Establishment of glioma prognosis nomogram based on the function of meox1 in promoting the progression of cancer.

Background: Gliomas stand out as highly predominant malignant nervous tumors and are linked to adverse treatment outcomes and short survival periods. Current treatment options are limited, emphasizing the need to identify effective therapeutic targets. The heterogeneity of tumors necessitates a personalized treatment approach with an effective grouping system. Meox1 has been implicated in promoting tumor progression in diverse cancers; nonetheless, its role in gliomas remains unelucidated. Material/methods: Utilized immunohistochemistry to assess the expression of Meox1 protein in glioma tissues. Proliferation and invasion assays were conducted on wild-type and meox1-overexpressed glioma cells using the CCK8 and Transwell assays, respectively. The expression levels of meox1 and its related genes in gliomas were obtained from Chinese Glioma Genome Atlas (CGGA), along with the corresponding patient survival periods. LASSO regression modeling was employed to construct a scoring system for patients with gliomas, categorizing them into high-/low-risk groups. Additionally, a nomogram for predicting the survival period of patients with glioma was developed using multivariate logistic analysis. Results: We attempted, for the first time, to demonstrate heightened expression of Meox1 in glioma tumor tissues, correlating with significantly increased invasion and proliferation abilities of glioma cells following meox1 overexpression. The scoring system effectively stratified patients with glioma into high-/low-risk groups, revealing differences in the survival period and immunotherapy efficacy between the two groups. The integration of this scoring system with other clinical indicators yielded a nomogram capable of effectively predicting the survival period of individuals with gliomas. Conclusions: Our study established a stratified investigation system based on the levels of meox1 and its related genes, providing a novel, cost-effective model for facilitating the prognosis prediction of individuals with glioma.

One-day versus three-day low-residue diet bowel preparation regimens before colonoscopy: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Although studies have shown that the quality of bowel preparation with low-residue diet (LRD) is as effective as that of clear fluid diet (CLD), there is currently no consensus on how long an LRD should last. The aim of this study was to compare a 1-day versus 3-day LRD on bowel preparation before colonoscopy. METHODS: A systematic review search was conducted in MEDLINE/PubMed, EMBASE, Web of Science, and Cochrane database from inception to April 2023. We identified randomized controlled trials (RCTs) that compared 1-day with 3-day LRD bowel cleansing regiments for patients undergoing colonoscopy. The rate of adequate bowel preparation, polyp detection rate, adenoma detection rate, tolerability, willingness to repeat preparation, and adverse events were estimated using odds ratios (OR) and 95% confidence interval (CI). We also performed meta-analysis to identify risk factors and predictors of inadequate preparation. RESULTS: Four studies published between 2019 and 2023 with 1927 participants were included. The present meta-analysis suggested that 1-day LRD was comparable with 3-day LRD for adequate bowel preparation (OR 0.89; 95% CI, 0.65-1.21; P = 0.45; I2 = 0%; P = 0.52). The polyp detection rate (OR 0.94; 95% CI, 0.77-1.14; P = 0.52; I2 = 23%; P = 0.27) and adenoma detection rate (OR 0.87; 95% CI, 0.71-1.08; P = 0.21; I2 = 0%; P = 0.52) were similar between the groups. There were significantly higher odds of tolerability in patients consuming 1-day LRD compared with 3-day LRD (OR 1.64; 95% CI, 1.13-2.39; P < 0.01; I2 = 47%; P = 0.15). In addition, constipation was identified as the independent predictor of inadequate preparation (OR 1.98; 95% CI, 1.27-3.11; P < 0.01; I2 = 0%; P = 0.46). CONCLUSION: The present study demonstrated that a 1-day LRD was as effective as a 3-day CLD in the quality of bowel preparation before colonoscopy and significantly improved tolerability of patients. In addition, constipation is an independent risk factor of poor bowel preparation, and the duration of LRD in patients with constipation still needs further clinical trials.

Silk Fibroin-Modified Liposome/Gene Editing System Knocks out the PLK1 Gene to Suppress the Growth of Lung Cancer Cells.

