Epidemiological Insights into Foodborne Pathogens Through qPCR Exploration of Prevalence - Beijing Municipality, China, January 2022-April 2023.

What is already known on this topic?: Foodborne diseases present a substantial global health risk. Traditional diagnostic methods have constraints, but advancements in molecular techniques, like quantitative polymerase chain reaction (qPCR), provide a hopeful solution. What is added by this report?: We examined 1,011 stool samples from individuals suspected of foodborne illnesses. Our analysis indicated a significant presence of Clostridium perfringens, Salmonella enterica, enterotoxigenic Escherichia coli (ETEC), and adenovirus. Notably, co-infections were identified in 71.22% of the samples. What are the implications for public health practice?: The data emphasize a notable prevalence of co-infections, highlighting the complexity of foodborne illnesses. This study underscores the significance of utilizing contemporary diagnostic methods in densely populated urban areas such as Beijing Municipality.

Applying dynamic contrast-enhanced MRI tracer kinetic models to differentiate benign and malignant soft tissue tumors.

BACKGROUND: To explore the potential of different quantitative dynamic contrast-enhanced (qDCE)-MRI tracer kinetic (TK) models and qDCE parameters in discriminating benign from malignant soft tissue tumors (STTs). METHODS: This research included 92 patients (41females, 51 males; age range 16-86 years, mean age 51.24 years) with STTs. The qDCE parameters (Ktrans, Kep, Ve, Vp, F, PS, MTT and E) for regions of interest of STTs were estimated by using the following TK models: Tofts (TOFTS), Extended Tofts (EXTOFTS), adiabatic tissue homogeneity (ATH), conventional compartmental (CC), and distributed parameter (DP). We established a comprehensive model combining the morphologic features, time-signal intensity curve shape, and optimal qDCE parameters. The capacities to identify benign and malignant STTs was evaluated using the area under the curve (AUC), degree of accuracy, and the analysis of the decision curve. RESULTS: TOFTS-Ktrans, EXTOFTS-Ktrans, EXTOFTS-Vp, CC-Vp and DP-Vp demonstrated good diagnostic performance among the qDCE parameters. Compared with the other TK models, the DP model has a higher AUC and a greater level of accuracy. The comprehensive model (AUC, 0.936, 0.884-0.988) demonstrated superiority in discriminating benign and malignant STTs, outperforming the qDCE models (AUC, 0.899-0.915) and the traditional imaging model (AUC, 0.802, 0.712-0.891) alone. CONCLUSIONS: Various TK models successfully distinguish benign from malignant STTs. The comprehensive model is a noninvasive approach incorporating morphological imaging aspects and qDCE parameters, and shows significant potential for further development.

Characteristics and survival of primary urothelial carcinoma of the prostate: A multi-center retrospective study of 18 cases.

OBJECTIVES: To explore the features, treatment, and outcomes of primary urothelial carcinoma of the prostate (PUCP) in a multicenter study. METHODS: The clinical and imaging features, pathological findings, treatment, and outcomes of patients diagnosed with PUCP from January 2011 to April 2022 at three institutions were collected and analyzed. The Kaplan-Meier method and log-rank test were used to assess survival rates of the overall group and survival differences between groups according to TNM stage. RESULTS: The study cohort comprised 18 patients with PUCP of mean age 72.4±7.8 years. Dysuria and urinary frequency were the most common symptoms (77.8 %). Sixteen (88.9 %) patients had normal serum total PSA concentrations. Most patients showed abnormalities on urinalysis. MRI was the most accurate diagnostic imaging method (88.9 %). As to immunohistochemistry findings, GATA-3 (81.8 %) and P63 (84.6 %) were positive in most examined patients; however, no lesions were positive for PSA. Three (17.6 %) patients with T1N0M0 and T2N0M0 tumors underwent radical cystectomy. Eleven (64.7 %) patients which almost all had T4 tumors received systematic therapy, most of them receiving chemotherapy with gemcitabine and cisplatin, and radiotherapy. The median overall survival was 42 months, and the median progression-free survival 25 months, the latter being significantly longer in patients with T1-2 than in those with T3-4 disease (p=0.035). CONCLUSION: PUCP, a rare but highly aggressive type of prostate cancer, should be considered in men with abnormalities on MRI and normal serum PSA concentrations. Positive GATA-3, P63, and negative PSA are typical immunohistochemistry features. Radical cystectomy and systematic therapies can be effective.

