsychotic Risperidone.

BACKGROUND: Risperidone, an atypical antipsychotic, impedes serotonin and dopamine receptor systems. Meanwhile, tumor necrosis factor-α (TNF-α) is known to participate in regulating osteoblast functions. Consequently, the current study aimed to investigate whether the influences of Risperidone on osteoblast functions are associated with TNF-α and special AT-rich sequence-binding protein (SATB2). METHODS: Firstly, we searched the DGIdb, MEM and GeneCards databases to identify the critical factors involved in the effects of Risperidone on osteoblasts, as well as their interactions. Afterwards, osteoblast cell line MC3T3-E1 was transduced with lentivirus carrying si-TNF-α, si-SATB2 or both and subsequently treated with Risperidone. Various abilities including differentiation, autophagy and apoptosis of osteoblasts were examined after different treatments. Finally, animal experiments were performed with Risperidone alone or together with lentivirus to verify the function of Risperidone in vivo and the mechanism. RESULTS: It was found that Risperidone might promote TNF-α expression, thereby inhibiting the expression of SATB2 to affect the autophagy and apoptosis in osteoblasts. Furthermore, as shown by our experimental findings, Risperidone treatment inhibited the differentiation and autophagy, and promoted the apoptosis of osteoblasts, as evidenced by elevated levels of OPG, p62, cleaved PARP1, cleaved caspase-3, cleaved caspase-8, and cleaved caspase-9, and reduced levels of LC3 II/I, Beclin1, collagen I, and RANKL. In addition, Risperidone was also found to elevate the expression of TNF-α to down-regulate SATB2, thereby inhibiting the differentiation and autophagy and enhancing the apoptosis of osteoblasts in vitro and in vivo. CONCLUSIONS: Collectively, our findings indicated that Risperidone affects the differentiation of osteoblasts by inhibiting autophagy and enhancing apoptosis via TNF-α-mediated down-regulation of SATB2.

Assessment of the Novel, Practical, and Prognosis-Relevant TNM Staging System for Stage I-III Cutaneous Melanoma.

Background: The clinical TNM staging system does not differ between the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging manual. A more practical TNM staging system for patients with stage I-III cutaneous melanoma are needed. Methods: Data were accessed from the Surveillance, Epidemiology, and End Results (SEER) open database. We divided the patients into 32 groups based on the T and N categories. The Kaplan-Meier survival curves and treatment guidelines were used to proposed a new TNM staging system. Cox proportional hazards model and 1000-person-years were used to verify accuracy. Results: This retrospective study included 68 861 patients from 2010 to 2015. The new proposed staging system was as follows: stage IA, T1aN0M0; stage IB, T1b/T2aN0M0; stage IIA, T3-4aN0M0 and T2bN0M0; stage IIB, T1-4aN1-2M0 and T3-4bN0M0; and stage III, T1-4aN3M0 and T1-4bN1-3M0. Hazard ratios for the new stages IB, IIA, IIB, and III, with stage IA as reference, were 4.311 (95% confidence interval [CI]: 3.217-5.778), 8.993 (95% CI: 6.637-12.186), 13.179 (95% CI: 9.435-18.407), and 20.693 (95% CI: 13.655-31.356), respectively (all p-values < 0.001). Cancer-specific mortality rates per 1000-person-years were 0.812 (95% CI: 0.674-0.978), 6.612 (95% CI: 5.936-7.364), 22.228 (95% CI: 20.128-24.547), 50.863 (95% CI: 47.472-54.496) and 120.318 (95% CI: 112.596-128.570) for stages IA, IB, IIA, IIB and III, respectively. Conclusion: We developed a more practical and prognosis-relevant staging system than that of the 8th edition AJCC manual for patients with stage I-III cutaneous melanoma. Treatments using this new model would improve the quality of life and survival rates of patients with melanoma.

Exploration of the Value of Combined UA, IL-6, and fPSA/tPSA in the Diagnosis of Prostate Cancer.

Objective: To investigate the differences in uric acid (UA), interleukin-6 (IL-6), and free prostatic-specific antigen (fPSA)/total prostatic-specific antigen (tPSA) (F/T) between patients with and without prostate cancer (PCa) in order to discover the value of the three indicators in improving PCa diagnostic accuracy. Methods: Patients with pathologically diagnosed PCa (PCa group, n = 25), patients with other benign prostate diseases (benign group, n = 25), and men who underwent normal physical examination (control group, n = 25) at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between October 2020 and January 2021 were included. The serum UA, IL-6, and F/T levels of participants in the three groups were measured, and the measured data were statistically analyzed. Results: There were statistically significant differences in IL-6 and F/T among the three groups (all P < 0.05), but there were no statistically significant differences in UA (P > 0.05). The area under the receiver operating characteristic (ROC) curve (AUC) for the three indicators was, respectively, as follows: PCa group-benign group 0.5416, 0.6776, and 0.6832; PCa group-control group 0.5432, 0.9536, and 0.9887; and benign group-control group 0.5000, 0.8784, and 0.9456. Logistic regression analysis indicated that IL-6 and F/T were independent predictors of PCa, with AUCs of 0.6776 and 0.6832, respectively, and a combined accuracy of 72.0%. Conclusion: These results suggest that IL-6 and F/T have a good detection effect for PCa screening. Compared with the detection of F/T alone, the combined detection of IL-6 and F/T can improve the diagnosis rate of PCa to a certain extent, providing effective guidance for the clinical diagnosis and treatment of patients. The value of UA needs to be further studied, and its feasibility in the diagnosis of PCa needs to be further explored.

