Synchronous removal of gaseous toluene and benzene and degradation process shifts in microbial fuel cell-biotrickling filter system.

Illustrating the biodegradation processes of multi-component volatile organic compounds (VOCs) will expedite the implication of biotechnology in purifying industrial exhaust. Here, performance shifts of microbial fuel cell and biotrickling filter combined system (MFC-BTF) are investigated for removing single and dual components of toluene and benzene. Synchronous removal of toluene (95 %) and benzene (97 %) are achieved by MFC-BTF accompanied with the output current of 0.41 mA. Elevated content of extracellular polymeric substance facilitates the mass transfer of benzene with the presence of toluene. Strains of Bacteroidota, Proteobacteria and Chloroflexi contribute to the removal of dual components VOCs. Empty bed reaction time and the VOCs concentration are the important factors influencing their dissolution in the system. The biodegradation of toluene and benzene proceeds with 2-hydroxymuconic semialdehyde and o-hydroxybenzoic acid as the main intermediates. These results provide a comprehensive understanding of multi-component VOCs removal by MFC-BTF and guide the system design, optimization, and scale-up.

Differential clinical outcomes after 3 versus 5 years in a comparison of preoperative chemotherapy with and without radiotherapy in locally advanced rectal cancer: A national cohort propensity score-matched study.

Background: Preoperative chemotherapy alone might be a good alternative to preoperative chemoradiotherapy for patients with locally advanced rectal cancer, yet long-term real-world data from the same cohort are lacking. Methods: Patients diagnosed with stage II-III rectal adenocarcinoma from 2011 to 2015 were randomly sampled from the SEER-Plus database to evaluate the superiority of preoperative chemoradiotherapy versus preoperative chemotherapy alone. Findings: A total of 1314 eligible patients were enrolled, with a median follow-up of 74.0 months. At 3-year follow-up, neither overall survival (OS) nor cancer-specific survival (CSS) was significantly different between the two treatment groups. At 5-year follow-up, CSS was similar across groups (HR 0.768, 95% CI 0.532-1.108; P = 0.156), but the 5-year OS was significantly better in the preoperative chemoradiotherapy group than in the preoperative chemotherapy group (HR 0.682, 95% CI 0.538-0.866; P = 0.002). Besides, the landmark analysis indicated a direct contrast in the CSS within 3 years (HR 1.101, 95% CI 0.598-2.029; P = 0.756) versus that at 3-5 years (HR 0.597, 95% CI 0.377-0.948; P = 0.027). The landmark analysis also showed directly contrasting OS outcomes within 3 years (HR 0.761, 95% CI 0.533-1.086; P = 0.130) versus those at 3-5 years (HR 0.621, 95% CI 0.451-0.857; P = 0.003). Interpretation: In patients with locally advanced rectal cancer under real-world treatment practices, the addition of preoperative radiotherapy to chemotherapy improves survival outcomes at 3-5 years' follow-up but not at 3-year follow-up.

Outcomes of preoperative chemotherapy for colorectal cancer with peritoneal metastasis underwent cytoreductive surgery.

BACKGROUND: This study aims to assess and compare the extent to which preoperative chemotherapy prior to CRS improves survival in patients diagnosed with CRCPM. METHODS: We included 251 patients from 2012 to 2019 in our center. Inverse probability of treatment weighting (IPTW) analysis was used to minimize the selection bias. Survival analysis was performed to compare the survival outcomes. Multivariate Cox regression analysis was conducted to identify prognostic factors. RESULT: The baseline characteristics were well balanced using IPTW (standardized mean difference < 0.1). Preoperative chemotherapy cannot significantly improve overall survival (HR, 1.03; 95% CI 0.71-1.49; P = 0.88). In subgroup analysis, we found that intestinal obstruction after preoperative chemotherapy significantly reduced survival (HR, 2.25; 95% CI 1.01-5.03; P = 0.048), while in the upfront surgery group, intestinal obstruction had no impact on prognosis. CONCLUSION: For CRCPM patients treated with CRS, preoperative chemotherapy does not seem to prolong overall survival. Furthermore, the emergence of intestinal obstruction after chemotherapy may compromise the effectiveness of treatment, resulting in a worse prognosis. This finding has important clinical implications for treatment decisions.