Deep Learning Radiomics Nomogram Based on Enhanced CT to Predict the Response of Metastatic Lymph Nodes to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer.

BACKGROUND: We aimed to construct and validate a deep learning (DL) radiomics nomogram using baseline and restage enhanced computed tomography (CT) images and clinical characteristics to predict the response of metastatic lymph nodes to neoadjuvant chemotherapy (NACT) in locally advanced gastric cancer (LAGC). METHODS: We prospectively enrolled 112 patients with LAGC who received NACT from January 2021 to August 2022. After applying the inclusion and exclusion criteria, 98 patients were randomized 7:3 to the training cohort (n = 68) and validation cohort (n = 30). We established and compared three radiomics signatures based on three phases of CT images before and after NACT, namely radiomics-baseline, radiomics-delta, and radiomics-restage. Then, we developed a clinical model, DL model, and a nomogram to predict the response of LAGC after NACT. We evaluated the predictive accuracy and clinical validity of each model using the receiver operating characteristic curve and decision curve analysis, respectively. RESULTS: The radiomics-delta signature was the best predictor among the three radiomics signatures. So, we developed and validated a DL delta radiomics nomogram (DLDRN). In the validation cohort, the DLDRN produced an area under the receiver operating curve of 0.94 (95% confidence interval, 0.82-0.96) and demonstrated adequate differentiation of good response to NACT. Furthermore, the DLDRN significantly outperformed the clinical model and DL model (p < 0.001). The clinical utility of the DLDRN was confirmed through decision curve analysis. CONCLUSIONS: In patients with LAGC, the DLDRN effectively predicted a therapeutic response in metastatic lymph nodes, which could provide valuable information for individualized treatment.

Incremental value of radiomics-based heterogeneity to the existing risk criteria in predicting recurrence of hepatocellular carcinoma after liver transplantation.

OBJECTIVES: The aim of the study was to evaluate the association between the radiomics-based intratumoral heterogeneity (ITH) and the recurrence risk in hepatocellular carcinoma (HCC) patients after liver transplantation (LT), and to assess its incremental to the Milan, University of California San Francisco (UCSF), Metro-Ticket 2.0, and Hangzhou criteria. METHODS: A multicenter cohort of 196 HCC patients were investigated. The endpoint was recurrence-free survival (RFS) after LT. A CT-based radiomics signature (RS) was constructed and assessed in the whole cohort and in the subgroups stratified by the Milan, UCSF, Metro-Ticket 2.0, and Hangzhou criteria. The R-Milan, R-UCSF, R-Metro-Ticket 2.0, and R-Hangzhou nomograms which combined RS and the four existing risk criteria were developed respectively. The incremental value of RS to the four existing risk criteria in RFS prediction was evaluated. RESULTS: RS was significantly associated with RFS in the training and test cohorts as well as in the subgroups stratified by the existing risk criteria. The four combined nomograms showed better predictive capability than the existing risk criteria did with higher C-indices (R-Milan [training/test] vs. Milan, 0.745/0.765 vs. 0.677; R-USCF vs. USCF, 0.748/0.767 vs. 0.675; R-Metro-Ticket 2.0 vs. Metro-Ticket 2.0, 0.756/0.783 vs. 0.670; R-Hangzhou vs. Hangzhou, 0.751/0.760 vs. 0.691) and higher clinical net benefit. CONCLUSIONS: The radiomics-based ITH can predict outcomes and provide incremental value to the existing risk criteria in HCC patients after LT. Incorporating radiomics-based ITH in HCC risk criteria may facilitate candidate selection, surveillance, and adjuvant trial design. KEY POINTS: • Milan, USCF, Metro-Ticket 2.0, and Hangzhou criteria may be insufficient for outcome prediction in HCC after LT. • Radiomics allows for the characterization of tumor heterogeneity. • Radiomics adds incremental value to the existing criteria in outcome prediction.

Dynamics analysis of the anterior cruciate ligament reconstruction surgery based on magnetic resonance imaging.