Polo-like protein kinase 1 (PLK1) plays a key role in lung cancer cell mitosis. The knockout of PLK1 gene by the CRISPR-Cas9 system can effectively inhibit the proliferation of tumor cells, but there is no suitable vector for in vivo delivery. In this study, CRISPR-Cas9 gene knockout plasmids encoding sgRNA, Cas9 and green fluorescent protein were constructed. Then, the plasmids were packaged with liposome (Lip) and cholesterol-modified Antheraea pernyi silk fibroin (CASF) to obtain the CASF/Lip/pDNA ternary complex. The CASF/Lip/pDNA complex was transfected into lung cancer cells A549 to investigate the transfection efficiency, the PLK1 gene knockout effect and the inhibitory effect on lung cancer cells. The results showed that the transfection efficiency of the CASF/Lip/pDNA complex was significantly higher than that of the Lip/pDNA binary complex, and the expression of PLK1 in cells transfected with CASF/Lip/pDNA complexes was significantly lower than that in cells transfected with Lip/pDNA complexes. The CASF/Lip/pDNA complex significantly increased the apoptosis rate and decreased the proliferation activity of lung cancer cells compared with Lip/pDNA complexes. The cytotoxicity of the complexes was evaluated by coculture with the human bronchial epithelial cells BEAS2B. The results showed that CASF/Lip/pDNA complexes exhibited lower cytotoxicity than Lip/pDNA complexes. The fibroin-modified liposome/PLK1 gene knockout system not only effectively inhibited the growth of lung cancer cells but also showed no obvious toxicity to normal cells, showing potential for clinical application in lung cancer therapy.

Molecular characterization of colorectal adenoma and colorectal cancer via integrated genomic transcriptomic analysis.

Introduction: Colorectal adenoma can develop into colorectal cancer. Determining the risk of tumorigenesis in colorectal adenoma would be critical for avoiding the development of colorectal cancer; however, genomic features that could help predict the risk of tumorigenesis remain uncertain. Methods: In this work, DNA and RNA parallel capture sequencing data covering 519 genes from colorectal adenoma and colorectal cancer samples were collected. The somatic mutation profiles were obtained from DNA sequencing data, and the expression profiles were obtained from RNA sequencing data. Results: Despite some similarities between the adenoma samples and the cancer samples, different mutation frequencies, co-occurrences, and mutually exclusive patterns were detected in the mutation profiles of patients with colorectal adenoma and colorectal cancer. Differentially expressed genes were also detected between the two patient groups using RNA sequencing. Finally, two random forest classification models were built, one based on mutation profiles and one based on expression profiles. The models distinguished adenoma and cancer samples with accuracy levels of 81.48% and 100.00%, respectively, showing the potential of the 519-gene panel for monitoring adenoma patients in clinical practice. Conclusion: This study revealed molecular characteristics and correlations between colorectal adenoma and colorectal cancer, and it demonstrated that the 519-gene panel may be used for early monitoring of the progression of colorectal adenoma to cancer.

Native T1 mapping for non-invasive quantitative evaluation of renal function and renal fibrosis in patients with chronic kidney disease.

Background: To investigate the role of native T1 mapping in the non-invasive quantitative assessment of renal function and renal fibrosis (RF) in chronic kidney disease (CKD) patients. Methods: A prospective analysis of 71 consecutive patients [no RF (0%): 9 cases; mild RF (<25%): 36 cases; moderate RF (25-50%): 17 cases; severe RF (>50%): 9 cases] who were clinically diagnosed with CKD that was pathologically confirmed and who underwent magnetic resonance imaging (MRI) examination between October 2021 and September 2022 was performed. T1-C (mean cortical T1 value), T1-M (mean medullary T1 value), ΔT1 (mean corticomedullary difference) and T1% (mean corticomedullary ratio) values were compared. Correlations between T1 parameters and clinical and histopathological values were analyzed. Regression analysis was performed to determine independent predictors of RF. The areas under the receiver operating characteristic curve (AUC) were calculated to assess the diagnostic value of RF. Results: The T1-C, ΔT1 and T1% values (P<0.05) were significantly different in the CKD group, but T1-M was not (P>0.05). The ΔT1 and T1% values showed significant differences in pairwise comparisons among CKD subgroups (P<0.05) except for CKD 2 and 3. ΔT1 and T1% were moderately correlated with the estimated glomerular filtration rate (ΔT1: rs=-0.561; T1%: r=-0.602), serum creatinine (ΔT1: rs=0.591; T1%: rs=0.563), blood urea nitrogen (ΔT1: rs=0.433; T1%: rs=0.435) and histopathological score (ΔT1: rs=0.630; T1%: rs=0.658). ΔT1 and T1%, but not T1-C, were independent predictors of RF (P<0.05). ΔT1 and T1% were set as -410.07 ms and 0.8222 with great specificity [ΔT1: 91.7% (77.5-98.2%); T1%: 97.2% (85.5-99.9%)] to identify mild RF and moderate-severe RF. The optimal cutoff values for differentiating severe RF from mild-moderate RF were -343.81 ms (ΔT1) and 0.8359 (T1%) with high sensitivity [both 100% (66.4-100%)] and specificity [ΔT1: 90.6% (79.3-96.9%); T1%: 94.3% (84.3-98.8%)]. Conclusions: ΔT1 and T1% overwhelm T1-C for assessment of renal function and RF in CKD patients. ΔT1 and T1% identify patients with <25% and >50% fibrosis, which can guide clinical decision-making and help to avoid biopsy-related bleeding.

Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial.

BACKGROUND AND AIMS: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). RESULTS: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. CONCLUSIONS: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).

Prepackaged formula low-residue diet vs. self-prepared low-residue diet before colonoscopy: A multicenter randomized controlled trial.

Background and aims: Compared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy. Methods: A multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758. Results: A total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions. Conclusion: Compared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT03943758.

Plasmid containing VEGF-165 and ANG-1 dual genes packaged with fibroin-modified PEI to promote the regeneration of vascular network and dermal tissue.

Reducing the cytotoxicity of cationic polymers is the major issue to their use as a gene delivery carrier. In this study, plasmids containing encoding vascular endothelial cell growth factor 165 and angiopoietin-1 were packaged with the conjugates of cationic fibroin (CSF) and polyethylenimine (PEI), instead of packaging pDNA with PEI alone, to prepare nanocomplexes (CSF+PEI)/pDNA. The complexes were loaded into a silk fibroin scaffold to enhance its function to induce microvascular network generation and dermal tissue regeneration. The results of transfecting EA.hy926 cells with the complexes in vitro showed that (CSF+PEI)/pDNA had a stronger transfection ability than PEI/pDNA. Importantly, compared with PEI as the gene carrier alone, the cell viability was significantly increased and the cytotoxicity was effectively reduced after the conjugate of CSF and PEI was used as the gene carrier. The results of angiogenesis in chick embryo chorioallantoic membranes showed that compared with scaffolds loaded with PEI/pDNA, the neovascularization ratio in scaffolds loaded with (CSF+PEI)/pDNA was significantly increased. In vivo experimental results of scaffolds implantation for full-thickness skin defects in SD rats showed that, compared with loading PEI/pDNA complex, loading (CSF+PEI)/pDNA complex in the scaffold more effectively promoted the formation of vascular network in the scaffold and accelerated the regeneration of dermal tissue. The gene delivery system established in this study has application potential not only in the regeneration of vascular-containing tissues, but also in tumor gene therapy.

Reduced Adenoma Miss Rate With 9-Minute vs 6-Minute Withdrawal Times for Screening Colonoscopy: A Multicenter Randomized Tandem Trial.

INTRODUCTION: Although the 9-minute mean withdrawal time (m-WT) is often reported to be associated with the optimal adenoma detection rate (ADR), no randomized trials of screening colonoscopy have confirmed the impact of a 9-minute m-WT on adenoma miss rate (AMR) and ADR. METHODS: A multicenter tandem trial was conducted in 11 centers. Seven hundred thirty-three asymptomatic participants were randomized to receive segmental tandem screening colonoscopy with a 9-minute withdrawal, followed by a 6-minute withdrawal (9-minute-first group, 9MF, n = 366) or vice versa (6-minute-first group, 6MF, n = 367). The primary outcome was the lesion-level AMR. RESULTS: The intention-to-treat analysis revealed that 9MF significantly reduced the lesion-level (14.5% vs 36.6%, P < 0.001) and participant-level AMR (10.9% vs 25.9%, P < 0.001), advanced adenoma miss rate (AAMR, 5.3% vs 46.9%, P = 0.002), multiple adenomas miss rate (20.7% vs 56.5%, P = 0.01), and high-risk adenomas miss rate (14.6% vs 39.5%, P = 0.01) of 6MF without compromising detection efficiency ( P = 0.79). In addition, a lower false-negative rate for adenomas ( P = 0.002) and high-risk adenomas ( P < 0.05), and a lower rate of shortening surveillance schedule ( P < 0.001) were also found in 9MF, accompanying with an improved ADR in the 9-minute vs 6-minute m-WT (42.3% vs 33.5%, P = 0.02). The independent inverse association between m-WT and AMR remained significant even after adjusting ADR, and meanwhile, 9-minute m-WT was identified as an independent protector for AMR and AAMR. DISCUSSION: In addition to increasing ADR, 9-minute m-WT also significantly reduces the AMR and AAMR of screening colonoscopy without compromising detection efficiency.