Low-intensity pulsed ultrasound alleviates doxorubicin-induced cardiotoxicity via inhibition of S100a8/a9-mediated cardiac recruitment of neutrophils.

Doxorubicin (DOX)-induced cardiotoxicity limits its broad use as a chemotherapy agent. The development of effective and non-invasive strategies to prevent DOX-associated adverse cardiac events is urgently needed. We aimed to examine whether and how low-intensity pulsed ultrasound (LIPUS) plays a protective role in DOX-induced cardiotoxicity. Male C57BL/6J mice were used to establish models of both acute and chronic DOX-induced cardiomyopathy. Non-invasive LIPUS therapy was conducted for four consecutive days after DOX administration. Cardiac contractile function was evaluated by echocardiography. Myocardial apoptosis, oxidative stress, and fibrosis were analyzed using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining, dihydroethidium (DHE) staining, and picrosirius red staining assays. RNA-seq analysis was performed to unbiasedly explore the possible downstream regulatory mechanisms. Neutrophil recruitment and infiltration in the heart were analyzed by flow cytometry. The S100a8/a9 inhibitor ABR-238901 was utilized to identify the effect of S100a8/a9 signaling. We found that LIPUS therapy elicited a great benefit on DOX-induced heart contractile dysfunction in both acute and chronic DOX models. Chronic DOX administration increased serum creatine kinase and lactate dehydrogenase levels, as well as myocardial apoptosis, all of which were significantly mitigated by LIPUS. In addition, LIPUS treatment prevented chronic DOX-induced cardiac oxidative stress and fibrosis. RNA-seq analysis revealed that LIPUS treatment partially reversed alterations of gene expression induced by DOX. Gene ontology (GO) analysis of the downregulated genes between DOX-LIPUS and DOX-Sham groups indicated that inhibition of neutrophil chemotaxis might be involved in the protective effects of LIPUS therapy. Flow cytometry analysis illustrated the inhibitory effects of LIPUS on DOX-induced neutrophil recruitment and infiltration in the heart. Moreover, S100 calcium binding protein A8/A9 (S100a8/a9) was identified as a potential key target of LIPUS therapy. S100a8/a9 inhibition by ABR-238901 showed a similar heart protective effect against DOX-induced cardiomyopathy to LIPUS treatment. LIPUS therapy prevents DOX-induced cardiotoxicity through inhibition of S100a8/a9-mediated neutrophil recruitment to the heart, suggesting its potential application in cancer patients undergoing chemotherapy with DOX.

Effect of BRAF mutation on the prognosis for patients with colorectal cancer undergoing cytoreductive surgery for synchronous peritoneal metastasis.

Background: KRAS/BRAF mutations (mutKRAS/mutBRAF) are unfavorable prognostic factors for colorectal cancer (CRC) metastases to the liver and lungs. However, their effects on the prognosis for patients with synchronous peritoneal metastasis (S-PM) of CRC after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are controversial. In the study, we aimed to determine the effects of mutKRAS/mutBRAF on the prognosis for patients with S-PM who received CRS. Methods: A total of 142 patients diagnosed with S-PM between July 2007 and July 2019 were included in this study. The demographics, mutKRAS/mutBRAF status, overall survival (OS), and progression-free survival (PFS) of the patients were evaluated. The Kaplan-Meier method and log-rank test were used to estimate the difference in survival between groups. Results: Among 142 patients, 68 (47.9%) showed mutKRAS and 42 (29.5%) showed mutBRAF. The median OS values were 8.4 and 34.3 months for patients with mutBRAF and BRAF wild-type, respectively (P < 0.01). However, KRAS status was not significantly associated with median OS (P = 0.76). Multivariate analysis revealed carcinoembryonic antigen, CRS, HIPEC, and mutBRAF as independent predictors for OS. Based on these findings, a nomogram was constructed. The C-index was 0.789 (95% confidence interval, 0.742-0.836), indicating good predictive ability of the model. Furthermore, the 1- and 2-year survival calibration plots showed good agreement between the predicted and actual OS rates. The area under curves of the 1- and 2-year survival predictions based on the nomogram were 0.807 and 0.682, respectively. Additionally, mutBRAF was significantly associated with lower PFS (P < 0.001). Conclusions: mutBRAF is an independent prognostic risk factor for S-PM. The established nomogram predicted the OS of patients with CRC having S-PM with high accuracy, indicating its usefulness as a valuable prognostic tool for the designated patient cohort.

