NEK2 contributes to radioresistance in esophageal squamous cell carcinoma by inducing protective autophagy via regulating TRIM21.

BACKGROUND: Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms. METHODS: Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM). RESULTS: In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21. CONCLUSION: These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.

Effect of exposures to multiple metals on blood pressure and hypertension in the elderly: a community-based study.

A chronic disease, hypertension (HTN) is prevalent among the elderly. Exploring the factors that influence HTN and blood pressure (BP) changes is of great public health significance. However, mixed exposure to multiple serum metals has had less research on the effects on BP and HTN for the elderly. From April to August 2019, 2372 people participated in the community physical examination program for the elderly in Tongling City, Anhui Province. We measured BP and serum levels of 10 metals and collected basic demographic information. We analyzed the relationship between metal levels and changes in BP and HTN by the least absolute shrinkage and selection operator regression, Bayesian kernel machine regression model, and generalized linear model. In multiple models, lead (Pb) and cadmium (Cd) were still significantly associated with HTN occurrence after adjusting for potential confounders (Pb: ORquartile 4 VS quartile 1 = 1.20, 95% CI 1.01-1.43; Cd: ORquartile 4 VS quartile 1 = 1.37, 95% CI 1.16-1.62). In the male subgroup, results were similar to those of the general population. In the female group, Cd was positively correlated with HTN and systolic blood pressure, while Pb was not. According to this study, Pb and Cd were correlated with BP and HTN positively, and there was a certain joint effect. To some extent, our findings provide clues for the prevention of hypertension in the elderly.

Microascones, Decahydrofluorene-Class Alkaloids from the Marine-Derived Fungus Microascus sp. SCSIO 41821.

Eight new decahydrofluorene-class alkaloids, microascones A and B (1 and 2), 2,3-epoxyphomapyrrolidone C (3), 14,16-epiascomylactam B (4), 24-hydroxyphomapyrrolidone A (5), and microascones C-E (6-8), along with five known analogs (9-13) were isolated from the marine-derived fungus Microascus sp. SCSIO 41821. Compounds 1 and 2 have an unprecedented complex macrocyclic alkaloid skeleton with a 6/5/6/5/6/5/13 polycyclic system. Their structures and absolute configurations were determined by spectroscopic analysis, quantum chemical calculations of ECD spectra, and 13C NMR chemical shifts. Compounds 10-13 showed selective enzyme inhibitory activity against PTPSig, PTP1B, and CDC25B, and 4, 9, and 10 exhibited strong antibacterial activity against seven tested pathogens. Their structure-bioactivity relationship was discussed, and a plausible biosynthetic pathway for 1-8 was also proposed.

Anlotinib in patients with recurrent platinum resistant/refractory ovarian cancer: a prospective, single arm, phase II study.

OBJECTIVE: This study aimed to prospectively evaluate the efficacy and safety of anlotinib in patients with platinum resistant/refractory ovarian cancer. METHODS: In this prospective, single arm, phase II study, patients with platinum resistant/refractory ovarian cancer received anlotinib (12 mg once daily; days 1-14; 21 days per cycle) until disease progression, unacceptable toxicity, or study withdrawal. The study was conducted between May 2019 and May 2021. The primary endpoint was objective response rate. Secondary endpoints were disease control rate, progression free survival, overall survival, and safety. An exploratory biomarker analysis was performed to evaluate the correlation of baseline TP53 mutation status with outcomes. RESULTS: 33 of 34 enrolled patients received at least one dose of anlotinib. The objective response rate was 31.2% (95% confidence interval (CI) 16.1% to 50.0%), with 2 (6.3%) complete and 8 (25.0%) partial responses. In total, 14 (43.8%) patients achieved stable disease, resulting in a disease control rate of 75.0% (95% CI 56.6% to 88.5%). With a median follow-up of 4.6 months (range 0.5-17.2) at data cut-off (September 16, 2022), median progression free survival was 5.3 months (95% CI 4.04 to 6.56) and median overall survival was not reached. In a subgroup analysis, patients with a TP53 mutation showed a trend towards worse progression free survival than those with the wild-type TP53 (4.4 months vs 8.4 months; hazard ratio 2.48 (95% CI 0.91 to 6.76), p=0.067). Common adverse events were hypertension (42.4%), hand-foot syndrome (27.3%), and fatigue (24.2%). Grade 3 events were reported in 3 (9.1%) patients and no grade 4-5 events or deaths were observed. CONCLUSION: Anlotinib showed antitumor activity with an acceptable safety profile in patients with platinum resistant/refractory ovarian cancer, and it might be a potential treatment in this population.