In clinical practice, anterior cruciate ligament (ACL) rupture is always repaired by the single-beam reconstruction method. Before the surgery, the surgeon made the diagnosis based on medical images, such as CT (computerized tomography) and MR (magnetic resonance) images. However, little is known about how biomechanics governs the biological nature for femoral tunnel position. In the present study, three volunteers' motion trails were captured by six cameras when they were doing squat movement. The medical image can reconstruct the structure of the ligaments and bones and a left knee model was reconstructed by MIMICS by MRI data of DICOM format. Finally, the effects of different femoral tunnel positions on ACL biomechanics were characterized by the inverse dynamic analysis method. The results showed that there were significant differences in the direct mechanical effects of the anterior cruciate ligament at different locations of the femoral tunnel (p < 0.05), the peak stress of ACL in the low tension area was 1097.24 ± 25.55 N, and the peak stress of ACL in the distal femur was 356.81 ± 15.39 N, both of which were much higher than that in the direct fiber area (118.78 ± 20.68 N).

A comparative study of modern total ankle replacement and ankle arthrodesis for ankle osteoarthritis at different follow-up times: a systematic review and meta-analysis.

PURPOSE: Total ankle replacement (TAR) or ankle arthrodesis (AA) is the main surgical treatment for end-stage ankle osteoarthritis. However, the therapeutic effect of the two surgical procedures at different follow-up times remains controversial. The purpose of this meta-analysis is to compare the short-term, medium-term, and long-term safety and efficiency of the two modern surgical treatments. METHODS: We conducted a comprehensive search in PubMed, EMBASE, Cochrane library databases, Web of Science, and Scopus. The main results were the patient's reported outcome measure (PROM) score, satisfaction, complications, reoperation, and surgery success rate. Different follow-up times and implant designs were used to evaluate the source of heterogeneity. We used a fixed effects model for meta-analysis and I2 statistic for evaluating heterogeneity. RESULTS: Thirty-seven comparative studies were included. In the short term, TAR significantly improved clinical scores (AOFAS score: WMD = 7.07, 95% Cl: 0.41-13.74, I2 = 0.0%; SF-36 PCS score: WMD = 2.40, 95% Cl: 2.22-2.58, I2 = 0.0%; SF-36 MCS score: WMD = 0.40, 95% Cl: 0.22-0.57, I2 = 0.0%; VAS for pain: WMD = - 0.50, 95% Cl: - 0.56-0.44, I2 = 44.3%) and had the lower incidence of revision (RR = 0.43, 95% CI: 0.23-0.81, I2 = 0.0%) and complications (RR = 0.67, 95% Cl: 0.50-0.90, I2 = 0.0%). In the medium term, there were still higher improvements in both the clinical scores (SF-36 PCS score: WMD = 1.57, 95% Cl: 1.36-1.78, I2 = 20.9%; SF-36 MCS score: WMD = 0.81, 95% Cl: 0.63-0.99, I2 = 48.8%) and the patient satisfaction (RR = 1.24, 95% Cl: 1.08-1.41, I2 = 12.1%) in the TAR group, but its total complications rate (RR = 1.84, 95% Cl: 1.26-2.68, I2 = 14.9%) and revision rate (RR = 1.58, 95% CI: 1.17-2.14, I2 = 84.6%) were significantly higher than that of the AA group. In the long term, there was no significant difference in clinical score and satisfaction, and a higher incidence of revision (RR = 2.32, 95% Cl: 1.70-3.16, I2 = 0.0%) and complications (RR = 3.18, 95% Cl: 1.69-5.99, I2 = 0.0%) was observed in TAR than in AA. The result of the third-generation design subgroup was consistent with that of the above pooled results. CONCLUSION: TAR had advantages over AA in the short term due to better performance in terms of PROMs, complications, and reoperation rates, but its complications become a disadvantage in the medium term. In the long term, AA seems to be favored because of lower complications and revision rates, although there is no difference in clinical scores.

An MRI-Based Radiomics Nomogram to Assess Recurrence Risk in Sinonasal Malignant Tumors.