The largest and heaviest giant juvenile fibroadenoma of the breast in the Chinese population: A case report.

RATIONALE: Fibroadenoma is the most common benign tumor of the breast, but giant juvenile fibroadenoma exceeding 20 cm is much rare. This report presents the largest and heaviest giant juvenile fibroadenoma in an 18-year-old Chinese girl. DIAGNOSIS AND INTERVENTIONS: An 18-year-old adolescent girl with a 2-year history of a large left breast mass with progressive expansion over 11 months. A 28 × 21 cm soft swelling occupied the entire outer quadrants of the left breast. The huge mass sagged below the belly button, resulting in high asymmetry of the shoulders. Contralateral breast examination results were normal except for hypopigmentary detected on the nipple-areola complex. Under general anesthesia, the lump was completely excised along the outer envelope of the tumor, while reserving excessive resection of the skin. The patient's postoperative recovery was uneventful, and the surgical wound healed well. OUTCOMES: A radial incision operation was finally performed to remove the huge mass and to preserve the normal breast tissue and the nipple-areolar complex, not only considering the aesthetics but also preserving the ability to lactate. LESSONS: Currently, there is a lack of clear guidelines regarding the diagnostic and treatment modalities for a giant juvenile fibroadenoma. The principle of surgical choice is to balance aesthetics and function preservation.

Hyperthermic intraperitoneal chemotherapy following up-front cytoreductive surgery versus cytoreductive surgery alone for isolated synchronous colorectal peritoneal metastases: A retrospective, observational study.

Background: To date, the value of hyperthermic intraperitoneal chemotherapy (HIPEC) following up-front resection for isolated synchronous colorectal peritoneal metastases seems controversial. Patients and Methods: This retrospective cohort study was conducted from September 1, 2012, to September 1, 2019, at a tertiary medical center in China. Patients with isolated synchronous colorectal peritoneal metastases were included in CRS plus HIPEC group or CRS alone group based on the treatment history. Overall survival and relapse-free survival were estimated using Cox proportional hazards regression analysis and Kaplan-Meier method. Results: 78 patients with isolated synchronous colorectal peritoneal metastases were identified among 396 patients with synchronous colorectal peritoneal metastases. 43 were in the cytoreductive surgery plus HIPEC group and 35 were in the cytoreductive surgery alone group. Among them, 61 patients had relapse-free survival data. The median peritoneal cancer index was 4 in all patients. After a median follow-up of 46.0 months, 5-year overall survival was 66.8% and the median relapse-free survival was 36.0 (95% CI, 6.8-65.1) months in the CRS plus HIPEC group. 5-year overall survival was 31.2% and the median relapse-free survival was 12.0 (95% CI, 9.0-15.0) months in the CRS alone group. Cox regression analyses showed that HIPEC was the independent prognostic factor for overall survival (P = 0.004) and relapse-free survival (P = 0.049). Conclusion: Findings of the present study suggest that HIPEC following up-front CRS could improve overall survival and relapse-free survival in patients with isolated synchronous colorectal peritoneal metastases.

A Prediction Model Intended for Exploratory Laparoscopy Risk Stratification in Colorectal Cancer Patients With Potential Occult Peritoneal Metastasis.