The impact of ambient air pollutants on childhood respiratory system disease and the resulting disease burden: a time-series study.

PURPOSE: The effects of air pollution on human health have long been a hot topic of research. For respiratory diseases, a large number of studies have proved that air pollution is one of the main causes. The purpose of this study was to investigate the risk of hospitalization of children with respiratory system diseases (CRSD) caused by six pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) in Hefei City, and further calculate the disease burden. METHOD: In the first stage, the generalized additive models were combined with the distributed lag non-linear models to evaluate the impact of air pollution on the inpatients for CRSD in Hefei. In the second stage, this study used the cost-of-illness approach to calculate the attributable number of hospitalizations and the extra disease burden. RESULT: Overall, all the six kinds of pollutants had the strongest effects on CRSD inpatients within lag10 days. SO2 and CO caused the highest and lowest harm, respectively, and the RR values were SO2 (lag0-5): 1.1 20 (1.053, 1.191), and CO (lag0-6): 1.002 (1.001, 1.003). During the study period (January 1, 2014 to December 30, 2020), the 7-year cumulative burden of disease was 36.19 million CNY under the WHO air pollution standards. CONCLUSION: In general, we found that six air pollutants were risk factors for CRSD in Hefei City, and create a huge burden of disease.

The combined effects of exposure to multiple PM2.5 components on overweight and obesity in middle-aged and older adults: a nationwide cohort study from 125 cities in China.

The prevalence of overweight or obesity increased rapidly over the past decades in most countries, including China. However, little evidence exists about the effects of long-term exposure to PM2.5 components on overweight or obesity, particularly in developing countries. We measured different weight stages according to body mass index (BMI), and investigated the effects of exposure to PM2.5 components (ammonium [[Formula: see text]], sulfate [[Formula: see text]], nitrate [[Formula: see text]], black carbon and organic matter) on different BMI levels in middle-aged and elderly people of China. Our study explored the effects of single and multiple air pollution exposures on overweight and obesity by using the Generalized Linear Model and Quantile g-Computation model (QgC). This study found a significantly positive association between five PM2.5 components and overweight/obesity. In the QgC model, there was still a positive association between multiple exposure to PM2.5 components and overweight when all PM2.5 components were considered as a whole. In addition, males, the elderly, and urban residents were also more sensitive to five PM2.5 components.

Irradiation-induced exosomal HMGB1 to confer radioresistance via the PI3K/AKT/FOXO3A signaling pathway in ESCC.

BACKGROUND: Radioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells. METHODS: Plasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group. RESULTS: The expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX. CONCLUSION: These findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.

Prognostic Significance of Prognostic Nutritional Index in Esophageal Squamous Cell Carcinoma Patients Undergoing Radical Radiotherapy: A Propensity Score Matching Analysis.

BACKGROUND: The preoperative prognostic nutritional index (PNI) is associated with postoperative complications and long-term survival of various cancers. However, its role in esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of this study was to identify the prognostic value of PNI in predicting survival in ESCC patients undergoing radical radiotherapy. METHODS: We retrospectively reviewed 354 ESCC patients undergoing radical radiotherapy. The time-dependent receiver operating characteristics was used to determine the optimal cutoff value. The association between PNI and survival was determined by Kaplan-Meier method and Cox regression model. Propensity score matching was applied to balance the baseline characteristics. RESULTS: PNI was positively correlated with hemoglobin (P < 0.001) and prealbumin (P < 0.001). The optimal cutoff value of PNI was set at 50.5. The 5-year overall survival (OS) in low PNI group and high PNI group were 20.8% and 34.0%, respectively (P < 0.001). The 5-year progression free survival in patients with low PNI and high PNI were 15.2% and 28.5%, respectively (P = 0.001). Multivariate analysis showed that PNI was a significant predictor for OS (P = 0.038). In the PSM analysis, PNI still remained an independent predictor for OS (P = 0.015). CONCLUSIONS: The PNI is a significant and independent predictor for OS of ESCC patients undergoing radical radiotherapy.