BACKGROUND: Sinonasal malignant tumors (SNMTs) have a high recurrence risk, which is responsible for the poor prognosis of patients. Assessing recurrence risk in SNMT patients is a current problem. PURPOSE: To establish an MRI-based radiomics nomogram for assessing relapse risk in patients with SNMT. STUDY TYPE: Retrospective. POPULATION: A total of 143 patients with 68.5% females (development/validation set, 98/45 patients). FIELD STRENGTH/SEQUENCE: A 1.5-T and 3-T, fat-suppressed fast spin echo (FSE) T2-weighted imaging (FS-T2WI), FSE T1-weighted imaging (T1WI), and FSE contrast-enhanced T1WI (T1WI + C). ASSESSMENT: Three MRI sequences were used to manually delineate the region of interest. Three radiomics signatures (T1WI and FS-T2WI sequences, T1WI + C sequence, and three sequences combined) were built through dimensional reduction of high-dimensional features. The clinical model was built based on clinical and MRI features. The Ki-67-based and tumor-node-metastasis (TNM) model were established for comparison. The radiomics nomogram was built by combining the clinical model and best radiomics signature. The relapse-free survival analysis was used among 143 patients. STATISTICAL TESTS: The intraclass/interclass correlation coefficients, univariate/multivariate Cox regression analysis, least absolute shrinkage and selection operator Cox regression algorithm, concordance index (C index), area under the curve (AUC), integrated Brier score (IBS), DeLong test, Kaplan-Meier curve, log-rank test, optimal cutoff values. A P value < 0.05 was considered statistically significant. RESULTS: The T1 + C-based radiomics signature had best prognostic ability than the other two signatures (T1WI and FS-T2WI sequences, and three sequences combined). The radiomics nomogram had better prognostic ability and less error than the clinical model, Ki-67-based model, and TNM model (C index, 0.732; AUC, 0.765; IBS, 0.185 in the validation set). The cutoff values were 0.2 and 0.7 and then the cumulative risk rates were calculated. DATA CONCLUSION: A radiomics nomogram for assessing relapse risk in patients with SNMT may provide better prognostic ability than the clinical model, Ki-67-based model, and TNM model. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 5.

Effect of melatonin on quality of life and symptoms in patients with cancer: a systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: This study systematically reviewed the effect of melatonin (MLT) on quality of life (QoL) and symptoms among patients with cancer. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Cochrane Library, PubMed, Embase, Web of Science, Medline, CINAHL, Scopus, ClinicalTrials.gov, China Biology Medicine (CBM), ProQuest and Open Grey were searched from inception to November 2021. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) assessing the effects of MLT on QoL, sleep quality, fatigue, depression, pain, stomatitis rate and stomatitis severity in adult patients with cancer, without language restrictions. Studies that reported the effects of MLT along with other interventions and had incomplete or absent outcome data were excluded. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data, and another two reviewers assessed the risk of bias. The risk of bias for each eligible study was assessed using the Cochrane assessment tool. The mean difference or standard mean difference (SMD) with 95% CIs was used in the computation of continuous variables to synthesise data. The relative risk was used for dichotomous outcomes. Heterogeneity was assessed and quantified (I2 statistic). RESULTS: A total of 19 qualified studies that included 2101 patients with cancer (MLT: 1078, control: 1023) were included in the meta-analysis. The results indicated that MLT had no significant effect on QoL (SMD=-0.01, 95% CI (-0.14 to 0.11), p=0.83), sleep quality (SMD=-0.18, 95% CI (-0.62 to 0.26), p=0.42), fatigue (SMD=-0.34, 95% CI (-0.73 to 0.06), p=0.10), pain (SMD=-0.34, 95% CI (-0.7 to 0.02), p=0.06) or stomatitis severity (RR=0.78, 95% CI (0.47 to 1.30), p=0.35). MLT reduced stomatitis rate among patients with cancer (RR=0.47, 95% CI (0.26 to 0.88), p=0.02), except those with head and neck cancer (RR=1.09, 95% CI (0.92 to 1.29), p=0.35). MLT eased depression in patients who received administration for more than 14 days (SMD=-0.14, 95% CI (-0.27 to -0.01), p=0.03) and those who underwent surgery (SMD=-0.17, 95% CI (-0.32 to -0.03), p=0.02). CONCLUSION: The findings showed that MLT did not improve the QoL, sleep quality, fatigue, pain or stomatitis severity among patients with cancer. It had a limited effect on decreasing the stomatitis rate and easing depression. Different treatments, durations and cancer types were the main sources of heterogeneity. Further large-scale RCTs are urgently needed. In addition, the effects of different combinations of MLT dosage and duration, administration types and joint measures are worthy of further study. PROSPERO REGISTRATION NUMBER: CRD42021292855.