Background: The early diagnosis of occult peritoneal metastasis (PM) remains a challenge due to the low sensitivity on computed tomography (CT) images. Exploratory laparoscopy is the gold standard to confirm PM but should only be proposed in selected patients due to its invasiveness, high cost, and port-site metastasis risk. In this study, we aimed to develop an individualized prediction model to identify occult PM status and determine optimal candidates for exploratory laparoscopy. Method: A total of 622 colorectal cancer (CRC) patients from 2 centers were divided into training and external validation cohorts. All patients' PM status was first detected as negative on CT imaging but later confirmed by exploratory laparoscopy. Multivariate analysis was used to identify independent predictors, which were used to build a prediction model for identifying occult PM in CRC. The concordance index (C-index), calibration plot and decision curve analysis were used to evaluate its predictive accuracy and clinical utility. Results: The C-indices of the model in the development and validation groups were 0.850 (95% CI 0.815-0.885) and 0.794 (95% CI, 0.690-0.899), respectively. The calibration curve showed consistency between the observed and predicted probabilities. The decision curve analysis indicated that the prediction model has a great clinical value between thresholds of 0.10 and 0.72. At a risk threshold of 30%, a total of 40% of exploratory laparoscopies could have been prevented, while still identifying 76.7% of clinically occult PM cases. A dynamic online platform was also developed to facilitate the usage of the proposed model. Conclusions: Our individualized risk model could reduce the number of unnecessary exploratory laparoscopies while maintaining a high rate of diagnosis of clinically occult PM. These results warrant further validation in prospective studies. Clinical Trial Registration: https://www.isrctn.com, identifier ISRCTN76852032.

Risk Factors for Synchronous Peritoneal Metastases in Colorectal Cancer: A Systematic Review and Meta-Analysis.

Background: Early detection of synchronous colorectal peritoneal metastases (CPMs) is difficult due to the absence of typical symptoms and the low accuracy of imaging examinations. Increasing the knowledge of the risk factors for synchronous CPM may be essential for early diagnosis and improving their management. This study aimed to identify the risk factors for synchronous CPM. Method: The study was registered at PROSPERO (CRD42020198548). The PubMed, Embase and Cochrane Library databases were searched for studies comparing the clinicopathological and molecular features between patients with or without synchronous CPM. The pooled data were assessed by a random-effects model. Results: Twenty-five studies were included. A synchronous CPM was positively associated with female sex (OR 1.299; 1.118 to 1.509; P = 0.001), PROK1/PROKR2-positivity (OR 2.244; 1.031 to 4.884; P = 0.042), right-sided colon cancer (OR 2.468; 2.050 to 2.970; P < 0.001), poorly differentiated grade (OR 2.560; 1.537 to 4.265; P < 0.001), BRAF mutation (OR 2.586; 1.674 to 3.994; P < 0.001), mucinous adenocarcinoma (OR 3.565; 2.095 to 6.064; P < 0.001), signet-ring cell carcinoma (OR 4.480; 1.836 to 10.933; P = 0.001), N1-2 (OR 5.665; 3.628 to 8.848; P < 0.001), T4 (OR 12.331; 7.734 to 19.660; P < 0.001) and elevated serum CA19-9 (OR 12.868; 5.196 to 31.867; P < 0.001). Conclusions: These evidence-based risk factors are indicators that could predict the presence of synchronous CPMs and can improve their management. Systematic Review Registration: www.crd.york.ac.uk/prospero, identifier: CRD42020198548.

Comprehensive Analysis of Microsatellite-Related Transcriptomic Signature and Identify Its Clinical Value in Colon Cancer.

Background: Microsatellite has been proved to be an important prognostic factor and a treatment reference in colon cancer. The transcriptome profile and tumor microenvironment of different microsatellite statuses are different. Metastatic colon cancer patients with microsatellite instability-high (MSI-H) are sensitive to immune checkpoint inhibitors (ICIs), but not fluorouracil. Efforts have been devoted to identify the predictive factors of immunotherapy. Methods: We analyzed the transcriptome profile of different microsatellite statuses in colon cancer by using single-cell and bulk transcriptome data from publicly available databases. The immune cells in the tumor microenvironment were analyzed by the ESTIMATION algorithm. The microsatellite-related gene signature (MSRS) was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression based on the differentially expressed genes (DEGs) and its prognostic value and predictive value of response to immunotherapy were assessed. The prognostic value of the MSRS was also validated in another cohort. Results: The MSI-H cancers cells were clustered differentially in the dimension reduction plot. Most of the immune cells have a higher proportion in the tumor immune microenvironment, except for CD56 bright natural killer cells. A total of 238 DEGs were identified. Based on the 238 DEGs, a neural network was constructed with a Kappa coefficient of 0.706 in the testing cohort. The MSRS is a favorable prognostic factor of overall survival, which was also validated in another cohort (GSE39582). Besides, MSRS is correlated with tumor mutation burden in MSI-H colon cancer. However, the MSRS is a barely satisfactory factor in predicting immunotherapy with the area under the curve (AUC) of 0.624. Conclusion: We developed the MSRS, which is a robust prognostic factor of overall survival in spite of a barely satisfactory immunotherapy predictor. Further studies may need to improve the predictive ability.

