Predictive value of CXCL1+_FAP+ phenotype in CAFs for distant metastasis and its correlation with PD-L1 expression in locoregionally advanced nasopharyngeal carcinoma patients.

OBJECTIVE: There is a lack of effective biomarkers for predicting the distant metastasis in nasopharyngeal carcinoma (NPC). We aimed to explore the expression of FAP+Cancer-associated fibroblasts (CAFs) derived CXCL1 in NPC and its predictive values for distant metastasis and correlation with PD-L1 expression. MATERIALS AND METHODS: A total of 345 patients with locoregionally advanced NPC were retrospectively enrolled (the training cohort: the validation cohort = 160:185). Co-expression of CXCL1 and FAP and the expression of PD-L1 were detected by multi-immunofluorescence staining and immunohistochemistry, respectively. The primary end-point was distant metastasis-free survival (DMFS). The Kaplan-Meier method was used to calculate the survival. The Cox proportional hazards model was used to assess prognostic risk factors. RESULTS: A novel CXCL1+_FAP+ phenotype in CAFs was identified in NPC and then used to divide patients into low and high risk groups. Both in the training cohort and validation cohort, patients in the high risk group had poorer DMFS, overall survival (OS), progression-free survival (PFS) and locoregional relapse-free survival (LRFS) than patients in the low risk group. Multivariate analysis revealed CXCL1+_FAP+ phenotype was an independent prognostic factor for DMFS, OS, PFS and LRFS. Further results showed patients in the high risk group had higher PD-L1 expression than those in the low risk group. CONCLUSION: Our study showed CXCL1+_FAP+ phenotype in CAFs could effectively classified locoregionally advanced NPC patients into different risk groups for distant metastasis and might be a potential biomarker for anti-PD-1/PD-L1 immunotherapy.

Evolution of genome and immunogenome in esophageal squamous cell carcinomas driven by neoadjuvant chemoradiotherapy.

Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is a standard treatment for locally advanced esophageal squamous cell carcinomas (ESCCs). However, the evolution of genome and immunogenome in ESCCs driven by NCRT remains incompletely elucidated. We performed whole-exome sequencing of 51 ESCC tumors collected before and after NCRT, 36 of which were subjected to transcriptome sequencing. Clonal analysis identified clonal extinction in 13 ESCC patients wherein all pre-NCRT clones disappeared after NCRT, and clonal persistence in 9 patients wherein clones endured following NCRT. The clone-persistent patients showed higher pre-NCRT genomic intratumoral heterogeneity and worse prognosis than the clone-extinct ones. In contrast to the clone-extinct patients, the clone-persistent patients demonstrated a high proportion of subclonal neoantigens within pre-treatment specimens. Transcriptome analysis revealed increased immune infiltrations and up-regulated immune-related pathways after NCRT, especially in the clone-extinct patients. The number of T cell receptor-neoantigen interactions was higher in the clone-extinct patients than in the clone-persistent ones. The decrease in T cell repertoire evenness positively correlated to the decreased number of clonal neoantigens after NCRT, especially in the clone-extinct patients. In conclusion, we identified two prognosis-related clonal dynamic modes driven by NCRT in ESCCs. This study extended our knowledge of the ESCC genome and immunogenome evolutions driven by NCRT.

Effect of cervical pillow in phacoemulsification surgery for age-related cataract patients: a prospective randomized controlled study.

PURPOSE: To explore the application effect of cervical pillow in phacoemulsification surgery for age-related cataract patients. METHODS: 104 cases of age-related cataract patients admitted to our hospital in June 2023 were enrolled and divided into the control group (traditional supine position) and the experimental group (the cervical pillow supine position) by the digital parity method (52 cases per group). The two groups were evaluated for the discomfort score, the satisfaction of patients and doctors, the head displacement rate, the number of displacement, the operation time and the time of body position during the operation and after the operation. RESULTS: There was no significant difference in the gender (P = 0.84), age (P = 0.86), course of disease (P = 0.82) and the time spent on position placement (P = 0.15) of the two groups. The patient in the experimental group had lower discomfort score (P = 0.0001), higher patients satisfaction (P = 0.0001) and higher doctors satisfaction (P = 0.0001) than patients in the control group. There was no significant difference between the experimental group and the control group in the proportion of intraoperative (P = 0.36) and postoperative pain (P = 0.65). Besides, the number of head transfers (P = 0.001), number of head shifts (P = 0.0001), the surgical time (P = 0.0001) and laparoscopic time (P = 0.0001) in the experimental group were significantly lower than those in the control group. CONCLUSION: The additional cervical pillow for age-related cataract patients in the traditional supine position during the operation will not increase the preparation time before the operation, but will help improve the patient satisfaction, improve the comfort and maintain a good position of the operative eye field, bringing obvious comfort and smooth operation for the surgeon in the operation, thus reducing the risk of the operation, shortening the operation time.