The value of artificial intelligence techniques in predicting pancreatic ductal adenocarcinoma with EUS images: A meta-analysis and systematic review.

Conventional EUS plays an important role in identifying pancreatic cancer. However, the accuracy of EUS is strongly influenced by the operator's experience in performing EUS. Artificial intelligence (AI) is increasingly being used in various clinical diagnoses, especially in terms of image classification. This study aimed to evaluate the diagnostic test accuracy of AI for the prediction of pancreatic cancer using EUS images. We searched the Embase, PubMed, and Cochrane Library databases to identify studies that used endoscopic ultrasound images of pancreatic cancer and AI to predict the diagnostic accuracy of pancreatic cancer. Two reviewers extracted the data independently. The risk of bias of eligible studies was assessed using a Deek funnel plot. The quality of the included studies was measured by the QUDAS-2 tool. Seven studies involving 1110 participants were included: 634 participants with pancreatic cancer and 476 participants with nonpancreatic cancer. The accuracy of the AI for the prediction of pancreatic cancer (area under the curve) was 0.95 (95% confidence interval [CI], 0.93-0.97), with a corresponding pooled sensitivity of 93% (95% CI, 0.90-0.95), specificity of 90% (95% CI, 0.8-0.95), positive likelihood ratio 9.1 (95% CI 4.4-18.6), negative likelihood ratio 0.08 (95% CI 0.06-0.11), and diagnostic odds ratio 114 (95% CI 56-236). The methodological quality in each study was found to be the source of heterogeneity in the meta-regression combined model, which was statistically significant (P = 0.01). There was no evidence of publication bias. The accuracy of AI in diagnosing pancreatic cancer appears to be reliable. Further research and investment in AI could lead to substantial improvements in screening and early diagnosis.

FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study.

No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0-14), intermediate risk (IR 15-17), and high risk (HR 18-28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.

Predicting Histological Healing and Recurrence in Ulcerative Colitis by Assessing Mucosal Vascular Pattern Under Narrow-Band Imaging Endoscopy.

This study investigated the predictive value of narrow-band imaging (NBI) endoscopic staging of different mucosal vascular patterns (MVPs) in patients with ulcerative colitis (UC) for histological healing or clinical recurrence of patients with UC. A total of 124 patients with UC in clinical remission attending the First Affiliated Hospital of Weifang Medical College were included in the study and underwent NBI colonoscopy. Inflammatory activity was assessed in the intestine using the Mayo endoscopic score (MES) and the MVP. Mucosal inflammation was histologically graded using the Nancy index (NI). The colons of 124 patients with UC were staged according to NBI endoscopic MVP staging criteria. The differences between NBI colonoscopy MVP typing and white light endoscopic MES in assessing histological healing (HH) were statistically significant (p < 0.001), and there was a moderate correlation between MES and the degree of HH (r = 0.471, p < 0.001). In addition, there was a significant correlation between the severity of mucosal activity determined by white light endoscopy (WLE) and MVP staging (r = 0.811, p < 0.001). The differences between NBI endoscopic MVP staging and white light endoscopic MES in assessing UC recurrence were statistically significant (p < 0.001). Spearman's correlation analysis showed a moderate correlation between NBI endoscopic MVP staging and clinical recurrence. NBI endoscopic MVP staging can predict HH and clinical recurrence status better than WLE.

Neoadjuvant study of niraparib in patients with HER2-negative, BRCA-mutated, resectable breast cancer.

This single-arm pilot study (NCT03329937) evaluated neoadjuvant niraparib antitumor activity and safety in patients with localized HER2-negative, BRCA-mutated breast cancer. Twenty-one patients received niraparib 200 mg once daily in 28-day cycles. After 2 cycles, tumor response (≥30% reduction from baseline) by MRI was 90.5% and 40.0% (6 of 15) of patients who received only niraparib (2-6 cycles) had pathological complete response; no new safety signals were identified. High niraparib intratumoral concentration was observed.