Residues of Culinary-Medicinal Winter Mushroom, Flammulina velutipes (Agaricomycetes), Cultivation as a Potential Source of Functional Skin Substitute with Multiple Bioactivities.

Residues generated during the cultivation of edible mushroom Flammulina velutipes are abundant and utilized with low efficiency. In this study, the composition and bioactivities of a skin substitute named TG05 obtained from residues of the F. velutipes cultivation process were investigated. The main composition of TG05 was considered to be chitin and it inhibited growth of Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa. TG05 also suppressed the inflammatory response through the inducible nitric oxide synthase signaling pathway. Inflammation was attenuated by reducing the expression of tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and prostaglandin E2 at the transcription level. Furthermore, TG05 exhibited antioxidant activities based on hydroxyl, 2,2-diphenyl-1-picryl-hydrazy, 2,2'-azobis-(3-ethylbenzothiazoline-6-sulfonic acid), superoxide anion radical scavenging activity, and reducing power assays. However, the effect of TG05 was independent of hyaluronidase inhibitory activity. Taken together, specific mechanisms related to the notable wound-healing-promoting activity of TG05 were demonstrated, mainly attributable to its antimicrobial, anti-inflammatory, and antioxidant activities. Therefore, TG05 may have potential for use as a functional biomaterial in various applications.

Hypoglycemia-Exacerbated Mitochondrial Connexin 43 Accumulation Aggravates Cardiac Dysfunction in Diabetic Cardiomyopathy.

Background: Diabetic cardiomyopathy (DCM) is a complex multifaceted disease responsible for elevated heart failure (HF) morbidity and mortality in patients with diabetes mellitus (DM). Patients with DCM exhibit subclinical diastolic dysfunction, progression toward systolic impairment, and abnormal electrophysiology. Hypoglycemia events that occur spontaneously or due to excess insulin administration threaten the lives of patients with DM-with the increased risk of sudden death. However, the molecular underpinnings of this fatal disease remain to be elucidated. Methods and Results: Here, we used the established streptozotocin-induced DCM murine model to investigate how hypoglycemia aggravates DCM progression. We confirmed connexin 43 (Cx43) dissociation from cell-cell interaction and accumulation at mitochondrial inner membrane both in the cardiomyocytes of patients with DM and DCM murine. Here, we observed that cardiac diastolic function, induced by chronic hyperglycemia, was further aggravated upon hypoglycemia challenge. Similar contractile defects were recapitulated using neonatal mouse ventricular myocytes (NMVMs) under glucose fluctuation challenges. Using immunoprecipitation mass spectrometry, we identified and validated that hypoglycemia challenge activates the mitogen-activated protein kinase kinase (MAPK kinase) (MEK)/extracellular regulated protein kinase (ERK) and inhibits phosphoinositide 3-kinase (PI3K)/Akt pathways, which results in Cx43 phosphorylation by Src protein and translocation to mitochondria in cardiomyocytes. To determine causality, we overexpressed a mitochondrial targeting Cx43 (mtCx43) using adeno-associated virus serotype 2 (AAV2)/9. At normal blood glucose levels, mtCx43 overexpression recapitulated cardiac diastolic dysfunction as well as aberrant electrophysiology in vivo. Our findings give support for therapeutic targeting of MEK/ERK/Src and PI3K/Akt/Src pathways to prevent mtCx43-driven DCM. Conclusion: DCM presents compensatory adaptation of mild mtCx43 accumulation, yet acute hypoglycemia challenges result in further accumulation of mtCx43 through the MEK/ERK/Src and PI3K/Akt/Src pathways. We provide evidence that Cx43 mislocalization is present in hearts of patients with DM hearts, STZ-induced DCM murine model, and glucose fluctuation challenged NMVMs. Mechanistically, we demonstrated that mtCx43 is responsible for inducing aberrant contraction and disrupts electrophysiology in cardiomyocytes and our results support targeting of mtCx43 in treating DCM.

Risk factors for developing peritoneal metastases after curative surgery for colorectal cancer: A systematic review and meta-analysis.