A new proposed tumor-node-metastasis-age staging system for stage IV medullary thyroid carcinoma based on the SEER database.

Medullary thyroid carcinoma (MTC) is a rare and lethal cancer. There are currently controversies regarding its staging. This study aimed to verify the significance of the patient's age in the prognosis of MTC and propose its addition to the current staging system. Data on cancer-specific survival (CSS) from the Surveillance, Epidemiology, and End Results database between 2010 and 2015 were used. X-Tile, nomograms, Cox proportional hazards regression analysis, Kaplan-Meier curves, and log-rank tests were used to evaluate mortality rates to create a new staging system. A total of 849 patients were included. Patients were divided into three categories based on their ages at diagnosis: ≤41 years, n = 224 (26.4%); 42-71 years, n = 516 (60.8%); and ≥72 years, n = 109 (12.8%). Independent factors for survival in the multivariate analysis included age (42-71 years, hazard ratio [HR], 2.81, 95% confidence interval [CI], 1.07-7.42; ≥72 years, HR, 8.71, 95% CI, 2.88-26.34), T stage (T2, HR, 3.60, 95% CI, 1.31-9.88), and M stage (M1, HR, 8.43, 95% CI, 4.40-16.16), with P<0.05. The Harrell's concordance index for tumor node metastasis (TNM) nomogram and TNM-age nomogram was 0.904 and 0.908, respectively. The areas under the curve (AUCs) for a 3-year CSS were 0.88 and 0.873, respectively. The corresponding AUCs for a 5-year CSS were 0.892 and 0.888, respectively. A new TNM-age staging system based on cancer-specific mortality rate analysis is proposed. This system provides a more accurate risk stratification and ensures more rational treatment measures for patients with stage IV MTC.

Surgical Disparities of Parathyroid Carcinoma: Long-Term Outcomes and Deep Excavation Based on a Large Database.

PURPOSE: Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients. METHODS: Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection. RESULTS: The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all P < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment. CONCLUSION: The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC.

Comparing the Value of Cystatin C and Serum Creatinine for Evaluating the Renal Function and Predicting the Prognosis of COVID-19 Patients.

Background: Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. Objective: This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. Methods: A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan-Meier survival, and curve fitting analyses. Results: When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity (p < 0.001), and elevated creatinine levels were independent predictors of death (p = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels (p < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Conclusions: Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death.

Refusal of cancer-directed surgery in male breast cancer.

ABSTRACT: It has been reported that some male breast cancer patients may refuse the recommended surgery, but the incidence rate in the United States is not clear. The purpose of this study was to identify the incidence, trends, risk factors, and eventual survival outcomes associated with the rejection of such cancer-directed surgery.We collected data on 5860 patients with male breast cancer (MBC) from the Surveillance, Epidemiology, and End Results database, including 50 patients refusing surgery as recommended. Kaplan-Meier survival analysis and Cox proportional hazard regression were used to identify the effects of refusing surgery on cancer-specific survival (CSS) and overall survival (OS). The association between acceptance or rejection of surgery and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age, race, clinical characteristics, and radiation.Of the 5860 patients identified, 50 (0.9%) refused surgery. Old age (≥65: hazard ratio [HR]: 3.056, 95% confidence interval [CI]: 1.738-5.374, P < .0001), higher AJCC stage (III: HR: 3.283, 95% CI: 2.134-5.050, P < .0001, IV: HR: 14.237, 95% CI: 8.367-24.226, P < .0001), progesterone receptor status (negative: HR: 1.633, 95% CI: 1.007-2.648, P = .047) were considered risk factors. Compared with the surgery group, the refusal group was associated with a poorer prognosis in both OS and CSS (χ2 = 94.81, P < .001, χ2 = 140.4, P < .001). Moreover, significant differences were also observed in OS and CSS among 1:3 matched groups (P = .0002, P < .001).Compared with the patients undergoing surgery, the patients who refused the cancer-directed surgery had poor prognosis in the total survival period, particularly in stage II and III. The survival benefit for undergoing surgery remained even after adjustment, which indicates the importance of surgical treatment before an advanced stage for male breast cancer patients.