Diagnostic yield using electromagnetic navigation bronchoscopy for peripheral pulmonary nodules <2 cm.

BACKGROUND: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation. OBJECTIVES: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm. DESIGN: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated. METHODS: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery. RESULTS: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010). CONCLUSION: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Laparoscopic liver resection is superior to radiofrequency ablation for small hepatocellular carcinoma: a systematic review and meta-analysis of propensity score-matched studies.

BACKGROUND: The approach in small hepatocellular carcinoma (HCC) is controversial, no prospective randomized trials to compare ablative or surgical approaches. We compared the surgical and oncological outcomes after laparoscopic hepatectomy (LH) and radiofrequency ablation (RFA) in small HCC patients based on matched cohort studies that performed propensity score matching (PSM). METHODS: We systemically searched the PubMed, Cochrane Library, Embase, Web of Science, and the Chinese BioMedical Literature (CBM) databases. All published propensity score-matched studies that compared LH and RFA for small HCC were included in this study. RESULTS: Eight studies with a total of 1273 small HCC cases were included. The results of the meta-analysis revealed that there was no significant difference in the 1- year overall survival (OS) rate between the two groups, whereas the LH group had significantly higher 3- year overall survival rate (RR = 1.14, 95% CI 1.08-1.20, p < 0.00001) as well as 1- and 3-year disease-free survival (DFS) rates (RR = 1.31, 95% CI 1.22-1.42, p < 0.00001; RR = 1.66, 95% CI 1.46-1.90, p < 0.00001) than the RFA group. Meanwhile, the local recurrence rate and intrahepatic distant recurrence rate were significantly lower in the LH group than in the RFA group (RR = 0.29, 95% CI 0.20-0.42, p < 0.00001; RR = 0.67, 95% CI 0.49-0.92, p = 0.01). In comparison with the LH group, the RFA group had a lower incidence of overall and major postoperative complications (RR = 1.81, 95% CI 1.47-2.24, p < 0.00001; RR = 2.76, 95% CI 1.48-5.12, p = 0.001), but there was no significant difference in postoperative mortality between the two groups. In addition, further comparison of single postoperative complications showed that the incidence of ascites was lower in the RFA group than in the LH group (RR = 3.62, 95% CI 1.64-7.96, p = 0.001), whereas there was no significant difference in the incidence of postoperative bleeding, abdominal infection and bile leakage between the two groups (RR = 3.50, 95% CI 0.74-16.61, p = 0.11; RR = 5.00, 95% CI 0.59-42.23, p = 0.14; RR = 4.00, 95% CI 0.45-35.23, p = 0.21). Besides, the hospital stay was shorter in the RFA group than in the LH group (MD = 4.29, 95% CI 2.06-6.53, p = 0.0002). CONCLUSIONS: Our meta-analysis demonstrated that in comparison with RFA in the treatment of small HCC, LH provided superior long-term OS and DFS together with lower rates of local and intrahepatic distant recurrence after surgery. However, RFA was associated with better short-term outcomes.

Existential distress and associated factors in advanced cancer patients: A cross-sectional study.