AIM: Proactive detection and treatment strategies have achieved encouraging survival outcomes for patients with early peritoneal metastases (PM), but these costly and invasive approaches can only be applied to selected high-risk patients. This meta-analysis aimed to identify the risk factors for metachronous PM after curative surgery for colorectal cancer (CRC). METHOD: The study was registered at PROSPERO (CRD42020219187). Databases were searched for studies comparing clinical and histopathological characteristics between patients with metachronous peritoneal metastases from colorectal cancer (pmCRC) and patients without (non-pmCRC). RESULTS: Thirty-six studies were included. Metachronous PM were positively associated with perforation (OR 1.920; 95% CI 1.144-3.223; P = 0.014), poor differentiation (OR 2.291; 1.603-3.275; P < 0.001), T4 (OR 2.897; 1.248-6.726; P = 0.013), N1-2 (OR 3.429; 2.684-4.381; P < 0.001), mucinous adenocarcinoma (OR 4.175; 1.798-9.692; P = 0.001), obstruction (OR 4.467; 1.919-10.398; P = 0.001), synchronous ovarian metastases (OR 5.005; 1.140-21.977; P = 0.033), positive peritoneal carcinoembryonic antigen mRNA (OR 9.472; 3.643-24.631; P < 0.001), elevated serum carcinoembryonic antigen (preoperative group, OR 3.545, 1.486-8.459, P = 0.004; postoperative group, OR 13.673, 2.222-84.129, P = 0.005), elevated serum cancer antigen 19-9 (preoperative group, OR 5.281, 2.146-12.994, P < 0.001; postoperative group, OR 18.646, 6.429-54.083, P < 0.001) and positive peritoneal cytology (OR 25.884; 11.372-58.913; P < 0.001). CONCLUSION: These evidence-based risk factors are conducive to designing early detection and proactive treatment strategies, enabling precision medicine.

CircARL8B Contributes to the Development of Breast Cancer Via Regulating miR-653-5p/HMGA2 Axis.

Circular RNAs (circRNAs) act as essential regulators in breast cancer (BC) progression. In this paper, we aimed to investigate the functions of circARL8B in BC. The levels of circARL8B, ADP Ribosylation Factor Like GTPase 8B (ARL8B), miR-653-5p and high-mobility group AT-hook 2 (HMGA2) mRNA were examined by qRT-PCR. The stability of circARL8B was determined by RNase R assay and Actinomycin D assay. Cell viability and metastasis were evaluated by Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The levels of cellular phospholipids and triglycerides were measured using relevant kits. Protein levels were measured by western blot analysis. The association between miR-653-5p and circARL8B or HMGA2 was verified by dual-luciferase reporter assay. A murine xenograft model was established to explore the function of circARL8B in vivo. CircARL8B was increased in BC tissues and cells. CircARL8B silencing inhibited cell viability, migration, invasion and fatty acid metabolism in BC cells in vitro and blocked tumor growth in vivo. MiR-653-5p was identified as the target of circARL8B and miR-653-5p was negatively modulated by circARL8B. The suppressive role of circARL8B silencing in BC cell progression was abolished by miR-653-5p downregulation. Moreover, HMGA2 was the target gene of miR-653-5p. HMGA2 overexpression abrogated the effect of miR-653-5p on BC cell development. In addition, circARL8B knockdown might block PGE2/PI3K/AKT/GSK-3ß/Wnt/ß-catenin pathway. Silencing of circARL8B inhibited cell viability, migration, invasion and fatty acid metabolism via miR-653-5p/HMGA2 axis in BC.

Diagnostic accuracy of quantitative fetal fibronectin to predict spontaneous preterm birth: A meta-analysis.