Ultrasound-guided transversus thoracic muscle plane-pectoral nerve block for postoperative analgesia after modified radical mastectomy: a comparison with the thoracic paravertebral nerve block.

BACKGROUND: Modified radical mastectomy (MRM) is the most effective and common type of invasive surgery for breast cancer. However, it causes moderate to severe acute pain and even lasts for a long postoperative period. Transversus thoracic muscle plane-pectoral nerve block (TTP-PECS) is a novel and promising interfacial plane block which can provide analgesia for MRM while thoracic paravertebral nerve block (TPVB) is also widely used for this purpose. This study compared the postoperative analgesia between the ultrasound-guided TTP-PECS and TPVB in patients undergoing MRM. METHODS: In this randomized controlled trial, eighty female breast cancer patients undergoing unilateral MRM with sentinel lymph node dissection (SLND) and axillary dissection (ALND) were enrolled. Patients were randomized to receive either ultrasound-guided TTP-PECS (TTP-PECS group, n = 40) or TPVB (TPVB group, n = 40) with 0.5% ropivacaine 30 ml. Evaluated variables included 24 h postoperative total PCA fentanyl consumption, including PCA background consumption and PCA press consumption (per bolus dosage multiply by the effective pressing times), and intraoperative fentanyl consumption, as well as postoperative flurbiprofen axetil requirement, duration of analgesia, blocking area, pain intensity at rest and during activity, ability to reduce the inflammatory response, and the quality of recovery 40 (QoR-40) score of patients. RESULTS: Compared with the TPVB, the main blocking area was T2-T6 in the TTP-PECS group, which was more suitable for the MRM. TTP-PECS has a longer analgesia duration than TPVB; 24 h postoperative total PCA fentanyl consumption, especially the PCA press consumption, and the postoperative flurbiprofen axetil requirement were decreased in the TTP-PECS group than those in the TPVB group. Furthermore, the VAS scores at rest and during activity and inflammatory response were lower in the TTP-PECS group compared with the TPVB group at 12 h postoperatively. Finally, the total QoR-40 score, especially for the scores of pain; emotional state; and patient support were better in the TTP-PECS group. CONCLUSION: Compared with the TPVB, TTP-PECS can provide better postoperative analgesia in patients undergoing MRM, simultaneously reduce the inflammatory response, and prompt early recovery. These results suggest that TTP-PECS is an attractive alternative to TPVB for postoperative analgesia of modified radical mastectomy.

Expression of Zeb1 in the differentiation of mouse embryonic stem cell.

Embryonic stem cells (ESCs) differentiation is a process of replication and refinement, and the directional lineage differentiation of ESCs involves the epithelial-mesenchymal transition (EMT)- mesenchymal-epithelial transition (MET) process. A previous study revealed that Zinc finger E-box-binding homeobox 1 (Zeb1) plays a vital role in EMT, which could repress E-cadherin promoter and induce an EMT in cells. To verify the expression of Zeb1 and its correlation with Lin28a in mouse ESCs differentiation, we performed qRT-PCR and western blots to detect the expression of Lin28a mRNA and protein after Zeb1 knockdown. The expression of Zeb1 decreased over time of mouse ESCs differentiation but significantly increased in mouse embryonal carcinoma cells. After knockdown of Zeb1, Lin28a and Vimentin expression were decreased, while E-cadherin expression increased both in mouse ESCs, EBs, GC1, and P19 cells. We found that Zeb1 promoted the invasive ability of mouse embryonal carcinoma cells. These results revealed that expression of Zeb1 decreased during the differentiation of ESCs, and Lin28a and EMT processes can be regulated by Zeb1, which need to be verified in the future studies.

Calcium phosphate-based nanomedicine mediated CRISPR/Cas9 delivery for prostate cancer therapy.