BACKGROUND: Advanced cancer patients often experience existential distress (ED). However, the factors associated with ED remain unclear. This study investigated the current state of ED and identified the associated factors in Chinese patients with advanced cancer. METHODS: A cross-sectional study was conducted among 352 advanced cancer patients from 3 tertiary hospitals in Fujian, China. Participants were invited to complete the Existential Distress Scale, Number Rating Scale, Self-Perceived Burden Scale, Quality of Life Concerns in the End-of-Life Questionnaire, and Hospital Anxiety and Depression Scale. OBJECTIVES: This study aimed to investigate the level of existential distress among advanced cancer patients in China and identify the associated factors. RESULTS: A total of 352 advanced cancer patients were recruited for this study. The average score for ED was 8.48 ± 7.12 among the advanced cancer patients. Multiple regression showed that the associated factors included depression (ß = 0.32, p = 0.000), self-perceived burden (SPB) (ß = 0.18, p = 0.001), the presence of a spouse (ß = -0.10, p = 0.050), and reception of government subsidies (ß = 0.17, p = 0.001). The factors accounted for 30.1% of the total variance in ED (F = 8.472, p < 0.001). SIGNIFICANCE OF RESULTS: Among the advanced cancer patients queried, ED was found to be positively influenced by depression, SPB, and reception of government subsidies and negatively influenced by the presence of a spouse. Depression was the most important risk factor, and thus future ED interventions should target depression.

Concurrent chemoradiotherapy versus radiotherapy alone in older patients with stage II nasopharyngeal carcinoma after intensity-modulated radiotherapy: A propensity score-matched cohort study.

BACKGROUND AND PURPOSE: Whether concurrent chemoradiotherapy (CCRT) benefits the older (age ≥ 60 years) patients with stage II nasopharyngeal carcinoma (NPC) has not been determined. This study aimed to compare the outcomes and toxicities of CCRT with Intensity-Modulated Radiotherapy (IMRT) alone in older patients with stage II NPC. MATERIALS AND METHODS: Between January 2010 and December 2017, 220 older (age ≥ 60 years) patients with stage II NPC were analyzed. A pair of 53 patients were matched between the CCRT group and RT group by using propensity score matching (PSM) in terms of age, sex, pathological type, T and N stage, ACE-27 scores, CRP, LDH and Hb. Cancer-specific survival (CSS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) were analysed by the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to assess the prognostic risk factors by using a Cox's proportional hazards regression model. Treatment toxicities were clarified and compared between the two groups by using the χ2 test. RESULTS: The median follow-up time of the whole cohort was 82.0 months (range, 11-151 months). PSM analysis indicated that compared with the RT group, significantly higher 5-year CSS (98.1 % vs. 83.0 %, P = 0.02), PFS (98.1 % vs. 79.2 %, P = 0.01) and DMFS (100.0 % vs. 92.4 %, P = 0.04) were observed in the CCRT group. Multivariate analysis showed that CCRT was an independent prognostic factor predicting CSS (HR, 0.34; 95 % CI, 0.15-0.79; P = 0.01), PFS (HR, 0.48; 95 % CI, 0.25-0.93; P = 0.03), and LRRFS (HR, 0.36; 95 % CI, 0.14-0.90; P = 0.03), and a higher ACE-27 score predicted a worse CSS. Patients in the CCRT group experienced higher frequencies of the acute toxicities than patients in the RT group. Late complications were comparable between the two groups. CONCLUSION: CCRT significantly improved the survival benefits for the older patients with stage II NPC compared with IMRT alone without adding late complications, whereas increased some of the treatment-associated acute toxicities.

Comparison of Postoperative Outcomes Between Near-Infrared Fluorescent Imaging-Guided Mediastinal Lymphadenectomy and Conventional Surgery for Esophageal Cancer.

BACKGROUND: The study aimed to evaluate the efficacy of using near-infrared fluorescent imaging (NIRF) imaging with indocyanine green as an intraoperative tool for achieving complete mediastinal lymph node (LN) resection. PATIENTS AND METHODS: Between September 2019 and July 2021, patients with potential for esophagectomy due to middle and lower thoracic esophageal cancer were enrolled in this study. All patients were scheduled for NIRF-guided mediastinal lymphadenectomy during esophageal cancer surgery and were appropriately assigned to the NIRF group. Patients who underwent esophagectomy between September 2017 and September 2019 were assigned to the historical control group upon satisfying the inclusion/exclusion criteria. Surgical outcomes and the number of removed LNs were compared between the two groups using 1:1 propensity score matching. RESULTS: Of 67 eligible patients, 59 patients were included in the NIRF group after postsurgical exclusions. The operative time was significantly shorter in the NIRF group than in the historical control group [180 (140-420) min versus 202 (137-338) min; P < 0.001]. The incidence of postoperative chylothorax and hoarseness were significantly lower in the NIRF group than in the historical control group (0% versus 10.2 %; P = 0.036, 3.4% versus 13.6%; P = 0.047). The number of dissected total LNs, mediastinal LNs, and negative LNs was significantly larger in the NIRF group than in the historical control group. The number of overall metastatic LNs and abdominal LNs was comparable between the two groups. CONCLUSIONS: NIRF imaging can assist in the thorough and complete mediastinal LNs dissections without increasing complications in patients undergoing esophagectomy.