Development and validation of a nomogram to predict anastomotic leakage in colorectal cancer based on CT body composition.

Background: Anastomotic leakage (AL) is one of the most serious postoperative complications. This study aimed to investigate the predictive value of preoperative body composition for AL in patients with colorectal cancer (CRC). Methods: We first reviewed data from 3,681 patients who underwent radical CRC resection 2013-2021 in our hospital, and 60 patients were diagnosed with AL after surgery. We designed a nested case-control study and two controls were randomly selected for each case according to the time and position of surgery. Body composition was measured at the level of the third lumbar vertebra based on computed tomography (CT) images. The risk factors of AL were analyzed by univariate and multivariate analysis. Nomogram was built using binary regression analysis and assessed for clinical usefulness, calibration, and discrimination. Results: In the multivariate analysis, gender, blood glucose, nutrition risk screening (NRS), skeletal muscle area (SMA) and visceral fat area (VFA) were independent risk factors for developing anastomotic leakage after surgery. The prognostic model had an area under the receiver operating characteristic curve of 0.848 (95% CI, 0.781-0.914). The calibration curve showed good consistency between the predicted and observed outcomes. Decision curve analysis indicated that patients with colorectal cancer can benefit from the prediction model. Conclusions: The nomogram that combined with gender, blood glucose, NRS, SMA, and VFA had good predictive accuracy and reliability to AL. It may be conveniently for clinicians to predict AL preoperatively and be useful for guiding treatment decisions.

Multi-parametric MRI-based radiomics signature for preoperative prediction of Ki-67 proliferation status in sinonasal malignancies: a two-centre study.

OBJECTIVE: To assess the predictive ability of a multi-parametric MRI-based radiomics signature (RS) for the preoperative evaluation of Ki-67 proliferation status in sinonasal malignancies. METHODS: A total of 128 patients with sinonasal malignancies that underwent multi-parametric MRIs at two medical centres were retrospectively analysed. Data from one medical centre (n = 77) were used to develop the predictive models and data from the other medical centre (n = 51) constitute the test dataset. Clinical data and conventional MRI findings were reviewed to identify significant predictors. Radiomics features were determined using maximum relevance minimum redundancy and least absolute shrinkage and selection operator algorithms. Subsequently, RSs were established using a logistic regression (LR) algorithm. The predictive performance of RSs was assessed using calibration, decision curve analysis (DCA), accuracy, and AUC. RESULTS: No independent predictors of high Ki-67 proliferation were observed based on clinical data and conventional MRI findings. RS-T1, RS-T2, and RS-T1c (contrast enhancement T1WI) were established based on a single-parametric MRI. RS-Combined (combining T1WI, FS-T2WI, and T1c features) was developed based on multi-parametric MRI and achieved an AUC and accuracy of 0.852 (0.733-0.971) and 86.3%, respectively, on the test dataset. The calibration curve and DCA demonstrated an improved fitness and benefits in clinical practice. CONCLUSIONS: A multi-parametric MRI-based RS may be used as a non-invasive, dependable, and accurate tool for preoperative evaluation of the Ki-67 proliferation status to overcome the sampling bias in sinonasal malignancies. KEY POINTS: • Multi-parametric MRI-based radiomics signatures (RSs) are used to preoperatively evaluate the proliferation status of Ki-67 in sinonasal malignancies. • Radiomics features are determined using maximum relevance minimum redundancy (mRMR) and least absolute shrinkage and selection operator (LASSO) algorithms. • RSs are established using a logistic regression (LR) algorithm.