HMGB1 induces radioresistance through PI3K/AKT/ATM pathway in esophageal squamous cell carcinoma.

BACKGROUND: To explore the effect of HMGB1 on the radio-sensitivity of esophageal cancer cells through regulating the PI3K/Akt/ATM pathway. METHODS AND RESULTS: We observed the expression of HMGB1 and p-ATM in biopsies of esophageal cancer patients with immunohistochemical staining. Western blot and RT-qPCR were applied to detect the protein and RNA related to PI3K/Akt/ATM pathway, respectively. In addition, we inhibited the PI3K/Akt pathway with ly294002 and activated it with IGF1, then we explored the invasion, proliferation ability, and apoptosis of esophageal cancer cells in vitro by transwell, CCK8 assay, and flow cytometry respectively. In vivo, xenograft tumor model was established in nude mice to study the effect of HMGB1 on radioresistance via PI3K/AKT/ATM Signaling Pathway. The survival rate in patients with single positive/double negative expression of HMGB1 and p-ATM was significantly higher than in those with both positive expression of HMGB1 and p-ATM, the depletion of HMGB1 combined with ly294002 significantly inhibited cell proliferation and invasion ability, meanwhile, the addition of IGF1 reversed it. Meanwhile, depletion of HMGB1 and ly294002 promoted apoptosis and arrested the cancer cells in G0/G1 cell cycle with the decreased expression of Cyclin D1 and CDK4 and improved P16. We further validated these results in vivo, the application of HMGB1 silencing promoted apoptosis of xenograft tumors after radiation, especially combined with pathway inhibitor ly294002. CONCLUSIONS: Esophageal cancer patients with high expression of HMGB1 and p-ATM have a poor prognosis after chemo-radiotherapy. Down-regulation of HMGB1 may promote the radio-sensitivity of esophageal cancer cells through regulating PI3K/Akt/ATM pathway.

Identification of epigenetic genes for predicting prognosis and immunotherapy response of ovarian cancer.

BACKGROUND: Epigenetic factors play a critical role in tumour development and progression. The aim of this study was to construct and validate a robust epigenetic gene set-based signature for predicting prognosis of ovarian cancer. METHODS: By using LASSO Cox regression model, we screened out the most useful prognostic epigenetic factors and a prognostic signature was developed based on them. Survival receiver operating characteristic was used to test the prognostic accuracy of signature in training and validation sets. The associations between the risk scores and immune cell infiltration, tumour purity, immune checkpoint inhibitor genes expression were also assessed in ovarian cancer . RESULTS: A total of 26 epigenetic factors were identified to develop the prognostic signature. In the training set, the prognosis of high-risk patients was strikingly poorer than that of low-risk patients (hazard ratio: 2.11, 95% confidence interval: 1.65-2.72, P < 0.001). Similar results were further observed in the internal validation set (hazard ratio: 1.69, 95% confidence interval: 1.07-2.63, P = 0.020) and external validation set (hazard ratio:1.95, 95% confidence interval: 1.41-2.69; P < 0.001). Survival receiver operating characteristic at 5 year showed the epigenetic signature (area under the curve = 0.700) performed better than other clinical features in predicting prognosis. Distinct difference in immune activation related pathways, immune cells infiltration, tumour purity reflected by immune and stromal score and immune checkpoint inhibitor genes gene expression was observed between high- and low-risk samples. CONCLUSIONS: This study constructed an epigenetic signature that was capable of predicting postoperative outcomes and may also serve as potential biomarker for immunotherapy responses for ovarian cancer.

The bright future of nanotechnology in lymphatic system imaging and imaging-guided surgery.