BACKGROUND: Use of quantitative fetal fibronectin (fFN) testing to predict spontaneous preterm birth (sPTB) is gaining attention owing to its absolute measurement of fFN concentration and increased positive predictive value compared with qualitative testing. OBJECTIVE: To assess the predictive values of quantitative fFN for sPTB in different predefined thresholds using systematic review and meta-analysis. SEARCH STRATEGY: Five major databases (PubMed, ScienceDirect, Web of Science, Embase, Cochrane library) were searched for eligible studies. SELECTION CRITERIA: Observational studies of the diagnostic accuracy of different quantitative fFN thresholds on delivery outcomes were included. DATA COLLECTION AND EXTRACTION: Articles were reviewed independently by two authors and data were extracted. Sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curves were extracted and calculated. MAIN RESULTS: Fifteen studies were included. To detect sPTB at less than 34 weeks of gestation, pooled sensitivities for thresholds of 10, 50, 200, and 500 ng/ml were 0.78, 0.56, 0.33, and 0.11, respectively. Pooled specificities were 0.63, 0.84, 0.96, and 0.99, respectively. CONCLUSIONS: Based on the results of the meta-analysis, the threshold of 10 ng/ml fFN may be a new choice for the prediction of sPTB. The improved diagnostic accuracy of quantitative testing over qualitative testing can provide additional discriminatory information for clinical practice.

Small molecule CDS-3078 induces G2/M phase arrest and mitochondria-mediated apoptosis in HeLa cells.

The tumor suppressor p53 serves important roles in cell cycle arrest and apoptosis, and its activation increases the sensitivity of cancer cells to radiotherapy or chemotherapy. In the present study, the small molecule 2-[1-(4-(benzyloxy)phenyl)-3-oxoisoindolin-2-yl)-2-(4-methoxyphenyl)] acetic acid (CDS-3078) significantly increased p53 mRNA expression levels in a dose-dependent manner. Treatment with CDS-3078 increased p53 expression levels and p53-mediated activation of its downstream target genes in HeLa cells. Additionally, p53+/+ HeLa cells treated with CDS-3078 presented with dysfunctional mitochondria, as indicated by the decrease in Bcl-2 levels, the increase in Bcl-2 homologous antagonist killer and the increase in cytochrome c release from the mitochondria to the cytoplasm. The present results suggested that CDS-3078 treatment significantly induced G2/M phase cell cycle arrest. Therefore, CDS-3078 administration induced apoptosis via p53-mediated cell cycle arrest, causing mitochondrial dysfunction and resulting in apoptotic cell death in cervical cancer cells. Collectively, the present results suggested that CDS-3078 may be a potential anticancer agent.

Long noncoding RNA HOTAIR promotes breast cancer development by targeting ZEB1 via sponging miR-601.

BACKGROUND: Breast cancer (BC) is a common malignancy worldwide. It has been reported that long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) is abnormally expressed in BC. However, the role of HOTAIR in the malignancy of BC is worth further discussion. This study aims to clarify the function and molecular mechanism of HOTAIR in BC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression of HOTAIR, microRNA (miR)-601 and zinc finger E-box binding homeobox 1 (ZEB1). Cell counting kit-8 (CCK-8) and transwell assay were used to detect the proliferation, migration and invasion of cells. Further, the protein levels of AKT, phosphorylated-AKT (p-AKT), ZEB1 and Ki-67 were confirmed by western blot (WB) assay. Moreover, dual-luciferase reporter assay was applied to examine the targeting relationship between HOTAIR and miR-601 or miR-601 and ZEB1. In addition, animal experiments were conducted to verify the effect of HOTAIR on BC tumor growth in vivo. RESULTS: HOTAIR was upregulated in BC tissues and cells, and its knockdown suppressed the proliferation, migration, invasion and the activity of AKT signaling pathway of BC cells. HOTAIR could serve as a sponge of miR-601. Further experiments revealed that miR-601 inhibitor could reverse the inhibition effect of HOTAIR silencing on the progression of BC. Meanwhile, ZEB1 was a target of miR-601, and its overexpression could invert the suppression effect of miR-601 overexpression on the progression of BC. Additionally, ZEB1 expression was regulated by HOTAIR and miR-601. Furthermore, interference of HOTAIR could attenuate BC tumor growth in vivo. CONCLUSION: In short, this study demonstrated that HOTAIR promoted the proliferation, migration, invasion of BC through regulating the miR-601/ZEB1 axis, which provided a theoretical basis for the research on lncRNA-directed therapeutics in BC.

Histone H2A-peptide-hybrided upconversion mesoporous silica nanoparticles for bortezomib/p53 delivery and apoptosis induction.