Predictors for the risk of permanent pacemaker implantation after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a less invasive treatment than surgery for severe aortic stenosis. However, its use is restricted by the fact that many patients eventually require permanent pacemaker implantation (PPMI). This meta-analysis was performed to identify predictors of post-TAVR PPMI. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched. Relevant studies that met the inclusion criteria were included in the pooling analysis after quality assessment. RESULTS: After pooling 67 studies on post-TAVR PPMI risk in 97,294 patients, balloon-expandable valve use was negatively correlated with PPMI risk compared with self-expandable valve (SEV) use (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.37-0.53). Meta-regression analysis revealed that history of coronary artery bypass grafting and higher Society of Thoracic Surgeons (STS) risk score increased the risk of PPMI with SEV utilization. Patients with pre-existing cardiac conduction abnormalities in 28 pooled studies also had a higher risk of PPMI (OR: 2.33, 95% CI: 1.90-2.86). Right bundle branch block (OR: 5.2, 95% CI: 4.37-6.18) and first-degree atrioventricular block (OR: 1.97, 95% CI: 1.38-2.79) also increased PPMI risk. Although the trans-femoral approach was positively correlated with PPMI risk, the trans-apical pathway showed no statistical difference to the trans-femoral pathway. The approach did not increase PPMI risk in patients with STS scores >8. Patient-prosthesis mismatch did not influence post-TAVR PPMI risk (OR: 0.88, 95% CI: 0.67-1.16). We also analyzed implantation depth and found no difference between patients with PPMI after TAVR and those without. CONCLUSIONS: SEV selection, pre-existing cardiac conduction abnormality, and trans-femoral pathway selection are positively correlated with PPMI after TAVR. Pre-existing left bundle branch block, patient-prosthesis mismatch, and implantation depth did not affect the risk of PPMI after TAVR.

N6-methyladenosine (m6A) RNA modification in the pathophysiology of heart failure: a narrative review.

Background and Objective: Heart failure is the end-stage of various cardiovascular diseases. Recent progress in molecular biology has facilitated the understanding of the mechanisms of heart failure development at the molecular level. N6-adenosine methylation (m6A) is a post-transcriptional modification of RNA. Recent research work reported that m6A regulates gene expression and subsequently affects the activation of cell signaling pathways related to heart failure. Moreover, m6A regulators like methyltransferase-like 3 (METTL3) were reported to participate in myocardium hypertrophy. However, the current research work related to the role of m6A participating in the occurrence of heart failure is rare in some aspects like immune cell infiltration and diabetic heart diseases. Thus, it is reasonable to review the current achievements and provide further study orientation. Methods: We searched related literature using the keywords: m6A AND heart failure in PubMed, Web of Science and Medline. The language was confined to English. The published year of searched literature ranged from 2012 to 2022. The searched results were put into Endnote software for management. Two authors investigated the searching terms and reviewed the full text of selected terms. Key Content and Findings: m6A and its regulators are involved in the metabolism of various types of RNAs. m6A modification can regulate various types of cell signaling pathways related to the heart failure via interaction with m6A regulators. m6A and its regulators broadly participate in the myocardium fibrosis, myocardium hypertrophy, myocardial cell apoptosis, and ischemic reperfusion injury. Specifically, m6A participates in the cell apoptosis via regulation of autophagy flux. However, the current research work does not have enough evidence to prove that m6A regulator played its specific effect on the target transcript via regulating the m6A level. Conclusions: m6A and its regulators participates in the progression of heart failure via modifying the RNA level. Future investigation of m6A should focus on the interaction between the m6A regulators and targeted transcript. Besides, the regulation role of m6A in immune cell infiltration and diabetic heart diseases should also be focused.

Identification of a Novel Epigenetic Signature CHFR as a Potential Prognostic Gene Involved in Metastatic Clear Cell Renal Cell Carcinoma.

Metastasis is the main cause of clear cell renal cell carcinoma (ccRCC) treatment failure, and the key genes involved in ccRCC metastasis remain largely unknown. We analyzed the ccRCC datasets in The Cancer Genome Atlas database, comparing primary and metastatic ccRCC tumor records in search of tumor metastasis-associated genes, and then carried out overall survival, Cox regression, and receiver operating characteristic (ROC) analyses to obtain potential prognostic markers. Comprehensive bioinformatics analysis was performed to verify that the checkpoint with forkhead associated and ring finger domains (CHFR) gene is a reliable candidate oncogene, which is overexpressed in ccRCC metastatic tumor tissue, and that high expression levels of CHFR indicate a poor prognosis. A detailed analysis of the methylation of CHFR in ccRCC tumors showed that three sites within 200 bp of the transcription initiation site were significantly associated with prognosis and that hypomethylation was associated with increased CHFR gene expression levels. Knockdown of CHFR in ccRCC cells inhibited cell proliferation, colony formation, and migration ability. In summary, our findings suggest that the epigenetic signature on CHFR gene is a novel prognostic feature; furthermore, our findings offer theoretical support for the study of metastasis-related genes in ccRCC and provided new insights for the clinical treatment of the disease.