Lymphatic system is identified the second vascular system after the blood circulation in mammalian species, however the research on lymphatic system has long been hampered by the lack of comprehensive imaging modality. Nanomaterials have shown the potential to enhance the quality of lymphatic imaging due to the unparalleled advantages such as the specific passive targeting and efficient co-delivery of cocktail to peripheral lymphatic system, ease molecular engineering for precise active targeting and prolonged retention in the lymphatic system of interest. Multimodal lymphatic imaging based on nanotechnology provides a complementary means to understand the kinetics of lymphoid tissues and quantify its function. In this review, we introduce the established approaches of lymphatic imaging used in clinic and summarize their strengths and weaknesses, and list the critical influence factors on lymphatic imaging. Meanwhile, the recent developments in the field of pre-clinical lymphatic imaging are discussed to shed new lights on the design of new imaging agents, the improvement of delivery methods and imaging-guided surgery strategies.

Liposuction in cancer-related lower extremity lymphedema: an investigative study on clinical applications.

BACKGROUND: Lymphedema is a progressive, noncurable condition consisting of increases in subcutaneous fat and interstitial fluid in the limbs and fibrosis during later stages. The disease most commonly affects the limbs following injury to or removal of the lymph nodes. The aim of this study was to investigate the therapeutic outcomes of liposuction for cancer-related lower extremity lymphedema. METHODS: Sixty-two patients with cancer-related lymphedema in the unilateral lower extremity were recruited for this study, and all patients underwent liposuction. The volume of hemorrhage and lipids, the operation time, and the volume changes of the affected extremity were compared by applying the t tests, and the subjective feelings of patients were compared with the chi-square tests. RESULTS: The total lipid volume was 2539 ± 1253.5 ml, and the hemorrhage volume was 828 ± 311.8 ml. For the comparison of objective indices, (1) the percent volume differences (PVDs) before surgery, intraoperatively, and at the 3-month follow-up were 5.5 ± 12.2 vs. 11.6 ± 18.4 vs. 43.2 ± 23.7, P < 0.05, respectively; (2) greater lipid volumes and higher liposuction rates were observed for female patients, as was a smaller volume of hemorrhage; (3) greater hemorrhage volumes were observed in patients with a history of recurrent erysipelas; and (4) greater lipid volumes and liposuction rates (LRs) and smaller hemorrhage volumes were observed for stage II than for stage III patients. CONCLUSIONS: Liposuction is an effective therapy for cancer-related lower extremity lymphedema. Sex, stage, and recurrent erysipelas history influence the course and effect of liposuction.

A Facile and Highly Efficient Approach to Obtain a Fluorescent Chromogenic Porous Organic Polymer for Lymphatic Targeting Imaging.

Porous organic polymers have an open architecture, excellent stability, and tunable structural components, revealing great application potential in the field of fluorescence imaging, but this part of the research is still in its infancy. In this study, we aimed to tailor the physical and chemical characteristics of indocyanine green using sulfonic acid groups and conjugated fragments, and prepared amino-grafted porous polymers. The resulting material had excellent solvent and thermal stability, and possessed a relatively large pore structure with a size of 3.4 nm. Based on the synergistic effect of electrostatic bonding and π-π interactions, the fluorescent chromogenic agent, indocyanine green, was tightly incorporated into the pore cavity of POP solids through a one-step immersion method. Accordingly, the fluorescent chromogenic POP demonstrated excellent imaging capabilities in biological experiments. This preparation of fluorescent chromogenic porous organic polymer illustrates a promising application of POP-based solids in both fluorescence imaging and biomedicine applications.

A combined radiomics and clinical variables model for prediction of malignancy in T2 hyperintense uterine mesenchymal tumors on MRI.