Continuous archwire technique for the correction of completely transposed maxillary incisors.

Tooth transposition is an uncommon disorder related to ectopic eruption; it can be classified as complete or incomplete on the basis of the position of the crowns and roots of transposed teeth. Aligning the transposed teeth to a normal sequence is always complex and challenging, especially in patients with complete transposition. The segmented archwire technique with cantilever or loops has been used in many transposition patients; however, it requires considerable laboratory work and is sometimes uncomfortable for the patient. In this case report, we present a novel orthodontic treatment for an 8-year-old boy with unilateral complete transposition of the maxillary central incisor and lateral incisor (Mx.I2.I1). During the alignment stage, the lateral incisor was moved palatally to bypass the central incisor, using a 0.012-in nickel-titanium wire continuously. Active orthodontic treatment was conducted for 44 months, and the final outcome was esthetically and functionally effective. Stable and satisfactory results were achieved within 4 years of follow-up.

Novel analysis of prognosis of young patients with stage II differentiated thyroid cancer based on AJCC 8.0 and 6.0 criteria to implement the staging system.

BACKGROUND: The incidence of thyroid cancer among young adults is increasing; however, the clinical challenges specific to this population, such as diagnosis, reduced healthcare access, and inconsistent care, have received limited attention. Here, we conducted a subgroup analysis on a series of relatively young patients with differentiated thyroid carcinomas (DTCs), focusing on those with distant metastases at stage II, to obtain a deeper understanding of the factors influencing survival. METHODS: Information on <45- or <55-year-old patients at any T/N stage with distant metastasis (M1) was extracted from the SEER database according to the staging system in the 6th and 8th American Joint Committee on Cancer (AJCC) editions, respectively. Patient mortality was evaluated using Cox proportional hazards regression analyses and Kaplan-Meier analyses with log-rank tests. RESULTS: Both cancer-specific and all-cause mortality rates per 1,000 person-years for patients ≥35 years old significantly differed from those of patients <35 years old. DTC-specific survival curves also significantly differed between these age groups, according to both the AJCC 6.0 and 8.0-based analyses (P=0.0017 and P<0.001, respectively), as did patient survival curves (P=0.0003, P<0.001, respectively). The multivariate Cox regression model also revealed that poor OS was strongly predicted by race (P<0.001) in the analysis based on the criteria of 8th AJCC staging system. CONCLUSIONS: Age is a risk factor for disease-specific and overall survival (OS) in young patients with stage II DTC, and young male patients exhibited poorer survival than females. Race also emerged as a potential risk factor for young patients in stage II. These findings offer guidance for improving the older and newer versions of the AJCC staging system.

Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database.

OBJECTIVES: In this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer. MATERIALS AND METHODS: Cox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate. RESULTS: A total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4-2.3, p < 0.001; HR = 1.9, 95% CI: 1.6-2.3, p < 0.001; HR = 1.4, 95% CI: 1.0-1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2-1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3-1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9-1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects. CONCLUSION: Patients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.

Synergic effects of histology subtype, lymph node metastasis, and distant metastasis on prognosis in differentiated thyroid carcinoma using the SEER database.

BACKGROUND: Differentiated thyroid carcinoma (DTC) is the most common clinical type of thyroid carcinoma. There are rare reports on the synergic effects of the different clinicopathological risk factors on the prognosis of it. METHODS: We retrospectively reviewed data on 86,032 DTC patients from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were conducted to evaluate the correlation between clinicopathological factors and the prognosis of DTC. Relative excess risk (RERI) of synergic effect, attributable proportion (AP) of synergic effect, and synergy index (SI) were calculated to assess synergic effects. Kaplan-Meier analyses with log-rank tests was used to plot the survival curve affected by different risk factors. RESULTS: Histology subtype, lymph node metastasis (LNM) status, and distant metastasis (DM) were independent risk factors for cancer-specific survival (CSS) and all-cause survival (ACS) in the multivariate analysis (all, P<0.001). Patients' age at diagnosis, sex, extrathyroidal extension, and radiation also influenced prognosis (all, P<0.001). The cancer-specific mortality (CSM) and all-cause mortality (ACM) rates per 1,000 person-years were higher in patients with follicular thyroid carcinoma (FTC) and in those with N1 stage and M1 stage disease. Furthermore, we observed a significant synergic effect between histology subtype and N stage, as well as histology subtype and M stage for the CSM of DTC (RERI =48.806, AP =0.853, SI =7.565; RERI =37.889, AP =0.430, SI =1.771, respectively). However, no synergic effect was observed in the case of the N stage and M stage for the CSM of DTC (RERI =7.928, AP =0.084, SI =1.093). CONCLUSIONS: Patients with histology subtype of FTC and N1 stage, histology subtype of FTC and M1 stage had significant additive synergic effects on DTC prognosis for CSM.