The effect of body mass index on quality of life in modified single stoma cutaneous ureterostomy or ileal conduit after radical cystectomy.

OBJECTIVE: To explore the influence of postoperative body mass index (BMI) change on postoperative quality of life (QOL) in patients undergoing radical cystectomy (RC) plus modified single stoma cutaneous ureterostomy (MSSCU) or ileal conduit (IC). METHODS: Patients were divided into two groups according to different BMI change patterns: patients experiencing an elevated postoperative BMI level, along with a clinically significant increase in their BMI (an increase of more than 10%) were categorized as Group 1, while patients experiencing a decrease postoperative BMI level, along with a clinically significant reduction in their BMI (a decrease of more than 5%) were categorized as Group 2. Spearman correlation analysis was used to examine the correlations between quality-of-life scores and postoperative clinical parameters. RESULTS: Spearman correlation analysis showed that postoperative BMI, late complications and catheter-free state were significantly associated with postoperative global QoL and symptom scale in MSSCU and postoperative global QoL and physical scale in IC patients. Additionally, postoperative BMI, catheter-free state and the use of adjuvant therapy were associated with bad performance in many scales of QoL like body image, future perspective, social scale, future perspective (MSSCU), and abdominal bloating (IC) (Table 2, p<0.05). Patients in Group 2 with significant weight loss had a better Global QoL, a lower rate of stomal stricture and a higher catheter-free state compared with those in Group 1 in both IC and MSSCU patients. MSSCU patients in Group 2 could achieve a comparable Global QoL as to IC patients in Group 1. CONCLUSION: Controlling the substantial increase in body weight after surgery contributes to improving QoL, reducing the occurrence of stomal stricture, and ensuring a postoperative catheter-free state in BCa patients undergoing MSSCU.

Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

BACKGROUND AND OBJECTIVES: Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. METHODS: A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). RESULTS: In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. CONCLUSION: Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach.

Effect of Intrathoracic or Cervical Anastomosis After Esophagectomy on Quality of Life.

PURPOSE: We aimed to perform serial quality-of-life (QoL) evaluations and comparisons in patients after esophagectomy with intrathoracic anastomosis (IA) or cervical anastomosis (CA). METHODS: Between November 2012 and March 2015, patients who underwent esophagectomy with IA or CA for mid-esophageal to distal esophageal or gastroesophageal junction cancer were followed up. QoL was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) and esophagus-specific questionnaire (EORTC QLQ-OES18) before surgery, at discharge, and at 1, 6, 12, and 24 months after discharge. Linear mixed-effect models were used to assess the mean score differences (MDs) of each QoL scale between the two techniques, and changes in QoL over time. Potential confounders were adjusted. RESULTS: In total, 219 patients were analyzed (IA, n = 127; CA, n = 92). All patients' QoL decreased immediately after esophagectomy. Global QoL and most functioning and symptom scales exhibited a return to baseline levels within 2 years of discharge, except for physical functioning and several symptoms (dyspnea, diarrhea, dysphagia, and reflux). There was no difference in overall health score between the two groups (MD 2, 95% confidence interval [CI] - 1 to 6). Compared with IA, patients with CA reported more trouble with taste (MD - 12, 95% CI - 19 to - 4) and talking (MD - 11, 95% CI - 19 to 2) at discharge. No differences in long-term QoL were found between groups. CONCLUSIONS: CA was associated with more trouble with taste and talking in the short term than IA. The long-term QoL did not differ between the two approaches.

Th1-involved immune infiltrates improve neoadjuvant chemoradiotherapy response of esophageal squamous cell carcinoma.