OBJECTIVE: This study aims to develop a machine learning model for prediction of malignancy in T2 hyperintense mesenchymal uterine tumors based on T2-weighted image (T2WI) features and clinical information. METHODS: This retrospective study included 134 patients with T2 hyperintense uterine mesenchymal tumors (104 patients in training cohort and 30 in testing cohort). A total of 960 radiomics features were initially computed and extracted from each 3D segmented tumor depicting on T2WI. The support vector machine (SVM) classifier was applied to build computer-aided diagnosis (CAD) models by using selected clinical and radiomics features, respectively. Finally, an observer study was conducted by comparing with two radiologists to evaluate the diagnostic performance. The area under the receiver operating characteristic (ROC) curve (AUC) was computed to assess the performance of each model. RESULTS: Comparing with the T2WI-based radiomics model (AUC: 0.76 ± 0.09) and the clinical model (AUC: 0.79 ± 0.09), the combined model significantly improved the AUC value to 0.91 ± 0.05 (p < 0.05). The clinical-radiomics combined model yielded equivalent or higher performance than two radiologists (AUC: 0.78 vs. 0.91, p = 0.03; 0.90 vs.0.91, p = 0.13). There was a significant difference between the AUC values of two radiologists (p < 0.05). CONCLUSIONS: It is feasible to predict malignancy risk of T2 hyperintense uterine mesenchymal tumors by combining clinical variables and T2WI-based radiomics features. Machine learning-based classification model may be useful to assist radiologists in decision-making. KEY POINTS: • Radiomics approach has the potential to distinguish between benign and malignant mesenchymal uterine tumors. • T2WI-based radiomics analysis combined with clinical variables performed well in predicting malignancy risk of T2 hyperintense uterine mesenchymal tumors. • Machine learning-based classification model may be useful to assist radiologists in characterization of a T2 hyperintense uterine mesenchymal tumor.

Talaromyoxaones A and B: Unusual Oxaphenalenone Spirolactones as Phosphatase Inhibitors from the Marine-Derived Fungus Talaromyces purpureogenus SCSIO 41517.

(+)- and (-)-talaromyoxaones A and B (1 and 2, respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2'H,3H,4'H-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin (3) and (+)- or (-)-abeopyrenulin (4) were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds 1 and 2 showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC50 values of 1.3-3.4 µM, and the potential modes of action for 1 were investigated by a preliminary molecular docking study.

Effect of SIB-IMRT-based selective dose escalation of local tumor on the prognosis of patients with esophageal cancer.

BACKGROUND: To investigate the effect of SIB-IMRT-based selective dose escalation to local tumor on the prognosis of patients with esophageal cancer (EC). METHODS: A total of 302 EC patients were enrolled. The prognostic factors of the entire group were initially analyzed, and the composition ratios of the two groups and the different doses of each fraction for PTV were compared. The propensity-score matching (PSM) was carried out (1:1 ratio), and the prognostic factors for the two groups were analyzed according to the results of COX. RESULTS: The median overall survival (OS) for all patients was 30.0 months (23.495-36.505 months), and the median disease-free survival (DFS) was 21.3 months (7.698-24.902 months). In multivariate analysis, chemotherapy, cTNM stage and dose-per-fraction for the PTV were independent prognostic factors for OS (P = 0.013, 0.000, 0.028) and DFS (P = 0.033, 0.000, 0.047). Multivariate analysis of patients after PSM revealed that cTNM staging and dose-per-fraction were the independent prognostic factors for OS (P = 0.000, 0.015). Chemotherapy, cTNM staging and dose-per-fraction for the PTV were the independent prognostic factors for DFS (P = 0.025, 0.010, 0.015). There was no significant difference in grade ≥ 2 acute toxicities between the two groups. A subgroup analysis of patients with a single dose of 2 Gy and > 2 Gy in the SIB-IMRT group showed that OS and DFS of the latter were significantly better than those of the former. CONCLUSION: The selective dose escalation to local tumors based on SIB-IMRT technique can improve the survival of patients received radical radiotherapy without increasing toxicities.

Sports Augmented Cognitive Benefits: An fMRI Study of Executive Function with Go/NoGo Task.