Introduction: Erythropoietin producing hepatocyte receptor A2 (EphA2) is widely presented in the tumor cells, closely related to tumor cell migration, not cell apoptosis and proliferation. Based on its high expression in castration-resistant prostate cancer (CRPC), we herein develop a CRISPR-Cas9-based genome-editing nanomedicine to target erythropoietin producing hepatocyte receptor A2 for the treatment of castration-resistant prostate cancer. Methods: To this end, TAT was designed to stabilize the distribution of calcium, and then bound to ribonucleoprotein (RNP) to form nanoparticles RNP@CaP-TAT. Results: This nanoparticle has a simple synthesis process with good biocompatible, to achieve the knockout of tumor cells (PC-3) targeting erythropoietin producing hepatocyte receptor A2 gene and to effectively suppress the migration of tumor cells. Discussion: This delivery genome editing system provides a promising gene therapy strategy for the treatment of castration-resistant prostate cancer, showing good potential against castration-resistant prostate cancer tumor metastasis. In addition, it can be extended to other types of cancer with highly heterogeneous gene expression.

Impact of 9-Minute Withdrawal Time on the Adenoma Detection Rate: A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Although current quality indicators of colonoscopy recommend 6 minutes as the minimum standard for withdrawal time (WT), the impact of a WT longer than 6 minutes on neoplasia detection is unclear. METHODS: A multicenter randomized controlled trial involving 1027 patients was conducted from January 2018 to July 2019. Participants were randomly divided into a 9-minute (n = 514) and 6-minute (n = 513) WT group, and a timer was used to adjust the withdrawal speed. The primary outcome was the adenoma detection rate (ADR). RESULTS: Intention-to-treat analysis showed a significantly higher ADR in the 9-minute versus 6-minute WT group (36.6% vs. 27.1%, P = .001). Prolonging WT from 6 to 9 minutes significantly increased ADR of the proximal colon (21.4% vs. 11.9%, P < .001) as well as of the less experienced colonoscopists (36.8% vs. 23.5%, P = .001). Improvements were also observed in the polyp detection rate (58.0% vs. 47.8%, P < .001), and mean number of polyps and adenomas detected per colonoscopy (1.1 vs. 0.9, P = .002; 0.5 vs. 0.4, P = .008, respectively). The higher ADRs in 9-minute WT were also confirmed by the per-protocol (PP) analysis and subgroup analyses, with an increased rate of sessile serrated lesion detection in the 9-minute WT by PP analysis (4.0% vs. 1.3%, P = .04). Multivariate logistic regression demonstrated that the 9-minute WT was independently associated with increased ADR (P = .005). CONCLUSIONS: Prolonging WT from 6 to 9 minutes significantly improved ADR, especially in the proximal colon and for less experienced colonoscopists. A 9-minute WT benchmark should be considered as one of the quality indicators of colonoscopy. ClinicalTrials.gov (identifier, NCT03399045).

Study on the Melting Temperature of CaF2-CaO-MgO-Al2O3-TiO2 Slag under the Condition of a Fixed Ratio of Titanium and Aluminum in the Steel during the Electroslag Remelting Process.

During the process of electroslag remelting (ESR) of steel containing titanium and aluminum, the activity ratio between titania and alumina in CaF2-CaO-MgO-Al2O3-TiO2 slag must be fixed in order to guarantee the titanium and aluminum contents in the ESR ingots. Under the condition of fixed activity ratio between titania and alumina in the slag, the melting temperature of slag should be investigated to improve the surface quality of ESR ingots. Therefore, this paper focuses on finding a kind of slag with low melting temperature that can be used for producing steel containing titanium. In the current study, the thermodynamic equilibrium of 3[Ti] + 2(Al2O3) = 4[Al] + 3(TiO2) between SUS321 steel and the two slag systems (CaF2:MgO:CaO:Al2O3:TiO2 = 46:4:25:(25 - x):x and CaF2:MgO:CaO:Al2O3:TiO2 = 46:4:(25 - 0.5 x):(25 - 0.5 x):x) are studied in an electrical resistance furnace based on Factsage software. After obtaining the equilibrium slag with fixed activity ratio between titania and alumina, the melting temperatures of the two slag systems are studied using slag melting experimental measurements and phase diagrams. The results show that the slag systems CaF2:MgO:CaO:Al2O3:TiO2 = 46:4:25:(25 - x):x, which consists of pre-melted slag S0 (CaF2:MgO:CaO:Al2O3 = 46:4:25:25) and pre-melted slag F1 (CaF2:MgO:CaO:TiO2 = 46:4:25:25), can not only control the aluminum and titanium contents in steel, but also have the desired low melting temperature property.

The Role of PSA Density among PI-RADS v2.1 Categories to Avoid an Unnecessary Transition Zone Biopsy in Patients with PSA 4-20 ng/mL.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.