Neoadjuvant chemoradiotherapy (NCRT) followed by surgery is recommended for locally advanced esophageal squamous cell carcinoma (ESCC) treatment. Patients who achieve a pathological complete response (pCR) have better survival. Our study aimed to discover immune-associated predictors of pCR in ESCC. Herein, we found that Th1-cell infiltration inferred from RNA sequencing was higher in the pCR group than in the non-pCR group. Multiplexed immunohistochemistry (mIHC) confirmed that Th1-, CD8+ T-, NK-, NKT-, and dendritic-cell infiltration was positively associated with pCR. The spatial relationships between Th1 cells and CD8+ T, NK, NKT, dendritic, or ESCC cells were significant pCR predictors. The active and desert subtypes were identified based on immune cell infiltration, and showed different pCR rates. In vitro experiments confirmed that Th1 cells inhibited the proliferation and improved the chemosensitivity and radiosensitivity of ESCC cells. Th1 cells upregulated interferon-gamma response signaling and antigen presentation pathways and downregulated lipid metabolism and MAPK pathways of ESCC cells. These findings highlight the important role of Th1 cells as the predictor of pCR and the regulator of chemosensitivity and radiosensitivity of ESCC, and suggest elevating Th1-infiltration as a strategy to improve NCRT response.

Impacts of neoadjuvant chemoradiotherapy on the immune landscape of esophageal squamous cell carcinoma.

BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the most common approach for locally advanced resectable esophageal squamous cell carcinoma (ESCC) patients. How neoCRT impacts ESCC tumor immune microenvironment (TIME) has not been fully understood. METHODS: Single-cell RNA sequencing (scRNA-seq) was conducted to examine the neoCRT-driven cellular and molecular dynamics in 8 pre- and 7 post-neoCRT ESCC samples from 8 male patients. FINDINGS: scRNA-seq data of about 112,000 cells were obtained. Expression programs of cell cycle, epithelium development, immune response, and extracellular structure in pre-treatment tumor cells were related to neoCRT response. Spearman correlation between CD8+ T cells' cytotoxicity and expression of checkpoint molecules was prominent in pre-neoCRT intermediate activated/exhausted CD8+ T cells. NeoCRT increased CD8+ T cells' infiltration but promoted their exhaustion in both major and minor responders. NeoCRT promoted differentiation of Th but demoted that of Treg cells in major responders. Maturation of cDC1s and expression of M2 macrophage markers increased while the number of cDC2s decreased after neoCRT. Higher activities of immune-related pathways in pre-neoCRT CD8+ T cells and macrophages, as well as a pronounced decrease of them after neoCRT, correlated with better neoCRT response. Interactions between intermediate activated/exhausted CD8+ T and macrophages, cDC1s, and LAMP3+ cDCs decreased after neoCRT. INTERPRETATION: Our comprehensive picture of the neoCRT-related immune changes provides deeper insights into immunological mechanisms associated with ESCC response to neoCRT, which may aid in future development of immune-strategies for improving ESCC treatment. FUNDING: This work was supported by the National Natural Science Foundation of China (82072607).

Role of 18F-FDG-PET/CT in Combination With Neutrophil-Lymphocyte Ratio in the Diagnosis of Upper Urinary Tract Lesion: Can We Accurately Predict Malignant Tumor?

OBJECTIVE: To explore whether preoperative 18Fluorine-Fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) in combination with neutrophil-lymphocyte ratio (NLR) could accurately predict malignant lesions of upper urinary tract (UUT). METHODS AND MATERIALS: The clinicopathologic data of a total of 252 patients with UUT lesions receiving surgical treatment at our center from January 2012 to November 2019 were retrospectively analyzed. All patients performed routine preoperative hematological examination, urine cytology, computed tomography urography (CTU), and 18F-FDG-PET/CT. Clinicopathologic data between 179 cases with malignancy (Group 1) and 73 cases with benign lesions (Group 2) were compared. Multivariate logistic regression analysis was used to explore the independent predictors of malignant UUT lesions. Receiver operating characteristic (ROC) curve was used to evaluate the predictive ability. RESULTS: Among all patients, univariate analysis showed that NLR, hydronephrosis, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis revealed that NLR, CTU indicating malignancy, and PET/CT indicating malignancy were independent predictors of malignant UUT lesions; the area under ROC curve (AUC) of NLR, CTU, PET/CT, combining CTU and NLR, combining PET/CT and NLR, and combining PET/CT and CTU were 0.735, 0.788, 0.857, 0.863, 0.913, and 0.919, respectively, for postoperative pathological malignancy. Among 68 patients undergoing ureteroscopy biopsy, univariate analysis suggested that NLR, positive urine exfoliation cytology, CTU indicating malignancy, and PET/CT indicating malignancy were significantly associated with malignant UUT lesions; multivariate analysis demonstrated that positive urine cytology, PET/CT indicating malignancy, and NLR were independent predictors of malignant UUT lesions; the AUC of NLR, ureteroscopy biopsy, and combining PET/CT and NLR were 0.768, 0.853, and 0.839, respectively, for postoperative pathological malignancy. CONCLUSIONS: Combining preoperative NLR and PET/CT performed well in differentiating benign from malignant UUT lesions, which could not be identified by traditional imaging or urine cytology. Combining preoperative NLR and PET/CT could be used to reduce unnecessary ureteroscopy biopsy, which might result in tumor cell dissemination and risk of associated complications.