Exercise is believed to have significant cognitive benefits. Although an array of experimental paradigms have been employed to test the cognitive effects on exercising individuals, the mechanism as to how exercise induces cognitive benefits in the brain remains unclear. This study explores the effect of dynamic neural network processing with the classic Go/NoGo task with regular exercisers. We used functional magnetic resonance imaging to analyze the brain activation of areas involved in executive function, especially inhibitory control. Nineteen regular joggers and twenty-one subjects as a control group performed the task, and their brain imaging data were analyzed. The results showed that at the attentive visual period, the frontal and parietal areas, including the prefrontal cortex, putamen, thalamus, lingual, fusiform, and caudate, were significantly enhanced in positive activities than the control group. On the other hand, in the following inhibitory control processing period, almost the same areas of the brains of the exercise group have shown stronger negative activation in comparison to the control group. Such dynamic temporal response patterns indicate that sports augment cognitive benefits; i.e., regular jogging increases the brain's visual attention and inhibitory control capacities.

Capsule retention caused by cryptogenic multifocal ulcerous stenosing enteritis.

INTRODUCTION: cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare illness. Capsule retention (CR) has been reported in a few cases of CMUSE. METHODS: we present four cases of CMUSE with CR. None of the patients showed any symptoms or signs of small bowel obstruction before capsule endoscopy (CE). All patients denied a history of non-steroidal anti-inflammatory drugs intake, radiotherapy treatment or abdominal surgery. RESULTS: CE disclosed circumferential stenosis with or without ulcers in the small bowel, some accompanied by mucosal edema, white spots and nodules. All patients underwent an elective surgery to remove the retained capsule and resect the lesions. CONCLUSION: CE plays a positive role in diagnosing CMUSE. CE findings are as important as CR to alert about the diagnosis of CMUSE.

Discovery of naphthacemycins as a novel class of PARP1 inhibitors.

Poly (ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear protein that plays important roles in a variety of nuclear processes, and it has been proved a prominent target in oncology for its key function in DNA damage repair. In this study, we discovered a series of naphthacemycins as a new class of PARP1 inhibitors from a microbial metabolites library via high-throughput screening. Compound I, one of this series of compounds, could reduce cellular poly (ADP-ribose) level, trap PARP1 on the damaged DNA and elevate the level of γ-H2AX, and showed the selective cytotoxicity against BRCA1-deficient cell line. Our study provided a potential scaffold for the development of new PARP1 inhibitors in cancer therapy.

Unipedal Diagnostic Lymphangiography Followed by Sequential CT Examinations in Patients With Idiopathic Chyluria: A Retrospective Study.

OBJECTIVE: The objective of our study was to investigate the clinical value of diagnostic lymphangiography followed by sequential CT examinations in patients with idiopathic chyluria. MATERIALS AND METHODS: Thirty-six patients with idiopathic chyluria underwent unipedal diagnostic lymphangiography and then underwent sequential CT examinations. The examinations were reviewed separately by two radiologists. Abnormal distribution of contrast medium, lymphourinary leakages, and retrograde flow were noted, and the range and distribution of lymphatic vessel lesions were recorded. The stage of idiopathic chyluria based on CT findings and the stage based on clinical findings were compared. Therapeutic management and follow-up were recorded. Statistical analyses were performed. RESULTS: Compared with CT studies performed after lymphangiography, diagnostic lymphangiography showed a unique capability to depict lymphourinary leakages in three patients. Lymphourinary fistulas and abnormal dilated lymphatic vessels were found in and around kidney in all patients. CT depicted retrograde flow of lymph fluid in 47.2% of patients. The consistency in staging chyluria based on CT findings and clinical findings was fair (κ = 0.455). Twenty-nine patients underwent conservative therapy, and seven underwent surgery. Surgical therapy was superior to conservative management (no recurrence, 85.7% of patients who underwent surgery vs 62.1% of patients who underwent conservative therapy; p = 0.025). CONCLUSION: From assessing the drainage of contrast medium on unipedal diagnostic lymphangiography and the redistribution of contrast medium on sequential CT examinations, it is possible to detect the existence of lymphourinary fistulas, the precise location of lymphatic anomalies, the distribution of collateral lymphatic vessels, and hydrodynamic pressure abnormality in the lymph circulation in patients with idiopathic chyluria. CT staging of chyluria provides additional information that can be used to guide therapeutic management.