New proposed tumor-node-metastasis staging system for medullary thyroid carcinoma based on the Surveillance, Epidemiology, and End Results database.

BACKGROUND: Medullary thyroid carcinoma (MTC) has been separated into its own chapter in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. However, controversies still exist for the staging of MTC. This study aimed to identify prognostic differences among patients with MTC to define a more accurate staging system. METHODS: Data on cancer-specific survival from the Surveillance, Epidemiology, and End Results database between 2010 and 2014 were used for this study. Kaplan-Meier (K-M) curves, Cox proportional hazards regression analysis, and mortality per 1000-person-years were used to evaluate the mortality rate to create the new staging system. RESULTS: A total of 960 cases were included in this analysis. The mortality rates of 24 different groups, which were classified using T stage (T1-4), N stage (N0-1b), and M stage (M0-1) were assessed using K-M curves. Cox proportional hazards regression analysis and mortality per 1000-person-years were used to classify patients, as stage I (T1-3N0-1aM0, 654, 68.34%), stage II (T1-3N1bM0, 181, 18.91%), stage III (T4N0-1bM0, 58, 6.06%), and stage IV (T1-4N0-1bM1, 64, 6.69%). The hazard ratios of stages II, III, and IV, using stage I as a reference, were 5.281 (95% confidence interval [CI], 1.236-22.562), 20.603 (95% CI, 4.400-96.467), and 55.717 (95% CI, 14.307-216.988), respectively. The mortality rates per 1000-person-years of stages I, II, III, and IV were 2.036 (95% CI, 0.657-6.312), 14.867 (95% CI, 6.679-33.092), 98.287 (95% CI, 54.432-177.478), and 224.199 (95% CI, 146.180-343.860), respectively. CONCLUSIONS: Compared with the current AJCC tumor-node-metastasis (TNM) staging system for MTC, this new proposed TNM staging system, which is based on cancer-specific mortality rate analysis, provides more accurate risk stratification and can ensure more rational treatment measures.

Clinical characteristics of emergency surgery patients infected with coronavirus disease 2019 (COVID-19) pneumonia in Wuhan, China.

BACKGROUND: We aimed to investigate clinical symptoms and epidemiologic features of emergency surgery patients infected with the 2019 novel coronavirus disease (COVID-19). More than 5 million people worldwide have been diagnosed with COVID-19 since December 2019 to the time of this publication. Thousands of emergency operations have been carried out since December 2019. To date, however, no literature has focused on the clinical symptoms of emergency surgery patients with COVID-19 pneumonia. METHODS: We conducted a retrospective cohort study of 164 emergency surgery patients with or without COVID-19 pneumonia in Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1, 2020, to January 20, 2020. For this report, the final date of follow-up was February 5, 2020. The associated clinical, laboratory, epidemiologic, demographic, radiologic, and outcome data were collected and analyzed. RESULTS: Of the 164 emergency surgery patients, the median age was 41 years (interquartile range, 29-89), and 136 (82.9%) were women. The associated main clinical symptom included fever (93 [56.7%])，dry cough (56 [34.2%]), fatigue (86 [52.4%]), nausea (78 [47.6%]), and dizziness (77 [47%]). Of 54 emergency surgery patients infected with COVID-19, the median age was 46 years (interquartile range: 25-89), and 45 (83.3%) were women. The pathologic clinical symptoms investigated included fever (54 [100%]), fatigue (48 [88.9%]), nausea (52 [96.3%]), dizziness (46 [85.2%]), and dry cough (44 [81.5%]). The lymphopenia (0.37 × 109/L [interquartile range: 0.23-0.65]) and increased C-reactive protein (24.7 × 109/L [interquartile range: 13.57-38]) were observed. The preoperative fever and postoperative fever in emergency surgery patients with or without COVID-19 pneumonia were analyzed in this study. Of 54 emergency surgery patients with COVID-19, 15 (27.8%) showed preoperative fever, 54 (100%) had postoperative fever. Of 110 emergency surgery patients without COVID-19, 5 (4.5%) had preoperative fever, 31 (28.2%) patients had postoperative fever. In emergency surgery patients with COVID-19, the fever lasted more than 7 days, markedly exceeded the length of time non-COVID-19 patients experienced fever (approximately 3 days). Furthermore, 43 health care workers were exposed to emergency surgery patients with COVID-19 pneumonia and were infected with COVID-19 pneumonia. CONCLUSION: In our study, the clinical symptoms of emergency surgery patients infected with COVID-19 displayed marked differences from those reporting common COVID-19 pneumonia. In addition, the health care workers were suspected to have been exposed to a great risk when caring for emergency surgery patients with COVID-19 pneumonia. Management guidelines of emergency surgery patients are described in in this report.