Modeling iron release from cast iron pipes in an urban water distribution system caused by source water switch.

Significant iron release from cast iron pipes in water distribution systems (WDSs), which usually occurs during the source water switch period, is a great concern of water utilities because of the potential occurrence of "red water" and customer complaints. This study developed a new method which combined in-situ water stagnation experiments with mathematical models and numerical simulations to predict the iron release caused by source water switch. In-situ water stagnation experiments were conducted to determine the total iron accumulation in nine cast iron pipes in-service in Beijing when switching the local water to treated Danjiangkou Reservior water. Results showed that the difference in the concentration increment of total iron in 24 hr (ΔCITI,24), i.e. short-term iron release, caused by source water switch was mainly dependent on the difference in the key quality parameters (pH, hardness, nitrate, Larson Ratio and dissolved oxygen (DO)) between the two source waters. The iron release rate (RFe) after switch, i.e. long-term iron release, was closely related to the pipe properties as well as the DO and total residual chlorine (TRC) concentrations. Mathematical models of ΔCITI,24 and RFe were developed to quantitatively reveal the relationship between iron release and the key quality parameters. The RFe model could successfully combine with EPANET-MSX, a numerical simulator of water quality for WDSs to extend the iron release modeling from pipe level to network level. The new method is applicable to predicting iron release during source water switch, thus facilitating water utilities to take preventive actions to avoid "red water".

Long Noncoding RNA MALAT1 Regulates the Progression of Atherosclerosis by miR-330-5p/NF-κB Signal Pathway.

ABSTRACT: Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported to be related to atherosclerosis (AS) progression. However, the underlying mechanism of MALAT1 in AS remains unknown. Quantitative real-time polymerase chain reaction was performed to detect the expression of MALAT1 and miR-330-5p. Western blot was applied to assess the protein levels of cluster of differentiation 36, interleukin-1ß, interleukin-6 and tumor necrosis factor-α, phosphorylation of nuclear factor kappa-B inhibitor alpha and phosphorylation of p65. Flow cytometry assay, cell counting kit 8 assay, triglyceride, and total cholesterol detection assays were used to detect the apoptosis, viability, and lipid indexes of THP-1 macrophages-derived foam cells. Online database starbasev2.0 was used to predict the binding sequences between MALAT1 and miR-330-5p and it was verified by dual-luciferase reporter system and RNA immunoprecipitation assay. Besides, an AS mice model was used to evaluate the effect of MALAT1 in vivo. As a result, MALAT1 was overexpressed, whereas miR-330-5p was downregulated in THP-1 macrophages-derived foam cells. MiR-330-5p was a target of MALAT1. MALAT1 depletion inhibited cell formation, apoptosis, and inflammation in THP-1 macrophages-derived foam cells. Besides, MALAT1 overexpression promoted the inflammation in AS mice model, which promoted the pathogenesis of AS. Furthermore, miR-330-5p regulated the nuclear factor kappa light chain enhancer of activated B cells (NF-κB) pathway in THP-1 macrophages-derived foam cells. Moreover, MALAT1 regulated NF-κB signal pathway to mediate the pathogenesis of AS by sponging miR-330-5p. MALAT1 sponges miR-330-5p to activate NF-κB signal pathway in THP-1 macrophages-derived foam cells. This finding may provide a novel biomarker for AS diagnosis.

Identification of marker genes and cell subtypes in castration-resistant prostate cancer cells.