The Clinical Relevance and Tumor Promoting Function of C19orf10 in Kidney Renal Clear Cell Carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common primary renal neoplasms. Currently, there are few molecular indicators and therapeutic targets that can be used in diagnostic and prognostic assessment. In this study, we identified the C19orf10 expression in KIRC specimens and explored the diagnostic and prognostic value of C19orf10 in KIRC using TCGA and CPTAC database. Loss-of- and gain-of- function of C19orf10 was performed to investigate the roles of C19orf10 on KIRC cell viability, proliferation, migration and invasion via CCK-8, Edu incorporation and Transwell assays respectively. C19orf10 was overexpressed in KIRC tissues and the elevated C19orf10 expression was closely associated with clinicopathological characteristics of KIRC including histological grade, TNM stage, metastatic status. Silencing C19orf10 significantly suppressed the viability, proliferation, migration and invasion ability, while overexpression of C19orf10 promoted the progression and malignant phenotype in KIRC cells. Furthermore, C19orf10 exerted its carcinogenic function by regulating ZO-1 and PTEN/Akt signaling pathway. Moreover, the Kaplan-Meier survival analysis, Cox regression analysis and receiver operating curve analysis showed that patients with C19orf10 overexpression have poor survival time. C19orf10 could discriminate KIRC patients with high-risk from low-risk. Taken together, C19orf10 contributes to KIRC development via ZO-1 and PTEN/Akt signaling pathway and C19orf10 could serve as a potential diagnostic and prognostic candidate and therapeutic target of KIRC.

Nomogram for Predicting Chemotherapy-Induced Nausea and Vomiting for Breast Cancer Patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatment. The factors influencing CINV in breast cancer patients remain unclear. In this study, we developed a nomogram for predicting the occurrence of CINV in this group using prospective clinical data. We pooled data from multiple studies which focused on the emetogenic chemotherapy. Then, we collected 334 breast cancer patients at Hunan Cancer Hospital (training set) to analyze the demographic and clinical variables. Using multivariate logistic regression, we identified the five significant factors that were associated with CINV: history of CINV, chemotherapy regimen, chemotherapy cycle, metastasis, and symptoms of distress. Then, we construct a prediction nomogram. The external validation set comprised an additional 66 patients. The reliability of the nomogram was assessed by bootstrap resampling. The C-index was 0.78 (95% confidence interval [CI], 0.73-0.85) for the training set and 0.74 (95% CI, 0.62-0.85) for the validation set. Calibration curves showed good concordance between predicted and actual occurrence of CINV. In conclusions, our nomogram model can reliably predict the occurrence of CINV in breast cancer patients based on five significant variables, which might be useful in clinical decision-making.

PAPP-A functions as a tumor suppressor and is downregulated in renal cell carcinoma.

Pregnancy-associated plasma protein A (PAPP-A) is a proteolytic enzyme produced by the placenta. The expression and role of PAPP-A in renal cell carcinoma (RCC) remain elusive. The aim of this study was to investigate the role and the molecular mechanisms of PAPP-A in RCC. Initially, we evaluated the expression of PAPP-A in samples from patients with RCC and cell lines by quantitative PCR, western blot and immunohistochemical staining, and examined the role of PAPP-A in RCC cells by cell viability, colony formation and Transwell assays. Next, we investigated the molecular mechanisms regulating the tumor suppressor function of PAPP-A. Our results demonstrated that PAPP-A is expressed at low levels in RCC tissues and cells. Clinical data analysis revealed a significant correlation between PAPP-A expression and RCC-related death (P < 0.0115). Overexpression of PAPP-A inhibited viability, proliferation, migration and invasion of RCC cells. Furthermore, PAPP-A overexpression significantly increased phosphorylation of c-Jun N-terminal kinase and decreased the expression of cyclin D1, phosphorylated glycogen synthase kinase-3ß and ß-catenin. This study is the first to report that downregulation of PAPP-A is associated with poor prognosis in patients with RCC. In conclusion, PAPP-A may serve as a novel prognostic marker and potentially as a therapeutic target in patients with RCC.