The design and development of advanced gene/drug codelivery nanocarrier with good biocompatibility for cancer gene therapy is desirable. Herein, we reported a gene delivery nanoplatform to synergized bortezomib (BTZ) for cancer treatment with histone H2A-hybrided, upconversion luminescence (UCL)-guided mesoporous silica nanoparticles [UCNPs(BTZ)@mSiO2-H2A]. The functionalization of H2A on the surface of UCNPs(BTZ)@mSiO2 nanoparticles realized the improvement of biocompatibility and enhancement of gene encapsulation and transfection efficiency. More importantly, then UCNPs(BTZ)@mSiO2-H2A/p53 induced specific and efficient apoptotic cell death in p53-null cancer cells and restored the functional activity of tumor suppressor p53 by the success of co-delivery of BTZ/p53. Moreover, the transfection with UCNPs(BTZ)@mSiO2-H2A/p53 in p53-deficient non-small cell lung cancer cells changed the status of p53 and substantially enhanced the p53-mediated sensitivity of encapsulated BTZ inside the UCNPs(BTZ)@mSiO2/p53. Meanwhile, core-shell structured mesoporous silica nanoparticles UCNPs@mSiO2 as an UCL agent can detect the real-time interaction of nanoparticles with cells and uptake/penetration processes. The results here suggested that the as-developed UCNPs(BTZ)@mSiO2-H2A/p53 nanoplatform with coordinating biocompatibility, UCL image, and sustained release manner might be desirable gene/drug codelivery nanocarrier for clinical cancer therapy.

Risk factors for axillary lymph node metastases in clinical stage T1-2N0M0 breast cancer patients.

Axillary lymph node metastasis (ALNM) is commonly the earliest detectable clinical manifestation of breast cancer when distant metastasis emerges. This study aimed to explore the influencing factors of ALNM and develop models that can predict its occurrence preoperatively.Cases of sonographically visible clinical stage T1-2N0M0 breast cancers treated with breast and axillary surgery at West China Hospital were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to evaluate associations between ALNM and variables. Decision tree analyses were performed to construct predictive models using the C5.0 packages.Of the 1671 tumors, 541 (32.9%) showed axillary lymph node positivity on final surgical histopathologic analysis. In multivariate logistic regression analysis, tumor size (P < .001), infiltration of subcutaneous adipose tissue (P < .001), infiltration of the interstitial adipose tissue (P = .031), and tumor quadrant locations (P < .001) were significantly correlated with ALNM. Furthermore, the accuracy in the decision tree model was 69.52%, and the false-negative rate (FNR) was 74.18%. By using the error-cost matrix algorithm, the FNR significantly decreased to 14.75%, particularly for nodes 5, 8, and 13 (FNR: 11.4%, 9.09%, and 14.29% in the training set and 18.1%,14.71%, and 20% in the test set, respectively).In summary, our study demonstrated that tumor lesion boundary, tumor size, and tumor quadrant locations were the most important factors affecting ALNM in cT1-2N0M0 stage breast cancer. The decision tree built using these variables reached a slightly higher FNR than sentinel lymph node dissection in predicting ALNM in some selected patients.

CDS-1548 induces apoptosis in HeLa cells by activating caspase 3.

Cervical cancer continues to be a threat to female health globally. In the present study, the potential anticancer activity of 2-[2-hydroxyl-1-(4-methoxy phenyl) ethyl]-3-(4-benzyloxy phenyl) isoindolin-1-one (CDS-1548), was evaluated in HeLa cells. CDS-1548 is an organic small-molecule compound characterized by two chiral centers, with the nuclear parent 1H-isoindolin-1-one. CDS-1548 administration significantly elevated the transcriptional activity of p53 and its downstream target genes in a dose-dependent manner. Additionally, CDS-1548 treatment increased the expression levels of p53 and mouse double minute 2 homolog, as well as inducing apoptosis in HeLa cells. Furthermore, CDS-1548 treatment downregulated the expression of B-cell lymphoma 2, upregulated Bcl-2 homologous antagonist killer, promoted the release of cytochrome c from mitochondria to cytoplasm, and activated the production of caspase 3 and 9. Collectively, these results suggested that CDS-1548 inhibited HeLa cell proliferation by promoting G2/M cell cycle phase arrest and inducting of mitochondria-mediated apoptosis.