The diverse tumor cell populations may be the critical roles in relapse and resistance to treatment in prostate cancer patients. This study aimed to identify new marker genes and cell subtypes among castration-resistant prostate cancer (CRPC) cells. We downloaded single-cell RNA seq profiles (GSE67980) from the Gene Expression Omnibus (GEO) database. Principal component (PC) analysis and t-Distributed Stochastic Neighbor Embedding (TSNE) analysis were performed to identify marker genes. CRPC cells were clustered and annotated. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses among marker genes were performed. A total of 1500 genes with larger standardized variance were obtained. The top 20 genes were demonstrated in each identified 20 PCs. PC with P-value < 0.05 was selected, including PC1, PC7, PC8, and PC14. The TSNE analysis classified cells as two clusters. The top 6 genes in cluster 0 included HBB, CCL5, SLITRK4, GZMB, BBIP1, and PF4V1. Plus, the top 6 genes in cluster 1 included MLEC, CCT8, CCT3, EPCAM, TMPRSS2, EIF4G2. The GO analysis revealed that these marker genes were mainly enriched in RNA catabolic process, translational initiation, mitochondrial inner membrane, cytosolic part, ribosome, cell adhesion molecule binding, cadherin binding, and structural constituent of ribosome. The KEGG analysis showed that these marker genes mainly enriched in metabolism associated pathways, including carbon metabolism, cysteine and methionine metabolism, propanoate metabolism, pyruvate metabolism, and citrate cycle pathways. To conclude, our results provide essential insights into the spectrum of cellular heterogeneity within human CRPC cells. These marker genes, GO terms and pathways may be critical in the development and progression of human CRPC.

Identification of Prostate Cancer-Related Circular RNA Through Bioinformatics Analysis.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignant tumors worldwide. Accumulating evidence has suggested that circular RNAs (circRNAs) are involved in the development and progression of various cancers, and they show great potential as novel biomarkers. However, the underlying mechanisms and specific functions of most circRNAs in PCa remain unknown. Here, we aimed to identify circRNAs with potential roles in PCa from the PCa expression profile. METHODS: We used data downloaded from the Gene Expression Omnibus to identify circRNAs that were differentially expressed between PCa samples and adjacent non-tumor samples. Relative expression levels of identified circRNAs were validated by quantitative real-time PCR. Micro (mi)RNA response elements were predicted by the CircInteractome database, and miRNA target genes were predicted by miRDB, miRTarBase, and TargetScan databases. Gene ontology (GO) enrichment analysis and pathway analysis revealed the potential biological and functional roles of these target genes. A circRNA-miRNA-mRNA interaction network was constructed by Cytoscape. The interaction between circRNAs and miRNAs in PCa was thoroughly reviewed in the PubMed. Finally, the mRNA expression of these genes was validated by the Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The expression of proteins encoded by these genes was further validated by the Human protein Atlas (HPA) database. RESULTS: A total of 60 circRNAs that were differentially expressed between PCa and healthy samples were screened, of which 15 were annotated. Three circRNAs (hsa_circ_0024353, hsa_circ_0085494, hsa_circ_0031408) certified the criteria were studied. The results of quantitative real-time PCR demonstrated that the expression of hsa_circ_0024353 was significantly downregulated in PC-3 cells when compared with RWPE-1 cells, while the expression of hsa_circ_0031408 and hsa_circ_0085494 was significantly upregulated in PC-3 cells when compared with RWPE-1 cells. GO and Kyoto Encyclopedia of Genes and Genomes analyses found that target genes were mainly enriched in metabolic processes and pathways involving phosphoinositide 3-kinase-Akt signaling, hypoxia-inducible factor-1 signaling, p53 signaling, and the cell cycle. A total of 11 miRNA target genes showing differential expression between PCa and healthy samples were selected, and their mRNA and protein expression were validated by GEPIA and HPA databases, respectively. Of these, PDE7B, DMRT2, and TGFBR3 were identified as potentially playing a role in PCa progression. Finally, three circRNA-miRNA-mRNA interaction axes were predicted by bioinformatics: hsa_circ_0024353-hsa-miR-940-PDE7B, hsa_circ_0024353-hsa-miR-1253-DMRT2, and hsa_circ_0085494-hsa-miR-330-3p-TGFBR3. CONCLUSION: This study identified three circRNA-miRNA-mRNA interaction axes that might provide novel insights into the potential mechanisms underlying PCa development.